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[ "The structures of compounds bound to E7R have been deposited in the Protein Data Bank under accession code 4NB3.", "\n\nIntroduction {#sec1}\n============\n\nReplication protein A (RPA) is a single stranded DNA (ssDNA)--binding protein complex that is essential for DNA replication, damage response, and repair.^[@ref1],[@ref2]^ In response to DNA lesion formation, RPA rapidly coats ssDNA,^[@ref1],[@ref3]^ preventing the formation of aberrant DNA structures at replication foci and recruiting a number of checkpoint proteins to initiate the response to DNA damage.^[@ref4]^ Increased activity of DNA damage response and repair pathways is observed in a number of human cancers and has been linked to resistance to radiation or chemotherapy treatment.^[@ref5]^ Thus, compounds targeting these pathways may have utility in patients undergoing cancer therapy.", "\n\nRPA70 is the largest of the RPA subunits and contains three high-affinity ssDNA binding domains that serve as the DNA-anchoring core of the entire complex (RPA70A, -B, -C).^[@ref1],[@ref2]^ Binding to ssDNA is mediated by oligosaccharide/oligonucleotide binding (OB) folds that are present on all subunits.^[@ref6]−[@ref8]^ The basic cleft in the OB fold present on the N-terminal domain, RPA70N, binds to several partner proteins that are important for mediating the response to DNA damage, including ATRIP (ATR-interacting protein), RAD9, MRE11, and p53.^[@ref4],[@ref9]−[@ref11]^ We hypothesize that the selective inhibition of the RPA70N basic cleft will specifically disrupt these protein--protein interactions, leading to the inhibition of a subset of RPA functions, attenuation of the DNA damage response, and the selective killing of cancer cells.", "\n\nToward the discovery of a probe molecule that binds tightly to RPA70N and inhibits its interaction with other proteins, we and others have previously reported small molecules that bind to RPA70N.^[@ref12]−[@ref14]^ We used an NMR-based screen to identify fragments that bind to RPA70N, and, on the basis of X-ray structures of the screening hits and analogues when bound to the protein, have obtained analogues with improved affinity. ", "Recently, we have discovered compounds that bind to RPA70N with submicromolar affinity^[@ref12]^ that were obtained by linking together small molecules that bind to two adjacent sites.", "\n\nAn alternative approach for targeting protein--protein interactions is the use of stapled helix peptides. ", "Hydrocarbon stapling has been shown to increase the affinity, stability, and cellular permeability of peptide sequences that bind to protein targets.^[@ref15]−[@ref17]^ NMR experiments have demonstrated that homologous peptides derived from the partner proteins ATRIP, RAD9, and MRE11 bind competitively to the basic cleft of RPA70N.^[@ref18]^ Further, the three peptides share a region of similar primary sequence with p53 and contain a mix of conserved acidic and hydrophobic amino acid residues.^[@ref19]^ An X-ray crystal structure of a chimeric protein containing portions of RPA70N and p53 reveals that a part of the p53 transactivation domain (residues 47--57) folds into helices that bind into the basic cleft in the OB fold of RPA70N.^[@ref19]^ These binding interactions in the cleft are stabilized by both electrostatic and hydrophobic interactions. ", "We have previously measured the binding affinity of these peptides to RPA70N and found that the ATRIP-derived sequence binds more tightly than the Rad9, MRE11, and p53 peptides.^[@ref20]^\n\nHere we describe the discovery of stapled helix peptides, based on the ATRIP sequence, that bind tightly to the protein--protein interaction site in the basic cleft of RPA70N and inhibit the interactions of RPA70N with other peptides/proteins. ", "The binding affinity was optimized by traditional methods, as well as a novel method that can efficiently select and incorporate unnatural amino acids into the peptides. ", "Peptides in which an unnatural amino acid was incorporated displayed a 1--2 orders of magnitude improvement in binding affinity compared to peptides with natural amino acids, penetrate cells, and may serve as useful tools for studying RPA function and the therapeutic potential of inhibiting RPA.", "\n\nResults and Discussion {#sec2}\n======================\n\nAlanine Scanning of the ATRIP Peptide {#sec2.1}\n-------------------------------------\n\nTo better understand the peptide structure--activity-relationships (SARs) of the ATRIP-derived peptide and to elucidate the sequence positions suitable for affinity-optimizing point mutations, we performed an alanine scan in which each amino acid was replaced by an alanine residue (Table [1](#tbl1){ref-type=\"other\"}). ", "Affinity of the mutated peptides was measured using an FPA competition assay with FITC-ATRIP as a probe.^[@ref20]^\n\n###### Alanine Scan of an ATRIP-Derived Peptide\n\n![](", "jm-2013-01730y_0011){#GRAPHIC-d518e377-autogenerated}\n\nAlanine mutations are shown in bold red.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay.", "\n\nSouza-Fagundes et al.^[@ref20]^\n\nResidues D1, F2, T3, D6, L7, E9, L10, D11, and L13 were found to be important for binding to RPA70N, as replacement of each of these with an alanine resulted in a significant loss of binding affinity. ", "Interestingly, although D5 is conserved in the ATRIP and corresponding RAD9, MRE11, and p53 sequences, replacement with an alanine leads to a peptide equipotent with the parent, suggesting that this residue does not contribute significantly to binding to RPA70N. Similarly, despite the conservation of E8 in three out of the four RPA70N binding partners, no loss of binding was observed when E8 was replaced with alanine. ", "In contrast, an almost complete loss of binding was observed when F2 was replaced with an alanine (peptide-02). ", "Two ATRIP amino acid mutations led to a slight improvement in affinity: E8A (peptide-07, *K*~d~ = 22 μM) and T12A (peptide-11, *K*~d~ = 17 μM). ", "However, when combined into one peptide sequence (peptide-14), the individual positive effects on the binding affinity were not additive.", "\n\nATRIP Amino Acid Substitutions Inspired by p53 {#sec2.2}\n----------------------------------------------\n\nIn an attempt to improve the binding affinity of the ATRIP peptide, we substituted the hydrophobic residues WF from the p53 peptide into the corresponding positions of the ATRIP peptide (Table [2](#tbl2){ref-type=\"other\"}). ", "These residues form a hydrophobic motif within p53 (IEQWF) that is not present within the ATRIP sequence. ", "Although individual substitution of L10 or D11 with W or F, respectively, did not improve binding relative to peptide-14 (peptide-15 and peptide-16), a 10-fold improvement in affinity was observed when these replacements were combined (peptide-17, *K*~d~ = 2.7 μM). ", "This effect may be attributed to a clustering of the two residues, leading to the formation of a hydrophobic binding core.^[@ref19],[@ref21]^ To further optimize the potency, we substituted positions 8 and 12 of peptide-17 with alanines, as those mutations were found to increase the binding affinity to RPA70N. Whereas the E8A mutation results in a dramatic loss of affinity in the context of the WF motif (peptide-18), the binding of peptide-19 (T12A mutation) was increased by a factor of 2 relative to peptide 17. ", "A FITC moiety was attached to peptide-19 to facilitate direct measurement of binding affinity to RPA70N; the new peptide-20 has an affinity of 480 nM (approximately an additional 3-fold increase). ", "While the basis for the binding improvement due to the FITC label is not well understood, a similar effect was noted with the ATRIP peptide.^[@ref20]^\n\n###### Amino Acid Substitutions\n\n![](", "jm-2013-01730y_0012){#GRAPHIC-d518e438-autogenerated}\n\nSubstituted residues are indicated in bold red.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay.", "\n\nSouza-Fagundes et al.^[@ref20]^\n\n*K*~d~ values of FITC-labeled peptides determined by direct binding experiments.", "\n\nReduction of Overall Peptide Charge {#sec2.3}\n-----------------------------------\n\nPeptide-20 has a net negative charge of −6. ", "Empirical evidence has suggested that a neutral or positive overall charge is optimal for achieving cellular penetrance.^[@ref17]^ We therefore examined the relative importance of the negatively charged residues in peptide-19 by replacing aspartic and glutamic acid residues with their amide analogues. ", "In addition, we tested the replacement of D and E residues with alanines (in the context of the optimized WFA containing peptide-19) to elucidate which negatively charged amino acids could be substituted with an uncharged residue without leading to an unacceptable decrease in RPA70N affinity (Table [3](#tbl3){ref-type=\"other\"}). ", "While replacement of some negatively charged amino acids is tolerated, other substitutions are accompanied by a severe drop in binding affinity, as might be expected for a peptide binding to a protonated basic cleft. ", "For example, changing D1 to an asparagine was tolerated with a relatively minimal loss of affinity (peptide-21), an alanine substitution of D5 did not reduce the potency compared to an N substitution (peptide-22 and peptide-23), and substitution of D6 with an asparagine produced better binding than the corresponding alanine (peptide-24 and peptide-25). ", "However, for E8, an alanine substitution sharply reduced the binding affinity (peptide-26), while minimal loss of affinity was observed for substituting E9 with either an alanine or glutamine (peptide-27 and peptide-28). ", "On the basis of these results, we combined the least deleterious amino acid substitutions to produce a FITC-labeled peptide (peptide-29) with a net negative charge of −2. ", "However, the reduction in charge came at the expense of a nearly 50-fold loss in binding to RPA70N compared to peptide-20.", "\n\n###### Charge Abrogation of Peptide-19\n\n![](", "jm-2013-01730y_0006){#GRAPHIC-d518e487-autogenerated}\n\nCharge replacement mutations are shown in bold red. ", "Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values derived from IC~50~ values measured in an FPA competition assay unless otherwise noted.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nShortening of the Peptide Sequence {#sec2.4}\n----------------------------------\n\nConcomitant with our efforts to reduce the net negative charge of the peptides, we examined the effect of peptide length on binding affinity and the possibility of improving the properties of the peptides.^[@ref22]^ If the ATRIP-derived peptides adopt a helix with the same length as p53 upon binding to RPA70N, several N- and the C-terminal residues may not be part of the secondary structure and thus are potential candidates for removal. ", "The alanine scan revealed that all residues at the N-terminus are essential for interacting with RPA70N (Table [1](#tbl1){ref-type=\"other\"}). ", "In contrast, minimal loss of binding affinity was observed when residues at the C-terminus were replaced by alanine (peptide-12 and peptide-13). ", "Therefore, we tested whether shortening of peptide-20 by one, two, or three residues at the C-terminus would be tolerated (Table [4](#tbl4){ref-type=\"other\"}).", "\n\n###### Binding Affinity of Shortened Peptides\n\n![](", "jm-2013-01730y_0007){#GRAPHIC-d518e532-autogenerated}\n\nDeleted residues are indicated by bold red dashes. ", "3,4-Dichlorophenylalanine is shown as a bold green Z. Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nRemoving the C-terminal residue (S15) had almost no effect on the binding of peptide-30 to RPA70N, and the removal of the last two C-terminal amino acids (A-S) led to a peptide with improved binding affinity to RPA70N (peptide-31). ", "However, removing one additional residue (L13) resulted in a 3-fold decrease in binding affinity (peptide-32).", "\n\nUnnatural Amino Acid Substitutions {#sec2.5}\n----------------------------------\n\nIn order to further improve binding to RPA70N, we explored the possibility of incorporating unnatural amino acids. ", "Such peptides can be difficult and expensive to synthesize and thus must be carefully designed. ", "To identify suitable locations for incorporation of a designed unnatural amino acid, we exploited findings from our small molecule discovery efforts. ", "We have previously reported the use of an NMR-based fragment screen to discover compounds that bind to a hydrophobic pocket near S55,^[@ref12]^ suggesting that this pocket represents an important binding \"hot spot\" on RPA70N (Figure [1](#fig1){ref-type=\"fig\"}A). ", "Consistent with this finding, that same pocket is occupied by F54 of the WF motif within the p53 peptide (Figure [1](#fig1){ref-type=\"fig\"}B).^[@ref19]^ Optimization of multiple series of fragment hits has established that a 3,4-dichloro-substituted phenyl ring displays significantly improved binding affinity to RPA70N compared to an unsubstituted phenyl group.^[@ref12],[@ref14]^ Thus, we hypothesized that a peptide containing a 3,4-dichloro-substituted phenylalanine in place of a phenylalanine would have improved binding affinity to RPA70N (Figure [1](#fig1){ref-type=\"fig\"}C). ", "Indeed, a peptide containing an unnatural amino acid with a 3,4-dichlorophenyl moiety (peptide-33) showed a \\>100-fold improvement in affinity (Table [4](#tbl4){ref-type=\"other\"}). ", "An X-ray structure of peptide-33 when complexed with RPA70N confirmed that the side chain of the 3,4-dichlorophenylalanine binds to the RPA70N hot spot located above S55, in a manner similar to the binding mode of the phenylalanine of p53 (Figure [1](#fig1){ref-type=\"fig\"}D).", "\n\n![", "X-ray structures of fragments and peptides in complex with RPA70N reveal a preferred binding site within the basic cleft. (", "A) Overlay of cocrystal structures of fragments bound to RPA70N. (B) Superpositioned structures of RPA70N bound to fragments and the p53 peptide (red). (", "C) The dichlorophenyl ring of an elaborated compound (yellow) binds in the same hydrophobic pocket as F54 of the p53 peptide (red). (", "D) Superposition of RPA70N/p53 peptide (red)^[@ref19]^ and RPA70N/peptide-33 (blue).](jm-2013-01730y_0002){#fig1}\n\nStapled Helix Peptides {#sec2.6}\n----------------------\n\nThe use of a hydrocarbon staple for helical peptides is a promising approach to improve upon the poor characteristics of linear peptides by imparting increased protease resistance, affinity, and cell permeability.^[@ref15]−[@ref17]^ Three stapling patterns have been shown to stabilize helical conformations: *i*, *i* + 3; *i*, *i* + 4; and *i*, *i* + 7.^[@ref17]^ On the basis of the results from the mutational analyses, we employed the *i*, *i* + 4 configuration using residues 5 and 9 to evaluate stapled helix peptides with varying overall net charge (Table [5](#tbl5){ref-type=\"other\"}). ", "Although peptide-34 had a slightly reduced binding affinity compared to its unstapled counterpart (peptide-31), the negative charge was reduced. ", "As expected, further reduction of the charge yielded an additional loss in affinity (peptide-35, peptide-36, and peptide-37). ", "Once again, we compensated for the loss in affinity due to charge abrogation by substituting F12 with a dichlorophenylalanine (peptide-38 and peptide-39). ", "Incorporation of this motif alone led to a 31- and 175-fold increase in affinity, respectively, resulting in peptides that represent the optimal balance of potency and overall net charge.", "\n\n###### Binding Affinities of Peptides\n\n![](", "jm-2013-01730y_0008){#GRAPHIC-d518e630-autogenerated}\n\nα-(4-Pentenyl)alanine staples are depicted as a red X. 3,4-Dichlorophenylalanine is shown as a bold green Z. Amino acid changes incorporated from earlier peptides are shown in blue.", "\n\n*K*~d~ values determined by direct binding experiments.", "\n\nSelectivity {#sec2.7}\n-----------\n\nTo verify the utility of the stapled helix peptides as specific inhibitors of the RPA70N protein--protein interactions, we evaluated the ability of the peptides to bind to the other OB-fold-containing domains of RPA that bind to ssDNA.", "\n\n{#fig2}\n\nBy use of a direct binding FPA assay, peptide-37 and peptide-39 were examined for their ability to bind to RPA70A/B, which contains the core ssDNA binding unit, and RPA70C/32D/14 (Figure [2](#fig2){ref-type=\"fig\"}). ", "Peptide-37 shows very little selectivity in binding to the different OB-fold containing domains; while this peptide binds to RPA70N with a *K*~d~ of 7.4 μM, it binds the other domains with similar affinity (12--15 μM). ", "In contrast, peptide-39, which binds to RPA70N with an affinity of 0.042 μM, binds to RPA70A/B and RPA70C/32D/14 with a *K*~d~ of only 2.4 μM, exhibiting 50-fold selectivity for binding to RPA70N. The incorporation of the dichlorophenyl moiety not only produces a significant increase in potency but also appears to impart a significant increase in selectivity for RPA70N over other OB-fold containing domains. ", "To confirm that peptide-39 does not functionally displace RPA from ssDNA, we conducted an electrophoretic mobility shift assay (EMSA). ", "Increasing concentrations of peptide-39 were incubated with RPA and ssDNA and subjected to separation on a polyacrylamide gel. ", "No change in the percent of RPA bound to radiolabeled ssDNA was observed, indicating that although peptide-39 can bind weakly to other OB-fold containing domains in a biochemical assay, this 2 μM binding affinity is not sufficient to displace full-length RPA from ssDNA (Figure [3](#fig3){ref-type=\"fig\"}). ", "Thus, peptide-39 possesses a suitable selectivity profile for use as a probe of RPA70N function in cells.", "\n\n{#fig3}\n\nCell Penetrance {#sec2.8}\n---------------\n\nSeveral studies have demonstrated that stapled helix peptides gain entry to mammalian cells through active endocytosis.^[@ref15],[@ref23],[@ref24]^ Further, overall peptide charge is a key determinant of cellular penetrance, with increased positive charge leading to more efficient uptake. ", "We examined the ATRIP-derived stapled helix peptides for their ability to enter mammalian cells. ", "Peptides were incubated for 24 h with U2OS cells, fixed, and visualized by confocal microscopy for direct observation of the FITC label (Figure [4](#fig4){ref-type=\"fig\"}). ", "As expected, peptide-34, with a net charge of −4, was the least efficient at penetrating cells. ", "In contrast, the remaining peptides were observed inside the cells in a pattern consistent with internalization through endocytosis. ", "Diffuse cytosolic staining and fluorescence within the nucleus were also observed, as exemplified by peptide-37 and peptide-39.", "\n\n{#fig4}\n\nConclusions {#sec3}\n===========\n\nTo discover a peptide that binds tightly to RPA70N and penetrates cells, we initiated optimization of a 15 amino acid ATRIP-derived peptide that binds to RPA70N with an affinity of 29 μM and possesses a net charge of −5. ", "Through alanine scanning, natural amino acid substitutions, and shortening of the peptide sequence, we identified key residues responsible for binding to RPA70N, improved the binding affinity, and ascertained which amino acids could be substituted to reduce the overall negative charge. ", "However, because of the electrostatic characteristics of the pocket, substitutions that reduced the peptide charge universally led to a decrease in binding affinity. ", "Despite these improvements and the knowledge gained, the resulting peptides were still unsuitable for use as a chemical probe for the study of RPA70N as a cancer target because of insufficient binding affinity.", "\n\nTo further improve the binding affinity, we sought to incorporate an unnatural amino acid into our peptides. ", "Historically, this strategy has not been widely employed because of difficulties in choosing which amino acid to replace and which unnatural amino acid to use as a replacement. ", "Indeed, most peptide optimizations typically involve only the use of natural amino acid substitutions. ", "Here we have demonstrated a strategy to efficiently design unnatural amino acid substitutions for peptide optimization. ", "The optimization process involves the identification of a binding hot spot using a fragment-based screen and subsequent structural characterization of important molecular interactions that might be exploited for affinity improvements. ", "Structural knowledge of the residue that normally occupies this hotspot, along with SAR information gleaned from fragment hits and optimization of these hits, then guides the efficient targeted replacement of an amino acid with an optimized variant.", "\n\nWe have demonstrated this strategy by capitalizing on a wealth of SAR and structural information from compounds identified from a NMR-based fragment screen. ", "In multiple prior instances, the presence of a 3,4-dichlorophenyl moiety has produced improvements in binding affinity.^[@ref12],[@ref14]^ Thus, we applied this substitution pattern to a phenylalanine residue that had been previously determined to occupy the same binding hot spot identified in the fragment screen. ", "The addition of two halogens produced highly significant gains in binding affinity in both stapled and unstapled peptides.", "\n\nIn total, by combining peptide optimization studies, small molecule SAR, and structural information on peptide and small molecule binding modes, we improved the affinity of the modified peptide by almost 1000-fold. ", "The optimized stapled helix peptide obtained from this work binds tightly to RPA70N with an affinity of 0.042 μM, is selective for binding to RPA70N versus other OB folds of RPA, has a reduced overall net negative charge, and penetrates cells. ", "This compound may serve as a useful tool to study the biology of RPA and validate RPA as a cancer target. ", "Moreover, the new approach that we have employed to optimize the peptides may be a useful general method for optimizing peptides that bind to other protein targets and thus expand the utility of stapled helix peptides as chemical tools and therapeutic agents.", "\n\nExperimental Details {#sec4}\n====================\n\nProtein Expression and Purification {#sec4.1}\n-----------------------------------\n\nRecombinant RPA70N (RPA70~1--120~), RPA70AB (RPA70~181--422~), and RPA70NAB (RPA70~1--422~) constructs were prepared as described previously.^[@ref20],[@ref25]−[@ref27]^ Proteins were expressed in *Escherichia coli* host Rosetta (RPA70AB, RPA70NAB) or BL21-DE3 (RPA70N) cells (Novagen). ", "Cells were grown in LB medium containing kanamycin (RPA70AB, RPA70NAB) or ampicillin (RPA70N) at 37 °C, induced with 0.1 M IPTG when the OD reached 0.6, and harvested after 4 h using a JLA 8.1 Beckman rotor at 7500 rpm and 4 °C. ", "Pellets were stored at −20 °C. ", "Human RPA70N was purified using a Ni sepharose column (GE Healthcare). ", "Following His-tag cleavage and a Ni sepharose column repass to remove the cleaved tag, RPA70N was obtained at greater than 95% purity as judged by sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS--PAGE) analysis. ", "Finally, RPA70N samples were dialyzed against assay buffer (50 mM HEPES, 75 mM NaCl, 5 mM DTT, pH 7.5) for use in fluorescence polarization studies. ", "RPA70AB samples were purified using nickel affinity chromatography in 10 mM HEPES (pH 7.5), 500 mM NaCl, 5 mM BME, and 10% glycerol using an elution gradient from 20 to 300 mM imidazole. ", "Cleavage of the His tag with TEV protease was performed through overnight dialysis in a buffer containing 10 mM HEPES (pH 7.5), 200 mM NaCl, 5 mM BME. ", "A second Ni column purification step was used to remove the His tag. ", "Size exclusion chromatography using a Superdex S75 column equilibrated with the dialysis buffer was used as a last step of purification. ", "RPA70AB protein was concentrated, and stock solutions were frozen in liquid nitrogen and kept at −80 °C. ", "A similar procedure described previously^[@ref26]^ was used for RPA70NAB samples using Ni column buffer 30 mM MES (pH 6.5), 500 mM NaCl, 5 mM BME and cleaving with H3C protease. ", "The size exclusion chromotography step was performed using a Superdex S200 column and a buffer containing 30 mM MES (pH 6.5), 200 mM NaCl, 10 mM BME, 5% glycerol.", "\n\nPeptide Synthesis {#sec4.2}\n-----------------\n\nAll linear peptides, with and without fluorescein isothiocyanate (FITC), were purchased from GenScript USA Inc. FITC groups were attached to the N-terminus of peptide sequences via an aminohexanoic acid (Ahx) linker. ", "Hydrocarbon stapled peptides were purchased from New England Peptide LLC. ", "Staples were incorporated by placing modified α-(4-pentenyl)alanine residues at predetermined locations within the peptide sequence, separated by three amino acids. ", "Peptides were purified by the manufacturer using high-performance liquid chromatography to \\>95% purity. ", "Unlabeled peptides were dissolved as 10 mM stock solutions in assay buffer (50 mM HEPES, 75 mM NaCl, 5 mM DTT, pH 7.5). ", "FITC-labeled peptides were dissolved in DMSO to a final concentration of 1 mM.\n\nFluorescence Polarization Anisotropy Assays {#sec4.3}\n-------------------------------------------\n\n*K*~d~ determination and FPA competition assays were conducted as described previously^[@ref20]^ with minor modifications. ", "For direct *K*~d~ determination of FITC-labeled peptides, increasing concentrations of purified RPA were added to 25 nM peptide in a total of 50 μL assay buffer. ", "Anisotropy was measured, and data were fit to a single site binding model using Prism. ", "For competition experiments, unlabeled peptides were titrated into assay buffer containing RPA70N and FITC-labeled peptide probe. ", "Assays were conducted at a protein concentration equal to the *K*~d~ of the FITC-peptide--protein interaction. ", "Therefore, 50 nM FITC-ATRIP was used with 6 μM RPA70N; 25 nM peptide-31 was used with 350 nM RPA70N. Anisotropy was measured and plotted against compound concentration using a four-parameter logistic fit to generate an IC~50~; this value was converted to *K*~d~, as previously described.^[@ref20]^\n\nGel Mobility Shift Assay {#sec4.4}\n------------------------\n\nThe gel mobility shift assays were performed as previously described^[@ref28]^ with the following modifications. ", "Purified RPA (12 nM final concentration) and increasing concentrations of peptide-39 (0, 0.1, 1, 10, 100 μM final concentration) were incubated with radiolabeled 50-nucleotide ssDNA probe (6 nM final concentration) at room temperature for 20 min. ", "The samples were separated by electrophoresis prior to autoradiography and quantitation.", "\n\nFluorescence Microscopy {#sec4.5}\n-----------------------\n\nU2OS cells were plated at 3 × 10^4^ cells/well in eight-chamber slides (BD Falcon). ", "After 24 h, cells were washed once with PBS and incubated for 24 h with stapled helix peptides in serum-free medium. ", "Medium was removed, and cells were fixed in 4% paraformaldehyde/PBS for 1 h at room temperature. ", "Cells were rinsed three times with PBS and mounted on a coverslip with Vectashield (Vector Laboratories) mounting medium containing DAPI. ", "Slides were imaged on a confocal microscope (Zeiss LSM 710).", "\n\nCrystallization of RPA70N:Peptide-33 Complex {#sec4.6}\n--------------------------------------------\n\nLyophilized peptide-33 (FITC-Ahx-DFTADDLEEWZAL-NH~2~) was added directly to 700 μM RPA70N E7R at a 2.5:1 (peptide-33/E7R RPA70N) ratio and initially screened against a variety of conditions. ", "Following optimization of the initial crystallization conditions, the buffer condition of 100 mM Bis-Tris, pH 6.5, 200 mM ammonium acetate, 25% PEG 3350 was found to produce crystals that showed a strong green color, indicative of the presence of FITC. ", "Prior to data collection, crystals were soaked in mother liquor containing 20% 2-methyl-2,4-pentanediol (MPD) and were flash-frozen in liquid nitrogen. ", "X-ray diffraction data were initially collected on an in-house rotating anode source and later at sector 21 (Life Sciences Collaborative Access Team, LSCAT) at the Advanced Photon Source. ", "All data were processed by HKL2000.^[@ref29]^ The proteins crystallized in space group *C*121 and contained two peptide-33:E7R RPA70N complexes in the asymmetric unit. ", "Initial phases were obtained by molecular replacement with PHASER^[@ref30]^ using the E7R RPA70N structure (4IPC)^[@ref27]^ as a search model. ", "Iterative cycles of model building and refinement were performed using COOT^[@ref31]^ and Phenix.^[@ref32]^ Following modeling of waters, peptide-33, including its covalently attached FITC, was placed into electron density at the basic cleft and refined. ", "The structure of this complex has been deposited in the Protein Data Bank under the accession code 4NB3.", "\n\nCrystallographic results and refinement statistics. ", "This material is available free of charge via the Internet at <http://pubs.acs.org>.", "\n\nSupplementary Material\n======================\n\n###### \n\njm401730y_si_001.pdf\n\n^\\#^ A.O.F.: Novartis Institutes for BioMedical Research (NIBR), Global Discovery Chemistry, Emeryville, California 94608, United States.", "\n\n^∞^ B.V.: The Institute for Applied Cancer Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.", "\n\n^¶^ E.M.S.-F.: Physiology and Biophysics Department, Federal University of Minas Gerais, Av. ", "Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil.", "\n\nThe authors declare no competing financial interest.", "\n\nThis work was supported by a postdoctoral fellowship from the Deutscher Akademischer Austausch Dienst (DAAD) to A.O.F., a National Institutes of Health National Research Service Award (NRSA) F32 ES021690 to M.D.F., NIH Grant CA102792 to D.C., and funding from the National Council for Scientific and Technological Development---CNPq and Federal University of Minas Gerais/Brazil to E.M.S.-F. We thank Dr. Cheryl Arrowsmith (Ontario Cancer Institute, Toronto, Canada) for kindly providing the ^1^H and ^15^N backbone NMR assignments of RPA70N.\n\nRPA\n\n: replication protein A\n\nFPA\n\n: fluorescence polarization anisotropy\n\nLE\n\n: ligand efficiency\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "Social Media Optimization Trends For 2017\n\nIt’s anticipated that the Development of Snap will Result in new opportunities, which is interesting at least, in 2017. ", "In the past couple of months Breeze, understood previously and more broadly as Snap Chat, has obtained improved by leaps and bounds. ", "Experts are predicting big things with this platform at the days beforehand. ", "Breeze has been effective in altering important trends in addition to user expectations from the sphere of social networking marketing. ", "Due to Snap, the moment focused perspective of communicating is back. ", "It has meant more spontaneous and lives content. ", "It’s helped programmers create more programs that are concentrated towards the mobile platforms.", "\n\nSnap has also brought forth perpendicular videos and forced them a Portion of the mainstream. ", "But now it’s seeking to produce products which happen to fall beyond the purview of the attention domain – which of exchanging messages. ", "It’s seeking to bring about real world eyeglasses because of its customers so that they have the ability to capture visual information about a first-person basis. ", "So far as.", "\n\nSocial networking Optimization is worried; Snap will be there right at the center of matters. ", "It’s also expected to offer a few significant league advertising opportunities also. ", "Twitter fatigue will get worse Experts believe that maybe not everybody is well with Twitter and moving. ", "But Many Brands and celebrities active on Twitter. ", "They are trying to gain Twitter followers in 2017.", "\n\nTwitter fatigue will get worse\n\nAhead in 2017, it’s not expected to have any better. ", "Actually, within the past couple of decades, a lot of folks have been stating that Twitter will probably die a natural death. ", "But, there are also the ones that consider that in most likelihood Twitter will be there for one more year in the least. ", "But, they’re also stating that Twitter fatigue increases appreciably in 2017. ", "Twitter is famous for its brief updates delivered at a breakneck speed but in addition, it contributes to a great deal of incoming and outgoing tweets.", "\n\nWhen it began it was rather fascinating for the simple reason that it was brand new. ", "But now users are becoming used to it and are requesting something that’s a whole lot different. ", "They would like it to be larger, have higher details, and have more interesting content. ", "Additionally, they wish for the speed to become slower. ", "Instagram actually has already begun to slow down its rate of updates.", "\n\nMore sensational experiences\n\nYes, this is exactly what users will desire in 2017 and they desire Social media to meet this function, to be the supplier as it had been. ", "No more can it suffice users to say social websites they’re attending an Occasion – they should show other people how it seems to be attending that event reside. ", "This can be achieved by means of live videos and 360-degree graphics.", "\n\nEven Real-time posting could resolve the conundrum to an extent too. ", "The fundamental Idea is to create others – that aren’t there – feel a portion of the entire show. ", "They ought to feel They Are a real and natural part of the whole experience even as it continues to unravel.", "\n\nSIMILAR NEWS\n\nThere are certain promotional ideas that can truly help you get the website traffic as well as rise success of video clip on buying you Tube comments, However, there is a trouble that this takes a great deal of time to get the sort and also customers for the video. …", "\n\nAre you planning to Boost YouTube Sights? ", "There can be any type of a number of factors for services as well as individuals to want to reach a larger target market. ", "Among the lot more effective means to acquire a bigger target market is to buy YouTube views advertise YouTube …\n\nRunning a picture for your web site is as awesome as running a large range of phrases. ", "So, you should utilize images from a variety of the things which you may be offering, in addition, to showcase them all working on the online audience. ", "Because situation applies Instagram as well …" ]

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[ "Pierre Karl Péladeau nuit au retour des Nordiques à Québec, a affirmé jeudi le chef de la Coalition avenir Québec, François Legault. ", "Selon lui, les propriétaires de la Ligue nationale de hockey (LNH) seront réfractaires à accorder une franchise à un homme d'affaires qui dirige un parti indépendantiste.", "\n\n«Ce que j'entends à Montréal, c'est que tant que M. Péladeau sera là, ce sera difficile de lui donner une équipe», a laissé tomber le chef caquiste avant une réunion de ses députés.", "\n\nIl dit douter que les propriétaires des autres franchises canadiennes acceptent d'accueillir au sein de leur groupe le chef d'un parti politique voué à l'indépendance du Québec. ", "M. Péladeau est l'actionnaire de contrôle de Québecor, l'entreprise qui gère l'amphithéâtre de Québec et qui tente de convaincre la Ligue nationale de hockey (LNH) de ramener le hockey professionnel dans la Vieille Capitale.", "\n\nM. Legault croit que les autres propriétaires useront de leur droit de veto pour barrer la route à M. Péladeau.", "\n\n«Le fait que M. Péladeau soit un indépendantiste, on sait très bien, que ce soit les propriétaires de Toronto ou du Canadien, ce ne sont pas des indépendantistes et ils n'aiment pas ça, l'indépendance du Québec», a dit M. Legault.", "\n\nLa sortie de François Legault a été qualifiée de « ridicule » par le député péquiste Pascal Bérubé. ", "Il note que les Nordiques ont rejoint la LNH en 1979, alors que René Lévesque était au pouvoir et à quelques mois du premier référendum sur l'indépendance.", "\n\n«Je crois que Québec est une capitale présentement, puis on est une capitale d'un pays, et ça ne changera pas, a dit M. Bérubé. ", "Cette ville-là est une ville de hockey avec des amateurs de hockey qui aiment le hockey, qui ne mélangent pas ça avec la politique.»", "\n\nM. Bérubé y voit la preuve que le chef caquiste sent la soupe chaude dans les élections partielles de Chauveau et Jean-Talon, deux circonscriptions vacantes de la région de Québec.", "\n\nCe n'est pas la première fois qu'un politicien soupçonne le PQ de nuire au retour des Nordiques. ", "Jean Charest l'avait fait lors de la campagne électorale de 2012. ", "À l'époque, M. Legault a qualifié ses commentaires de «désespérés».", "\n\nLe ministre libéral Sam Hamad, responsable de la Capitale nationale, a dit ne pas vouloir nuire aux efforts de Québecor pour ramener le hockey professionnel à Québec, jeudi. ", "Il a toutefois laissé entendre que l'incertitude économique que pourrait entraîner l'élection d'un gouvernement péquiste risque de jouer dans la décision des autorités de la LNH.", "\n\n«Il ne faut pas être naïf», a dit M. Hamad. ", "La condition politique c'est la stabilité et la stabilité, c'est un facteur important pour l'économie.", "\n\nLorsque Pierre Karl Péladeau s'est lancé en politique, en mars 2014, le commissaire adjoint de la LNH, Bill Daly, a affirmé à Sportsnet que les allégeances politiques de l'homme d'affaires n'auraient pas d'impact sur un éventuel processus d'expansion.", "\n\nUn porte-parole de la ligue, Frank Brown, a refusé de commenter la sortie de M. Legault jeudi.", "\n\n«Il n'y a pas de commentaire à faire puisque nous ne sommes pas dans un processus formel d'expansion», a-t-il indiqué dans un courriel." ]

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[ "Linear fluorocarbon polymers have been extensively utilized as binders and wet proofing agents in cell electrodes having finely divided active material. ", "According to a typical electrode forming technique a fluorocarbon polymer may be incorporated in a cell plate by mixing the polymer with a particulate active material to form an aqueous paste. ", "Since fluorocarbons are hydrophobic, this is accomplished by first dispersing the fluorocarbon in an aqueous solution containing a minor amount of a surface active agent, usually less than 5 percent by weight. ", "The surfactant allows the polymer to be uniformly dispersed in the water, so that in the pasty mixture of water, surfactant, active material particles, and polymer, the latter is uniformly distributed. ", "The aqueous paste is spread onto a current collector or other support usually with a doctor blade or by calendering so that the paste is uniformly distributed over the desired active area of the cell plate.", "\nWhile teflonated materials as described above have been found to be adequate, it is found that for electrodes comprised of zinc or cadmium, certain deficiencies are encountered which are alleviated by the binder defined herein." ]

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[ "Talking exclusively to Digital Spy, the Lincoln Burrows star recalled just how close he came to cracking his skull open in the shocking incident.", "\n\n\"I think I was in shock, so the scary factor disappeared,\" he said. \"", "I was running into a prison and there was an explosion above my head.", "\n\n\"The pain I felt wasn't pain like a knife slowly cutting into your arm, it was much more. ", "It's very hard to articulate what kind of pain it was – but I rested down on one knee and I remember thinking, 'What the f**k was that?' ", "And blood was just pouring out.\"", "\n\nView photos\n\nPhoto credit: Getty Images\n\nExplaining that he knew something was wrong at that point, Dominic said his stuntman looked at him \"like he had seen a ghost\".", "\n\n\"I said to him, 'What's going on?' ", "And he wouldn't tell me what the f**k was going on. ", "He eventually said, 'Your skull. ", "It's split. ", "I can see to your skull in two places.'", "\n\n\"And then I saw this shadow to the left of my face and I thought, 'What is going on here?' ", "And it was my nose, which had been smashed to the other side.\"", "\n\nAfter \"going through a very calm state\" because they were working in a remote location, Dominic revealed he \"had a moment of thinking, 'Oh I am probably going to die here'\".", "\n\n\"It was bizarre, but I just assumed that I was going to pass out at any moment,\" he went on. \"", "I thought the skull was cracked, blood was going to leak into my brain and I was going to pass out – and I wasn't going to wake up again.", "\n\n\"But I was very calm and my beautiful girlfriend Anna; she was there to support me. ", "Within five minutes I realised what was going on. ", "I stood up and said, 'Get me to a hospital'.\"", "\n\nView photos\n\nPhoto credit: Fox\n\nDominic explained that after his operation, the plastic surgeon said he was \"a very lucky man\" and \"should have died\".", "\n\n\"Because of my build and playing years of rugby, I have this thick neck, so that held my neck in place when the iron bar fell on me,\" he continued. \"", "The only real injury I have still is whiplash. ", "Apparently, I have extra layers of skin around my skull, so that prevented the bar from actually cracking my skull.", "\n\n\"Within two or three days, I was ready to get back to work. ", "My recovery was extraordinary. ", "Within a couple of weeks, I was fine. ", "Wentworth [Miller] was tremendous support and he was greatly concerned about my health. ", "I was just a very lucky guy.\"", "\n\nAside from his terrifying ordeal, Dominic also revealed he was \"over Prison Break\" by the end of season 4...\n\n\"It had been a long process of shooting 22 episodes a year and my creative juices were spent, so I was ready to go onto a different journey,\" he recalled.", "\n\n\"The fact that we had eight years to think about it, it was a novelty in a way going back and seeing how things were.\"" ]

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[ "The Redskins’ Week 15 win at Jacksonville kept Washington’s playoff hopes alive and pushed back relentless offseason talk for at least a few more days. ", "Regardless, there’s no stopping 2019 free agency and the NFL Draft from occurring. ", "There’s also no denying some clear needs and concerns for the current roster going forward.", "\n\nIn conjunction with my latest 2019 first-round NFL mock draft, here’s a quick look at the primary positional concerns for next season. ", "Have fun quibbling at the order, which likely changes multiple times over the coming weeks. ", "I've changed my mind three times since starting the list.", "\n\n<<SEE THE 2019 NFL MOCK DRAFT 6.0>>\n\n1. ", "Quarterback – Much speculation surrounds Alex Smith’s recovery from his broken right leg including concerns over possible infections from the compound fracture. ", "From the football perspective, his playing career could be in jeopardy. ", "Smith’s hefty contract remains on the books with salary cap hits of $20.4 and $21.4 million over the next two years. ", "That limits Washington’s options since a notable free agent signing or a first round selection makes would put a huge chunk of the team’s asset allocation into one position. ", "But does Colt McCoy and a Day 2 selection sound appealing?", "\n\n2. ", "Inside linebacker – Between Mason Foster’s private messages and Zach Brown seeing the writing on the wall, fair to say that it’s been a rough month for this unit. ", "That the Redskins risked plenty to claim Reuben Foster shows their level of concern at the position. ", "Washington needs a speed upgrade inside.", "\n\n3. ", "Left guard – The Redskins had a need here this past offseason and never addressed it. ", "The problem remains. ", "Don’t expect a Jay Gruden-coached team to select another guard in the first, but fixing this whole is necessary.", "\n\n4. ", "Edge rusher – Preston Smith, another 2019 free agent, only has 3.5 sacks and five tackles for loss. ", "That’s 1.5 sacks more than 2017 second-round pick Ryan Anderson. ", "Even if Smith stays, the Redskins need more production opposite Ryan Kerrigan. ", "Edge rusher might be the odds-on-favorite for their first-round pick considering the need and draft strengths.", "\n\n5. ", "Cornerback – Washington played this season with two true veterans and four players with a combined one year of NFL experience. ", "The top option, Josh Norman, enters the fourth year of his five-year, $75 million contract. ", "He only counts as $6 million in dead cap space, meaning the Redskins could move on if interested.", "\n\n6. ", "Wide receiver – Jamison Crowder enters free agency. ", "Whether the Redskins make retaining the slot threat a priority or not, this group lacks a go-to option.", "\n\n<<SEE THE 2019 NFL MOCK DRAFT 6.0>>\n\nMORE REDSKINS NEWS:" ]

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[ "Q:\n\nМожно ли как то обработать undefined?", "\n\nЕсть скрипт, который на сайте отображает город посетителя в шапке справа вот в таком вот виде. ", "Но бывает так, что иногда скрипт вместо города выдаёт undefined. ", "И собственно вопрос: А можно как-то дописать/переписать скрипт, чтобы если undefined то вместо него показывало например текст: Доставка до вашего места? ", "Помогите пожалуйста это исправить.", "\n<!-- ", "Определение города посетителя -->\n <script src=\"http://code.jquery.com/jquery-1.10.2.min.js\" type=\"text/javascript\"></script>\n <script src=\"https://api-maps.yandex.ru/2.0/?load=package.full&lang=ru-RU\" type=\"text/javascript\"></script>\n <script type=\"text/javascript\">\n $(document).ready(function(){\n ymaps.ready(function(){\n var geolocation = ymaps.geolocation;\n //$('#cou').html('Ваша страна: '+geolocation.country);\n $('#tow').html('Выдача заказов в г. '", "+geolocation.city);\n //$('#reg').html('Ваш регион: '+geolocation.region);\n });\n });\n </script>\n<!-- ", "Определение города посетителя -->\n\n<span id=\"tow\">... определяется ...</span>\n\nA:\n\nМожно, воспользуемся проверкой if else - если условие внутри if (здесь) верно, то выполнятся команды внутри { } после if. ", "А если неверно - то выполнятся команды внутри { } после else. ", "Восклицательный знак является отрицанием, т.е. !", "= можно прочитать как \"не равно\".", "\n....\n\nvar geolocation = ymaps.geolocation;\n\nif (geolocation.city !", "= undefined) { // если не undefined\n\n $('#tow').html('Выдача заказов в г. '", "+geolocation.city); // выводим город\n\n} else { // иначе\n\n $('#tow').html('Доставка до вашего места'); // выводим надпись\n\n}\n\n....\n\n" ]

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[ "Semi-synthetic DNA-protein conjugates: novel tools in analytics and nanobiotechnology.", "\nThis article reports on the syntheses, characterization and applications of semi-synthetic conjugates composed of nucleic acids, proteins and inorganic nanoparticles. ", "For example, self-assembled oligomeric networks consisting of streptavidin and double-stranded DNA are applicable as reagents in immunoassays, model systems for ion-switchable nanoparticle networks as well as nanometer-scaled 'soft material' standards for scanning probe microscopy. ", "Covalent conjugates of single-stranded DNA and streptavidin are utilized as biomolecular adapters for the immobilization of biotinylated macromolecules at solid substrates via nucleic acid hybridization. ", "This 'DNA-directed immobilization' allows for reversible and site-selective functionalization of solid substrates with metal and semiconductor nanoparticles or, vice versa, for the DNA-directed functionalization of gold nanoparticles with proteins, such as immunoglobulins and enzymes. ", "This approach is applicable for the detection of chip-immobilized antigens. ", "Moreover, covalent DNA-protein conjugates allow for their selective positioning along single-stranded nucleic acids, and thus for the construction of nanometre-scale assemblies composed of proteins and/or nanoclusters. ", "Examples include the fabrication of functional biometallic nanostructures from gold nanoparticles and antibodies, applicable as diagnostic tools in bioanalytics." ]

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[ "Facing off\n\nThis piece represents the opinion of The Bowdoin Orient editorial board.", "\n\nFebruary 3, 2012\n\nThe students behind Mass Deactivation presented a challenge to the Bowdoin community this week, urging students to deactivate their Facebook accounts for exactly one month starting on February 8. ", "The premise of the experiment is to re-experience what life would be like without the social network, and creators Tyler Patton '12 and Ruiqi Tang '13 think that Bowdoin—as close-knit as it is tech-saturated—is the perfect environment in which to do so. ", "And they're right.", "\n\nThere could not be a better time to participate in this experiment. ", "Facebook just filed a $5 billion IPO to become a publicly traded company, which means that starting this spring it will be beholden to shareholders, and must find ways to increase profitability by selling even more user information to advertisers and other third parties. ", "With change afoot, perhaps we should examine just how much of our private information we really want to be converted into currency.", "\n\nWe are also the last generation of college students that will remember what it was to socialize without Facebook. ", "Our lives were probably not any simpler without Facebook, but they were certainly less plugged-in. ", "We had to go to greater lengths to meet people and to keep in touch with friends and family. ", "Perhaps we took more active roles in building personal relationships before we had a mini-feed to tell us what our friends were doing.", "\n\nThe most compelling aspect of this experiment is its call for collective action. ", "As the site points out, deactivating a Facebook account does not completely disconnect you from the online world. ", "You will inevitably still be surrounded by people posting photos, liking statuses, and creating events. ", "And as Facebook reminds users who attempt to deactivate, your friends might miss you when you're gone. ", "As such, this experiment \"could literally be the last time for the rest of your life that you and the people around you exist without Facebook.\" ", "What would it be like to attend a party no one will see photos of the next day? ", "Or to approach someone at that party without having done some reconnaissance on their profiles first?", "\n\nTo achieve the mass participation that will make this experiment meaningful, its creators must extend their advertising campaign such that it reaches more people. ", "They must push beyond those who already harbor misgivings about Facebook and attempt to attract heavy users who might notice the greatest difference in their lives without an account. ", "While the cryptic flyers simply reading \"massdeactivation.blogspot.com\" are intriguing, they do not explain the very exciting nature of the project. ", "It would be unfortunate to lose potential participants just because they forget to look up the mysterious URL upon returning to their dorm rooms.", "\n\nAdditionally, we urge the creators to survey participants at the end of the experiment and to make the results public. ", "Did people find that Facebook enriches or compromises their social lives? ", "Did they feel more or less lonely, bored or connected to people when they did not have an account? ", "Collecting and distributing this information will be thought-provoking for those who participate in the experiment, as well as for those who choose not to join, and may even prompt similar experiments elsewhere. ", "Facebook does not make the path to deactivation obvious, but we believe it is worth following, if only for a month." ]

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[ "<?", "php\n\nnamespace Runalyze\\Tests\\Parser\\Activity\\FileType;\n\nuse Runalyze\\Parser\\Activity\\Common\\Data\\ActivityDataContainer;\nuse Runalyze\\Parser\\Activity\\Common\\Filter\\DefaultFilterCollection;\nuse Runalyze\\Parser\\Activity\\Common\\ParserInterface;\nuse Runalyze\\Parser\\Common\\FileContentAwareParserInterface;\nuse Runalyze\\Parser\\Common\\FileTypeConverterInterface;\n\nabstract class AbstractActivityParserTestCase extends \\PHPUnit_Framework_TestCase\n{\n /** @var null|ActivityDataContainer|ActivityDataContainer[] */\n protected $Container;\n\n /** @var int */\n protected $NumberOfActivities = 0;\n\n /** @var string[] */\n protected $FilesToClear = [];\n\n protected function tearDown()\n {\n foreach ($this->FilesToClear as $file) {\n if (file_exists($file)) {\n unlink($file);\n }\n }\n }\n\n /**\n * @return string\n */\n protected function pathToTestFiles()\n {\n return TESTS_ROOT.'/testfiles/';\n }\n\n /**\n * @param FileTypeConverterInterface $converter\n * @param FileContentAwareParserInterface $parser\n * @param string $file file path relative to 'testfiles/'\n * @param string[] $expectedOutputFiles\n * @param bool $completeAfterwards\n */\n protected function convertAndParseFile(FileTypeConverterInterface $converter, FileContentAwareParserInterface $parser, $file, array $expectedOutputFiles, $completeAfterwards = true)\n {\n $outputFile = $converter->convertFile($this->pathToTestFiles().$file);\n\n if (!", "is_array($outputFile)) {\n $outputFile = [$outputFile];\n }\n\n $this->FilesToClear = $outputFile;\n $path = $this->pathToTestFiles();\n $outputFile = array_map(function ($file) use ($path) {\n return str_replace($path, '', $file);\n }, $outputFile);\n\n $this->assertEquals($expectedOutputFiles, $outputFile);\n\n $this->parseFiles($parser, $outputFile, $completeAfterwards);\n }\n\n protected function parseFiles(FileContentAwareParserInterface $parser, array $files, $completeAfterwards = true)\n {\n $tmpContainer = [];\n\n foreach ($files as $currentFile) {\n $this->parseFile($parser, $currentFile, $completeAfterwards);\n\n if (!", "is_array($this->Container)) {\n $tmpContainer[] = $this->Container;\n } else {\n $tmpContainer = $tmpContainer + $this->Container;\n }\n }\n\n $this->NumberOfActivities = count($tmpContainer);\n $this->Container = 1 == $this->NumberOfActivities ? ", "$tmpContainer[0] : $tmpContainer;\n }\n\n /**\n * @param FileContentAwareParserInterface $parser\n * @param string $file file path relative to 'testfiles/'\n * @param bool $completeAfterwards\n */\n protected function parseFile(FileContentAwareParserInterface $parser, $file, $completeAfterwards = true)\n {\n $this->parseFileContent($parser, file_get_contents($this->pathToTestFiles().$file), $completeAfterwards);\n }\n\n /**\n * @param FileContentAwareParserInterface $parser\n * @param string $fileContent\n * @param bool $completeAfterwards\n */\n protected function parseFileContent(FileContentAwareParserInterface $parser, $fileContent, $completeAfterwards = true)\n {\n $parser->setFileContent($fileContent);\n $parser->parse();\n\n $this->setContainerFrom($parser, $completeAfterwards);\n }\n\n /**\n * @param ParserInterface $parser\n * @param bool $completeAfterwards\n * @param bool $runFilter\n */\n protected function setContainerFrom(ParserInterface $parser, $completeAfterwards = true, $runFilter = true)\n {\n $filterCollection = new DefaultFilterCollection();\n $this->NumberOfActivities = $parser->getNumberOfActivities();\n $this->Container = [];\n\n for ($i = 0; $i < $this->NumberOfActivities; ++$i) {\n $this->Container[] = $parser->getActivityDataContainer($i);\n\n if ($completeAfterwards) {\n $this->Container[$i]->completeContinuousData();\n }\n\n if ($runFilter) {\n $this->Container[$i]->filterActivityData($filterCollection);\n }\n\n if ($completeAfterwards) {\n $this->Container[$i]->completeActivityData();\n }\n }\n\n if (1 == $this->NumberOfActivities) {\n $this->Container = $this->Container[0];\n }\n }\n\n /**\n * @param array $expectedRounds [[duration [s], distance [km]], ...]\n * @param int $deltaDuration [s]\n * @param float $deltaDistance [km]\n */\n protected function checkExpectedRoundData(array $expectedRounds, $deltaDuration = 0, $deltaDistance = 0.0)\n {\n $this->checkExpectedRoundDataFor($this->Container, $expectedRounds, $deltaDuration, $deltaDistance);\n }\n\n /**\n * @param ActivityDataContainer $container\n * @param array $expectedRounds [[duration [s], distance [km]], ...]\n * @param int $deltaDuration [s]\n * @param float $deltaDistance [km]\n */\n protected function checkExpectedRoundDataFor(ActivityDataContainer $container, array $expectedRounds, $deltaDuration = 0, $deltaDistance = 0.0)\n {\n $this->assertEquals(count($expectedRounds), $container->Rounds->count());\n\n foreach ($expectedRounds as $i => $expectedRoundData) {\n $this->assertEquals($expectedRoundData[0], $container->Rounds[$i]->getDuration(), 'Round #'.$i.' ", "has wrong duration.', ", "$deltaDuration);\n $this->assertEquals($expectedRoundData[1], $container->Rounds[$i]->getDistance(), 'Round #'.$i.' ", "has wrong distance.', ", "$deltaDistance);\n }\n }\n\n /**\n * @param array $expectedPauses [[time index [s], duration [km](, hr start [bpm], hr end [bpm])], ...]\n * @param int $deltaDuration [s]\n */\n protected function checkExpectedPauseData(array $expectedPauses, $deltaDuration = 0)\n {\n $this->assertEquals(count($expectedPauses), $this->Container->Pauses->count());\n\n foreach ($expectedPauses as $i => $expectedPauseData) {\n $this->assertEquals($expectedPauseData[0], $this->Container->Pauses[$i]->getTimeIndex(), 'Pause #'.$i.' ", "has wrong time index.', ", "$deltaDuration);\n $this->assertEquals($expectedPauseData[1], $this->Container->Pauses[$i]->getDuration(), 'Pause #'.$i.' ", "has wrong duration.', ", "$deltaDuration);\n\n if (isset($expectedPauseData[2]) && isset($expectedPauseData[3])) {\n $this->assertEquals($expectedPauseData[2], $this->Container->Pauses[$i]->getHeartRateAtStart(), 'Pause #'.$i.' ", "has wrong heart rate at start.');", "\n $this->assertEquals($expectedPauseData[3], $this->Container->Pauses[$i]->getHeartRateAtEnd(), 'Pause #'.$i.' ", "has wrong heart rate at end.');", "\n }\n }\n }\n}\n" ]

{ "pile_set_name": "Github" }

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[ "---\nabstract: |\n We present a physical model to explain the behavior of long-term, time series measurements of chloride, a natural passive tracer, in rainfall and runoff in catchments \\[[*Kirchner et al.*]{}, [*", "Nature, 403*]{}(524), 2000\\]. ", "A spectral analysis of the data shows the chloride concentrations in rainfall to have a white noise spectrum, while in streamflow, the spectrum exhibits a fractal $1/f$ scaling. ", "The empirically derived distribution of tracer travel times $h(t)$ follows a power-law, indicating low-level contaminant delivery to streams for a very long time. ", "Our transport model is based on a continuous time random walk (CTRW) with an event time distribution governed by $\\psi(t)\\sim\n A_{\\beta}t^{-1-\\beta}$. The CTRW using this power-law $\\psi(t)$ (with $0<\\beta<1$) is interchangeable with the time-fractional advection-dispersion equation (FADE) and has accounted for the universal phenomenon of anomalous transport in a broad range of disordered and complex systems. ", "In the current application, the events can be realized as transit times on portions of the catchment network. ", "The travel time distribution is the first passage time distribution $F(t; l)$ at a distance $l$ from a pulse input (at $t=0$) at the origin. ", "We show that the empirical $h(t)$ is the catchment areal composite of $F(t; l)$ and that the fractal $1/f$ spectral response found in many catchments is an example of the larger class of transport phenomena cited above. ", "The physical basis of $\\psi(t)$, which determines $F(t; l)$, is the origin of the extremely long chemical retention times in catchments.", "\nauthor:\n- 'H. Scher'\n- 'G. Margolin'\n- 'R. Metzler'\n- 'J. Klafter'\n- 'B. Berkowitz'\ntitle: 'The dynamical foundation of fractal stream chemistry: The origin of extremely long retention times'\n---\n\nIntroduction\n============\n\nThe distribution of travel times required for chemical substances to travel through a catchment is an important hydraulic quantity, determining the retention of pollutants until they are eventually released to a stream or lake. ", "The same distribution controls the transport of chemicals in subsurface hydrological systems. ", "The nature of this distribution determines the expected ecological impact of contaminants.", "\n\nIn a long-term catchment study conducted at Plynlimon, Wales, [*Kirchner et al.*]{} ", "\\[2000\\] (hereafter denoted KFN) compare the (input) time series of the concentration $c_R(t)$ of chloride tracer in the rainfall to the (output) time series of the concentration $c_s(t)$ into the Hafren stream. ", "They relate the concentrations through the convolution integral $$\\label{conv}\nc_s(t)={\\textstyle\\int_0^\\infty}h(t')c_R(t-t')dt'$$ where the effective travel time distribution $h(t)$ governs the lag time between injection of the tracer through rainfall and outflow to the stream.", "\n\nKFN observe that the streamflow (volume of water) responds rapidly to storm rainfall inputs while the $c_s(t)$ response is highly damped (i.e., low-level contaminant delivery to streams for a very long time). ", "The timescales of catchment hydrologic and chemical response are resolved using spectral methods [@duffy] (in which the input/output response can be compared at each (time) wavelength). ", "The spectral power of the water fluxes of rainfall and streamflow coincide while the spectra of $c_s(t)$ show strong attenuation on all wavelengths less than 5-10 years. ", "Further, the $c_R(t)$ spectra scale as white noise in sharp contrast to the fractal $1/f$ scaling of the $c_s(t)$ spectra. ", "Using these results in the Fourier transform of the convolution in (\\[conv\\]), with $f$ denoting frequency, and $C_s$, $H$ and $C_R$ representing the respective Fourier transforms, $$\\label{amp}\nC_s(f)=H(f)C_R(f)$$ and the relation of the power spectra is $$\\label{power}\n|C_s(f)|^2=|H(f)|^2|C_R(f)|^2$$ Since $|C_R(f)|^2$ is nearly a white noise spectrum (a constant) one has $|H(f)|^2 \\propto |C_s(f)|^2$. From the measured power-law scaling of $|C_s(f)|^2\n\\propto f^{-0.97}$, KFN conclude that $$\\label{htail}\nh(t) \\sim t^{-m}$$ (from $H(f)\\sim f^{-(1-m)}$), where $m \\approx 0.5$.\n\nIn order to ensure that $h(t)$ is integrable and possesses a finite average travel time, KFN arbitrarily chose the gamma distribution $$\\label{tddk}\nh(t)=\\frac{t^{\\gamma-1}}{\\varrho^{\\gamma}\\Gamma(\\gamma)}\ne^{-t/\\varrho}$$ with $\\gamma=0.48$ and $\\varrho=1.9$ years, with a characteristic travel time $T_h \\equiv\\int_0^{\\infty}h(t)t dt=\\gamma\\varrho$. Due to the relatively large value of $\\varrho$, essentially the entire data correspond to the power-law $h(t)\\sim t^{\\gamma-1}$ with the power spectrum $|C_s(f)|^2 \\propto|H(f)|^2\\sim f^{-2\\gamma}$. KFN refer to similar scaling between $f^{-0.7}$ and $f^{-1.2}$ found in Scandinavian and North American field sites, which indicates a certain ubiquity to fractal, scale-free forms (which is the issue we address in this letter).", "\n\nTransport models\n================\n\nThe first step to understanding transport in the catchment is the clarification of the meaning of (\\[conv\\]). ", "The $h(t)$ is the [*effective*]{} response to a pulse of rain falling on the entire area of the catchment. ", "Every point of this area is a source of chloride and the stream is a line sink for the chloride. ", "We simplify the area to be a rectangle of width $\\lambda$ about this stream sink (with periodic boundary conditions on the sides perpendicular to the stream[@ctrw]). ", "The sink or absorbing boundary ensures the correct “counting rate\" of chloride at the arriving point, i.e., the first passage time distribution $F(t;l)$ is the appropriate travel time distribution from a pulse source at point $l$. In terms of this [*intrinsic*]{} distribution, $$\\label{eq:gen}\nc_{s}(t;l_s) = \\int_0^\\infty \\sum_{l\\in \\Omega}F(t';l-l_s) c_{R}\n(t-t';l)dt'$$ where $c_{s}(t;l_s)$ is the chloride concentration at the stream position $l_s$ at time $t$, $\\Omega$ is the size of the catchment and $c_{R}(t;l)$ the rain-input at a position $l$ in $\\Omega$. We can consider the sampling positions $\\{l_s \\}$ of $c_{s}$ to be a small region compared to $\\Omega$ and hence $c_{s}(t;l_s) \\approx\nc_{s}(t)$. To do the $l$-sum we assume that the rainfall is distributed uniformly in $\\Omega$, $c_{R}(t;l) \\approx\nc_{R}(t)$. Hence, we recover (\\[conv\\]) now with $$\\label{eff}\nh(t) \\equiv \\sum_{l\\in \\Omega}F(t;l)$$ The distribution $F(t;l)$ must be integrable in time and thus so $h(t)$ for a finite $\\Omega$. The basis of comparison for various transport approaches is the computation in (\\[eff\\]).", "\n\nAdvection-dispersion equation (ADE)\n-----------------------------------\n\nThe textbook approach to transport of passive tracers in both surface and subsurface systems usually focuses on the advection-dispersion equation (ADE) $$\\label{dae}\n\\partial {\\cal W}/\\partial t+v\\partial {\\cal W}/\\partial x=D\\partial^2 {\\cal\nW}/\\partial x^2$$ e.g., for 1d with constant $v$ the average fluid velocity and $D$ the dispersion coefficient. ", "This equation governs the temporal evolution of the probability density function (pdf) ${\\cal W}(x,t)$ of finding a tracer particle, which undergoes dispersive motion, at a certain position $x$ at time $t$ after release at $t=0$. The pdf ${\\cal W}$ is the normalized concentration profile.", "\n\nThe travel time distribution belonging to (\\[dae\\]) can be obtained by the Laplace Transform ($LT$) technique. ", "This yields the $LT$ $\\tilde{{\\cal F}}(u;x)\\equiv\\int_0^{\\infty}{\\cal F}(t;x)e^{-ut}dt$ of the first passage time from $x$ to the absorbing boundary at $x=0$, $\\tilde{{\\cal F}}(u;x)=\n\\exp\\left(x\\left[v-\\sqrt{4Du+v^2}\\right]/(2D)\\right)$. $LT$ inversion delivers the travel time distribution \\[gauss\\] [F]{}(t;x) = () which when inserted for $F(t;x)$ in (\\[eff\\]) yields $$\\begin{aligned}\n\\label{int}\nh(t) \\! \\! \\! \\! &", "\\propto& \\! \\! \\! \\! ", "\\int_0^\\lambda {\\cal F}(t;x)dx =\\frac\n{v}{2}\\bigl[{\\rm erf}(z) +{\\rm erf}\\left(\\frac {P_e}{4z}-z \\right) \n\\nonumber \\\\&+&\n\\! \\! \\! \\! ", "\\frac {\\exp(-z^2)-\\exp\\left(-(\\frac\n{P_e}{4z}-z)^{2}\\right)}{\\sqrt{\\pi}z}\\bigr]\\end{aligned}$$ where the Peclet number $P_e\\equiv \\lambda v/D$, $z \\equiv \\frac {1}{2}\\sqrt{v^{2}t/D}$ and erf$(z)$ is the error function (the same result (\\[int\\]) was also derived in [*Kirchner et al.*]{}, ", "2001). ", "For $t<0.1 D/v^2$, $h(t)\\sim t^{-\\frac{1}{2}}$ which is similar to (\\[htail\\]) for $m\n\\approx 0.5$. \\[This upper limit on the time range holds for $P_e\\ge1$; for $P_e<1$ the limit is smaller.\\] The range is estimated by assuming $D$ to be the macrodispersion, $D=v\\alpha$, where $\\alpha$ is the dispersivity. ", "Assuming $v\\approx 10^2$ m/yr and on the km scale $\\alpha \\sim (1-10^2)$ m, $t<0.1\\alpha/v \\sim (10^{-3}-10^{-1})$ yr. ", "One needs $v\\approx 10$ m/yr and $\\alpha\n\\sim 10^2$ m in (\\[int\\]), for $h(t) \\sim t^{-\\frac{1}{2}}$ to partially overlap the time range of observation of this dependence [@kirchner]. ", "Moreover, this behavior is only the same as (\\[htail\\]) in the special case where $m$ (or $\\gamma$) = $\\frac {1}{2}$. The catchment data (spectral power $\\sim \nf^{-2\\gamma}$) quoted above cover a range of $0.7\\leq 2\\gamma\\leq 1.2$.\n\nFor large $t$, $h(t)$ in (\\[int\\]) exhibits an exponential decrease $\\sim t^{-\\frac{3}{2}}$ $\\exp\\left(-v^2(4D)^{-1}t\\right)$ which is faster than (\\[tddk\\]). ", "The decrease in $h(t)$ at large $t$ ($t>>\\lambda/v$) is due to the finite size of the catchment and not an arbitrary limiting time. ", "The relation between the operative time range of (\\[htail\\]) and $\\lambda$ will be determined in the following.", "\n\nContinuous-time random walk and time-fractional-ADE\n---------------------------------------------------\n\nAs shown above the standard treatment of the transport using the ADE yields a marginal accounting of the data. ", "A transport model must determine a $F(t;l)$ that when inserted in (\\[eff\\]) gives rise to (\\[htail\\]) for over three decades of time [@kirchner]. ", "As we will show this is best expedited with a non-Gaussian form of $F(t;l)$. A particularly dispersive form of $F(t;l)$ is associated with anomalous transport which has been observed in a wide range of disordered and complex systems: electron hopping/multiple-trapping in amorphous semiconductors [@ctrw], particle migration in fracture networks [@till], contaminant transport in heterogeneous porous media [@bescher], anomalous diffusion[@report], and Hamiltonian chaos[@pt]. ", "There are key common features in these anomalous transport phenomena, e.g., non-Gaussian propagation of an initial pulse of particles with a mean position $\\ell(t)$ and standard deviation $\\sigma(t)$ exhibiting the same sublinear dependence on $t$ (in the presence of a bias or head). ", "A continuous time random walk (CTRW) transport process has successfully accounted for these unusual basic features. ", "The anomalous behavior is an outcome of a CTRW governed by a long-tail distribution of the individual transition times or event times (which have to be defined in each physical context, e.g., trap release), $$\\label{psi}\n\\psi(t)\\sim A_{\\beta}t^{-1-\\beta}$$ where $A_{\\beta}$ is a constant. ", "Over the observation time range in which (\\[psi\\]) obtains we have for the propagating plume $P(l,t)$ $$\\ell (t) \\sim t^\\beta, \\qquad\\sigma(t) \\sim t^\\beta\\qquad0<\\beta<1$$ The highly dispersive nature of this $P(l,t)$ can be discerned by the ratio $\\sigma(t)/\\ell (t)\\sim$ constant, instead of the familiar $1/\\sqrt{t}$ for a Gaussian plume. ", "The latter is produced for $\\beta>2$ (while for $1<\\beta<2$ one has an intermediate $t$-dependence).", "\n\nThe CTRW accounts naturally for the cumulative effects of a sequence of transitions which constitutes the particle transport. ", "The formalism of the CTRW has been well documented in the literature \\[[*Berkowitz and Scher*]{}, 1998; [*Metzler and Klafter*]{}, 2000\\]. ", "For brevity we show the key equation for our purpose here in Laplace space (for three dimensions) $$\\label{1stP}\n\\tilde{F}({\\bf s},u)=\\tilde{P}({\\bf s},u)/\\tilde{P}(0,u) \\qquad\n\\qquad {\\bf s} \\ne 0$$ where the particle starts at the origin at $t=0^+$, $\\tilde{P}({\\bf\ns},u)$ is the $LT$ of $P({\\bf s},t)$, the probability density to find the particle on ${\\bf s}$ at time $t$ (plume), and $\\tilde{F}({\\bf s},u)$ is the $LT$ of $F({\\bf s},t)$, the probability per time for the particle to first arrive at ${\\bf s}$ at time $t$.\n\nExplicit evaluations for $\\tilde{F}({\\bf s},u)$ have been determined for symmetric situations (e.g., plane (line) source to plane (line) sink) and with the use of (\\[psi\\]) [@ctrw]. ", "The symmetric cases allow a reduction of the problem to a one-dimensional form of $F$ which we write as $F(t; x)$ and $$\\label{ltF}\n\\tilde{F}(u;x)=\\exp(-xu^{\\beta}/\\bar{l}) \\qquad(0<\\beta<1)$$ ($u$ dimensionless). ", "The inverse $LT$ of $\\tilde{F}(u;x)$ has been expressed in terms of a class of Fox $H$-functions [@report], but it is more expedient to work directly with (\\[ltF\\]) in the evaluation of $h(t)$, which will be considered in the next section.", "\n\nMathematically, the CTRW (in the special case using (\\[psi\\]) and $(0<\\beta<1)$) is interchangeable with the time-fractional advection-dispersion equation (FADE) [@report] $$\\label{fda}\n\\frac{\\partial W}{\\partial t}=\\, _0D_t^{1-\\beta}\\left(-v_{\\beta}\n\\frac{\\partial}{\\partial x}+d_{\\beta}\\frac{\\partial^2}{\\partial x^2}\n\\right)W(x,t)$$ where the Riemann-Liouville operator is defined in terms of the convolution [@report], $$\\label{rl}\n_0D_t^{1-\\beta}W(x,t)=\\frac{1}{\\Gamma(\\beta)}\\frac{d}{dt}\\int_0^tdt'\n\\frac{W(x,t')}{(t-t')^{1-\\beta}},\\, 0<\\beta<1.$$ The form of FADE (\\[fda\\]) is the natural generalization of the ADE (\\[dae\\]) for power-law forms of $\\psi$. The solutions of FADE reproduce those of the CTRW in this special case, and in the spatial continuum limit they form a natural bridge between the CTRW and the ADE [@tipm].", "\n\nLong Retention Times\n====================\n\nWe proceed to insert (\\[ltF\\]) into the $LT$ of (\\[eff\\]) to obtain $$\\label{eq:lth}\n\\tilde{h}(u) \\propto \\int_0^\\lambda\n\\exp(-lu^{\\beta}/\\bar{l})dl=\\bar{l}u^{-\\beta}(1-\\exp(-\\lambda\nu^{\\beta}/\\bar{l}))$$ where $\\bar{l}$ is the mean step distance. ", "The expression for $\\tilde{h}(u)$ in (\\[eq:lth\\]) has been thoroughly studied in another context [@ctrw]; the main features are $$h(\\tau)\\sim\\left\\{\\begin{array}{ll}\n\\tau^{\\beta-1}, & \\tau<\\tau^*\\\\\n\\tau^{-\\beta-1}, & \\tau>\\tau^*\n\\end{array}\\right.", "\n\\label{scaling}$$ ($\\tau$ dimensionless time). ", "The exponent for $\\tau>\\tau^*$ ensures that $h(\\tau)$ is integrable. ", "On a log-log plot $h(\\tau)$ is two constant slopes, $\\beta-1$, $-1-\\beta$, with a turnover range between them. ", "The center time of this range, $\\tau^*$, can be estimated as the time for the argument of the exponent in (\\[eq:lth\\]) to be $\\sim\nO(1)$ (using $u \\sim 1/\\tau$) $$\\label{tau}\n\\tau^{*} \\sim (\\frac {1-\\beta}{\\beta})^{\\frac {1-\\beta}{\\beta}}(\\beta\n\\lambda/\\bar{l})^{\\frac {1}{\\beta}}$$ (The $\\beta$-factors derive from a more detailed analysis \\[[*Scher and Montroll*]{}, 1975, Appendix C\\].) ", "For $\\beta =\\frac{1}{2}$, in (\\[eq:lth\\]) one can do the inverse $LT$ and obtain $h(\\tau) \\sim (\\pi\n\\tau)^{-\\frac{1}{2}}(1-\\exp(-\\lambda^2 /4\n\\bar{l}^2 \\tau))$, clearly showing (\\[scaling\\])-(\\[tau\\]).", "\n\nThe change from $\\tau$ to $t$ is model dependent (to be discussed below). ", "We use $\\tau = v_ot/\\bar{l}\\varepsilon$, where $v_o$ is a characteristic velocity (of the velocity distribution) and $\\varepsilon$ is a constant. ", "For $\\beta = \\frac{1}{2}$, $v_o \\sim$ 100 m/yr, $\\lambda \\sim \\frac{1}{2}$ km, $\\bar{l} \\sim$ 30 m and $\\varepsilon \\sim \\frac{1}{2}$, one has (from (\\[tau\\]) with $\\tau^* = v_ot^*/\\bar{l}\\varepsilon$), $t^* \\sim$ 10 yr, which is a reasonable time scale for the change from $h(t) \\sim t^{\\beta-1}$. Hence, our scaling result (\\[scaling\\]) agrees with the KFN data (\\[htail\\]) over the measurement time range ($>$ 3 decades for t$\\le$ 10 yrs) with $\\beta=\\gamma$ ($\\equiv 1-m$). ", "The $t$-“cutoff\" for $h(t)$ in (\\[scaling\\]) is algebraic, $t^{-\\beta-1}$, not exponential as in (\\[tddk\\])! ", "This behavior of $h(t)$ is indicative of extremely long chemical retention times in catchments. ", "The turnover to the $t^{-\\beta-1}$ dependence (in (\\[scaling\\])) is a prediction of the CTRW theory and has not yet been observed. ", "A finite value of $T_h$ depends on a change in the behavior of (\\[psi\\]). ", "For $t\n\\gg t^*$, the tail of $\\psi(t)$ becomes steeper and for $\\beta>2$, the [*intrinsic*]{} arrival time distribution evolves to ${\\cal F}(t;x)$.\n\nIndependent tests of our transport model can be obtained with experiments using a different tracer (d) and boundary conditions. ", "For injection of the tracer d at various catchment points $\\{ {\\bf x}\n\\}$, the concentration in the stream $c_{d}(t;{\\bf l_s})$ is proportional to $F({\\bf\nx}-{\\bf l_s},t)$, determined for these boundary conditions. ", "\\[This result answers the question raised by [*Stark and Stieglitz*]{} \\[2000\\] about a site-specific spill.\\] This is also a method for obtaining a value of $\\beta$, which determines the shape of $F({\\bf x},t)$.\n\nThere are many different physical mechanisms (cf. ", "Refs. ", "above) that can give rise to the $\\psi(t)$ in (\\[psi\\]) that has generated our results for $h(t)$. The common features are the representation of the transport process as a series of transitions \\[[*Berkowitz and Scher*]{}, 1998, 2001\\] and the encounter within this series of a sufficient number of transition-times that are much larger than the median one. ", "These relatively few long-time events, which can be due to release from traps/stagnant-regions and/or passage through low velocity segments, can have a dominant influence on the overall transport. ", "The relative weighting of these events is expressed by the exponent of the power-law in (\\[psi\\]).", "\n\nThe hydrologic environments beneath the catchment subregions can contain a sufficient number of these low velocity sections and stagnant dead-ends. ", "The local slope (and interconnection [@rinaldo]) of the catchment side-channels also affects the velocity distribution. ", "The subsurface of the catchment basin can be modeled as a heterogeneous porous medium and/or a random fracture network [@bescher]. ", "In the latter the fragment-length distribution, $f(s)$, and the fragment-velocity histogram, $\\Phi({\\bf \\xi})$, are mapped onto the probability rate for a transit time t (through a fragment) with a displacement [**s**]{}, ([**s**]{},t) ([****]{})f(s) where $|{\\bf \\xi}|=1/v$, $\\hat{\\bf \\xi}=\\hat{\\bf v}$, $t=s\\xi$ and $\\psi (t) \\equiv \\sum_s \\psi ({\\bf s},t)$. The anomalous transport observed in the fracture network particle tracking simulations is due to the power-law tail of $\\Phi({\\bf \\xi}) \\rightarrow \\xi^{-1-\\beta}$ at large $\\xi$. This is the expected behavior to be found in the catchment subsurface $\\Phi_c({\\bf \\xi})$ distribution because this hydrologic environment is the same as ones modeled successfully by the CTRW theory \\[[*Berkowitz and Scher*]{}, 1998, 2001\\]. ", "The experiments outlined above can test these properties.", "\n\nConclusion\n==========\n\nIn this letter we introduce the phenomenon of anomalous transport into an analysis of the comparison of the power spectra of the time series of chloride in rainfall and in (stream) runoff. ", "An [*effective*]{} distribution of travel times $h(t)$ is derived (by KFN from the data) which we show is composed of the summation from all sites of the source distribution $F({\\bf s},t)$ in the catchment. ", "The latter, in turn, is composed of a sequence of transitions governed by a power-law (tail) distribution (\\[psi\\]). ", "The results agree naturally with the data reported from a number of catchment studies, in the sense of a power-law scaling of $h(t)$ over decades of $t$ in the observational time range (using reasonable parameters). ", "A consequence of our transport model is a power-law “cutoff” of $h(t)$ predicting extremely long chemical retention times with subsequent impact on the long-term effects of contaminants on these ecosystems.", "\n\nWe thank James W. Kirchner and Colin Stark for a critical reading of the manuscript. ", "RM acknowledges the DFG and the European Commission within the Emmy Noether and SISITOMAS programmes, and BB acknowledges the European Commission (Contract EVK1-CT-2000-00062), for financial support.", "\n\nBerkowitz, B., and H. Scher, Theory of anomalous chemical transport in fracture networks, [*Phys. ", "Rev. E*]{}, [*57*]{}(5), 5858-5869, 1998.", "\n\nBerkowitz, B., and H. Scher, The role of probabilistic approaches to transport theory in heterogeneous media, [*Transp. ", "Porous Media*]{}, [*42*]{}(1-2), 241-263, 2001.", "\n\nDuffy, C. J., and L. W. Gelhar, A frequency domain approach to water quality modeling in groundwater: Theory, [*Wat. ", "Resour. ", "Res.*]{}, [*", "21*]{}(8), 1175-1184, 1985.", "\n\nKirchner, J. W., X. Feng and C. Neal, Fractal stream chemistry and its implications for contaminant transport in catchments, [*Nature, 403*]{}, 524-527, 2000.", "\n\nKirchner, J. W., X. Feng and C. Neal, Catchment-scale advection and dispersion as a mechanism for fractal scaling in stream tracer concentrations, [*J. Hydrol., ", "254*]{}, 82-101, 2001.", "\n\nKlafter, J., M. F. Shlesinger, and G. Zumofen, Beyond Brownian motion, [*Phys. ", "Today, 49*]{}(2), 33-39, 1996.", "\n\nKosakowski, G., B. Berkowitz and H. Scher, Analysis of field observations of tracer transport in a fractured till, [*J. Contam. ", "Hydrol.*]{}, [*", "47*]{}, 29-51, 2001.", "\n\nMetzler, R., and J. Klafter, The random walk’s guide to anomalous diffusion: A fractional dynamics approach, [*Phys. ", "Rep.*]{}, [*339*]{}(1), 1-77, 2000 (and refs. ", "therein).", "\n\nRodriguez-Iturbe, I., and A. Rinaldo, [*Fractal River Basins: Chance and Self-Organization*]{}, Cambridge Univ. ", "Press, New York, 1997.", "\n\nScher, H., and E. W. Montroll, Anomalous transit-time dispersion in amorphous solids, [*Phys. ", "Rev. B*]{}, [*12*]{}(6), 2455-2477, 1975.", "\n\nStark, C. P., and M. Stieglitz, The sting in a fractal tail, [*Nature*]{}, [*403*]{}, 493-495, 2000.", "\n" ]

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[ "[Undifferentiated pleomorphic sarcoma detected in the descending colon: report of a case].", "\nUndifferentiated pleomorphic sarcoma was a well-known tumor that usually involves the soft tissues. ", "However, in the alimentary tract, it was seldom reported. ", "A 55-year-old man was admitted to our hospital with lower abdominal pain. ", "Endoscopic examination showed a protruding tumor occupied the lumen of the descending colon. ", "Because of the colon obstruction by the tumor, a left hemicolectomy with en bloc lymph node dissection was performed. ", "Main occupied lesion of the tumor was mesenterium and submucosa, with no epithelial dysplasia. ", "Also, dissemination of the tumor was recognized in the mesenterium and greater omentum. ", "Based on histological and immunohistological studies, the tumor was diagnosed as undifferentiated pleomorphic sarcoma." ]

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[ "Both shortening and its classier cousin, margarine, took off for obvious reasons—who wouldn’t want a butter substitute that was cheaper, lasted longer, and came with free cookbooks? (", "All the recipes called for Crisco, of course.)", "\n\nSensing competition, dairy farmers convinced several states to stop allowing the more appetizing-looking, yellow-colored margarine in the early 20th century, but the bans were largely repealed by the late 1950s, and the golden-hued spread once again became the norm.", "\n\nA 1961 Time magazine article railed against the dangers of saturated fat (the kind found in butter and lard), and eventually some consumers began to view margarine and shortening as healthier alternatives.", "\n\nOddly, some health groups also trumpeted hydrogenated oil's benefits.", "\n\nIn the 1980s, some scientists began to associate heart disease with saturated fats, and in response, groups such as the Center for Science in the Public Interest and the National Heart Savers Association (NHSA) began to hound manufacturers for “poisoning America ... by using saturated fats,” and as a result “nearly all targeted firms responded by replacing saturated fats with trans fats,” as David Schleifer wrote in 2012 for the journal Technology and Culture.", "\n\nAt the time, many restaurants used beef fat for frying, which groups like CSPI believed was far worse than hydrogenated oils, based on the research of the time. ", "Schleifer writes:\n\n[CSPI’S 1986] Fast-Food Guide specifically criticized Taco Bell, Arby’s, Hardee’s, and Wendy’s for frying in beef fat and tropical oils (that is, coconut and palm oils). ", "But it praised Burger King for switching to vegetable shortening in 1986, which it described as “a great boon to Americans’ arteries.” ", "The guide also praised KFC, writing that the chain was “fortunately” frying in “partially saturated soybean oil . . . ", "that is much less saturated than beef fat.”", "\n\nTwo years later, the same group released the report Saturated Fat Attack, which described trans fats as “more healthful” than saturated fats, Schleifer wrote.", "\n\nIn 1990, a New York Times food writer said CSPI’s campaign prompted fast-food chains to “slim down” by switching to frying in shortening.", "\n\n***\n\nIn the 1990s, the health risks of trans fats began to eclipse those of the saturated variety. ", "A 1990 New England Journal of Medicine found that they raised “bad” cholesterol levels. ", "A 1993 Harvard study found that eating partially hydrogenated vegetable oils increased the risk of heart attacks. ", "Today, it’s estimated that trans fats contribute to thousands of early deaths each year.", "\n\nThe food industry even funded its own study with the goal of proving that trans fats were perfectly safe. ", "However, it only confirmed the earlier findings, and food manufacturers quickly began developing alternatives to hydrogenated oils. ", "Today, even Crisco has changed its recipe, and it now has less that half a gram of trans fat per serving. ", "Which means zero, if you use FDA-label math.", "\n\nSurprisingly, it was the same organization, CSPI, that later urged the FDA to add trans fats to food labels, and nutrition panels have been required to list the substance since 2006. ", "Though American consumption of trans fat has declined precipitously in recent years, it's still common in food such as microwave popcorn, margarine, and some coffee creamers. ", "But probably not for much longer." ]

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[ "Four-quadrant gate\n\nA four-quadrant gate is a type of boom barrier gate protecting a grade crossing.", "\nIt has a gate mechanism on both sides of the tracks for both directions of automotive traffic. ", "The exit gates blocking the road leading away from the tracks in this application are equipped with a delay, and begin their descent to their horizontal position several seconds after the entrance gates do, so as to avoid trapping highway vehicles on the crossing.", "\nMany people consider four-quadrant gates to be safer than two-quadrant gates because they prevent drivers from illegally driving their vehicles around lowered gates to try to beat a train.", "\n\nIn the UK, such crossings are categorised as 'Manually Controlled Barriers' (MCB) because they are always manually controlled, usually from a signal box. ", "Some are known as MCB-CCTV level crossings, because they are supervised by video link to the signal box from which they are remotely controlled.", "\n\nThe first four-quadrant gate in the United States was installed in 1952. ", "They have become common for new installations and replacements since. ", "Unlike the UK, many are automated by the rail line's signal system. ", "The first quad gate installation in the country with sensors to detect vehicles stopped in the tracks was installed in Groton, Connecticut in 1998. ", "Eight of the eleven remaining grade crossings on the Northeast Corridor now have such setups.", "\n\nReferences\n\nCategory:Level crossings\nCategory:Protective barriers\nCategory:Road infrastructure\nCategory:Street furniture\n\nFurther reading" ]

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[ "Introduction\n============\n\nClinical teaching in is an important part of nursing education ([@B1]). ", "Understanding the factors that influence the quality and quantity of clinical education is helpful in solving the related problems ([@B2]). ", "Nurses are repeatedly exposed to situations that may cause them to suffer and reduce their ability to serve the patients ([@B3]). ", "Therefore, assessment of clinical skills by undergraduate nursing programmers is important to be considered ([@B4]). ", "The importance of clinical nursing education is undeniable in personal, professional and clinical skills development ([@B5]). ", "Through nursing education, nursing students will be able to obtain necessary knowledge and skills to assist public health ([@B6]). ", "Success in this subject requires the adoption of effective approaches to familiarize the students with new knowledge and essential needs of the clients ([@B7]). ", "The existing clinical education does not meet the clinical skills competence of the students. ", "Because of the large gap between theoretical and clinical nursing education, recognition of clinical education problems is important ([@B5], [@B8], [@B9]). ", " Due to their immediate attendance in this process, the students are the best and most reliable sources for detection of these problems ([@B10]). ", "Some studies have proposed the clinical education challenges from the students' perception, such as uunavailability of qualified instructors, lack of sufficient facilities, lack of cooperation of the staff in clinical education, lack of procedures to be practiced by students, lack of clinical education tasks, mismatch between objectives and the content of clinical education curriculum, lack of acquisition of prerequisites before entering the clinical fields, lack of appropriate opportunities for learning, lack of motivation among students, knowledge deficit about the profession, implementation of learned objectives in clinical setting , students\\' lack of awareness about the objectives and evaluation methods ([@B11]-[@B15]). ", "Given the central role of students in clinical education, understanding their attitude toward the implementation of this method of education is necessary. ", "To obtain a reliable finding, this multicenter research was conducted with special focus on perceptions of clinical education among senior nursing students.", "\n\nMethods\n=======\n\nThis is a descriptive cross-sectional study aiming to determine the nursing students' perspectives on clinical education (2012-2013). ", "Stratified sampling was done on bachelor nursing students who entered the clinical environment. ", "The samples were selected from each school (Tehran University of Medical Sciences, Islamic Azad University, Baqiyatallah University of Medical Sciences, Army University of Medical Sciences, Shahed University, Shahid Beheshti University of Medical Sciences). ", "After a pilot study on 15 students, by taking the mean of 11.21, standard deviation of 1.72 and a maximum sampling error (d=0.02), 150 students were selected. ", "Data collection instrument included a researcher made questionnaire consisting of 31 questions in Likert style ranking (yes, somewhat, and no) in five domains: objectives and curriculum, clinical instructor, how to deal with students in clinical settings, supervision and evaluation. ", "Content and face validity was evaluated and confirmed by 10 nursing faculty academic members. ", "Cronbach\\'s alpha =93% was obtained for 20% of the samples. ", "Between the two phases of questionnaire completion, the interclass correlation coefficient (ICC) was 0.556. ", "All ethical issues including  obtaining the approval of research council of  Shahed University, introducing the researcher to the subjects, allowing voluntary participation, and informing the students about the research objectiveswere considered. ", "Also, the participants were assured that all the information would be confidential. ", "To identify clinical education status, the percentages of negative and positive percpectives were extracted. ", "The mean and standard deviation of each domain of the questionnaire was calculated. ", "Chi-square test was used to compare the clinical education for nursing students' perspective according to their socio-demographic characteristics (age, gender, work experience in the clinical settings and the working time). ", "Non-parametric tests (Mann-Whitney and Kruskal-Wallis) were used to compare the level of students\\' perspectives on clinical education in each of the domains. ", "The statistical analysis was performed through SPSS 14 ( SPSS Inc, Chicago ,IL ,USA). ", "The significance level for analyses was set at α=5.", "\n\nResults\n=======\n\nThe mean age of the students was 21.7±1.68 years (range: 19-28 years). ", "66% (n=97) of them were male. ", "Among the students, 30.1% (n=44) had an experience of student work in hospital. ", "The mean work time was 3.58 ± 0.48 months. ", "In the domain of clinical educational objectives, the most positive scores (agreement) were related to \\\"presenting job description to the student \\\" and \\\"providing clinical education objectives on the first day of education\\\" with 54% of responses for each item, and the lowest score (disagreement) were \\\"Coordination between educational objectives and expectations of staff from students \\\" belonged to 33.6% of responses. ", "The mean percentage of positive responses (agree view) was in the domain of educational objectives (44.24%) and for negative responses (opposing views) it was 22.41%. ", "In domain of instructor, the most score (agree views) was \\\"expectation of clinical instructor to students' on time attendance at the field\\\"(74.5%) and the lowest score (opposing views) belonged to \\\"clinical instructor in dealing with the problem reduces the students' stress \\\"(22.1%). ", "In domain of clinical instructor, 79.53% of responses were positive (agree views) and 18.5% negative (opposing views). ", "In domain of interaction with students, the most score (agree views) was related to\\\" strengthen the self-assurance of students by the instructor and staff\\\" (46.6%) and the lowest score (opposing view) was given to \\\"empowering the students to make decisions in patient care planning \\\"(25.7%). ", "In domain of interaction with students, 39.75% of the responses were positive (agree views) and 22.53% negative (opposing views). ", "In domain of clinical environment, the most score (agree views) was related to \\\"sufficient number of patients for learning\\\" (45.9%) and the lowest one (opposing views view) belonged to \\\"motivation for occupation through clinical environment\\\" (72.2%). ", "In domain of clinical environment, 35.3% of responses were positive (agree views) and 33.66% negative (opposing views). ", "The most positive responses (agree views) was related to clinical instructor (81.5%) and the most negative ones (opposing views) to clinical environment (33.66%) ([Table 1](#T1){ref-type=\"table\"}).", "\n\n###### \n\nThe students\\' perspective about clinical education domains\n\n --------------------------------------------------------------------------------------------\n **Domains of clinical education** Positive responses\\ Negative responses\\\n N (%) N (%) \n ------------------------------------------------ --------------------- ---------------------\n Education objectives 114 (77.59%) 36 (22.41%)\n\n Instructor 123 (81.50%) 27 (18.50%)\n\n How to deal with students in clinical settings 117 (77.47%) 33 (22.53%)\n\n Clinical environment 114 (66.34%) 36 (33.66%)\n\n Evaluation and supervision 116 (76.85%) 34 (23.15%)\n --------------------------------------------------------------------------------------------\n\nMale and female students had different perspectives in learning objectives (p=0.001), instructor (p=0.046), how to deal with students in clinical settings (p=0.005), clinical environment (p=0.001), evaluation and supervision (p=0.005). ", "Also, male students were more positive than females in all domains of clinical education. ", "The perspective of clinical education did not differ by age or work experience. ", "But, nursing students had differ perspective on educational objectives, (p=0.039), monitoring/evaluation (p\\<0.001), and interacting with students (p=0.032) according to the duration of their work. ", "The mean of supervision and evaluation decreased with increase in the work experience (p=0.002) ([Table 2](#T2){ref-type=\"table\"}).", "\n\n###### \n\nThe students\\' perspective of clinical education domains by gender and work years\n\n **Domains of clinical education** **Gender** **Mean rank** ***p***\n ------------------------------------------------ ------------ --------------- ---------\n Learning objectives Male 79.75 0.001\n Female 56.17 \n Instructor Male 75.82 0.046\n Female 61.35 \n How to deal with students in clinical settings Male 79.86 0.005\n Female 59.15 \n Clinical environment Male 79.09 0.001\n Female 54.29 \n Evaluation and supervision Male 79.15 0.005\n Female 59.60 \n Evaluation and supervision \\<6 month 60.96 0.002\n 6-12 month 43.78 \n \\>12 month 38.97 \n\nDiscussion\n==========\n\nFindings showed that most students believed that tasks and objectives are presented at the beginning of clinical education. ", "However, there were low ratings to educational objectives and staff expectations of students; it means a challenge or an obstacle in these items. ", "Accordingly, in Delaram's study (2013), students have outlined discrepancy between the staff expectations and objectives of clinical education ([@B15]).", "\n\nSimilarly, in Khadivzadeh's research (2004), most of the students considered the clinical education objectives as clear and consistent with the content of clinical education ([@B16]). ", "In contrast to our findings, Taghinejad (2008), Zaighami (2004) and Ebrahami (2004) stated that nursing students have considered the lack of clear job description and inappropriateness clinical education with objectives as the major problems in clinical education ([@B5], [@B11], [@B12]). ", "In the instructor domain, the most positive responses were related to instructor expectation of timely students' attendance at clinical field and the most negative responses belonged to the ability to reduce the students' stress in dealing with problems. ", "Similarly, Delaram (2013) suggest students' timely attendance as the strengths of clinical education from the students' perspective ([@B15]).", "\n\nIn some studies, different opinions are presented about the clinical instructor characteristics. ", "For example, in the study conducted by Ebrahimi (2004) the lack of support and insufficient justification for nursing profession were clinical education barriers related to the instructor ([@B12]). ", "Gignac-Caille (2002) showed that the students\\' interpersonal relationships as the clinical capabilities can be effective in the performance of clinical instructors ([@B17]). ", "The findings of this study showed that most of the students responded c appropriately with the instructor and were supported to increase the ability for dealing with stress in clinical practice. ", "But, Tavakoli Ghochani (2009) in determining the characteristics of an effective clinical instructor revealed that the students had given lower scores to interpersonal interaction by the instructor ([@B18]).", "\n\nFakhr Movahedi's in his study (2013) showed that nursing students scored the clinical instructors' behaviors above average ([@B1]). ", "In domain of \"how to deal with students in the clinical environment\", most of the students responded positively to reinforcing self-assurance by the instructor and staff and the most negative responses were given to authority to make decisions to planning patient care. ", "Similar to this finding, Delaram (2013) showed students are not authorized to make decisions in patient care at clinical education ([@B15]). ", "Also, Mohammadi (2004) described the most important problems as the lack of cooperation and improper communication with students in clinical education ([@B19]).", "\n\nAccordingly, \"sufficient number of patients for learning\" was the strength and \"effectiveness of motivation for future jobs\" was at a disadvantage from the nursing students' perspective. ", "In other studies, the lack of the necessary educational aids, great number of students and forcing students to perform the duties of the staff, the lack of adequate facilities, lack of possible implementation learned items in clinical environment were the most negative points from the nursing students' perspective ([@B16], [@B19], [@B20]). ", "Henderson (2006) investigated the students\\' perception of the psycho-social clinical learning environment and showed that the stable clinical environment can support further learning and impart more knowledge to students in clinical education ([@B21]).", "\n\nPayne and Glaspie (2013) found that students\\' performance is not influenced by the perception of the clinical learning environment. ", "In other words, a well-accepted clinical education environment may not have significant effect on the student outcomes ([@B22]). ", "O\\'Mara (2013) studied the nursing students\\' experiences of challenges related to the clinical learning environment. ", "Nursing students perceived these challenges in relation to clinical environment and learning experiences, so it has affected their learning opportunities and professional identity ([@B23]).", "\n\nAccording to the findings, the least ratings were monitoring and evaluation (complete supervision on clinical education and giving information on how to evaluate at the first session of education), respectively. ", "Consistent with this result, in Baraz's study (2008) clinical evaluation from the nursing students' perspective was weak ([@B24]). ", "One of the objectives of this study was to investigate the relationship between students' work experience and their perception of monitoring and evaluation in clinical education. ", "So, by increasing of students' work experience, there was more negative perception to monitoring and evaluation. ", "This could be due to increasing clinical experience, more formal interactions with other nurses, and ongoing assessment by superiors such as nursing supervisors in their work place. ", "The other finding was the difference between male and female nursing students' perceptions on clinical education. ", "However, the gender differences and its related reasons in how students perceive the clinical education issues should be studied carefully in future research.", "\n\nOne of the limitations of this study is that only students from Tehran university nursing school were studied. ", "So, generalization of the findings should be made with caution. ", "Also, the conservative responses to questions could affect the accuracy of the results. ", "In any case, by creating appropriate conditions for responding to the questionnaire and using non-parametric methods, this limitation was reduced.", "\n\nConclusion\n==========\n\nClinical education is a very complex process and involves many different dimensions. ", "Given the influence of nursing education on the community health, provision of facilities and revising in evaluation systems of students is recommended. ", "In the present study, there was an attempt to determine the most important barriers and strengths of clinical education from the students' perspective. ", "In this regard, particular topics in the area of instructor had been confirmed by students. ", "However, the domains of clinical environment, monitoring and evaluation did not show a favorable condition from the students' perception.", "\n\nThis study describes the issues related to nursing students\\' perceptions of clinical education. ", "Therefore, determining the students\\' perspectives can improve the quality of nursing clinical education. ", "It is recommended that studies on nursing students' perspectives in the years of their academic education (from entering clinical education until graduation) should be conducted using cross-sectional or longitudinal methods and compared with postgraduate period.", "\n\nThis study was approved by the research council of Shahed University (Code: 117/152662/9102). ", "The authors appreciate all nursing students and colleagues for their help in this project.", "\n\n**Conflict of interest:**The authors declare that there are no conflicts of interest.", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "1. ", "Field of the Invention\nThe present invention relates to satellite dish antenna mounts, and more particularly to a conveniently transported mount assembly useful to combine into a dish antenna mount that may be generally fixed at various selected orientations.", "\n2. ", "Description of the Prior Art\nThe transmission of television and other similar signals has gone through several evolutions, first in the form of broadband radio signal then followed by various land lines or cable networks. ", "In each instance either the physical burden of various in-ground or overhead cables or the width of the useable electromagnetic spectrum have limited the number of available programming sources. ", "The granulation of available programming bandwidths, however, has recently gone through a dramatic evolutionary step with the recent advent of transmission techniques relying on geosynchronous satellites each serving as the signal emitting source for a particular program grouping, this evolution then being further reinforced by legislation like the Telecommunications Act of 1996.", "\nIn this latter method the satellites associated with each particular signal group are distributed equatorially above the Earth, with a singular line of sight set of coordinates then ascribed to each geographic location. ", "These alignment coordinates are then used for orienting the sensing axes of highly polarized antennae generally known as a satellite dish. ", "The fixed nature of the viewing coordinates has led to a generally universal, more or less permanent, installation process with the fixed satellite dish mounting structure positioned adjacent the residence that is serviced thereby and the installation process then providing the customer garnering mechanism for a particular program source.", "\nIn typical practice the coordinates for each antenna location are expressed as a corrected magnetic North azimuth and degrees of elevation from the local horizontal plane. ", "As a consequence installation facility has become generally widespread and along with the wide acceptance of satellite programming by fixed residences there has also now emerged a robust trend to implement movable structures like recreational vehicles or motor homes with deployable antenna mounts. ", "These deployable mounts most often follow the earlier practices of satellite based surveying or measuring antennae typically supported on an adjustable tripod, such as those described in U.S. Pat. ", "No. ", "4,767,090 issued to Hartman, et al.; ", "U.S. Pat. ", "No. ", "5,249,766 issued to Vogt; U.S. Pat. ", "No. ", "5,614,918 issued to Dinardo, et al.; ", "U.S. Pat. ", "No. ", "5,769,370 issued to Ashjace; U.S. Pat. ", "No. ", "6,450,464 issued to Thomas; and others. ", "Similar tripod mounted structures are also commercially sold, as for example the tripod mount sold under the model designation TR-2000 Tripod/Base Mount by the Winegard Company, 3000 Kirkwood Street, Burlington, Iowa 52601-2000. ", "While suitable for the purposes intended each of the foregoing entail complex assortments of parts which include metal structures that distort or wholly obliterate any magnetic compass reading, while those made wholly of plastic like the antenna mount sold under the mark or model xe2x80x9cThe Buoyxe2x80x9d by Camping World, Three Springs Road, P.O. Box 90017, Bowling Green, Ky. 42102-9017, lack the leveling indicia for alignment precision. ", "Thus either the resulting measurement and erection complexity or lack of precision have unnecessarily detracted from the use convenience and proliferation of the deployable mount has been less than ringing in the recent past. ", "A conveniently assembled, non-metallic mount structure is therefore extensively desired and it is one such structure that is disclosed herein.", "\nAccordingly, it is the general purpose and object of the present invention to provide an erectable antenna mount assembly all the parts thereof being formed from non-magnetic materials.", "\nOther objects of the present invention are to provide a conveniently erected antenna mount assembly supported on a base container that is selectively ballasted by storing water therein.", "\nFurther objects of the invention are to provide an array of cooperating parts that are conveniently interlocked and thereafter aligned to support an antenna dish.", "\nYet additional objects of the invention are to provide an interlocking array of parts that is easily assembled to form a satellite dish antenna mount provided with structural interlocks that are engaged without substantial ambiguity.", "\nBriefly, these and other objects are accomplished within the present invention by providing a generally hollow base formed as an annular liquid container having the central opening therein keyed and dimensioned for conforming orthogonal receipt of a similarly keyed end of a cylindrical mount. ", "The other end of the mount is then provided with a selectively releasable universal swivel fixed by threaded advancement of the bottom end of a support post extending therefrom. ", "The support post, in turn, terminates at the other end in a dished cavity into which a leveling bubble assembly is placed which is then useful to align the support post on the cylindrical mount to a generally vertical alignment regardless of the inclination of the hollow base. ", "Once aligned the base is then filled with water to provide ballast fixing the base on the ground.", "\nPreferably the hollow base, the cylindrical mount and the support post are all formed of a polymeric material structure, such as polyvinyl chloride or other generally rigid polymer structure having material properties that allow the machining and cutting thereof. ", "Similarly, the pivoting mechanism fixing the support post alignment relative the cylindrical mount also comprises non-magnetic components, the non-ferrous assembly therefore allowing use of an inexpensive magnetic compass to assist in the orientation of the base along a predetermined azimuth. ", "In this manner the induced magnetic distortion errors that are usually associated with unwanted distortions of the local magnetic field are wholly avoided. ", "This cooperative structural arrangement is further simplified by way of a threaded extension of the mounting post into a domed ball surface captured between a cap on the end of the cylindrical mount by a helical spring and a dished surface within the cylinder opposing the threaded extension or the post so that a partial turn thereof then provides the frictional interlock to fix its generally vertical alignment as determined by the bubble level seated in the free end of the post. ", "A satellite dish antenna, conventionally provided with elevation adjustment, can then be fixed to the mounting post along the azimuth referenced to the compass.", "\nOne will appreciate that the planform of the base container and its several surfaces may be variously shaped for clear visual indication of the azimuth alignment thereof. ", "Moreover various storage provisions may be formed in the surfaces of the container that retain the compass and the component array of the cylindrical support assembly. ", "In this manner a convenient, easily transported and easily aligned antenna mount assembly is provided that is useful at all geographic locations." ]

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[ "1. ", "Field of the Invention\nThe present invention relates to an installation apparatus of a sterilization verifying device and an installation method.", "\n2. ", "Description of the Related Art\nIt is preferable that a sterilizing effect is verified in an object for sterilization to verify the sterilizing effect inside the object, but conventionally it is practically impossible to mount an indicator capable of verifying a sterilizing effect into an object for sterilization. ", "Thus, a device for creating a virtual environment which is similar to an interior environment of the object for sterilization to verify a sterilizing effect is used.", "\nJapanese Patent Application Laid-Open No. ", "2005-176939 discusses a technology for mounting an indicator to a device for verifying a sterilizing effect. ", "Specifically the technology is for mounting an indicator into an indicator case from a cap of an end of the indicator case. ", "In Japanese Patent Application Laid-Open No. ", "2005-176939, the device for verifying a sterilizing effect is a precision instrument, and thus in order to replace an indicator, a part for mounting the indicator of the device needs to be opened to mount the indicator and finally the part for mounting the indicator of the device needs to be closed, which is very inconvenient. ", "In particular, operators or nurses in charge of sterilizing operations in the medical field are mostly women, and thus the opening/closing operation of such a device is not suitable for weak women." ]

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[ "Q:\n\nCopy files with renaming\n\nI have a huge file tree. ", "Some files have same name but in different case, e.g., some_code.c and Some_Code.c.", "\nSo when I'm trying to copy it to an NTFS/FAT filesystem, it asks me about whether I want it to replace the file or skip it.", "\nIs there any way to automatically rename such files, for example, by adding  (1) to the name of conflict file (as Windows 7 does)?", "\n\nA:\n\nMany GNU tools such as cp, mv and tar support creating backup files when the target exists. ", "That is, when copying foo to bar, if there is already a file called bar, the existing bar will be renamed, and after the copy bar will contain the contents of foo. ", "By default, bar is renamed to bar~, but the behavior can be modified:\n # If a file foo exists in the target, then…\ncp -r --backup source target # rename foo → foo~\ncp -r --backup=t source target # rename foo → foo.~1~ (or foo.~2~, etc)\n\nThere are other variants, such as creating numbered backups only when one already exists. ", "See the coreutils manual for more details.", "\n\nA:\n\nI tried \napropos copy | grep \"(1)\" \n\nto find possible candidates, and mcopy showed up. ", "\nman mcopy \n\nshows a promising option -D clash-option isn't that cool? ", "But not so cool - it isn't described. ", "But there are some hints to mtools.dvi, which I searched on my system, without success, and via google, without success, but then, with google, I searched directly for mcopy clash-option and found this site. ", "\nI made a short test\nmcopy -D A f* a \n\nto tests for autorename and targetdir a - instead of autorenaming it asked me for every file to ignore or override, that stupid s... . ", "\nMy version is mtools-4.0.10 and the help page is from 1996 - 15 years old. ", "Should we really lost some features, meanwhile? ", "\nI would split the work into two steps: \n\nMake a short function, which generates a unique name for a file, if that name is occupied. ", "\nRun find, and execute that script for every file you wish to copy. ", "\n\nShall we assist in this approach? :)", "\nHere is a script, to autorename files: \n#!", "/bin/bash\n\nname=$1\ntarget=$2\n\nautorename () {\nname=$1\ntarget=$2\nno=$3 \n\ntest -e ${target}/${name}.$no && autorename ${name} ${target} $((no+1)) || cp ${name} ${target}/${name}.$no \n\n}\n\ntest -e ${target}/${name} && autorename ${name} ${target} 0 || cp ${name} ${target} \n\nand this is my test invocation:\nfind -maxdepth 1 -name \"fo*\" -type f -exec ./autorename.sh {} /mnt/hidden/test/a \";\"\n\nNote: -maxdepth, -name and -type where used to restrict the number of affected files dramatically. ", "\nI didn't test the script for deeper file structures, nor for blanks in filenames and other, funky characters like linefeed, pagefeed and so on. ", "\nI used .1 because it doesn't make trouble in most commands, while a ( and a ) often need masking. ", "\n\n" ]

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[ "Health experts have developed a package of food taxes and subsidies that would save Australia $3.4bn in healthcare costs without affecting household food budgets.", "\n\nLinda Cobiac, a senior research fellow at the University of Melbourne’s school of public health, led the research published on Wednesday in the journal Plos Medicine.", "\n\nCobiac and her team used international data from countries that already have food and beverage taxes such as Denmark, but tweaked the rate of taxation and also included a subsidy for fresh fruit and vegetables so the total change to the household budget would be negligible.", "\n\nThey then modelled the potential impact on the Australian population of introducing taxes on saturated fat, salt, sugar and sugar-sweetened beverages, and a subsidy on fruits and vegetables. ", "Their simulations found the combination of the taxes and subsidy could result in 1.2 additional years of healthy life per 100 people alive in 2010, at a net cost-saving of $3.4bn to the health sector.", "\n\n“Few other public health interventions could deliver such health gains on average across the whole population,” Cobiac said.", "\n\nThe sugar tax produced the biggest gains in health, followed by the salt tax, the saturated fat tax and the sugar-sweetened beverage tax.", "\n\nThe fruit and vegetable subsidy, while cost-effective when added to the package of taxes, did not lead to a net health benefit on its own, the researchers found.", "\n\nA co-author of the paper, Prof Tony Blakely, said this was because although a fruit and vegetable subsidy alone would encourage people to eat more fresh foods, previous studies of consumer behaviour had found they would spend the money saved on sugary foods.", "\n\nThe researchers suggest introducing a tax of $1.37 for every 100 grams of saturated fat in those foods with a saturated fat content of more than 2.3%, excluding milk; a salt tax of 30 cents for one gram of sodium above Australian maximum recommended levels; a sugar-sweetened beverage tax of 47 cents a litre; a fruit and vegetable subsidy of 14 cents for every 100 grams; and a sugar tax of 94 cents for every 100ml in ice-cream with more than 10 grams of sugar per 100 grams; and 85 cents for every 100 grams in all other products.", "\n\nThe taxes exclude fresh fruits, vegetables, meats and many dairy products.", "\n\n“You need to include both carrots and sticks to change consumer behaviour and to encourage new taxes,” Blakely said. “", "That’s where this paper is cutting edge internationally.", "\n\n“We have worked out the whole package of taxes with minimal impact on the budget of the household, so you can see an overall gain for the government. ", "The government would be less interested in the package if it was purely punitive, but this provides subsidies and savings to health spending that could be reinvested back into communities and services.”", "\n\nHe said taxing junk foods also prompted food manufacturers to change their products and make them healthier to avoid the taxes.", "\n\n“For those who might say this is an example of nanny state measures, let’s consider that we don’t mind asbestos being taken out of buildings to prevent respiratory disease, and we’re happy for lead to be taken from petrol. ", "We need to change the food system if we are going to tackle obesity and prevent disease.”", "\n\nA health economist at the Grattan Institute, Stephen Duckett, said the researchers had put together a careful and strong study and set of tax and subsidy suggestions. “", "This is a very good paper,” he said.", "\n\n“In my view, we should be starting to tax sugary drinks as a first step. ", "Nearly every week there’s a new study citing the benefits of a sugary drinks tax and and nearly every month another country adopts it as a policy. ", "It’s quickly being seen as an appropriate thing to do to address the obesity epidemic.”", "\n\nA Grattan Institute report published in November found introducing an excise tax of 40 cents for every 100 grams of sugar in beverages as part of the fight against obesity would trigger a 15% drop in the consumption of sugary drinks. ", "Australians and New Zealanders consume an average of 76 litres of sugary drinks per person every year.", "\n\nIn a piece for the Medical Journal of Australia published on Monday, the chair of the Council of Presidents of Medical Colleges, Prof Nicholas Talley, wrote that “the current lack of a coordinated national approach is not acceptable”.", "\n\nMore than one in four Australian children are now overweight or obese, as are more than two-thirds of all adults.", "\n\nTalley proposed a six-point action plan, which included recognising obesity as a chronic disease with multiple causes. ", "He also called for stronger legislation to reduce unhealthy food marketing to children and to reduce the consumption of high-sugar beverages, saying a sugar-sweetened beverage tax should be introduced.", "\n\n“There is evidence that the food industry has been a major contributor to obesity globally,” he wrote. “", "The health of future generations should not be abandoned for short-term and short-sighted commercial interests.”" ]

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[ "We've seen our share of construction near the radio station at 82nd Street and Quaker Avenue, so of course the guys at Pure Water Ice & Tea Company (3333 82nd Street) had to find something humorous to say.", "\n\nWhen dealing with ongoing construction like this, residents are constantly re-routing themselves to avoid the latest lane closures. ", "But as frustrating as traffic backups may be, a sense of humor definitely goes a long way toward making the best of it.", "\n\nIt's not the first time the business has gotten into the funny sign game, either. ", "During Texas Tech's 2018 football season, they put up signs trolling both UT and Oklahoma.", "\n\nThank you, Pure Water, for adding some humor to our otherwise strenuous trek through lane closures and construction. ", "And thank you to Lubbock resident Annette Castellano for sharing the hilarious picture with us." ]

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[ "// Copyright 2014 the V8 project authors. ", "All rights reserved.", "\n// Use of this source code is governed by a BSD-style license that can be\n// found in the LICENSE file.", "\n//\n// Flags: --typed-array-max-size-in-heap=64\n\nfunction TestArray(constructor) {\n function Check(a) {\n a[0] = \"\";\n assertEquals(0, a[0]);\n a[0] = {};\n assertEquals(0, a[0]);\n a[0] = { valueOf : function() { return 27; } };\n assertEquals(27, a[0]);\n }\n Check(new constructor(1));\n Check(new constructor(100));\n}\n\nTestArray(Uint8Array);\n" ]

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[ "December 3-6, 2012\n\nEnthusiasm for bereavement support group counseling has burgeoned in recent years. ", "And, while training opportunities that advance our understanding of the bereavement process have become more available recently, less work has been done on the support group models of care. ", "This seminar helps fill this gap; topics covered will include:\n\nSupport group leadership skills\n\nBarriers to effectiveness in support group counseling\n\nDetailed guidelines for operational practices (such as size of group, length and frequency of sessions)" ]

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[ "BBC tries to stoke racial tensions in Scotland\n\nMy letter of complaint:\n\nDear Sir / Madam,\n\nOn Tuesday 10th of March the BBC website reported on an opinion poll commissioned by the BBC into attitudes to immigration in Scotland. ", "The article, entitled “BBC poll suggests 64% of Scots want immigration reduced”, can be found here: http://www.bbc.co.uk/news/uk-scotland-31800374\n\nThe BBC guidelines on opinion polls clearly state “We should not headline the results of an opinion poll unless it has prompted a story which itself deserves a headline and reference to the poll’s findings is necessary to make sense of it”.", "\n\nThe guideline exists for an excellent reason, which is that it is not the BBC’s role to determine the political questions of the day, but rather to report on them.", "\n\nThis is especially egregious behaviour in a tense pre-election context. ", "I find it hard to imagine what the BBC hoped to achieve by commissioning this poll in the first place.", "\n\nYours\n\nAlistair Davidson\n\n[UPDATE: Scotland 2015, the BBC’s flagship current affairs show, is following up on this story by inviting UKIP on to debate the main Scottish parties, except the Greens.]", "\n\n[UPDATE 2: And “the debate will continue” on Morning Call tomorrow. ", "Joy!]" ]

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[ "The present invention relates to a novel amine having the name 2-(3-(aminomethyl)-3,5,5-trimethylcyclohexyl)propane-1,3-diamine (AM-CPDA), referred to hereinbelow as AM-CPDA, to a process for its production and to its use.", "\n2-(3-(aminomethyl)-3,5,5-trimethylcyclohexyl)propane-1,3-diamine (AM-CPDA), referred to hereinbelow as AM-CPDA, has the chemical structure depicted in structural formula 1.", "\n\nIt is known that amines may be employed as hardeners in epoxy systems. ", "Epoxy resins are prepolymers comprising two or more epoxy groups per molecule. ", "The reaction of these resins with a range of hardeners affords crosslinked polymers. ", "An overview of possible resins and hardeners, their use and properties is given in H. Schumann, “Handbuch Betonschutz durch Beschichtung”, Expert Verlag 1992, pages 396-428." ]

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[ "Theresa May will launch a fresh bid to win support for her rejected Brexit deal by trying to bypass the European Union and secure a bilateral Brexit treaty with Ireland, according to reports.", "\n\nThe move, which comes as No 10 expresses extreme concern at a backbench bid to give parliament control of Brexit, would see the UK try to convince Ireland to agree a plan for keeping the Northern Ireland border open after Britain leaves the EU.", "\n\nOfficials are said to believe that such an agreement could remove the need for the controversial backstop part of Ms May’s Brexit deal, which is the leading cause of Tory and DUP opposition to the plan and the main reason it was overwhelmingly rejected by MPs last week.", "\n\nMs May will update the Commons on Monday on how she plans to proceed after the crushing defeat.", "\n\nUnder the new proposal being discussed by No 10, the Sunday Times reports, the UK would try to convince the Irish government to negotiate a treaty that would remove the need for the backstop, which Brussels insisted on as an insurance policy to ensure an open border is maintained even if the EU and UK cannot agree a trade deal.", "\n\nThe arrangement would see the UK enter into a temporary customs union with the EU, and Northern Ireland agree to abide by European rules on goods until a subsequent deal was reached.", "\n\nA Downing Street source said talk of a bilateral agreement with Ireland was \"not something we recognise\".", "\n\nLiam Fox, the international trade secretary, appeared to confirm the plan, however, telling the BBC’s Andrew Marr Show: “We have to compromise on the backstop. ", "If we’re to get the agreement through, we absolutely have to do that. ", "The question is how we find a way to do that.”", "\n\nAsked what such a compromise might involve, he said: “It’s getting an agreement with Ireland on an alternative mechanism to ensure that we don’t get friction across the Norther Ireland-Ireland border.”", "\n\nMr Fox said both the UK and Irish government shared a desire to preserve an open border in Northern Ireland, adding: “The question is can we achieve what the Irish government wants and what we want by a different mechanism.”", "\n\nThe government will “explore ways” to “find an alternative mechanism to ensure that we give the Irish government what they want, which is that we end up with no hard border”, he added.", "\n\nBrexit deal vote: Opposing groups of protesters gather by parliament Show all 20 1 /20 Brexit deal vote: Opposing groups of protesters gather by parliament Brexit deal vote: Opposing groups of protesters gather by parliament Brexit supporters outside parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester adjusts her pro-EU wig AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament A message to Jeremy Corbyn in support of a people’s vote Getty Brexit deal vote: Opposing groups of protesters gather by parliament A mock Titanic captained by Theresa May heads towards an iceberg in a stunt by campaigning group Avaaz AP Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters outside parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides are in close contact outside of parliament PA Brexit deal vote: Opposing groups of protesters gather by parliament Paintings of Theresa May and Jeremy Corbyn Getty Brexit deal vote: Opposing groups of protesters gather by parliament Former Ukip leader Nigel Farage speaks to the media at the protests outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament A pro-Brexit protester in Parliament Square Getty Brexit deal vote: Opposing groups of protesters gather by parliament Opposing protesters share the space outside parliament Getty Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester holds EU balloons outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters stand on Westminster Bridge PA Brexit deal vote: Opposing groups of protesters gather by parliament Former Ukip leader Nigel Farage speaks to the media at the protests outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament Anti-Brexit protesters demonstrate outside the Houses of Parliament EPA Brexit deal vote: Opposing groups of protesters gather by parliament A pro-Brexit protester sets up outside parliament Reuters Brexit deal vote: Opposing groups of protesters gather by parliament An Avaaz campaigner holds a People’s Vote life float Reuters Brexit deal vote: Opposing groups of protesters gather by parliament A demonstrator holds a sign advocating a no-deal Brexit outside parliament AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament An anti-Brexit protester waves an EU flag on Westminster Bridge PA Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides demonstrate outside parliament AFP/Getty Brexit deal vote: Opposing groups of protesters gather by parliament Protesters of opposing sides stand near parliament Reuters\n\nDublin moved swiftly to pour cold water on the suggestion.", "\n\nSimon Coveney, the Irish foreign minister, wrote on Twitter: “As Brexit dominates news coverage, no surprise that some analysis today gets it wrong. ", "I can reassure you the Irish government’s commitment to the entire [withdrawal agreement] is absolute – including the backstop to ensure, no matter what, an open border between Ireland + NI and the [Good Friday Agreement] are protected.”", "\n\nAnd an Irish government source told the Sunday Times that a bilateral treaty “doesn’t sound like something we would entertain”.", "\n\nMs May’s chief of staff, Gavin Barwell, has reportedly told cabinet ministers that, if the plan fails, the prime minister could seek to secure more support for her deal by announcing she will step down in May.\n\nMs May briefed her cabinet on her next steps during a conference call on Sunday afternoon.", "\n\nThe latest twist comes as a cross-party group of backbenchers prepares to try to amend whatever plan Ms May puts forward in order to give parliament the right to seize control of Brexit.", "\n\nThe proposal, led by former attorney general Dominic Grieve, would remove the government’s power to choose what parliament debates and instead prioritise any motion backed by 300 MPs from at least five parties – significantly less than a Commons majority.", "\n\nJeremy Corbyn says Theresa May's Brexit plan is 'quite clearly a dead deal'\n\nA separate plan being worked on by senior parliamentarians, including Labour’s Yvette Cooper and former Tory ministers Nick Boles and Nicky Morgan, would force the government to delay Brexit if a deal is not approved within weeks.", "\n\nA Downing Street spokesperson said: “The British public voted to leave the European Union and it is vital that elected politicians deliver upon that verdict.", "\n\n“Any attempt to remove the government’s power to meet the legal conditions of an orderly exit at this moment of historic significance is extremely concerning.”", "\n\nIn a sign of growing concern among Eurosceptics that the amendments could lead to Brexit being delayed or reversed, leading Tory Brexiteer Jacob Rees-Mogg, a vocal critic of Ms May’s deal, said it would be better to leave the EU on the terms of the prime minister’s plan than not leave at all.", "\n\nWriting in the Mail on Sunday, he called on the Conservatives to “come together in the national interest”. ", "He added: “If I had to choose between no deal and Mrs May’s original accord, I would have no hesitation of opting for no-deal Brexit, but even Mrs May’s deal would be better than not leaving at all." ]

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[ "Hundreds of schoolchildren have been drafted in to make Amazon's Echo Dot and Kindle devices illegally in China, a report has revealed.", "\n\nInvestigators at Amazon supplier Foxconn's factory found children were working gruelling night-shifts in order to meet demands in the city of Hengyang in Hunan Province.", "\n\nTeenagers are encouraged by local schools and colleges to become 'interns' at the factory, where their teachers are paid to accompany them to work.", "\n\nMore than 1,000 youngsters stand for hours on end throughout the night doing repetitive work which requires little technical training, China Labor Watch found.", "\n\nHuang Xuehua, 24, from Guangdong province works inside a Foxconn factory in the township of Longhua in the southern Guangdong province\n\nThe dorm room interior where workers live at the Foxconn factory in Hengyang in Hunan Province\n\nOne 17-year-old was required to apply a layer of plastic film to around 3,000 Echo Dots every day\n\nThe Foxconn plant in Hunon province also makes Amazon Kindle e-book reading devices (pictured, office buildings in Silicon Valley)\n\nOne 17-year-old told The Guardian she was required to apply a layer of plastic film to around 3,000 Echo Dots every day.", "\n\nShe was initially told she would work eight-hour shifts, five days a week, but that soon jumped to ten-hours a day in a six day week.", "\n\n'I tried telling the manager of my line that I didn’t want to work overtime.' ", "She told The Guardian, 'But the manager notified my teacher and the teacher said if I didn’t work overtime, I could not intern at Foxconn and that would affect my graduation and scholarship applications at the school.", "\n\n'I had no choice, I could only endure this'\n\nChinese law allows children aged 16 and over to work in factories, but they are not supposed to work overtime or during the night.", "\n\nMany of the workers are packed in factory dorm rooms which were found to be lacking fire exits, extinguishers and had squalid bathrooms.", "\n\nChina Labor Watch investigators could find no presence of a labour union and staff were subjected to verbal abuse by line managers.", "\n\nMore than 40 percent of the workforce at the Foxconn plant are dispatch workers - poorly trained and denied sick leave - in violation of China's 10 percent law on dispatch workers.", "\n\nThe exterior of the Foxconn plant in the city of Hengyang in Hunan Province\n\nChinese law mandates dispatch workers must receive at least 24 hours of training, China Labor Watch found those in Hengyang received just eight.", "\n\nWorkers at the factory were also required to put in 100 hours of overtime per month in 'peak season,' despite it being illegal to work anymore than 36 hours of overtime.", "\n\nDuring the off season workers made an average of just £290 a month, while the average workers in Hengyang take home £600.", "\n\nFoxconn, a Taiwanese multinational, which also makes iPhones for Apple admitted to the Guardian it had employed students illegally and would take remedial action.", "\n\nIn a statement provided to the paper it said: 'We have doubled the oversight and monitoring of the internship program with each relevant partner school to ensure that, under no circumstances, will interns [be] allowed to work overtime or nights.", "\n\n'There have been instances in the past where lax oversight on the part of the local management team has allowed this to happen and, while the impacted interns were paid the additional wages associated with these shifts, this is not acceptable and we have taken immediate steps to ensure it will not be repeated.'", "\n\nWorkers eat their lunch at a restaurant inside a Foxconn factory in the township of Longhua in Shenzhen\n\nHowever, Foxconn defended its use of children and said it provided an 'opportunity to gain practical work experience and on-the-job training.'", "\n\nAmazon, whose chairman Jeff Bezos is the richest man in the world, said it would address the allegations with Foxconn at the highest level.", "\n\nAmazon's statement to China Labor Watch said: 'Amazon recognizes our responsibility to ensure the well-being of factory workers manufacturing products for Amazon ...\n\n'Where appropriate, Amazon uses independent auditors to verify compliance with expectations in our Supplier Code of Conduct.'" ]

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[ ". ", "Opoziția e altundeva, nu e în partid\", a declarat Mang.", "\n\n\n\nGabriela Firea a transmis vineri că nu se află în fruntea niciunei răzmerițe, dar că se va alătura oricărei inițiative pentru „modernizarea” PSD și că Liviu Dragnea a oferit primele 3 locuri de pe lista pentru europarlamentare „la cel puțin 30 de colegi”. „", "Dovada cea mai bună a faptului că am dreptate este modul în care Liviu Dragnea a înțeles să răspundă la acuzațiile pe care i le-am adus. ", "În loc să creeze cadrul unei dezbateri deschise și principiale în partid, a găsit de cuviință să-i convoace la sediul central pe liderii de organizații, unul câte unul, sau în grupuri mici, după afinități și, sub pretextul unor discuții referitoare la organizarea referendumului, să încerce să-i intimideze sau, după caz, să-i fidelizeze, cu amenințări mai mult sau mai puțin voalate, sau cu promisiuni mai mult sau mai puțin iluzorii. ", "Doar din informațiile pe care le am eu, a oferit primele 3 locuri pe lista de la europarlamentare la cel puțin 30 de colegi!\", ", "a spus aceasta.", "\n\n\n\nEa a conchis că PSD s-a prăbușit în sondaje. „", "Mulți dintre colegii sau votanții noștri văd în Liviu Dragnea simbolul luptei împotriva statului paralel și a președintelui Iohannis. ", "Este o percepție pur subiectivă, pentru că faptele arată cu totul altceva. ", "După alegerile din 2016, în ciuda multor măsuri bune, cu mare impact în rândul populației, PSD s-a prăbușit în sondaje ca intenție de vot, în timp ce toți adversarii noștri capitalizează această scădere, valul de ură împotriva PSD nu a fost niciodată atât de puternic, iar noi înfruntăm această realitate sub conducerea unui președinte vulnerabil din multe puncte de vedere, cu o cotă de încredere cu mult sub cea a partidului. ", "În condițiile acestea, e limpede pentru oricine că bătăliile politice care ne așteaptă în 2019 sunt pierdute din start! ", "În mai puțin de 4 luni, Bucureștiul va deveni capitala Europei pentru jumătate de an, odată cu preluarea de către România a președinției rotative a Consiliului Uniunii Europene. ", "Cred că avem acum o ultimă șansă de a ne prezenta în fața opiniei publice din întreaga Uniune ca partid modern, democratic, pro-european, capabil să susțină cu legitimitate interesele românilor\", a afirmat acesta.", "\n\n\n\n\n\n\n\n„Am avut în această după amiază o întâlnire cu colegii din PSD din Transilvania. ", "Am discutat câteva ore, fiecare cu argumentele sale, despre direcția în care trebuie să se îndrepte pe termen scurt și mediu Partidul Social Democrat. ", "M-am bucurat enorm să văd că părerile coincid în cele mai multe privințe și am stabilit că începând de astăzi vom vorbi între noi, membrii PSD din Transilvania, mult mai des și vom avea poziții unitare atunci când se va vorbi despre viitorul nostru\", a scris sâmbătă, pe Facebook, Gabriel Zetea, vicepreședinte PSD și președinte PSD Maramureș.", "Potrivit acestuia, organizațiile județene PSD din Ardeal susțin „fără rezerve” Guvernul. „", "Susținem fără rezerve Guvernul PSD-ALDE și aplicarea în continuare a Programului de Guvernare. ", "Toate atacurile și disensiunile publice între membrii PSD cu funcții de conducere de la București trebuie să înceteze rapid pentru a ne concentra pe rezultatele guvernării și pentru a ne putea ține de cuvântul dat românilor în 2016. ", "Cerem președintelui Liviu Dragnea convocarea în cel mai scurt timp posibil a unei ședințe (sau a câte ședințe este nevoie) a Comitetului Executiv Național pentru a clarifica eventualele nemulțumiri a unor colegi. ", "PSD este un partid democratic unde fiecare are dreptul să își exprime liber punctul de vedere dar ne dorim să auzim nemulțumirile în cadrul ședințelor statutare ale partidului și nu în mass media\", a precizat Zetea.", "Zetea spunea vineri că „nimeni nu va achiesa” în partid la ideea schimbării din funcție a liderului formațiunii, Liviu Dragnea, atâta vreme cât nu există o „alternativă conturată” și că, personal, el nu vede „astăzi” această alternativă în PSD.De asemenea, președintele PSD Bihor, Ioan Mang, declara vineri că este nevoie de organizarea ”rapidă” a unei ședințe CExN , săptămâna viitoare, pentru a se stabili prin vot dacă partidul „este pe ideea dnei Firea sau nu”.", "„Părerea mea personală este că, întrucât dna Firea a ieșit astăzi cu alte știri și cu alte...trebuie organizat un CEx și stabilit dacă partidul este pe ideea dnei Firea sau nu. ", "Dânsa, până la urmă, și oricine din partidul ăsta trebuie să înțeleagă că dacă ai o propunere o discuți în partid, se supune la vot, dacă propunerea ta are voturile necesare, în regulă. ", "Dacă nu, subiectul este rămâi în partid și respecți decizia majorității sau pleci, că nu putem să stăm așa la infinit, decidem una și a doua zi ieșim pe presă și spunem altceva\", a declarat Ioan Mang.", "Întrebat dacă vrea ca Gabriela Firea să fie propusă spre sancționare în PSD dacă va continua cu declarațiile publice critice, Mang a răspuns afirmativ. „", "Nu numai dna Firea, oricine. ", "Dacă discuția are loc în partid și majoritatea decide că nu se urmează acea cale, discuția trebuie să înceteze pentru un membru care vrea să rămână în partid, într-o situație în care cel mai important lucru este să ne realizăm programul de guvernare. ", "Dacă vom discuta doar despre noi, în loc să muncim, să ne facem treaba, nu am făcut nimic\", a precizat liderul PSD Bihor.", "Mang a mai declarat că a participat joi, la sediul central PSD, la o discuție între „mai mulți colegi\", în prezența președintelui PSD Liviu Dragnea, privind convocarea unei ședințe CExN. „Ideea a fost dacă e nevoie de Comitet Executiv rapid, adică în următoarele două săptămâni. ", "Nu a fost o decizie, a fost o discuție între colegi, am fost mai mulți colegi\", a spus el. ", "Liderul județean PSD a apreciat că, din punctul său de vedere, o ședință CExN organizată săptămâna viitoare ar putea să „închidă\" subiectul presupusei scrisori a nemulțumiților din partid.", "„Poate dacă îl facem mai repede, săptămâna viitoare, se încheie odată subiectul de presă, că nu există nicio scrisoare, nu a semnat nimeni, cu câți am discutat, inclusiv cu dl Stănescu, nu există o astfel de scrisoare, adică până la urmă trebuie să închidem subiectul ăsta. ", "Altfel, lumea începe să dea telefoane, mă sună" ]

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[ "\nShow HN: Instantly Find anything across your email, cloud drives, and more - ranmancan\nhttps://www.justgoferit.com/get-gofer\n======\nranmancan\nHey All,\n\nI'm part of the team at Gofer - a free productivity tool to easily find and\nmanage information from across your different apps and services.", "\n\nWe're looking for productivity enthusiasts who would like to receive early\naccess and try it out :)\n\nGofer features many cool things, such as smart auto-tagging, allowing to\nintuitively slice and dice your way to a file or mail in seconds. ", "It's also\nSAFE, because it runs on the desktop, so no personal information ever leaves\nyour computer. ", "Only the local instance receives permission to read your data.", "\n\nIts free for anyone to use (we'll be adding paid premium features in the\nfuture).", "\n\nHappy to hear your thoughts!", "\n\n" ]

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[ "/*\n * Copyright 2017-2020 original authors\n *\n * Licensed under the Apache License, Version 2.0 (the \"License\");\n * you may not use this file except in compliance with the License.", "\n * You may obtain a copy of the License at\n *\n * https://www.apache.org/licenses/LICENSE-2.0\n *\n * Unless required by applicable law or agreed to in writing, software\n * distributed under the License is distributed on an \"AS IS\" BASIS,\n * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\n * See the License for the specific language governing permissions and\n * limitations under the License.", "\n */\npackage io.micronaut.core.util;\n\nimport edu.umd.cs.findbugs.annotations.", "Nullable;\nimport java.lang.reflect.", "Array;\nimport java.util.*;", "\n\n/**\n * Utility methods for working with arrays.", "\n *\n * @author Graeme Rocher\n * @since 1.0\n */\npublic class ArrayUtils {\n\n /**\n * An empty object array.", "\n */\n public static final Object[] EMPTY_OBJECT_ARRAY = new Object[0];\n\n /**\n * Concatenate two arrays.", "\n *\n * @param a The first array\n * @param b The second array\n * @param <T> The array type\n * @return The concatenated array\n */\n public static <T> T[] concat(T[] a, T... b) {\n int bLen = b.length;\n\n if (bLen == 0) {\n return a;\n }\n int aLen = a.length;\n if (aLen == 0) {\n return b;\n }\n\n @SuppressWarnings(\"unchecked\")\n T[] c = (T[]) Array.newInstance(a.getClass().getComponentType(), aLen + bLen);\n System.arraycopy(a, 0, c, 0, aLen);\n System.arraycopy(b, 0, c, aLen, bLen);\n\n return c;\n }\n\n /**\n * Concatenate two byte arrays.", "\n *\n * @param a The first array\n * @param b The second array\n * @return The concatenated array\n */\n public static byte[] concat(byte[] a, byte... b) {\n int bLen = b.length;\n\n if (bLen == 0) {\n return a;\n }\n int aLen = a.length;\n if (aLen == 0) {\n return b;\n }\n\n byte[] c = new byte[aLen + bLen];\n System.arraycopy(a, 0, c, 0, aLen);\n System.arraycopy(b, 0, c, aLen, bLen);\n\n return c;\n }\n\n /**\n * Whether the given array is empty.", "\n *\n * @param array The array\n * @return True if it is\n */\n public static boolean isEmpty(Object[] array) {\n return array == null || array.length == 0;\n }\n\n /**\n * Whether the given array is not empty.", "\n *\n * @param array The array\n * @return True if it is\n */\n public static boolean isNotEmpty(Object[] array) {\n return !", "isEmpty(array);\n }\n\n /**\n * Produce a string representation of the given array.", "\n *\n * @param array The array\n * @return The string representation\n */\n public static String toString(@Nullable Object[] array) {\n String delimiter = \",\";\n return toString(delimiter, array);\n }\n\n /**\n * Produce a string representation of the given array.", "\n *\n * @param delimiter The delimiter\n * @param array The array\n * @return The string representation\n */\n public static String toString(String delimiter, @Nullable Object[] array) {\n if (isEmpty(array)) {\n return \"\";\n }\n List<Object> list = Arrays.asList(array);\n return CollectionUtils.toString(delimiter, list);\n }\n\n /**\n * Produce an iterator for the given array.", "\n * @param array The array\n * @param <T> The array type\n * @return The iterator\n */\n public static <T> Iterator<T> iterator(T...array) {\n if (isNotEmpty(array)) {\n return new ArrayIterator<>(array);\n } else {\n return Collections.emptyIterator();\n }\n }\n\n /**\n * Produce an iterator for the given array.", "\n * @param array The array\n * @param <T> The array type\n * @return The iterator\n */\n public static <T> Iterator<T> reverseIterator(T...array) {\n if (isNotEmpty(array)) {\n return new ReverseArrayIterator<>(array);\n } else {\n return Collections.emptyIterator();\n }\n }\n\n /**\n * Iterator implementation used to efficiently expose contents of an\n * Array as read-only iterator.", "\n *\n * @param <T> the type\n */\n private static final class ArrayIterator<T> implements Iterator<T>, Iterable<T> {\n\n private final T[] _a;\n private int _index;\n\n private ArrayIterator(T[] a) {\n _a = a;\n _index = 0;\n }\n\n @Override\n public boolean hasNext() {\n return _index < _a.length;\n }\n\n @Override\n public T next() {\n if (_index >= _a.length) {\n throw new NoSuchElementException();\n }\n return _a[_index++];\n }\n\n @Override public void remove() {\n throw new UnsupportedOperationException();\n }\n\n @Override public Iterator<T> iterator() {\n return this;\n }\n }\n\n /**\n * Iterator implementation used to efficiently expose contents of an\n * Array as read-only iterator.", "\n *\n * @param <T> the type\n */\n private static final class ReverseArrayIterator<T> implements Iterator<T>, Iterable<T> {\n\n private final T[] _a;\n private int _index;\n\n private ReverseArrayIterator(T[] a) {\n _a = a;\n _index = a.length > 0 ? ", "a.length : -1;\n }\n\n @Override\n public boolean hasNext() {\n return _index > -1;\n }\n\n @Override\n public T next() {\n if (_index >= -1) {\n throw new NoSuchElementException();\n }\n return _a[_index--];\n }\n\n @Override public void remove() {\n throw new UnsupportedOperationException();\n }\n\n @Override public Iterator<T> iterator() {\n return this;\n }\n }\n}\n" ]

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[ "Donald West VanArtsdalen\n\nDonald West VanArtsdalen (sometimes listed as Van Artsdalen; October 21, 1919 – May 21, 2019) was a Senior United States District Judge of the United States District Court for the Eastern District of Pennsylvania.", "\n\nEducation and career\n\nBorn in Doylestown, Pennsylvania, VanArtsdalen received a Bachelor of Laws form the University of Pennsylvania Law School in 1948. ", "He was in the Canadian Army from 1940 to 1942, and a United States Army Sergeant from 1942 to 1945. ", "He was in private practice in Doylestown from 1948 to 1970, including a period as district attorney for Bucks County, Pennsylvania from 1954 to 1958.", "\n\nFederal judicial service\n\nOn September 10, 1970, President Richard Nixon nominated VanArtsdalen to a new seat on the United States District Court for the Eastern District of Pennsylvania created by 84 Stat. ", "294. ", "VanArtsdalen was confirmed by the United States Senate on October 8, 1970, and received his commission on October 15, 1970. ", "He assumed senior status on October 21, 1985. ", "He died on May 21, 2019, aged 99, after battling leukemia.", "\n\nReferences\n\nSources\n\nExternal links\n\nCategory:1919 births\nCategory:2019 deaths\nCategory:People from Doylestown, Pennsylvania\nCategory:Military personnel from Pennsylvania\nCategory:Deaths from cancer in Pennsylvania\nCategory:Deaths from leukemia\nCategory:County district attorneys in Pennsylvania\nCategory:Judges of the United States District Court for the Eastern District of Pennsylvania\nCategory:United States district court judges appointed by Richard Nixon\nCategory:University of Pennsylvania Law School alumni\nCategory:20th-century American judges" ]

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[ "Q:\n\nIntegral problem, how do I solve?", "\n\n$$\\int_0^a e^{1-2x}\\, dx = \\frac e4$$\nMy problem is solving for $a$ \n\nA:\n\nAnother way to solve it using a change of variable (Even though it is easier to factor out one $e$ of course...):\n$$\nt = 1 -2x \\\\\ndt = -2 dx \\implies dx = \\frac{-dt}{2} \\\\ \nx = 0 \\implies t = 1-2\\cdot 0 = 1\\\\\nx = a \\implies t = 1-2a\n$$\nThen\n$$\n\\int_0^a e^{1-2x} = \\int_1^{1-2a} e^t \\cdot \\frac{-dt}{2} = -\\frac{1}{2} [e^t]^{1-2a}_1 = -\\frac{1}{2} (e^{1-2a}-e)\n$$\nSo you want \n$$\n -\\frac{1}{2} (e^{1-2a}-e) = e/4 \\implies -\\frac{1}{2}(e^{-2a} -1) = 1/4 \\implies e^{-2a} = \\frac{1}{2}\n$$\nTaking log :\n$$\n-2a = -\\ln(2) \\implies a = \\ln(2)/2\n$$\n\n" ]

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[ "Computer Game Development, Design, and Programming\n\nChris Sawyer is the designer and developer behind Transport Tycoon (first published 1994),\n\nthe widely acclaimed RollerCoaster Tycoon game franchise (first published 1999),\n\nand Chris Sawyer's Locomotion (published 2004).", "\n\nLatest News\n\nDecember 22nd 2016\n\nRollerCoaster Tycoon® Classic arrives on iPad, iPhone, and Android devices!", "\n\nThe Original RollerCoaster Sim: Experience all the fun from the original\n\nRollerCoaster Tycoon® and RollerCoaster Tycoon® 2 games,\n\nwith a new app that combines the best elements of Chris Sawyer's classic titles!", "\n\n\n\nOctober 2013\n\nTransport Tycoon now available for iPad, iPhone, and Android devices!", "\n\n\"19 years after the original Transport Tycoon launched for PC, 31X Ltd and the team at Origin8\n\nare thrilled to launch Transport Tycoon on mobile platforms. ", "Bringing in countless\n\ntweaks and improvements over the original, while still maintaining the appeal, depth\n\nand complexity that the fans love, Transport Tycoon on mobile is the greatest\n\nversion of the greatest business simulation game ever made. ", "A uniquely enthralling game\n\nnow releasing on the perfect platform – not only do the new touch screen controls\n\nallow players to reach out and directly influence their business empires, the game genuinely\n\nfeels at home on these devices.\"", "\n\n" ]

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[ "Iatrogenic bismuth poisoning. ", "Case report.", "\nA case of bismuth intoxication following the intraoral use of BIPP-impregnated gauze packs is presented. ", "This report illustrates the need for caution when using potentially toxic compounds in the oral cavity where significant quantities can be absorbed to produce symptoms of poisoning." ]

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[ "Customer reviews of our Baptism and Christening Invitations\n\nMay 4, 2014Perfect design\n\n\"The card was perfect for my daughters christening invite. ", "The paper itself wasn't cheap feeling. ", "It was nice and thick and seemed more expensive then it was.\"", "\n\nMay 30, 2013Simply perfect!", "\n\n\"Absolutely LOVE the quality of this invitation - first time ordering from the Studio Basics line, so I wasn't sure what to expect. ", "The paper itself is a nice card stock, design was simple but elegant and the photo and text print was clear and even better in person. ", "Would definitely recommend.\"", "\n\nMarch 26, 2013Classy and modern\n\n\"I picked this style for my daughter's baptism cuz it wasn't too religious. ", "It's classy and modern. ", "Beautiful impression, thick paper so it doesn't seem cheap. ", "I'm very hands-on, and it was amazingly simple to create this invitation!\"", "\n\nJanuary 27, 2013Excellent quality\n\n\"I used this product for my son's baptism invitation and it was amazing the quality and how easy it was to personalize it. ", "My family kept it as a photo and framed it.\"", "\n\nOctober 29, 2012Just a Beauty\n\n\"The overall rating and quality is A+. ", "My baby's picture turned out so beautiful, it just fits in the card so perfectly. ", "I just changed the font to a bigger size. ", "I am so happy with my baptism invitation from Tiny Prints. ", "I am excited to send it to my family. ", "thank you.\"" ]

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[ "Freezing of tissue-limits for the autoradiographic localization of diffusible substances.", "\nFrozen thin sections and sections from freeze-dried and embedded tissue are used for the autoradiographic localization of diffusible substances at the electron microscope level. ", "The presence of ice crystals in such sections may limit the autoradiographic resolution. ", "Ice crystals are formed during freezing and may grow during subsequent processing of tissue. ", "The contribution of ice crystal growth to the final image was estimated by measuring the distribution of the ice crystal sizes in freeze-etch replicas and in sections from freeze-dried and embedded tissues. ", "A surface layer (10-15 mu) without visible ice crystals was present in both preparations. ", "Beneath this surface layer the diameter of ice crystals increased towards the interior with the same relationship between crystal size and distance from the surface in the freeze-etch preparation as in the freeze-dry preparation. ", "Ice crystal growth occurring during a much longer time during freeze-drying compared to freeze-etching does not significantly contribute to the final image in the electron microscope. ", "The formation of ice crystals during freezing determines to a large extent the image (and therefore the autoradiographic resolution) of freeze-dry preparations and this probably holds also for thin cryosections of which examples are given." ]

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[ "Chicken tortilla soup\n\nHang on a minute. ", "I have to stop laughing and catch my breath. ", "Oh, come on. ", "I’m just kidding. ", "I really am thoughtful, but if Jim reads this post, he might have something to say about the “ever” part.", "\n\nSo anyway, Jim’s been asking for hearty soups for lunch. ", "It’s convenient to make a big pot of soup, then dole it out into single portions and freeze them for another time. ", "At work, he just pops one in the microwave and gets a nice filling lunch. ", "And healthy too.", "\n\nI haven’t made this before, but he really liked it. ", "It’s a bit spicy for me, but if you’d like to do a less spicy version, just use a green pepper instead of the chipotle peppers. ", "Squeezing a little lime juice on at the table really adds a nice touch.", "\n\nHeat olive oil in a large pot over medium heat. ", "Cook onions until translucent. ", "Add garlic and cook another 1-2 minutes. ", "Add the spices (except cilantro) and heat for an additional minute. ", "Next, add cilantro, tomatoes, carrots, peppers, chicken broth, frozen corn, black beans, and shredded chicken. ", "If soup is too thick, add up to 1 c. water to thin it a little. ", "Simmer, partly covered, for 1 hour.", "\n\nWhen ready to serve, place tortilla on baking sheet and broil until brown and crispy. ", "Cool slightly and break into pieces. ", "Ladle soup into bowl, top with tortilla pieces and Mexican blend shredded cheese. ", "Squeeze a wedge of lime over soup just before eating.", "\n\nHa, ha… My husband might question the ‘ever’ part too. ", "I do love him all the time, but sometimes expressing it seems to take a backseat to everything else. ", "Do you think that if I make him this soup I would redeem myself? ;)", "\n\nNice wife! ", "This soup looks lovely. ", "I just made tortilla soup for the very first time recently and have been thinking about it ever since–we just loved it! ", "My recipe is a little different than this but yours looks equally delicious!", "\n\nLOL, I’m not even going to start with you because it would be the “pot calling the kettle black”.", "\n\nThe soup looks great and I love spicy food.", "\n\nHey, Michelle do you have to let the (any)soup defrost some before nuking it? ", "And do you freeze and nuke in plastic? ", "What’s your thoughts on that? ", "I’ve heard & read both are major no-no’s. ", "Thanks!", "\n~ingrid\n\nLonely Scrapbooker – Yea for you! ", "I’m glad you finally made one of my recipes, Diana! : ) ", "And even happier that you like it!", "\n\nIngrid – The plastic container stuff is hard to figure out. ", "I know that some folks say not to reheat in them, but we do anyway. ", "But really just for Jim and me, not for the kids. ", "If I had frozen spaghetti sauce or something that we were all eating, I do transfer that to a pot to reheat it, but for single servings of things like soup, I don’t bother to do that. ", "You’ve got me thinking though, and I’m going to read up on it more. : )" ]

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[ "Cybersecurity firm Kaspersky Lab said a new malware named Duqu 2.0 was used to target Iran nuclear talks venues\n\nA leading cybersecurity firm claims several venues for international negotiations over Iran's nuclear programme have been targeted by a surveillance virus, reportedly linked to Israeli intelligence.", "\n\nKaspersky Lab ZAO said it discovered several of its own internal systems had been infected by highly sophisticated malicious malware earlier this year.", "\n\nAs the company researchers set off to investigate the cyber-attack, they found out that the same virus had been used to infiltrate a series of other targets in the West and the Middle East, including, most notably, hotels where the Iranian delegates met with the P5+1 group to discuss Tehran nuclear ambitions.", "\n\nKaspersky, a Moscow-based firm, said the \"highly sophisticated\" malware platform was a developed version of Duqu, which it described as \"one of the most skilled, mysterious and powerful threat actors in the APT [advanced persistent threat] world\".", "\n\nIt added that the level of complexity of Duqu 2.0 was so high that they believe its use could only be part of \"a nation-state-sponsored campaign.\"", "\n\n\"The people behind Duqu are one of the most skilled and powerful APT groups and they did everything possible to try to stay under the radar,\" said Costin Raiu, Director of Kaspersky Lab's Global Research & Analysis Team.", "\n\n\"This highly sophisticated attack used up to three zero-day exploits, which is very impressive – the costs must have been very high.\"", "\n\nThe firm added that perpetrators were confident they could act with impunity as the high-quality of Duqu 2.0 would let their activity go unnoticed.", "\n\n\"To stay hidden, the malware resides only in kernel memory, so anti-malware solutions might have problems detecting it. ", "It also doesn't directly connect to a command-and-control server to receive instructions. ", "Instead, the attackers infect network gateways and firewalls by installing malicious drivers that proxy all traffic from the internal network to the attackers' command and control servers,\" explained Raiu.", "\n\nKaspersky didn't name Israel as a suspect but the previous version of Duqu was very similar to the infamous Stuxnet worm, believed to have been developed by the US and Israel.", "\n\nIsrael has long opposed the nuclear talks, as it considered a positive outcome could have greatly increased Tehran's threats to Israel's security. ", "Disagreement on the issue also dragged Israel-US relations to a record low.", "\n\nIn March, Washington directly accused Israeli spies of having snooped on the talks to gather intelligence used to fuel opposition to the nuclear deal in the US congress.", "\n\nKaspersky's revelation that venues where the 'P5+1' group met their Iranian governments were targeted is likely to substantiate the claim.", "\n\nThe company didn't identify the hotels and said the attack on its own internal systems was primarily aimed at acquire information \"on the company's newest technologies\".", "\n\n\"Kaspersky Lab is confident that its clients and partners are safe and that there is no impact on the company's products, technologies and services,\" the firm said in a statement.", "\n\nDuqu was a sophisticated piece of malware discovered in 2011 having been used in a number of intelligence-gathering attacks against a range of industrial targets. ", "It had a number of similarities to the infamous Stuxnet worm, leading many to believe it was developed by the US and Israel.", "\n\nDuqu 2.0 is an evolution of the original malware and is believed to have been created by the same group of attackers by Symantec, and is once again being used to hit very specific targets including the P5+1 nuclear talks and the events marking the 70th anniversary event of the liberation of Auschwitz-Birkenau.", "\n\nThe highly stealthy malware would have gone completely undetected while gathering a lot of highly sensitive information before uploading that data remotely to command-and-control servers." ]

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[ "Ireland: IRSP members arrested in Waterford\n\nSome disturbing events have been taking place in the south\nof Ireland, where two IRSP members have been arrested and are being held under\nthe notorious “section 30”. ", "This is clearly a case of political victimisation\nand should be condemned by all socialists.", "\n\nThe true nature of the twenty-six county state has reared\nits ugly head as two members of the Irish Republican Socialist Party, 26-year-old John O'Donoghue and\n55-year-old James Butler were arrested for allegedly being part of an\nillegal organisation, the Irish National Liberation Army.", "\n\nBoth men were arrested under the notorious section 30 which\nhas granted the twenty-six county state powers that add up to internment. ", "Both\ncomrades have denied membership of the INLA, but on June 20,and the\nonly evidence against them being the word of one Gardai officer, they were\nremanded in custody none the less.", "\n\nThis bears a frightening reminisce to the days of internment\nof republicans by British imperialism in the six countries during the troubles.", "\nInternment was used as a weapon to smash resistance to British imperialism and\nweaken the movements of the working class in the six counties. ", "It would not be\nthe first time either that internment has been used by the twenty-six county\nstate to stifle the movement of Irish working people.", "\n\nIn the aftermath of the formation of the twenty-six county\nstate hundreds of republicans and socialists were interned in an effort to end\nresistance to both imperialism and capitalism in Ireland, to maintain British\nimperialism's domination of the island. ", "Many leaders were executed. ", "The ruling\nclass will go to any length to maintain its political power, and as socialists\nwe must organise against such detentions and demand the immediate repeal of\nsection 30.", "\n\nRather than an effort to crack down on serious crime as it\nhas been presented, \"operation anvil\" has amounted to no less than an attack on\nthe IRSP by the forces of the Irish ruling class, as was quite rightly\nrecognised by IRSP Ard\nComhairle (executive committee) member Pól Little when he stated:\n\n\"This is clearly an attack on the IRSP as well as radical\npolitical agitation within the 26 Counties. ", "Today we have two individuals who\nface substantial prison terms on the word of a single Gardai officer, all\nbecause of their political orientation.\"", "\n\nThese arrests amount to nothing less than an attack on\nworking class militants in Ireland. ", "The authorities are worried at the recent\ngrowth of the IRSP and the newfound success of its attempts to build a mass\nworking class based movement. ", "One of those arrested had only been a member of\nthe IRSP for a few weeks and yet is allegedly a hardened fighter. ", "Clearly\nrather than trying to fight crime the Gardai are yet again being used to attack\nthe IRSP and prevent the growth of revolutionary socialist ideas in Ireland.", "\n\nYet these attacks will not prevent the growth of\nsocialism in Ireland. ", "The Cumman (branch) in Waterford that these two arrested\nmen belong to is a recent addition to the IRSP. ", "The Irish working class has\nlong struggled against bitter repression both from the twenty-six county state\nand British imperialism. ", "These arrests are a naked display of the brutality of\nthe ruling class in Ireland and expose that their real interests lie in\nmaintaining the status quo; they will continue to act as the gatekeepers of\nBritish imperialism. ", "In the long run interment merely increases resentment and\ndestroys any illusions that there exists any real form of democracy or free\npolitical association in Ireland.", "\n\nAs internationalists we must oppose this political\nrepression and join the fight for the freedom of these Irish comrades.", "\n\n- For the\nimmediate release without charge of John O'Donoghue and James Butler." ]

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[ "Effect of two cleaning processes for bone allografts on gentamicin impregnation and in vitro antibiotic release.", "\nBone allografts are a useful and sometimes indispensable tool for the surgeon to repair bone defects. ", "Microbial contamination is a major reason for discarding allografts from bone banks. ", "To improve the number of safe allografts, we suggest chemical cleaning of the grafts followed by antibiotic impregnation. ", "Comparison of two chemical cleaning processes for bone allografts aiming for antibiotic impregnation and consequently delivery rates in vitro. ", "Bone chips of 5-10 mm were prepared from human femoral heads. ", "Two cleaning methods (cleaning A and cleaning B) based on solutions containing hydrogen peroxide, paracetic acid, ethanol and biological detergent were carried out and compared. ", "After the cleaning processes, the bone chips were impregnated with gentamicin. ", "Bacillus subtilis bioassay was used to determine the gentamicin release after intervals of 1-7 days. ", "Differences were compared with non-parametric Mann-Whitney U tests. ", "The zones of inhibition obtained from the bone grafts cleaned with both cleaning processes were similar between the groups. ", "The concentration of the released antibiotic was decreasing gradually over time, following a similar pattern for both groups. ", "The cleaning procedure A as well as the cleaning procedure B for bone allografts allowed the impregnation with gentamicin powder in the same concentrations in both groups. ", "The delivery of gentamicin was similar for both groups. ", "Both cleaning procedures were easy to be carried out, making them suitable for routine use at the bone banks." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Pro-inflammatory cytokine, matrix metalloproteinases and TIMP-1 are involved in wound healing after mastectomy in invasive breast cancer patients.", "\nMastectomy provides a good model to study the wound healing process after surgery. ", "The involved factors include selectins, pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinases (MMPs), and their natural inhibitors (TIMPs). ", "In the present study, we observed the kinetic changes of these factors in the process of wound healing after a mastectomy, and analyzed the relationship between these factors and the clinical outcomes. ", "Twenty-nine patients, who received a modified radical mastectomy, were recruited to this study. ", "The wound was inspected daily for the presence of flap necrosis, infection and seroma. ", "Drain fluid was collected on days 1, 2 and 5. ", "IL-6, P-selectin, MMP-2, 3, 9 and TIMP-1 were screened by ELISA kits for their impacts on wound healing after mastectomy. ", "IL-6 demonstrated the highest level on Day 1 after operation and was negatively correlated with MMP-2, which in turn showed a consistently negative correlation with MMP-9 for days 1, 2 and 5. ", "Incidences of seroma formation and skin flap necrosis were 27.6% and 20.7%, respectively. ", "Seroma formation was associated with low MMP-2 levels on Day 5. ", "While skin flap necrosis seemed to correlate with high MMP-2 levels and low levels of MMP-9 and TIMP-1. ", "IL-6, P-selectin, MMP-2, MMP-3, MMP-9 and TIMP-1 are important in the process of wound healing after mastectomy. ", "A low MMP-2 level correlates with the formation of seroma, while MMP-2, MMP-9 and TIMP-1 are associated with skin flap necrosis." ]

{ "pile_set_name": "PubMed Abstracts" }

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