gebhart/patrepeval huggingface dataset:
High-performance scientific computing using C++ (1992)

Concepts from mathematics and physics often map well to object-oriented software since the original concepts are of an abstract nature. We describe our experiences with developing high-performance shock-wave physics simulation codes in C++ and discuss the software engineering issues which we have encountered. The primary enabling technology in C++ for allowed us to share software between our development groups is operator overloading for a number of &amp;quot;numeric&amp;quot; objects. Unfortunately, this enabling feature can also impact the efficiency of our computations. We describe the techniques we have utilized for minimizing this difficulty. Introduction Developers of scientific software systems are tasked to implement abstract ideas and concepts. The software implementation of algorithms and ideas from physics, mechanics and mathematics should in principle be complementary to the mathematical abstractions. Often these ideas are very naturally implemented in an object-oriented style. For example...
HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription (1996)

Increased histone acetylation has been correlated with increased transcription, and regions of heterochromatin are generally hypoacetylated. In investigating the cause-and-effect relationship between histone acetylation and gene activity, we have characterized two yeast histone deacetylase complexes. Histone deacetylase-A (HDA) is an approximately 350-kDa complex that is highly sensitive to the deacetylase inhibitor trichostatin A. Histone deacetylase-B (HDB) is an approximately 600-kDa complex that is much less sensitive to trichostatin A. The HDA1 protein (a subunit of the HDA activity) shares sequence similarity to RPD3, a factor required for optimal transcription of certain yeast genes. RPD3 is associated with the HDB activity. HDA1 also shares similarity to three new open reading frames in yeast, designated HOS1, HOS2, and HOS3. We find that both hda1 and rpd3 deletions increase acetylation levels in vivo at all sites examined in both core histones H3 and H4, with rpd3 deletions having a greater impact on histone H4 lysine positions 5 and 12. Surprisingly, both hda1 and rpd3 deletions increase repression at telomeric loci, which resemble heterochromatin with rpd3 having a greater effect. In addition, rpd3 deletions retard full induction of the PHO5 promoter fused to the reporter lacZ. These data demonstrate that histone acetylation state has a role in regulating both heterochromatic silencing and regulated gene expression.
Role of Micafungin in the Antifungal Armamentarium (2007)

Serious infections caused by opportunistic molds remain a major problem for public health. Immune deficiency following organ transplantation and aggressive cancer treatment has greatly increased the incidence of systemic mycoses, and invasive aspergillosis in patients with AIDS is associated with significant morbidity and mortality. Amphotericin B is the first-line therapy for systemic infection because of its broad-spectrum and fungicidal activity. However, considerable side effects limit its clinical utility. The echinocandins are large lipopeptide molecules that inhibit the synthesis of 1,3-beta-D-glucan, a key component of the fungal cell wall. Three echinocandins have reached the market, and some others are in early clinical development. Caspofungin was the first echinocandin to be licensed for clinical use in most countries. Micafungin is licensed for clinical use in Japan, China, Taiwan, Jordan, Korea, Hong-Kong and the US, and anidulafungin is currently licensed in the US. The novel class of echinocandins represents a milestone in antifungal drug research that has further expanded our therapeutic options. Studies to date have shown that micafungin exhibits extremely potent antifungal activity against clinically important fungi, including Aspergillus and azole-resistant strains of Candida. In animal studies, micafungin is as efficacious as amphotericin B with respect to improvement of survival rate. Micafungin is also characterized by a linear pharmacokinetic profile and substantially fewer toxic effects. Micafungin is a poor substrate for the cytochrome P450 enzymes, and compared to azoles, fewer drug interactions are described. No dose adjustments of the drug are required in the presence of mycophenolate mofetil, cyclosporin, tacrolimus, prednisolone, or sirolimus. Strategies using this new echinocandin agent will benefit a large number of patients with severe immune dysfunction.
Granuloma Formation Induced in Mice by Chemically Defined Mycobacterial Fractions (1969)

Amounts of trehalose-6,6-dimycolate as small as 1 to 5 mug can, after intravenous injection, induce in the lungs of mice formation of tubercles in which the cellular composition is indistinguishable from that in tubercles formed after an infection with living BCG bacilli. The strongest cellular response in mice was induced by cord factor from Mycobacterium kansasii; the weakest was induced by cord factor from the BCG strain of M. bovis. It was found that three intravenous injections of cord factor induced a more extensive cellular response than did one injection of the same total amount of cord factor. Mice treated intravenously with cord factor were protected against an intravenous challenge with the virulent H37Rv strain of M. tuberculosis. The cellular response in the lungs of mice to intraperitoneal injections of living BCG and cord factor was very weak compared with that after intravenous injections. Intraperitoneal vaccination of mice with cord factor did not protect the mice against a challenge with virulent tubercle bacilli. Mice vaccinated intraperitoneally with BCG were immunized although no granulomas, or very few, were present in the lungs at the time of the challenge. The significance of the cellular response induced by cord factor is discussed.
A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo. (1997)

Osteoclastic bone degradation requires intimacy between the matrix and the resorptive cell. While the precise role the integrin alpha(v)beta3 plays in the process is not yet understood, occupancy of the heterodimer by soluble ligand or by blocking antibody effectively inhibits bone resorption in vitro and in vivo, suggesting that alpha(v)beta3 blockade may prevent postmenopausal osteoporosis. Thus, we identified a synthetic chemical peptide mimetic, beta-[2-[[5-[(aminoiminomethyl)amino]-1-oxopentyl]amino]-1-+ ++oxoethyl]amino-3-pyridinepropanoic acid, bistrifluoroacetate (SC56631) based upon the alpha(v)beta3 ligand, Arg-Gly-Asp (RGD), which recognizes the isolated integrin, and its relative, alpha(v)beta5, as effectively as does the natural peptide. The mimetic dampens osteoclastic bone resorption in vitro and in vivo. Most importantly, intravenous administration of the mimetic prevents the 55% loss of trabecular bone sustained by rats within 6 wk of oophorectomy. Histological examination of bones taken from SC56631-treated, oophorectomized animals also demonstrates the compound's bone sparing properties and its capacity to decrease osteoclast number. Thus, an RGD mimetic prevents the rapid bone loss that accompanies estrogen withdrawal.
The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb (2000)

Mice carrying a targeted disruption of BmprIB were generated by homologous recombination in embryonic stem cells. BmprIB(-/-) mice are viable and, in spite of the widespread expression of BMPRIB throughout the developing skeleton, exhibit defects that are largely restricted to the appendicular skeleton. Using molecular markers, we show that the initial formation of the digital rays occurs normally in null mutants, but proliferation of prechondrogenic cells and chondrocyte differentiation in the phalangeal region are markedly reduced. Our results suggest that BMPRIB-mediated signaling is required for cell proliferation after commitment to the chondrogenic lineage. Analyses of BmprIB and Gdf5 single mutants, as well as BmprIB; Gdf5 double mutants suggests that GDF5 is a ligand for BMPRIB in vivo. BmprIB; Bmp7 double mutants were constructed in order to examine whether BMPRIB has overlapping functions with other type I BMP receptors. BmprIB; Bmp7 double mutants exhibit severe appendicular skeletal defects, suggesting that BMPRIB and BMP7 act in distinct, but overlapping pathways. These results also demonstrate that in the absence of BMPRIB, BMP7 plays an essential role in appendicular skeletal development. Therefore, rather than having a unique role, BMPRIB has broadly overlapping functions with other BMP receptors during skeletal development.
A Raman and infrared spectroscopic investigation of biological hydroxyapatite (1990)

Raman spectra were acquired on ox femur samples treated with hydrazine to remove the organic components of bone. A large increase in the signal-noise ratio of the mineral spectrum resulted from the exposure of the mineral surface and the removal of fluorescent components of the organic matrix. The effect of hydrazine treatment of the mineral matrix has been reinvestigated and shown to be slight on the basis of second derivative FTIR data. This is the first time that this high resolution technique has been applied to biological minerals.
Protease specificity determination by using cellular libraries of peptide substrates (CLiPS) (2006)

We report a general combinatorial approach to identify optimal substrates of a given protease by using quantitative kinetic screening of cellular libraries of peptide substrates (CLiPS). A whole-cell protease activity assay was developed by displaying fluorescent reporter substrates on the surface of Escherichia coli as N-terminal fusions. This approach enabled generation of substrate libraries of arbitrary amino acid composition and length that are self-renewing. Substrate hydrolysis by a target protease was measured quantitatively via changes in whole-cell fluorescence by using FACS. FACS enabled efficient screening to identify optimal substrates for a given protease and characterize their cleavage kinetics. The utility of CLiPS was demonstrated by determining the substrate specificity of two unrelated proteases, caspase-3 and enteropeptidase (or enterokinase). CLiPS unambiguously identified the caspase-3 consensus cleavage sequence DXVDG. Enteropeptidase was unexpectedly promiscuous, but exhibited a preference for substrates with the motif (D/E)RM, which were cleaved substantially faster than the canonical DDDDK recognition sequence, widely used for protein purification. CLiPS provides a straightforward and versatile approach to determine protease specificity and discover optimal substrates on the basis of cleavage kinetics.
Preparation of Cationic Nanogels for Nucleic Acid Delivery (2012)

Cationic nanogels with site-selected functionality were designed for the delivery of nucleic acid payloads targeting numerous therapeutic applications. Functional cationic nanogels containing quaternized 2-(dimethylamino)ethyl methacrylate and a cross-linker with reducible disulfide moieties (qNG) were prepared by activators generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) in an inverse miniemulsion. Polyplex formation between the qNG and nucleic acid exemplified by plasmid DNA (pDNA) and short interfering RNA (siRNA duplexes) were evaluated. The delivery of polyplexes was optimized for the delivery of pDNA and siRNA to the Drosophila Schneider 2 (S2) cell-line. The qNG/nucleic acid (i.e., siRNA and pDNA) polyplexes were found to be highly effective in their capabilities to deliver their respective payloads.
Reaction of Sulfur Dioxide with Limestone and the Influence of Pore Structure (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReaction of Sulfur Dioxide with Limestone and the Influence of Pore StructureMiloslav Hartman and Robert W. CoughlinCite this: Ind. Eng. Chem. Process Des. Dev. 1974, 13, 3, 248–253Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://doi.org/10.1021/i260051a010RIGHTS & PERMISSIONSArticle Views429Altmetric-Citations103LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (666 KB) Get e-Alerts
Suicidal Thoughts and Behavior With Antidepressant Treatment (2012)

Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies.
Separation and Detection of Smokeless Powder Additives by Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC/MS/MS), (2013)

A reversed phase gradient ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) method has been developed for the analysis of smokeless powders. A total of 20 different components were separated by UPLC and detected by MS/MS in multiple reaction monitoring (MRM) mode. These compounds included diphenylamines, centralites, nitrotoluenes, nitroglycerin, and various phthalates. Simultaneous positive and negative electrospray ionization (ESI) was used along with negative atmospheric pressure chemical ionization (APCI) to detect all compounds in a single analysis. Analysis times were under 8 min with a gradient of 10-73% organic at a flow rate of 0.500 mL/min. With this method, ultraviolet and MRM limits of detection ranging from 0.08 to 2.6 ng and 0.4-64 ng injected were achieved. Commercially available smokeless powders were also extracted with methylene chloride and characterized using the developed UPLC/MS/MS method. The procedure permits the determination of compositional differences between different brands as well as lot-to-lot variations.
Structure of the DNA-SspC Complex: Implications for DNA Packaging, Protection, and Repair in Bacterial Spores (2004)

Bacterial spores have long been recognized as the sturdiest known life forms on earth, revealing extraordinary resistance to a broad range of environmental assaults. A family of highly conserved spore-specific DNA-binding proteins, termed alpha/beta-type small, acid-soluble spore proteins (SASP), plays a major role in mediating spore resistance. The mechanism by which these proteins exert their protective activity remains poorly understood, in part due to the lack of structural data on the DNA-SASP complex. By using cryoelectron microscopy, we have determined the structure of the helical complex formed between DNA and SspC, a characteristic member of the alpha/beta-type SASP family. The protein is found to fully coat the DNA, forming distinct protruding domains, and to modify DNA structure such that it adopts a 3.2-nm pitch. The protruding SspC motifs allow for interdigitation of adjacent DNA-SspC filaments into a tightly packed assembly of nucleoprotein helices. By effectively sequestering DNA molecules, this dense assembly of filaments is proposed to enhance and complement DNA protection obtained by DNA saturation with the alpha/beta-type SASP.
Plug‐Based Microfluidics with Defined Surface Chemistry to Miniaturize and Control Aggregation of Amyloidogenic Peptides (2009)

Small with control: For miniaturization of protein aggregation experiments the interfacial chemistry must be controlled to avoid protein aggregation caused by interfacial adsorption. Plug-based microfluidics with defined surface chemistry (see schematic picture) can then be used to perform hundreds of aggregation experiments with volume-limited samples, such as cerebrospinal fluid from mice.
Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sources (1980)

Slow reacting substance(s) of anaphylaxis (SRS-A) was isolated from both human (lung) and rat sources and compared with three synthetic SRS-As of known structure-leukotrienes (LTs) C-1, C-2, and D. Reversed-phase liquid chromatography was used both as a final purification step and a means of comparison of biologically derived and synthetic substances. Two major peaks of SRS-A activity of both rat and human origin corresponded chromatographically with LTC-1 and LTD, respectively, and had equivalent specific activities on the guinea pig ileum. With guinea pig ileum, the specific activities (units/pmol) for synthetic leukotrienes and anaphylactic peaks were (mean +/- SEM): synthetic LTC-1, 1.93 +/- 0.13; SRS-A(rat) peak I, 1.69 +/- 0.43; synthetic LTD, 6.10 +/- 1.15; SRS-A(rat) peak II, 7.14 +/- 0.51; and SRS-A(hu) peak II, 1.90. Both synthetic LTC-1 and LTD and their SRS-A natural counterparts had a preferential contractile activity on guinea pig peripheral airway compared to central airways and were at least 200 times more active than histamine on peripheral airways on a molar basis. Leukotriene D is the major SRS-A of human lung and accounts for almost all of the biological activity. It likely is formed from leukotriene C-1 in vivo by an enzymic process of the well-known gamma-glutamyltransferase type.
Indium Metal and Its Halides in Organic Synthesis (2000)

This review highlights the applications of indium metal and indium(III) halides in organic synthesis with particular reference to regio-, stereo-, and chemoselectivity. Indium-mediated reactions include the regioselective allylation of alkynes, the stereoselective debromination of vic-aryl-substituted dibromides, the homocoupling of alkyl/aryl halides, and the reduction of α-halocarbonyl compounds. Indium trichloride has been used as a Lewis acid catalyst in epoxide rearrangements, in the synthesis of α-amino phosphonates, and in the construction of the quinoline system. Indium triiodide has proven to be a very efficient catalyst for transesterification processes.
Use of multidimensional fiber grating strain sensors for damage detection in composite pressure vessels (2005)

Arrays of multi-axis fiber grating strain sensors have been integrated into a composite pressure vessel test article, and are used to monitor changes in the transverse and axial strain fields during curing and pressure cycling near cut tow and Teflon tape defects. These changes in the multi-axis strain due to four pressure cycles and repeated impacts are measured and compared to ultrasonic and eddy current scans. Examples of the remote detection of damage using transverse strain and transverse strain gradients is given as well as data showing the ability of the system to distinguish broken tow and delamination defects.
Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease (1990)

To quantitate the contributions of the large hydrophobic residues in staphylococcal nuclease to the stability of its native state, single alanine and glycine substitutions were constructed by site-directed mutagenesis for each of the 11 leucine, 9 valine, 7 tyrosine, 5 isoleucine, 4 methionine, and 3 phenylalanine residues. In addition, each isoleucine was also mutated to valine. The resulting collection of 83 mutant nucleases was submitted to guanidine hydrochloride denaturation using intrinsic tryptophan fluorescence to monitor the equilibrium constant between the native and denatured states. From analysis of these data, each mutant protein's stability to reversible denaturation (delta GH2O) and sensitivity to guanidine hydrochloride (mGuHCl or d(delta G)/d[GuHCl]) were obtained. Four unexpected trends were observed. (1) A striking bipartite distribution was found for sites of mutations that altered mGuHCl: mutations that increased this parameter only involved residues that contribute side chains to the major hydrophobic core centered around a five-strand beta-barrel, whereas mutations that caused mGuHCl to decrease clustered around a second, smaller and less well-defined hydrophobic core. (2) The average stability loss for mutants in each of the six residue classes was 2-3 times greater than that estimated on the basis of the free energy of transfer of the hydrophobic side chain from water to n-octanol. (3) The magnitude of the stability loss on substituting Ala or Gly for a particular type of amino acid varied extensively among the different sites of its occurrence in nuclease, indicating that the environment surrounding a specific residue determines how large a stability contribution its side chain will make.(ABSTRACT TRUNCATED AT 250 WORDS)
Dehydrobenzol und N‐Methyl‐pyrrol (1958)

Abstract In Fortführung der Untersuchungen über die dienophilen Eigenschaften von Dehydrobenzol wurde dieses mit N ‐Methyl‐pyrrol in Reaktion gebracht, wobei die aus einer 1.4‐Addition hervorgehenden Verbindungen VI und VII als Haupt‐produkte zu isolieren waren. Ihr Entstehungschemismus wird diskutiert und zum Schluß auf die Bedeutung des H OFMANN ‐Abbaus bei endo ‐Ammonium‐hydroxyden hingewiesen.
HEALTH CARE CONTRAPTION (1994)

You could almost hear the jaws dropping when Ira Magaziner, the White House's guru at guruing, said over the weekend, "The government is going to set standards, guarantee high-quality, affordable care, and then get out of the way." As any of the health care reformers who used to gather at Jackson Hole could tell you, a lot of what's already wrong with the medical economy arises from Washington's habit of creating entitlements while trying to conceal from taxpayers how much they really cost... The whole Clinton health care scheme advances behind a phalanx of euphemism aimed at muddying up what's really going on here. It would spawn huge new bureaucracies, but these will travel under the alias "purchasing alliance." Price controls are subsumed under the MBAish-sounding "global budgets," and the taxes that would finance the thing are called "premiums"... It's odd to see people who are so obviously far behind the rest of the world's learning curve. In Sweden, Germany and most other serious places they're pulling U-turns and beginning to dismantle their expensive welfare bureaucracies...