gebhart/patrepeval huggingface dataset:
Immunological Effects of Thalidomide and Its Chemical and Functional Analogs (2002)

Thalidomide has recently shown considerable promise in the treatment of a number of conditions, such as leprosy and cancer. Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity. Novel compounds with improved immunomodulatory activity and side effect profiles are also being evaluated. These include selective cytokine inhibitory drugs (SelCIDs), with greatly improved TNF-alpha inhibitory activity, and immunomodulatory drugs (IMiDs) that are structural analogs of thalidomide, with improved properties. A third group recently identified within the SelCID group, with phosphodiesterase type 4-independent activity, is in the process of being characterized in laboratory studies. This review describes the emerging immunological properties of thalidomide, from a historical context to present-day clinical applications, most notably in multiple myeloma but also in other cancers, inflammatory disease, and HIV. We also describe the laboratory studies that have led to the characterization and development of SelCIDs and IMiDs into potentially clinically relevant drugs. Early trial data suggest that these novel immunomodulatory compounds may supercede thalidomide to become established therapies, particularly in certain cancers. Further evidence is required, however, to correlate the clinical efficacy of these compounds with their known immunomodulatory, antiangiogenic, and antitumor properties.
Pholipomycin, a new member of phosphoglycolipid antibiotics. II. Physico-chemical properties and comparison with other members of this family of antibiotics. (1977)

Physico-chemical characterization of pholipomycin revealed that this antibiotic is a new member of phosphoglycolipid antibiotics. Pholipomycin was differentiated from other members by the products formed on acid hydrolysis as follows: the presence of glucosamine, a 257 nm chromophore and moenocinol-type C25 lipids, but the absence of glucose, 6-deoxyglucosamine and glycine.
The Impact of Sonication on the Structure and Properties of Stain‐Etch Porous Silicon (1994)

The influence of sonication on the surface structure and chemical stability of porous silicon (PS) thin films prepared by an open‐circuit stain‐etch is described. An analysis of differences in surface morphologies by atomic force microscopy between samples prepared either in the presence or absence of sonication reveals that sonication generates a relatively rougher, thicker film as evidenced by the magnitudes of average and root‐mean square surface roughness and the maximum height of surface features. These differences result in stain‐etch porous Si films possessing greater chemical stability to exposure to reagents such as water and organoamines.
Heat mitigation of a core/cladding Yb-doped fiber amplifier using anti-Stokes fluorescence cooling (2019)

A core/cladding Yb-doped fiber amplifier configuration is presented that relies on anti-Stokes fluorescence cooling for effective heat mitigation in high-power operation. In the proposed design, the inner cladding of the double-clad fiber is doped with the same ion as in the core; therefore, the excess heat generated from the background absorption is removed by the anti-Stokes fluorescence in both core and inner cladding. We consider silica and ZBLAN glasses for the host material in the core/cladding Yb-doped fiber amplifier. The model incorporates the spatial profiles of the signal and pump intensities as well as the amplified spontaneous emission. The total linear heat density and temperature distribution in the fiber amplifier are calculated. The results show that the anti-Stokes fluorescence cooling in the core/cladding Yb-doped configuration can mitigate the generated heat effectively in high-power operation, which obviates the need for an external cooling system.
The rice genome encodes two vacuolar invertases with fructan exohydrolase activity but lacks the related fructan biosynthesis genes of the Pooideae (2006)

* Fructans are believed to contribute to cold and drought tolerance in several plant families (Poaceae, Asparagaceae and Asteraceae), but it is not clear why the ability to accumulate these polymers is found in some genera (e.g. Triticum) but not in others (e.g. Oryza). * As fructan biosynthesis enzymes (FBEs) evolved from vacuolar invertases (VINs), we searched the rice genome sequence for genes related to both FBE and VIN genes of wheat and other members of the Pooideae. We compared them at the levels of exon-intron structure, protein sequence, and the enzymatic properties of recombinant proteins after expression in the yeast Pichia pastoris. * We found that rice possesses two VIN genes (OsVIN1 and OsVIN2) and no FBE genes. FBE genes appear to have arisen in the Pooideae by a series of gene duplications from an ancestor of wheat TaVIN3. Recombinant TaVIN2, OsVIN1 and OsVIN2 behaved as invertases with no FBE activity, but possessed high fructan exohydrolase activity, especially OsVIN1. * The engineering of fructan accumulation into rice for greater stress tolerance could founder on endogenous exohydrolases, but the fact that OsVIN1 transcripts are absent from peduncles of well watered and drought-stressed plants removes one potential obstacle to this endeavour.
IncI2 plasmids specify sensitivity to filamentous bacteriophage IKe (1983)

Bacterial strains carrying the derepressed incompatibility group IncI2 plasmids TP114drp-l or R721pilc were lysed by the filamentous bacteriophages IKe, I2-2, and X. Phage I2-2 was serologically related to IKe, but phage X was not. Phage IKe adsorbed to the tips of thick pili determined by the IncI2 plasmids, but not to the well-known thin I2 pili.
National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004 (2004)

] Hospitals participating in the NNIS System provide general medical-surgical inpatient services to adults or children requiring acute care. Identity of the nearly 300 hospitals currently participating in the NNIS System is confidential.
The adjuvant properties of a nontoxic monophosphoryl lipid A in hyporesponsive and aging mice. (1987)

The immunomodulatory action of a nontoxic monophosphoryl lipid A (MPL) and a toxic diphosphoryl lipid A (DPL) fraction derived from endotoxins of the heptoseless mutants of bacteria were studied. Both derivatives retained the ability characteristic of lipopolysaccharides, i.e., to enhance antibody formation in young adult mice when injected along with antigen and suppress antibody production when given 1 day before antigen. In aging mice, a model of immunodeficiency, a marked restoration of antibody formation was observed when antigen was injected together with either MPL or DPL. Levels of antibody in the aging mice became comparable with those observed in young adult mice. Moreover, both MPL and DPL enhanced antibody production significantly in the endotoxin low-responder mouse strains C3H/HeJ and C57Bl/10 ScN, whereas phenol-water-extracted endotoxin from an Rd mutant was ineffective. MPL and DPL also acted as suppressive agents when administered prior to antigen in the C3H/HeJ strain. Thus, the results from these studies show that the toxic properties of lipid A can be removed without eliminating immunomodulating activity and certain forms of lipid A can overcome the immunologic lesions of immunodeficient and hyporesponsive animals.
Invited Commentary: A calculation of all possible oligosaccharide isomers both branched and linear yields 1.05 × 1012 structures for a reducing hexasaccharide: the Isomer Barrier to development of single-method saccharide sequencing or synthesis systems (1994)

The number of all possible linear and branched isomers of a hexasaccharide was calculated and found to be > 1.05 x 10(12). This large number defines the Isomer Barrier, a persistent technological barrier to the development of a single analytical method for the absolute characterization of carbohydrates, regardless of sample quantity. Because of this isomer barrier, no single method can be employed to determine complete oligosaccharide structure in 100 nmol amounts with the same assurance that can be achieved for 100 pmol amounts with single-procedure Edman peptide or Sanger DNA sequencing methods. Difficulties in the development of facile synthetic schemes for oligosaccharides are also explained by this large number. No current method of chemical or physical analysis has the resolution necessary to distinguish among 10(12) structures having the same mass. Therefore the 'characterization' of a middle-weight oligosaccharide solely by NMR or mass spectrometry necessarily contains a very large margin of error. Greater uncertainty accompanies results performed solely by sequential enzyme degradation followed by gel-permeation chromatography or electrophoresis, as touted by some commercial advertisements. Much of the literature which uses these single methods to 'characterize' complex carbohydrates is, therefore, in question, and journals should beware of publishing structural characterizations unless the authors reveal all alternate possible structures which could result from their analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Highly Fluorescent Semiconducting Polymer Dots for Biology and Medicine (2013)

In recent years, semiconducting polymer nanoparticles have attracted considerable attention because of their outstanding characteristics as fluorescent probes. These nanoparticles, which primarily consist of π-conjugated polymers and are called polymer dots (Pdots) when they exhibit small particle size and high brightness, have demonstrated utility in a wide range of applications such as fluorescence imaging and biosensing. In this review, we summarize recent findings of the photophysical properties of Pdots which speak to the merits of these entities as fluorescent labels. This review also highlights the surface functionalization and biomolecular conjugation of Pdots, and their applications in cellular labeling, in vivo imaging, single-particle tracking, biosensing, and drug delivery. We discuss the relationship between the physical properties and performance, and evaluate the merits and limitations of the Pdot probes for certain imaging tasks and fluorescence assays. We also tackle the current challenges of Pdots and share our perspective on the future directions of the field.
Magnetoresistance andV-Icurves of Ag-sheathed (Bi,Pb)2Sr2Ca2Cu3O10+ytape (1994)

The magnetoresistance and the V-I curves (I&gt;${\mathit{I}}_{\mathit{c}}$) of a well-characterized Ag-clad (Bi,Pb${)}_{2}$${\mathrm{Sr}}_{2}$${\mathrm{Ca}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{10+\mathit{y}}$ tape (BPSCCO) with ${\mathit{J}}_{\mathit{c}}$(77 K, B=0)=10 kA/${\mathrm{cm}}^{2}$ have been analyzed in the temperature (T) range 80--110 K and magnetic field (B) up to 60 mT. The results obtained after the correction for the parallel conduction through the Ag sheathing and BPSCCO core are similar to those for corresponding single crystals and the epitaxial thin films. The effective activation energy for the flux creep ${\mathit{U}}_{0}$ is larger than those for the single crystals and thin films of Bi-Sr-Ca-Cu-O (BSCCO) compound. The variations of the differential resistance ${\mathit{R}}_{\mathit{f}}$ (deduced from V-I curves at I\ensuremath{\gg}${\mathit{I}}_{\mathit{c}}$) with T and B are consistent with those for the conventional type-II superconductors at elevated temperatures and low fields. Hence the unusual features deduced from the total dissipation in similar tapes are probably due to improper data analysis. The analysis presented here relies on the homogeneity of dissipation within the core which has to be checked for each tape.
Malaria Transmitted to Humans by Mosquitoes Infected from Cultured Plasmodium falciparum (1986)

Malaria was transmitted to six normal human volunteers by mosquitoes infected from cultured gametocytes of Plasmodium falciparum. This method, which offers advantages over other methods of infecting volunteers, will be useful for evaluating the efficacy of human malaria vaccines.
Proteome research: Complementarity and limitations with respect to the RNA and DNA worlds (1997)

A methodological overview of proteome analysis is provided along with details of efforts to achieve high-throughput screening (HTS) of protein samples derived from two-dimensional electrophoresis gels. For both previously sequenced organisms and those lacking significant DNA sequence information, mass spectrometry has a key role to play in achieving HTS. Prototype robotics designed to conduct appropriate chemistries and deliver 700-1000 protein (genes) per day to batteries of mass spectrometers or liquid chromatography (LC)-based analyses are well advanced, as are efforts to produce high density gridded arrays containing > 1000 proteins on a single matrix assisted laser desorption ionisation/time-of-flight (MALDI-TOF) sample stage. High sensitivity HTS of proteins is proposed by employing principally mass spectrometry in an hierarchical manner: (i) MALDI-TOF-mass spectrometry (MS) on at least 1000 proteins per day; (ii) electrospray ionisation (ESI)/MS/MS for analysis of peptides with respect to predicted fragmentation patterns or by sequence tagging; and (iii) ESI/MS/MS for peptide sequencing. Genomic sequences when complemented with information derived from hybridisation assays and proteome analysis may herald in a new era of holistic cellular biology. The current preoccupation with the absolute quantity of gene-product (RNA and/or protein) should move backstage with respect to more molecularly relevant parameters, such as: molecular half-life; synthesis rate; functional competence (presence or absence of mutations); reaction kinetics; the influence of individual gene-products on biochemical flux; the influence of the environment, cell-cycle, stress and disease on gene-products; and the collective roles of multigenic and epigenetic phenomena governing cellular processes. Proteome analysis is demonstrated as being capable of proceeding independently of DNA sequence information and aiding in genomic annotation. Its ability to confirm the existence of gene-products predicted from DNA sequence is a major contribution to genomic science. The workings of software engines necessary to achieve large-scale proteome analysis are outlined, along with trends towards miniaturisation, analyte concentration and protein detection independent of staining technologies. A challenge for proteome analysis into the future will be to reduce its dependence on two-dimensional (2-D) gel electrophoresis as the preferred method of separating complex mixtures of cellular proteins. Nonetheless, proteome analysis already represents a means of efficiently complementing differential display, high density expression arrays, expressed sequence tags, direct or subtractive hybridisation, chromosomal linkage studies and nucleic acid sequencing as a problem solving tool in molecular biology.
Disease Progression in a Transgenic Model of Familial Amyotrophic Lateral Sclerosis Is Dependent on Both Neuronal and Non-Neuronal Zinc Binding Proteins (2002)

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause one form of familial amyotrophic lateral sclerosis, a progressive disorder of motor neurons leading to weakness and death of affected individuals. Experiments using both transgenic mice expressing mutant SOD1 and SOD1 knock-out mice have demonstrated that disease is caused by a toxic gain of function and not by a loss of normal SOD1 activity. Precise mechanisms underlying mutant SOD1 toxicity are unclear but may involve abnormal interactions between zinc and SOD1. The metallothioneins (MTs) represent a family of zinc binding proteins that can function as zinc chaperones for apo-SOD1 in vitro. We hypothesized that manipulation of metallothioneins in vivo might alter the disease phenotype of transgenic mice expressing G93A SOD1 and therefore crossed this line with MT-I and MT-II or MT-III knock-out mice. G93A SOD1 mice deficient of either MT-I and MT-II or MT-III exhibited significant reductions in survival compared with G93A SOD1 mice. In addition, motor dysfunction was markedly accelerated in G93A SOD1 mice deficient in metallothioneins with regard to onset (MT-I and MT-II) or progression (MT-III). These results indicate that the disease course in G93A SOD1 mice is dependent on levels of metallothionein expression. Because MT-I and MT-II are expressed in glia whereas MT-III is found in neurons, these results also indicate that primary changes within non-neuronal cells can affect mutant SOD1-induced disease and do so in ways distinct from primary neuronal changes.
Dynamic hierarchical self-organizing neural networks (2002)

In this paper, we integrate the concept of self-organizing feature maps and the architecture of dynamic trees to develop dynamic hierarchical self-organizing neural networks. The proposed network is capable of allocating new neurons dynamically during the learning process and then determining its own topology. A fuzzy membership function which measures the similarity of the input data is employed in the weight updating procedure and used as an criterion to allocate new neurons. Unlike the conventional self-organizing neural networks, the training samples are not input in sequence to update the weights. Instead, the weight updating procedure takes into account all the training data at one time. All these provide the proposed networks several advantages including revelation of hierarchical structure in data, dynamic allocation of neurons, short learning time, and short search time. To demonstrate their capabilities, the proposed networks are applied to solve the image segmentation problems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes (2003)

In T lymphocytes, sustained calcium (Ca2+) influx through Ca2+ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca2+ channels (VDCCs) play a role in Ca2+ mobilization during T lymphocyte activation. However, the role of VDCCs in otherwise nonexcitable cells is still poorly understood. We used RT-PCR to identify a transcript encoding the pore-forming alpha1F-subunit of an L-type Ca2+ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca2+ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca2+ channel agonist, (+/-) Bay K 8644, and antagonist, nifedipine, on the human Jurkat T cell leukemia line, human peripheral blood T lymphocytes and mouse splenocytes. We found that treatment of T lymphocytes with (+/-) Bay K 8644 increased intracellular Ca2+ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca2+ influx, the activity of Erk1/2 and nuclear factor of activated T cells (NFAT), interleukin-2 (IL-2) production, and IL-2 receptor expression. Nifedipine also significantly suppressed splenocyte proliferation in an in vitro mixed lymphocyte reaction and the proliferation of male antigen (H-Y)-specific T cell receptor-transgenic CD8+ T cells in transplanted male mice in vivo. Taken together these novel findings indicate that an L-type Ca2+ channel plays a significant role in the Ca2+ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo.
Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. (1993)

Taxol inhibited HeLa cell proliferation by inducing a sustained mitotic block at the metaphase/anaphase boundary. Half-maximal inhibition of cell proliferation occurred at 8 nM taxol, and mitosis was half-maximally blocked at 8 nM taxol. Inhibition of mitosis was associated with formation of an incomplete metaphase plate of chromosomes and an altered arrangement of spindle microtubules that strongly resembled the abnormal organization that occurs with low concentrations of vinblastine and other antimitotic compounds. No increase in microtubule polymer mass occurred below 10 nM taxol. The mass of microtubules increased half-maximally at 80 nM taxol and attained maximal levels (5 times normal) at 330 nM taxol. At submicromolar concentrations, taxol suppressed growing and shortening at the ends of microtubules reassembled in vitro from bovine brain tubulin in a manner that resembled suppression by vinblastine. Taxol was concentrated in HeLa cells several hundredfold to levels that were similar to those which suppressed dynamic instability in vitro. The results indicate that taxol shares a common antiproliferative mechanism with vinblastine. At its lowest effective concentrations, taxol appears to block mitosis by kinetically stabilizing spindle microtubules and not by changing the mass of polymerized microtubules.
Definition of an efficient synthetic poly(A) site. (1989)

We constructed and analyzed a synthetic poly(A) (SPA) site that was based on the highly efficient poly(A) signal of the rabbit beta-globin gene. By use of the SPA, we demonstrate that the minimum sequences required for efficient polyadenylation are the AATAAA sequence and a GT/T-rich sequence with the correct spacing of 22-23 nucleotides between them. When placed downstream of the poly(A) site of the human alpha 2-globin gene, the SPA is used exclusively. We predict that the SPA, with its more extensive GT/T-rich sequence, is a more efficient poly(A) site than alpha-globin. Also, we compared the use of the SPA when it is placed either in the exon 3 or intron 2 of the rabbit beta-globin gene. When in the exonic position, SPA is used 10-fold more than the regular poly(A) site of rabbit beta-globin. In contrast, when it is in the intronic location, no detectable use of SPA is observed; however, the deletion of the donor site of intron 2 reactivates the intronic positioned SPA. These results indicate that the splicing of intron 2 in the rabbit beta-globin gene occurs ahead of polyadenylation and have important implications for termination of transcription. Polyadenylation, although required for termination of transcription, is not sufficient; therefore, additional termination signals for RNA polymerase II must exist.
Long-term use of magnesium hydroxide as a phosphate binder in patients on hemodialysis. (1987)

The long-term use of magnesium hydroxide [Mg(OH)2] as a phosphate binder was investigated in 18 patients on chronic hemodialysis. All patients received a basal treatment with oral calcium carbonate. Vitamin D supplements were not used. In period I each patient ingested aluminum hydroxide [Al(OH)3], in period II Mg(OH)2 and in period III Mg(OH)2 and Al(OH)3 together. During period II and III a dialysate devoid of Mg was used. Mg(OH)2 doses were adjusted to prevent severe hypermagnesemia and diarrhea. The mean dose of Mg(OH)2 in period II was 2.4 +/- 0.6 and in period III 2.6 +/- 1.2 g/day. Serum phosphate increased significantly in period II and fell again in period III. Despite a halving of the Al(OH)3 dose in period III, serum Al was similar in period I and period III (55.8 +/- 19.1 vs 57.1 +/- 27.3 microg/l). Parathyroid hormone (PTH) concentration fell in period II and decreased even further in period III. We conclude that oral Mg(OH)2 may reduce the required Al(OH)3 dose, however, without an effect on serum Al concentration. The observed suppression of parathyroid activity needs further study.