gebhart/patrepeval huggingface dataset:
Relationship between insulin A chain regions and insulin biological activities (2000)

AIM:To study the relationship between insulin A chain regions and insulin biological activities, we designed a series of insulin analogues with changes at A21, A12-18 of C terminal helical region and A8-10 located in the region of A6-A11 intra-chain disulphide bond.METHODS:Insulin A-chain analogues were prepared by stepwise Fmoc solid phase manual synthesis and then combined with natural B-chain of porcine insulin to yield corresponding insulin analogues. Their biological activities were tested by receptor binding, mouse convulsion and immunological assay.RESULTS: A21Ala Ins retains 70.3% receptor binding capacity and 60% in vivo biological activity.DesA13-14, A21Ala Ins and DesA12-13-14-15, A21Ala Ins still have definite biological activity,7.9% and 4.0% receptor binding,and 6.2% and 3.3% in vivo biological activity respectively. A15Asn, A17Pro, A21Ala Ins maintains 10.4% receptor binding and 10% in vivo biological activity. A8His, A9Arg, A10Pro, A21Ala Ins, A8His, A9Lys, A10Pro, A21Ala Ins and A8His, A9Lys, A10Arg, A21Ala Ins have 51.9%, 44.3% and 32.1% receptor binding respectively,50%, 40% and 30% in vivo biological activity respectively, and 28.8%, 29.6% and 15.4% immunological activity respectively.CONCLUSION:A21Asn can be replaced by simple amino acid residues.The A chains with gradually damaged structural integrity in A12-18 helical region and the demolition of the A12-18 helical region by the substitution of Pro and Asn for A17Glu and A15Gln respectively can combine with the B chain and the combination products show definite biological activity, the helical structure of A12-18 is essential for biological activities of insulin. A8-10 is not much concerned with biological activities, but is much more important antigenically in binding to its antibodies, these results may help us design a new type of insulin analogue molecule.
Common Principles of Protein Translocation Across Membranes (1996)

Most major systems that transport proteins across a membrane share the following features: an amino-terminal transient signal sequence on the transported protein, a targeting system on the cis side of the membrane, a hetero-oligomeric transmembrane channel that is gated both across and within the plane of the membrane, a peripherally attached protein translocation motor that is powered by the hydrolysis of nucleoside triphosphate, and a protein folding system on the trans side of the membrane. These transport systems are divided into two families: export systems that export proteins out of the cytosol, and import systems that transport proteins into cytosol-like compartments.
Cost burden of treatment resistance in patients with depression. (2010)

Early identification of TRD patients, using a claims-based algorithm, may support targeted interventions for these patients.
VI.B.4 DOE Chemical Hydrogen Storage Center of Excellence (2005)

Partners: Intematix Corporation, Xiao-Dong Xiang Millennium Cell Inc., Ying Wu Northern Arizona University (NAU), Clinton F. Lane Pacific Northwest National Laboratory (PNNL), Christopher L. Aardahl Pennsylvania State University (Penn State), Digby D. Macdonald Rohm and Haas Company, Suzanne W. Linehan US Borax, David Schubert University of Alabama, David A. Dixon University of California, Davis (UC Davis), Philip P. Power University of California, Los Angeles (UCLA), M. Frederick Hawthorne University of Pennsylvania (Penn), Larry G. Sneddon University of Washington (UW), Karen I. Goldberg
Hepatitis B and C viruses: molecular identification and targeted antiviral therapies. (1998)

Four agents are in clinical development for the treatment of chronic hepatitis B infection. These nucleoside analogs are incorporated into the growing DNA chain and terminate replication. Lamivudine, a cytadine analog that inhibits the synthesis of negative strand DNA from pre-genomic RNA, predictably inhibits replication and improves liver enzymes and histology in infected individuals. Following cessation of treatment, relapse is common, and genetic causes of viral resistance have been described. Other drugs for HBV infection include famciclovir, a guanosine analog that has also shown to suppress replication in immunocompetent as well as in immunocompromised patients; lobucavir, a guanosine analog; and adevfovir, an adenine nucleotide analog. The future of drug therapy against HBV likely includes combination agents with one or more nucleoside/nucleotide analogs and immune stimulants, such as interferon, or therapeutic vaccines. Recent advances in the treatment of HCV have been less impressive. An effective vaccine is greatly needed yet development in the near future is unlikely. Recommendations for therapy of chronic HCV have been proposed following the National Institutes of Health Consensus Conference. Interferon alpha is advised in patients with elevated serum alanine aminotransferases and liver histology demonstrating active hepatitis, regardless of level of pretreatment viremia or infecting genotype. Therapy should be continued for three months, at which time response should be assessed. If a biochemical and/or virological response has been achieved, treatment should be continued for a year. Trials are underway to evaluate interferon in combination with ribavirin. Recent identification of the crystalline structure of the HCV NS3 protease promises development of effective inhibitors of this critical viral enzyme.
Nematode.net update 2008: improvements enabling more efficient data mining and comparative nematode genomics (2008)

Nematode.net (http://nematode.net) is a publicly available resource dedicated to the study of parasitic nematodes. In 2000, the Genome Center at Washington University (GC) joined a consortium including the Nematode Genomics group in Edinburgh, and the Pathogen Sequencing Unit of the Sanger Institute to generate expressed sequence tags (ESTs) as an inexpensive and efficient solution for gene discovery in parasitic nematodes. As of 2008 the GC, sampling key parasites of humans, animals and plants, has generated over 500,000 ESTs and 1.2 million genome survey sequences from more than 30 non-Caenorhabditis elegans nematodes. Nematode.net was implemented to offer user-friendly access to data produced by this project. In addition to sequence data, the site hosts: assembled NemaGene clusters in GBrowse views characterizing composition and protein homology, functional Gene Ontology annotations presented via the AmiGO browser, KEGG-based graphical display of NemaGene clusters mapped to metabolic pathways, codon usage tables, NemFam protein families which represent conserved nematode-restricted coding sequences not found in public protein databases, a web-based WU-BLAST search tool that allows complex querying and other assorted resources. The primary aim of Nematode.net is the dissemination of this diverse collection of information to the broader scientific community in a way that is useful, consistent, centralized and enduring.
Silanediol Protease Inhibitors: From Conception to Validation (2005)

Abstract Silanediols are isosteric with the unstable hydrated carbonyl group, but are most commonly associated with polymerization to give silicone polymers. Placement of a silanediol in a dipeptide analogue yields a new kind of nonhydrolyzable transition‐state‐analogue protease inhibitor. Both metallo and aspartic protease inhibitors have been prepared using silanediols, with enzyme inhibition in the low nanomolar range. Structure–activity comparisons with known inhibitors, efficacy in whole cell assays, and a crystal structure of a silanediol inhibitor bound to the thermolysin active site establish these silanediol inhibitors as effective and predictable new protease inhibitor tools. Recent chemistry developments have led to efficient and streamlined preparation of these inhibitors. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Histamine H1-receptor blockade in humans affects psychomotor performance but not memory (2008)

Results from recent animal studies suggest an important role for histamine in memory functioning. Histaminergic drugs might prove beneficial for people suffering from memory impairment. To determine if histamine is involved in memory functioning this study evaluates the effects of histaminergic dysfunction on memory performance by administrating a H1-antagonist to humans. The study was conducted according to a 4-way, double-blind, crossover design in 20 healthy female volunteers, aged 18-45 years. On each test day subjects completed three test sessions: before and around 2 and 4 h after administration of single oral doses of dexchlorpheniramine 2 mg or 4 mg, scopolamine 1 mg or placebo. Drug effects were assessed using tests of memory, psychomotor and attention performance, and subjective alertness. Results showed that dexchlorpheniramine impaired performance in tests of spatial learning, reaction time, tracking and divided attention but showed no effects on working memory, visual memory, word learning or memory scanning. Scopolamine induced a similar pattern of effects. In addition, both drugs decreased subjective alertness. In conclusion results show that dexchlorpheniramine and scopolamine clearly impaired performance on psychomotor and attention tasks but do not suggest a specific role of the histaminergic system in learning and memory in humans.
Yield-Aware Cache Architectures (2006)

One of the major issues faced by the semiconductor industry today is that of reducing chip yields. As the process technologies have scaled to smaller feature sizes, chip yields have dropped to around 50% or less. This figure is expected to decrease even further in future technologies. To attack this growing problem, we develop four yield-aware micro architecture schemes for data caches. The first one is called yield-aware power-down (YAPD). YAPD turns off cache ways that cause delay violation and/or have excessive leakage. We also modify this approach to achieve better yields. This new method is called horizontal YAPD (H-YAPD), which turns off horizontal regions of the cache instead of ways. A third approach targets delay violation in data caches. Particularly, we develop a variable-latency cache architecture (VACA). VACA allows different load accesses to be completed with varying latencies. This is enabled by augmenting the functional units with special buffers that allow the dependants of a load operation to stall for a cycle if the load operation is delayed. As a result, if some accesses take longer than the predefined number of cycles, the execution can still be performed correctly, albeit with some performance degradation. A fourth scheme we devise is called the hybrid mechanism, which combines the YAPD and the VACA. As a result of these schemes, chips that may be tossed away due to parametric yield loss can be saved. Experimental results demonstrate that the yield losses can be reduced by 68.1% and 72.4% with YAPD and H-YAPD schemes and by 33.3% and 81.1% with VACA and Hybrid mechanisms, respectively, improving the overall yield to as much as 97.0%
Melting behavior of a covalently closed, single-stranded, circular DNA (1989)

We synthesized the 26-residue deoxynucleotide sequence d(TTCCT5GGAATTCCT5GGAA) which folds intramolecularly to form a dumbbell-shaped, double-hairpin structure with a gap between the 3' and the 5' ends. We used T4 polynucleotide kinase to phosphorylate the 5' end followed by T4 DNA ligase to close the 3' and 5' ends. Melting of the dumbbell structure formed by this ligated sequence produces a covalently closed, single-stranded, circular final state. We employed calorimetric and spectroscopic techniques to characterize thermodynamically the melting behavior of the ligated molecule and compared it with the corresponding melting behavior of its unligated precursor. This comparison allowed us to characterize uniquely the influence of single-stranded ring closure on intramolecular duplex melting. The data reveal that ring closure produces a thermally more stable structure which exhibits significantly altered melting thermodynamics. We rationalize these thermodynamic differences in terms of differential solvation and differential counterion association between the ligated and unligated molecules. We also note the importance of such constrained dumbbell structures as models for hairpins, cruciforms, and locally melted domains within naturally occurring DNA polymers.
Mast cells and basophils (2000)

Mast cells and basophils are effector cells in IgE-associated immune responses, such as those that contribute to asthma and other allergic diseases and to host resistance to parasites. Recent work shows that mast cells can also participate in innate immunity to bacterial infection and that the expression of such mast cell-dependent natural immunity can be significantly enhanced by long-term treatment of mice with the kit ligand, stem cell factor. However, mast cells may also influence many other biologic responses, including tissue remodeling and angiogenesis. This review discusses certain recent findings about the differentiation, phenotype, and function of basophils and mast cells, as well as briefly considering evolving concepts about the roles of these cells in health and disease.
Non-Parametric Bayesian Dictionary Learning for Sparse Image Representations (2009)

Abstract—Nonparametric Bayesian methods are considered for recovery of imagery based upon compressive, incomplete, and/or noisy measurements. A truncated beta-Bernoulli process is em-ployed to infer an appropriate dictionary for the data under test and also for image recovery. In the context of compressive sensing, significant improvements in image recovery are manifested using learned dictionaries, relative to using standard orthonormal image expansions. The compressive-measurement projections are also optimized for the learned dictionary. Additionally, we consider simpler (incomplete) measurements, defined by measuring a subset of image pixels, uniformly selected at random. Spatial interrelationships within imagery are exploited through use of the Dirichlet and probit stick-breaking processes. Several example results are presented, with comparisons to other methods in the literature. Index Terms—Bayesian nonparametrics, compressive sensing, dictionary learning, factor analysis, image denoising, image inter-polation, sparse coding.
Hydrogen redistribution and gettering in AlCu/Ti thin films (1991)

Redistribution and uptake of hydrogen was found to occur during anneals in forming gas (90% N2+10% H2) of thin-film AlCu/Ti/AlCu sandwich layers deposited on a thin layer of SiO2. Annealing at 350 or 400 °C for 30 min caused the Ti-containing layer to getter hydrogen, which came from both the upper and lower interfaces of the SiO2 and from the gas. The uptake kinetics from the gas were surface limited. The hydrogen distribution was influenced by the formation of TiAl3, in which the solubility of hydrogen was found to be negligible. Hydrogen in partly reacted layers was found to be associated with unreacted titanium.
Mechanism of DNA Release from Cationic Liposome/DNA Complexes Used in Cell Transfection, (1996)

To understand how DNA is released from cationic liposome/DNA complexes in cells, we investigated which biomolecules mediate release of DNA from a complex with cationic liposomes. Release from monovalent[1,2-dioleoyl-3(1)-1(trimethylammonio)propane] or multivalent (dioctadecylamidoglycylspermine) lipids was quantified by an increase of ethidium bromide (EtBr) fluorescence. Plasmid sensitivity to DNAse I degradation was examined using changes in plasmid migration on agarose gel electrophoresis. Physical separation of the DNA from the cationic lipid was confirmed and quantified on sucrose density gradients. Anionic liposomes containing compositions that mimic the cytoplasmic-facing monolayer of the plasma membrane (e.g. phosphatidylserine) rapidly released DNA from the complex. Release occurred near a 1/1 charge ratio (-/+) and was unaffected by ionic strength or ion type. Water soluble molecules with a high negative linear charge density such as dextran sulfate or heparin also released DNA. However, ionic water soluble molecules such as ATP, tRNA, DNA, poly(glutamic acid), spermidine, spermine, or histone did not, even at 100-fold charge excess (-/+). On the basis of these results, we propose that after the cationic lipid/DNA complex is internalized into cells by endocytosis it destabilizes the endosomal membrane. Destabilization induces flip-flop of anionic lipids from the cytoplasmic-facing monolayer, which laterally diffuse into the complex and form a charge neutral ion pair with the cationic lipids. This results in displacement of the DNA from the cationic lipid and release of the DNA into cytoplasm. This mechanism accounts for a variety of observations on cationic lipid/DNA complex-cell interactions.
Identification of a novel glucose transporter-like protein—GLUT-12 (2002)

Facilitative glucose transporters exhibit variable hexose affinity and tissue-specific expression. These characteristics contribute to specialized metabolic properties of cells. Here we describe the characterization of a novel glucose transporter-like molecule, GLUT-12. GLUT-12 was identified in MCF-7 breast cancer cells by homology to the insulin-regulatable glucose transporter GLUT-4. The GLUT-12 cDNA encodes 617 amino acids, which possess features essential for sugar transport. Di-leucine motifs are present in NH(2) and COOH termini at positions similar to the GLUT-4 FQQI and LL targeting motifs. GLUT-12 exhibits 29% amino acid identity with GLUT-4 and 40% to the recently described GLUT-10. Like GLUT-10, a large extracellular domain is predicted between transmembrane domains 9 and 10. Genomic organization of GLUT-12 is highly conserved with GLUT-10 but distinct from GLUTs 1-5. Immunofluorescence showed that, in the absence of insulin, GLUT-12 is localized to the perinuclear region in MCF-7 cells. Immunoblotting demonstrated GLUT-12 expression in skeletal muscle, adipose tissue, and small intestine. Thus GLUT-12 is potentially part of a second insulin-responsive glucose transport system.
Overexpression of Follistatin-Like 3 in Gonads Causes Defects in Gonadal Development and Function in Transgenic Mice (2004)

Activin has numerous biological activities including regulation of follicular development, spermatogenesis, and steroidogenesis within the gonads. Activities of activin are regulated by follistatin (FST), an activin binding protein, and perhaps follistatin-like 3 (FSTL3; also known as FLRG and FSRP). FSTL3 is a recently described member of the FST family having an overall structure and activity profile similar to that of FST, including binding and neutralization of activin. FSTL3 is most highly expressed in the placenta and testis, whereas FST is highest in the ovary and kidney, suggesting that FSTL3 has biological actions that do not entirely overlap those of FST. To investigate the role of local FSTL3 as a potential regulator of activin action in gonad development and function, we examined FSTL3 expression in the mouse testis. FSTL3 protein was localized to Leydig cells, spermatagonia, and mature spermatids in normal male mice. We then created transgenic mice using a human FSTL3 cDNA driven by the mouse alpha-inhibin promoter. Three of five transgenic founders were fertile and were bred to establish lines. In the highest expressing line 3, transgene expression was largely restricted to gonads, with pituitary, adrenal, brain, and uterine expression being substantially lower. Gonad weights, sperm counts, and fertility were significantly reduced in transgenic males, and reduced litter size was evident in line 3 females. Within the testis, highest transgene expression was observed in Sertoli cells, and although most tubules showed evidence of normal spermatogenic development, degenerating tubules devoid of germ cells and Leydig cell hyperplasia were also evident in every line 3 animal examined. Ovaries from line 3 females contained fewer antral follicles and more apparent follicular atresia. Although circulating human FSTL3 levels were undetectable, FSH and LH levels in adult transgenic mice were not significantly different from wild-type animals. However, testosterone levels were significantly increased at d 21 and significantly reduced at d 60 compared with wild-type males. These results suggest that FSTL3 is likely to be a local regulator of activin action in gonadal development and gametogenesis and, further, that activin appears to have important actions in gonadal development and function that are critical for normal reproduction.
Evidence for the expression of four myelin basic protein variants in the developing human spinal cord through cDNA cloning (1987)

Four human myelin basic protein (MBP) variants with molecular masses of 21.5, 20.2, 18.5, and 17.3 kilodaltons (kDa) have been identified in the developing human spinal cord and their structures determined through an analysis of cDNA clones of their mRNAs. The 20.2-kDa MBP mRNA encoded a novel MBP variant, the structure of which has not been reported in any species. Its amino acid sequence was identical with that of the 21.5-kDa MBP except for a deletion of 11 amino acid residues encoded by exon 5 of the MBP gene. All four human MBP variants were identical except for the insertion of deletion of two peptide fragments corresponding to those encoded by exons 2 and 5 of the MBP gene. In this study, no mature human MBP cDNAs missing exon 6 sequences were identified. This suggests that, unlike the mouse, the four human MBP mRNAs encoding these MBP variants arise by the alternative splicing of only exons 2 and 5 from the primary MBP gene transcript. This indicates that the predominant MBP splicing pathways in human and mouse are different. Immunoblots of human fetal spinal cords (11-21 weeks) indicated that MBP expression turned on abruptly between 14 and 16 weeks. Expression of the 20.2-kDa MBP variant was most evident at 16 weeks and its relative proportion declined thereafter, suggesting that its expression was developmentally regulated.
PD‐L1 expression in cutaneous squamous cell carcinoma correlates with risk of metastasis (2016)

This survey documents PD-L1 expression in cutaneous squamous cell carcinoma and shows a positive correlation between the degree PD-L1 expression and pathologic findings related to risk of metastasis including large diameter, higher histological grade and tumor thickness.
The FadR·DNA Complex (2001)

In Escherichia coli, the expression of fatty acid metabolic genes is controlled by the transcription factor, FadR. The affinity of FadR for DNA is controlled by long chain acyl-CoA molecules, which bind to the protein and modulate gene expression. The crystal structure of FadR reveals a two domain dimeric molecule where the N-terminal domains bind DNA, and the C-terminal domains bind acyl-CoA. The DNA binding domain has a winged-helix motif, and the C-terminal domain resembles the sensor domain of the Tet repressor. The FadR.DNA complex reveals how the protein interacts with DNA and specifically recognizes a palindromic sequence. Structural and functional similarities to the Tet repressor and the BmrR transcription factors suggest how the binding of the acyl-CoA effector molecule to the C-terminal domain may affect the DNA binding affinity of the N-terminal domain. We suggest that the binding of acyl-CoA disrupts a buried network of charged and polar residues in the C-terminal domain, and the resulting conformational change is transmitted to the N-terminal domain via a domain-spanning alpha-helix.