gebhart/patrepeval huggingface dataset:
Structure of Complex of Synthetic HIV-1 Protease with a Substrate-Based Inhibitor at 2.3 Å Resolution (1989)

The structure of a complex between a peptide inhibitor with the sequence N-acetyl-Thr-Ile-Nle-psi[CH2-NH]-Nle-Gln-Arg.amide (Nle, norleucine) with chemically synthesized HIV-1 (human immunodeficiency virus 1) protease was determined at 2.3 A resolution (R factor of 0.176). Despite the symmetric nature of the unliganded enzyme, the asymmetric inhibitor lies in a single orientation and makes extensive interactions at the interface between the two subunits of the homodimeric protein. Compared with the unliganded enzyme, the protein molecule underwent substantial changes, particularly in an extended region corresponding to the "flaps" (residues 35 to 57 in each chain), where backbone movements as large as 7 A are observed.
Biochemical Evidence for the Oligomeric (Possibly Trimeric) Structure of the Major Inner Capsid Polypeptide (45K) of Rotaviruses (1985)

The major structural polypeptide of rotaviruses is p45K (VP6), which forms the morphological subunit of the inner capsid. Such subunits show a trimeric structure when examined with the electron microscope. Treatment of single-capsid rotavirus particles with 1.5 M-CaCl2 removes p45K, resulting in the generation of smooth cores. Sucrose density gradient centrifugation analysis of the removed p45K revealed that it has a sedimentation coefficient close to 7.3S, compatible with an oligomeric (possibly trimeric) structure. Polyacrylamide gel electrophoresis under reducing or non-reducing conditions indicated that p45K has intramolecular but not intermolecular disulphide bonds, suggesting that interactions between p45K monomers may be due to some other type of association, such as hydrophobic or charge interactions. Velocity sedimentation of infected cell extracts revealed that native p45K also behaves as an oligomeric protein. Such results were confirmed using p45K partially purified by DEAE-cellulose chromatography. The evidence obtained indicated that all p45K present in the virion is in the oligomeric form, not associated by disulphide bonding, and that most native p45K present in the infected cells is also in the oligomeric form, probably as a consequence of early protein-protein interaction in rotavirus morphogenesis.
Partial parsing via finite-state cascades (1996)

Finite state cascades represent an attractive architecture for parsing unrestricted text. Deterministic parsers specified by finite state cascades are fast and reliable. They can be extended at modest cost to construct parse trees with finite feature structures. Finally, such deterministic parsers do not necessarily involve trading off accuracy against speed — they may in fact be more accurate than exhaustive search stochastic context free parsers.
Serine Phosphorylation of SLP76 Is Dispensable for T Cell Development but Modulates Helper T Cell Function (2017)

The adapter protein SLP76 is a key orchestrator of T cell receptor (TCR) signal transduction. We previously identified a negative feedback loop that modulates T cell activation, involving phosphorylation of Ser376 of SLP76 by the hematopoietic progenitor kinase 1 (HPK1). However, the physiological relevance of this regulatory mechanism was still unknown. To address this question, we generated a SLP76-S376A-expressing knock-in mouse strain and investigated the effects of Ser376 mutation on T cell development and function. We report here that SLP76-S376A-expressing mice exhibit normal thymocyte development and no detectable phenotypic alterations in mature T cell subsets or other lymphoid and myeloid cell lineages. Biochemical analyses revealed that mutant T cells were hypersensitive to TCR stimulation. Indeed, phosphorylation of several signaling proteins, including SLP76 itself, phospholipase Cγ1 and the protein kinases AKT and ERK1/2, was increased. These modifications correlated with increased Th1-type and decreased Th2-type cytokine production by SLP76-S376A T cells, but did not result in significant changes of proliferative capacity nor activation-induced cell death susceptibility. Hence, our results reveal that SLP76-Ser376 phosphorylation does not mediate all HPK1-dependent regulatory effects in T cells but it fine-tunes helper T cell responses.
Monitoring human immunodeficiency virus type 1-infected patients by ratio of antibodies to gp41 and p24 (1989)

Antibody responses of 85 patients to human immunodeficiency virus type 1 antigens were quantitated by densitometric analysis of Western blot (immunoblot) assays. All patients had been classified into the following three clinical categories: asymptomatic (ASY), acquired immunodeficiency syndrome (AIDS)-related complex (ARC), or AIDS. Fifty of the patients were monitored for 6 to 29 months. The gp41/p24 antibody ratio was examined in three studies. In the first study, initial specimens from each patient were analyzed. The mean gp41/p24 antibody ratios were 1.5 (ASY), 3.2 (ARC), and 5.4 (AIDS). Of ASY patients, 79% had antibody ratios of less than 2.0. In contrast, 72% of patients with AIDS had ratios of greater than or equal to 2.0. In the second study, serially obtained specimens from ASY, ARC, and AIDS patients were analyzed. These patients were further grouped according to progression of their clinical condition. Of ASY patients whose clinical condition progressed to ARC, 80% consistently had ratios of greater than or equal to 2.0. Of ARC patients whose clinical condition progressed to AIDS, 71% consistently had ratios of greater than or equal to 2.0. Of AIDS patients who died during the study, 100% consistently had ratios of greater than or equal to 2.0. No patients were treated with azidothymidine during the first two studies. In the third study, AIDS patients were monitored before and during treatment with azidothymidine. During treatment, ratios stabilized or improved transiently in five of seven patients. In these three studies, a gp41/p24 antibody ratio of less than 2.0 correlated with a benign clinical state and a ratio of greater than or equal to 2.0 correlated with AIDS or progression to AIDS.
Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. (1981)

Mouse myeloid leukemia cells can be induced to differentiate into macrophages in vitro by 1 alpha,25-dihydroxyvitamin D3, the active form of vitamin D3. The minimal concentration of 1 alpha,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. The degree of cell differentiation in various markers induced by 12 nM 1 alpha,25-dihydroxyvitamin D3 was nearly equivalent to that induced by 1 microM dexamethasone, the most potent known stimulator. Among several markers of the differentiation by 1 alpha,25-dihydroxyvitamin D3, phagocytic activity was induced within 24 hr, and this was followed by induction of lysozyme and locomotive activities. Similar changes were also induced by 0.01-1 microM 1 alpha-hydroxyvitamin D3. 25-Hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 showed only weak inducing activity. These results suggest the possibility that, in addition to its wellknown biological activities in enhancing intestinal calcium transport and bone mineral mobilization, 1 alpha, 25-dihydroxyvitamin D3 is involved in the differentiation of bone marrow cells.
Improving Virtual Machine Migration in Federated Cloud Environments (2010)

Cloud federation is the future of the cloud computing. In such new emerging scenarios, the "hot" and "cold" migration imply the movement of a virtual machine disk-image from a server placed in a cloud provider to a server placed in another one, with a consequent consumption of bandwidth and cloud resources. This paper aims to reduce such costs proposing a Composed Image Cloning (CIC) methodology. Our approach does not consider the disk-image of a VM as a single monolithic block, but as a combination between "composable" and "user data" blocks. Since the former may be cloned locally in the destination clouds, the amount of data which have to be transferred may be reduced. In order to test our strategy we implemented a real test bed extending the OpenQRM platform. Experiments show the validity of the proposed approach in large-scale federated cloud environments, where the amount of data transferred significantly reduces when the number of live migrations increases.
Genetic Manipulation of Commercial Yeast Strains (1986)

(1986). Genetic Manipulation of Commercial Yeast Strains. Biotechnology and Genetic Engineering Reviews: Vol. 4, No. 1, pp. 1-38.
Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate (2012)

The authors report the case of an 80-year-old man who had heavily pretreated castration refractory carcinoma of the prostate and heart failure. Following the introduction of spironolactone to manage his heart failure, the patient experienced clinical and biochemical progression of his prostate cancer. Within 2 weeks of withdrawing spironolactone the patient's prostate-specific antigen returned its previous level. This is the first reported case of clinical and biochemical progression of prostate cancer following the introduction of spironolactone. The authors propose that spironolactone is a selective androgen receptor modulator. Spironolactone should be used in caution with men with prostate cancer, and should not be used to treat oedema, hypokalaemia and hypertension associated with the newly licensed hormonal therapy abiraterone acetate.
Identification and Immunogenicity of Group AStreptococcusCulture Supernatant Proteins (2000)

Extracellular proteins made by group A Streptococcus (GAS) play critical roles in the pathogenesis of human infections caused by this bacterium. Although many extracellular GAS proteins have been identified and characterized, there has been no systematic analysis of culture supernatant proteins. Proteins present in the culture supernatant of strains of serotype M1 (MGAS 5005) and M3 (MGAS 315) mutants lacking production of the major extracellular cysteine protease were separated by two-dimensional gel electrophoresis and identified by amino-terminal amino acid sequencing and interrogation of available databases, including a serotype M1 genome sequence. In the aggregate, amino-terminal amino acid sequence data for 66 protein spots were generated, 53 unique sequences were obtained, and 44 distinct proteins were identified. Sixteen of the 44 proteins had apparent secretion signal sequences and 27 proteins did not. Eight of the 16 proteins with apparent secretion signal sequences have not been previously described for GAS. Antibodies against most of the apparently secreted proteins were present in sera from mice infected subcutaneously with MGAS 5005 or MGAS 315. Humans with documented GAS infections (pharyngitis, acute rheumatic fever, and severe invasive disease) also had serum antibodies reacting with many of the apparently secreted proteins, indicating that they were synthesized in the course of GAS-human interaction. The genes encoding four of the eight previously undescribed and apparently secreted culture supernatant proteins were cloned, and the proteins were overexpressed in Escherichia coli. Western blot analysis with these recombinant proteins and sera from GAS-infected mice and humans confirmed the immunogenicity of these proteins. Taken together, the data provide new information about the molecular aspects of GAS-host interactions.
Molecular characterization of pregnancy‐associated plasma protein‐A by electrophoresis (1990)

Gradient polyacrylamide gel electrophoresis, isoelectric focusing and multidimensional immunoelectrophoretic techniques have been applied in order to physico-chemically characterize pregnancy-associated plasma protein-A (PAPP-A). By lectin affinity immunoelectrophoresis, PAPP-A contained sialic acid, glucose/mannose and N-acetyl-alpha-D-galactosamine. Immunoelectrophoretic analyses after incubation with various glycolases confirmed these findings and demonstrated that PAPP-A contained glucuronic acid, perhaps in chondroitin sulphate moities, thus indicating that PAPP-A may be a proteoglycan rather than a glycoprotein. Analysis by metal chelate and dye ligand affinity immunoelectrophoresis demonstrated many similarities between PAPP-A and alpha 2-macroglobulin (alpha 2M). However, unlike alpha 2M, PAPP-A did not form immunologically reactive complexes when incubated with proteases. Furthermore, as demonstrated by autoradiographic studies, PAPP-A did not contain internal thiolester groups, thus indicating that PAPP-A cannot inhibit proteases by molecular entrapment and, despite the homotetrameric molecular conformation, PAPP-A and alpha 2M may not have evolved from a common ancestral protein.
High Fidelity of Yellow Fever Virus RNA Polymerase (2003)

Three consecutive plaque purifications of four chimeric yellow fever virus-dengue virus (ChimeriVax-DEN) vaccine candidates against dengue virus types 1 to 4 were performed. The genome of each candidate was sequenced by the consensus approach after plaque purification and additional passages in cell culture. Our data suggest that the nucleotide sequence error rate for SP6 RNA polymerase used in the in vitro transcription step to initiate virus replication was as high as 1.34 x 10(-4) per copied nucleotide and that the error rate of the yellow fever virus RNA polymerase employed by the chimeras for genome replication in infected cells was as low as 1.9 x 10(-7) to 2.3 x 10(-7). Clustering of beneficial mutations that accumulated after multiple virus passages suggests that the N-terminal part of the prM protein, a specific site in the middle of the E protein, and the NS4B protein may be essential for nucleocapsid-envelope interaction during flavivirus assembly.
Androgen Receptor Expression in Prostate Cancer Cells Is Suppressed by Activation of Epidermal Growth Factor Receptor and ErbB2 (2009)

Prostate cancers (PCa) that relapse after androgen deprivation therapies [castration-resistant PCa (CRPC)] express high levels of androgen receptor (AR) and androgen-regulated genes, and evidence from several groups indicates that ErbB family receptor tyrosine kinases [epidermal growth factor (EGF) receptor (EGFR) and ErbB2] may contribute to enhancing this AR activity. We found that activation of these kinases with EGF and heregulin-beta1 rapidly (within 8 hours) decreased expression of endogenous AR and androgen-regulated PSA in LNCaP PCa cells. AR expression was similarly decreased in LAPC4 and C4-2 cells, but not in the CWR22Rv1 PCa cell line. The rapid decrease in AR was not due to increased AR protein degradation and was not blocked by phosphatidylinositol 3-kinase (LY294002) or MEK (UO126) inhibitors. Significantly, AR mRNA levels in LNCaP cells were markedly decreased by EGF and heregulin-beta1, and experiments with actinomycin D to block new mRNA synthesis showed that AR mRNA degradation was increased. AR mRNA levels were still markedly decreased by EGF and heregulin-beta1 in LNCaP cells adapted to growth in androgen-depleted medium, although AR protein levels did not decline due to increased AR protein stability. These findings show that EGFR and ErbB2 can negatively regulate AR mRNA and may provide an approach to suppress AR expression in CRPC.
Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells (2007)

Transcription factors play a key role in integrating and modulating biological information. In this study, we comprehensively measured the changing abundances of mRNAs over a time course of activation of human peripheral-blood-derived mononuclear cells ("macrophages") with lipopolysaccharide. Global and dynamic analysis of transcription factors in response to a physiological stimulus has yet to be achieved in a human system, and our efforts significantly advanced this goal. We used multiple global high-throughput technologies for measuring mRNA levels, including massively parallel signature sequencing and GeneChip microarrays. We identified 92 of 1,288 known human transcription factors as having significantly measurable changes during our 24-h time course. At least 42 of these changes were previously unidentified in this system. Our data demonstrate that some transcription factors operate in a functional range below 10 transcripts per cell, whereas others operate in a range three orders of magnitude greater. The highly reproducible response of many mRNAs indicates feedback control. A broad range of activation kinetics was observed; thus, combinatorial regulation by small subsets of transcription factors would permit almost any timing input to cis-regulatory elements controlling gene transcription.
A Biosynthetic Route to Dehydroalanine‐Containing Proteins (2007)

It's not natural: The nonnatural amino acid phenylselenocysteine has been genetically incorporated into proteins in E. coli in response to the amber nonsense codon TAG. Oxidative elimination followed by Michael addition led to incorporation of (S)-hexadecyl- and (S)-mannosylcysteine into green fluorescent protein. This approach provides a useful method to modify protein side chains and backbone structures. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z702305_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Evaluation of biodegradable microspheres as vaccine adjuvant for hepatitis B surface antigen. (1992)

Biodegradable microspheres were evaluated as vaccine adjuvants based on their ability to provide prolonged release of incorporated agents. Hepatitis B surface antigen (HBSA) prepared by recombinant DNA technology was chosen as a model antigen and encapsulated into polyglycolic acid (PGA) by solvent extraction and solvent evaporation techniques. Five microsphere formulations were prepared to evaluate effect of microsphere size and the presence of immunostimulants such as muramyl dipeptide (MDP) or aluminum hydroxide. The microspheres were characterized for size distribution, surface morphology and antigenicity. Guinea pigs were chosen as the animal model for evaluation of antigenicity of the formulations. The animals were divided into seven groups of four animals each and the microsphere formulations were injected intraperitoneally, using alum adsorbed HBSA as positive control and placebo microspheres as negative control. Blood samples were withdrawn from the animals by toe clipping at two, four, six and sixteen weeks and plasma was analyzed for antibodies against hepatitis B by an enzyme linked immunoassay. At sixteen weeks, the animals were reinjected and evaluated for antibody response at two, four and six weeks post second injection. Antibody response to the microspheres was higher than control. Smaller size microspheres elicited earlier antibody response while the larger size microspheres provided delayed and longer duration of antibody production. Microspheres with MDP potentiated the antibody response. The results demonstrate the applicability of biodegradable microspheres for immunization against hepatitis B.
Amyloid precursor protein in aged nonhuman primates. (1991)

In individuals with Alzheimer disease and in aged nonhuman primates, deposits of amyloid occur in senile plaques in brain parenchyma and in the walls of some meningeal and cortical vessels. Amyloid is primarily composed of beta/A4, a 4-kDa peptide derived from the transmembrane form of an amyloid precursor protein (APP). We examined the distribution of beta/A4 and APP (outside the beta/A4 domain) in cerebral cortices of monkeys ranging in age from 4 to 41 years. In all animals, APP immunoreactivity was present in cell bodies, proximal dendrites, and axons of cortical neurons. In aged animals, all of which showed senile plaques, large APP-positive axons were conspicuous, and APP immunoreactivity was present in neurites around beta/A4-immunoreactive plaques. In some plaques, APP-immunoreactive elements were located in proximity to deposits of beta/A4. The presence of APP immunoreactivity in neuronal perikarya, dendrites, axons, and in neurites within beta/A4-containing plaques supports the hypothesis that neurons can serve as one source of amyloid deposited in brain parenchyma.
An Essential Role for Albumin in the Interaction of Endotoxin with Lipopolysaccharide-binding Protein and sCD14 and Resultant Cell Activation (2002)

Experiments utilizing endotoxin aggregates, lipooligosaccharides (LOS) isolated from metabolically labeled Neisseria meningitidis serotype group B, demonstrate that albumin is an essential component of lipopolysaccharide binding protein- (LBP) and sCD14-dependent 1) disaggregation of LOS and 2) LOS activation of human umbilical vein endothelial cells (HUVEC). Aggregates of LOS (LOS(agg)) with an apparent M(r) >or= 2 x 10(7) were isolated by gel sieving on Sephacryl HR S500 in buffered balanced salts solution plus albumin. Incubation of LOS(agg) with LBP and sCD14 promoted LOS(agg) disaggregation in an albumin-dependent fashion to complexes that contain LOS and sCD14, but no LBP, with an apparent M(r) approximately 60,000 (LOS:sCD14) as determined by Sephacryl S200 chromatography. Isolation by gel filtration of LOS(agg):protein aggregates formed by the interaction of LOS(agg) with either LBP or sCD14 alone revealed that the sequence of LOS-protein interactions as well as the step(s) at which albumin is necessary for the production of bioactive LOS:sCD14 were specific. Efficient generation of LOS:sCD14 required 1) interaction of LOS(agg) with LBP before interaction with CD14 and 2) the presence of albumin during the interaction of LBP with LOS(agg). Activation of HUVEC by LOS(agg), as measured by IL-8 production, required both LBP and sCD14 and was thirty times more potent in the presence of albumin. In contrast, LOS:sCD14 did not require additional LBP, sCD14, or albumin to activate HUVEC but depended on the presence of albumin for optimal solubility/stability once formed. The albumin effect is apparently specific, because neither ovalbumin nor gelatin substituted for albumin in facilitating LBP:sCD14-dependent disaggregation of LOS(agg) or activation of endothelial cells. These results indicate that albumin is an essential facilitator of LBP/sCD14-induced LOS disaggregation that is required for activation of endothelial cells by LOS(agg).
Wafer-Scale Assembly of Highly Ordered Semiconductor Nanowire Arrays by Contact Printing (2007)

Controlled and uniform assembly of "bottom-up" nanowire (NW) materials with high scalability presents one of the significant bottleneck challenges facing the integration of nanowires for electronic applications. Here, we demonstrate wafer-scale assembly of highly ordered, dense, and regular arrays of NWs with high uniformity and reproducibility through a simple contact printing process. The assembled NW pitch is shown to be readily modulated through the surface chemical treatment of the receiver substrate, with the highest density approaching approximately 8 NW/mum, approximately 95% directional alignment, and wafer-scale uniformity. Such fine control in the assembly is attained by applying a lubricant during the contact printing process which significantly minimizes the NW-NW mechanical interactions, therefore enabling well-controlled transfer of nanowires through surface chemical binding interactions. Furthermore, we demonstrate that our printing approach enables large-scale integration of NW arrays for various device structures on both rigid silicon and flexible plastic substrates, with a controlled semiconductor channel width ranging from a single NW ( approximately 10 nm) up to approximately 250 microm, consisting of a parallel array of over 1250 NWs and delivering over 1 mA of ON current.