gebhart/patrepeval huggingface dataset:
Tofacitinib Suppresses Antibody Responses to Protein Therapeutics in Murine Hosts (2014)

Immunogenicity remains the "Achilles' heel" of protein-based therapeutics. Anti-drug Abs produced in response to protein therapeutics can severely limit both the safety and efficacy of this expanding class of agent. In this article, we report that monotherapy of mice with tofacitinib (the JAK inhibitor) quells Ab responses to an immunotoxin derived from the bacterial protein Pseudomonas exotoxin A, as well as to the model Ag keyhole limpet hemocyanin. Thousand-fold reductions in IgG1 titers to both Ags were observed 21 d post immunization. In fact, suppression was evident for all IgG isotypes and IgM. A reduction in IgG3 production was also noted with a thymus-independent type II Ag. Mechanistic investigations revealed that tofacitinib treatment led to reduced numbers of CD127+ pro-B cells. Furthermore, we observed fewer germinal center B cells and the impaired formation of germinal centers of mice treated with tofacitinib. Because normal Ig levels were still present during tofacitinib treatment, this agent specifically reduced anti-drug Abs, thus preserving the potential efficacy of biological therapeutics, including those used as cancer therapeutics.
Fast approximate spectral clustering (2009)

Spectral clustering refers to a flexible class of clustering procedures that can produce high-quality clusterings on small data sets but which has limited applicability to large-scale problems due to its computational complexity of O(n3) in general, with n the number of data points. We extend the range of spectral clustering by developing a general framework for fast approximate spectral clustering in which a distortion-minimizing local transformation is first applied to the data. This framework is based on a theoretical analysis that provides a statistical characterization of the effect of local distortion on the mis-clustering rate. We develop two concrete instances of our general framework, one based on local k-means clustering (KASP) and one based on random projection trees (RASP). Extensive experiments show that these algorithms can achieve significant speedups with little degradation in clustering accuracy. Specifically, our algorithms outperform k-means by a large margin in terms of accuracy, and run several times faster than approximate spectral clustering based on the Nystrom method, with comparable accuracy and significantly smaller memory footprint. Remarkably, our algorithms make it possible for a single machine to spectral cluster data sets with a million observations within several minutes.
Historical Survey of Daylighting Calculations Methods and Their Use in Energy Performance Simulations (2009)

This paper traces the historical development of different daylighting calculation methods. Over the years there have been several developments in daylighting calculation methods. The last two decades have seen a number of new ideas and approaches in daylight calculation procedures. Recently, selected methods have been incorporated into the building energy performance simulation tools. This paper reviews selected tools in terms of their calculation of daylighting use in buildings with an emphasis on the daylighting algorithms these tools use.
In vitro immunization. Effect of growth and differentiation factors on antigen-specific B cell activation and production of monoclonal antibodies to autologous antigens and weak immunogens. (1986)

The antigen-specific activation of murine nonimmunized B lymphocytes subsequently used in hybridization experiments has been investigated by using phylogenetically conserved antigens or autologous immunogens. This in vitro immunization was supported by B cell growth and differentiation factors derived from phorbol myristate acetate-stimulated EL-4 thymoma cells and mixed lymphocyte cultures (MLC). A filter immuno-plaque assay was used to evaluate the effect of different activation procedures on the number of antigen-specific plaque-forming cells (PFC). We first determined the requirement for MLC-derived lymphokines in the in vitro immunization. An optimal number of antigen-specific PFC was obtained when using 33 to 50% of the supernatant from a 48-hr MLC to support the activation. B cell growth and differentiation factors derived from EL-4 cultures were then tested for their abilities to potentiate the number of PFC by using both unseparated spleen cells and highly purified Ig-positive B cells as target cells. The combination of lymphokines found in supernatants from 25% EL-4 thymoma culture and 33% MLC yielded the highest number of PFC when used to support an in vitro immunization. This optimal factor preparation was used to determine the kinetics (4 to 7 days) and the dose response (0.01 to 10 micrograms antigen/ml) of antigen-specific B cell activation before using the immunized splenocytes as parental cells in cell fusion experiments. Mouse albumin and hemoglobin, actin (25 micrograms/ml), RNA polymerase II (5 micrograms/ml), as well as syngeneic mouse serum were used to immunize BALB/c spleen cells in vitro. We obtained antigen-specific PFC by using all of the different immunogens, including syngeneic mouse serum, and the in vitro immunized cells were then used in hybridization experiments. The specific efficiencies of each fusion that made use of cells immunized with mouse albumin, hemoglobin, syngeneic mouse serum, actin, or RNA polymerase II were 12, 31, 33, 52, and 22%, respectively, which illustrated the apparent lack of immune tolerance found when the immunization was performed in culture.
Characterization of a monoclonal antibody to human sex hormone binding globulin (1984)

We have produced a monoclonal hybridoma cell line ( S1B5 ) that secretes an IgG2 alpha immunoglobulin with a high affinity (Kd 0.38 X 10(-11) M) for 125I-labelled sex hormone binding globulin (SHBG), and which will specifically immunoprecipitate SHBG from serum. The antibody is produced in high titre in culture medium and ascites fluid, and can be purified to apparent homogeneity by protein A affinity chromatography. When examined by isoelectrofocusing , a characteristic series of bands, which bind 125I-SHBG, are observed at pH 8.5-9. Competitive, superimposable, displacement of 125I-SHBG from the antibody is achieved with dilutions of human, chimpanzee and gorilla sera at comparable SHBG concentrations. Partial cross-reaction is observed with sera from other Old World primates, but not with sera from New World monkeys or any other vertebrate species studied.
Expression of ets-1 transcription factor in human head and neck squamous cell carcinoma and effect of histamine on metastatic potential of invasive tumor through the regulation of expression of ets-1 and matrix metalloproteinase-3 (2005)

Ets-1 expression in HNSCCs has no prognostic value; however, ets-1 plays an important role in tumor-host interaction. Histamine may accelerate the spread of HNSCC through an ets-1-related mechanism.
High endothelial differentiation in human lymphoid and inflammatory tissues defined by monoclonal antibody HECA-452. (1988)

Lymphocyte traffic into lymph nodes and into mucosa-associated lymphoid tissues is regulated by specialized postcapillary high endothelial venules (HEVs). The authors have produced a rat monoclonal antibody, HECA-452, that detects a human endothelial cell differentiation antigen selectively expressed on high endothelium. In immunoperoxidase studies, HECA-452 intensely stains all HEVs within lymphoid organs. In normal nonlymphoid tissues the antibody stains no vascular endothelium. The antibody, in addition to reacting with high endothelium, cross-reacts with a set of monocytic cells. In pathologic states such as autoimmune thyroiditis and Crohn's disease, known for the development of dense, frequently organized, lymphocytic infiltrates, HECA-452 detects HEV-like vessels containing luminal and intramural lymphocytes, presumably in the process of extravasating. The antigen was not expressed at detectable levels by venules in less heavily infiltrated chronic inflammatory sites nor in acutely inflamed tissues. In lymphoid malignancies, the only vessels stained were morphologically characteristic HEVs in association with areas of residual normal lymphoid tissue or reactive lymphocytic infiltrates. The specificity of HECA-452 for high endothelial cells confirms the highly specialized nature of these vessels and will permit studies of the regulation of high endothelial cell differentiation in vivo and in vitro. The HECA-452 antigen is preserved in paraffin sections of sublimate formaldehyde- and also routinely formalin-fixed tissues. Thus, HECA-452 will be widely applicable for the immunohistologic detection of endothelium specialized for the support of highly increased lymphocyte extravasation in inflammatory sites.
Silver Nanoparticle−Oligonucleotide Conjugates Based on DNA with Triple Cyclic Disulfide Moieties (2007)

We report a new strategy for preparing silver nanoparticle-oligonucleotide conjugates that are based upon DNA with cyclic disulfide-anchoring groups. These particles are extremely stable and can withstand NaCl concentrations up to 1.0 M. When silver nanoparticles functionalized with complementary sequences are combined, they assemble to form DNA-linked nanoparticle networks. This assembly process is reversible with heating and is associated with a red shifting of the particle surface plasmon resonance and a concomitant color change from yellow to pale red. Analogous to the oligonucleotide-functionalized gold nanoparticles, these particles also exhibit highly cooperative binding properties with extremely sharp melting transitions. This work is an important step toward using silver nanoparticle-oligonucleotide conjugates for a variety of purposes, including molecular diagnostic labels, synthons in programmable materials synthesis approaches, and functional components for nanoelectronic and plasmonic devices.
The role of lanreotide Autogel®in the treatment of acromegaly (2007)

Acromegaly is a rare disease, but all clinicians have to be aware of the diagnosis in order to minimize the negative consequences of increased levels of growth hormone and IGF-I, and the possible impact of a pituitary macroadenoma. Surgery remains the first-line therapy and may alleviate both hormonal excess and symptoms due to tumor mass effects. Postoperatively, however, many patients may need adjunctive therapy. Somatostatin analogs were marketed for clinical use in the 1980s. The depot formulations of the synthetic somatostatin analogs octreotide and lanreotide, octreotide acetate long-acting repeatable and lanreotide sustained release, were developed by incorporating the analogs into microspheres. The advantage of the new formulation of lanreotide, lanreotide Autogel<sup>®</sup>, is the prefilled syringe of lanreotide and water. The choice of analog should be individualized for each patient based on level of efficacy, adverse event profile and preferred mode of administration. Approximately a third of acromegalic patients are resistant to the currently available somatostatin analogs. Monotherapy using cabergoline or pegvisomant is clinically available. Adding cabergoline to a somatostatin analog may be advantageous in selected patients and promising data exist regarding combination therapy with pegvisomant. Radiotherapy is still an option; however, although treating comorbidities and avoiding hypopituitarism is very important, radiotherapy should only be used for selected patients where treatment targets cannot be achieved by using the other therapies.
TNFα suppresses link protein and type II collagen expression in chondrocytes: Role of MEK1/2 and NF‐κB signaling pathways (2003)

Tumor necrosis factor alpha (TNFalpha) inhibits matrix synthesis by chondrocytes in rheumatoid arthritis and osteoarthritis; however, the underlying signaling pathways are poorly characterized. This study investigated the TNFalpha-activated pathways regulating expression of two key components of the cartilage matrix-link protein and type II collagen. In rat articular chondrocytes, TNFalpha decreased link protein and type II collagen mRNA to undetectable levels within 48 h. Levels of link protein mRNA recovered more readily than type II collagen mRNA following removal of the cytokine. TNFalpha-mediated reduction in mRNA of both matrix molecules occurred at the level of transcription and, for link protein, mRNA stability. Turnover of type II collagen and link protein mRNA was dependent on new protein synthesis. In both prechondrocytes and articular chondrocytes, TNFalpha induced concentration-dependent activation of MEK1/2 and NF-kappaB, but not p38 or JNK. Sustained activation of NF-kappaB was observed for up to 72 h following continuous or transient exposure to TNFalpha. Using pharmacological and molecular approaches, the MEK1/2 and NF-kappaB pathways were found to mediate inhibition of type II collagen and link protein gene expression by TNFalpha. Both prechondrocytes and articular chondrocytes are targets of TNFalpha. This study identifies pathways through which TNFalpha perturbs the synthesis and organization of articular cartilage matrix during inflammation.
A malaria transmission-directed model of mosquito life cycle and ecology (2011)

The ability to model a spectrum of local vector species with different ecologies and behaviours allows local customization of packages of interventions and exploration of the effect of proposed new tools.
Identification of members of several homeobox genes in a planarian using a ligation-mediated polymerase chain reaction technique (1996)

I have used a novel single-sided specific polymerase chain reaction (PCR) strategy inspired by ligation-mediated PCR to clone fragments of divergent homeobox genes from a flatworm, the planarian Polycelis nigra. Eight homeobox-containing fragments were amplified, belonging to the Hox, msh, NK-1 and NK-2 classes. Together with the results obtained from several genomes of platyhelminths, my screening shows the presence of the same array of homeodomain developmental regulators in planarians, traditionally regarded as primitive metazoans in terms of body plan, as in coelomate organisms. However, the presence of a Ubx/abd-A homolog may indicate that platyhelminths are more closely related to protostomes than to deuterostomes and supports the idea that flatworms have inherited an elaborate HOX cluster (seven or eight genes) from their ancestor. Likely homologs of the fly genes tinman, bagpipe and S59 suggest that the mesoderm might be patterned by the same genes in all bilaterally symmetrical animals. Finally, a msh-like gene, a family known to be involved in inductive mechanisms in vertebrates, has been found. These results support the hypothesis that the tremendous diversity of metazoan body plans is specified by a largely conserved array of homeobox-containing developmental genes.
First Principles Study of the Li10GeP2S12 Lithium Super Ionic Conductor Material (2011)

Using ab initio MD simulations and energy calculations, we investigate the diffusivity, stability, and electrochemical window of the recently discovered superionic conductor Li10GeP2S12. We provide an explanation for the observed wide electrochemical stability of Li10GeP2S12 and demonstrate that Li10GeP2S12 is a 3D, rather than 1D. ion conductor.
Anaerobic work and power output during cycle ergometer exercise: Effects of bicarbonate loading (1991)

Eight trained male cyclists who competed regularly in track races, were studied under control, alkalotic (NaHCO3) and placebo (CaCO3) conditions in a laboratory setting to study the effect of orally induced metabolic alkalosis on 60 s anaerobic work and power output on a bicycle ergometer. Basal, pre- and post-exercise blood samples in the three conditions were analysed for pH, pCO2, pO2, bicarbonate, base excess and lactate. All blood gas measurements were within normal limits at basal levels. There were significant differences in the amount of work produced, and in the maximal power output produced by the cyclists in the experimental condition when compared to the control and placebo conditions (P less than 0.01). The post-exercise pH decreased in all three conditions (P less than 0.05) and post-exercise pCO2 increased significantly in the alkalosis trial (P less than 0.01). In the alkalotic condition, the pre-exercise base excess and HCO3- levels were both higher (P less than 0.05) than the basal levels, suggesting that the bicarbonate ingestion had a significant increase in the buffering ability of the blood. Post-exercise lactate levels were significantly higher (P less than 0.05) after the alkalotic trial when compared to the other two conditions, immediately post-exercise and for the next 3 min. Post-exercise lactate levels were higher than basal or pre-exercise levels (P less than 0.001). This was true immediately post-exercise and for the next 5 min. The results of this study suggest that NaHCO3 is an effective ergogenic aid when used for typically anaerobic exercise as used in this experiment. We feel that this ergogenic property is probably due to the accelerated efflux of H+ ions from the muscle tissue due to increased extracellular bicarbonate buffering.
Frequent Transmission of HTLV-III Among Spouses of Patients With AIDS-Related Complex and AIDS (1985)

Seven cases of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) associated with human T-cell leukemia (lymphotropic) virus (HTLV)-III infection were documented in married males whose family members consented to medical evaluation. Five spouses also had evidence of HTLV-III infection documented by isolation of virus and by detection of serum antibody directed against viral structural proteins. Three of the five HTLV-positive spouses also had clinical evidence of ARC. The remaining four spouses were clinically healthy. Eleven children (between 14 months and 13 years of age) were also evaluated for evidence of disease and exposure to HTLV-III. Only one 14-month-old child was seropositive for antibody to HTLV-III. These data support the opinion that close household contact to patients with ARC or AIDS is not an efficient mechanism for virus transmission, while demonstrating that HTLV-III can be transmitted by repeated heterosexual contact.
Iron–manganese: new class of metallic degradable biomaterials prepared by powder metallurgy (2008)

AbstractAbstractAn Fe–35 wt-%Mn alloy, aimed to be used as a metallic degradable biomaterial for stent applications, was prepared via a powder metallurgy route. The effects of processing conditions on the microstructure, mechanical properties, magnetic susceptibility and corrosion behaviour were investigated and the results were compared to those of the SS316L alloy, a gold standard for stent applications. The Fe35Mn alloy was found to be essentially austenitic with fine MnO particles aligned along the rolling direction. The alloy is ductile with a strength approaching that of wrought SS316L. It exhibits antiferromagnetic behaviour and its magnetic susceptibility is not altered by plastic deformation, providing an excellent MRI compatibility. Its corrosion rate was evaluated in a modified Hank's solution, and found superior to that of pure iron (slow in vivo degradation rate). In conclusion, the mechanical, magnetic and corrosion characteristics of the Fe35Mn alloy are considered suitable for further development of a new class of degradable metallic biomaterials.Keywords: FE–MN ALLOYDEGRADABLE BIOMATERIALSINTERINGMICROSTRUCTUREMECHANICAL PROPERTIESMAGNETIC SUSCEPTIBILITYCORROSION BEHAVIOURHANK'S SOLUTION
Glucagon-like Peptide 1 (GLP-1) in the Treatment of Diabetes (2004)

Glucagon-like peptide 1 (GLP-1) was discovered as an incretin (insulinotropic gut) hormone. Biological actions of GLP-1 in healthy and type 2 diabetic subjects include (a) stimulation of insulin secretion in a glucose-dependent manner, (b) suppression of glucagon, (c) reduction in appetite and food intake, (d) deceleration of gastric emptying. In animal experiments, in addition, (e) stimulation of beta-cell neogenesis, growth and differentiation in animal and tissue culture experiments, and (f) in vitro inhibition of beta-cell apoptosis induced by different agents have been observed. Since the incretin effect--the higher insulin secretory response to oral as compared to intravenous glucose loads - is reduced in patients with Type 2 diabetes, GLP-1 has been used to pharmacologically replace incretin. Intravenous GLP-1 can normalise, and subcutaneous GLP-1 can significantly lower plasma glucose in the majority of patients with Type 2 diabetes. The magnitude of this effect does not greatly depend on patient characteristics such as age, sex, obesity, or baseline insulin and glucagon, with minor influences of previous antidiabetic therapy and actual metabolic control. GLP-1 itself, however, is inactivated rapidly in vivo by the protease DPP IV and can only be used for short-term metabolic control, such as in intensive care units (potentially useful in patients with acute myocardial infarction, coronary surgery, cerebrovascular events, septicaemia, during the perioperative period and while on parenteral nutrition). For more long-term metabolic control, incretin mimetics (agonists at the GLP-1 receptor) with more favourable pharmacokinetic profiles should be used.
A Comparative Analysis of Synonymous Codon Usage Bias Pattern in Human Albumin Superfamily (2014)

Synonymous codon usage bias is an inevitable phenomenon in organismic taxa across the three domains of life. Though the frequency of codon usage is not equal across species and within genome in the same species, the phenomenon is non random and is tissue-specific. Several factors such as GC content, nucleotide distribution, protein hydropathy, protein secondary structure, and translational selection are reported to contribute to codon usage preference. The synonymous codon usage patterns can be helpful in revealing the expression pattern of genes as well as the evolutionary relationship between the sequences. In this study, synonymous codon usage bias patterns were determined for the evolutionarily close proteins of albumin superfamily, namely, albumin, α-fetoprotein, afamin, and vitamin D-binding protein. Our study demonstrated that the genes of the four albumin superfamily members have low GC content and high values of effective number of codons (ENC) suggesting high expressivity of these genes and less bias in codon usage preferences. This study also provided evidence that the albumin superfamily members are not subjected to mutational selection pressure.
Metabolic Response to Iron Deficiency in Saccharomyces cerevisiae (2010)

Iron is an essential cofactor for enzymes involved in numerous cellular processes, yet little is known about the impact of iron deficiency on cellular metabolism or iron proteins. Previous studies have focused on changes in transcript and proteins levels in iron-deficient cells, yet these changes may not reflect changes in transport activity or flux through a metabolic pathway. We analyzed the metabolomes and transcriptomes of yeast grown in iron-rich and iron-poor media to determine which biosynthetic processes are altered when iron availability falls. Iron deficiency led to changes in glucose metabolism, amino acid biosynthesis, and lipid biosynthesis that were due to deficiencies in specific iron-dependent enzymes. Iron-sulfur proteins exhibited loss of iron cofactors, yet amino acid synthesis was maintained. Ergosterol and sphingolipid biosynthetic pathways had blocks at points where heme and diiron enzymes function, whereas Ole1, the essential fatty acid desaturase, was resistant to iron depletion. Iron-deficient cells exhibited depletion of most iron enzyme activities, but loss of activity during iron deficiency did not consistently disrupt metabolism. Amino acid homeostasis was robust, but iron deficiency impaired lipid synthesis, altering the properties and functions of cellular membranes.