gebhart/patrepeval huggingface dataset:
The functioning antigens: beyond just as the immunological targets (2009)

Antigenic peptides derived from tumor-associated antigens (TAAs) facilitate peptide cancer vaccine therapies. With the recent progress in cancer immunity research, huge amounts of antigenic peptides have already been reported. Clinical trials using such peptides are underway now all over the world. Some reports have shown the efficacy of peptide vaccine therapies. However, others ended with unfavorable results, suggesting fundamental underlying problems. One major mechanism that negates the peptide vaccine therapy is tumor escape from immunological systems caused by loss of antigens. TAAs that are used in cancer vaccine therapies may be divided into two major groups: functioning antigens and nonfunctioning antigens. A 'functioning antigen' could be defined as a TAA that is essential for tumor growth, is expressed in several kinds of malignancies and shows homogenous expression in cancerous tissues. It is not difficult to imagine that antigen loss will occur easily with non-functioning antigens as a target of cancer vaccine therapy. Thus, it is essential to use functioning antigens for successful cancer vaccine therapy. In this review, we discuss the functioning antigens and their categorization in detail.
A Physiologic Flow Chamber Model to Define Intravascular Ultrasound Enhancement of Fibrin Using Echogenic Liposomes (2002)

This model can quantitate the components of IVUS enhancement of an interface produced by ELIP. This model may allow for further development and understanding of ELIP and other targeted ultrasound contrast agents.
Plasma Levels of Inter-α Inhibitor Proteins in Children with Acute Dengue Virus Infection (2010)

Background: Inter-a inhibitor proteins (IaIp) belong to a family of protease inhibitors that are involved in the haemostatic and the vascular system. Dengue viruses (DENV) infections are characterized by coagulopathy and increased vascular permeability. In this study we measured the concentration of IaIp during DENV infections and evaluated its potential as a biomarker.
Viral interference with antibody and complement (1998)

Viruses have evolved strategies to evade immunity mediated by antibody and complement. Herpesviruses and coronaviruses encode IgG Fc binding proteins that inhibit IgG activity, enabling the virus or infected cell to escape antibody attack. Herpesviruses, vaccinia virus and HIV-1 have the capacity to interfere with complement, either by incorporation of cellular complement regulatory proteins into the virion envelope or cell membrane, or by expression of viral molecules that mimic functions of complement regulatory proteins. The structure and biological activities of herpes simplex virus type 1 (HSV-1) glycoproteins gE, gI and gC are described. These glycoproteins protect HSV from immune attack; HSV-1 gE/gI form a complex that binds the Fc domain of IgG while gC is a C3b binding complement regulatory protein, providing a survival advantage to the virus in vitro and in vivo by inhibiting immune functions.
Local Structure of Sodium Aluminum Metaphosphate Glasses (2003)

High‐resolution solid‐state 31 P, 27 Al, and 23 Na nuclear magnetic resonance (NMR), Raman spectroscopy, differential scanning calorimetry, and density measurements were used to characterize the local structure of the glasses (1− x )(NaPO 3 ) 3 · x Al(PO 3 ) 3 . A systematic increase in density, glass transition temperature ( T g ), and frequencies of P–O stretching vibrations for terminal nonbridging oxygens (NBOs) was observed as the Al content was increased. A change of slope in the behavior of T g as a function of x was clearly detected around x = 0.25 ± 0.03. Also, changes of behavior in the 23 Na NMR line shape and in the Raman band of the PO 2 symmetric vibration are detected for concentrations higher than x = 0.17. According to these facts, a reorganization of the network affecting the degree of connectivity between phosphate chains is proposed to explain the observed behaviors of T g and P–NBO vibrations in these glasses.
Functional Coupling of γ-Aminobutyric Acid Receptors to Chloride Channels in Brain Membranes (1985)

gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, is believed to act by increasing membrane conductance of chloride ions. In this study it was found that GABA agonists increased the uptake of chloride-36 by cell-free membrane preparations from mouse brain. This influx was rapid (less than 5 seconds), and 13 micromolar GABA produced a half-maximal effect. The GABA antagonists (bicuculline and picrotoxin) blocked the effect of GABA, whereas pentobarbital enhanced the action. This may be the first demonstration of functional coupling among GABA and barbiturate receptors and chloride channels in isolated membranes. The technique should facilitate biochemical and pharmacological studies of GABA receptor-effector coupling.
Control of Culture Environment for Improved Polyethylenimine-Mediated Transient Production of Recombinant Monoclonal Antibodies by CHO Cells (2006)

In this study we describe optimization of polyethylenimine (PEI)-mediated transient production of recombinant protein by CHO cells by facile manipulation of a chemically defined culture environment to limit accumulation of nonproductive cell biomass, increase the duration of recombinant protein production from transfected plasmid DNA, and increase cell-specific production. The optimal conditions for transient transfection of suspension-adapted CHO cells using branched, 25 kDa PEI as a gene delivery vehicle were experimentally determined by production of secreted alkaline phosphatase reporter in static cultures and recombinant IgG4 monoclonal antibody (Mab) production in agitated shake flask cultures to be a DNA concentration of 1.25 microg 10(6) cells(-1) mL(-1) at a PEI nitrogen:DNA phosphate ratio of 20:1. These conditions represented the optimal compromise between PEI cytotoxicity and product yield with most efficient recombinant DNA utilization. Separately, both addition of recombinant insulin-like growth factor (LR3-IGF) and a reduction in culture temperature to 32 degrees C were found to increase product titer 2- and 3-fold, respectively. However, mild hypothermia and LR3-IGF acted synergistically to increase product titer 11-fold. Although increased product titer in the presence of LR3-IGF alone was solely a consequence of increased culture duration, a reduction in culture temperature post-transfection increased both the integral of viable cell concentration (IVC) and cell-specific Mab production rate. For cultures maintained at 32 degrees C in the presence of LR3-IGF, IVC and qMab were increased 4- and 2.5-fold, respectively. To further increase product yield from transfected DNA, the duration of transgene expression in cell populations maintained at 32 degrees C in the presence of LR3-IGF was doubled by periodic resuspension of transfected cells in fresh media, leading to a 3-fold increase in accumulated Mab titer from approximately 13 to approximately 39 mg L(-1). Under these conditions, Mab glycosylation at Asn297 remained essentially constant and similar to that of the same Mab produced by stably transfected GS-CHO cells. From these data we suggest that the efficiency of transient production processes (protein output per rDNA input) can be significantly improved using a combination of mild hypothermia and growth factor(s) to yield an extended "activated hypothermic synthesis".
Metabolic Balances of Strontium in Man (1976)

Stable strontium balances were determined in man under strictly controlled dietary conditions in control studies and during both oral and intravenous administration of stable strontium. The diet contained about 1 mg strontium per day and most of this (88%) was excreted in stool while 17.5 per cent was excreted in urine, so that the balance was very slightly negative. During the oral intake of 1536 mg strontium per day, given as the lactate, the urinary and the fecal strontium excretions increased markedly and the balance became strongly positive. During the 6-day periods of intravenous infusions of stable strontium as the gluconate, 30-40 per cent of the infused amount was excreted in the urine and 5-10 per cent in stool. A high percentage of the strontium retained during both oral and intravenous administration was excreted in 30 days after the discontinuation of the strontium administration and there was no evidence of long term retention. The administration of stable strontium, given either orally or intravenously, was associated with an increase of the urinary calcium excretion.
Mhc-DRB Genes and the Origin of New World Monkeys (1995)

The major histocompatibility complex (Mhc) is a family of loci characterized by its relatively rapid evolutionary turnover, large genetic distances between genes, and long persistence of allelic lineages effected by balancing selection. These features render the Mhc highly suitable for answering questions concerning speciation and adaptive radiation. The aim of the present study was to use Mhc-DRB genes to make inferences about the founding population of the Platyrrhini. Three segments, each approximately 300 base pairs in length, of the platyrrhine DRB genes were amplified by the polymerase chain reaction and sequenced. The segments were derived from intron 2, exon 3, and exon 6 of DRB genes from different species of New World monkeys. The results of the study have revealed that on a phylogenetic tree, all of the tested platyrrhine genes appear to form a single cluster, while all catarrhine DRB genes form a distinct cluster, although the bootstrap values fail to provide statistically significant support for the separation of these two clades. This observation suggests that the multiple platyrrhine genes originated from a single ancestral gene after the divergence of the Platyrrhini and Catarrhini and thus contradicts the results of an earlier study in which some exon 2 DRB sequences appeared to predate the split of the two primate groups. The inconsistency in the DRB gene phylogeny can be explained by postulating convergent evolution for the peptide-binding region of the DRB exon 2 sequences. The phylogeny of the platyrrhine DRB genes (except for exon 2) is relatively "shallow"; the distances between genes are relatively short (in comparison to the catarrhine DRB genes), and there is a tendency for sequences of individual species to cluster together. The phylogeny of the platyrrhine DRB genes is consistent with the postulate that a small population founded the group and that there is an ongoing adaptive radiation from small, relatively isolated founding populations.
In Vivo, In Situ Tissue Analysis Using Rapid Evaporative Ionization Mass Spectrometry (2009)

Beam me up: A novel mass spectrometric ionization technique based on rapid evaporation of biological tissues (see picture) can be used to analyze vital tissues during surgical intervention as well as for processed tissue specimens. A tissue identification system based on principal-component analysis was developed. The method differentiates malignant tumor cells from the surrounding healthy tissue.
Global landscape of recent inferred Darwinian selection for Homo sapiens (2005)

By using the 1.6 million single-nucleotide polymorphism (SNP) genotype data set from Perlegen Sciences [Hinds, D. A., Stuve, L. L., Nilsen, G. B., Halperin, E., Eskin, E., Ballinger, D. G., Frazer, K. A. & Cox, D. R. (2005) Science 307, 1072-1079], a probabilistic search for the landscape exhibited by positive Darwinian selection was conducted. By sorting each high-frequency allele by homozygosity, we search for the expected decay of adjacent SNP linkage disequilibrium (LD) at recently selected alleles, eliminating the need for inferring haplotype. We designate this approach the LD decay (LDD) test. By these criteria, 1.6% of Perlegen SNPs were found to exhibit the genetic architecture of selection. These results were confirmed on an independently generated data set of 1.0 million SNP genotypes (International Human Haplotype Map Phase I freeze). Simulation studies indicate that the LDD test, at the megabase scale used, effectively distinguishes selection from other causes of extensive LD, such as inversions, population bottlenecks, and admixture. The approximately 1,800 genes identified by the LDD test were clustered according to Gene Ontology (GO) categories. Based on overrepresentation analysis, several predominant biological themes are common in these selected alleles, including host-pathogen interactions, reproduction, DNA metabolism/cell cycle, protein metabolism, and neuronal function.
PTEN Associates with the Vault Particles in HeLa Cells (2002)

PTEN is a tumor suppressor that primarily dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to down-regulate the phosphoinositide 3-kinase/Akt signaling pathway. Although the cellular functions of PTEN as a tumor suppressor have been well characterized, the mechanism by which PTEN activity is modulated by other signal molecules in vivo remains poorly understood. In searching for potential PTEN modulators through protein-protein interaction, we identified the major vault protein (MVP) as a dominant PTEN-binding protein in a yeast two-hybrid screen. MVP is the major structural component of vault, the largest intracellular ribonucleoprotein particle. Co-immunoprecipitation confirmed the interaction between PTEN and MVP in transfected mammalian cells. More importantly, we found that a significant portion of endogenous PTEN associates with vault particles in human HeLa cells. Deletion mutation analysis demonstrated that MVP binds to the C2 domain of PTEN and that PTEN interacts with MVP through its EF hand-like motif. Furthermore, the in vitro binding experiments revealed that the interaction of PTEN with MVP is Ca(2+)-dependent.
Improved Part-of-Speech Tagging for Online Conversational Text with Word Clusters (2018)

We consider the problem of part-of-speech tagging for informal, online conversational text. We systematically evaluate the use of large-scale unsupervised word clustering and new lexical features to improve tagging accuracy. With these features, our system achieves state-of-the-art tagging results on both Twitter and IRC POS tagging tasks; Twitter tagging is improved from 90% to 93% accuracy (more than 3% absolute). Qualitative analysis of these word clusters yields insights about NLP and linguistic phenomena in this genre. Additionally, we contribute the first POS annotation guidelines for such text and release a new dataset of English language tweets annotated using these guidelines. Tagging software, annotation guidelines, and large-scale word clusters are available at: http://www.ark.cs.cmu.edu/TweetNLP This paper describes release 0.3 of the “CMU Twitter Part-of-Speech Tagger” and annotated data.
Testing Strategies in the Initial Management of Patients with Community-Acquired Pneumonia (2003)

The initial management of patients suspected of having community-acquired pneumonia is challenging because of the broad range of clinical presentations, potential life-threatening nature of the illness, and associated high costs of care. The initial testing strategies should accurately establish a diagnosis and prognosis in order to determine the optimal treatment strategy. The diagnosis is important in determining the need for antibiotic therapy, and the prognosis is important in determining the site of care. This paper reviews the test characteristics of the history, physical examination, and laboratory findings, individually and in combination, in diagnosing community-acquired pneumonia and predicting short-term risk for death from the infection. In addition, we consider the implications of these test characteristics from the perspective of decision thresholds. The history and physical examination cannot provide a high level of certainty in the diagnosis of community-acquired pneumonia, but the absence of vital sign abnormalities substantially reduces the probability of the infection. Chest radiography is considered the gold standard for pneumonia diagnosis; however, we do not know its sensitivity and specificity, and we have limited data on the costs of false-positive and false-negative results. In the absence of empirical evidence, the decision to order a chest radiograph needs to rely on expert opinion in seeking strategies to optimize the balance between harms and benefits. Once community-acquired pneumonia is diagnosed, a combination of history, physical examination, and laboratory items can help estimate the short-term risk for death and, along with the patient's psychosocial characteristics, determine the appropriate site of treatment.
The Danger Model: A Renewed Sense of Self (2002)

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.
Dynamic Study of the Rectal Detrusor Activity at Defecation (1991)

The dynamics of the rectal detrusor at defecation was studied in 29 normal and 10 constipated subjects. The rectal pressure was measured by a ureteral catheter with terminal side holes, while the intra-abdominal pressure was measured by a Foley catheter introduced into the urinary bladder. Simultaneous recording of fecal flow was performed by fecoflowmetry. Assessment of the findings in normal subjects has shown a pre-evacuation rectal pressure elevation which reached its peak with the start of fecal flow and then fell gradually as the flow increased. This was in contrast to the constipated patients in whom the elevated pre-evacuation rectal pressure continued through the whole act of evacuation. Quantitative analysis of the rectal pressure curve could also differentiate between normal and constipated subjects. The significant parameters are the opening pressure and time, the pressure time and the evacuation pressure. The simultaneous recording of the intra-abdominal pressure demonstrates its share in the increase of the rectal pressure.
Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo (2006)

The activity and stability of the p53 tumor suppressor are regulated by the human homologue of the mouse double minute 2 (Hdm2) oncoprotein. It has been hypothesized that small molecules disrupting the Hdm2:p53 complex would allow for the activation of p53 and result in growth suppression. We have identified small-molecule inhibitors of the Hdm2:p53 interaction using our proprietary ThermoFluor microcalorimetry technology. Medicinal chemistry and structure-based drug design led to the development of an optimized series of benzodiazepinediones, including TDP521252 and TDP665759. Activities were dependent on the expression of wild-type (wt) p53 and Hdm2 as determined by lack of potency in mutant or null p53-expressing cell lines or cells engineered to no longer express Hdm2 and wt p53. TDP521252 and TDP665759 inhibited the proliferation of wt p53-expressing cell lines with average IC(50)s of 14 and 0.7 micromol/L, respectively. These results correlated with the direct cellular dissociation of Hdm2 from wt p53 observed within 15 minutes in JAR choriocarcinoma cells. Additional activities of these inhibitors in vitro include stabilization of p53 protein levels, up-regulation of p53 target genes in a DNA damage-independent manner, and induction of apoptosis in HepG2 cells. Administration of TDP665759 to mice led to an increase in p21(waf1/cip1) levels in liver samples. Finally, TDP665759 synergizes with doxorubicin both in culture and in an A375 xenograft model to decrease tumor growth. Taken together, these data support the potential utility of small-molecule inhibitors of the Hdm2:p53 interaction for the treatment of wt p53-expressing tumors.
Behaviour of packaging materials during high pressure thawing.: Note (1998)

These preliminary data serve as proof of concept that there may be a genetic predisposition to developing high-grade cervical dysplasia in African American HIV-infected women. Given the small sample size, the results need to be validated in a separate cohort.
Fractionation−Reconstitution Experiments Provide Insight into the Role of Endoxylanases in Bread-Making (1999)

The impact mechanism of endoxylanases in straight dough bread-making was investigated in fractionation-reconstitution experiments. To this end, two European flours with different bread-making characteristics were separated in gluten, prime starch, a squeegee fraction (SQF), and a water-extractable fraction. Whereas the former fractions contained negligible levels of arabinoxylan (AX), the latter contained, respectively, most of the water-unextractable AX (WU-AX) and all of the water-extractable AX (WE-AX). In vitro modification with a Bacillus subtilis endoxylanase allowed controlled solubilization of WU-AX from SQF and controlled degradation of solubilized AX and WE-AX from the water-extractables. It followed from bread-making tests with the reconstituted flours that endoxylanases exert positive loaf volume effects in bread-making by lowering the concentration of WU-AX and increasing that of total soluble AX. Limited degradation of WE-AX and significant breakdown of solubilized AX by endoxylanases, on the other hand, resulted in volume losses when compared to their nondegraded counterparts. The volume increasing effects of endoxylanases are therefore related to their ratio of solubilizing to degrading activity and thus to their substrate specificity.
Origins and complexes: the initiation of DNA replication (2001)

Eukaryotic DNA is organized for replication as multiple replicons. DNA synthesis in each replicon is initiated at an origin of replication. In both budding yeast, Saccharomyces cerevisiae and fission yeast, Schizosaccharomyces pombe, origins contain specific sequences that are essential for initiation, although these differ significantly between the two yeasts with those of S. pombe being more complex then those of S. cerevisiae. However, it is not yet clear whether the replication origins of plants contain specific essential sequences or whether origin sites are determined by features of chromatin structure. In all eukaryotes there are several biochemical events that must take place before initiation can occur. These are the marking of the origins by the origin recognition complex (ORC), the loading onto the origins, in a series of steps, of origin activation factors including the MCM proteins, and the initial denaturation of the double helix to form a replication "bubble". Only then can the enzymes that actually initiate replication, primase and DNA polymerase-alpha, gain access to the template. In many cells this complex series of events occurs only once per cell cycle, ensuring that DNA is not re-replicated within one cycle. However, regulated re-replication of DNA within one cell cycle (DNA endoreduplication) is relatively common in plants, indicating that the "once-per-cycle" controls can be overridden.