gebhart/patrepeval huggingface dataset:
Selection of a Macaque Fab with Framework Regions Like Those in Humans, High Affinity, and Ability To Neutralize the Protective Antigen (PA) of Bacillus anthracis by Binding to the Segment of PA between Residues 686 and 694 (2005)

Human anthrax infection cannot always be treated successfully by antibiotics, as highlighted by recent bioterrorist attacks; thus, adjunct therapies are clearly needed for the future. There is a particular need to further develop adjunct therapies that can neutralize secreted toxins, such as antibodies directed towards the 83-kDa protective antigen (PA(83)). In the absence of human donors, we immunized a macaque (Macaca fascicularis) with PA(83) to obtain such antibodies suitable as an adjunct therapy for human anthrax infection. By using bone marrow as a template, we PCR amplified specific Fab-encoding genes and cloned them as an immune library (10(7) clones). We isolated a high-affinity (equilibrium dissociation constant [K(D)], 3.4 nM), highly neutralizing (50% inhibitory concentration, 5.6 +/- 0.13 nM) Fab (designated 35PA(83)) from this library by panning. Its epitope was localized by Pepscan analysis between residues 686 and 694 of PA(83) and is part of the region which directly interacts with the cell receptor. 35PA(83) may thus neutralize the anthrax toxin by competing directly for its receptor. The genes encoding 35PA(83) were similar to those of a human immunoglobulin germ line and were assigned to subgroups of human V, (D), or J genes by IMGT/V-QUEST analysis. The 35PA(83) framework regions were 92% identical to a representative allele of each subgroup. When compared to framework regions coded by related human germ line genes, only 2 of 74 (VH) or 75 (VK) analyzed amino acids of 35PA(83) have different chemical characteristics. A very high degree of identity with human framework regions makes 35PA(83) well suited for expression as a whole primatized immunoglobulin G and demonstrates the practicality of using macaque Fabs when immunized human plasma cell donors are not available.
Trastuzumab therapy in metastatic bladder carcinoma The proof of concept (2014)

About 10% of metastatic urothelial carcinoma overexpress oncogenic HER2/neu receptor. Recent preliminary data suggest that patients with this particular molecular subset could benefit from trastuzumab therapy, which specifically targets the receptor and thus inhibits downstream activation pathway. Here we report a case illustrating this clinical benefit, with complete response reported as third line therapy in a heavily pretreated patient with diffuse metastatic urothelial carcinoma of the bladder. It also highlights the usefulness of 18-Fluorodeoxyglucose Positron Emission Tomography (18-FDG PET) as a biomarker for response to trastuzumab.
Two Recommendations on the Pursuit of Happiness (2008)

While any improvement in wealth and consumption will likely increase happiness, the increased happiness may or may not last long. In this article we offer two recommendations to make the increased happiness sustainable. The first one—to invest resources to promote adaptation‐resistant rather than adaptation‐prone consumption—seeks to make the increased happiness sustainable within a generation. The second recommendation—to invest resources to promote inherently evaluable rather than inherently inevaluable consumption—seeks to make the increased happiness sustainable across generations.
Gene expression profiling of single cells on large-scale oligonucleotide arrays (2006)

Over the last decade, important insights into the regulation of cellular responses to various stimuli were gained by global gene expression analyses of cell populations. More recently, specific cell functions and underlying regulatory networks of rare cells isolated from their natural environment moved to the center of attention. However, low cell numbers still hinder gene expression profiling of rare ex vivo material in biomedical research. Therefore, we developed a robust method for gene expression profiling of single cells on high-density oligonucleotide arrays with excellent coverage of low abundance transcripts. The protocol was extensively tested with freshly isolated single cells of very low mRNA content including single epithelial, mature and immature dendritic cells and hematopoietic stem cells. Quantitative PCR confirmed that the PCR-based global amplification method did not change the relative ratios of transcript abundance and unsupervised hierarchical cluster analysis revealed that the histogenetic origin of an individual cell is correctly reflected by the gene expression profile. Moreover, the gene expression data from dendritic cells demonstrate that cellular differentiation and pathway activation can be monitored in individual cells.
3p21 is a recurrent treatment-related breakpoint in myelodysplastic syndrome and acute myeloid leukemia (1996)

In this study we report 11 cases with chromosome abnormalities involving 3p21. Nine cases were diagnosed as myelodysplastic syndrome (MDS), and two as acute myeloid leukemia (AML). Six of nine MDS cases were secondary to a primary malignant disease. In two patients, AML was secondary to breast cancer and polycythemia vera (PV). Seven of eleven patients had a history of intensive polychemotherapy and/or radiation therapy for 3.5 to 5 years. The mean interval from initial therapy to secondary disease was 13.2 years. Complex chromosomal aberrations were found in all 11 cases. Band 3p21 was involved in translocations in 9 patients and in deletions in 2 patients. A t(3;16)(p21;p13) was found in two cases. Additional abnormalities frequently included a -5, -7, as well as deletions or rearrangements of these 2 chromosomes. Data reported in this paper suggest that 3p21 is a recurrent treatment-related breakpoint in MDS and AML and is likely to contain a gene involved in the pathogenesis of this disease.
Anti-CD45 inhibition of human B cell proliferation depends on the nature of activation signals and the state of B cell activation. A study with anti-IgM and anti-CDw40 antibodies. (1989)

The proliferation of human peripheral and tonsillar B cells stimulated with the anti-CDw40 mAb 626.1 and/or anti-IgM antibody (Ab) in the presence of anti-CD45 mAb A.1.1 was investigated. The anti-CD45 mAb suppressed the anti-CDw40-stimulated proliferation of peripheral blood B cells but had no effect on the proliferation of unfractionated tonsillar B cells stimulated similarly. When tonsillar B cells were separated according to their sizes, the anti-CDw40-induced proliferation of small tonsillar B cells was inhibited by the anti-CD45 mAb, whereas large tonsillar B cells were resistant. In contrast, anti-IgM-induced proliferation of human B cells was always significantly inhibited by the anti-CD45 mAb regardless of cell size and tissue origin. The anti-CD45 mAb also inhibited the anti-IgM-induced initial rise in intracellular [Ca2+] and the G0-G1 cell cycle transition of small tonsillar B cells. However, co-stimulation with anti-IgM/anti-CDw40 Ab resulted in the resistance to the anti-CD45 inhibitory effect on proliferation of peripheral blood B cells and the majority of tonsillar B cells. In contrast, B cell proliferation co-stimulated with anti-IgM Ab/and B cell growth factors were always suppressed by the anti-CD45 mAb. These results demonstrate that certain activational signal mechanisms utilized by anti-CDw40/anti-IgM Ab and anti-IgM Ab/B cell growth factors are different in that B cells stimulated with these agents differ in their sensitivity to the anti-CD45 mAb. Moreover, both the activational state of human B cells and the nature of activation signals given determine their response to the inhibitory signals delivered by the anti-CD45 mAb.
Construction Project Performance Management Using BSC and Data Warehouse (2009)

Many companies have managed their business performance in order to achieve their enterprise purpose. Performance management which applied concept of BSC (Balanced Scorecard) is widely used all over the world. In the construction industry, BSC-based performance management is currently introduced with needs of balanced performance evaluation. However, most companies actually have intermediate level of adapting BSC. It is important to understand its process or and structure. Therefore, this paper is focused on making performance management process and defining each phase of it. In addition, the model and system are established with putting them together. With developing performance process in construction, the construction companies are supposed to detect the deficiencies of the current performance management systems and take some opportunity to be helped for supporting their decision-making. In conclusion, this paper will provide the construction industry with the opportunities to enhance the values of performance management system and construction application.
Security holes... who cares (2003)

We report on an observational study of user response following the OpenSSL remote buffer overflows of July 2002 and the worm that exploited it in September 2002. Immediately after the publication of the bug and its subsequent fix we identified a set of vulnerable servers. In the weeks that followed we regularly probed each server to determine whether it had applied one of the relevant fixes. We report two primary results. First, we find that administrators are generally very slow to apply the fixes. Two weeks after the bug announcement, more than two thirds of servers were still vulnerable. Second, we identify several weak predictors of user response and find that the pattern differs in the period following the release of the bug and that following the release of the worm. 1
Stearyl-norleucine-vasoactive intestinal peptide (VIP): a novel VIP analog for noninvasive impotence treatment (1994)

The present report relates to pharmaceutical composition for the treatment of male impotence. The transdermal application of a potent derivative of vasoactive intestinal peptide (VIP) coupled to a suitable hydrophobic moiety (e.g. stearyl-VIP) in a suitable ointment composition (e.g. Sefsol) enhances sexual activity and erection formation in a variety of impotence models in rats (sterile rats, diabetic rats, and animals with high blood pressure). Furthermore, exchange of the methionine in position 17 with norleucine enhances biological activity. Thus, stearyl-Nle17-VIP may be considered useful for the treatment of impotence.
Matrix metalloproteinase‐9 concentrations in critically ill patients (2001)

Matrix metalloproteinase‐9 is involved in the processing of cytokines during sepsis. We studied 10 critically ill patients within 12 h of fulfilling the American Consensus Conference criteria for severe sepsis and compared the results with 12 critically ill non‐septic control patients and eight healthy subjects. Total matrix metalloproteinase‐9 concentrations were measured on days 1, 2 and 3. The median admission Acute Physiological and Chronic Health Evaluation II score was 19.5 (range 13–27) in the septic patients and 20.5 (range 7–28) in the non‐septic patients. Four patients from each group died within 28 days. Matrix metalloproteinase‐9 concentrations were elevated significantly in both groups of patients compared with healthy subjects (p = 0.0004) but there was no difference between patients with and without sepsis. Matrix metalloproteinase‐9 levels did not change with time, and there was no difference between survivors and those who died. We conclude that matrix metalloproteinase‐9 represents a non‐specific marker of systemic inflammation.
Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1β (2003)

There is good evidence that the n-3 polyunsaturated fatty acids (PUFAs) in fish oil have antiinflammatory effects and reduce the pathogenesis of atherosclerosis. However, the mechanisms underlying these actions are largely unknown. This study was designed to investigate the effects of membrane incorporation of two major components of fish oil [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], on rat smooth muscle cells (SMCs) activation induced by interleukin-1 beta (IL1 beta). We compared their effects with those of n-6 arachidonic acid (AA). Expression of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 adhesion molecules involved in SMCs migration was enhanced by AA, whereas EPA and DHA had no similar effects. We established that AA potentiates IL1 beta-induced expression of the type IIA secreted phospholipase A2 (sPLA2) gene, whereas EPA and DHA reduce this stimulation. EPA and DHA also abolished proinflammatory prostaglandin PGE2 production by inhibiting the IL1 beta-induced production of cyclooxygenase-2 (COX-2) mRNA. Much interest was then focused on three transcriptional factors implicated in inflammation control and especially in modulating rat sPLA2 and COX-2 gene transcription: nuclear factor-kappa B, CCAAT/enhancer binding protein beta, and E26 transformation-specific-1. electrophoretic mobility shift assay revealed that the binding activity of all three factors was increased by AA and reduced (or not affected) by n-3 PUFA. These results indicate that EPA and DHA act in opposition to AA by modulating various steps of the inflammatory process induced by IL1 beta, probably by reducing mitogen-activated protein kinase p42/p44 activity.
18 O Labeling: a tool for proteomics (2001)

An evaluation of the proteolytic labeling and quantification of proteins for diagnostic purposes using trypsin and 18O-enriched H2O is presented. We demonstrate that comparative or relative quantitation can be performed effectively with this approach. We have developed a protocol that allows the conservation of the labeled peptides in natural abundance water without fear of back-exchange providing that pH is sufficiently low to quench the catalytic activity of trypsin, but not so low as to promote chemical back-exchange. Because the labeling efficiency depends on the nature of the peptide, a simple linear relationship between the relative 16O/18O digest buffer mixture content (x) and labeling efficiency (y) does not exist; rather it follows a probability based y = x(2) relationship. As such, the extent of peptide labeling using 16O/18O digest buffer mixture ratios may deviate significantly from that expected based on a linear relationship. The evaluation of the relative Ziptip efficiency indicated a loss in sample recovery as the peptide concentration was reduced using normal conditions, suggesting that there is a limit below which there are diminishing returns. In addition, the adsorptive losses due to Speedvac dry down and recovery indicated modest (20%) losses that may vary widely (0-50%) from peptide to peptide. The in-solution digestion efficiency of standard protein mixtures as a function of concentration revealed a linear decrease with decreasing concentration. This is consistent with enzyme kinetic effects and emphasizes a potential quantitation error that could arise when evaluating differential expression based on peptide detection. The results from our studies demonstrate the power of 18O labeling as an optimization tool for proteomics process development.
Treatment of Septic Shock with Human Monoclonal Antibody HA-1A (1994)

In this trial, HA-1A was not effective in reducing the 14-day mortality rate in patients with gram-negative bacteremia and septic shock. These data do not support using septic shock as an indication for HA-1A treatment. If HA-1A is effective in reducing the mortality rate in patients dying from endotoxemia, these patients must be identified using other treatment criteria.
Speculations on Difference between Tricyclic and Selective Serotonin Reuptake Inhibitor Antidepressants on Their Cardiac Effects. Is There Any? (1999)

The cardiovascular effects and toxicity of tricyclic antidepressants (TCAs) have been well documented in medical literature. The most common manifestation of such effects is slowing of intraventricular conduction, manifested by prolonged PR, QRS and QT intervals on the standard electrocardiogram (ECG) and postural hypotension. In contrast to TCAs, selective serotonin reuptake inhibitors (SSRIs), including fluoxetine and citalopram, are considered to cause less effect on cardiac impulse conduction. In addition, these compounds induced significantly less anticholinergic, antihistaminergic and cardiotoxic side-effects than TCAs. However, there is an increasing number of case reports on dysrhythmias, like atrial fibrillation or bradycardia and syncope associated with fluoxetine and another SSRI treatment and overdose. Although such reports have not been common, they do raise concerns. In cardiac tissues isolated from canine, rabbit, rat and guinea pig hearts we have found that fluoxetine and citalopram inhibited cardiac Na+ and Ca2+ channels. These direct cardiac electrophysiological effects were similar to those of observed for tricyclic antidepressants clomipramine and imipramine. The inhibition of cardiac Ca2+ and Na+ channels by fluoxetine may explain most cardiac side-effects observed occasionally with the drug and mild but significant bradycardia reported during chronic treatment. Our results suggest that fluoxetine and citalopram may have antiarrhythmic (class I + IV type), as well as proarrhythmic properties (due to impairment of atrioventricular or intraventricular conduction and shortening of repolarization). Taking all these into consideration, in depressed patients having also severe cardiac disorders, ECG control may be suggested during fluoxetine and probable another SSRI therapy. The primary goal of this review is to compare these direct cardiac effects of fluoxetine and citalopram to those of previously reported for TCAs. This paper also summarizes the recently observed effects of fluoxetine apparently not related to the blockage of 5-HT transporter based on literature.
Exploring Attention Mechanism for Acoustic-based Classification of Speech Utterances into System-directed and Non-system-directed (2019)

Voice controlled virtual assistants (VAs) are now available in smartphones, cars, and standalone devices in homes. In most cases, the user needs to first "wake-up" the VA by saying a particular word/phrase every time he/she wants the VA to do something. Eliminating the need for saying the wake-up word for every interaction could improve the user experience. This would require the VA to have the capability of understanding whether the user is talking to it or not. In other words, the challenge is to distinguish between system-directed and non-system-directed speech utterances. In this paper, we present a number of neural network architectures for tackling this classification problem based on using only the acoustic signal. It is shown that a model comprised of convolutional, recurrent, and feed-forward layers can achieve an equal error rate (EER) of below 20% for this task. In addition, we investigate the use of an attention mechanism for helping the model to focus on the more important parts of the signal and to improve handling of variable length inputs sequences. The results show that the proposed attention mechanism significantly improves the model accuracy achieving an EER of 16.25% and 15.62% on two distinct realistic datasets.
Adaptation of Influenza A Viruses to Cells Expressing Low Levels of Sialic Acid Leads to Loss of Neuraminidase Activity (2001)

Influenza A viruses possess two virion surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA binds to sialyloligosaccharide viral receptors, while the NA removes sialic acids from the host cell and viral sialyloligosaccarides. Alterations of the HA occur during adaptation of influenza viruses to new host species, as in the 1957 and 1968 influenza pandemics. To gain a better understanding of the contributions of the HA and possibly the NA to this process, we generated cell lines expressing reduced levels of the influenza virus receptor determinant, sialic acid, by selecting Madin-Darby canine kidney cells resistant to a lectin specific for sialic acid linked to galactose by alpha(2-3) or alpha(2-6) linkages. One of these cell lines had less than 1/10 as much N-acetylneuraminic acid as its parent cell line. When serially passaged in this cell line, human H3N2 viruses lost sialidase activity due to a large internal deletion in the NA gene, without alteration of the HA gene. These findings indicate that NA mutations can contribute to the adaptation of influenza A virus to new host environments and hence may play a role in the transmission of virus across species.
Low levels of C‐peptide have clinical significance for established Type 1 diabetes (2015)

Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.
Robust Detection of Premature Ventricular Contractions Using a Wave-Based Bayesian Framework (2009)

Detection and classification of ventricular complexes from the ECG is of considerable importance in Holter and critical care patient monitoring, being essential for the timely diagnosis of dangerous heart conditions. Accurate detection of premature ventricular contractions (PVCs) is particularly important in relation to life-threatening arrhythmias. In this paper, we introduce a model-based dynamic algorithm for tracking the ECG characteristic waveforms using an extended Kalman filter. The algorithm can work on single or multiple leads. A "polargram"--a polar representation of the signal--is introduced, which is constructed using the Bayesian estimations of the state variables. The polargram allows the specification of a polar envelope for normal rhythms. Moreover, we propose a novel measure of signal fidelity by monitoring the covariance matrix of the innovation signals throughout the filtering procedure. PVCs are detected by simultaneous tracking the signal fidelity and the polar envelope. Five databases, including 40 records from MIT-BIH arrhythmia database, are used for differentiating normal, PVC, and other beats. Performance evaluation results show that the proposed method has an average detection accuracy of 99.10%, aggregate sensitivity of 98.77%, and aggregate positive predictivity of 97.47%. Furthermore, the method is capable of 100% accuracy for records that contain only PVCs and normal sinus beats. The results illustrate that the method can contribute to, and enhance the performance of clinical PVC detection.
Selective Cardiovascular Effects of Stress and Cigarette Smoking (1983)

The purpose of the present study was to determine how cigarette smoking and psychological stress combine to affect cardiovascular function. Stress was operationally defined as playing a series of difficult video games under challenging instructional conditions. Following an initial test game, 51 smokers were randomly assigned to a 2 (smoke vs. sham smoke) X 2 (stress vs. no stress) design. The results showed that the subjects who sham smoked (inhaled unlit cigarettes) under no stress evidenced minimal changes in cardiovascular parameters. Subjects who smoked under no stress evidenced approximately 12 mmHg increase in systolic blood pressure (SBP) and 9 mmHg increases in diastolic blood pressure (DBP), and a 15 beat-per-minute increase in heart rate (HR). These effects were similar in magnitude to those seen in subjects who sham smoked under stress. By contrast, subjects who smoked under stress showed markedly larger increases in all cardiovascular parameters, approximately doubling the magnitude of the observed response over that seen with either smoking or stress alone. Correlational analyses suggested the presence of stable individual differences in autonomic lability or sensitivity. Possible mechanisms are suggested whereby stress and smoking may combine to heighten the risk for coronary disease.