gebhart/patrepeval huggingface dataset:
Mutant KRAS as a critical determinant of the therapeutic response of colorectal cancer (2014)

Mutations in the <i>KRAS</i> oncogene represent one of the most prevalent genetic alterations in colorectal cancer (CRC), the third leading cause of cancer-related death in the US. In addition to their well-characterized function in driving tumor progression, <i>KRAS</i> mutations have been recognized as a critical determinant of the therapeutic response of CRC. Recent studies demonstrate that <i>KRAS</i>-mutant tumors are intrinsically insensitive to clinically-used epidermal growth factor receptor (EGFR) targeting antibodies, including cetuximab and panitumumab. Acquired resistance to the anti-EGFR therapy was found to be associated with enrichment of <i>KRAS</i>-mutant tumor cells. However, the underlying molecular mechanism of mutant-KRAS-mediated therapeutic resistance has remained unclear. Despite intensive efforts, directly targeting mutant KRAS has been largely unsuccessful. This review summarizes the recent advances in understanding the biological function of <i>KRAS</i> mutations in determining the therapeutic response of CRC, highlighting several recently developed agents and strategies for targeting mutant KRAS, such as synthetic lethal interactions.
Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses (2020)

Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs.
726. Colensenone (1962)

P. K. Grant and R. M. Carman, J. Chem. Soc., 1962, 3740 DOI: 10.1039/JR9620003740
Morphology-Aware Statistical Machine Translation Based on Morphs Induced in an Unsupervised Manner (2007)

In this paper, we apply a method of unsupervised morphology learning to a state-of-the-art phrase-based statistical machine translation (SMT) system. In SMT, words are traditionally used as the smallest units of translation. Such a system generalizes poorly to word forms that do not occur in the training data. In particular, this is problematic for languages that are highly compounding, highly inflecting, or both. An alternative way is to use sub-word units, such as morphemes. We use the Morfessor algorithm to find statistical morphemelike units (called morphs) that can be used to reduce the size of the lexicon and improve the ability to generalize. Translation and language models are trained directly on morphs instead of words. The approach is tested on three Nordic languages (Danish, Finnish, and Swedish) that are included in the Europarl corpus consisting of the Proceedings of the European Parliament. However, in our experiments we did not obtain higher BLEU scores for the morph model than for the standard word-based approach. Nonetheless, the proposed morph-based solution has clear benefits, as morphologically well motivated structures (phrases) are learned, and the proportion of words left untranslated is clearly reduced. 1.
2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a (HPPH) in a nude rat glioma model: Implications for photodynamic therapy (2001)

Twenty-four hours after injection of 0.5 mg/kg HPPH, tumor-to-brain drug ratios ranged from 5:1 to 15:1. Enhanced survival was observed in each of the HPPH/PDT-treated animal groups. These data suggest that HPPH may be a useful adjuvant for the treatment of malignant gliomas.
Change begets change: emerging role of the human resources development practitioner. (1990)

This article has discussed three essential role shifts for the HRD practitioner: reactor to initiator, "pair-of-hands" to collaborator, and problem solving consultant to action learning facilitator. These shifts in role are required for the process of helping manage organizational change in our hospitals. Ongoing learning will be the essential ingredient to successfully manage change in health care organizations. This continual learning is not for clients alone, but is also required by HRD practitioners who want to be taken seriously as contributing to the achievement of their organization's future vision. While the effective HRD practitioner will need to continually experiment with new approaches, a starting point today is with the role changes described in this article.
[Toxicology of carteolol]. (1983)

Studies of the acute toxicity of 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite) in various species by different modes of administration revealed comparatively slight necropsy and histological changes despite characteristic clinical features of poisoning, There were only minor discrepancies in LD50 between the different species, and no sex differences were observed. The LD50 was 2000-4000 times the therapeutic dose. Death is thought to be due to excessive enhancement of the pharmacological action of the sympathomimetic component with extreme abnormalities of blood distribution and interference with cardiac and lung function. In subchronic and chronic toxicity tests in rats no effects due to the drug were demonstrable for doses of up to 150 mg/kg. In dogs the highest dose free from side-effects was between 3 and 30 mg/kg. Above 10 times the therapeutic dose there was some increase in brown adipose tissue, but this is not thought to be of any pathological significance. No teratogenic effects were detected in experiments on mice, rats and rabbits, and no embryotoxic or fetotoxic activity was seen except for doses high enough to produce toxic effects in the mother animals. No carcinogenic properties were identified. Tests for mutagenic effects (S. typhimurium, E. coli, cytogenetic studies in rats, dominant lethal test) yielded negative results.
Mechanistic Studies of Cu Electropolishing in Phosphoric Acid Electrolytes (2004)

Electropolishing of Cu and Cu/Ta/Si wafer samples were studied using a rotating disk electrode in a variety of phosphoric acid-based electrolytes, including several with ethanol and other species added as diluents. Diluents allow a wide range of water concentrations to be accessed and also reduce the dissolution rate during Cu electropolishing, simplifying possible applications to damascene processing. The measured limiting current densities are subject to a Levich analysis, demonstrating that water is the acceptor species involved in the rate-determining step. The effective diffusion coefficient that is determined is in almost exact agreement with that previously obtained from the electrohydrodynamic impedance, which does not require knowledge of the limiting species. © 2004 The Electrochemical Society. All rights reserved.
Klebsiella pneumoniae liver abscess in diabetic patients: association of glycemic control with the clinical characteristics (2013)

Glycemic control in diabetic patients played an essential role in the clinical characteristics of KPLA, especially in metastatic complications from KPLA.
Development of real-time NASBA assays with molecular beacon detection to quantify mRNA coding for HHV-8 lytic and latent genes (2002)

These real-time NASBA assays with beacon detection provide tools for further study of HHV-8 expression in patient material.
Molecular cloning and nucleotide sequence of cDNA encoding the human liver S-adenosylmethionine synthetase. (1991)

cDNA clone for human liver S-adenosylmethionine synthetase (liver-specific isoenzyme) was isolated from a cDNA library of human liver poly(A)+ RNA. The cDNA sequence encoded a polypeptide consisting of 395 amino acid residues with a calculated molecular mass of 43675 Da. Alignment of the predicted amino acid sequence of this protein with that of rat liver S-adenosylmethionine synthetase showed a high degree of similarity. The coding region of the human liver S-adenosylmethionine synthetase cDNA sequence was 89% identical at the nucleotide level and 95% identical at the amino acid level to the sequence for rat liver S-adenosylmethionine synthetase.
Long-term sensitization training in Aplysia leads to an increase in the expression of BiP, the major protein chaperon of the ER. (1992)

Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in Aplysia californica requires RNA and protein synthesis. These long-term behavioral changes are accompanied by long-term facilitation of the synaptic connections between the gill and siphon sensory and motor neurons, which are similarly dependent on transcription and translation. In addition to showing an increase in over-all protein synthesis, long-term facilitation is associated with changes in the expression of specific early, intermediate, and late proteins, and with the growth of new synaptic connections between the sensory and motor neurons of the reflex. We previously focused on early proteins and have identified four proteins as members of the immunoglobulin family of cell adhesion molecules related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER resident protein involved in the folding and assembly of secretory and membrane proteins. Behavioral training increases the steady-state level of BiP mRNA in the sensory neurons. The increase in the synthesis of BiP protein is first detected 3 h after the onset of facilitation, when the increase in overall protein synthesis reaches its peak and the formation of new synaptic terminals becomes apparent. These findings suggest that the chaperon function of BiP might serve to fold proteins and assemble protein complexes necessary for the structural changes characteristic of long-term memory.
XRCE's Participation to CLEF 2007 Domain-Specific Track. (2007)

Our participation to CLEF07 (Domain-specific Track) was motivated this year by assessing several query translation and expansion strategies that we recently designed and developed. One line of research and development was to use our own Statistical Machine Translation system (called Matrax) and its intermediate outputs to perform query translation and disambiguation. Our idea was to benefit from Matrax ’ flexibility to output more than one plausible translations and to train its Language Model component on the CLEF07 target corpora. The second line of research consisted in designing algorithms to adapt an initial, general probabilistic dictionary to a particular pair (query, target corpus); this constitutes some extreme viewpoint on the “bilingual lexicon extraction and adaptation ” topic that we are investigating since now more than 6 years. For this strategy, our main contributions lie in a pseudo-feedback algorithm and an EM-like optimisation algorithm that realize this adaptation. A third axis was to evaluate the potential impact of “Lexical Entailment ” models in a cross-lingual framework, as they were only used in a monolingual setting up to now. Experimental results on CLEF-2007 corpora (domain-specific track) show that the dictionary adaptation mechanisms appear quite effective in the CLIR framework, exceeding in certain cases the performance of much more complex Machine Translation systems and even the performance of the monolingual baseline. In most cases also, Lexical Entailment models, used as query expansion mechanisms, turned out to be beneficial.
Association Between Immunogenicity and Adsorption of a RecombinantStreptococcus pneumoniaeVaccine Antigen by an Aluminum Adjuvant (2006)

The impact on immunogenicity of the degree of adsorption of three Streptococcus pneumoniae (Sp) vaccine antigens to aluminum adjuvants was studied. The three antigens evaluated (Sp1, Sp2 and Sp3) were highly adsorbed by aluminum hydroxide adjuvant, but not adsorbed by aluminum phosphate adjuvant. All of the Sp antigens adjuvanted with aluminum hydroxide elicited higher antibody responses in mice than formulations prepared with aluminum phosphate or non-adjuvanted antigen. Varying the percent aluminum-bound Sp antigen in the formulated vaccine affected the observed antibody responses. These observations suggest that the antibody response observed for Sp antigens in this study is stimulated by a depot effect of the antigen bound to an aluminum adjuvant.
Recruitment of the Tinman Homolog Nkx-2.5 by Serum Response Factor Activates Cardiac α-Actin Gene Transcription (1996)

We recently showed that the cardiogenic homeodomain factor Nkx-2.5 served as a positive acting accessory factor for serum response factor (SRF) and that together they provided strong transcriptional activation of the cardiac alpha-actin promoter, depending upon intact serum response elements (SREs) (C. Y. Chen, J. Croissant, M. Majesky, S. Topouz, T. McQuinn, M. J. Frankovsky, and R. J. Schwartz, Dev. Genet. 19:119-130, 1996). As shown here, Nkx-2.5 and SRF collaborated to activate the endogenous murine cardiac alpha-actin gene in 10T1/2 fibroblasts by a mechanism in which SRF recruited Nkx-2.5 to the alpha-actin promoter. Activation of a truncated promoter consisting of the proximal alpha-actin SRE1 occurred even when Nkx-2.5 DNA-binding activity was blocked by a point mutation in the third helix of its homeodomain. Investigation of protein-protein interactions showed that Nkx-2.5 was bound to SRF in the absence of DNA in soluble protein complexes retrieved from cardiac myocyte nuclei but could also be detected in coassociated binding complexes on the proximal SRE1. Recruitment of Nkx-2.5 to an SRE depended upon SRF DNA-binding activity and was blocked by the dominant negative SRFpm1 mutant, which allowed for dimerization of SRF monomers but prevented DNA binding. Interactive regions shared by Nkx-2.5 and SRF were mapped to N-terminal/helix I and helix II/helix III regions of the Nkx-2.5 homeodomain and to the N-terminal extension of the MADS box. Our study suggests that physical association between Nkx-2.5 and SRF is one way that cardiac specified genes are activated in cardiac cell lineages.
Measuring phase synchrony in brain signals (1999)

This article presents, for the first time, a practical method for the direct quantification of frequency-specific synchronization (i.e., transient phase-locking) between two neuroelectric signals. The motivation for its development is to be able to examine the role of neural synchronies as a putative mechanism for long-range neural integration during cognitive tasks. The method, called phase-locking statistics (PLS), measures the significance of the phase covariance between two signals with a reasonable time-resolution (<100 ms). Unlike the more traditional method of spectral coherence, PLS separates the phase and amplitude components and can be directly interpreted in the framework of neural integration. To validate synchrony values against background fluctuations, PLS uses surrogate data and thus makes no a priori assumptions on the nature of the experimental data. We also apply PLS to investigate intracortical recordings from an epileptic patient performing a visual discrimination task. We find large-scale synchronies in the gamma band (45 Hz), e.g., between hippocampus and frontal gyrus, and local synchronies, within a limbic region, a few cm apart. We argue that whereas long-scale effects do reflect cognitive processing, short-scale synchronies are likely to be due to volume conduction. We discuss ways to separate such conduction effects from true signal synchrony.
Thioredoxin‐interacting protein deficiency induces Akt/Bcl‐xL signaling and pancreatic beta‐cell mass and protects against diabetes (2008)

Pancreatic beta-cell loss through apoptosis represents a key factor in the pathogenesis of diabetes; however, no effective approaches to block this process and preserve endogenous beta-cell mass are currently available. To study the role of thioredoxin-interacting protein (TXNIP), a proapoptotic beta-cell factor we recently identified, we used HcB-19 (TXNIP nonsense mutation) and beta-cell-specific TXNIP knockout (bTKO) mice. Interestingly, HcB-19 mice demonstrate increased adiposity, but have lower blood glucose levels and increased pancreatic beta-cell mass (as assessed by morphometry). Moreover, HcB-19 mice are resistant to streptozotocin-induced diabetes. When intercrossed with obese, insulin-resistant, and diabetic mice, double-mutant BTBRlep(ob/ob)txnip(hcb/hcb) are even more obese, but are protected against diabetes and beta-cell apoptosis, resulting in a 3-fold increase in beta-cell mass. Beta-cell-specific TXNIP deletion also enhanced beta-cell mass (P<0.005) and protected against diabetes, and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) revealed a approximately 50-fold reduction in beta-cell apoptosis in streptozotocin-treated bTKO mice. We further discovered that TXNIP deficiency induces Akt/Bcl-xL signaling and inhibits mitochondrial beta-cell death, suggesting that these mechanisms may mediate the beta-cell protective effects of TXNIP deficiency. These results suggest that lowering beta-cell TXNIP expression could serve as a novel strategy for the treatment of type 1 and type 2 diabetes by promoting endogenous beta-cell survival.
Overexpression of c-met as a Prognostic Indicator for Transitional Cell Carcinoma of the Urinary Bladder: A Comparison With p53 Nuclear Accumulation (2002)

PURPOSE: The c-met proto-oncogene encodes a receptor tyrosine kinase (Met) and has been shown to play a role in oncogenesis. Given that high titers of hepatocyte growth factor, the specific ligand for Met, are excreted in the urine and tend to reflect disease activity of bladder cancer, we performed this study to examine the clinical significance of Met in human bladder cancer. MATERIALS AND METHODS: We studied the mRNA expression and genomic alteration of c-met in five bladder cancer cell lines. Significance of Met overexpression was then compared with p53 nuclear accumulation (TP53) in primary bladder cancer (n = 142 patients). RESULTS: Expression of c-met mRNA tended to positively correlate with differentiation of cancer cell lines in the absence of point mutation. High expression of Met was found in seven cases (4.9%), low expression in 32 cases (22.5%), and negative expression in 103 cases (72.5%). Expression of Met was positively associated with histologic grade, stage classification, tumor size, and nodular tumor growth (P &lt; .05, respectively); however, it was not related to TP53 status. Factors that predicted disease progression were tumor stage, Met status, and TP53 accumulation (P &lt; .05, respectively). Indicators for poor long-term survival were invasive cancer, multiple tumors, and Met overexpression (P = .0006, .01, and .04, respectively). CONCLUSION: The c-met proto-oncogene plays a more important role in the progression of bladder carcinogenesis than p53. Evaluation of Met expression could identify a subset of bladder cancer patients who may require a more intensive treatment strategy.
Optimum Settings for Automatic Controllers (1942)

Abstract In this paper, the three principal control effects found in present controllers are examined and practical names and units of measurement are proposed for each effect. Corresponding units are proposed for a classification of industrial processes in terms of the two principal characteristics affecting their controllability. Formulas are given which enable the controller settings to be determined from the experimental or calculated values of the lag and unit reaction rate of the process to be controlled. These units form the basis of a quick method for adjusting a controller on the job. The effect of varying each controller setting is shown in a series of chart records. It is believed that the conceptions of control presented in this paper will be of assistance in the adjustment of existing controller applications and in the design of new installations.
Dehydroepiandrosterone Reduces Serum Low Density Lipoprotein Levels and Body Fat but Does not Alter Insulin Sensitivity in Normal Men* (1988)

To assess the effects of dehydroepiandrosterone (DHEA) on body fat mass, serum lipid levels, and tissue sensitivity to insulin, five normal men were given placebo and five normal men were given oral DHEA [1600 mg/day (554.7 mmol/day)] for 28 days in a randomized, double blind study. In the DHEA group serum DHEA-S levels rose 2.5- to 3.5-fold, and mean (+/- SEM) serum androstenedione rose from 4.3 +/- 0.6 to 8.6 +/- 1.2 nmol/L (P less than 0.004, by paired t test), but serum total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and estrone levels did not change. In the DHEA group the mean percent body fat decreased by 31%, with no change in weight. This suggests that the reduction in fat mass was coupled with an increase in muscle mass. DHEA administration also resulted in a fall in mean serum total cholesterol concentration (4.82 +/- 0.21 vs. 4.48 +/- 0.29 nmol/L; P less than 0.05), which was due almost entirely to a fall of 7.5% in mean serum low density lipoprotein cholesterol (3.21 +/- 0.11 vs. 2.97 +/- 0.14 nmol/L; P less than 0.01). No changes in anthropometric parameters or serum lipid levels occurred in the placebo group. Tissue sensitivity to insulin, assessed by the hyperinsulinemic-euglycemic clamp technique, did not change in either the placebo or DHEA groups. These results suggest that in normal men DHEA administration reduces body fat, increases muscle mass, and reduces serum low density lipoprotein cholesterol levels. Tissue sensitivity to insulin was unaffected by short term DHEA administration.
Molecular analysis of sialoside binding to sialoadhesin by NMR and site-directed mutagenesis (1999)

The molecular interactions between sialoadhesin and sialylated ligands have been investigated by using proton NMR. Addition of ligands to the 12 kDa N-terminal immunoglobulin-like domain of sialoadhesin result in resonance shifts in the protein spectrum that have been used to determine the affinities of sialoadhesin for several sialosides. The results indicate that alpha2, 3-sialyl-lactose and alpha2,6-sialyl-lactose bind respectively 2- and 1.5-fold more strongly than does alpha-methyl-N-acetylneuraminic acid (alpha-Me-NeuAc). The resonances corresponding to the methyl protons within the N-acetyl moiety of sialic acid undergo upfield shifting and broadening during titrations, reflecting an interaction of this group with Trp2 in sialoadhesin as observed in co-crystals of the terminal domain with bound ligand. This resonance shift was used to measure the affinities of mutant and wild-type forms of sialoadhesin in which the first three domains are fused to the Fc region of human IgG1. Substitution of Arg97 by alanine completely abrogated measurable interaction with alpha-Me-NeuAc, whereas a conservative substitution with lysine resulted in a 10-fold decrease in affinity. These results provide the first direct measurement of the affinity of sialoadhesin for sialosides and confirm the critical importance of the conserved arginine in interactions between sialosides and members of the siglec family of sialic acid-binding, immunoglobulin-like lectins.
DNA MISMATCH REPAIR (2005)

DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects mismatches generated during DNA replication and escape proofreading. MMR proteins also participate in many other DNA transactions, such that inactivation of MMR can have wide-ranging biological consequences, which can be either beneficial or detrimental. We begin this review by briefly considering the multiple functions of MMR proteins and the consequences of impaired function. We then focus on the biochemical mechanism of MMR replication errors. Emphasis is on structure-function studies of MMR proteins, on how mismatches are recognized, on the process by which the newly replicated strand is identified, and on excision of the replication error.