gebhart/patrepeval huggingface dataset:
Senile Dementia of Lewy Body Type and Alzheimer Type Are Biochemically Distinct in Terms of Paired Helical Filaments and Hyperphosphorylated Tau Protein (Part 1 of 2) (1994)

We have used biochemical assays to examine cingulate and occipital cortices from age-matched cases of Alzheimer's disease (AD; n = 12), senile dementia of the Lewy body type (SDLT; n = 13), Parkinson's disease (PD; 5 non-demented cases and 7 cognitively impaired cases) and controls (n = 11) for paired helical filaments (PHFs), phosphorylated and normal tau protein and beta/A4-protein. Whereas cingulate cortex is characterised by relatively high densities of cortical Lewy bodies in the SDLT cases and lower numbers in PD, these inclusion bodies were absent in the cingulate cortex from AD and control cases. Protease-resistant PHFs and hyperphosphorylated tau protein were found in AD and, at low levels, in a minority of SDLT cases. Qualitatively, both of these preparations were indistinguishable in SDLT from those found in AD but levels of both parameters in SDLT were less than 5% of those in AD. SDLT, PD and control groups did not differ from each other in terms of the quantity of protease-resistant PHFs or the level of hyperphosphorylated tau. Furthermore, PHF accumulation did not distinguish between PD cases with or without dementia. The levels of normal tau protein did not differ between the four groups. beta/A4 protein levels did not distinguish between PD and control groups, between AD and SDLT groups, or between SDLT and control groups for either cingulate or occipital cortices. Thus extensive accumulation of PHFs in either neurofibrillary tangles or dystrophic neurites is not a feature of either SDLT or PD. Our findings provide molecular support for the neuropathological and clinical separation of SDLT as a form of dementia that is distinct from AD.
Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili (1998)

We have used Escherichia coli as a model system to investigate the initiation of biofilm formation. Here, we demonstrate that E. coli forms biofilms on multiple abiotic surfaces in a nutrient-dependent fashion. In addition, we have isolated insertion mutations that render this organism defective in biofilm formation. One-half of these mutations was found to perturb normal flagellar function. Using defined fli, flh, mot and che alleles, we show that motility, but not chemotaxis, is critical for normal biofilm formation. Microscopic analyses of these mutants suggest that motility is important for both initial interaction with the surface and for movement along the surface. In addition, we present evidence that type I pili (harbouring the mannose-specific adhesin, FimH) are required for initial surface attachment and that mannose inhibits normal attachment. In light of the observations presented here, a working model is discussed that describes the roles of both motility and type I pili in biofilm development.
Characterizing the experience of agitation in patients with bipolar disorder and schizophrenia (2018)

Community based patients with schizophrenia and bipolar disorder reported frequently experiencing agitation episodes which they defined most commonly as feeling uneasy, restless or nervous. A range of coping strategies were reported but they were not always successful, highlighting an area of unmet need in this population.
A portable multimedia terminal (1992)

A personal communications system (PCS) that centers on integration of services to provide access to data and communications using a specialized, wireless multimedia terminal is described. The possible applications and support systems for such a terminal are outlined. Several of the major design issues behind portable multimedia terminals, including spectrally efficient picocellular networking, low-power digital design, video data compression, and integrated wireless RF transceivers, are discussed. It is argued that optimizing performance in each of these areas is crucial in meeting the performance requirements of the overall system and providing a small, lightweight terminal for personal communications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Use of Prevotella bryantii 25A and a commercial probiotic during subacute acidosis challenge in midlactation dairy cows (2012)

The objective of this study was to determine the efficacy of Prevotella bryantii 25A as a probiotic during a subacute ruminal acidosis (SARA) challenge using a commercial probiotic as a positive control. Six multiparous ruminally fistulated cows (BW=685 ± 65 kg; (mean ± SD) in the mid-phase of lactation (70 to 148 DIM) received the following treatments in a replicated 3×3 Latin square design: (1) total mixed ration (TMR; control, CON), (2) TMR + 2g/head per day of a probiotic combination of Enterococcus faecium and Saccharomyces cerevisiae (EFSC), or (3) TMR + Prevotella bryantii 25A. The Latin square consisted of 3 wk of adaptation to the respective treatments during which the animals were fed ad libitum once per day a conventional early-lactation TMR and 1.5 kg of hay. The adaptation was followed by 4 d of SARA (no hay) and 10d of rest (adaptation diet without probiotics). Dry matter intake and milk production were depressed during SARA (22.0 and 31.8 kg/d, respectively) compared with adaptation (24.4 and 34.0 kg/d, respectively) and did not recover during rest (22.3 and 30.7 kg/d, respectively). During SARA, P. bryantii 25A had no effect on rumen pH, whereas EFSC reduced the percentage of time with pH <6.0 (71%) compared with CON (85%) and increased maximum pH. The EFSC treatment tended to increase mean pH over 24h (5.65) compared with CON (5.45). Proportion of time with pH <5.6 tended to be lower with EFSC (46%) than with CON (62%). Populations of bacteria considered to be the most important cellulose digesters in the rumen (Ruminococcus flavefaciens, Ruminococcus albus, and Fibrobacter succinogenes) were also monitored during these treatments using culture-independent real-time PCR methods. The population of R. flavefaciens was similar between the 2 feeding phases, whereas F. succinogenes and R. albus were lower during SARA compared with rest. In light of the present study, P. bryantii 25A did not prove to be an effective preventative for SARA. The role of EFSC in regulating rumen pH was confirmed, with a possible effect of maintaining R. flavefaciens populations during SARA.
Off-target Effects in CRISPR/Cas9-mediated Genome Engineering (2015)

CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%)-RGEN (RNA-guided endonuclease)-induced mutations at sites other than the intended on-target site-is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype-phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology.
The evolving role of autologous peripheral stem cell transplantation following high-dose therapy for malignancies [editorial] (1991)

Over the last decade, transplantation of circulating autologous hematopoietic stem cells to facilitate the recovery of bone marrow (BM) function following administration of marrow ablative anti-cancer therapy has been used with increasing frequency. During that time, a number of indications for peripheral stem cell transplantation (PSCT) emerged
OTIMIZAÇÃO DO SISTEMA PSEUDO-TERNÁRIO AL2O3-MNO-TIO2 USANDO O MODELO DE KAPOOR-FROHBERG-GAYE (2006)

Incluses no-metlicas so produtos inevitveis na metalurgia dos aos, apresentando efeito significativo sobre diversas propriedades, tais como: resistncia a fadiga, ductilidade, resistncia corroso, entre o u t r a s . Alm disto, tem-se observado que incluses no-metlicas podem alterar as transformaes de fase dos aos, especialmente aquelas associadas decomposio da aust e n i t a ( 2 -4 ) que podem ser aproveitadas favoravelmente em vrios tipos de metais depositados por solda na nucleao macia de ferrita acicular e, eventualmente, na produo de produtos n e a r-n e t -s h a p e, com espessuras muito finas
Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol (1999)

The lipid composition of cellular membranes is regulated to maintain membrane fluidity. A key enzyme involved in this process is the membrane-bound stearoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids. A proper ratio of saturated to monounsaturated fatty acids contributes to membrane fluidity. Alterations in this ratio have been implicated in various disease states including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, hypertension, neurological diseases, immune disorders, and cancer. The regulation of stearoyl-CoA desaturase is therefore of considerable physiological importance and its activity is sensitive to dietary changes, hormonal imbalance, developmental processes, temperature changes, metals, alcohol, peroxisomal proliferators, and phenolic compounds. Two mouse and rat SCD genes (SCD1 and SCD2) and a single human SCD gene have been cloned and characterized. In the past several years we have studied the dietary influences on the genetic expression of the mouse stearoyl-CoA desaturase. The expression of the mouse SCD genes is regulated by polyunsaturated fatty acids and cholesterol at the levels of transcription and mRNA stability. Promoter elements that are responsible for the polyunsaturated fatty acid repression colocalize with the promoter elements for SREBP-mediated regulation of the SCD genes. It is the goal of this review to provide an overview of the genetic regulation of the stearoyl-CoA desaturase in response to dietary polyunsaturated fatty acids and cholesterol.
Lymphocyte Transformation by Pim-2 Is Dependent on Nuclear Factor-κB Activation (2004)

Pim-2 is a transcriptionally regulated oncogenic kinase that promotes cell survival in response to a wide variety of proliferative signals. Deregulation of Pim-2 expression has been documented in several human malignancies, including leukemia, lymphoma, and multiple myeloma. Here, we show that the ability of Pim-2 to promote survival of cells is dependent on nuclear factor (NF)-kappaB activation. Pim-2 activates NF-kappaB-dependent gene expression by inducing phosphorylation of the oncogenic serine/threonine kinase Cot, leading to both augmentation of IkappaB kinase activity and a shift in nuclear NF-kappaB from predominantly p50 homodimers to p50/p65 heterodimers. Blockade of NF-kappaB function eliminates Pim-2-mediated survival in both cell lines and primary cells, and both Cot phosphorylation and expression are required for the prosurvival effects of Pim-2. Although Pim-2 cooperates with Myc to promote growth factor-independent cell proliferation, this feature is abrogated by NF-kappaB blockade. The ability of Pim-2 to serve as an oncogene in vivo depends on sustained NF-kappaB activity. Thus, the transcriptional induction of Pim-2 initiates a novel NF-kappaB activation pathway that regulates cell survival.
IFN-γ Inhibits Gastric Carcinogenesis by Inducing Epithelial Cell Autophagy and T-Cell Apoptosis (2011)

IFN-γ mediates responses to bacterial infection and autoimmune disease, but it is also an important tumor suppressor. It is upregulated in the gastric mucosa by chronic Helicobacter infection; however, whether it plays a positive or negative role in inflammation-associated gastric carcinogenesis is unexplored. To study this question, we generated an H(+)/K(+)-ATPase-IFN-γ transgenic mouse that overexpresses murine IFN-γ in the stomach mucosa. In contrast to the expected proinflammatory role during infection, we found that IFN-γ overexpression failed to induce gastritis and instead inhibited gastric carcinogenesis induced by interleukin-1beta (IL-1β) and/or Helicobacter infection. Helper T cell (Th) 1 and Th17 immune responses were inhibited by IFN-γ through Fas induction and apoptosis in CD4 T cells. IFN-γ also induced autophagy in gastric epithelial cells through increased expression of Beclin-1. Finally, in the gastric epithelium, IFN-γ also inhibited IL-1β- and Helicobacter-induced epithelial apoptosis, proliferation, and Dckl1(+) cell expansion. Taken together, our results suggest that IFN-γ coordinately inhibits bacterial infection and carcinogenesis in the gastric mucosa by suppressing putative gastric progenitor cell expansion and reducing epithelial cell apoptosis via induction of an autophagic program.
Low-loss fluorinated poly(arylene ether sulfide) waveguides with high thermal stability (2001)

Some novel cross-linkable fluorinated poly(arylene ether sulfides) (FPAESI) were synthesized for use in optical waveguide applications. The materials have high thermal stability, high optical transparency in the infrared communication region, and much less birefringence than other thermally stable fluorinated polyimides. The refractive index of FPAESI after storage at 100/spl deg/C for 1000 h remains almost constant, demonstrating their thermal stability. Furthermore, the refractive index of the material can be easily controlled by changing the fluorine content of the materials. The propagation loss of channel waveguides, which were fabricated using reactive ion etching was less than 0.42 dB/cm and 0.4 dB/cm at the wavelength of 1.55 /spl mu/m for TE and TM polarizations, respectively.
Resistance of ICAM-1–deficient mice to metastasis overcome by increased aggressiveness of lymphoma cells (2000)

Our recent finding that resistance to lymphoma cell metastasis in intercellular adhesion molecule-1-(ICAM-1)-deficient mice was manifested after homing suggested that the mechanism could involve the capacity of ICAM-1 to induce, via leukocyte function-associated antigen-1 (LFA-1) signaling, the expression of new genes necessary for migration and survival of lymphoma cells after homing. This hypothesis would imply that lymphoma cells, on repeated metastatic cycles, would acquire such a highly aggressive phenotype that they no longer require contact with ICAM-1 at later stages of metastasis. We addressed this question by generating highly aggressive lymphoma variants to determine if increased tumorigenicity would allow lymphoma cells to grow into tumors in ICAM-1-deficient mice. We found that on repeated in vivo passages, a selective pressure favored the lymphoma cells that constitutively express high levels of matrix metalloproteainse-9 (MMP-9), a gene associated with a poor clinical outcome in non-Hodgkins's lymphoma. We further found that although the parent lymphoma cells could not grow tumors in ICAM-1-deficient mice, the aggressive lymphoma variants could. This indicates that, at late stages of the disease, tumor cells with a high metastatic efficiency, encoded by the repertoire of selected genes, no longer require some of the signals normally delivered by cell adhesion molecules. In light of these findings, the possibility of inhibiting dissemination of lymphoma cells at the late stage of the disease by acting against cell adhesion molecules must be reconsidered. (Blood. 2000;95:314-319)
Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene? (2012)

Androgen receptor (AR) signaling exerts an antiestrogenic, growth-inhibitory influence in normal breast tissue, and this role may be sustained in estrogen receptor α (ERα)-positive luminal breast cancers. Conversely, AR signaling may promote growth of a subset of ERα-negative, AR-positive breast cancers with a molecular apocrine phenotype. Understanding the molecular mechanisms whereby androgens can elicit distinct gene expression programs and opposing proliferative responses in these two breast cancer phenotypes is critical to the development of new therapeutic strategies to target the AR in breast cancer.
Synthetic cannabinoid ajulemic acid exerts potent antifibrotic effects in experimental models of systemic sclerosis (2012)

AjA prevents progression of fibrosis in vivo and inhibits fibrogenesis in vitro by stimulating PPAR-γ signalling. Since therapeutic doses of AjA are well tolerated in humans, it is suggested that AjA as an interesting molecule targeting fibrosis in patients with scleroderma.
Abstract 2348: Discovery of AZD6738, a potent and selective inhibitor with the potential to test the clinical efficacy of ATR kinase inhibition in cancer patients. (2013)

Abstract AZD6738 is a potent and selective inhibitor of ataxia telangiectasia and rad3 related (ATR) kinase with the potential to be used in the clinic. We report the discovery of a morpholino-pyrimidine series and its subsequent optimisation to the pre-clinical candidate AZD6738 which has a good overall balance of potency, selectivity, pharmacokinetic and biopharmaceutical properties suitable for oral dosing. ATR is a serine/threonine protein kinase involved in DNA damage response signalling caused by DNA replication associated stress. Activation of ATR at stalled replication forks leads to suppression of replication fork origin firing, promotes repair and S/G2-cell cycle checkpoints to prevent premature mitosis and maintain genomic integrity. Failure to resolve damage leads to genomic instability and if sufficiently high, cell death. Stalled replication forks may collapse leading to formation of DNA double stranded breaks and activation of the ataxia telangiectasia mutated (ATM) kinase. ATM works in conjunction with ATR to efficiently resolve replication associated DNA damage creating a co-dependency with loss of one leading to a greater reliance on the other to maintain genomic stability. ATM is frequently inactivated across B-cell malignancies, head and neck, breast and lung cancers through chromosomal deletion, promoter hypermethylation or mutation. ATM-deficient tumours are hypothesised to be more reliant on ATR for survival and specific inhibition of ATR may lead enhanced anti-tumour activity while minimizing normal tissue toxicity. AZD6378 has the potential to test the clinical efficacy of ATR inhibition in cancer patients as monotherapy against ATM-deficient tumours or in combination with chemo or radiotherapy. Citation Format: Clifford D. Jones, Kevin Blades, Kevin M. Foote, Sylvie M. Guichard, Philip J. Jewsbury, Thomas McGuire, Johannes W. Nissink, Rajesh Odedra, Kin Tam, Pia Thommes, Paul Turner, Gary Wilkinson, Christine Wood, James W. Yates. Discovery of AZD6738, a potent and selective inhibitor with the potential to test the clinical efficacy of ATR kinase inhibition in cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2348. doi:10.1158/1538-7445.AM2013-2348
METEOR: An Automatic Metric for MT Evaluation with Improved Correlation with Human Judgments (2005)

We describe METEOR, an automatic metric for machine translation evaluation that is based on a generalized concept of unigram matching between the machineproduced translation and human-produced reference translations. Unigrams can be matched based on their surface forms, stemmed forms, and meanings; furthermore, METEOR can be easily extended to include more advanced matching strategies. Once all generalized unigram matches between the two strings have been found, METEOR computes a score for this matching using a combination of unigram-precision, unigram-recall, and a measure of fragmentation that is designed to directly capture how well-ordered the matched words in the machine translation are in relation to the reference. We evaluate METEOR by measuring the correlation between the metric scores and human judgments of translation quality. We compute the Pearson R correlation value between its scores and human quality assessments of the LDC TIDES 2003 Arabic-to-English and Chinese-to-English datasets. We perform segment-bysegment correlation, and show that METEOR gets an R correlation value of 0.347 on the Arabic data and 0.331 on the Chinese data. This is shown to be an improvement on using simply unigramprecision, unigram-recall and their harmonic F1 combination. We also perform experiments to show the relative contributions of the various mapping modules. 1
Osteoblast and chondrocyte interactions during coculture on scaffolds (2003)

Examining matrix and substrate-dependent effects on the formation of functional bone-cartilage interfaces.
The Fire at Cocoanut Grove (2014)

On November 28, 1942, a fire broke out at The Cocoanut Grove Nightclub, in Boston, Massachusetts. The fire claimed the lives of hundreds, and injured 170 patients who were treated at either Boston City Hospital or the Massachusetts General Hospital. With extraordinary leadership and scientific focus, this tragedy led to many important advances in burn management, including improvements in burn wound care, the first descriptions of inhalation injury, formulas to guide fluid resuscitation, and the initial studies of antimicrobial therapy with burns. This overview describes the treatment of the Cocoanut Gove victims, and how it transformed the management of burns forever.
Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants (2016)

First generation EGFR TKIs (gefitinib, erlotinib) provide significant clinical benefit for NSCLC cancer patients with oncogenic EGFR mutations. Ultimately, these patients' disease progresses, often driven by a second-site mutation in the EGFR kinase domain (T790M). Another liability of the first generation drugs is severe adverse events driven by inhibition of WT EGFR. As such, our goal was to develop a highly potent irreversible inhibitor with the largest selectivity ratio between the drug-resistant double mutants (L858R/T790M, Del/T790M) and WT EGFR. A unique approach to develop covalent inhibitors, optimization of reversible binding affinity, served as a cornerstone of this effort. PF-06459988 was discovered as a novel, third generation irreversible inhibitor, which demonstrates (i) high potency and specificity to the T790M-containing double mutant EGFRs, (ii) minimal intrinsic chemical reactivity of the electrophilic warhead, (iii) greatly reduced proteome reactivity relative to earlier irreversible EGFR inhibitors, and (iv) minimal activity against WT EGFR.
Statistical data preparation: management of missing values and outliers (2017)

Missing values and outliers are frequently encountered while collecting data. The presence of missing values reduces the data available to be analyzed, compromising the statistical power of the study, and eventually the reliability of its results. In addition, it causes a significant bias in the results and degrades the efficiency of the data. Outliers significantly affect the process of estimating statistics (<i>e.g.</i>, the average and standard deviation of a sample), resulting in overestimated or underestimated values. Therefore, the results of data analysis are considerably dependent on the ways in which the missing values and outliers are processed. In this regard, this review discusses the types of missing values, ways of identifying outliers, and dealing with the two.