gebhart/patrepeval huggingface dataset:
Editorial: Curbing our Enthusiasm for Fecal Transplantation in Ulcerative Colitis (2013)

Given the known dysbiosis of gut microflora in inflammatory bowel disease, there has been great enthusiasm about the potential for fecal microbiota transplantation (FMT) as a treatment. This editorial accompanies a prospective series of five patients with ulcerative colitis who underwent FMT, but did not achieve remission. I discuss the important observations from this study and point out that the lack of clinical efficacy and observed side effects warrant caution in the ongoing pursuit of this treatment option.
Server selection using dynamic path characterization in wide-area networks (2002)

Replication is a commonly proposed solution to problems of scale associated with distributed services. However, when a service is replicated, each client must be assigned a server. Prior work has generally assumed the assignment to be static. In contrast, we propose a dynamic server selection, and show that it enables application-level congestion avoidance. Using tools to measure the available bandwidth and round trip latency (RTT), we demonstrate the dynamic server selection and compare it to previous static approaches. We show that because of the variability of paths in the Internet, dynamic server selection consistently outperforms static policies, reducing response times by as much as 50%. However, we also must adopt a systems perspective and consider the impact of the measurement method on the network. Therefore, we look at alternative low-cost approximations and find that the careful measurements provided by our tools can be closely approximated by much lighter-weight measurements. We propose a protocol using this method which is limited to at most a 1% increase in network traffic but which often costs much less in practice.
Intraspecies Diversity of Cryptococcus laurentii as Revealed by Sequences of Internal Transcribed Spacer Regions and 28S rRNA Gene and Taxonomic Position of C. laurentii Clinical Isolates (2000)

The intraspecies diversity of an opportunistic yeast pathogen, Cryptococcus laurentii, was revealed by analysis of the sequences of the internal transcribed spacer regions and the 28S rRNA gene. Ten strains of C. laurentii were grouped into two major phylogenetic groups and were further divided into at least seven species. Four of the strains isolated from patients did not represent a single species but showed heterogeneity. These results suggest that C. laurentii is a genetically heterogeneous species, and this must be taken into consideration when identifying C. laurentii clinical isolates.
4-Oxo-1,4-dihydropyridines as Selective CB2Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series (2010)

Growing evidence shows that CB(2) receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective CB(2) agonists, we describe here the medicinal chemistry approach leading to the development of CB(2) receptor inverse agonists with a 4-oxo-1,4-dihydropyridine scaffold. The compounds reported here show high affinity and potency at the CB(2) receptor while showing only modest affinity for the centrally expressed CB(1) cannabinoid receptor. Further, we found that the functionality of this series is controlled by its C-6 substituent because agonists bear a methyl or a tert-butyl group and inverse agonists, a phenyl or 4-chlorophenyl group, respectively. Finally, in silico studies suggest that the C-6 substituent could modulate the conformation of W6.48 known to be critical in GPCR activation.
Photonic A/D conversion using low-temperature-grown gaas msm switches integrated with Si-CMOS (2003)

By linking the unique capabilities of photonic devices with the signal processing power of electronics, photonically sampled analog-to-digital (A/D) conversion systems have demonstrated the potential for superior performance over all-electrical A/D conversion systems. We adopt a photonic A/D conversion scheme using low-temperature (LT)-grown GaAs metal-semiconductor-metal (MSM) photoconductive switches integrated with Si-CMOS A/D converters. The large bandwidth of the LT GaAs switches and the low timing jitter and short width of mode-locked laser pulses are combined to accurately sample input frequencies up to several tens of gigahertz. CMOS A/D converters perform back-end digitization, and time-interleaving is used to increase the total sampling rate of the system. We outline the development of this system, from optimization of the LT GaAs material, speed and responsivity measurements of the switches, bandwidth and linearity characterization of the first-stage optoelectronic sample-and-hold, to integration of the switches with CMOS chips. As a final proof-of-principle demonstration, a two-channel system was fabricated with LT GaAs MSM switches flip-chip bonded to CMOS A/D converters. When operated at an aggregate sampling rate of 160 megasamples/s, the prototype system exhibits ∼3.5 effective number of bits (ENOB) of resolution for input signals up to 40 GHz.
Identification and Validation of Commonly Overexpressed Genes in Solid Tumors by Comparison of Microarray Data (2004)

Cancers originating from epithelial cells are the most common malignancies. No common expression profile of solid tumors compared to normal tissues has been described so far. Therefore we were interested if genes differentially expressed in the majority of carcinomas could be identified using bioinformatic methods. Complete data sets were downloaded for carcinomas of the prostate, breast, lung, ovary, colon, pancreas, stomach, bladder, liver, and kidney, and were subjected to an expression analysis using SAM. In each experiment, a gene was scored as differentially expressed if the q value was below 25%. Probe identifiers were unified by comparing the respective probe sequences to the Unigene build 155 using BlastN. To obtain differentially expressed genes within the set of analyzed carcinomas, the number of experiments in which differential expression was observed was counted. Differential expression was assigned to genes if they were differentially expressed in at least eight experiments of tumors from different origin. The identified candidate genes ADRM1, EBNA1BP2, FDPS, FOXM1, H2AFX, HDAC3, IRAK1, and YY1 were subjected to further validation. Using this comparative approach, 100 genes were identified as upregulated and 21 genes as downregulated in the carcinomas.
Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs. (1990)

The effect of myocardial ischemia, induced by long-term exercise, on regional myocardial function and coronary collateral development was examined in pigs after gradual occlusion of the left circumflex coronary artery (LCx) with an ameroid occluder. Thirty days after surgery, regional myocardial function and blood flow were assessed during exercise in 22 pigs separated into exercise (n = 12) and sedentary groups (n = 10). The exercise group trained on a treadmill for 25 +/- 1 days, 30-50 min/day, at heart rates of 210-220 beats/min. After 5 weeks, another exercise test was performed. In the exercise group, after training, we observed an improvement in systolic wall thickening, expressed as a percentage of rest, in the collateral-dependent LCx region from 64 +/- 8% to 87 +/- 6% (p less than 0.01) at moderate exercise levels (220 beats/min) and from 45 +/- 7% to 73 +/- 7% (p less than 0.01) at severe exercise levels (265 beats/min). Transmural myocardial blood flow in the LCx region expressed as a ratio of flow in the nonoccluded region of the left ventricle also increased significantly (p less than 0.01) during severe exercise after 5 weeks. The sedentary group showed an improvement in systolic wall thickening in the LCx region during moderate exercise compared with the initial exercise test (p less than 0.05) but no significant change in systolic wall thickening or myocardial blood flow ratios during severe exercise after 5 weeks. We conclude that long-term exercise after gradual LCx coronary artery occlusion in pigs improves myocardial function and coronary collateral reserve in collateral-dependent myocardium during exercise.
Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells (2015)

The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.
In Vitro Selection of Protein and Peptide Libraries Using mRNA Display (2009)

In vitro genetic approaches are powerful solutions to the protein design problem. mRNA display is an in vitro selection technique enabling the design of peptide and protein ligands ranging from one to over 100 amino acids. Libraries containing more than 10 trillion unique sequences can be synthesized and sieved with exquisite control over binding stringency and specificity.
Cold‐induced ependymin expression in zebrafish and carp brain: implications for cold acclimation (1999)

Cold acclimation has been suggested to be mediated by alternations in the gene expression pattern in the cold-adapted fish. To investigate the mechanism of cold acclimation in fish brain at the molecular level, relevant subsets of differentially expressed genes of interest were identified and cloned by the PCR-based subtraction suppression hybridization. Characterization of the selected cold-induced cDNA clones revealed one encoding ependymin. This gene was shown to be brain-specific. The expression of ependymin was induced by a temperature shift from 25 degrees C to 6 degrees C in Cyprinus carpio or 12 degrees C in Danio rerio. Activation of ependymin was detected 2 h after cold exposure and peaked at more than 10-fold at 12 h. This peak level remains unchanged until the temperature returns to 25 degrees C. Although the amount of soluble ependymin protein in brain was not changed by cold treatment, its level in the fibrous insoluble polymers increased 2-fold after exposure to low temperature. These findings indicate that the increase in ependymin expression is an early event that may play an important role in the cold acclimation of fish.
Circulating Vascular Cell Adhesion Molecule-1 Correlates With the Extent of Human Atherosclerosis in Contrast to Circulating Intercellular Adhesion Molecule-1, E-Selectin, P-Selectin, and Thrombomodulin (1997)

Secondary prevention of atherosclerosis, especially before the onset of symptoms, appears desirable and could be possible with a serum marker detecting atherosclerosis. Circulating, shedded forms of adhesion molecules may serve as such because their expression is upregulated in atherosclerotic plaques. In 52 patients with peripheral arterial vascular disease (Fontaine class IIa, 7 patients; class IIb, 29 patients; and class III, 16 patients), the extent of atherosclerosis was evaluated on the basis of angiograms of a large portion of the arterial system. The area diseased by atherosclerosis was determined by the percentage of vessel wall irregularities of the following calculated segments: aorta (distal from the kidney arteries), common iliac artery, external iliac artery, common femoral artery, lateral circumflex femoral artery, and popliteal artery. The maximal surface area that could exhibit atherosclerotic changes was 250 cm2. The serum concentration of circulating vascular cell adhesion molecule-1 (VCAM-1) correlated with the extent of atherosclerosis (r = .8, P < .001). In contrast, circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin (as markers for endothelial cell damage) did not correlate with the extent of atherosclerosis. Furthermore, circulating VCAM-1 could be used to indicate stages of atherosclerosis with a high degree of statistical significance. The potential bias of factors such as age, diabetes mellitus, hypercholesterolemia, arterial hypertension, renal failure, and history of myocardial infarction on the correlation of circulating VCAM-1 with the extent of atherosclerosis could be excluded by multivariate analysis. These findings suggest an important role of VCAM-1 in atherosclerosis and may serve as the basis for further evaluation of circulating VCAM-1 as a potential serum marker for atherosclerosis.
Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism (2000)

A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has lipolytic and antilipogenic activity similar to that of the intact hormone. Here we report its effect on lipid metabolism in rodent models of obesity and in human adipose tissue to assess its potential as a pharmacological agent for the treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight gain in AOD-9401-treated animals was significantly lower than that of saline-treated controls. Food consumption did not differ between the two groups. Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced lipogenic activity and increased lipolytic activity in this tissue. Increased catabolism was also reflected in an acute increase in energy expenditure and glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD-9401 increased in vitro lipolytic activity and decreased lipogenic activity in isolated adipose tissue from obese rodents and humans. Together, these findings indicate that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals. The marked lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest that this small synthetic hGH peptide has potential in the treatment of human obesity.
Cantidad y calidad antioxidante de alimentos de origen vegetal consumidos en Cuba (2000)

En estudios epidemiologicos se ha encontrado que las frutas y vegetales de la dieta pueden ser protectores contra algunas enfermedades cronicas. La cantidad y calidad antioxidante de 8 frutas, 15 vegetales, 3 leguminosas, 4 viandas (raices tuberculos y platano), varias bebidas y leche han sido medidas a traves del contenido de fenoles totales, el estatus antioxidante total (TAS) y la inhibicion a la peroxidacion lipidica en homogenato de cerebro (IC50). A traves de los indices elaborados TAS x Fenoles totales (Fenoles) y Fenoles / IC50 se encontro que los alimentos, en base al peso humedo, que reportaron mejores caracteristicas antioxidantes fueron entre las frutas: la guayaba, el mamey, el platano fruta y la naranja; para los vegetales: la remolacha, el ajo, el berro, el aguacate y la cebolla; dentro de las legumbres: los frijoles colorados y negros; entre las viandas: el platano maduro y verde y para las bebidas: el te y el guarapo (jugo de cana de azucar). Ligeras variaciones fueron encontradas en el orden de las propiedades antioxidantes con relacion al peso seco
Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix (2008)

Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.
Context-Sensitive Keyword Search and Ranking for XML. (2005)

Traditionally, keyword-search-based information retrieval (IR) has focused on “flat ” documents, which either do not have any inherent structure or have structure that is not exploited by the IR system. Thus, even if users wanted to search over only specific
Inhibitor repurposing reveals ALK, LTK, FGFR, RET and TRK kinases as the targets of AZD1480 (2017)

Many tyrosine kinase inhibitors (TKIs) have failed to reach human use due to insufficient activity in clinical trials. However, the failed TKIs may still benefit patients if their other kinase targets are identified by providing treatment focused on syndromes driven by these kinases. Here, we searched for novel targets of AZD1480, an inhibitor of JAK2 kinase that recently failed phase two cancer clinical trials due to a lack of activity. Twenty seven human receptor tyrosine kinases (RTKs) and 153 of their disease-associated mutants were in-cell profiled for activity in the presence of AZD1480 using a newly developed RTK plasmid library. We demonstrate that AZD1480 inhibits ALK, LTK, FGFR1-3, RET and TRKA-C kinases and uncover a physical basis of this specificity. The RTK activity profiling described here facilitates inhibitor repurposing by enabling rapid and efficient identification of novel TKI targets in cells.
Expression of the FLT3 gene in human leukemia-lymphoma cell lines. (1994)

The FLT3 gene encodes a protein that appears to function as a receptor for a hematopoietic growth factor; together with the KIT and FMS receptors, FLT3 belongs to the superfamily of receptors with tyrosine kinase activity. We examined the expression of FLT3 mRNA in 36 human leukemia-lymphoma cell lines using Northern blot analysis. FLT3 transcripts were found in seven of seven pre B-ALL cell lines (derived from cases with pre B-acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast crisis), and in one of six B-cell lines (namely in a cell line established from a hairy cell leukemia). FLT3 message was not detected in five T-cell, five myeloid, four monocytic, four erythroid and five megakaryocytic cell lines. Two major mRNA species were expressed differentially by positive cell lines. KIT mRNA expression was also investigated in the same panel of cell lines, but was found only in cell lines with erythroid and megakaryocytic features (and not in any of the FLT3-positive cell lines). The pattern of expression of FLT3 contrasts with the transcription of FMS and KIT and suggests that the FLT3 product may play a role primary in immature lymphoid cells.
Cavitation bubble-driven cell and particle behavior in an ultrasound standing wave (2005)

The behavior of human erythrocytes and 1-microm-diameter fluorescent latex beads in the presence of Optison contrast agent in a single half-wavelength (lambda/2) ultrasound standing wave (USSW) resonator has been studied. The particle movements were observed with an epi-fluorescent microscope and the velocity of the particles and cells was measured by particle image velocimetry (PIV). Acoustic emissions were monitored with a microphone and a spectrum analyzer. Optison contrast agent disintegrated immediately on exposure to ultrasound of 0.98-MPa acoustic pressure amplitude or higher in a chamber driven at its resonance frequency of 1.56 MHz. A discrete cloud of active microbubbles, detected at the pressure node plane, disappeared gradually and was completely lost within 15 s. The microscopy showed three-dimensional regions of circulation of both 1-microm tracer particles and erythrocytes in planes perpendicular to the pressure node plane. A numerical simulation showed that, for parameters that conform to the experimental conditions, a bubble of a subresonance size moves towards and translates about a pressure node plane. This result is in agreement with the experimental observation that the particle and cell circulation is induced by the presence and/or translational motion of microbubbles at the pressure node plane.
Multimedia traffic management principles for guaranteed ATM network performance (1990)

A framework is presented for the specification of performance requirements, and several high-level design principles for performance-driven ATM traffic controls based on resource reservation are developed. Simulation results illustrate that to guarantee performance levels, bursty traffic should be statistically multiplexed only if connection peak rates are low relative to the network link speed or burst durations are short. A pragmatic traffic management approach that favors simplicity and robustness in the traffic control design rather than optimizing bandwidth efficiency is stressed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Generation of influenza A virus from cloned cDNAs — historical perspective and outlook for the new millenium (2002)

Influenza virus reverse genetics has reached a level of sophistication where one can confidently generate virus entirely from cloned DNAs. The new systems makes it feasible to study the molecular mechanisms of virus replication and pathogenicity, as well as to generate attenuated live virus vaccines, gene delivery vehicles, and possibly other RNA viruses from cloned cDNAs. During the next decade, one can anticipate the translation of influenza virus reverse genetics into biomedically relevant advances.
Flagellin Is the Major Proinflammatory Determinant of Enteropathogenic Salmonella (2003)

Abstract The gastroenteritis-causing pathogen Salmonella typhimurium induces profound transcriptional changes in intestinal epithelia resulting in the recruitment of neutrophils whose presence is the histopathologic hallmark of salmonellosis. Here we used cDNA microarray expression profiling to define the molecular determinants that mediate such changes in model intestinal epithelia. Enteropathogenic Salmonella induced a classical proinflammatory gene expression program similar to that activated by the canonical proinflammatory agonist TNF-α. Nonproinflammatory bacteria, both commensals (Escherichia coli) and systemic pathogens (S. typhi), did not activate this expression profile. While S. typhimurium strains lacking the SPI-1-encoded type III system were fully proinflammatory, strains lacking the genes for the flagellar structural component flagellin were nearly devoid of proinflammatory signaling. Lastly, the epithelial proinflammatory response could be largely recapitulated by basolateral addition of purified flagellin. Thus, S. typhimurium flagellin is the major molecular trigger by which this pathogen activates gut epithelial proinflammatory gene expression.