gebhart/patrepeval huggingface dataset:
Hemodilution, central blood volume, and renal responses after an isotonic saline infusion in humans (1997)

To test the hypothesis that hemodilution is a mediator of the renal responses to an isotonic saline infusion in the supine position, eight males underwent 1) intravenous infusion of 1.5 liter of saline over 21 min (Saline), 2) infusion of 1.5 liter of saline in combination with lower body negative pressure for 3 h (LBNP+Saline) to maintain central blood volume unchanged, and 3) a control study without infusion or LBNP. During the Saline series, central venous pressure (CVP) and left atrial diameter (LAD) increased by 4.4 +/- 0.6 mmHg and 2.6 +/- 0.4 mm (P < 0.05), respectively, whereafter they declined toward preinfusion levels. During LBNP+Saline, CVP and LAD were unchanged. Plasma colloid osmotic pressure remained unchanged during control and showed identical decreases by 5 mmHg (P < 0.05) in the Saline and LBNP+Saline series. During the 3rd h of LBNP, renal sodium excretion (U(Na)V) peaked at 296 +/- 55 micromol/min vs. a higher value of 383 +/- 54 micromol/min (P < 0.05) during Saline. The increase in U(Na)V above that of control during the 3rd h of LBNP+Saline constituted 48% of that during Saline. Plasma renin activity and plasma aldosterone concentration showed similar patterns of decrease after saline infusion irrespective of LBNP, whereas plasma norepinephrine was elevated late in the LBNP period compared with during Saline and control (P < 0.05). It is concluded that the maintenance of a constant CVP and LAD reduces the natriuresis of acute saline loading by about one-half. Thus hemodilution in conjunction with suppression of renin and aldosterone release (independent of change in CVP and LAD) might account for the remaining natriuresis of infusion.
Selective and tunable gradient device for cell culture and chemotaxis study (2009)

This article describes a microfluidic device for cell culture and chemotaxis studies under various temporal and spatial concentration gradients of the medium or chemoattractant. Vertical membranes formed using in situ fabrication are employed to avoid fluid flow inside the cell observation chamber. Thus, the medium and chemoattractants are primarily provided by diffusion, maintaining cell-cell communication via secreted factors. Neutrophils were used to demonstrate the capability of the device for chemotaxis research. Experiments exhibited successful migration up a concentration gradient of interleukin 8.
Efficacy and Toxicity Related to Treatment of Hepatocellular Carcinoma with 90Y-SIR Spheres: Radiobiologic Considerations (2010)

Radioactive <sup>90</sup>Y-selective internal radiation (SIR) sphere therapy is increasingly used for the treatment of nonresectable hepatocellular carcinoma (HCC). However, the maximum delivered dose is limited by severe injury to the nontarget tissue, including liver parenchyma. Our study aimed to implement radiobiologic models for both tumor control probability (TCP) and normal-tissue complication probability (NTCP) to describe more effectively local response and the liver toxicity rate, respectively. <b>Methods:</b> Patients with documented HCC, adequate bone marrow parameters, and regular hepatic and pulmonary function were eligible for the study. Patients who had pulmonary shunt greater than 20% of <sup>99m</sup>Tc-labeled macroaggregated albumin or any uncorrectable delivery to the gastrointestinal tract, reverse blood flow out of the liver, or complete portal vein thrombosis were excluded. Patients received a planned activity of the <sup>90</sup>Y-SIR spheres, determined using the empiric body surface area method. The dose distribution was determined using posttreatment (3-dimensional) activity distribution and Monte Carlo dose voxel kernel calculations, and the mean doses to healthy liver and tumor were calculated for each patient. Response was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) and recommendations of the European Association for the Study of the Liver (EASL). Criteria were used to assess possible liver toxicities. The parameters of TCP and NTCP models were established by direct maximization of the likelihood. <b>Results:</b> Seventy-three patients were treated. With an average dose of 110 Gy to the tumor, complete or partial response was observed in 74% and 55% of patients according to the EASL guideline and RECIST, respectively, and the predicted TCPs were 73% and 55%, respectively. With a median liver dose of 36 Gy (range, 6–78 Gy), the ≥grade 2 (G2), ≥grade 3 (G3), and ≥grade 4 (G4) liver toxicities were observed in 32% (23/73), 21% (15/73), and 11% (8/73) of patients, respectively. The parameters describing the ≥G2 liver toxicity data using the NTCP model were a tolerance dose of the whole organ leading to a 50% complication probability of 52 Gy (95% confidence interval, 44–61 Gy) and a slope of NTCP versus dose of 0.28 (95% confidence interval, 0.18–0.60), assuming <i>n</i> = 1. <b>Conclusion:</b> The radiobiologic approach, based on patient-specific dosimetry, could improve the <sup>90</sup>Y-microsphere therapeutic approach of HCC, maintaining an acceptable liver toxicity.
Interdependence of Cell Growth and Gene Expression: Origins and Consequences (2010)

In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated.
Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms (2009)

Abstract Aims Chronic pudendal nerve stimulation (CPNS) is a logical alternative particularly in those who fail sacral stimulation. We evaluated symptoms, complications, and satisfaction after CPNS. Methods We retrospectively reviewed patients having a tined lead placed at the pudendal nerve via the ischial‐rectal approach. Demographics, history, complications, and pre‐implant voiding diary data were collected. In those responding to CPNS, post‐implant symptom changes were measured with the Interstitial Cystitis Symptom and Problem indices (ICSI‐PI) and voiding diaries at 3, 6, and 12 months, and a mailed survey. Results The majority of 84 patients (78.6% female; age 51.8 ± 16.9 years) had interstitial cystitis/painful bladder syndrome, or overactive bladder. Pudendal response (≥ 50% improvement) occurred in 60/84 (71.4%), however 5 of these chose sacral neuromodulation. Almost all (93.2%) who had previously failed sacral neuromodulation responded to pudendal stimulation. Outcomes were evaluated in 55 continuing on CPNS (median follow up 24.1 months). Seven complications requiring 5 revisions, and 4 other re‐operations occurred. Five were explanted. Over time, significant improvements in frequency ( P &lt; 0.0001), voided volume ( P &lt; 0.0001), incontinence ( P &lt; 0.0001), and urgency ( P = 0.0019) occurred. ICSI‐PI scores significantly improved over 12 months ( P &lt; 0.0001). Survey responses indicated that most still had a device (35/40; 87.5%) continuously in use (24/29; 82.8%), and overall bladder, pelvic pain, incontinence, urgency, and frequency symptoms had improved. Conclusions CPNS is a reasonable alternative in complex patients refractory to other therapies including sacral neuromodulation. Continued research is needed to fully assess long‐term outcomes and identify predictors of success. Neurourol. Urodynam. 29:1267–1271, 2010. © 2009 Wiley‐Liss, Inc.
Levetiracetam: a review of its use in epilepsy. (2011)

Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group, and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracetam and placebo treatment groups, with most events being mild to moderate in severity. Levetiracetam is not associated with cognitive impairment or drug-induced weight gain, but has been associated with behavioural adverse effects in some patients.
The Human Lumbar Endplate (1996)

The authors identified three matrix turnover phases, related to age and grade of degeneration. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of Type II collagen. Phase II (aging and maturation) is distinguished by a drop in synthetic activity and a reduction in denaturation of Type II collagen. Phase III (degenerative) is illustrated by an increase in Type II collagen denaturation and Type I procollagen synthesis, both related to grade of tissue degeneration.
Ty1 in vitro integration: effects of mutations in cis and in trans. (1994)

Mutations within the TYB gene of Ty1 encoding integrase (IN) as well as alterations in its substrate, a linear DNA molecule, were examined for their effects on in vitro IN activity, using a recently developed physical assay. Five different codon-insertion mutations, two frameshift mutations, and one missense mutation, previously identified as transposition-deficient mutations, were tested. Virus-like particles, the source of IN, from two different protease mutants and a reverse transcriptase mutant exhibited near-normal to normal IN activity. Two frameshift mutations mapping within the phylogenetically variable C-terminal domain of IN resulted in significant in vitro IN activity. In contrast, three mutations within the amino-terminal conserved domain of IN completely abolished IN activity. When the substrate termini were mutated, we found that substrates with as few as 4 bp of Ty1 termini were capable of efficiently generating integration products. Surprisingly, certain substrates that lacked obvious similarity to Ty1 termini were also readily integrated into both linear and circular targets, whereas others were not used as substrates at all. Termini rich in adenosine residues were among the more active substrates; however, certain substrates lacking terminal adenosine residues can form small quantities of integration products, including complete integration reactions.
Progression of Colorectal Cancer Is Associated with Multiple Tumor Suppressor Gene Defects but Inhibition of Tumorigenicity Is Accomplished by Correction of Any Single Defect via Chromosome Transfer (1992)

Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.
Murine Plasmacytoid Pre-Dendritic Cells Generated from Flt3 Ligand-Supplemented Bone Marrow Cultures Are Immature APCs (2002)

The putative counterparts of human plasmacytoid pre-dendritic cells (pDCs) have been described in vivo in mouse models and very recently in an in vitro culture system. In this study, we report that large numbers of bone marrow-derived murine CD11c(+)B220(+) pDCs can be generated with Flt3 ligand (FL) as the sole exogenous differentiation/growth factor and that pDC generation is regulated in vivo by FL because FL-deficient mice showed a major reduction in splenic pDC numbers. We extensively analyzed bone marrow-derived CD11c(+)B220(+) pDCs and described their immature APC phenotype based on MHC class II, activation markers, and chemokine receptor level of expression. CD11c(+)B220(+) pDCs showed a nonoverlapping Toll-like receptor pattern of expression distinct from that of classical CD11c(+)B220(-) dendritic cells and were poor T cell stimulators. Stimulation of CD11c(+)B220(+) pDCs with oligodeoxynucleotides containing certain CpG motifs plus CD40 ligand plus GM-CSF led to increased MHC class II, CD80, CD86, and CD8alpha expression levels, to a switch in chemokine receptor expression that affected their migration, to IFN-alpha and IL-12 secretion, and to the acquisition of priming capacities for both CD4(+) and CD8(+) OVA-specific TCR-transgenic naive T cells. Thus, the in vitro generation of murine pDCs may serve as a useful tool to further investigate pDC biology as well as the potential role of these cells in viral immunity and other settings.
Postvaccine Genetic Structure ofStreptococcus pneumoniaeSerotype 19A from Children in the United States (2005)

Serotype 19A is, at present, the most important cause of IPD by replacement serotypes, and it is increasingly drug resistant. CC199 is the predominant CC among type 19A serotypes in children <5 years old. Our data suggest that some of the increase in rates of infection with serotype 19A may be due to serotype switching within certain vaccine type strains.
Unroofing Sequence and Foreland Basin Development of the Central Alaska Range: Implications from the Nenana Gravel - Abstract (1999)

Facies architecture, petrofacies, and 40 Ar/ 39 Ar analyses of sediments from key measured sections in the Nenana Gravel reveal a history of uplift and erosion of the central Alaska Range during the first half of the late Cenozoic orogeny. Nenana Gravel deposits within the Cantwell trough are very coarse, contain unconformities marked by thin coal beds, and were deposited within drainages that either were tectonically disrupted and became stagnant or became antecedent to subsequent structures. These sections were deposited in a wedge-top depozone on top of the deforming orogenic wedge. Sections just north of the Mt. Healy Anticline (our term for the regional anticlinal upland of schist forming the northern margin of the Cantwell trough) characterize deposition in a foredeep to wedge-top transitional depozone. Gravel aggradation began here shortly after deposition of the Grubstake tephra, recently re-dated at 6.4 ± 0.6 Ma, in the form of a distal to proximal transitional alluvial braidplain dominated by sandy and gravelly stream-flow deposits. This timing is in close agreement with estimates on the onset of rapid uplift and denudation of the McKinley pluton provided independently by fission track thermochronology (Fitzgerald et al., 1995). Two coarsening upward megasequences are next. Each records a transition from stream-flow to sheetflood deposits. We interpret this facies transition as indicative of increasing sedimentation rate, probably due to the tectonically induced stripping of unconsolidated Nenana Gravel and Usibelli Group deposits upstream. Statistical analysis of a pebble count dataset collected by Clyde Wahrhaftig nearly 50 years ago reveals successive erosion of rocks from three south to north source areas. They are 1), rocks south of the Denali fault (DF) and the upper Cantwell Formation, 2), the lower Cantwell Formation and terranes within the Cantwell trough uplifted along steep re-activated thrust faults, and 3), Nenana Gravel and Usibelli Group deposits in the Cantwell trough and schist of the Mt. Healy Anticline. Pebble counts from distal sections also indicate that growing schist uplands emergent in the mid to late Nenana Gravel time diverted braidplain deposits from the south and were themselves a local source of alluvial deposits. We take this as evidence for the basinward progression of the underlying orogenic wedge. 40 Ar/ 39 Ar analysis of potassium feldspar grains from sands and granitic clasts collected from the Suntrana Creek section independently supports this model by indicating that granite plutons south of the DF were eroded early in the orogeny and that plutons north of the DF were not eroded until during stage 2.
Learning to detect violent videos using convolutional long short-term memory (2017)

Developing a technique for the automatic analysis of surveillance videos in order to identify the presence of violence is of broad interest. In this work, we propose a deep neural network for the purpose of recognizing violent videos. A convolutional neural network is used to extract frame level features from a video. The frame level features are then aggregated using a variant of the long short term memory that uses convolutional gates. The convolutional neural network along with the convolutional long short term memory is capable of capturing localized spatio-temporal features which enables the analysis of local motion taking place in the video. We also propose to use adjacent frame differences as the input to the model thereby forcing it to encode the changes occurring in the video. The performance of the proposed feature extraction pipeline is evaluated on three standard benchmark datasets in terms of recognition accuracy. Comparison of the results obtained with the state of the art techniques revealed the promising capability of the proposed method in recognizing violent videos.
Retinoid-Mediated Signaling Pathways in CD38 Antigen Expression in Myeloid Leukemia Cells (1999)

The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellular calcium from ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain leukemias. Presently, there is little information available on the factors that regulate the expression of CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of CD38 antigen by retinoids (vitamin A and related compounds). At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induced expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor.