gebhart/patrepeval huggingface dataset:
Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with pancreatic ductal adenocarcinoma (PDA). (2017)

4128 Background: PDA is a lethal and increasingly common malignancy and tissue samples for genomic characterization may be limited. As PDA has a high and consistent frequency of KRAS, p53 and CDKN2A mutations it serves as a robust indication to test the utility of ctDNA in accurately characterizing genomic alterations (GA). A prior study suggested significant differences between ctDNA and tissue base profiling but assays were not conducted on the same platform (PMID27833075). We undertook this study to see whether ctDNA could recapitulate the known genomic hallmarks of tumor based profiling. Methods: Hybrid-capture based genomic profiling of 62 genes (FoundationACT) was performed on ctDNA from 78 pts with advanced PDA with samples received in the course of clinical care. The fraction of ctDNA in the blood was estimated using the maximum somatic allele frequency (MSAF) for each sample. Frequencies of alterations in these common drivers were then compared to those seen in tumors of pts who underwent comprehensive genomic profiling (CGP) tissue testing performed on the same core platform, FoundationOne, and The Cancer Genome Atlas (TCGA). Results: Pt characteristics: Median age 65 (range, 47-88); Female (33) /Male (45). FoundationACT results show that 53/78 (68%) cases had MSAF &gt;0 (56%-78%%, 95% CI). ≥1 GA was reported in 81% of the cases with evidence of ctDNA in the blood. The most common GA detected by FoundationACT (based on cases with evidence of ctDNA in blood) vs FoundationOne were in KRAS (59% vs 89%, p&lt; 0.0001), TP53 (69% vs.74%, p=0.19), and CDKN2A (14% vs.45%). Other detected clinically relevant GA detected by FoundationACT included: BRCA1, ERBB2, NF1, PIK3CA. Conclusions: This study demonstrates significant differences between the established driver oncogenic alterations for PDA, as assessed by ct DNA and tissue based genomic profiling which are unlikely to be explained by differences in assay, but rather novel cancer biology. At present use of ctDNA genomic profiling in PDA should not routinely replace tissue based genomic characterization. [Table: see text]
Globus pallidus deep brain stimulation for generalized dystonia: Clinical and PET investigation (1999)

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) in a patient with severe idiopathic generalized dystonia resulted in immediate improvement of all aspects of dystonia. During joystick movement, GPi DBS reduced PET activation bilaterally in the primary motor, lateral premotor, supplementary motor, anterior cingulate, and prefrontal areas and ipsilaterally in the lentiform nucleus. Altering basal ganglia function with GPi DBS reverses the overactivity of certain motor cortical areas present in dystonia.
Investigation of One-dimensional Stress-Release Mechanism in Sand from Model Test (2013)

This paper explores stress release induced by unloading in dry sand. A series of model tests were carried out to measure stresses developed in testing sand during loading and those released during unloading for different boundary conditions. It was found that stress in the sand increased linearly with applied load. At the onset of unloading, almost no stress release was observed. Significant stress release took place when the shear stress in the sand induced by unloading exceeded the frictional resistance and caused movement of sand particles. The initiation and the magnitude of stress release depend on the stress condition prior to unloading, the decrease of external load, and also the frictional resistance in sand. A new conceptual stress-release model was next developed based on the model test results by considering the fundamental frictional behavior of granular materials.
In vitro and In vivo Optical Imaging Using Water-Dispersible, Noncytotoxic, Luminescent, Silica-Coated Quantum Rods (2010)

A facile method for synthesis of monodisperse, biocompatible, silica coated CdSe/CdS/ZnS quantum rods (QRs) and their use as probes for in vitro and in vivo optical bioimaging is presented. The silica coating procedure involves condensation-polymerization of the precursor tetraethylorthosilicate (TEOS) over QRs encapsulated within the reverse micellar core of Igepal CO-520/cyclohexane microemulsion. The silica-coated QRs have been characterized by TEM, DLS, and photoluminescence spectroscopy. The silica shell thickness has also been shown to be tuned by varying the ratio of TEOS and QRs. Confocal bioimaging of different cell lines (Panc 1 and RAW), treated with silica coated QRs, has shown a robust uptake of the nanoparticles, without the need of specific targeting molecules. To evaluate the cytotoxicity of the nanoparticles, MTS assay has been carried out over a period of 48 h. In vivo imaging of subcutaneously xenografted tumor-bearing mice, following direct intratumoral injection of the nanoparticles, have shown fluorescence from the tumor within 10 min of injection. This study suggests that these silica-coated QRs can be potentially used for long-term targeted imaging studies in vitro and in vivo.
Cortical GABA Interneurons in Neurovascular Coupling: Relays for Subcortical Vasoactive Pathways (2004)

The role of interneurons in neurovascular coupling was investigated by patch-clamp recordings in acute rat cortical slices, followed by single-cell reverse transcriptase-multiplex PCR (RT-mPCR) and confocal observation of biocytin-filled neurons, laminin-stained microvessels, and immunodetection of their afferents by vasoactive subcortical cholinergic (ACh) and serotonergic (5-HT) pathways. The evoked firing of single interneurons in whole-cell recordings was sufficient to either dilate or constrict neighboring microvessels. Identification of vasomotor interneurons by single-cell RT-mPCR revealed expression of vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) in interneurons inducing dilatation and somatostatin (SOM) in those eliciting contraction. Constrictions appeared spatially restricted, maximal at the level of neurite apposition, and were associated with contraction of surrounding smooth muscle cells, providing the first evidence for neural regulation of vascular sphincters. Direct perfusion of VIP and NO donor onto the slices dilated microvessels, whereas neuropeptide Y (NPY) and SOM induced vasoconstriction. RT-PCR analyses revealed expression of specific subtypes of neuropeptide receptors in smooth muscle cells from intracortical microvessels, compatible with the vasomotor responses they elicited. By triple and quadruple immunofluorescence, the identified vasomotor interneurons established contacts with local microvessels and received, albeit to a different extent depending on interneuron subtypes, somatic and dendritic afferents from ACh and 5-HT pathways. Our results demonstrate the ability of specific subsets of cortical GABA interneurons to transmute neuronal signals into vascular responses and further suggest that they could act as local integrators of neurovascular coupling for subcortical vasoactive pathways.
Simple accurate expressions for planar spiral inductances (1999)

We present several new simple and accurate expressions for the DC inductance of square, hexagonal, octagonal, and circular spiral inductors. We evaluate the accuracy of our expressions, as well as several previously published inductance expressions, in two ways: by comparison with three-dimensional field solver predictions and by comparison with our own measurements, and also previously published measurements. Our simple expression matches the field solver inductance values typically within around 3%, about an order of magnitude better than the previously published expressions, which have typical errors ground 20% (or more). Comparison with measured values gives similar results: our expressions (and, indeed, the field solver results) match within around 5%, compared to errors of around 20% for the previously published expressions. (We believe most of the additional errors in the comparison to published measured values is due to the variety of experimental conditions under which the inductance was measured.) Our simple expressions are accurate enough for design and optimization of inductors or of circuits incorporating inductors. Indeed, since inductor tolerance is typically on the order of several percent, "more accurate" expressions are not really needed in practice.
Experimental quasiparticle dynamics in a superconducting, imaging x-ray spectrometer (1997)

We present an experimental study of the time scales for various quasiparticle processes in a superconducting single photon spectrometer. Processes studied include quasiparticle recombination, diffusion, trapping, tunneling, and energy redistribution. Experiments were performed with a double junction, imaging x-ray detector whose charge output provides a measure of the photon energy. Time scales are extracted with a simple model and the values of several parameters, including the diffusion constant and recombination time, are found to differ from theoretical predictions. These results provide guidelines for performance analysis, device scaling, and future designs.
The inherited diseases of hemoglobin are an emerging global health burden (2010)

It is estimated that in excess of 300,000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries. As these countries go through an epidemiologic transition, with a reduction in childhood and infant mortality due to improved public health measures, babies who would have previously died of these diseases before they were recognized are now surviving to present for diagnosis and treatment. Hence, they are presenting an increasing global health burden. Because of their uneven distribution in high-frequency populations, reflecting their complex population genetics, the true magnitude of this burden is still unknown. In many poor countries there are virtually no facilities for the diagnosis and management of these conditions, and even in richer countries there are limited data about their frequency, clinical course, or mortality. Without this information, it will be impossible to persuade governments about the increasing importance of these diseases. The situation will only be improved by concerted action on the part of the hematology community of the richer countries together with input from the major international health organizations and funding agencies.
Packet reservation multiple access for local wireless communications (1989)

Simulation work is reported indicating that packet reservation multiple access (PRMA) allows a variety of information sources to share the same wireless access channel. Some of the sources, such as speech terminals, are classified as periodic and others, such as signaling, are classified as random. Packets from all sources contend for access to channel time slots. When a periodic information terminal succeeds in gaining access, it reserves subsequent time slots for uncontested transmission. Both computer simulations and a listening test reveal that PRMA achieves a promising combination of voice quality and bandwidth efficiency.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Structural Characterization and Biological Evaluation of Small Interfering RNAs Containing Cyclohexenyl Nucleosides (2007)

CeNA is an oligonucleotide where the (deoxy)ribose sugars have been replaced by cyclohexenyl moieties. We have determined the NMR structure of a CeNA:RNA duplex and have modeled this duplex in the crystal structure of a PIWI protein. An N puckering of the ribose nucleosides, a 2H3 conformation of the cyclohexenyl nucleosides, and an A-like helix conformation of the backbone, which deviates from the standard A-type helix by a larger twist and a smaller slide, are observed. The model of the CeNA:RNA duplex bound to the PIWI protein does not show major differences in the interaction of the guide CeNA with the protein when compared with dsRNA, suggesting that CeNA modified oligonucleotides might be useful as siRNAs. Incorporation of one or two CeNA units in the sense or antisense strands of dsRNA led to similar or enhanced activity compared to unmodified siRNAs. This was tested by targeting inhibition of expression of the MDR1 gene with accompanying changes in P-glycoprotein expression, drug transport, and drug resistance.
Progesterone Suppression of Estrogen-Stimulated Prolactin Secretion and Estrogen Receptor Levels in Rat Pituitary Cells* (1979)

The effects of progesterone, testosterone, corticosterone,and TRH on estrogen-induced PRL synthesis andcytoplasmic estrogen receptor levels were studied in a clonalstrain of rat pituitary tumor cells (GH3). PRL synthesis wasmeasured as the amount of hormone which accumulated in theculture medium (micrograms per mg cell protein/24 h), andreceptor levels were measured as specific [3H]estradiol bindingin the GH3 cells (picomoles per mg cell protein). 17Β-Estradiol (10-8M) stimulated PRL synthesis 2.1-fold, while progesterone (10-6 M) and corticosterone (10-6 M) bothdecreased PRL synthesis to about 0.9 times control levels. Testosterone(10-6 M) and TRH (3 x 10-7 M) increased PRL synthesis1.2- and 1.8-fold, respectively. The combined treatmentwith 17Β-estradiol plus progesterone increased PRL synthesis1.2-fold, while the simultaneous treatment with either 17Β8-estradiol and corticosterone or 17Β-estradiol and testosterone stimulated PRL synthesis to values not significantly different from those in cultures treated with 17/8-estradiol alone. In contrast, the stimulatory effects of 17Β-estradiol and TRH were additive. The antagonistic effects of progesterone on estrogen-induced PRL synthesis were not due to competition with 17Β-estradiol for binding to the estrogen receptor. Treatment with progesterone, but not with the other hormones, reduced estrogen receptor levels in the GH3 cells, but did not change the binding affinity between [3H]estradiol and its receptor. The inhibitory effect of progesterone was significant (P < 0.03) at 10-10 M and maximal at 10-6 M, decreasing specific [3H]estradiol binding from 0.283 ± 0.007 in control cultures to 0.055 ± 0.006 (mean ± SE) pmol/mg cell protein. The progesterone effect was detectable after 2 days and maximal after 4 days of treatment. These data suggest strongly that progesterone inhibits estrogen- induced PRL synthesis by decreasing the number of available receptor sites.
Coherence in Spontaneous Radiation Processes (1954)

By considering a radiating gas as a single quantum-mechanical system, energy levels corresponding to certain correlations between individual molecules are described. Spontaneous emission of radiation in a transition between two such levels leads to the emission of coherent radiation. The discussion is limited first to a gas of dimension small compared with a wavelength. Spontaneous radiation rates and natural line breadths are calculated. For a gas of large extent the effect of photon recoil momentum on coherence is calculated. The effect of a radiation pulse in exciting "super-radiant" states is discussed. The angular correlation between successive photons spontaneously emitted by a gas initially in thermal equilibrium is calculated.
An introduction to neural networks (1998)

From the Publisher:
An Introduction to Nueral Networks will be warmly welcomed by a wide readership seeking an authoritative treatment of this key subject without an intimidating level of mathematics in the presentation.
Does differential adhesion govern self‐assembly processes in histogenesis? Equilibrium configurations and the emergence of a hierarchy among populations of embryonic cells (1970)

Abstract The differential adhesion hypothesis attributes sorting‐out behavior of embryonic cells to differences in the strengths of their intercellular adhesions. It suggests that cells in mixed populations rearrange themselves to minimize their total adhesive free energy. The final configuration adopted is viewed as approaching a moststable or equilibrium configuration, with the less cohesive cell/population tending to envelop the more cohesive one. The hypothesis enables two predictions to be made. First, if the final configuration adopted by a mixed cell population indeed approximates an equilibrium configuration, the same final configuration should be approached irrespective of the starting configuration. Second, comparison of the equilibrium configurations for all possible pair‐combinations of a series of cell populations of different types should reveal a hierarchy of “preference” for the internal position, reflecting a hierarchy of cellular cohesiveness. These predictions have been tested and confirmed. First, any particular pair of tissues approaches the same final configuration, irrepective of whether the cells are initially randomly intermixed or tissue fragments are laterally joined. Second, the predicted hierarchy of preference for the internal position has been found, consistent with a hierarchy of cellular cohesiveness. An effort has been made to clarify confusions that have arisen concerning the differential adhesion hypothesis. It is particularly stressed that the hypothesis offers an explanation for cell population behavior in terms of relative strengths of cell adhesions and makes no proposals concernnig the chemistry of adhesion. However, the value of equilibrium configurations in guiding biochemical investigations of cell surface adhesives is pointed out, as is the relevance of the present observations to natural morphogenetic events.
Effects of Perinatal Exposure to Phthalate/Adipate Esters on Hypothalamic Gene Expression and Sexual Behavior in Rats (2006)

Our previous research has identified the granulin (grn) and p130 genes as sex steroid-regulated genes in the neonatal rat hypothalamus that might be involved in sexual differentiation of the brain. Since phthalate/adipate esters such as di-n-butyl phthalate (DBP), diisononyl phthalate (DINP), and di-2-ethylhexyl adipate (DEHA) are suspected to interfere with the endocrine system as environmental endocrine disruptors having estrogenic or antiandrogenic properties, these chemicals may affect sexual differentiation of the brain. The present study assessed the effects of perinatal exposure to DBP, DINP, and DEHA on grn and p130 mRNA expressions in the hypothalamus on postnatal day (PND) 7 and sexual behaviors after maturation in rats. Maternal rats were given a phytoestrogen-free diet containing different doses of DBP (20, 200, 2,000, and 10,000 ppm), DINP (40, 400, 4,000, and 20,000 ppm) and DEHA (480, 2,400, and 12,000 ppm) from gestational day 15 to the day of weaning (PND 21). DBP and DINP exposure during the perinatal period resulted in an increase in hypothalamic grn and p130 mRNA levels in females and males, respectively, but DEHA exposure decreased expression levels of grn in males and p130 in females, although the effects were not dose-dependent. After maturation, male rats that were exposed to several doses of DBP, DINP, and DEHA displayed decreased copulatory behavior. The lordosis quotient was decreased in females perinatally exposed to DBP, DINP, and DEHA at all the doses used. On the other hand, serum levels of LH and FSH in both sexes and the estrous cycles in females were not affected by the treatments. These results suggest that inappropriate expression of grn and/or p130 genes in the brains of male and female neonatal rats by perinatal exposure to these chemicals may exert permanent effects on the hypothalamus, thereby decreasing sexual behavior after maturation.
Isolation and characterisation of an anticryptococcal protein in human cerebrospinal fluid (2001)

An earlier study reported that human cerebrospinal fluid (CSF) has fungistatic activity for Cryptococcus neoformans. The present study reports that molecular sieve fractionation of concentrated CSF yielded three protein peaks, one of which (p2) had anticryptococcal activity. On a DEAE-Sephacel anion-exchange column the active molecular sieve peak (p2) gave two peaks that contained anticryptococcal activity. The first (DEAE-1) eluted with 0.1 M NaCl and the second (DEAE-2) eluted with 0.2 M NaCl in buffer. Fungistatic activity of DEAE-1 was reversed by FeCl3. Moreover, FeCl3 reversed inhibition of C. neoformans growth by CSF. In contrast, activity of DEAE-2 was not reversed by FeCl3, indicating that inhibition was produced by an iron-independent mechanism. Immunoblot assays showed that transferrin was present in DEAE-1 but not in DEAE-2, whereas albumin was present in DEAE-2 but not in DEAE-1. On NuPAGE, DEAE-1 protein migrated as a single band corresponding to transferrin and DEAE-2 protein gave a single band corresponding to albumin. In control experiments, human serum albumin subjected to the same isolation protocol acquired anticryptococcal activity similar to that of DEAE-2. Therefore, CSF albumin (DEAE-2) activity was associated with the isolation protocol. These data indicate that transferrin, present in or isolated from CSF, sequesters trace amounts of ferric iron, inhibits growth of C. neoformans and acts as an innate defence mechanism.
Defect-Tolerant Design and Optimization of a Digital Microfluidic Biochip for Protein Crystallization (2010)

Protein crystallization is a commonly used technique for protein analysis and subsequent drug design. It predicts the 3-D arrangement of the constituent amino acids, which in turn indicates the specific biological function of a protein. Protein crystallization experiments are typically carried out in well-plates in the laboratory. As a result, these experiments are slow, expensive, and error-prone due to the need for repeated human intervention. Recently, droplet-based ¿digital¿ microfluidics have been used for executing protein assays on a chip. Protein samples in the form of nanoliter-volume droplets are manipulated using the principle of electrowetting-on-dielectric. We present the design of a multi-well-plate microfluidic biochip for protein crystallization; this biochip can transfer protein samples, prepare candidate solutions, and carry out crystallization automatically. To reduce the manufacturing cost of such devices, we present an efficient algorithm to generate a pin-assignment plan for the proposed design. The resulting biochip enables control of a large number of on-chip electrodes using only a small number of pins. Based on the pin-constrained chip design, we present an efficient shuttle-passenger-like droplet manipulation method and test procedure to achieve high-throughput and defect-tolerant well loading.
Introduction Humans, History, Folly, and Fortune (2008)

At the risk of stating the obvious, I believe in the centrality of human beings in human history. It is human beings who create systems and institutions, be they economic or political or legal or social or whatever, though of course these are often shaped in response to circumstances created by Nature or some other nonhuman agency. Sometimes these human creations seem to take on a life of their own and the human factor ends up pushed into the background. What I would like to do in this book is to restore pride of place to that human factor and draw attention to how human behaviour — with all its erraticisms — has helped shape history.KeywordsHuman FactorHuman CreationRisk GambleFaulty LinkHuman PathThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.