gebhart/patrepeval huggingface dataset:
Blood supply of subcutaneous tissue in the leg and its clinical application (1995)

The vascular anatomy of the subcutaneous or adipose layer of the leg is described. The major arteries of the distal thigh and leg were injected with either a colored latex or an India ink and gelatin mixture to demonstrate the principal sources of blood supply to the skin and the superficial tissues of the leg. Microdissection and the technique of Spalteholz for dehydrating and clearing the tissues (rendering them transparent) facilitated the study of the direct and indirect arterial branches which form the three principal networks: the deep fascia, the subcutaneous or adipose layer, and the skin or the dermoepidermic layer. The results are of practical importance since the fascio-subcutaneous tissue layer can be used as a flap for covering soft tissue defects of the leg.
Central mechanisms for the hypertensive effects of preproadrenomedullin-derived peptides in conscious rats (1998)

Peptides derived from postranslational processing of preproadrenomedullin exert potent hypotensive effects in the periphery. One of those peptides, adrenomedullin (AM) also has been demonstrated to act centrally in conscious rats to inhibit water drinking and salt appetite and, in anesthetized rats, surprisingly to increase blood pressure. We examined the effects of AM and the other postranslational product, proadrenomedullin NH2-terminal 20 peptide (PAMP), on blood pressure in conscious rats. Both AM and PAMP elicited dose-related increases in mean arterial pressure after cerebroventricular administration. The hypertensive effects of both AM and PAMP and of ANG II were blocked by peripheral administration of phentolamine, indicating actions of the peptides in brain to stimulate sympathetic nervous system function. Blockade of central ANG II receptors with saralasin prevented the hypertensive effects of both ANG II and PAMP, suggesting recruitment of endogenous angiotensinergic systems by central PAMP. The structural homolog of AM, calcitonin gene-related peptide (CGRP), at similar doses did nto significantly affect blood pressure. Furthermore, the hypertensive effects of ANG II, AM, and PAMP were not abrogated by prior administration of the CGRP antagonist. We hypothesize that AM and PAMP exert cardioprotective effects in brain, which may counterbalance the volume-unloading actions of the peptides in the periphery.
Changes in central hemodynamics during experimental septic shock in conscious rats. (1987)

This study describes the hemodynamic, metabolic, and respiratory effects of a 4-h continuous intravenous infusion of live Escherichia coli bacteria (10(9)/h) in conscious, unrestrained rats. The early response to bacterial infusion was moderate hypotension and a marked and sustained increase in heart rate and respiratory rate. During later stages of bacteria infusion a marked decrease in stroke volume and cardiac output was observed, while total peripheral resistance increased. Arterial blood gas measurements showed an early primary respiratory alkalosis, while later stages of bacteria infusion were accompanied by progressive development of metabolic acidosis. This small-sized animal shock model may be useful for further studies, particularly since conscious rats were used to avoid the influence of anesthesia upon the development of septic shock.
Construction of Phylogenetic Trees (1967)

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ChemInform Abstract: Excited‐State Dipole Moments of Dual Fluorescent 4‐(Dialkylamino) benzonitriles (I). Influence of Alkyl Chain Length and Effective Solvent Polarity. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Leukotrienes in cardiovascular disease (2001)

Intensive research into the leukotrienes as inflammatory mediators in asthma has tended to overshadow the intriguing evidence suggesting their involvement in cardiovascular disease. Cysteinyl-leukotrienes (Cys-LTs) fulfil many of Dale’s postulates for a pathophysiological contribution to angina, myocardial infarction and pulmonary hypertension. The development of safe and specific Cys-LT receptor antagonists now provides an opportunity to delineate their role in these conditions definitively. This paper will outline the data from animal and human studies in vitro and in vivo that suggest that Cys-LT contribute in particular to coronary artery disease (CAD) and that point towards new therapeutic roles for anti-LT drugs.
CRISPR–Cas9 Structures and Mechanisms (2017)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes. The use of CRISPR-Cas9 as an RNA-programmable DNA targeting and editing platform is simplified by a synthetic single-guide RNA (sgRNA) mimicking the natural dual trans-activating CRISPR RNA (tracrRNA)-CRISPR RNA (crRNA) structure. This review aims to provide an in-depth mechanistic and structural understanding of Cas9-mediated RNA-guided DNA targeting and cleavage. Molecular insights from biochemical and structural studies provide a framework for rational engineering aimed at altering catalytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for the development of Cas9-based therapies against genetic diseases.
On Ideal Lattices and Learning with Errors over Rings (2013)

The “learning with errors” (LWE) problem is to distinguish random linear equations, which have been perturbed by a small amount of noise, from truly uniform ones. The problem has been shown to be as hard as worst-case lattice problems, and in recent years it has served as the foundation for a plethora of cryptographic applications. Unfortunately, these applications are rather inefficient due to an inherent quadratic overhead in the use of LWE. A main open question was whether LWE and its applications could be made truly efficient by exploiting extra algebraic structure, as was done for lattice-based hash functions (and related primitives). We resolve this question in the affirmative by introducing an algebraic variant of LWE called ring-LWE , and proving that it too enjoys very strong hardness guarantees. Specifically, we show that the ring-LWE distribution is pseudorandom, assuming that worst-case problems on ideal lattices are hard for polynomial-time quantum algorithms. Applications include the first truly practical lattice-based public-key cryptosystem with an efficient security reduction; moreover, many of the other applications of LWE can be made much more efficient through the use of ring-LWE.
Biomarkers in cancer screening, research and detection: present and future: a review (2006)

Biomarkers provide a powerful and dynamic approach to understanding the spectrum of malignancies with applications in observational and analytic epidemiology, randomized clinical trials, screening, diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer a means for homogeneous classification of a disease and risk factor, and they can extend one's basic information about the underlying pathogenesis of disease. The goals in cancer research include finding biomarkers that can be used for the early detection of cancers, design individual therapies, and to identify underlying processes involved in the disease. Because so many myriad processes are involved in the diseased states, the goal is similar to 'finding a needle in a haystack'. However, the development of many -omic technologies, such as genomics and proteomics, has allowed us to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of biomarkers and signalling molecules associated with cell growth, cell death and cellular metabolism. These are also facilitating in monitoring the functional disturbance, molecular and cellular damage, and damage response. This brief review describes the development of biomarkers in cancer research and detection with emphasis on different proteomic tools for the identification and discovery of new biomarkers, different clinical assays to detect various biomarkers in different specimens, role of biomarkers in cancer screening and last but not the least, the challenges in this direction of cancer research.
Structure-Based View of Epidermal Growth Factor Receptor Regulation (2008)

High-resolution X-ray crystal structures determined in the past six years dramatically influence our view of ligand-induced activation of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Ligand binding to the extracellular region of EGFR promotes a major domain reorganization, plus local conformational changes, that are required to generate an entirely receptor-mediated dimer. In this activated complex the intracellular kinase domains associate to form an asymmetric dimer that supports the allosteric activation of one kinase. These models are discussed with emphasis on recent studies that add details or bolster the generality of this view of activation of this family of receptors. The EGFR family is implicated in several disease states, perhaps most notably in cancers. Activating tumor mutations have been identified in the intracellular and extracellular regions of EGFR. The impact of these tumor mutations on the understanding of EGFR activation and of its inhibition is discussed.
Formation of a High-Density Deuterium Plasma Focus (1965)

During the early investigation of the high-energy, low-pressure mode of a coaxial hydromagnetic gun, a second mode of action was established for large gas fillings. This particular mode, previously reported was found to lead to a high-density plasma focus situated at a distance ∼1–1.5 cm beyond the face of the center electrode. The plasma focus has the following properties; particle density ρ ∼ 2–3 × 1019/cm3, temperature T ∼ 1–3 keV, time duration t ∼ 0.2–0.3 μsec, and volume ∼15 mm3. Neutron yields &amp;gt;1010/burst and soft x rays are observed. These results are remarkably similar to those reported by Petrov et al. and Filippov et al. of the USSR using a metal wall pinch tube apparatus. The average velocity vz of the current sheath in the gun proper is found to depend on the fourth root of the applied voltage squares, divided by the mass density according to the simple ``snowplow'' ``M'' theory. The current sheath is found to be nonplanar and mass pickup by the advancing sheath is nonlinear with radius. The sudden collapse of the radial current sheath toward the axis at the center electrode end is most likely caused by the rapid conversion of stored magnetic energy into radial sheath motion (v̄r ∼ 3.5 × 107 cm/sec) forming in essence a super dense pinch effect.
A bimetallic iron(iii) catalyst for CO2/epoxide coupling (2010)

A novel di-iron(III) catalyst for the copolymerisation of cyclohexene oxide and CO(2) to yield poly(cyclohexene carbonate), under mild conditions, is reported. The catalyst selectivity was completely changed on addition of an ammonium co-catalyst to yield only the cis-isomer of the cyclic carbonate, also under mild conditions. Additionally, the catalyst was active for propylene carbonate and styrene carbonate production at 1 atm pressure.
LAMBDA — Large Area Medipix3-Based Detector Array (2012)

Medipix3 is a photon-counting readout chip for X-ray detection. It has a small pixel size (55 μm) and a high frame rate with zero dead time, which makes it attractive for experiments at synchrotrons. Using Medipix3, DESY are developing the LAMBDA (Large Area Medipix3-Based Detector Array) system. A single LAMBDA module carries either a single large silicon sensor of 1536 by 512 pixels, or two smaller high-Z sensors. The sensor is bonded to 12 Medipix3 chips, and mounted on a ceramic carrier board. The readout system for the module then provides a fast FPGA, a large RAM and four 10 Gigabit Ethernet links to allow operation at high frame rates. Multiple modules may then be tiled together a larger area. Currently, the first large silicon modules have been constructed and tested at low speed, and the firmware for fast readout is being developed.
Lateral mobility of proteins in liquid membranes revisited (2006)

The biological function of transmembrane proteins is closely related to their insertion, which has most often been studied through their lateral mobility. For >30 years, it has been thought that hardly any information on the size of the diffusing object can be extracted from such experiments. Indeed, the hydrodynamic model developed by Saffman and Delbrück predicts a weak, logarithmic dependence of the diffusion coefficient D with the radius R of the protein. Despite widespread use, its validity has never been thoroughly investigated. To check this model, we measured the diffusion coefficients of various peptides and transmembrane proteins, incorporated into giant unilamellar vesicles of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) or in model bilayers of tunable thickness. We show in this work that, for several integral proteins spanning a large range of sizes, the diffusion coefficient is strongly linked to the protein dimensions. A heuristic model results in a Stokes-like expression for D, (D proportional, variant 1/R), which fits literature data as well as ours. Diffusion measurement is then a fast and fruitful method; it allows determining the oligomerization degree of proteins or studying lipid-protein and protein-protein interactions within bilayers.
Hepatotoxicity of antifungal agents. (2005)

Antifungal agents have been implicated in numerous cases of hepatotoxicity throughout the past few decades. Hepatotoxic reactions to antifungal agents range from slight, asymptomatic abnormalities in liver function tests to potentially fatal fulminant hepatic failure. Clinically significant hepatic injury resulting from antifungal therapy most commonly manifests as acute hepatocellular, cholestatic or mixed hepatocellular-cholestatic reactions. In general, reactions usually resolve on cessation of therapy, but some antifungal agents may induce chronic liver damage. This review will summarize the hepatotoxicity profiles of the major classes of antifungal agents and will provide recommendations for drug monitoring in order to minimize the risk of hepatotoxicity.
Immunoassay techniques with fluorescent phycobiliprotein conjugates. (1983)

We describe immunoassay techniques that take advantage of the novel properties of phycobiliprotein fluorescent dyes. These dyes, which can be isolated from a wide variety of algae, exhibit extremely high absorptivities, high quantum efficiencies, and excitation and emission bands across the visible spectrum. These stable, hydrophilic proteins can easily be linked to antibodies by conventional protein cross-linking reagents. One assay technique presented here demonstrates the use of phycobiliproteins in a solid-phase "sandwich" assay, which achieves picomolar sensitivity. In the other technique the unique spectral properties of phycobiliproteins are applied to fluorescence excitation transfer immunoassay.
Distribution of blood viscosity values and biochemical correlates in healthy adults (1996)

Increases in the viscosity of blood and plasma predict clinical manifestations of atherothrombotic vascular disease. The clinical utility of viscosity measurements in cardiovascular risk factor analysis requires reference values established from a healthy disease-free population. A cohort of 126 (71 men, 55 women) healthy nonsmoking adults had fasting blood analysis after a 12-14-h fast. Viscosity measurements were made on samples of whole blood, plasma, and serum at 37 degrees C with a coaxial cylinder microviscometer. The mean blood viscosity at shear rates of 100, 50, and 1 s-1 were 3.26 +/- 0.43, 4.37 +/- 0.60, and 5.46 +/- 0.84 mPa.s, respectively. Men had significantly higher blood viscosity values than women at each shear rate. The differences in blood viscosity did not remain significant after blood viscosity values were normalized to a hematocrit of 45%, except at 100 s-1. For the entire group, normalized blood viscosity values at each measured rate correlated inversely with HDL cholesterol and positively with fibrinogen. The mean plasma viscosity was 1.39 +/- 0.08 mPa.s and the mean serum viscosity was 1.27 +/- 0.06 mPa.s. Plasma viscosity correlated with fibrinogen (r = 0.51, P < 0.0001), total serum protein (r = 0.33, P < 0.0001), and triglyceride concentrations (r = 0.33, P < 0.0015). Serum viscosity correlated with total serum protein (r = 0.50, P < 0.0001) and LDL cholesterol (r = 0.24, P = 0.0065). This study provides reference values for the viscosity of blood, plasma, and serum that may assist in evaluating hemorheological profiles.
The architecture of the Obelix-an improved Internet search engine (2005)

Contemporary Internet search engines can hardly cope with enormous amounts of indexed data, and very seldom succeed in extracting useful information. In order to anticipate the usefulness of a Web page, the proposed solution keeps track of users' actions on a Web page. A modified Web client informs a dedicated server of users' actions performed on a Web page, such as printing, bookmarking or mailing. The search algorithm relies on this information when ranking pages according to their usefulness. The paper describes the proposed paradigm in detail and focuses on the architecture of the server dedicated to collecting information of users' actions. The server's architecture is based on reconfigurable technology and VCC HOT II reconfigurable boards.
The Potential Therapeutic Effects of THC on Alzheimer's Disease (2014)

The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.
The radiosensitizing agent 7-hydroxystaurosporine (UCN-01) inhibits the DNA damage checkpoint kinase hChk1. (2000)

The investigational anticancer agent 7-hydroxystaurosporine (UCN-01) abrogates the G2 checkpoint in tumor cells and sensitizes them to the lethal effects of genotoxic anticancer agents. On the basis of the role of the Cdc25C phosphatase in maintenance of this damage-inducible checkpoint, we hypothesized that UCN-01 inhibits a component of the signal transduction pathway that modulates Cdc25C phosphorylation. Of the three kinases known to phosphorylate Cdc25C on Ser216, both checkpoint kinase 1 (hChk1) and Cdc25C-associated protein kinase 1 (cTAK1) were potently inhibited by UCN-01 with IC50s of 11 and 27 nM, respectively. Treatment of K562 erythroblastoid leukemia cells with similar drug concentrations resulted in decreased levels of Ser216 phosphorylation of Cdc25C and complete disruption of the y-radiation-induced G2 checkpoint. In contrast to hChk1, the hChk2 kinase was 100-fold more resistant to inhibition by UCN-01 (IC50, 1040 nM). These results suggest that disruption of the DNA damage-induced G2 checkpoint by UCN-01 is mediated through the inhibition of the Cdc25C kinases, hChk1 and cTAK1, and that hChk2 activity is not sufficient to enforce the G2 checkpoint in cells treated with a pharmacological inhibitor of hChk1.
A multiple valued logic: a tutorial and appreciation (1988)

This tutorial places the developments and potential of multiple-valued signals and logic in the relevant context of binary and two-valued signals. It covers: the role of multivalued logic (MVL) in the binary world; multivalued representation; binary-related radices; multivalued functions; storage techniques in MVL; and implementation issues. An overview of applications is included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium (1999)

The T cell cytokine IL-17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down-regulated by IL-4 and IL-13. These results indicate that IL-17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL-17, some Th1-like T cells appear to mediate synovial inflammation.