gebhart/patrepeval huggingface dataset:
Future directions in the clinical management of amyloid light-chain amyloidosis (2013)

Amyloid light-chain (AL) amyloidosis results from extracellular deposition of fibril-forming monoclonal immunoglobulin light chains (LCs) usually secreted by a plasma cell (PC) clone. Misfolded LCs deposit as unique fibrils leading to organ failure and eventually death. Survival for untreated patients remains poor, and restrictive cardiomyopathy, nephrotic syndrome or hepatic failure greatly worsen outcome. Conventional chemotherapy and novel therapy with immunomodulatory drugs or proteasome inhibitors (PIs) eradicate PCs but generate adverse toxicities, and sustained responses are limited. Moreover, only 20% of patients with AL amyloidosis are eligible for stem cell transplant. The molecular events deregulated in AL amyloidosis remain undefined, and effective therapies based upon the biology of the disease are lacking. Impressive hematologic response rates obtained with bortezomib provide practice-changing data to advocate their introduction early in the treatment course. Bortezomib and the emerging second-generation PIs alone or combined with dexamethasone and alkylating agents may enhance hematologic and organ responses in AL amyloidosis.
Experimental and Numerical Studies on the Deformation of a Flexible Wire in an Injection Moulding Process (2020)

The application of thermoplastic materials is state of the art due to their fast cycle times in production and large freedom of shaping. To enhance the performance and functionality, additional materials or elements are embedded into the bulk material. While typically fibres are added for mechanical reinforcement, recent research also focusses on the integration of conductor wires to integrate electrical functions. During the manufacturing process, the interaction with the thermoplastic melt can lead to breakage or undesired deformation of the flexible elements respectively wires. For a proper process and component design, this local fluid-structure-interaction must be understood and considered. There are different numerical approaches to meet this challenge. In the present work, the suitability of established modelling techniques and solvers is evaluated and compared with experimental investigations. For this purpose, solid flexible wires are overmoulded with polypropylene using an injection moulding testing set-up. In the experimental investigations, the deflection of the wire is evaluated for different process settings. For the numerical simulations, solvers from ABAQUS and Moldflow including the Wire Sweep Module and the Core Shift Module are used. The comparison of the simulations and the experiments shows, that the different solver’s results clearly deviate from each other and the experiment depending on the wire length. While some approaches seem to be very promising, it can be concluded that the longer the wire, the worse the simulation quality.
A 1-/spl mu/m Bipolar VLSI Technology (1980)

A 1-/spl mu/m VLSI process technology has been developed for the fabrication of bipolar circuits. The process employs electron-beam slicing writing, plasma processing, ion implantation, and low-temperature oxidation/annealing to fabricate bipolar device structures with a minimum feature size of 0.9 /spl mu/m. Both nonisolated I/sup 2/L and isolated Schottky transistor logic (STL) devices and circuits have been fabricated with this process technology. The primary demonstration vehicle is a seated LSI, I/sup 2/L, 4-bit processor chip (SBP0400) with a minimum feature size of 1 /spl mu/m. Scaled SPB0400's have been fabricated that operate at clock speeds 3X higher than their full-size counterparts at 50-mA chip current. Average propagation delay has been measured as a function of minimum feature size for both I/sup 2/L and STL device designs. Power-delay products of 14 fJ for I/sup 2/L and 30 fJ for STL have been measured.
Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection (2000)

In endemic areas, asymptomatic infection by the malaria parasite Plasmodium falciparum was found associated with elevated percentages of human host's mononuclear cell spontaneous in-vitro apoptosis. In Dielmo, a village where malaria is holoendemic, apoptosis was age-and parasite-dependent. In-vitro exposure of peripheral blood mononuclear cells (PBMC) to the parasite extract induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-CD95 antibodies led to a detectable increase in the mean percentage of apoptotic nuclei found in the cultures carried out in the presence of P. falciparum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promoted the viability of PBMC in cultures while IL-1alpha or IFN-gamma had no obvious impact and TNFalpha gave conflicting results. IL-2 was the most efficient cytokine at rescuing PBMC from cell death and this effect was associated with a strong increase in T cell activation. In contrast, IL-4 and IL-10 had no such effect on T cell activation, hence they acted as survival factors and not through their mitogenic activity. Taken together, these different observations suggested that the levels of in-vitro apoptosis observed were not only associated with parasite infection, but also potentially modulated by the human host through different pathways.
Binding of Factor VIII to von Willebrand Factor Is Enabled by Cleavage of the von Willebrand Factor Propeptide and Enhanced by Formation of Disulfide-Linked Multimers (1998)

von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.
Supplementary Figures 1-14 from Targeting the Fanconi Anemia/BRCA Pathway Circumvents Drug Resistance in Multiple Myeloma (2023)

Supplementary Figures 1-14 from Targeting the Fanconi Anemia/BRCA Pathway Circumvents Drug Resistance in Multiple Myeloma
Explaining Explanations: An Overview of Interpretability of Machine Learning (2018)

There has recently been a surge of work in explanatory artificial intelligence (XAI). This research area tackles the important problem that complex machines and algorithms often cannot provide insights into their behavior and thought processes. XAI allows users and parts of the internal system to be more transparent, providing explanations of their decisions in some level of detail. These explanations are important to ensure algorithmic fairness, identify potential bias/problems in the training data, and to ensure that the algorithms perform as expected. However, explanations produced by these systems is neither standardized nor systematically assessed. In an effort to create best practices and identify open challenges, we describe foundational concepts of explainability and show how they can be used to classify existing literature. We discuss why current approaches to explanatory methods especially for deep neural networks are insufficient. Finally, based on our survey, we conclude with suggested future research directions for explanatory artificial intelligence.
Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes (2004)

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN- with normal BRS (BRS+; n = 10), 2) CAN- with impaired BRS (BRS-; n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (+/-SE) QTc lengthened from 377 +/- 9 ms (baseline) to a maximum during hypoglycemia of 439 +/- 13 ms in BRS+ subjects and from 378 +/- 5 to 439 +/- 10 ms in control subjects. Peak QTc tended to be lower in CAN+ (baseline, 383 +/- 6; maximum, 408 +/- 10) and BRS- groups (baseline, 380 +/- 8; maximum, 421 +/- 11; F = 1.7, P = 0.18). Peak epinephrine concentrations (nmol/l) were 3.1 +/- 0.8 (BRS+), 2.6 +/- 0.5 (BRS-), 1.4 +/- 0.3 (CAN+), and 5.7 +/- 0.8 (control subjects). These data do not indicate that those with CAN are at particular risk for abnormal cardiac repolarization during hypoglycemia. Indeed, they suggest that such patients may be relatively protected, perhaps as a result of attenuated sympatho-adrenal responses.
Dietary fat increases renal injury in SHR in the absence of changes in insulin sensitivity or blood pressure (2007)

Obesity and hypertension are cardiovascular risk factors that contribute to the progression of end‐stage renal disease. The aim of this study was to elucidate events and mechanisms involved in renal injury in an animal model of obesity and hypertension. Male 8 week‐old SHR and WKY rats were fed high fat (HF, 36%) or normal fat diet (NF, 7%) for 10 weeks (n=5 per group). Ten weeks HF increased body weight gain but did not alter blood pressure in SHR or WKY. In euglycemic clamp experiments in both strains, glucose infusion rates of 35 to 40 mg/kg/min were required to maintain blood glucose at 125 mg/dL, indicating insulin sensitivity. Plasma leptin levels were increased by HF from 4.8 ± 0.6 and 4.5 ± 0.9 ng/ml to 13.4 ± 0.7 and 8.2 ± 0.7 ng/ml in WKY and SHR respectively (P&lt;0.05). Albumin excretion, a marker for renal injury, increased to 867 ± 125 in HF SHR compared to 519 ± 63 μg/day in NF SHR (P&lt;0.05). WKY excreted lower levels of albumin which was unaltered by diet. Urinary MCP‐1 reached 38 ± 10 and 33 ± 7 ng/day in the HF WKY and SHR compared to 13 ± 4 and 14 ± 4 ng/day in the NF WKY and SHR respectively (P&lt;0.05). Plasma 8‐Isoprostane increased with HF from 1008 to 1468 pg/day in WKY and 810 to 952 pg/day in SHR. Our results indicate that ten weeks HF diet exacerbates renal injury in SHR in the absence of changes in blood pressure or insulin sensitivity. We demonstrate that hyperleptinemia, oxidative stress and inflammation may contribute to the renal injury.
Protection by imidazol(ine) drugs and agmatine of glutamate‐induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor (1999)

This study was designed to assess the potential neuroprotective effect of several imidazol(ine) drugs and agmatine on glutamate-induced necrosis and on apoptosis induced by low extracellular K+ in cultured cerebellar granule cells. Exposure (30 min) of energy deprived cells to L-glutamate (1-100 microM) caused a concentration-dependent neurotoxicity, as determined 24 h later by a decrease in the ability of the cells to metabolize 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) into a reduced formazan product. L-glutamate-induced neurotoxicity (EC50=5 microM) was blocked by the specific NMDA receptor antagonist MK-801 (dizocilpine). Imidazol(ine) drugs and agmatine fully prevented neurotoxicity induced by 20 microM (EC100) L-glutamate with the rank order (EC50 in microM): antazoline (13)>cirazoline (44)>LSL 61122 [2-styryl-2-imidazoline] (54)>LSL 60101 [2-(2-benzofuranyl) imidazole] (75)>idazoxan (90)>LSL 60129 [2-(1,4-benzodioxan-6-yl)-4,5-dihydroimidazole](101)>RX82 1002 (2-methoxy idazoxan) (106)>agmatine (196). No neuroprotective effect of these drugs was observed in a model of apoptotic neuronal cell death (reduction of extracellular K+) which does not involve stimulation of NMDA receptors. Imidazol(ine) drugs and agmatine fully inhibited [3H]-(+)-MK-801 binding to the phencyclidine site of NMDA receptors in rat brain. The profile of drug potency protecting against L-glutamate neurotoxicity correlated well (r=0.90) with the potency of the same compounds competing against [3H]-(+)-MK-801 binding. In HEK-293 cells transfected to express the NR1-1a and NR2C subunits of the NMDA receptor, antazoline and agmatine produced a voltage- and concentration-dependent block of glutamate-induced currents. Analysis of the voltage dependence of the block was consistent with the presence of a binding site for antazoline located within the NMDA channel pore with an IC50 of 10-12 microM at 0 mV. It is concluded that imidazol(ine) drugs and agmatine are neuroprotective against glutamate-induced necrotic neuronal cell death in vitro and that this effect is mediated through NMDA receptor blockade by interacting with a site located within the NMDA channel pore.
Hot wire chemical vapor deposition of isolated carbon single-walled nanotubes (2002)

Hot wire chemical vapor deposition (HWCVD) has been employed for the continuous generation of carbon single-walled nanotube (SWNT) materials. Interestingly, transmission electron microscopy analyses revealed only the presence of isolated SWNTs, rather than nanotubes existing in bundles. An analysis of the growth mechanism explaining the production of isolated SWNTs is provided. Also, the Raman radial breathing modes (RBMs) of the isolated HWCVD-generated nanotubes are compared to the RBMs of small bundles of nanotubes deposited by a conventional CVD technique having a similar diameter distribution.
Genetic Encoding of Three Distinct Noncanonical Amino Acids Using Reprogrammed Initiator and Nonsense Codons (2021)

We recently described an orthogonal initiator tRNA (<i>i</i>tRNA<sup>Ty2</sup>) that can initiate protein synthesis with noncanonical amino acids (ncAAs) in response to the UAG nonsense codon. Here, we report that a mutant of <i>i</i>tRNA<sup>Ty2</sup> (<i>i</i>tRNA<sup>Ty2</sup><sub>AUA</sub>) can efficiently initiate translation in response to the UAU tyrosine codon, giving rise to proteins with an ncAA at their N-terminus. We show that, in cells expressing <i>i</i>tRNA<sup>Ty2</sup><sub>AUA</sub>, UAU can function as a dual-use codon that selectively encodes ncAAs at the initiating position and predominantly tyrosine at elongating positions. Using <i>i</i>tRNA<sup>Ty2</sup><sub>AUA</sub>, in conjunction with its cognate tyrosyl-tRNA synthetase and two mutually orthogonal pyrrolysyl-tRNA synthetases, we demonstrate that UAU can be reassigned along with UAG or UAA to encode two distinct ncAAs in the same protein. Furthermore, by engineering the substrate specificity of one of the pyrrolysyl-tRNA synthetases, we developed a triply orthogonal system that enables simultaneous reassignment of UAU, UAG, and UAA to produce proteins containing three distinct ncAAs at precisely defined sites. To showcase the utility of this system, we produced proteins containing two or three ncAAs, with unique bioorthogonal functional groups, and demonstrate that these proteins can be separately modified with multiple fluorescent probes.
EXPOSE-R2, the 3rd successful EXPOSE mission – a mission and mission ground reference overview (2016)

For nearly 2 years the 3rd ESA EXPOSE mission, the 2nd on the Russian Zvezda module of the ISS, exposed a variety of astrobiological samples to space and simulated Mars environmental conditions. Various chemical compounds and organisms like bacteria, archaea, fungi, plant seeds, lychens, mosses and animal eggs and larvae from the international experiments BIOMEX, BOSS, P.S.S. and the IBMP-experiment were exposed to space vacuums dryness, extraterrestrial short wavelength UV, radiation and temperature oscillation or Mars-like conditions comprised of a 980 Pa pressure CO₂ dominated gas mixture and solar UV modulated to simulate Mars surface solar radiation. The complete mission was simulated under ESA contract in the Planetary and Space Simulation facilities at DLR Cologne according to mission data received from the ISS and to UV radiation calculations by RedShift.
SOH Mach-Zehnder Modulators for 100 GBd PAM4 Signaling With Sub-1 dB Phase-Shifter Loss (2020)

We demonstrate 280 µm-long silicon-organic hybrid (SOH) modulators with optical phase-shifter losses of 0.7 dB and π-voltages of 1.5 V. We show OOK and PAM4 signaling at 100 GBd with a BER below the 7% HD-FEC limit.
A robust pose matching algorithm for covered body analysis for sleep apnea (2008)

Existing video monitoring techniques require clinicians to analyze substantial amounts of video data in diagnosis of sleep apnea. Analysis of the covered human body from video is a challenging task as traditional computer vision methods such as correlation, template matching, background subtraction, contour models and related techniques for object tracking become ineffective because of the large degree of occlusion for long periods. In condition of persistent heavy occlusion, difficulties arise from night vision, large variances of image features according to the occlusion level, the shifting of the cover surface with movements, obscuration of the bodiespsila edges by the cover, and wrinkle noises. We propose a near real time method to robustly estimate the pose of fully/partially covered or uncovered human body. The proposed method contains a novel weak human model to accommodate large variances of image features and a strong pose recognition model derived from a stylized pose detector used for people tracking by Ramanan et al.. We improve the stylized pose detection model by modifying the cost formula and template representation to overcome weak cues and strong noise due to heavy occlusion. In evaluation, the experimental results show that the proposed model is promising to estimate the pose of a human body with fully or partially covered or without covered.
Scale Invariant Metrics of Volumetric Datasets (2015)

Nature reveals itself in similar structures of different scales. A child and an adult share similar organs yet dramatically differ in size. Comparing the two is a challenging task to a computerized approach as scale and shape are coupled. Recently, it was shown that a local measure based on the Gaussian curvature can be used to normalize the local metric of a surface and then to extract global features and distances. In this paper we consider higher dimensions; specifically, we construct a scale invariant metric for volumetric domains which can be used in analysis of medical datasets such as computed tomography (CT) and magnetic resonance imaging (MRI).
<title>Cell adhesion and guidance by micropost-array chemical sensors</title> (2002)

An array of ~50,000 individual polymeric micropost sensors was patterned across a glass coverslip by a photoimprint lithographic technique. Individual micropost sensors were ~3-micrometers tall and ~8-micrometers wide. The O<SUB>2</SUB>-sensitive micropost array sensors (MPASs) comprised a ruthenium complex encapsulated in a gas permeable photopolymerizable siloxane. The pH-sensitive MPASs comprised a fluorescein conjugate encapsulated in a photocrosslinkable poly(vinyl alcohol)-based polymer. PO<SUB>2</SUB> and pH were quantitated by acquiring MPAS luminescence images with an epifluorescence microscope/charge coupled device imaging system. O<SUB>2</SUB>-sensitive MPASs displayed linear Stern-Volmer quenching behavior with a maximum I<SUB>o</SUB>/I of ~8.6. pH-sensitive MPASs displayed sigmoidal calibration curves with a pK<SUB>a</SUB> of ~5.8. The adhesion of undifferentiated rat pheochromocytoma (PC12) cells across these two polymeric surface types was investigated. The greatest PC12 cell proliferation and adhesion occurred across the poly(vinyl alcohol)-based micropost arrays relative to planar poly(vinyl alcohol)-based surfaces and both patterned and planar siloxane surfaces. An additional advantage of the patterned MPAS layers relative to planar sensing layers was the ability to direct the growth of biological cells. Preliminary data is presented whereby nerve growth factor-differentiated PC12 cells grew neurite-like processes that extended along paths defined by the micropost architecture.
Studies on Anti-ulcerogenic Protein in Inflamed Rabbit Skin Tissues. III. Anti-ulcerogenic Peptide (Gly-Ser-His-Lys) Obtained from Tissues Infected with Vaccinia Virus (1984)

During our studies on the active moiety of anti-ulcerogenic protein in rabbit skin tissues infected with vaccinia virus, we obtained a tetrapeptide, Gly-Ser-His-Lys (GSHL), as the smallest essential residue. The action of this peptide widely covered against various experimental ulcers in rats induced by pylorus-ligation, restraint plus water immersionstress (minimum effective dose, mg/kg, i. v. ; 5.0), aspirin (5.0), histamine (5.0), cortisone (2.5/d), cysteamine (10) and acetic acid (1.0/d). In the respect of minimum effective dose, the effect of GSHL was 5-20 fold stronger than that of cimetidine, except for acetic acidinduced ulcers. Histological finding of acetic acid-induced ulcers revealed that GSHL treatment shortened an apparent defect of mucosa, a true defect of mucosa and rupture of muscaliris mucosae, and that it increased healing index and mucosal regeneration index. The peptide significantly decreased serum gastrin level, increased mucosal and stromal hexosamine contents and also increased mucosal blood flow in stress-treated rats. It significantly inhibited gastric secretion in pylorus-ligated rats. The mechanism of the action of GSHL appears to be due to the restorative effect against defected mucosa and anti-secretory effect.
Actividades del IPNA-CSIC (La Laguna, Tenerife) entre Enero y Junio de 2010 (2010)

5 páginas, 6 fotos.-- Resumen de las actividades de divulgación científica del IPNA del 1er semestre del 2010.
Selected polysaccharides at comparison for their mucoadhesiveness and effect on precorneal residence of different drugs in the rabbit model (2009)

Mucoadhesive polysaccharides may prolong the residence of ophthalmic drugs in precorneal area. In this article, the mucoadhesiveness of arabinogalactan, tamarind seed polysaccharide, hyaluronan, hydroxyethylcellulose is compared in vivo, by the polymer residence time in rabbit tear fluid, and in vitro, by the polymer-induced increase of viscosity of a mucin dispersion. Polymer residence is prolonged by increased viscosity but shortened by reflex tearing caused by excessive viscosity. Tamarind seed polysaccharide is the most effective in prolonging the residence of ketotifen and diclofenac in precorneal area; hence, it is the optimal eyedrop additive as it is mucoadhesive while not increasing viscosity excessively.