gebhart/patrepeval huggingface dataset:
Structural Requirements for Efficient Processing and Activation of Recombinant Human UDP-N-acetylglucosamine:Lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (2006)

Mannose 6-phosphate-modified N-glycans are the determinant for intracellular targeting of newly synthesized lysosomal hydrolases to the lysosome. The enzyme responsible for the initial step in the synthesis of mannose 6-phosphate is UDP-N-acetylglucosamine:lysosomal-enzyme-N-acetylglucosmine-1-phosphotransferase(GlcNAc-phosphotransferase). GlcNAc-phosphotransferase is a multisubunit enzyme with an alpha2beta2gamma2 arrangement that requires a detergent for solubilization. Recent cloning of cDNAs and genes encoding these subunits revealed that the alpha- and beta-subunits are encoded by a single gene as a precursor, whereas the gamma-subunit is encoded by a second gene. The hydropathy plots of the deduced amino acid sequences suggested that the alpha- and beta-subunits but not the gamma-subunit contain transmembrane domains. Access to these cDNAs allowed us to express a soluble form of human recombinant GlcNAc-phosphotransferase by removing the putative transmembrane and cytoplasmic domains from the alpha- and beta-subunits. Because this modification prevented precursor processing to mature alpha- and beta-subunits, the native cleavage sequence was replaced by a cleavage site for furin. When the modified alpha/beta-subunits (alpha'/beta'-subunits) precursor and wild type gamma-subunit cDNAs were co-expressed in 293T or CHO-K1 cells, a furin-like protease activity in these cells cleaved the precursor and produced an active and processed soluble GlcNAc-phosphotransferase with an alpha'2beta'2gamma2-subunits arrangement. Recombinant soluble GlcNAc-phosphotransferase exhibited specific activity and substrate preferences similar to the wild type bovine GlcNAc-phosphotransferase and was able to phosphorylate a lysosomal hydrolase, acid alpha-glucosidase in vitro.
Bivalent Brain Shuttle Increases Antibody Uptake by Monovalent Binding to the Transferrin Receptor (2016)

The blood-brain barrier (BBB) is an obstacle for antibody passage into the brain, impeding the development of immunotherapy and antibody-based diagnostics for brain disorders. In the present study, we have developed a brain shuttle for active transport of antibodies across the BBB by receptor-mediated transcytosis. We have thus recombinantly fused two single-chain variable fragments (scFv) of the transferrin receptor (TfR) antibody 8D3 to the light chains of mAb158, an antibody selectively binding to Aβ protofibrils, which are involved in the pathogenesis of Alzheimer's disease (AD). Despite the two TfR binders, a monovalent interaction with TfR was achieved due to the short linkers that sterically hinder bivalent binding to the TfR dimer. The design enabled efficient receptor-mediated brain uptake of the fusion protein. Two hours after administration, brain concentrations were 2-3% of the injected dose per gram brain, comparable to small molecular drugs and 80-fold higher than unmodified mAb158. After three days, fusion protein concentrations in AD transgenic mouse brains were 9-fold higher than in wild type mice, demonstrating high <i>in vivo</i> specificity. Thus, our innovative recombinant design markedly increases mAb158 brain uptake, which makes it a strong candidate for improved Aβ immunotherapy and as a PET radioligand for early diagnosis and evaluation of treatment effect in AD. Moreover, this approach could be applied to any target within the brain.
Time-of-flight PET data determine the attenuation sinogram up to a constant (2012)

In positron emission tomography (PET), a quantitative reconstruction of the tracer distribution requires accurate attenuation correction. We consider situations where a direct measurement of the attenuation coefficient of the tissues is not available or is unreliable, and where one attempts to estimate the attenuation sinogram directly from the emission data by exploiting the consistency conditions that must be satisfied by the non-attenuated data. We show that in time-of-flight PET, the attenuation sinogram is determined by the emission data except for a constant and that its gradient can be estimated efficiently using a simple analytic algorithm. The stability of the method is illustrated numerically by means of a 2D simulation.
Feature Learning Using Synaptic Competition in a Dynamically-Sized Neuromorphic Architecture (2017)

Neuromorphic computing takes inspiration from how the brain works to explore novel computing paradigms. Recently, neuromorphic architectures using spiking neurons were proposed for unsupervised learning of pattern- and feature-based representations. These approaches typically use a common WTA architectural motif of lateral inhibition that introduces competition between the neurons. In this paper, we propose an alternative WTA architectural motif of synaptic competition that introduces competition between the synapses. As the WTA mechanism is moved from neurons to synapses, neuronal activation is not constrained during the learning, and the architecture operates well in an online setting. Moreover, we show how the synaptic competition results provide information about novelty in the input, based on which we develop a feature-learning architecture that dynamically adjusts its size to the complexity of the dataset. We compare the performance of the proposed architecture to lateral inhibition on the task of unsupervised feature learning. Finally, we demonstrate high-accuracy results from an experimental realization of the architecture using a prototype neuromorphic platform with phase-change-based synapses.
GPS Meteorology: Direct Estimation of the Absolute Value of Precipitable Water (1996)

A simple approach to estimating vertically integrated atmospheric water vapor, or precipitable water, from Global Positioning System (GPS) radio signals collected by a regional network of ground-based geodetic GPS receiver is illustrated and validated. Standard space geodetic methods are used to estimate the zenith delay caused by the neutral atmosphere, and surface pressure measurements are used to compute the hydrostatic (or “dry”) component of this delay. The zenith hydrostatic delay is subtracted from the zenith neutral delay to determine the zenith wet delay, which is then transformed into an estimate of precipitable water. By incorporating a few remote global tracking stations (and thus long baselines) into the geodetic analysis of a regional GPS network, it is possible to resolve the absolute (not merely the relative) value of the zenith neutral delay at each station in the augmented network. This approach eliminates any need for external comparisons with water vapor radiometer observations and delivers a pure GPS solution for precipitable water. Since the neutral delay is decomposed into its hydrostatic and wet components after the geodetic inversion, the geodetic analysis is not complicated by the fact that some GPS stations are equipped with barometers and some are not. This approach is taken to reduce observations collected in the field experiment GPS/STORM and recover precipitable water with an rms error of 1.0–1.5 mm.
An extended family of Fc receptor relatives (2005)

A surprising number of Fc receptor (FcR) relatives have been recognized recently with the potential capacity to modulate innate and adaptive immune responses. The six human FcR homologs (FcRH1-6), which belong to a phylogenetically conserved gene family, have variable numbers of extracellular immunoglobulin domains of five different subtypes. FcRH immunoregulatory potential is implicated by the presence of consensus tyrosine-based activation or inhibition motifs in their cytoplasmic tails. All but one of these new receptors, FcRH6, are expressed on B cells at different stages in differentiation. Their ligands, function, and prospective roles as diagnostic B cell markers and therapeutic targets are topics of intense interest.
A coded-aperture technique allowing x-ray phase contrast imaging with conventional sources (2007)

Phase contrast imaging ͑PCI͒ solves the basic limitation of x-ray imaging, i.e., poor image contrast resulting from small absorption differences.Up to now, it has been mostly limited to synchrotron radiation facilities, due to the stringent requirements on the x-ray source and detectors, and only one technique was shown to provide PCI images with conventional sources but with limits in practical implementation.The authors propose a different approach, based on coded apertures, which provides high PCI signals with conventional sources and detectors and imposes practically no applicability limits.They expect this method to cast the basis of a widespread diffusion of PCI.
An improved synthetic route to huperzine A; new analogues and their inhibition of acetylcholinesterase (1993)

A bicycloannulation approach to huperzine A is detailed together with syntheses of the methylene analogue 8, the diamino compound 12 and their inhibition of acetylcholinesterase.
Localization and control of activity in peripheral nerves (2008)

Interest in the field of the natural control of human limb using physiological signals has risen dramatically in the past 20 years due to the success of the brain machine interface. Cortical signals carry significant information but are difficult to access. The peripheral nerves of the body carry both command and sensory signals and are far more accessible. While numerous studies have documented the selective stimulation properties of, conventionally round, nerve cuff electrodes (i.e., transverse geometry) and even self-sizing electrodes, recording the activity levels from individual fascicles using these electrodes is still an unsolved problem. Moreover, the control algorithms for the control of joint movement with multiple contact electrodes such as the flat interface nerve electrode (FINE) have been difficult to implement. We propose solutions to both these problems by using beam forming techniques to detect the location and the activity in various fascicles. We also developed a control algorithm that separates the dynamic from the passive properties to solve the redundancy problem in multiple joint problems. This techniques could find application in the natural control of artificial limbs from peripheral nerve signals for patients with amputated limbs or to restore function in patients with stroke or paralyzed limbs.
Embedded multiple description scalar quantizers for progressive image transmission (2003)

Robust progressive image transmission over unreliable channels with variable bandwidth requires multiple description coding (MDC) systems that produce highly error-resilient embedded bit-streams. The proposed embedded multiple description scalar quantizers (EMDSQ) meet the desired features consisting of a high redundancy level, fine grain rate adaptation and progressive transmission of each description. Experimental results show that EMDSQ yield better rate-distortion performance in comparison to the multiple description uniform scalar quantizers (MDUSQ) previously proposed in the literature. Moreover, the generalized form of EMDSQ targeting an arbitrary number of channels is proposed, which offers the possibility of designing realistic coders for practical multi-channel communication systems.
A Novel Joint Precoder and Receiver Design with Imperfect CSI for Multi-User MIMO Downlink (2014)

This paper studies the design of a linear precoder and receiver for the downlink of multi-user multiple-input multiple-output (MIMO) systems with imperfect channel state information (CSI). First, we modify the regularized block diagonalization scheme for the case of imperfect CSI, where we assume the variance of the channel estimation error is known. Next, we propose a novel joint design for the optimized precoder and receiver pair based on the minimum mean square error (MMSE) criterion, where we introduce two transmit channel matrices designed for high signal-to-noise ratio conditions. We compare the performance of these schemes with the generalized MMSE channel inversion filtering via numerical analysis. The results demonstrate the superiority of our joint precoder and receiver design.
Simulation and process flow of radiation sensors based on chalcogenide glasses for in situ measurement capability (2012)

Abstract In this work we present data about electronic devices based on a planar structure; inert electrode/nanophase chalcogenide glass/inert electrode in close proximity with a source of silver (Ag) oriented laterally over the chalcogenide glass film. The conductivity of the devices changes with radiation and it can be measured by contacting the two inert electrodes. Spacing of the electrodes was chosen after an in‐depth investigation into the electric field (E‐field) and E‐field energy displacement simulations with the aid of COMSOL multi‐physics software. Simulations have been used to enlighten a specific device structure to perform in situ measurements. Bias voltages, inert electrode material and thickness of the films were used as standards for all different types of simulations while only varying the spacing and the geometries to affect the E‐fields. It has been established from the experimental results that a 1 V bias is the most appropriate for the device performance and this is the voltage used in the simulations. The key motivation for this research is to find appropriate dimensions and geometry, which do not cause a change in conduction as a direct result of the applied E‐field, but rather effectively contribute to the establishment of only the radiation induced change of the device conductivity. The process flow for the device fabrication is described and data from the device performance are presented as well. The radiation induced Ag doping is mapped in the device volume using electron dispersion X‐ray spectroscopy (EDS) (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fibre optic temperature sensing; a new tool for temperature measurements in boreholes (1996)

Abstract Usually, the temperature in boreholes is determined using a standard temperature probe. The logging technique is either "stop and go", or the probe is lowered as a moving probe into the borehole using a controlled speed. Distributed temperature probe arrays installed permanently in a borehole are an alternative to moving probes and can be applied especially for temperature monitoring even under conditions where moving probes cannot be used. The distributed optical fiber sensing technique represents a new approach for temperature measurements. The basis for this method is given in Boiarski (1993), Dakin et al. (1985), Farries and Rogers (1984), Hartog and Gamble (1991), Rogers (1988), Rogers (1993). First results using fiber optic temperature sensing in boreholes and temperature monitoring for studying geotechnical and environmental problems (e.g., waste deposits) are published in Hurtig et al. (1993; 1994; 1995) and Hurtig and Schroetter (1993).
Knockdown of miR-23, miR-27, and miR-24 Alters Fetal Liver Development and Blocks Fibrosis in Mice (2016)

MicroRNAs (miRNAs) regulate cell fate selection and cellular differentiation. miRNAs of the miR23b polycistron (miR-23b, miR-27b, and miR-24) target components of the TGF-β signaling pathway and affect murine bile ductular and hepatocyte cell fate selection in vitro. Here we show that miR-23b polycistron miRNAs directly target murine Smad4, which is required for TGF-β signaling. Injection of antagomirs against these miRNAs directly into E16.5 murine fetuses caused increased cytokeratin expression in sinusoids and primitive ductular elements throughout the parenchyma of newborn mice. Similar antagomir injection in newborn mice increased bile ductular differentiation in the liver periphery and reduced hepatocyte proliferation. Antagomir injection in newborn Alb/TGF-β1 transgenic mice that develop fibrosis inhibited the development of fibrosis, and injection of older mice caused the resolution of existing fibrosis. Furthermore, murine stellate cell activation, including ColA1 and ACTA2 expression, is regulated by miR-23b cluster miRNAs. In summary, knockdown of miR-23b cluster miRNAs in fetal and newborn liver promotes bile duct differentiation and can block or revert TGF-β-induced liver fibrosis that is dependent on stellate cell activation. These data may find practical application in the highly needed development of therapies for the treatment of fibrosis.
Liver Replacement Therapy (2012)

The realization of a support device able to effectively replace liver function in patients with hepatic failure has thus far been an elusive goal. The complexity of liver metabolic, synthetic, detoxifying, and excretory functions make artificial hepatic support extremely challenging. Currently, no specific treatment is available to reverse acute or acute-on-chronic liver failure, and morbidity and mortality of these syndromes are still high. Present management strategies are supportive, while waiting for spontaneous liver regeneration or liver transplant. Because of the scarcity of donor organs, liver support strategies are needed for patients with inadequate liver function until an appropriate organ becomes available for transplantation or until their liver recovers from injury. Currently available liver support systems comprise nonbiological systems (e.g., hemodiafiltration, albumin dialysis, and plasma exchange) and bioartificial systems utilizing viable liver cells. The role for these novel systems and their impact on survival or other clinically important outcomes are controversial. Development and use of bioartificial systems are limited by the inherent cost.
A capacitance solver for incremental variation-aware extraction (2008)

Lithographic limitations and manufacturing uncertainties are resulting in fabricated shapes on wafer that are topologically equivalent, but geometrically different from the corresponding drawn shapes. While first-order sensitivity information can measure the change in pattern parasitics when the shape variations are small, there is still a need for a high-order algorithm that can extract parasitic variations incrementally in the presence of a large number of simultaneous shape variations. This paper proposes such an algorithm based on the wellknown method of floating random walk (FRW). Specifically, we formalize the notion of random path sharing between several conductors undergoing shape perturbations and use it as a basis of a fast capacitance sensitivity extraction algorithm and a fast incremental variational capacitance extraction algorithm. The efficiency of these algorithms is further improved with a novel FRW method for dealing with layered media. Our numerical examples show a 10X speed up with respect to the boundary-element method adjoint or finite-difference sensitivity extraction, and more than 560X speed up with respect to a non-incremental FRW method for a high-order variational extraction.
Ovarian antibodies, FSH and inhibin B: independent markers associated with unexplained infertility (2000)

Premature menopause and unexplained infertility are associated with ovarian antibodies, a marker of ovarian autoimmunity. In premature menopause, FSH is also elevated while in unexplained infertility FSH concentrations are often normal. The relationship of ovarian antibodies and FSH and inhibin B, as markers of follicle function, was investigated in unexplained infertility. Ovarian antibodies were determined by immunoassay in comparison to normal controls (n = 12); 51.9% were positive at two SD (P < 0.05) and 38.5% were positive at three SD above the control mean (P < 0.01). In this study three SD above the control mean was considered positive. In unexplained infertility, three out of 10 (30%) had elevated day 3 FSH (>10 mIU/ml) and ovarian antibodies, while 17/42 (40%) had normal FSH (<10 mIU/ml) and ovarian antibodies. In women with normal FSH, two out of seven (29%) had low inhibin B concentrations (<33 pg/ml) and ovarian antibodies, and 15/35 (43%) had normal inhibin B concentrations (> 33 pg/ml) and ovarian antibodies. Similarly, when women with and without ovarian antibodies were compared there was no difference in mean FSH or mean inhibin B concentrations. Thus, unlike other endocrine autoimmune disorders, hormone concentrations are not predictors of potential ovarian autoimmunity. This suggests that in unexplained infertility ovarian antibodies are an independent marker of potential ovarian failure, and may precede changes in regulatory hormones.
Immunization of experimental animals with dihydrolipoamide acetyltransferase, as a purified recombinant polypeptide, generates mitochondrial antibodies but not primary biliary cirrhosis (1989)

The availability of recombinant mitochondrial autoantigens may permit the experimental study of the pathophysiology of primary biliary cirrhosis. Previously, we demonstrated that high-titer antibodies to the 74 kD mitochondrial autoantigen dihydrolipoamide acetyltransferase could be generated when BALB/c mice were immunized with purified recombinant protein. Based on these data, we attempted an 8-month study to induce antibodies and liver dysfunction by immunizing AKR/J, C3H/J and CBA/HeJ mice as well as rats, guinea pigs, rabbits and rhesus monkeys with purified recombinant human dihydrolipoamide acetyltransferase. Antibodies to dihydrolipoamide acetyltransferase were readily induced and detected in all species of experimental animals with species and strain differences in the titer of the responses. Of particular interest, rabbits and guinea pigs produced antibodies which were specifically reactive with the functional site of dihydrolipoamide acetyltransferase, whereas the other strains and species produced antibodies to other epitopes on the molecule. Finally, similar to data on humans with primary biliary cirrhosis, the pyruvate dehydrogenase enzyme pathway was inhibited in the presence of immunized animal sera. These data imply that features other than simply an antibody response to mitochondrial enzymes are required for the development of primary biliary cirrhosis. Further studies will be necessary to determine the mechanisms by which mitochondrial proteins elicit an immune response.
ChemInform Abstract: ANTIMYCOTIC AZOLES. 6. SYNTHESIS AND ANTIFUNGAL PROPERTIES OF TERCONAZOLE, A NOVEL TRIAZOLE KETAL (1983)

Abstract Ausgehend von dem Triazol (II) erhält man mit (I) die an Kieselgel chromatographisch trennbaren Triazolyl‐Derivate (III) und (IV).
How to tell an airport from a home (2010)

Today's Internet services increasingly use IP-based geolocation to specialize the content and service provisioning for each user. However, these systems focus almost exclusively on the current position of users and do not attempt to infer or exploit any qualitative context about the location's relationship with the user (e.g., is the user at home? on a business trip?). This paper develops such a context by profiling the usage patterns of IP address ranges, relying on known user and machine identifiers to track accesses over time. Our preliminary results suggest that rough location categories such as residences, workplaces, and travel venues can be accurately inferred, enabling a range of potential applications from demographic analyses to ad specialization and security improvements.