gebhart/patrepeval huggingface dataset:
The spatial distribution and relative abundance of gap-junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system (1993)

Electrical coupling between heart muscle cells is mediated by specialised regions of sarcolemmal interaction termed gap junctions. In previous work, we have demonstrated that connexin42, a recently identified gap-junctional protein, is present in the specialised conduction tissues of the avian heart. In the present study, the spatial distribution of the mammalian homologue of this protein, connexin40, was examined using immunofluorescence, confocal scanning laser microscopy and quantitative digital image analysis in order to determine whether a parallel distribution occurs in rat. Connexin40 was detected by immunofluorescence in all main components of the atrioventricular conduction system including the atrioventricular node, atrioventricular bundle, and Purkinje fibres. Quantitation revealed that levels of connexin40 immunofluorescence increased along the axis of atrioventricular conduction, rising over 10-fold between atrioventricular node and atrioventricular bundle and a further 10-fold between atrioventricular bundle and Purkinje fibres. Connexin40 and connexin43, the principal gap-junctional protein of the mammalian heart, were co-localised within atrioventricular nodal tissues and Purkinje fibres. By applying a novel photobleach/double-labelling protocol, it was demonstrated that connexin40 and connexin43 are co-localised in precisely the same Purkinje fibre myocytes. A model, integrating data on the spatial distribution and relative abundance of connexin40 and connexin43 in the heart, proposes how myocyte-type-specific patterns of connexin isform expression account for the electrical continuity of cardiac atrioventricular conduction.
A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters (2006)

A striking feature of the human genome is the dearth of CpG dinucleotides (CpGs) interrupted occasionally by CpG islands (CGIs), regions with relatively high content of the dinucleotide. CGIs are generally associated with promoters; genes, whose promoters are especially rich in CpG sequences, tend to be expressed in most tissues. However, all working definitions of what constitutes a CGI rely on ad hoc thresholds. Here we adopt a direct and comprehensive survey to identify the locations of all CpGs in the human genome and find that promoters segregate naturally into two classes by CpG content. Seventy-two percent of promoters belong to the class with high CpG content (HCG), and 28% are in the class whose CpG content is characteristic of the overall genome (low CpG content). The enrichment of CpGs in the HCG class is symmetric and peaks around the core promoter. The broad-based expression of the HCG promoters is not a consequence of a correlation with CpG content because within the HCG class the breadth of expression is independent of the CpG content. The overall depletion of CpGs throughout the genome is thought to be a consequence of the methylation of some germ-line CpGs and their susceptibility to mutation. A comparison of the frequencies of inferred deamination mutations at CpG and GpC dinucleotides in the two classes of promoters using SNPs in human-chimpanzee sequence alignments shows that CpGs mutate at a lower frequency in the HCG promoters, suggesting that CpGs in the HCG class are hypomethylated in the germ line.
An overview on data representation learning: From traditional feature learning to recent deep learning (2016)

Since about 100 years ago, to learn the intrinsic structure of data, many representation learning approaches have been proposed, either linear or nonlinear, either supervised or unsupervised, either “shallow” or “deep”. Particularly, deep architectures are widely applied for representation learning in recent years, and have delivered top results in many tasks, such as image classification, object detection and speech recognition. In this paper, we review the development of data representation learning methods. Specifically, we investigate both traditional feature learning algorithms and state-of-the-art deep learning models. The history of data representation learning is introduced, while available online resources (e.g., courses, tutorials and books) and toolboxes are provided. At the end, we give a few remarks on the development of data representation learning and suggest some interesting research directions in this area.
Micropatterns of a Cell-Adhesive Peptide on an Amphiphilic Comb Polymer Film (2002)

We report in this paper a generic method to modify the surfaces of common polymeric biomaterials that enables spatially resolved attachment and growth of mammalian cells in a biologically relevant milieu. We demonstrate that an amphiphilic comb polymer presenting short oligoethylene glycol side chains can be coated onto a number of different polymeric biomaterials, namely polystyrene, poly(methyl methacrylate), and poly(ethylene terephthalate) from a methanol/water mixture. The comb polymer film is stable in water and presents reactive COOH groups at the oligoethylene glycol chain ends, thereby permitting the surface of the comb polymer to be patterned with a cell adhesive, arg-gly-asp peptide. The micropatterned surfaces spatially confine the attachment and growth of fibroblasts for ∼24 h in 10% serum to the patterned regions.
Gain and linewidth enhancement factor in InAs quantum-dot laser diodes (1999)

Amplified spontaneous emission measurements are investigated below threshold in InAs quantum-dot lasers emitting at 1.22 μm. The dot layer of the laser was grown in a strained quantum well (QW) on a GaAs substrate. Ground state gain is determined from cavity mode Fabry-Perot modulation. As the injection current increases, the gain rises super-linearly while changes in the index of refraction decrease. Below the onset of gain saturation, the linewidth enhancement factor is as small as 0.1, which is significantly lower than that reported for QW lasers.
1-Chloro-2-deoxy-3,5-di-

p

-toluoyl-D-

erythro

-pentosyl Chloride - A Versatile Synthetic Intermediate (1991)

Abstract Syntheses of 1b-d is described using 1-chloro-2-deoxy-3,5-di-p-toluoyl-D-erythro-pentosyl chloride.
Promising diagnostic and therapeutic circRNAs for skeletal and chondral disorders (2021)

Circular RNAs (circRNAs) belong to a highly conserved subtype of non-coding RNAs, produced by the back-splicing of specific regions of pre-mRNA. CircRNAs have wide-ranging effects on eukaryotic physiology and pathology by acting as transcription regulators, miRNA sponges, protein sponges, and templates for translation. Skeletal and chondral disorders are the leading causes of pain and disability, especially for elders, affecting hundreds of millions of people worldwide. Plenty of evidence have shown that circRNAs are dysregulated and play vital roles in the occurrence and progression of skeletal and chondral disorders. Herein, we systematically summarize the emerging roles and underlying molecular mechanisms of hub circRNAs in the pathogenesis of several representative skeletal and chondral disorders. Our findings may provide further insight into the mechanistic details of the role of circRNA in bone or cartilage metabolism, and highlight the promising application of circRNAs in serving as potential diagnostic or therapeutic targets for the prevention and treatment of skeletal and chondral disorders.
An approach to electrical studies of single nanocrystals (1996)

We present electrical measurements of single Au and CdSe nanocrystals. The devices are fabricated using a hybrid scheme which combines electron beam lithography and wet chemistry to bind nanocrystals in tunneling contact between two closely spaced metallic leads. The current–voltage characteristics of these devices exhibit a Coulomb staircase with a charging energy of ∼50 meV. This technique is readily adapted to the study of a host of nanocrystals made by solution chemistry.
IBM S/390 Parallel Enterprise Server G5 fault tolerance: A historical perspective (1999)

Fault tolerance in IBM S/390® systems during the 1980s and 1990s had three distinct phases, each characterized by a different uptime improvement rate. Early TCM-technology mainframes delivered excellent data integrity, instantaneous error detection, and positive fault isolation, but had limited on-line repair. Later TCM mainframes introduced capabilities for providing a high degree of transparent recovery, failure masking, and on-line repair. New challenges accompanied the introduction of CMOS technology. A significant reduction in parts count greatly improved intrinsic failure rates, but dense packaging disallowed on-line CPU repair. In addition, characteristics of the microprocessor technology posed difficulties for traditional in-line error checking. As a result, system fault-tolerant design, particularly in CPUs and memory, underwent another evolution from G1 to G5. G5 implements an innovative design for a high-performance, fault-tolerant single-chip microprocessor. Dynamic CPU sparing delivers a transparent concurrent repair mechanism. A new internal channel provides a high-performance, highly available Parallel Sysplex® in a single mainframe. G5 is both the culmination of decades of innovation and careful implementation, and the highest achievement of S/390 fault-tolerant design.
Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals (2005)

We investigated human alternative protein isoforms of >2600 genes based on full-length cDNA clones and SwissProt. We classified the isoforms and examined their co-occurrence for each gene. Further, we investigated potential relationships between these changes and differential subcellular localization. The two most abundant patterns were the one with different C-terminal regions and the one with an internal insertion, which together account for 43% of the total. Although changes of the N-terminal region are less common than those of the C-terminal region, extension of the C-terminal region is much less common than that of the N-terminal region, probably because of the difficulty of removing stop codons in one isoform. We also found that there are some frequently used combinations of co-occurrence in alternative isoforms. We interpret this as evidence that there is some structural relationship which produces a repertoire of isoformal patterns. Finally, many terminal changes are predicted to cause differential subcellular localization, especially in targeting either peroxisomes or mitochondria. Our study sheds new light on the enrichment of the human proteome through alternative splicing and related events. Our database of alternative protein isoforms is available through the internet.
Chemical Vapor Deposition of Epitaxial Silicon from Silane at Low Temperatures: II . Plasma Enhanced Deposition (1989)

The deposition of epitaxial silicon films at temperatures from 600°–800°C by both very low‐pressure chemical vapor deposition (VLPCVD) and plasma‐enhanced chemical vapor deposition (PECVD) has been examined. The VLPCVD deposition process was described in detail in Part I of this series. Plasma enhancement of the deposition process led to enhanced growth rates without a change in the apparent activation energy, and the mild ion bombardment (plasma) exposure during deposition introduced no observable stacking faults or dislocations. The effects of plasma power, argon dilution, and hydrogen dilution on the efficiency of the plasma deposition enhancement with very low total pressures (1–10 mtorr) were examined. Under the conditions employed here, power coupling efficiency is relatively low and growth rate enhancement does not become significant until temperatures are below 700°C. The implications of these observations for future PECVD applications for epitaxial deposition are discussed.
Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells (1997)

The loss of tyrosinase, the key enzyme in melanin synthesis, has been implicated in the dedifferentiation of malignant melanocytes. The presence of tyrosinase transcripts and antigenic peptides in melanoma tumors prompted us to investigate whether the basis for the loss of the enzyme was proteolytic degradation. Toward this aim, we followed the kinetics of synthesis, degradation, processing, chaperone binding, inhibitor sensitivity, and subcellular localization of tyrosinase in normal and malignant melanocytes. We found that, in amelanotic melanoma cell lines, tyrosinase failed to reach the melanosome, the organelle for melanin synthesis, because it was retained in the endoplasmic reticulum (ER) and then degraded. Tyrosinase appeared mostly as a 70-kDa core-glycosylated, endoglycosidase H-sensitive, immature form bound to the ER chaperone calnexin and had a life-span of only 25% of normal. Maturation and transit from the ER to the Golgi compartment was facilitated by lowering the temperature of incubation to 31 degrees C. Several proteasome inhibitors caused the accumulation of an approximately 60-kDa tyrosinase doublet that was more prominent in malignant than in normal melanocytes and promoted, to various degrees, the maturation of tyrosinase in melanoma cells and the translocation of the enzyme to melanosomes. The appearance of ubiquitinated tyrosinase after treatment of normal melanocytes with N-acetyl-L-leucinyl-L-leucinal-L-norleucinal reinforced our notion that some tyrosinase is normally degraded by proteasomes. Proteolysis of tyrosinase by proteasomes is consistent with the production of antigenic tyrosinase peptides that are presented to the immune system by major histocompatibility complex class I molecules.
HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3 (2004)

HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca 2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca 2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P 3 (also known as LPB 3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P 3 -deficient mice, Akt phosphorylation and Ca 2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P 3mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.
Spectral beam combining of high-power fiber lasers (2004)

We have demonstrated spectral beam combining of two high power fiber lasers and obtained more than 40 W output power from the system. The system consists of two 30 W fiber lasers, a diffraction grating and a resonator. Both fiber lasers have broadband fiber Bragg gratings on the rear sides and share the diffraction grating and output coupler on the output sides. The wavelengths of the fiber lasers are determined by the optical dispersion provided by the grating and the collimating lens, as well as the fiber spacing. A model that analyzes dependence of laser line-width on beam quality of an SBC system is given in this paper. We also model a novel configuration that can significantly improve beam quality. The experimental results have shown that control of fiber laser line-width is the key to achieving high power SBC lasers. In addition, a new approach using three gratings is proposed and has been proven by the experiment. The new approach consists of three gratings, in which one grating is used by the SBC cavity to lock wavelengths while the other two combine the collimated beams without beam quality reduction. This approach has successfully improved beam quality M<sup>2</sup> from 11 to 2.0.
NMR of macromolecules : a practical approach (1993)

Sample preparation Instrumentation and pulse sequences Resonance assignment strategies for small proteins Stable isotope labelling and resonance assignments in larger proteins Effects of chemical exchange on NMR spectra NMR studies of protein-ligand interactions NMR of nucleic acids from spectrum to structure 1H NMR studies of oligosaccharides Structure determination from NMR data Analysis of NMR data Structure determination from NMR data Computational approaches.
Generation of Human Antigen-Specific Monoclonal IgM Antibodies Using Vaccinated “Human Immune System” Mice (2010)

This work provides the proof-of-concept for the usefulness of this novel method based on the immunization of humanized mice for the rapid generation of human mAbs against a wide range of antigens.
Identification of Novel Low Molecular Weight CXCR4 Antagonists by Structural Tuning of Cyclic Tetrapeptide Scaffolds (2005)

A highly potent CXCR4 antagonist, compound 2, was previously found by using two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries based on the pharmacophore of a 14-mer peptidic antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by disulfide and olefin bridges were synthesized to find novel scaffold structures different from that of cyclic pentapeptides. These compounds contain a reduced number of peptide bonds compared to compound 2. Furthermore, several analogues with chemical modification of the side chain of Arg(4) in 2 were also prepared. From these, several new leads possessing high to moderate CXCR4-antagonistic activity were characterized.
A new method of antitumor therapy with a high dose of TNF perfusion for unresectable liver tumors. (2000)

There are primary and secondary malignant liver tumors for which principal treatment is surgical resection. There is no established treatment for unresectable malignant liver tumors, however, and the prognosis for these is quite poor. An effective treatment for malignant liver tumors is thus urgently needed. Recent advances in molecular biology have uncovered the structures and/or functions of many cytokines thought to have a strong relation with the mechanisms of the antitumor effect of biological therapies. Availability of those cytokines in large amounts and homogeneously owing to advances in recombinant technology makes it possible to use them clinically. Among cytokines demonstrating antitumor activities, tumor necrosis factor-alpha (TNF-alpha) is one of the strongest. However, severe toxicity such as hypotension, abnormalities in liver function, leukopenia, chill and thrombus formation makes TNF-alpha difficult to use systemically as an antitumor drug. To enhance cytotoxicity while decreasing the side effects, especially hypotension, we developed a mutein called TNF-SAM2 by protein-engineering. The biological activity of TNF-SAM2 was more beneficial than TNF-alpha for antitumor therapy, since its side effects were milder. In contrast, using the isolated limb perfusion (ILP) method against malignant melanoma and soft tissue sarcoma of the extremities in combination with TNF-alpha and melphalan, a high response rate of 70-100% was observed. These observations led to the re-evaluation of TNF as an antitumor drug. A preliminary clinical trial was done using TNF-alpha combined with the formation of a closed circuit (isolated hepatic perfusion method) targeting the liver and a response rate of over 75% was achieved against malignant liver tumors. To isolate the liver from the systemic circulation, however, required a laparotomy, so that patients were subjected to excessive surgical stress. Isolated hypoxic hepatic perfusion (IHHP) using balloon catheters is a treatment developed to overcome such stress and we are planning to do clinical trials of IHHP with TNF-SAM2 in combination with a chemotherapeutic agent against malignant liver tumor patients. IHHP combined with TNF-SAM2 and a chemotherapeutic agent might be more beneficial in antitumor effects as well as in maintaining good quality of life (QOL) for the patient.
Heat transfer analysis of Staphylococcus aureus on stainless steel with microwave radiation (1999)

Staphylococcus aureus (NCTC 6571; Oxford strain) on stainless steel discs was exposed to microwave radiation at 2450 MHz and up to 800 W. Cell viability was reduced as the exposure time increased, with complete bacterial inactivation at 110 s, attaining a temperature of 61.4 degrees C. The low rate of temperature rise, RT, of the bacterial suspension as compared with sterile distilled water or nutrient broth suggests a significant influence of the microwave sterilization efficacy on the thermal properties of the micro-organisms. The heat transfer kinetics of thermal microwave irradiation suggest that the micro-organism has a power density at least 51-fold more than its surrounding liquid suspension. When the inoculum on the stainless steel disc was subjected to microwave radiation, heat conduction from the stainless steel to the inoculum was the cause of bacteriostasis with power absorbed at 23.8 W for stainless steel and 0.16 W for the bacteria-liquid medium. This report shows that the microwave killing pattern of Staph. aureus on stainless steel was mainly due to heat transfer from the stainless steel substrate and very little direct energy was absorbed from the microwaves.
ApoC‐I and ApoC‐III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke (2004)

Early diagnosis and immediate therapeutic interventions are crucial factors to reduce the damage extent and the risk of death. Currently, the diagnosis of stroke relies on neurological assessment of the patient and neuro-imaging techniques including computed tomography and/or magnetic resonance imaging scan. An early diagnostic marker of stroke, ideally capable to discriminate ischemic from hemorrhagic stroke would considerably improve patient acute management. Using surface-enhanced laser desorption/ionization (SELDI) technology, we aimed at finding new early diagnostic plasmatic markers of stroke. Strong anionic exchange (SAX) SELDI profiles of plasma samples from 21 stroke patients were compared to 21 samples from healthy controls. Seven peaks appeared to be differentially expressed with significant p values (p < 0.05). Proteins were stripped from the SAX chips, separated on a one-dimensional electrophoresis (1-DE) gel and stained using mass spectrometry (MS)-compatible silver staining. Following in-gel tryptic digestion, the peptides were analyzed by MS. Four candidate proteins were identified as apolipoprotein CI (ApoC-I), apolipoprotein CIII (ApoC-III), serum amyloid A (SAA), and antithrombin-III fragment (AT-III fragment). Assessment of ApoC-I and ApoC-III levels in plasma samples using a sandwich enzyme-linked immunosorbent assay (ELISA) allowed to distinguish between hemorrhagic (n = 15) and ischemic (n = 16) stroke (p < 0.001). To the best of our knowledge, ApoC-I and ApoC-III are the first reported plasmatic biomarkers capable to accurately distinguish between ischemic and hemorrhagic stroke in a small number of patients. It requires further investigation in a large cohort of patients.