gebhart/patrepeval huggingface dataset:
Targeting intracellular and extracellular alpha-synuclein as a therapeutic strategy in Parkinson's disease and other synucleinopathies (2012)

Counteracting intracellular and extracellular effects of α-Synuclein represents a valid therapeutic target in neurodegeneration. In particular, strategies that target α-Synuclein through limitation of its burden at the transcriptional and post-transcriptional level, inhibition of its aggregation or of aberrant phosphorylation states, immunization or attenuation of its secretion and propagation may be therapeutic options.
Femtosecond pulse amplification at 250 kHz with a Ti:sapphire regenerative amplifier and application to continuum generation (1992)

Ultrashort optical pulses have been amplified to 1.7 μJ of energy at a repetition rate of 250 kHz with a novel cw argon-pumped Ti:sapphire regenerative amplifier. Acousto-optic switching of the amplifier is used to achieve the high repetition rate. Chirped-pulse amplification is used to avoid nonlinear effects in the amplifier. After recompression, 1-μJ, 130-fs pulses are obtained and are used to generate a white-light continuum in an ethylene glycol jet.
Membrane Protein–Lipid Interactions in Mixed Micelles Studied by NMR Spectroscopy with the Use of Paramagnetic Reagents (2004)

For solution NMR studies of the structure and function of membrane proteins, these macromolecules have to be reconstituted and solubilized in detergent micelles. Detailed characterization of the mixed detergent/protein micelles is then of key importance to validate the results from such studies, and to evaluate how faithfully the natural environment of the protein in the biological membrane is mimicked by the micelle. In this paper, a selection of paramagnetic probes with different physicochemical properties are used to characterize the 60 kDa mixed micelles consisting of about 90 molecules of the detergent dihexanoylphosphatidylcholine (DHPC) and one molecule of the Escherichia coli outer-membrane protein X (OmpX), which had previously been extensively studied by solution NMR techniques. The observation of highly selective relaxation effects on the NMR spectra of OmpX and DHPC from a water-soluble relaxation agent and from nitroxide spin labels attached to lipophilic molecules, confirmed data obtained previously with more complex NMR studies of the diamagnetic OmpX/DHPC system, and yielded additional novel insights into the protein-detergent interactions in the mixed micelles. The application of paramagnetic probes to the well-characterized OmpX/DHPC system indicates that such probes should be widely applicable as an efficient support of NMR studies of the topology of mixed membrane protein-detergent micelles.
Video codec incorporating block-based multihypothesis motion-compensated prediction (2000)

Multi-hypothesis prediction extends motion compensation with one prediction signal to the linear superposition of several motion-compensated prediction signals. These motion- compensated prediction signals are referenced by motion vectors and picture reference parameters. This paper proposes a state-of-the-art video codec based on the ITU-T Recommendation H.263 that incorporates multi-hypothesis motion-compensated prediction. In contrast to B-Frames, reference pictures are always previously decoded pictures. It is demonstrated that two hypotheses are efficient for practical video compression algorithms. In addition, it is shown that multi-hypothesis motion-compensated prediction and variable block size prediction can be combined to improve the overall coding gain. The encoder utilizes rate- constrained coder control including rate-constrained multi- hypothesis motion estimation. The advanced 4-hypothesis codec improves coding efficiency up to 1.8 dB when compared to the advanced prediction codec with ten reference frames for the set of investigated test sequences.
Studies of the glomerular mesangium and the juxtaglomerular apparatus in the genetically diabetic mouse. (1980)

Intact and uninephrectomized genetically diabetic (db/db) mice (C57BL/KsJ) and their nondiabetic littermates (dm/m) had renal biopsies performed at 6 months of age. Renal tissues were studied by regular light microscopy and by a variety of immunohistochemical techniques. Intact db/db mice had peripheral mesangial thickening as compared to db/m mice. This thickening, predominantly due to increased mesangial matrix material, extended to the glomerular hilum and the extraglomerular mesangium of the juxtaglomerular apparatus. This abnormality was markedly increased an uninephrectomized db/db mice (db/db-UN) compared to intact db/db mice. Db/m-UN animals had slightly greater mesangial thickness than intact db/mice but less than that of db/db mice. Intact db/db mice had increased mesangial IgM staining compared to db/m mice and these differences were magnified by uninephrectomy. The IgM staining, especially in the diabetic mice, involved the peripheral mesangium and the glomerular hilum extending into extraglomerular mesangium and the distal tubule at the level of the macula densa. The tubular staining in the region of the juxtaglomerular apparatus was between the tubular basement membrane and the epithelial cells and between epithelial cells. The distal tubular epithelial cell cytoplasm also showed increased staining for IgM as the tubule coursed away from the glomerulus. These studies amplify the argument that alterations in glomerular hemodynamics influence the rate of development of diabetic glomerular lesions. Further, these diabetic mice appear to represent an important model for the study of mesangial macromolecular processing mechanisms.
Development of a fast and easy method for Escherichia coli genome editing with CRISPR/Cas9 (2016)

In this study, we developed a fast and easy genome editing procedure based on CRISPR/Cas9 system that only required the work of one plasmid construction and one transformation, which allowed modification of a chromosome locus within 3 days and could be performed continuously for multiple loci.
Public Safety on Wharves (1999)

A recent escalation in the number of legal actions being brought against wharf owners; in conjunction with both an increasing general perception that all public facilities are safe and the need to provide appropriate access for the disabled; has given rise to a requirement for passenger facilities to be designed to meet far higher safety standards than was acceptable in the past. There does not however appear to be a single reference standard for these safety requirements. Accordingly, a range of publications (both Australian and overseas) have been examined to establish a consensus of the likely acceptable safety standards for public wharves. It is evidenced from this review that vessel access should be either across a gangway or from wide landings; that the vessel/landing gap should be less than 100 mm in all situations where no gangway is provided; and that stairways and landings should have non-slip surfaces and edge highlighting. Consideration should also be given to replacing stairways with ramps to provide safe access for wheelchairs. Pedestrians should be kept separate from any fuelling and vehicular activities and non-desirable pastimes such as diving and fishing should be discouraged or carefully controlled.
Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG (2009)

The Escherichia coli McrA protein, a putative C(5)-methylcytosine/C(5)-hydroxyl methylcytosine-specific nuclease, binds DNA with symmetrically methylated HpaII sequences (Cm5CGG), but its precise recognition sequence remains undefined. To determine McrA's binding specificity, we cloned and expressed recombinant McrA with a C-terminal StrepII tag (rMcrA-S) to facilitate protein purification and affinity capture of human DNA fragments with m5C residues. Sequence analysis of a subset of these fragments and electrophoretic mobility shift assays with model methylated and unmethylated oligonucleotides suggest that N(Y > R) m5CGR is the canonical binding site for rMcrA-S. In addition to binding HpaII-methylated double-stranded DNA, rMcrA-S binds DNA containing a single, hemimethylated HpaII site; however, it does not bind if A, C, T or U is placed across from the m5C residue, but does if I is opposite the m5C. These results provide the first systematic analysis of McrA's in vitro binding specificity.
Raman spectroscopy as a probe of graphene and carbon nanotubes (2007)

Progress in the use of Raman spectroscopy to characterize graphene samples for the number of graphene layers and doping level they contain is briefly reviewed. Comparisons to prior studies on graphites and carbon nanotubes are used for inspiration to define future promising directions for Raman spectroscopy research on few layer graphenes.
A Catheter Based Method to Activate Urethral Sensory Nerve Fibers (2003)

To our knowledge this study provides the first documentation of generating bladder contractions via intraurethral electrical stimulation in cats and humans. This method provides a research tool for future studies to investigate these pathways in humans. Preliminary human results suggest that urethral afferent mediated neural pathways demonstrated in animal models exist in humans and support the development of neural prostheses using electrical stimulation of these nerves to restore control of bladder function in individuals with neurological disorders or SCI.
Cell cholesterol efflux: integration of old and new observations provides new insights (1999)

Numerous studies using a variety of cell/acceptor combinations have demonstrated differences in cholesterol efflux among cells. These studies also show that different acceptors, ranging from simple molecules like cyclodextrins to serum, stimulate efflux through a variety of mechanisms. By combining early observations with data derived from recent studies, it is now possible to formulate a model for cell cholesterol efflux which proposes that an array of different mechanisms, including aqueous diffusion, lipid-free apolipoprotein membrane microsolubilization, and SR-BI-mediated cholesterol exchange contribute to cholesterol flux. In this model the relative importance of each mechanism would be determined both by the cell type and the nature of the extracellular cholesterol acceptor.
Cell-based analysis of Chikungunya virus E1 protein in membrane fusion (2012)

Cells expressing amino acid substitutions of conserved protein E1 residues of E1-G91 and E1-H230 lost most of the CHIKV E1-mediated membrane fusion activity. Cells expressing mutations of less-conserved amino acids, E1-V178A and E1-A226V, retained membrane fusion activity to levels similar to those expressing wild type E1, but their fusion properties of pH threshold and cholesterol dependence were slightly altered.
Effects on renal hemodynamics of intra-arterial infusions of angiotensins I and II (1983)

Experiments were conducted in anesthetized dogs to evaluate the differences between the effects of intrarenal conversion of angiotensin I (ANG I) to angiotensin II (ANG II) and those of circulating ANG II on renal blood flow (RBF), glomerular filtration rate (GFR), peritubular capillary pressure (PCP), proximal tubular free-flow pressure (PTP), and stop-flow pressure (SFP). Equiconstrictor doses of ANG I and ANG II were infused into the renal arteries of dogs kept on normal and high sodium diets. In clearance experiments, RBF decreased by 23% (low dose) and 33% (high dose) during the infusion of either ANG I or ANG II; GFR was significantly reduced only during the ANG I infusion. In micropuncture experiments, in which the GFR responses were similar, there were significant reductions in PTP (23 +/- 3%) and PCP (33 +/- 3%) during the intrarenal ANG I infusion; SFP was not altered significantly. Afferent and efferent arteriolar resistances increased significantly during ANG I infusion as well as during infusion of ANG II. These results indicate that during intra-arterial infusion of ANG I, the conversion to ANG II within the kidney occurs early enough to decrease glomerular filtration rate through an apparent increase in preglomerular resistance.
Inhibition of experimental autoimmune encephalomyelitis by a nonimmunogenic non-self peptide that binds to I-Au (1992)

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory neurologic disease initiated by myelin basic protein-reactive CD4+ T cells, which are restricted by a particular MHC class II molecule. Recent studies have utilized inhibitor peptides that bind to restricting MHC class II molecules in order to inhibit EAE, presumably by means of competing with encephalitogenic epitopes. However, these studies leave open the possibility of alternative explanations, such as Ag-specific nonresponsiveness and immunodominance. In order to demonstrate that competition for MHC binding alone can inhibit EAE, the inhibitor peptide should ideally be structurally unrelated and nonimmunogenic yet physically associate with the MHC class II molecule. In this study, we show that the OVA-323-339 peptide, which is unrelated to the disease-inducing peptide, binds to A alpha uA beta u. However, although OVA-323-339 is extremely immunogenic in A alpha dA beta d-expressing BALB/c mice, it is nonimmunogenic in (PL/J x SJL)F1 and PL/J mice expressing A alpha uA beta u. When administered as a coimmunogen with Ac1-11, OVA-323-339 inhibited induction of EAE in (PL/J x SJL)F1 mice. Myelin basic protein-89-101, which does not bind A alpha uA beta u, had no effect on the disease process. This study provides evidence that MHC class II binding alone can modulate the induction of EAE. The use of a nonimmunogenic non-self peptide to modulate an autoimmune disease minimizes the potential complications of immunodominance or alternative regulatory mechanisms associated with immunogenic peptide therapies and further confirms the MHC-blocking model of immunosuppression.
T cell regulation of autoimmune interstitial nephritis. (1990)

Research in organ-specific autoimmunity has been greatly facilitated over the past decade by advances in cellular and molecular immunology. Such studies have greatly expanded our understanding of autoimmune effector mechanisms and the nature of the target antigens recognized by these mediators. Another facet of organ-specific autoimmunity concerns the definition of those factors that determine host susceptibility to disease. This review outlines studies performed in two models of autoimmune interstitial nephritis that focus on issues of susceptibility and tolerance to parenchymal self antigens. In both models, antigen-specific regulatory T cells modulate the effector limb of the nephritogenic immune response and the pattern of interstitial injury. This modulation can be either stimulatory or inhibitory. The dominant regulatory effect is linked to genes in the major histocompatibility locus and is tightly correlated with disease expression. Regulatory T cells which inhibit the nephritogenic immune response can also be cultured in vitro and are highly efficacious as a therapeutic modality. These studies provide both the background and requisite reagents for delineating the mechanism(s) underlying antigen-specific T cell regulation.
Comparison of Killer Ig-Like Receptor Genotyping and Phenotyping for Selection of Allogeneic Blood Stem Cell Donors (2005)

The repertoire of killer Ig-like receptors (KIRs) can be determined at the level of DNA, RNA, or surface protein expression for selection of blood stem cell donors. We compared genotyping and phenotyping of the four inhibitory KIRs that are important in transplantation for leukemia in 73 unrelated persons. In 5 (7%) of the 68 individuals in whom the KIR2DL1 gene was present and in 10 (15%) of the 67 in whom KIR3DL1 was present, the corresponding receptor was not expressed by NK cells, as determined by flow cytometry analysis. In contrast, one or both allelic forms of KIR2DL2/KIR2DL3 were expressed by a high proportion of NK cells in all 73 individuals. However if both KIR2DL2 and KIR2DL3 genes were present, KIR2DL3 was preferentially expressed, as transcripts of KIR2DL2 was not detectable by RT-PCR in 42% of these individuals. In total, repertoire assessment for the four KIRs by genotyping vs phenotyping was not in complete agreement in 18 (25%) of the 73 individuals. Furthermore, among the samples that tested positive for the expression of a certain KIR gene, the levels of transcripts and surface expression varied considerably as measured by both real-time quantitative PCR and flow cytometry analysis. Extension of this comparative analysis to include all 12 KIR family members showed that KIR2DL3 and KIR3DL2 were the only genes whose transcripts were consistently detectable. These results caution the use of genotyping alone for donor selection or leukemia-relapse prognostication because some KIRs may be expressed at a very low level.
Designing Surface‐Confined Coordination Oligomers (2010)

Designer materials: HOMO–LUMO engineering of coordination-based oligomers covalently bound to silicon or glass has been achieved by the use of a partially fluorinated chromophore (see graphic). The experimental and computationally derived physical chemical properties of these assemblies are compared to their non-fluorinated analogues. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
T Cells Responsive to Myelin Basic Protein in Patients with Multiple Sclerosis (1990)

Gene mutation in vivo in human T lymphocytes appears to occur preferentially in dividing cells. Individuals with multiple sclerosis (MS) are assumed to have one or more populations of diving T cells that are being stimulated by autoantigens. Mutant T cell clones from MS patients were isolated and tested for reactivity to myelin basic protein, an antigen that is thought to participate in the induction of the disease. The hypoxanthine guanine phosphoribosyltransferase (hprt) clonal assay was used to determine mutant frequency values in MS patients with chronic progressive disease. Eleven of 258 thioguanine-resistant (hprt-) T cell clones from five of the six MS patients who were tested proliferated in response to human myelin basic protein without prior in vitro exposure to this antigen. No wild-type clones from these patients, nor any hprt- or wild-type clones from three healthy individuals responded to myelin basic protein. Thus, T cell clones that react with myelin basic protein can be isolated from the peripheral blood of MS patients.
Seronegative Lyme Disease (1988)

The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder. Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean ( +/- SEM) stimulation index of 17.8 +/- 3.3, similar to that (15.8 +/- 3.2) in 18 patients with chronic Lyme disease who had detectable antibodies. The T-cell response of both groups was greater than that of a control group of healthy subjects (3.1 +/- 0.5; P less than 0.001). We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.
Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. (1988)

A monoclonal antibody (904) that binds to a leukocyte cell adhesion-promoting glycoprotein, (Mo1; CD11b/CD18) was administered (1 mg/kg, iv.) to open chest anesthetized dogs 45 min after the induction of regional myocardial ischemia. Ischemia was produced by occluding the left circumflex coronary artery (LCX) for 90 min and then reperfusing for 6 h. There was no difference between control and antibody treated groups with respect to arterial blood pressure, heart rate, or LCX blood flow. Administration of antibody produced no observable effect on circulating neutrophil counts, suggesting that antibody-bound neutrophils were not cleared from the circulation. The mean size of myocardial infarct expressed as percentage of the area at risk of infarction that resulted was reduced by 46% with anti-Mo1 treatment (25.8 +/- 4.7%, n = 8) compared to control (47.6 +/- 5.7%, n = 8; P less than 0.01). The area at risk of infarction was similar between groups. Circulating (serum) antibody excess was confirmed in all 8 anti-Mo1 treated dogs by immunofluorescence analysis. Analysis of ST segment elevation on the electrocardiogram as an indicator of the severity of ischemia suggests that the anti-Mo1 reduces infarct size independent of the severity of ischemia. An additional group of dogs (n = 5) was tested with a control monoclonal antibody of the same subtype (murine IgG1) and was found to produce no significant reduction in myocardial infarct size. Accumulation of neutrophils within the myocardium was significantly attenuated with 904 treatment when analyzed by histological methods. These data demonstrate that administration of anti-Mo1 monoclonal antibody after the induction of regional myocardial ischemia results in reduced myocardial reperfusion injury as measured by ultimate infarct size.
Lead Optimization of Thiazolo[5,4‐c]piperidines: 3‐Cyclobutoxy Linker as a Key Spacer for H3R Inverse Agonists (2012)

The simpler, the better: H(3) histamine receptor (H(3)R) are of interest as therapeutic targets in cognitive and somnolence disorders. Here, lead optimization of H(3)R inverse agonists bearing a thiazolo[5,4-c]piperidine group gave rise to a clinical candidate with a much simpler unprecedented benzamide scaffold, displaying decreased hERG activity while maintaining high brain receptor occupancies.
Concise Review: Stem/Progenitor Cells for Renal Tissue Repair: Current Knowledge and Perspectives (2013)

The kidney is a specialized low-regenerative organ with several different types of cellular lineages; however, the identity of renal stem/progenitor cells with nephrogenic potential and their preferred niche(s) are largely unknown and debated. Most of the therapeutic approaches to kidney regeneration are based on administration of cells proven to enhance intrinsic reparative capabilities of the kidney. Endogenous or exogenous cells of different sources were tested in rodent models of ischemia-reperfusion, acute kidney injury, or chronic disease. The translation to clinics is at the moment focused on the role of mesenchymal stem cells. In addition, bioproducts from stem/progenitor cells, such as extracellular vesicles, are likely a new promising approach for reprogramming resident cells. This concise review reports the current knowledge about resident or exogenous stem/progenitor populations and their derived bioproducts demonstrating therapeutic effects in kidney regeneration upon injury. In addition, possible approaches to nephrogenesis and organ generation using organoids, decellularized kidneys, and blastocyst complementation are surveyed.