gebhart/patrepeval huggingface dataset:
Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. (1994)

Anti-CD3 monoclonal antibodies suppress immune responses by transient T-cell depletion and antigenic modulation of the CD3/T-cell receptor complex. Anti-CD3 treatment of adult nonobese diabetic (NOD) mice, a spontaneous model of T-cell-mediated autoimmune insulin-dependent diabetes mellitus, significantly inhibits the autoimmune process. Short-term low-dose anti-CD3 treatment (5 micrograms/day i.v. for 5 consecutive days) prevented the occurrence of an accelerated form of the disease induced by cyclophosphamide. More unexpectedly, when applied to adult NOD females within 7 days of the onset of full-blown diabetes, the same anti-CD3 regimen induced a complete remission of overt disease (i.e., a return to permanent normoglycemia) in 64-80% of mice. This remission was durable (> 4 months) and was not associated with the disappearance of insulitis (mononuclear cell infiltration of the islets). The immunosuppression was apparently specific for beta-cell-associated antigens, since mice showing anti-CD3-induced remission rejected histoincompatible skin grafts normally, whereas they did not destroy syngeneic islet grafts, unlike control untreated overtly diabetic NOD females. These results open major therapeutic perspectives. They strongly suggest that self-tolerance can be restored in adult mice once autoimmunity is fully established and confirm that this effect can be obtained by transient targeting of the CD3/T-cell receptor without massive T-cell debulking.
Specific interactions between Porphyromonas gingivalis fimbriae and human extracellular matrix proteins (1999)

The interactions of the extracellular matrix (ECM) proteins (laminin, elastin, fibronectin, type I collagen, thrombospondin and vitronectin) with the fimbriae of Porphyromonas gingivalis were analyzed based on surface plasmon resonance (SPR) spectroscopy using a biomolecular interaction analyzing system (BIAcore). The BIAcore profiles demonstrated that fimbriae specifically bound to all of the ECM proteins with significant association constants (Ka). Vitronectin showed the highest affinity to fimbriae (Ka=3.79×106 M−1), while the affinity of laminin was lowest (Ka=2.15×106 M−1). A synthetic peptide which is a potent inhibitor of fimbrial binding to salivary proteins was not significantly effective on the fimbrial interactions with the ECM proteins. Using polystyrene microtiter plates revealed that P. gingivalis fimbriae bound markedly to immobilized fibronectin and type I collagen, while the interaction of fimbriae with the other ECM proteins was not clearly demonstrated. These results suggest that interactions between fimbriae and the ECM proteins occur with specific affinities which are not mediated by mechanisms identical to those of salivary proteins. It was also shown that SPR spectroscopy is a useful method to analyze these specific interactions.
Measurement of single kidney function using dynamic contrast‐enhanced MRI: Comparison of two models in human subjects (2006)

DCE-MRI of the kidneys provides data that correlate well with reference measures of SK-GFR. However, further work, including image registration, is needed to isolate measurement of glomerular filtration to the level of the renal cortex.
Pudendal neuromodulation with a closed-loop control strategy to improve bladder functions in the animal study (2013)

The aim of this study was to develop a new closed-loop control strategy for improving bladder emptying and verify its performance in animal experiments. Two channel outputs of electrical currents triggered by intravesical pressure (IVP)-feedback signals were set to automatically regulate the rat's pudendal nerve for selective nerve stimulation and blocking. Under this experimental design, a series of in-vivo animal experiments were conducted on anesthetized rats. Our results showed that the IVP-feedback control strategy for dual-channel pudendal neuromodulation performed well in animal experiments and could be utilized to selectively stimulate and block the pudendal nerve to augment bladder contraction and restore external urethral sphincter (EUS) bursting activity to simultaneously improve bladder emptying. This study demonstrates the feasibility of the IVP-based feedback-control strategy with animal experiments, and the results could provide a basis for developing a sophisticated neural prosthesis for restoring bladder function in clinical use or the relative neurophysiological study.
Pathological and therapeutic interactions between bacteriophages, microbes and the host in inflammatory bowel disease (2015)

The intestinal microbiome is a dynamic system of interactions between the host and its microbes. Under physiological conditions, a fine balance and mutually beneficial relationship is present. Disruption of this balance is a hallmark of inflammatory bowel disease (IBD). Whether an altered microbiome is the consequence or the cause of IBD is currently not fully understood. The pathogenesis of IBD is believed to be a complex interaction between genetic predisposition, the immune system and environmental factors. In the recent years, metagenomic studies of the human microbiome have provided useful data that are helping to assemble the IBD puzzle. In this review, we summarize and discuss current knowledge on the composition of the intestinal microbiota in IBD, host-microbe interactions and therapeutic possibilities using bacteria in IBD. Moreover, an outlook on the possible contribution of bacteriophages in the pathogenesis and therapy of IBD is provided.
Monomolecular DNA Nanoparticles for Intravenous Delivery of Genes (2005)

Delivery is the major obstacle to success of nucleic-acid-based therapies. We have neutralized DNA with a cationic detergent (C12CCP) obtained by amide bond formation between dodecanoic acid, cysteinyl-cysteine, and diaminopropane. Subsequent detergent polymerization by formation of intermolecular disulfide bonds within the condensed plasmid DNA leads to 32-nm-large neutral particles. (C12CCP)n/DNA complexes are more stable than those formed with other gene delivery agents toward exchange with extracellular polyanions such as glycosaminoglycans. Yet exposure to phosphatidylserine, an ubiquitous intracellular anionic lipid, still releases DNA from the complexes for transcription of the carried gene. Pharmacokinetics and biodistribution in mice showed that 25% of the complexes were still circulating after 30 min (2% for other cationic lipid vectors) in a form essentially not bound to blood cells. Altogether, straightforward control over size and surface charge, stability toward aggregation or exchange, and favorable pharmacokinetics make these complexes attractive vehicles for reaching tumor metastases after injection in the blood circulation.
Association Energetics of Cross-Reactive and Specific Antibodies (2009)

HyHEL-8, HyHEL-10, and HyHEL-26 (HH8, HH10, and HH26, respectively) are murine monoclonal IgG(1) antibodies which share over 90% variable-region amino acid sequence identity and recognize identical structurally characterized epitopes on hen egg white lysozyme (HEL). Previous immunochemical and surface plasmon resonance-based studies have shown that these antibodies differ widely in their tolerance of mutations in the epitope. While HH8 is the most cross-reactive, HH26 is rigidified by a more extensive network of intramolecular salt links and is highly specific, with both association and dissociation rates strongly affected by epitope mutations. HH10 is of intermediate specificity, and epitope mutations produce changes primarily in the dissociation rate. Calorimetric characterization of the association energetics of these three antibodies with the native antigen HEL and with Japanese quail egg white lysozyme (JQL), a naturally occurring avian variant, shows that the energetics of interaction correlate with cross-reactivity and specificity. These results suggest that the greater cross-reactivity of HH8 may be mediated by a combination of conformational flexibility and less specific intermolecular interactions. Thermodynamic calculations suggest that upon association HH8 incurs the largest configurational entropic penalty and also the smallest loss of enthalpic driving force with variant antigen. Much smaller structural perturbations are expected in the formation of the less flexible HH26 complex, and the large loss of enthalpic driving force observed with variant antigen reflects its specificity. The observed thermodynamic parameters correlate well with the observed functional behavior of the antibodies and illustrate fundamental differences in thermodynamic characteristics between cross-reactive and specific molecular recognition.
Methods for optimizing antiviral combination therapies (2003)

Abstract Motivation: Despite some progress with antiretroviral combination therapies, therapeutic success in the management of HIV-infected patients is limited. The evolution of drug-resistant genetic variants in response to therapy plays a key role in treatment failure and finding a new potent drug combination after therapy failure is considered challenging. Results: To estimate the activity of a drug combination against a particular viral strain, we develop a scoring function whose independent variables describe a set of antiviral agents and viral DNA sequences coding for the molecular targets of the respective drugs. The construction of this activity score involves (1) predicting phenotypic drug resistance from genotypes for each drug individually, (2) probabilistic modeling of predicted resistance values and integration into a score for drug combinations, and (3) searching through the mutational neighborhood of the considered strain in order to estimate activity on nearby mutants. For a clinical data set, we determine the optimal search depth and show that the scoring scheme is predictive of therapeutic outcome. Properties of the activity score and applications are discussed. Contact: beerenwinkel@mpi-sb.mpg.de *To whom correspondence should be addressed. Keywords: HIV, antiretroviral therapy, drug resistance, SVM regression, therapy optimization, sequence space search.
Calculation of roc curves in multidimensional likelihood ratio based screening with Down's syndrome as a special case (1998)

S-PLUS programs for the analysis of screening performance are listed and described. The programs can be used without any special knowledge of S-PLUS. An example of the use of the programs is given.
Regulation of Hepatic Stellate Cell Differentiation by the Neurotrophin Receptor p75 NTR (2007)

Differentiation of hepatic stellate cells (HSCs) to extracellular matrix- and growth factor-producing cells supports liver regeneration through promotion of hepatocyte proliferation. We show that the neurotrophin receptor p75NTR, a tumor necrosis factor receptor superfamily member expressed in HSCs after fibrotic and cirrhotic liver injury in humans, is a regulator of liver repair. In mice, depletion of p75NTR exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75NTR-/- HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75NTR signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75NTR to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.
Estimation of the Surface Tension Components of Thiodiglycol (1998)

The total surface tension of thiodiglycol was determined experimentally, and its surface tension components were estimated: γLW = 42 ± 1 mJ m-2, γ+ = 1.1 ± 0.5 mJ m-2, and γ- = 25.0 ± 0.5 mJ m-2. The Lifshitz−van der Waals component was estimated from experimental values of thiodiglycol/n-alkane interfacial tensions, measured by the pendant drop method. The γ+ and γ- were estimated using the additional information of the contact angle of thiodiglycol on a solid substrate with known surface energy components. Three polymeric substrates were used independently with this purpose: PS, SAN2, and PMMA. The most consistent set of values was obtained using PMMA. The final establishment of the values for the surface tension components of thiodiglycol involved a trial and error procedure where the parameters were slightly changed to reproduce the previously calculated surface energy components of the three polymer substrates. This study reinforced the idea that the estimation of the surface free energy components of a liquid (or solid) is highly dependent on the calculation method and on the systems used to perform the calculations.
3D Image-Guided Automatic Pipette Positioning for Single Cell Experiments in vivo (2015)

We report a method to facilitate single cell, image-guided experiments including in vivo electrophysiology and electroporation. Our method combines 3D image data acquisition, visualization and on-line image analysis with precise control of physical probes such as electrophysiology microelectrodes in brain tissue in vivo. Adaptive pipette positioning provides a platform for future advances in automated, single cell in vivo experiments.
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression (2017)

clinicaltrials.gov identifier: NCT01998958.
Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy (2006)

Subcutaneous HHT is well tolerated and may have clinical activity in patients with CML after imatinib failure.
Novel maximum-power-point-tracking controller for photovoltaic energy conversion system (2001)

A novel maximum-power-point-tracking (MPPT) controller for a photovoltaic (PV) energy conversion system is presented. Using the slope of power versus voltage of a PV array, the proposed MPPT controller allows the conversion system to track the maximum power point very rapidly. As opposed to conventional two-stage designs, a single-stage configuration is implemented, resulting in size and weight reduction and increased efficiency. The proposed system acts as a solar generator on sunny days, in addition to working as an active power line conditioner on rainy days. Finally, computer simulations and experimental results demonstrate the superior performance of the proposed technique.
The Total Synthesis of Taxamairin B (1995)

Taxamairin B, a novel rearranged 9(10--&gt;20)-abeo-8,11,13-triene diterpene, has been synthesized by a short and efficient route. A friedal-Crafts annunation and the oxidation of the allylic and benzylic methene group are the key steps.
<title>RGB lasers for laser projection displays</title> (2000)

JENOPTIK Laser, Optik, Systeme GmbH has developed for the first industrial all-solid-state Red-Green-Blue laser system for large image projection systems. Compact in design (0.75 m<SUP>3</SUP>, 180 kg, 3 kW power consumption), the system consists of a modelocked oscillator amplifier subsystem with 7 ps pulse duration and 85 MHz pulse repetition frequency, an optical parametric oscillator, and several non-linear stages to generate radiation at 628 nm, 532 nm and 446 nm with an average output power above 18 W. Each of the three colors is modulated with the video signal in a contrast ratio of 1000:1 and coupled into a common low order multi mode fiber. The system architecture relies on efficiently manufacturable components. With the help of FEM analysis, new engineering design principles and subsequent climatic and mechanical tests, a length stability below 50 micrometers and an angle stability below 10 (mu) rad have been achieved. The design includes efficient laser diodes with integrated thermo- electric cooler and a lifetime above 10000 hours. The stability of the output power is better than +/- 2% in a temperature range from 5 degree(s)C to 40 degree(s)C. The system operates reliably for more than 10000 hours under field conditions. The design is based (among others) on work by Laser-Display-Technologie KG and the University of Kaiserslautern.
Nucleotide sequence and promoter analysis of SPO13, a meiosis-specific gene of Saccharomyces cerevisiae. (1990)

The SPO13 gene, required for meiosis I segregation in Saccharomyces cerevisiae, produces two developmentally regulated transcripts (1.0 and 1.4 kilobases) that differ in length at their 5' ends. The shorter transcript is sufficient to complement the spo13-1 mutation and contains a major open reading frame encoding a highly basic protein of 33.4 kilodaltons. A fragment upstream (-170 to -8) of the open reading frame confers meiosis-specific transcription on a spo13-HIS3 fusion. Deletions at the 5' end of spo13-lacZ fusions define a region between -140 and -80 that is essential for meiosis-specific expression. This region acts in an orientation-independent manner and is responsive to the MAT-RME regulatory cascade. It contains a 10-base-pair sequence, TAGCCGCCGA, found in a number of meiosis-specific genes, that appears to be required for SPO13 expression. This sequence is identical to URS1, a ubiquitous mitotic repressor element.
Shared Human T Cell Receptor V β Usage to Immunodominant Regions of Myelin Basic Protein (1990)

Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.
Chlorophyll and β‐carotene pigments in moroccan virgin olive oils measured by high‐performance liquid chromatography (1991)

Abstract Chlorophyll and β‐carotene concentrations were determined by high‐performance liquid chromatography (HPLC) in virgin olive oils, which were press‐extracted from green and semi‐black olives. Pheophytin A was found to be the major chlorophyll isomer in all oil samples. The occurrence of this pigment at higher concentrations in oil extracted from green olives is a possible indication of its time‐related destruction during olive ripening. Some evidence for the in vivo existence of pheophytin A is also presented. Beta‐carotene concentration in oils was found to decrease during olive ripening.
Truncated glucagon-like peptide-1 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Identification of a mammalian analogue of the reptilian peptide exendin-4. (1992)

To find mammalian analogues of exendin-4, a peptide from Helodermatidae venoms that interacts with newly discovered exendin receptors on dispersed acini from guinea pig pancreas, we examined the actions of recent additions to the vasoactive intestinal peptide/secretin/glucagon family of regulatory peptides. In every respect tested, the truncated form of glucagon-like peptide-1, GLP-1(7-36)NH2, mimicked the actions of exendin-4. Like exendin-4, GLP-1(7-36)NH2 caused an increase in acinar cAMP without stimulating amylase release. GLP-1(7-36)NH2-induced increases in cAMP were inhibited progressively by increasing concentrations of the specific exendin-receptor antagonist, exendin(9-39)NH2. In dispersed acini from guinea pig and rat pancreas, concentrations of GLP-1(7-36)NH2 that stimulated increases in cAMP caused potentiation of cholecystokinin-induced amylase release. Binding of 125I-[Y39]exendin-4 or 125I-GLP-1(7-36)NH2 to dispersed acini from guinea pig pancreas was inhibited by adding increasing concentrations of unlabeled exendin-4 or GLP-1(7-36)NH2. We conclude that the mammalian peptide GLP-1(7-36)NH2 interacts with exendin receptors on dispersed acini from guinea pig pancreas. Exendin(9-39)NH2, a competitive antagonist of the actions of GLP-1(7-36)NH2 in pancreatic acini, may be a useful tool for examining the physiological actions of this peptide.
The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility (2011)

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease.
Regioselective Cleavage Reaction of the Aromatic Methylenedioxy Ring. V. Cleavage with Sodium Alkoxides - Alcohols, Potassium tert-Butoxide - Alcohols, Dimsyl Anion - Methyl Alcohol, Metallic Sodium - Alcohols, and Sodium Cyanide in Dipolar Aprotic Solvents. (1992)

The reaction of aromatic methylenedioxy compounds containing electron-withdrawing groups with dimsyl anion-methyl alcohol, potassium tert-butoxide-alcohols, and metallic sodium-alcohols in dimethyl sulfoxide (DMSO), and with sodium alkoxides-alcohols in hexamethylphosphoramide, gave 3- and 4-hydroxybenzene derivatives in good yield by regioselective attack of the alkoxide ions on the methylenedioxy ring. The formation mechanism of alkoxide ions and the effect of DMSO in the cleavage reaction of the methylenedioxy ring are discussed on the basis of proton nuclear magnetic resonance (1H-NMR) spectra. The reactions of aromatic methylenedioxy compounds (3 and 22) with sodium cyanide in dipolar aprotic solvents gave 4-cyano-3-hydroxybenzene derivatives (23 and 24) by regioselective attack of the cyanide ion on the methylenedioxy ring. The reactions of aromatic methylenedioxy compounds (28-30) containing no electron-withdrawing group with MeONa-MeOH in dipolar aprotic solvents gave non-regioselective cleavage products (31 and 34).