gebhart/patrepeval huggingface dataset:
Remission Rates Following Antidepressant Therapy With Bupropion or Selective Serotonin Reuptake Inhibitors (2005)

Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.
The role of 5ht2c receptors in affective disorders (1998)

5-HT(2C) receptors are predominantly localised in the brain and their dysregulation may contribute to particular symptoms of anxiety and depression. The marked affinity of several clinically established psychotropic agents sites (e.g., tricyclic antidepressants, clozapine, fluoxetine) for 5-HT(2C) receptor has generated interest in the therapeutic potential of selective, high affinity 5-HT(2C) receptor ligands. Like the selective serotonin re-uptake inhibitor (SSRI) fluoxetine, high affinity selective agonists such as Ro 60-0175 and Ro 60-0332 have potent in vivo activity in animal models suggestive of therapeutic action against depression, obsessive-compulsive disorder (OCD) and panic disorders. In contrast, 5-HT(2C) receptor antagonists such as SB-200646A or SB-221284 show signs of anxiolytic-like activity in tests for conditioned and phobic-like anxiety in rodents whereas they are inactive in tests indicative of antidepressant, antiOCD and antipanic activity. These results are consistent with an important hypothesis proposing that 5-HT has a complex, dual action on the neural mechanism of anxiety by either facilitating or inhibiting different kinds of anxiety in different brain regions. They also suggest that 5-HT(2C) receptor subtypes play an important role in the therapeutic properties of SSRIs. Certain 5-HT(2C) receptor antagonists may possess negative efficacy at 5-HT(2C) receptors and, as inverse agonists, may control constitutive receptor activity possibly characterising some psychopathological states. Receptor variants exist in the human population and indicate possible associations between somatic mutations in the 5-HT(2C) receptor and psychopathology or response to drug treatment. Selective 5-HT(2C) receptor ligands may offer innovative and improved therapeutic opportunities for the biological treatment of specific aspects of psychiatric syndromes.
Potent peptide inhibitors of stromelysin based on the prodomain region of matrix metalloproteinases. (1994)

Stromelysin is secreted as an inactive zymogen that is activated in the extracellular space by cleavage of the His81-Phe82 bond with the release of the 81-amino acid propeptide domain. This segment contains a 12-amino acid sequence (MRKPRC75GVPDVG) that is highly conserved in all matrix metalloproteinases. Previous studies have shown that the hexapeptide, Ac-RCGVPD-NH2, and the pentapeptide, Ac-RCGVP-NH2, based on this region retain significant inhibitory activity. This new structure-activity relationship study of both peptides has shown that only Cys75 and Val77 are essential for inhibitory activity. Peptides based on this series inhibited stromelysin and collagenase with equal potency. Additional peptides spanning this region were synthesized in order to focus on these two sites. Significantly, isocysteine was substituted for Cys75 without significant loss of inhibitory activity. Tyr-(2,6-dichlorobenzyl) was substituted for Val77. The introduction of these 2 new residues into Ac-CGVP-NH2 produced a very potent inhibitor, Ac-isoCGY-(2,6 dichlorobenzyl)-P-NH2 with an IC50 of 3 microM. The following factors, acting in combination, determine the inhibitory activity of peptides in this series: distance between the sulfur atom and the peptide backbone, coordination geometry of the thiol side chain with the active-site zinc, and conformational flexibility of the side-chain.
The influence of banana stem extract on urinary risk factors for stones in normal and hyperoxaluric rats (1994)

Banana stem extract from the Musaceae family may be a useful agent in the treatment of patients with hyperoxaluric urolithiasis.
Evaluation of Tone Mapping Operators for HDR‐Video (2013)

Abstract Eleven tone‐mapping operators intended for video processing are analyzed and evaluated with camera‐captured and computer‐generated high‐dynamic‐range content. After optimizing the parameters of the operators in a formal experiment, we inspect and rate the artifacts (flickering, ghosting, temporal color consistency) and color rendition problems (brightness, contrast and color saturation) they produce. This allows us to identify major problems and challenges that video tone‐mapping needs to address. Then, we compare the tone‐mapping results in a pair‐wise comparison experiment to identify the operators that, on average, can be expected to perform better than the others and to assess the magnitude of differences between the best performing operators.
Factor XIIIa-mediated Cross-linking of Fibronectin in Fibroblast Cell Layers (1989)

Factor XIIIa cross-links plasma fibronectin as it is being assembled into the extracellular matrix of cultured human skin fibroblasts (Barry, E. L. R., and Mosher, D. F. (1988) J. Biol. Chem. 262, 10464-10469). We have further characterized this process. Fibroblasts were metabolically labeled with proline in the presence or absence of ascorbate and Factor XIIIa. Endogenous fibronectin in the extracellular matrix was cross-linked by Factor XIIIa. There was no evidence for cross-linking of collagenous proteins. Fibro-blast cell layers were incubated with iodinated 27-kDa heparin-binding or 70-kDa collagen- and heparin-binding amino-terminal fibronectin fragments. Factor XIIa cross-linked the fragments into high molecular weight aggregates. The amounts of cross-linked fragments reaches a steady state after 1 to 2 h, whereas intact fibronectin continues to be cross-linked for 24 h. When fibroblast cell layers were pulsed with iodinated fibronectin or amino-terminal fragments and Factor XIIIa was included in the chase media, the high molecular weight aggregates were formed in a step-wise manner. The smallest cross-linking steps were to high molecular weight extracellular matrix molecules forming approximately 270-, 300-, and 440-kDa complexes for the 27-kDa fragment, 70-kDa fragment, and intact fibronectin, respectively. When iodinated fibronectin was bound to fibroblast cell layers and chased into the matrix pool in the absence of Factor XIIIa, it could also be cross-linked into high molecular weight complexes when Factor XIIIa was added to the media. These results, therefore, indicate that both cellular and plasma fibronectin and amino-terminal fragments are cross-linked specifically by Factor XIIIa, that the cross-linking is probably to other fibronectin molecules rather than to collagenous proteins, and that both assembling and assembled fibronectin are substrates for Factor XIIIa.
Highly Active Water-Soluble Olefin Metathesis Catalyst (2006)

A novel water-soluble ruthenium olefin metathesis catalyst supported by a poly(ethylene glycol) conjugated saturated 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligand is reported. The catalyst displays improved activity in ring-opening metathesis polymerization, ring-closing metathesis, and cross-metathesis reactions in aqueous media.
A tone oriented voice excited vocoder (2005)

An LPC base-band vocoder is developed. The novel feature concerns the coding of the base-band. A model is set up for the base-band as a set of modulated tones. Algorithms are presented for the extraction of amplitude and phase/frequency of the tones. Implementation aspects as well as simulation results are discussed. Total bit rates in the order of 3,2-4.8 kbits are possible where approximately one half of the bits represents the base-band coding. Experiments have shown the coder to be robust to background noise.
Synthesis of 2,4,5-Trisubstituted Oxazoles (2005)

2,4,5-Trisubstituted oxazoles were synthesized in good yields starting from α-methylene ketones by nitrosation, condensation with aldehydes and reduction with zinc in acetic acid at 40 °C. (5-Methyl-2-phenyloxazol-4-yl)ethanol was prepared by reduction of ethyl (5-methyl-2-phenyloxazol-4-yl)acetate with LiAlH4.
An electron microscopic study of initial intramembranous osteogenesis (1969)

Abstract Calvariae of fetal mice were investigated with electron microscopy in order to demonstrate initial stages of immature, membrane bone calcification. As a consequence, nucleation sites for initial calcification of hydroxyapatite crystals in woven bone were found in extrusions from osteoblasts within the osteoid. Growth of the crystals epitaxially from these initial calcification loci into the surrounding collagen was spherulitic, forming discrete spheres referred to as “bone nodules”. These nodules, when coalesced, formed seams of bone. Decalcified, the organic substructure of the bone nodules was revealed. It contained a centrally disposed initial calcification locus, a peripheral zone of decomplexing collagen and an intermediate zone of altered collagen. Fully formed collagen fibrils remained interposed between most of the coalesced nodules. Polysaccharides were localized within the initial calcification locus and in the peripheral zone of the bone nodules where collagen was shown to be decomplexing.
Targeting of liposomes to cells expressing CD4 using glycosylphosphatidylinositol-anchored gp120. Influence of liposome composition on intracellular trafficking. (1994)

To test the concept that glycosylphosphatidylinositol (GPI)-anchored proteins might be useful as targeting molecules for liposomes, we engineered a GPI-anchored form of gp120 from human immunodeficiency virus type 1 (termed gp120DAF) using the GPI signal of decay-accelerating factor (DAF). We show that (i) purified gp120DAF spontaneously inserts into liposome membranes via the GPI anchor; (ii) liposomes bearing gp120DAF bind specifically to cells expressing CD4, the cellular receptor for gp120; and (iii) the receptor-bound liposomes are internalized and recycle in Chinese hamster ovary cells. To test whether the lipid composition of the liposome affects any of these processes, we compared small unilamellar liposomes containing only phosphatidylcholine and cholesterol in a 7:1 molar ratio with artificial viral envelopes that mimic the lipid composition of human immunodeficiency virus type 1. We show that when tagged with gp120DAF, both liposome preparations bind specifically to cells expressing CD4, and both are endocytosed. However, artificial viral envelope liposomes are transported to late endosomes or lysosomes in the cell interior, whereas phosphatidylcholine:cholesterol liposomes are confined to a population of vesicles that remain close to the plasma membrane. Since the binding and internalization of both liposome preparations are mediated by the same receptor, we conclude that the lipid composition of the liposome profoundly influences the subsequent intracellular trafficking of the liposome-receptor complex.
[Tissue concentration of methotrexate in osteosarcoma after high-dose infusion]. (1982)

Tissue concentrations of methotrexate (MTX) in osteosarcomas were examined with special reference to their histologic findings. Primary tumors in five cases and metastatic tumors in two cases were removed at 6-18 days after MTX administration. The concentrations of MTX in osteosarcoma tissues were higher than those in normal tissues and serum, ranging from 15.0 to 168 ng/g. Necrotic portions of the tumor lesion were less in MTX concentration than cellular portions. As the cellularity increased, the tumor tissue showed higher MTX concentration. Tissue concentrations of MTX in nude mice with transplanted osteosarcoma from human were also studied after the high-dose 3H-MTX infusion. MTX total, which contains dihydrofolate reductase-bound MTX, free MTX and its metabolites, decreased gradually with time in the tumor tissues. The concentrations of MTX total in tumor were proportional to the administrated dose and the clearances of MTX were prolonged according to the dose-increase of MTX. Tissue concentrations of MTX total in the lung, kidney and liver were higher than that in tumor itself at 192 hours after the injection. The value for MTX total includes some MTX active fraction which can inhibit the activity of dihydrofolate reductase. Tissue concentrations of MTX active also increased dose-dependently. The proportions of MTX active to MTX total in tumors decreased with the increment of the MTX dose, and the same findings were observed in the kidney and liver.
Continuous Relaxations for Discrete Hamiltonian Monte Carlo (2012)

Continuous relaxations play an important role in discrete optimization, but have not seen much use in approximate probabilistic inference. Here we show that a general form of the Gaussian Integral Trick makes it possible to transform a wide class of discrete variable undirected models into fully continuous systems. The continuous representation allows the use of gradient-based Hamiltonian Monte Carlo for inference, results in new ways of estimating normalization constants (partition functions), and in general opens up a number of new avenues for inference in difficult discrete systems. We demonstrate some of these continuous relaxation inference algorithms on a number of illustrative problems.
Therapeutic Use of Butyrylcholinesterase for Cocaine Intoxication (1997)

The most common complications of cocaine ingestion are on the cardiovascular and central nervous systems and produce chest pain and generalized seizures. In humans, decreased levels of butyrylcholinesterase (BChE) (EC 3.1.1.8) have been associated with sustained effects of cocaine and life-threatening complications. Administration of purified human BChE has previously been demonstrated to protect against cocaine-associated cardiovascular toxicity in rats. A shift in the metabolism of cocaine as well as enhanced metabolism may be the underlying mechanism of the enzyme. Therefore, levels of the parent drug and four metabolites were determined in rat plasma after i.p. administration of a lethal cocaine dose, followed by i.v. administration of BChE. Plasma and brain concentrations of cocaine were lowered by 80% after BChE administration. Furthermore, the metabolic profile of cocaine in the plasma was altered. The concentration of ecgonine methylester was doubled although the concentration of ecgonine, a secondary metabolite of cocaine, was reduced. The level of benzoylecgonine was reduced by one-half while norcocaine was absent. Cocaine-associated effects upon the central nervous system were also shown to be reduced by administration of BChE to conscious rats. Furthermore, our studies in the cat have also shown that purified BChE shifts the metabolic profile of cocaine (1 mg/kg) to the pharmacologically inactive products ecgonine methylester and ecgonine. Pretreatment with BChE (0.27, 1.0, and 10.0 mg/kg) ameliorated the hypertensive effects of cocaine (1 mg/kg) by reducing the duration and the extent of BP elevation by 66%. Administration of the enzyme, 1 min after cessation of cocaine infusion, resulted in an immediate attenuation in the cocaine-induced broadening of the QRS complex. These results suggest that BChE could be an effective and rapid therapy for the treatment of life-threatening cocaine-induced cardiovascular effects in human while clearing the total body burden of cocaine.
In Vivo Imaging of Proteolytic Activity in Atherosclerosis (2002)

These studies indicate that cathepsin B, and potentially other proteases, may serve as a biomarker for vulnerable plaques when probed with beacons. The tomographic in vivo imaging method as well as catheter-based optical sensing methods could be readily adapted to screening and potentially to the molecular profiling of a number of proteases in vulnerable plaque in vivo.
A gridless router based on hierarchical PB corner stitching structure (2003)

A multi-layer gridless area router is given in this paper. Based on corner stitching, this router adopts tile expansion to explore path for each net. A heuristic method that penalizes nodes deviating from the destination is devised to accelerate the algorithm. Besides, an enhanced interval tree is used to manage the intermediate data structure. In order to eliminate the effect that the routing order has on final results, a new gridless rip-up and rerouting algorithm is proposed. Test results indicate that the completion rate is improved after the rip-up and reroute process and the speed of this algorithm is satisfactory.
Efficiency of Timing Delays and Electrode Positions in Optimization of Biventricular Pacing: A Simulation Study (2009)

Electrode positions and timing delays influence the efficacy of biventricular pacing (BVP). Accordingly, this study focuses on BVP optimization, using a detailed 3-D electrophysiological model of the human heart, which is adapted to patient-specific anatomy and pathophysiology. The research is effectuated on ten heart models with left bundle branch block and myocardial infarction derived from magnetic resonance and computed tomography data. Cardiac electrical activity is simulated with the ten Tusscher cell model and adaptive cellular automaton at physiological and pathological conduction levels. The optimization methods are based on a comparison between the electrical response of the healthy and diseased heart models, measured in terms of root mean square error (E(RMS)) of the excitation front and the QRS duration error (E(QRS)). Intra- and intermethod associations of the pacing electrodes and timing delays variables were analyzed with statistical methods, i.e., t -test for dependent data, one-way analysis of variance for electrode pairs, and Pearson model for equivalent parameters from the two optimization methods. The results indicate that lateral the left ventricle and the upper or middle septal area are frequently (60% of cases) the optimal positions of the left and right electrodes, respectively. Statistical analysis proves that the two optimization methods are in good agreement. In conclusion, a noninvasive preoperative BVP optimization strategy based on computer simulations can be used to identify the most beneficial patient-specific electrode configuration and timing delays.
Pharmacokinetics, Safety, and Tolerability With Repeat Doses of GSK1265744 and Rilpivirine (TMC278) Long-Acting Nanosuspensions in Healthy Adults (2014)

These data support the potential application of dual-therapy 744 LA and RPV LA for treatment of HIV-1 infection.
Preclinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22 (2018)

Despite high remission rates following CAR-T cell therapy in B-ALL, relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may reduce the likelihood of antigen loss, thus improving sustained remission rates. A systematic approach to the generation of CAR constructs incorporating two target-binding domains led to several novel CD19/CD22 bivalent CAR constructs. Importantly, we demonstrate the challenges associated with the construction of a bivalent CAR format that preserves bifunctionality against both CD19 and CD22. Using the most active bivalent CAR constructs, we found similar transduction efficiency compared to that of either CD19 or CD22 single CARs alone. When expressed on human T cells, the optimized CD19/CD22 CAR construct induced comparable interferon γ and interleukin-2 <i>in vitro</i> compared to single CARs against dual-antigen-expressing as well as single-antigen-expressing cell lines. Finally, the T cells expressing CD19/CD22 CAR eradicated ALL cell line xenografts and patient-derived xenografts (PDX), including a PDX generated from a patient with CD19<sup>-</sup> relapse following CD19-directed CAR therapy. The CD19/CD22 bivalent CAR provides an opportunity to test whether simultaneous targeting may reduce risk of antigen loss.
Aktuelle Trends - Konjunktur in der Europäischen Währungsunion läuft in eine Delle (1999)

Seit Anfang 1999 veröffentlicht das IWH im vierteljährlichen Abstand einen Frühindikator der Konjunkturentwicklung des Euroraums. Der Indikator, der neben den Auftragseingängen sowie Unternehmer- und Verbraucherumfragen auch die Zinsstruktur berücksichtigt, läuft der tatsächlichen Entwicklung (gegenwärtig approximiert mit Hilfe des Index der Industrieproduktion) um ungefähr ein Quartal voraus und ermöglicht eine Trendprognose der wirtschaftlichen Aktivität.
Hematopoietic Stem Cell Gene Therapy for Adenosine Deaminase–Deficient Severe Combined Immunodeficiency Leads to Long-Term Immunological Recovery and Metabolic Correction (2011)

Genetic defects in the purine salvage enzyme adenosine deaminase (ADA) lead to severe combined immunodeficiency (SCID) with profound depletion of T, B, and natural killer cell lineages. Human leukocyte antigen-matched allogeneic hematopoietic stem cell transplantation (HSCT) offers a successful treatment option. However, individuals who lack a matched donor must receive mismatched transplants, which are associated with considerable morbidity and mortality. Enzyme replacement therapy (ERT) for ADA-SCID is available, but the associated suboptimal correction of immunological defects leaves patients susceptible to infection. Here, six children were treated with autologous CD34-positive hematopoietic bone marrow stem and progenitor cells transduced with a conventional gammaretroviral vector encoding the human ADA gene. All patients stopped ERT and received mild chemotherapy before infusion of gene-modified cells. All patients survived, with a median follow-up of 43 months (range, 24 to 84 months). Four of the six patients recovered immune function as a result of engraftment of gene-corrected cells. In two patients, treatment failed because of disease-specific and technical reasons: Both restarted ERT and remain well. Of the four reconstituted patients, three remained off enzyme replacement. Moreover, three of these four patients discontinued immunoglobulin replacement, and all showed effective metabolic detoxification. All patients remained free of infection, and two cleared problematic persistent cytomegalovirus infection. There were no adverse leukemic side effects. Thus, gene therapy for ADA-SCID is safe, with effective immunological and metabolic correction, and may offer a viable alternative to conventional unrelated donor HSCT.