gebhart/patrepeval huggingface dataset:
Asparagine-linked oligosaccharide structures determine clearance and organ distribution of pituitary and recombinant thyrotropin (1995)

The recombinant human TSH (rhTSH) with highly sialylated oligosaccharide chains showed higher in vivo bioactivity and a lower MCR than the predominantly sulfated pituitary human TSH (phTSH). The aim of the present study was to investigate the role of terminal carbohydrate residues in organ distribution and metabolic clearance of TSH using an in vivo rat model. The different 125I-labeled TSH preparations with distinct carbohydrate composition were injected i.v. At various time points (5-180 min) after bolus TSH injection, blood, liver, kidney, spleen, lung, heart, and thyroid samples were collected. TSH uptake was determined by trichloroacetic acid precipitation of [125I]TSH in the organ homogenates. The rhTSH (solely sialylated) was distributed predominantly to the kidneys 5, 15, and 30 min after injection. In contrast, phTSH (sulfated/sialylated) and bovine TSH (bTSH; solely sulfated) were cleared predominantly by the liver (at 5 min), with a later renal phase of clearance (at 30 min). Asialo-rhTSH was cleared by the liver with only minor involvement of other organs. The early liver uptake (at 5 min) was proportionally highest for the asialo-rhTSH and bTSH preparations and lowest for rhTSH, which correlated inversely with the serum levels and the degree of sialylation. Blockade of the N-acetylgalactosamine (GalNAc) sulfate receptors by injection of bovine LH resulted in a significant decrease in liver uptake of phTSH. Similarly, liver uptake of asialo-rhTSH was significantly inhibited by injection of asialo-fetuin. Thus, phTSH and bTSH preparations containing sulfated oligosaccharide chains are cleared at least in part by the GalNAc sulfate-specific receptors in the liver. In contrast, rhTSH with highly sialylated oligosaccharides in both subunits accumulates predominantly in the kidneys, even at the early phase of clearance, indicating that sialylated glycoprotein hormones escape from specific receptor-mediated clearance mechanisms in the liver. These data indicate that terminal sialic acid and GalNAc sulfate residues, each to a different extent, determine glycoprotein hormone distribution and thereby plasma level, which as we have shown previously is a major factor in determining the in vivo potency of TSH.
Fused‐ring systems containing 1,2,4‐benzo thiadiazines. II. Reactions of o‐amino‐n‐hydroxybenzenesulfonamides (1966)

Abstract o‐Amino‐ N ‐hydroxybenzenesulfonamides have been treated with aldehydes to prepare 2‐hydroxy‐1,2,4‐benzothiadiazine 1,1‐dioxides. These products have permitted the fusion of an additional ring to the “b” face of the benzothiadiazine. Analogs of the tricyclic compounds have been made in other ways.
评《资本与社会主义——何去何从?》 (1992)

真理开始只属于少数人,在科学领域如此,在经济学领域亦如此。任何一部有真知灼见的著作都会因其涉足新的观点、理论,进行新的探索而引起人们的关注。武科米利察教授撰写的二卷本《资本和社会主义——何去何从?》就是这样一部著作。这类著作在南斯拉夫经济学界还为数不多。此书副标题“当代社会-经济体制”是对本书研究对象的概括,即对当今世界全球性社会-经济结构进行对比分析。为此,作者除对社会制度不同的国家进行经济的比较外,还对当代社会一经济体制结构中的政治和社会问题进行了研
Windmill-Like Porphyrin Arrays as Potent Light-Harvesting Antenna Complexes (1998)

Up to 14 porphyrin rings are present in the title compounds 1, which are readily available with high regioselectivity from linear nickel–zinc porphyrins. Upon irradiation with light a rapid energy transfer from the peripheral porphyrin rings to the diporphyrin core takes place.
Anti-anginal Effect of Fasudil, a Rho-Kinase Inhibitor, in Patients With Stable Effort Angina: A Multicenter Study (2002)

Rho-kinase plays an important role in calcium sensitization for vascular smooth muscle (VSMC) contraction and may be involved in the inappropriate coronary vasoconstriction during exercise-induced myocardial ischemia. In this multicenter phase II study, the anti-anginal effect of fasudil, which is metabolized to a specific Rho-kinase inhibitor hydroxyfasudil after oral administration, was examined in patients with stable effort angina. In the phase IIa trial, after a 2-week washout period of anti-anginal drugs, 45 patients received increasing doses of fasudil (5, 10, and 20 mg TID for every 2 weeks). The fasudil treatment significantly prolonged the maximum exercise time and the time to the onset of 1-mm ST segment depression on treadmill exercise test (both p < 0.01), whereas blood pressure and heart rate during exercise were unchanged before and after the treatment. Higher doses of fasudil (20 and 40 mg TID) were subsequently tested in 22 patients in the same manner with similar positive results. In the phase IIb trial, after a 2-week washout period of anti-anginal drugs, 125 patients were assigned, in a double-blind manner, to a 4-week oral treatment with a different dose of fasudil (5, 10, 20, or 40 mg TID) and treadmill exercise test was performed before and after the treatment. Again, both maximum exercise time and time to the onset of 1-mm ST segment depression were prolonged in all groups. A significant dose-response relation was noted across the treatment groups for the exercise tolerance index that was determined by the combined effect of exercise time and ST segment depression (p = 0.006). Fasudil was well tolerated in both trials without any serious adverse reactions. These results suggest the efficacy and adequate safety profile of fasudil, the first drug in a novel class of vasodilators, for the treatment of stable effort angina.
Analysis of a New Doxorubicin Derivative (FCE 23762) and Related Compounds by High Performance Capillary Electrophoresis (1994)

Abstract High performance capillary electrophoresis was applied to analyse FCE 23762, a new antracycline analogue (doxorubicin derivative) with anti-tumor activity. It has been shown earlier that a FCE 23762 sample may contain two main impurities, one of the optical isomers of FCE 23762 and the most probable degradation product, adriamycinone. The pharmacologically active compound and its diastereomer were resolved in free zone electrophoresis experiments. Adriamycinone, a neutral compound, is baseline separated from the other two (cationic) compounds by micellar electrokinetic chromatography. The use of two different separation methods was advantageous for an efficient and sensitive analysis for the synthetic product of FCE 23762.
Imaging Stem Cell Implant for Cellular-Based Therapies (2008)

Stem cell-based cellular therapy represents a promising outlook for regenerative medicine. Imaging techniques provide a means for noninvasive, repeated, and quantitative tracking of stem cell implant or transplant. From initial deposition to the survival, migration and differentiation of the transplant/implanted stem cells, imaging allows monitoring of the infused cells in the same live object over time. The current review briefly summarizes and compares existing imaging methods for cell labeling and imaging in animal models. Several studies performed by our group using different imaging techniques are described, with further discussion on the issues with these current imaging approaches and potential directions for future development in stem cell imaging.
Field-Testing of a Helicopter UAV Obstacle Field Navigation and Landing System (2009)

Flight test results and lessons learned are presented for a helicopter UAV low-altitude navigation and landing system. Results are given for both urban and natural settings. The navigation component uses a quasi-3D A* approach to route planning that enables maneuver through complex terrain using real-time sensor data. The landing component performs landings to sites that it determines to be safe based on air vehicle and user-defined landing criteria. The primary terrain sensor is a hemispherical LADAR.
Surround inhibition among projection neurons is weak or nonexistent in the rat neostriatum (1994)

1. Antidromic activation of striatal spiny projection neurons by substantia nigra stimulation in vivo did not evoke inhibitory postsynaptic potentials (IPSPs) in the antidromically activated neurons, or in neighboring spiny neurons. 2. More generalized activation of projection cells by stimulation of the efferent pathway in slices did not evoke IPSPs in spiny neurons. Inhibitory mechanisms were operative in these slices, as indicated by the presence of an IPSP component in the orthodromic response to local stimulation. 3. Dual intracellular recordings, obtained from cells located within 50-200 microns of each other in striatal slices also failed to demonstrate any inhibition among striatal spiny cells. Spikes triggered in one spiny neuron by current injection failed to produce any postsynaptic potential in nearby spiny cells at resting or depolarized membrane potentials. Excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the cortex were not affected by spiking of neighboring cells. 4. It is impossible to rule out the presence of inhibition among striatal spiny neurons in all circumstances. However, the absence of demonstrable IPSPs in these experiments argue against the common view that mutual inhibition among spiny neurons is a central organizing principle of striatal function.
Exposing digital forgeries by detecting traces of resampling (2005)

The unique stature of photographs as a definitive recording of events is being diminished due, in part, to the ease with which digital images can be manipulated and altered. Although good forgeries may leave no visual clues of having been tampered with, they may, nevertheless, alter the underlying statistics of an image. For example, we describe how resampling (e.g., scaling or rotating) introduces specific statistical correlations, and describe how these correlations can be automatically detected in any portion of an image. This technique works in the absence of any digital watermark or signature. We show the efficacy of this approach on uncompressed TIFF images, and JPEG and GIF images with minimal compression. We expect this technique to be among the first of many tools that will be needed to expose digital forgeries.
Substrate Specificity of Heparanases from Human Hepatoma and Platelets (1998)

Heparan sulfate proteoglycans, attached to cell surfaces or in the extracellular matrix, interact with a multitude of proteins via their heparan sulfate side chains. Degradation of these chains by limited (endoglycosidic) heparanase cleavage is believed to affect a variety of biological processes. Although the occurrence of heparanase activity in mammalian tissues has been recognized for many years, the molecular characteristics and substrate recognition properties of the enzyme(s) have remained elusive. In the present study, the substrate specificity and cleavage site of heparanase from human hepatoma and platelets were investigated. Both enzyme preparations were found to cleave the single beta-D-glucuronidic linkage of a heparin octasaccharide. A capsular polysaccharide from Escherichia coli K5, with the same (-GlcUAbeta1,4-GlcNAcalpha1,4-)n structure as the unmodified backbone of heparan sulfate, resisted heparanase degradation in its native state as well as after chemical N-deacetylation/N-sulfation or partial enzymatic C-5 epimerization of beta-D-GlcUA to alpha-L-IdceA. By contrast, a chemically O-sulfated (but still N-acetylated) K5 derivative was susceptible to heparanase cleavage. O-Sulfate groups, but not N-sulfate or IdceA residues, thus are essential for substrate recognition by the heparanase(s). In particular, selective O-desulfation of the heparin octasaccharide implicated a 2-O-sulfate group on a hexuronic acid residue located two monosaccharide units from the cleavage site, toward the reducing end.
Home Use of an Artificial Beta Cell in Type 1 Diabetes (2015)

Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).
Design strategies for protein kinase inhibitors. (2004)

Deregulation of protein kinases due to mutation or overexpression is a hallmark of several diseases, for example, cancer, diabetes, inflammation and cardiovascular disorders. Consequently, there has been a growing interest in the discovery of protein kinase inhibitors as novel drugs. Here, we focus on key milestones and advances in protein kinase inhibitor drug discovery over the last year, with an emphasis on novel strategies such as targeting of single and multiple binding sites, inactive conformations of kinases, allosteric sites, regulatory domains and heat shock proteins. We will highlight recent developments for specific inhibitors in clinical studies for growth factor receptors, non-receptor tyrosine kinases and serine/threonine kinases.
Different roles of D‐amino acids in immune phenomena (1997)

Peptides and polypeptides either fully or partially built of D-amino acids interest researchers because of their advantages over all L peptides and polypeptides. In exploiting these characteristics, one should realize that the resulting molecules are nonetheless not inert, but rather may induce a unique immune response, which is hardly cross-reactive with the L-enantiomer. Moreover, cross-reaction between the L- and the D-sequences is limited also at the T cell level, probably due to different sterical conformations of the MHC-antigen-T cell receptor complexes formed. Polypeptides built exclusively of D-amino acids lead to antibody formation only at a relatively low concentration, otherwise they provoke immunological paralysis. The specificity of the immune response toward peptides containing D-amino acid residues is exquisite, and often D-amino acids play a dominant role in defining the specificity. Polypeptides composed exclusively of D-amino acids are thymus-independent antigens. Nevertheless, it is possible to prepare against them highly specific T cell hybridomas. In future plans for synthetic vaccines against infectious or autoimmune diseases, the inclusion of D-amino acids may be an advantage in terms of both specificity and efficacy, the latter because of longer persistence in an undigested form because they resist enzymatic degradation.
Lateral current transport path, a model for GaN-based light-emitting diodes: Applications to practical device designs (2002)

An advanced model to explain the current spreading phenomenon of a conventional GaN-based light-emitting diode is presented. For this work, an equivalent circuit, consisting of the two lateral resistance components of the p-transparent electrode and the n-type layer is proposed. Theoretical calculations clearly reveal that the current density crowds near the n or p pads according to the device parameters and has an exponential behavior as a function of the lateral length. Based on these results, appropriate device parameters including the critical transparent-electrode thickness were determined, leading to a perfectly uniform current distribution. It was even possible to demonstrate the ideal device geometry without the need for a transparent electrode such as an interdigitated structure.
Dynamic Characterizations of AlGaN/GaN HEMTs With Field Plates Using a Double-Gate Structure (2013)

A novel double-gate AlGaN/GaN HEMT, in which an additional top-gate covers the adjacent regions of a normal gate, was proposed and fabricated for the first time to compare the dynamic characteristics of AlGaN/GaN HEMTs with a source field plate (SFP) and a gate field plate (GFP). During the dynamic characterization, the device was configured in two operation modes: One is the SFP mode with the top gate biased at 0 V, and the other is the GFP mode applying the gate pulse signal on the top gate at the same time. Compared with an AlGaN/GaN HEMT without field plates, both GFP and SFP much improve the dynamic performances. Compared with the SFP, the GFP shows better dynamic performances with a ~ 34% reduction of switch-on delay time and ~ 6% reduction of dynamic on-state resistance. Studying the dynamic characteristics and applying negative voltage on the top gate during the off state, the mechanism differences between the GFP and the SFP are discussed in detail.
Construction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids (2003)

Abstract The spiro[pyrrolidine‐3,3′‐oxindole] ring system is found at the core of a number of alkaloids, which possess significant biological activity and are interesting, challenging targets for chemical synthesis. In the present review, we report on the different strategies for the synthesis of the spiro[pyrrolidine‐3,3′‐oxindole] ring system in the context of recent synthesis of coerulescine, horsfiline, elacomine, salacin, pteropodine, alstonisine, spirotryprostatin A and B, and strychnofoline. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
The green vaccine: A global strategy to combat infectious and autoimmune diseases (2009)

Plant derived oral green vaccines eliminate expenses associated with fermenters, purification, cold storage/transportation and sterile delivery. Green vaccines are expressed via the plant nuclear or chloroplast genomes. Chloroplast expression has advantages of hyper-expression of therapeutic proteins (10,000 copies of transgene per cell), efficient oral delivery and transgene containment via maternal inheritance. To date, 23 vaccine antigens against 16 different bacterial, viral or protozoan pathogens have been expressed in chloroplasts. Mice subcutaneously immunized with the chloroplast derived anthrax protective antigen conferred 100% protection against lethal doses of the anthrax toxin. Oral immunization (ORV) of F1-V antigens without adjuvant conferred greater protection (88%) against 50-fold lethal dose of aerosolized plague (Yersinia pestis) than subcutaneous (SQV) immunization (33%). Oral immunization of malarial vaccine antigens fused to the cholera antigen (CTB-AMA1/CTB-Msp1) conferred prolonged immunity (50% life span), 100% protection against cholera toxin challenge and inhibited proliferation of the malarial parasite. Protection was correlated with antigen-specific titers of intestinal, serum IgA & IgG1 in ORV and only IgG1 in SQV mice, but no other immunoglobulin. High level expression in edible plant chloroplasts ideal for oral delivery and long-term immunity observed should facilitate development of low cost human vaccines for large populations, at times of outbreak.
Isolation of a protein Z-dependent plasma protease inhibitor (1998)

Human protein Z (PZ) is a 62,000-Mr, vitamin K-dependent plasma protein whose structure is similar to coagulation factors VII, IX, X, protein C, and protein S, but whose function is not known. The procoagulant activity of factor Xa in a one-stage plasma coagulation assay is reduced when factor Xa is first incubated with PZ. This apparent inhibitory effect is time dependent, requires the presence of calcium ions and procoagulant phospholipids (rabbit brain cephalin), and appears predominantly related to the incubation period of PZ with cephalin. In serum the initial rate of inhibition of factor Xa with calcium ions and cephalin also is enhanced in the presence PZ. A PZ-dependent protease inhibitor (ZPI) has been isolated from plasma. ZPI is a 72,000-Mr single-chain protein with an N-terminal amino acid sequence of LAPSPQSPEXXA (X = indeterminate) and an estimated concentration in citrate-treated plasma of 1.0-1.6 microg/ml. In systems using purified components, the factor Xa inhibition produced by ZPI is rapid (>95% within 1 min by coagulation assay) and requires the presence of PZ, calcium ions, and cephalin. The inhibitory process appears to involve the formation of a factor Xa-PZ-ZPI complex at the phospholipid surface.
The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes (1996)

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.
Cell-Free DNA and Active Rejection in Kidney Allografts (2017)

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), <i>P</i><0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types ≥IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (<i>P</i>=0.05 for T cell-mediated rejection types ≥IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type ≥IB or ABMR) and levels >1% indicate a probability of active rejection.
Factors Determining the Performance of Copper-Based Atom Transfer Radical Polymerization Catalysts and Criteria for Rational Catalyst Selection (2006)

The performance of copper-based ATRP catalysts can be predicted based on the stability constants of the CuII and CuI complexes with the ligand L (βII and βI, respectively). Both βII and βI should be large in order to prevent catalyst deactivation through competitive coordination of monomer and/or polymer. A high βII/βI ratio is required for high catalytic activity. Catalysts for which the CuII complex is more halogenophilic are more active, and provide better polymerization control due to the less pronounced deactivator dissociation. If ATRP is carried out in aqueous media, in addition to the above requirements, the ratio βII/(βI)2[L] should be low to prevent disproportionation of the CuI complex. Acidic monomers may be polymerized if the ligands meet all outlined requirements and are also as weakly basic as possible.