gebhart/patrepeval huggingface dataset:
In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo (2002)

Recent findings implied that the progression of hematologic malignancies, like that of solid tumors, is dependent on neovascularization. Recent studies on patients with acute myeloid leukemia (AML) showed increased levels of leukocyte-associated vascular endothelial growth factor (VEGF) and neovascularization of the bone marrow. Murine (32D, M1) and human (HEL, U937, and UKE-1) leukemic cell lines and freshly isolated leukemic cells were analyzed for the expression of VEGF and VEGF receptor mRNA. The expression of VEGF and VEGF receptors KDR and neuropilin-1 (NRP-1) was detected in these cells. In a murine chloroma model, delivery of VEGF(165) using microencapsulation technology resulted in enhanced tumor growth and vascularization, whereas treatment with a VEGF antagonist soluble NRP-1 (sNRP-1) inhibited tumor angiogenesis and growth. In a systemic leukemia model, survival of mice injected with adenovirus (Ad) encoding for Fc-sNRP-1 (sNRP-1 dimer) was significantly prolonged as compared with mice injected with Ad-LacZ. Further analyses showed a reduction in circulating leukemic cells and infiltration of liver and spleen as well as bone marrow neovascularization and cellularity. Taken together, these results demonstrate that angiogenic factors such as VEGF promote AML progression in vivo. The use of VEGF antagonists as an antiangiogenesis approach offers a potential treatment for AML. Finally, our novel in vivo drug delivery model may be useful for testing the activities of other peptide antiangiogenic factors.
Identification of gamma-E-antibodies as a carrier of reaginic activity. (1967)

Summary The immunoglobulin having reaginic activity was purified from sera of ragweed sensitive patients by salt precipitation, diethylaminoethyl (DEAE)-cellulose column chromatography, gel filtration and DEAE-Sephadex column chromatography. The γG- and γA-globulins remaining in the purified samples were absorbed with rabbit anti-γG- and anti-γA-antibodies which had been precipitated with goat antibody against rabbit γ-globulin. On a weight basis, reaginic activity of the final preparation was about 1000 times more active than the original sera and the most active fraction gave positive P-K reactions at a dilution of 1:80,000. Human serum proteins detected in the preparation were γE- and γD-globulins. The antibody against antigen E was detected in γE-globulin but not in other immunoglobulins. It was also found that the reaginic activity and γE-antibody in the preparations were precipitated by anti-γE-antibody. The results indicate that reaginic activity is associated with γE-globulin. Evidence was presented that reaginic antibody against antigen E in the serum of one individual was γE-globulin of mostly κ chain type.
Intrathecal spermine and spermidine at high-doses induce antinociceptive effects in the mouse capsaicin test (2002)

The antinociceptive effects of intrathecally (i.t.) administered high doses of spermine and spermidine, endogenous polyamines, were examined in the mouse capsaicin test. Spermine (2.5-10 nmol) and spermidine (10 and 15 nmol), when administered i.t. 5 min before the injection of capsaicin solution (1600 ng) into the plantar surface of a hindpaw, produced a significant reduction of the nociceptive behavioral response. Ifenprodil (2 and 4 nmol), an antagonist of the polyamine recognition site on N-methyl-D-aspartate (NMDA) receptor ion-channel complex, co-administered with spermine or spermidine significantly inhibited antinociception induced by both polyamines. These results indicate that spermine- and spermidine-induced antinociception may be mediated via the polyamine recognition site on NMDA receptor ion-channel complex in the mouse spinal cord.
Feasible cone beam scanning methods for exact reconstruction in three-dimensional tomography (1990)

Feasible cone beam scanning methods that permit exact reconstruction in three-dimensional tomography are proposed, and their performances are investigated using the theory developed by Kirillov [Sov. Math. Dokl. 2, 268 (1961)], Tuy [SIAM J. Appl. Math. 43, 546 (1983)], and Smith [IEEE Trans. Med. Imaging MI-4, 14 (1985)]. The proposed methods move an apex of a cone on two circles that are perpendicular to each other (orthogonal scan) or on a few twists of a helical curve (helical scan). The obtainable information, the feasibility of reconstruction, and the redundancy of measurement by some typical cone beam scanning methods are analyzed using the relationship between the cone beam projections and the three-dimensional Radon transform. Consequently it is found that the proposed methods can obtain the complete information about the three-dimensional Fourier transform of an object with less redundant measurement. Moreover, based on the analysis, a practically implementable reconstruction algorithm suitable for the proposed methods is derived. Experiments performed with both numerical and real x-ray projections demonstrate the validity of the proposed scanning methods and the reconstruction algorithm. Especially when a large cone angle is used, the proposed methods greatly improve the spatial resolution and the quantitative accuracy of reconstruction as compared with the method of circular apex motion.
Synthesis and applications of metal silicidenanowires (2009)

Transition metal silicides represent an extremely broad set of refractory materials that are currently employed for many applications including CMOS devices, thin film coatings, bulk structural components, electrical heating elements, photovoltaics, and thermoelectrics. Many of these applications may be improved by making 1-dimensional nanomaterials. Chemical synthesis of silicide nanowires is more complicated compared to other classes of nanomaterials due to the complex phase behaviour between metals and silicon and the complex stoichiometries and structures of their resulting compounds. Recently, several synthetic strategies have been developed to overcome this challenge resulting in increasing reports of silicide nanowires in the literature. These strategies are highlighted in this feature article, along with future synthetic challenges and a review of the applications emerging from current silicide nanowires.
Molecular hydrogen complexes in catalysis: highly efficient hydrogen production from alcoholic substrates catalysed by ruthenium complexes (1988)

The complex [RuH2(N2)(PPh3)3] catalyses the thermal production of hydrogen from a range of different alcoholic substrates with rates corresponding to up to >1000 catalyst turnover h–1; the mechanism of the reaction is discussed and possible reasons for the high efficiency of this catalyst including the fact that loss of hydrogen occurs from a molecular hydrogen complex, are explored.
Towards gene therapy for renal diseases. (1998)

The rationale of the somatic gene therapy is the correction of diseases at the most fundamental level. Ideal gene therapy should be achieved by the replacement of the wrong gene sequence of genome with correct one. However, the gene technology to date is yet immature so as to correct the wrong gene sequence in vivo. Potentially, the present technology of gene transfer may provide: 1) correction of cellular dysfunction by expressing the deficient gene; 2) addition of new function for a cell by transferring an exogenous gene; 3) inhibition of unfavorable action of a cell by introducing a counteracting gene. In nephrology, the gene transfer targeted kidney has been challenged at the experimental level. HVJ-liposome method and recombinant adenovirus allow gene transfer to the particular cells in kidney in vivo. Ex vivo gene transfer using mesangial cells and macrophages are another option. Transplant kidney is also a good material for genetic engineering. The potential application of gene transfer is enormous while the therapeutic application have just begun to explored. We have been devoted to HVJ-liposome mediated gene transfer to the kidney and successfully demonstrated the suppression of the extracellular matrix accumulation of the glomeruli in the experimental glomerulonephritis through inhibition of the TGF-beta action by antisense oligonucleotides or soluble type receptor chimera for TGF-beta. We also applied this technology to the inhibition of interstitial fibrosis in unilateral ureter obstruction model. The new HVJ-liposome method improved in lipid composition allows gene transfer to tubulointerstitial fibroblast by retrograde approach from ureter. In consequence, introduced TGF-beta antisense suppressed the TGF-beta mRNA in concomitant with ameliorating interstitial fibrosis. We believe that the gene transfer technique will become common strategy to study the molecular aspect of the renal diseases and will be possibly applicable to molecular intervention in nephrology.
Augmentation of Glycogen Synthesis under Stringent Control in Escherichia coli1,2 (1980)

When Escherichia coli strain CP78 (rel+) was starved for isoleucine by the addition of valine, the amount of glucose in polymeric form in the cells increased markedly compared to that of the control cells. In contrast, this phenomenon was not seen in strain CP79 (rel-). The increase in CP78 was shown to be due to the increase of glycogen. These results indicate that glycogen synthesis was augmented under stringent control. This was confirmed using other isogenic pairs of rel+ and rel- strains starved for other amino acids. When the cultivation temperature of strains 10B601 (rel+) and 10B602 (rel-) possessing temperature-sensitive valyl-tRNA synthetase was shifted from 30 degrees C to 40 degrees C, no difference was observed in the response of glycogen synthesis between the two strains. These results indicate that protein synthesis was necessary for the augmentation of glycogen synthesis and that guanosine 5'-diphosphate 3'-diphosphate did not exert its effect through stimulation of the activity of pre-existing enzyme(s) involved in glycogen synthesis. These conclusions were supported by the results of experiments using chloramphenicol and rifampicin. The rates of glucose utilization of CP78 and CP79 were decreased to nearly the same extent by valine addition. This suggests that the regulation site of glycogen synthesis under stringent control resides in a step after the transport of glucose by the phosphotransferase system.
A randomized, double‐blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia (1996)

Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone.
Small Molecule Modulators of Histone Acetyltransferase p300 (2003)

Histone acetyltransferases (HATs) are a group of enzymes that play a significant role in the regulation of gene expression. These enzymes covalently modify the N-terminal lysine residues of histones by the addition of acetyl groups from acetyl-CoA. Dysfunction of these enzymes is often associated with the manifestation of several diseases, predominantly cancer. Here we report that anacardic acid from cashew nut shell liquid is a potent inhibitor of p300 and p300/CBP-associated factor histone acetyltranferase activities. Although it does not affect DNA transcription, HAT-dependent transcription from a chromatin template was strongly inhibited by anacardic acid. Furthermore, we describe the design and synthesis of an amide derivative N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) using anacardic acid as a synthon, which remarkably activates p300 HAT activity but not that of p300/CBP-associated factor. Although CTPB does not affect DNA transcription, it enhances the p300 HAT-dependent transcriptional activation from in vitro assembled chromatin template. However, it has no effect on histone deacetylase activity. These compounds would be useful as biological switching molecules for probing into the role of p300 in transcriptional studies and may also be useful as new chemical entities for the development of anticancer drugs.
Unmasking a hyaluronan‐binding site of the BX7B type in the H3 heavy chain of the inter‐α‐inhibitor family (2001)

The inter-alpha-inhibitor (I alpha I) family gathers together several plasma protease inhibitors such as I alpha I and pre-alpha-inhibitor (P alpha I) that are variously assembled from a set of polypeptide chain precursors designated H1P to H3P. In addition to their protease inhibitory activity, a major physiological function of I alpha I family members is hyaluronan (HA) binding and HA-dependent stabilization of the extracellular matrix surrounding various cell types. Also, binding of HA to these molecules has been shown to be an important event in tumor cell proliferation and rheumatoid arthritis. However, how HA and I alpha I family members first recognize each other has so far remained elusive. The so-called BX7B domain found in some HA-binding proteins is an HA-binding site in which B represents a basic amino-acid residue and X represents any nonacidic residue. This domain has now been identified in the N-terminal end of H3P that is a precursor of P alpha I. A series of wild-type or mutant recombinant H3P chains produced with a mouse cDNA expressed in Escherichia coli allowed us to demonstrate that this domain binds HA in a noncovalent fashion. Furthermore, unmasking this HA-binding activity required most of H3P to be trimmed off at its C-terminal end. The latter observation was confirmed with a natural, mature H3 chain purified from human plasma. Indeed, a thermolysin-generated, N-terminal fragment of this H3 chain strongly bound HA whereas the intact H3 chain did not. Therefore, in vivo, the HA-binding activity of the mature H3 chain within P alpha I may vary with the folding and/or fragmentation of this protein.
Design, Modelling and Characterization of Si/SiGe Structures for IR Bolometer Applications (2015)

This thesis presents SiGe(C)/Si(C) multi quantum well (MQW) layers individually or in combination with Si(C) Schottky diodes as material structures to detect infrared (IR) radiation. The performanc ...
Phase 1 dose‐escalation trial of tremelimumab plus sunitinib in patients with metastatic renal cell carcinoma (2010)

In this study of tremelimumab plus sunitinib, rapid-onset acute renal failure was observed unexpectedly, and further investigation of tremelimumab doses > 6 mg/kg plus sunitinib 37.5 mg daily is not recommended. Preclinical investigation may be warranted to understand the mechanism of renal toxicity.
ChemInform Abstract: Ternary Rare‐Earth Zinc Arsenides REZn2As3 (RE: La—Pr) Containing Defect Fluorite‐Type Slabs. (2013)

Abstract The title compounds are synthesized from the elements (silica tubes, 800 °C, 7 d) and characterized by powder XRD, single crystal XRD, magnetic measurements, and TB‐LMTO band structure calculations.
M-Walk: Learning to Walk over Graphs using Monte Carlo Tree Search (2018)

Learning to walk over a graph towards a target node for a given query and a source node is an important problem in applications such as knowledge base completion (KBC). It can be formulated as a reinforcement learning (RL) problem with a known state transition model. To overcome the challenge of sparse rewards, we develop a graph-walking agent called M-Walk, which consists of a deep recurrent neural network (RNN) and Monte Carlo Tree Search (MCTS). The RNN encodes the state (i.e., history of the walked path) and maps it separately to a policy and Q-values. In order to effectively train the agent from sparse rewards, we combine MCTS with the neural policy to generate trajectories yielding more positive rewards. From these trajectories, the network is improved in an off-policy manner using Q-learning, which modifies the RNN policy via parameter sharing. Our proposed RL algorithm repeatedly applies this policy-improvement step to learn the model. At test time, MCTS is combined with the neural policy to predict the target node. Experimental results on several graph-walking benchmarks show that M-Walk is able to learn better policies than other RL-based methods, which are mainly based on policy gradients. M-Walk also outperforms traditional KBC baselines.
Crystallographic Structural Studies of a Human Fc Fragment. II. A Complete Model Based on a Fourier Map at 3.5 Å Resolution (1976)

The crystal structure analysis of a human Fc fragment was pursued to 3.5 A resolution and a complete model was built and refined into the isomorphous Fourier map. The CH2 and CH3 domains show the immunoglobulin fold, with CH3 being closely similar to CH1, but CH2 intermediate in structure between V and CH3. The carbohydrate is rigidly attached to CH2, covering the C face. CH3 dimerizes as CH1-CL, but CH2 has no contact to the second chain. Residues involved in the lateral CH3-CH3 and the longitudinal CH3-CH2 contact are conserved in Ig classes and sub-classes. In IgM and IgE the two C-terminal domains also show this characteristic distribution of contact residues.
Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin (2012)

MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D′D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca 2+ it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. The MUC2-N aggregates were dissolved by removing Ca 2+ and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion.
Direct Catalytic Asymmetric Aldol Reaction (1999)

The direct catalytic asymmetric aldol reaction using aldehydes and unmodified ketones is described for the first time herein. This reaction was first found to be promoted by 20 mol % of anhydrous (R)-LLB (L = lanthanum, L = lithium, B = (R)-binaphthol moiety) at −20 °C, giving a variety of aldol products in ee's ranging from 44 to 94%. This asymmetric reaction has been greatly improved by developing a new heteropolymetallic asymmetric catalyst [(R)-LLB, KOH, and H2O]. Using 3−8 mol % of this catalyst, a variety of direct catalytic asymmetric aldol reactions were again found to proceed smoothly, affording aldol products in ee's ranging from 30 to 93% and in good to excellent yields. Interestingly, the use of this new heteropolymetallic asymmetric catalyst has realized a diastereoselective and enantioselective aldol reaction using cyclopentanone for the first time. It is also noteworthy that a variety of aldehydes, including hexanal, can be utilized for the current direct catalytic asymmetric aldol reaction. Chiral aldehydes containing α-hydrogen including (S)-hydrocinnamaldehyde-α-d have been found to produce the corresponding aldol products with negligible racemization (0−4%) at the α-position. One of the aldol products has been successfully converted to the key synthetic intermediates of epothilone A and bryostatin 7. The possible structure of the heteropolymetallic catalyst is also discussed. Finally, mechanistic studies have revealed a characteristic reaction pathway, namely that the reaction is kinetically controlled and the rate-determining step is the deprotonation of the ketone. This is consistent with the fact that the reaction rate is independent of the concentration of the aldehyde.
Induced remote ischemic pre-conditioning on ischemia-reperfusion injury in patients undergoing coronary artery bypass. (2010)

This study showed a significant reduction of enzyme marker CKMB in patients subjected to rIPC prior to CABG surgery. This suggests lesser degree of myocardial damage compared to control group in CABG patients.
Oxidative Stress and the JNK Pathway in Diabetes (2005)

Under diabetic conditions, oxidative stress is induced and the JNK pathway is activated, which is involved in deterioration of pancreatic beta-cell function found in diabetes. Oxidative stress and/or activation of the JNK pathway suppress insulin gene expression, accompanied by reduction of PDX-1 DNA binding activity. Treatment with antioxidants and/or suppression of the JNK pathway protect beta-cells from some of the toxic effects of hyperglycemia. The JNK pathway is also involved in the progression of insulin resistance; suppression of the JNK pathway in obese diabetic mice markedly improves insulin resistance and ameliorates glucose tolerance. The phosphorylation state of key molecules for insulin signaling is altered upon modification of the JNK pathway. Taken together, the JNK pathway plays a crucial role in progression of insulin resistance as well as beta-cell dysfunction found in diabetes and thus could be a potential therapeutic target for diabetes.
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence (2008)

The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a "lock and key" interaction is typical of innate receptor-ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.
Ligand interactions of the cation-independent mannose 6-phosphate receptor (1989)

The interaction of the bovine cation-independent mannose 6-phosphate receptor with a variety of phosphorylated ligands has been studied using equilibrium dialysis and immobilized receptor to measure ligand binding. The dissociation constants for mannose 6-phosphate, pentamannose phosphate, bovine testes beta-galactosidase, and a high mannose oligosaccharide with two phosphomonoesters were 7 X 10(-6) M, 6 X 10(-6) M, 2 X 10(-8) M, and 2 X 10(-9) M, and the mol of ligand bound/mol of receptor monomer were 2.17, 1.85, 0.9, and 1.0, respectively. We conclude that the cation-independent mannose 6-phosphate receptor has two mannose 6-phosphate-binding sites/polypeptide chain.