gebhart/patrepeval huggingface dataset:
Multistep Synthesis of Complex Boronic Acids from Simple MIDA Boronates (2008)

Due to its sensitivity to most synthetic reagents, it is typically necessary to introduce the boronic acid functional group just prior to its utilization. Overcoming this important limitation, we herein report that air- and chromatographically stable MIDA boronates are compatible with a wide range of common reagents which enables the multistep synthesis of complex boronic acid building blocks from simple B-containing starting materials. X-ray and variable temperature NMR studies link the unique stability of MIDA boronates to a kinetic inaccessibility of the potentially reactive boron p-orbital and/or nitrogen lone pair. These findings were collectively harnessed to achieve a short and modular total synthesis of (+)-crocacin C via the iterative cross-coupling of a structurally complex, MIDA-protected haloboronic acid building block.
Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage (2002)

The concomitant increase in AGEs and alteration of tensile properties of cartilage after ribose treatment suggest that aging-associated changes in AGEs have functional consequences for this tissue. The AGE-associated increases in strength and stiffness of cartilage may be beneficial by counteracting the decreases in these properties that are associated with degeneration. Conversely, the AGE-associated decrease in failure length, or increase in brittleness, together with increased stiffness may predispose cartilage to increased stress concentration, fracture, and aging-associated biomechanical dysfunction.
Immunological applications of single-domain llama recombinant antibodies isolated from a naïve library (2009)

We describe the rapid isolation of single-domain recombinant antibodies in VHH format from a pre-immune llama library created in our laboratory. Such naïve library has demonstrated to be a versatile tool and enabled the isolation of several different antibodies for any of the six proteins panned in parallel. The binders specific for human fibroblast growth factor receptor 1 (FGFR1) were successively analyzed in more detail and resulted suitable for both western blot and immunofluorescence analyses. Several milligrams per liter of antibodies were purified by affinity chromatography and used for kinetic and thermodynamic characterization. Their K(D) was in the nanomolar range and they apparently bound a FGF receptor 1 domain not overlapping the region recognized by its physiological ligand FGF. Altogether, the collected data indicate that the new library can enable the recovery of binders of high affinity, specificity and functionality in the conventional immunological tests, avoiding the necessity of further maturation steps. Such results confirmed recent reports of high affinity pre-immune IgNARs and supported the choice of using large single-domain recombinant antibody naïve libraries as an alternative to the preparation of immune libraries for selecting monoclonal antibodies, at convenient cost and time conditions.
From transcriptome analysis to immunogenomics: Current status and future direction (2009)

In 1994, we pioneered a complementary DNA (cDNA) sequencing project that aimed to predict the primary structures of unknown human proteins. Although our cDNA project was focused on the sequencing of large cDNAs, the following cDNA sequencing projects conducted by other groups have more extensively characterized mammalian transcriptome. In parallel, many groups have made a tremendous amount of effort to develop various resources for functional human genomics. In this context, to demonstrate the power of functional genomic approaches in practice, we have applied them for a comprehensive understanding of the immune system, which we term 'immunogenomics'. This mini-review first describes the historical background of our cDNA project and then provides perspectives on the present and future of immunogenomics based on our experiences.
Enzyme Therapy in Gaucher Disease Type 1: Effect of Neutralizing Antibodies to Acid β-Glucosidase (1997)

Gaucher disease type 1, a non-neuronopathic lysosomal storage disease, is caused by mutations at the acid beta-glucosidase locus. Periodic infusions of macrophage-targeted acid beta-glucosidase reverse hepatosplenomegaly, hematologic, and bony findings in many patients. Two patients receiving enzyme therapy developed neutralizing antibodies to acid beta-glucosidase that were associated with a lack of improvement or progressive disease. After initial improvement, case 1 had no additional response to 2 years of high-dose (50 U/kg every 2 weeks) enzyme therapy. Similarly, case 2 initially showed a favorable response to enzyme therapy that plateaued after 1 year of treatment. Both patients developed minor allergic reactions and antibodies to acid beta-glucosidase within the first 6 months of treatment. Enzyme therapy was discontinued in case 1, with resultant disease progression and need for splenectomy. An immunosuppression/tolerization protocol was initiated in case 2 because of disease progression and stable neutralizing antibody titers. The IgG neutralizing antibodies rapidly and completely inactivated the wild-type, but not the N370S, acid beta-glucosidase in vitro. Antibodies to human serum albumin and chorionic gonadotropin also developed. The finding of neutralizing antibodies to acid beta-glucosidase during enzyme therapy for Gaucher disease has significant implications for monitoring the therapeutic responses and for potential alternative future therapies for Gaucher disease.
Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis. (1990)

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.
Molecular mass measurement of polymerase chain reaction products amplified from human blood dna by electrospray ionization mass spectrometry (1995)

We report here on the first analysis of polymerase chain reaction (PCR) products amplified from a small amount of human blood DNA by electrospray ionization mass spectrometry (ESI-MS). Adenomatous polyposis coli (APC) gene fragment of about 50 base pairs (bp) with a relative molecular mass (M(r)) of approximately 15,000 u was amplified from human blood DNA by PCR. The accurate molecular mass of the PCR products was determined with an accuracy of approximately 0.005% by ESI-MS. The amount of DNA used was only 100 ng (approximately 50 zmol; the theoretically required amount of blood is therefore less than 1 microliter for PCR). The ESI-MS measurement of the PCR products proved to be a new accurate, sensitive and fast tool for gene diagnosis.
Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin. (1981)

Magnetically responsive albumin microspheres containing doxorubicin and magnetite (Fe3O4) were selectively targeted to Yoshida sarcoma tumors in rats by utilizing an extracorporeal magnet. Tumor cells were inoculated subcutaneously in the tail of rats, and the tumors were allowed to grow to an average size of 9 X 45 mm prior to initiating treatment. Drug-bearing microspheres (0.5 mg of doxorubicin per kg of body weight) were infused proximal to the tumor through the ventral caudal artery while the tumor was exposed to an external magnetic field of 5500 Oe for 30 min. Control animals received free doxorubicin administered either intravenously (5 mg/kg) or infused intraarterially (5 and 0.5 mg/kg), drug-bearing microspheres infused intraarterially (0.5mg/kg), without the external magnet, or placebo microspheres with magnetic localization. Of the 12 animals treated with a single dose in the experimental group, 9 exhibited total remission of the tumor, representing a disappearance of tumors as large as 60 mm in length. Marked tumor regression was observed in the remaining three rats, and no deaths or metastases occurred in the experimental group. In contrast, significant increases in tumor size with widespread metastases occurred in all control groups and most rats died. These experiments indicate that targeting of oncolytic agents to solid neoplasms by magnetic microspheres may be a means of increasing the efficacy and decreasing the toxicity of antitumor agents.
Antihyperlipidemic activities of Pleurotus ferulae on biochemical and histological function in hypercholesterolemic rats. (2011)

The present study suggests that 5% P. ferulae diet supplement provides health benefits, at least partially, by acting on the atherogenic lipid profile in hypercholesterolemic rats.
Reactivity of the Acridine Ring: One‐Pot Regioselective Single and Double Bromomethylation of Acridine and Some Derivatives. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Lateral and cross-lateral focusing of spherical particles in a square microchannel (2010)

The inertial migration of particles in micro-scale flows has received much attention due to its promising applications, such as the membrane-free passive separation of particles or cells. The particles suspended in rectangular channels are known to be focused near the center of each channel face as the channel Reynolds number (R(C)) increases due to the lift force balance and the hydrodynamic interactions of the particles with the wall. In this study, the three-dimensional positions of neutrally buoyant spherical particles inside a square microchannel are measured using the digital holographic microscopy technique, and a transition from the lateral tubular pinch to the cross-lateral focusing with increasing R(C) is reported. The particles are found to migrate first in the lateral direction and then cross-laterally toward the four equilibrium positions. A general criterion that can be used to secure the fully developed state of particle focusing in Lab-on-a-Chip applications is also derived. This criterion could be helpful for the accurate estimation of the design parameters of inertial microfluidic devices, such as R(C), channel length and width, and particle diameter.
Processing of Viral DNA Ends Channels the HIV-1 Integration Reaction to Concerted Integration*[boxs] (2005)

Retroviral DNA made by reverse transcription is blunt-ended, and the viral integrase protein must remove two nucleotides from each 3' end prior to integration into chromosomal DNA. Under most reaction conditions for integration in vitro, the majority of the reaction products are "half-site" products that result from integration of only one viral DNA end into one strand of the target DNA. Preprocessed DNA substrates are more efficient substrates for half-site reactions than are blunt-ended substrates, which require the removal of two nucleotides prior to integration. In contrast, we find that blunt-ended DNA is a better substrate for the biologically relevant reaction of concerted integration of pairs of viral DNA ends. The reaction pathway is channeled to concerted integration, and half-site integration products are reduced with blunt-ended DNA substrate that must first be processed by integrase. In addition, the terminal nucleotide requirements for concerted integration are more stringent than for the half-site reaction. Longer DNA is more efficient for the concerted reaction than is shorter DNA that is capable of efficient half-site integration. This suggests that nonspecific interactions of integrase with viral DNA distant from the termini contribute to the assembly of a complex that is competent for concerted integration. Finally, differential effects of mutation of a residue in the C-terminal domain of integrase on concerted versus half-site integration implicate protein-protein interactions involving this domain as important for concerted integration.
Performance evaluation of CROWNs: WDM multi-ring topologies (2002)

It is well known that the maximum node throughput achievable in a single channel ring network is inversely proportional to the number of connected nodes. Furthermore, in an optical medium network, the electronics required to elaborate in-transit data at each node creates a performance bottleneck for the whole communication system. Progress in WDM techniques has opened the possibility to overcome these problems by relying on a multi-channel, optical, solution. The paper presents and analyzes an approach to obtaining a concurrently accessed multi-ring all-optical WDM network (CROWN) with a node architecture in which in-transit packets pass through the node without being converted into the electronic domain. Using a single high speed transmitter and receiver per node, CROWN allows data to be maintained in the optical format while resolving receiver contentions. An original modeling technique, with an effective characterization of the principal aspects of the system behavior, is also provided for performance evaluation, showing that network capacity and network latency are improved under the proposed solution.
Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism (2017)

One quarter of patients suffering from acute critical illness such as severe trauma, sepsis, myocardial infarction (MI) or post cardiac arrest syndrome (PCAS) develop severe hemostatic aberrations and coagulopathy, which are associated with excess mortality. Despite the different types of injurious "hit", acutely critically ill patients share several phenotypic features that may be driven by the shock. This response, mounted by the body to various life-threatening conditions, is relatively homogenous and most likely evolutionarily adapted. We propose that shock-induced sympatho-adrenal hyperactivation is a critical driver of endothelial cell and glycocalyx damage (endotheliopathy) in acute critical illness, with the overall aim of ensuring organ perfusion through an injured microvasculature. We have investigated more than 3000 patients suffering from different types of acute critical illness (severe trauma, sepsis, MI and PCAS) and have found a potential unifying pathologic link between sympatho-adrenal hyperactivation, endotheliopathy, and poor outcome. We entitled this proposed disease entity, shock-induced endotheliopathy (SHINE). Here we review the literature and discuss the pathophysiology of SHINE.
An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells. (1976)

Extracts of serum-free medium, conditioned by contact with SV40-transformed BHK cells, stimulate DNA synthesis in cultured fibroblasts. From this source, we have purified a homogenous basic protein of 18,000 molecular weight, termed fibroblast derived growth factor. In submicrogram quantities, fibroblast derived growth factor stimulates DNA synthesis in mouse 3T3 cells, in the absence of added serum. Prior to the onset of DNA synthesis, both serum and fibroblast derived growth factor induce an array of nearly simultaneous biochemical changes in the membrane to 3T3 cells that include stimulation of the uptake of nucleosides, 2-deoxyglucose, and 86Rb+. These results strongly suggest that the early events are integral components of the proliferative response, rather than coincidental effects of nonmitogenic molecules present in serum.
Varicella-zoster virus infection: natural history, clinical manifestations, immunity and current and future vaccination strategies. (2018)

Varicella-zoster virus (VZV) is the etiologic agent of varicella (chicken pox), a childhood exanthematic disease that develops as a result of primary infection, and zoster (shingles), caused by reactivation of the virus persisting in a latent form in the dorsal sensory ganglia. Although varicella is generally a mild self-limiting illness, in immunocompromised subjects and adults it can have a serious clinical course that can lead to permanent damage of the central nervous system. In these and in most zoster cases, treatment with anti-herpetic drugs and/or immunotherapy is necessary. Because it is highly contagious, varicella is one of the most common exanthematic diseases. It is preventable by vaccination with an attenuated vaccine administered around the first year of age, and with a boost vaccination in school age. This article briefly describes the natural history and pathophysiology of VZV infection and its current epidemiology and provides an overview of current and future vaccine options to protect against varicella and/or zoster.
Virus-Specific CD8+Lymphocytes Share the Same Effector-Memory Phenotype but Exhibit Functional Differences in Acute Hepatitis B and C (2002)

Hepatitis B and hepatitis C viruses (HBV and HCV) are both noncytopathic and can cause acute and chronic infections of the liver. Although they share tropism for the same organ, development of chronic hepatitis is much more frequent following HCV infection, suggesting different mechanisms of viral persistence. In this study, we show that circulating HBV- and HCV-specific tetramer-positive CD8 cells during the acute phase of hepatitis B and C belong almost entirely to an effector-memory subset (CCR7(-) CD45RA(-)). Despite this phenotypic similarity, HBV- and HCV-specific CD8 cells show striking functional differences. HBV-specific tetramer-positive CD8 cells express high perforin content ex vivo, expand vigorously, and display efficient cytotoxic activity and gamma interferon (IFN-gamma) production upon peptide stimulation. A comparable degree of functional efficiency is maintained after the resolution of hepatitis B. In contrast, HCV-specific CD8 cells in the acute phase of hepatitis C express significantly lower levels of perforin molecules ex vivo and show depressed CD8 function in terms of proliferation, lytic activity, and IFN-gamma production, irrespective of the final outcome of the disease. This defect is transient, because HCV-specific CD8 cells can progressively improve their function in patients with self-limited hepatitis C, while the CD8 function remains persistently depressed in subjects with a chronic evolution.
Hybrid Rylene Arrays via Combination of Stille Coupling and C–H Transformation as High-Performance Electron Transport Materials (2012)

Hybrid rylene arrays have been prepared via a combination of Stille coupling and C-H transformation. The ability to extend the π system along the equatorial axis of rylenes not only leads to broadened light absorption but also increases the electron affinity, which can facilitate electron injection and transport with ambient stability.
Total synthesis of(.+-.)-dihydronepetalactone. (1991)

The cyclopropane derivatives are one of the most attractive starting materials for synthesizing iridoid monoterpenes. ^Wehave previously reported the synthesis ofdehydroiridodiol,lb) plinolslc) and hop ether le) starting
Hydrolysis of galactolipids by human pancreatic lipolytic enzymes and duodenal contents. (1995)

Monogalactosyldiacylglycerols (MGDG), digalactosyldiacylglycerols (DGDG) and sulfoquinovosyldiacylglycerols (SQDG) are major lipids in vegetable food. Their digestion and absorption are unknown. This study examines the hydrolysis of galactolipids in vitro with human duodenal contents, pancreatic juice, and purified human pancreatic lipases. Galactolipids were incubated with human duodenal contents, pancreatic juice, pure pancreatic carboxyl ester lipase (CEL), and colipase-dependent lipase with colipase (Lip-Col). Hydrolysis was estimated as release of free fatty acids and by the use of [3H]galactose or [3H]fatty acid-labeled DGDG. Pancreatic juice and duodenal contents hydrolyzed DGDG to fatty acids, digalactosylmonoacylglycerol (DGMG) and water-soluble galactose-containing compounds. The hydrolysis of DGDG was bile salt-dependent and had a pH optimum at 6.5-7.5. Human pancreatic juice released fatty acids from MGDG, DGDG, and SQDG. Purified CEL hydrolyzed all three substrates; the hydrolysis rate was MGDG > SQDG > DGDG. Pure Lip-Col had activity toward MGDG but had little activity against DGDG. Separation of pancreatic juice by Sephadex G100 gel filtration chromatography revealed two peaks with galactolipase activity that coincided with CEL (molecular mass 100 kD) and lipase (molecular mass 50 kD) peaks. In contrast to pure Lip-Col enzymes of the latter peak were as active against DGDG as against MGDG. Thus, DGDG is hydrolyzed both by CEL and by a pancreatic enzyme(s) with a molecular mass of 40-50 kD to fatty acids and lyso DGDG. MGDG, DGDG, and SQDG are all hydrolyzed by human pancreatic juice. Pure CEL hydrolyzed all three substrates.