gebhart/patrepeval huggingface dataset:
High Affinity Nanobodies against the Trypanosome brucei VSG Are Potent Trypanolytic Agents that Block Endocytosis (2011)

The African trypanosome Trypanosoma brucei, which persists within the bloodstream of the mammalian host, has evolved potent mechanisms for immune evasion. Specifically, antigenic variation of the variant-specific surface glycoprotein (VSG) and a highly active endocytosis and recycling of the surface coat efficiently delay killing mediated by anti-VSG antibodies. Consequently, conventional VSG-specific intact immunoglobulins are non-trypanocidal in the absence of complement. In sharp contrast, monovalent antigen-binding fragments, including 15 kDa nanobodies (Nb) derived from camelid heavy-chain antibodies (HCAbs) recognizing variant-specific VSG epitopes, efficiently lyse trypanosomes both in vitro and in vivo. This Nb-mediated lysis is preceded by very rapid immobilisation of the parasites, massive enlargement of the flagellar pocket and major blockade of endocytosis. This is accompanied by severe metabolic perturbations reflected by reduced intracellular ATP-levels and loss of mitochondrial membrane potential, culminating in cell death. Modification of anti-VSG Nbs through site-directed mutagenesis and by reconstitution into HCAbs, combined with unveiling of trypanolytic activity from intact immunoglobulins by papain proteolysis, demonstrates that the trypanolytic activity of Nbs and Fabs requires low molecular weight, monovalency and high affinity. We propose that the generation of low molecular weight VSG-specific trypanolytic nanobodies that impede endocytosis offers a new opportunity for developing novel trypanosomiasis therapeutics. In addition, these data suggest that the antigen-binding domain of an anti-microbial antibody harbours biological functionality that is latent in the intact immunoglobulin and is revealed only upon release of the antigen-binding fragment.
Cyclooxygenase-2???Specific Inhibitors and Cardiorenal Function: A Randomized, Controlled Trial of Celecoxib and Rofecoxib in Older Hypertensive Osteoarthritis Patients (2001)

Patients taking antihypertensive therapy and receiving cyclooxygenase-2-specific inhibitors should be monitored for the development of cardiorenal events. Patients receiving celecoxib experienced less edema and less destabilization of blood pressure control compared with those receiving rofecoxib.
Efficient Creation of 3D Models from Buildings’ Floor Plans (2011)

Nowadays, there is a huge need for efficient tools to produce virtual models, mostly urban, in several areas such as architecture, movies, games, virtual worlds and commercial applications. These models may be either generated "fictional" models or reconstructed models representing real world structures. This last option is the motivation behind this paper and past experience has shown us that, usually, it is harder to recreate existing models than trying to create new ones.
Macrophage inflammatory protein: its characteristics, biological properties and role in the regulation of haemopoiesis. (1993)

Studies on haemopoietic stem cells had led to the realisation that negative feedback inhibitors play an important role in regulating their proliferation. One such molecule was identified as MIP-1 alpha. One of a family of cytokines, originally recognised as inflammatory molecules, MIP-1 alpha is now potentially valuable as a means of manipulating and protecting haemopoietic (and possibly other) stem cells during chemotherapy. This short review briefly considers the structural classification of MIP-1 alpha and its molecular relatives and indicates some of the probable human/murine equivalent molecules outlining the evidence for the equivalence of MIP-1 alpha (murine) and LD78 (human). Sources of MIP-1 alpha/LD78 are identified as monocyte/macrophage and lymphocytic cells and their role in inflammatory responses is seen to be significant. All proliferation in haemopoietic tissue is now recognised as a major target for MIP-1 alpha action. In vitro it synergises with certain growth factors to promote progenitor cell colony formation, but effects are dependent on the maturational age of the cells promoted. With more primitive cells it is seen as inhibitory. This property is particularly valuable in vivo where MIP-1 alpha can protect stem cells against the effects of cytotoxic agents. Since it appears that leukaemic stem cell proliferation is not inhibited, MIP-1 alpha/LD78 present great potential for stem cell protection in the theatre of cytotoxic therapies.
Diagnosis and Monitoring of Hepatic Injury. I. Performance Characteristics of Laboratory Tests (2000)

Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, gamma-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.
CT-guided microwave ablation through the lungs for treating liver tumors near the diaphragm (2017)

CT-guided MWA was used on 131 tumors that were close to the diaphragm (distance between tumor and diaphragm ≤ 5 mm) in 117 patients with liver cancer. The tumors were divided into a < 3.0 cm group (Group I, n= 101) and a ≥ 3.0 cm group (Group II, n= 30) based on tumor diameters. The complications within 2 weeks following treatment were counted, and the safety and short-term efficacy of MWA were analyzed.
Nanowell surface enhanced Raman scattering arrays fabricated by soft-lithography for label-free biomolecular detections in integrated microfluidics (2005)

We describe a low-cost, ultrasensitive surface-enhanced Raman scattering (SERS) substrate in microfluidic biochips fabricated by soft lithography. A batch nanofabrication method is developed to create nanopillars structures on a silicon wafer as a master copy of molding, then the complementary nanowells structures on polydimethylsiloxane (PDMS) are created by soft lithography. The selective deposition of Ag thin film on the nanowells is applied to create SERS active sites before the integration with a glass-based microfluidic chip which functions as a sample delivery device and a transparent optical window for SERS spectroscopic imaging. Detections of Rhodamine 6G and adenosine SERS spectra are accomplished by using a 785nm laser with 300μW excitation power. The Raman scattering signal enhancement on the nanowell-based Ag SERS substrate is more than 107 times higher than the control sample (i.e. the smooth Ag layer on PDMS). Fabrication of ultrasensitive nanowell SERS substrate by economical and repeatable soft lithography method can contribute to the future microdevices for high throughput screening of functional genomics, proteomics, and cellular activities.
Effect of Vehicles on Diclofenac Permeation across Excised Rat Skin. (1995)

The in vitro percutaneous permeation of diclofenac from various vehicles was examined using rat abdominal skin as a model membrane. The oleaginous vehicles used in this study consisted of three components: i.e. fatty acid, fatty acid ester and nonpolar oil. The solubilities of sodium diclofenac in formulated vehicles were above 0.2 M. The effect of each oleaginous component in the vehicle on the permeation of diclofenac across the skin was in the following order: oleic acid > isostearic acid, diisopropyl adipate = diethyl sebacate > Panasate 875 and squalane > liquid paraffin. To clarify the reason for the differences in permeation among the fatty acid esters, the release of diclofenac through either porous or lipoidal membranes from these vehicles in vitro and the solubility of sodium diclofenac in the vehicles were studied. However, no relationship was observed between the release rate or solubility and skin permeability. The skin permeation of diclofenac increased following pretreatment with diisopropyl adipate or diethyl sebacate, but not with middle chain triglyceride (Panasate 875). These results suggested that the main reason may be the enhancement effect of fatty acid esters. Emulsions and creams containing 3% sodium diclofenac were prepared using the above oleaginous vehicles. A large flux and short lag time were observed in these preparations compared with an aqueous suspension of sodium diclofenac. The incorporation of urea significantly enhanced the permeation of diclofenac from these preparations. These results suggest that the emulsion and cream prepared in this study are useful for development for practical purposes.
[Use of high velocity mechanical injection for the transfer of foreign DNA into early mouse embryos]. (1991)

The possibility of high velocity mechanical transfer of foreign DNA into inner cell mass of mouse blastocyst was shown. Penetration of tungsten microparticles into early embryo cell nuclei and their localization on mitotic chromosomes was demonstrated. About 70% of developing embryos survived the bombardment. Total DNA of the mice born from bombarded embryos was analyzed by blot-hybridization and PCR with Southern hybridization. In three cases, the presence of the transferred plasmid DNA (pSV3-neo) was revealed.
Functional analysis of genes involved in the biosynthesis of isoprene in Bacillus subtilis (2007)

In comparison to other bacteria Bacillus subtilis emits the volatile compound isoprene in high concentrations. Isoprene is the smallest representative of the natural product group of terpenoids. A search in the genome of B. subtilis resulted in a set of genes with yet unknown function, but putatively involved in the methylerythritol phosphate (MEP) pathway to isoprene. Further identification of these genes would give the possibility to engineer B. subtilis as a host cell for the production of terpenoids like the valuable plant-produced drugs artemisinin and paclitaxel. Conditional knock-out strains of putative genes were analyzed for the amount of isoprene emitted. Differences in isoprene emission were used to identify the function of the enzymes and of the corresponding selected genes in the MEP pathway. We give proof on a biochemical level that several of these selected genes from this species are involved in isoprene biosynthesis. This opens the possibilities to investigate the physiological function of isoprene emission and to increase the endogenous flux to the terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate, for the heterologous production of more complex terpenoids in B. subtilis.
Structural Characterization of Four Genetic Variants of Human Serum Albumin Associated with Alloalbuminemia in Italy (1997)

A long‐term electrophoretic survey on plasma proteins, which was carried out in several clinical laboratories in Italy, identified 28 different genetic variants of human serum albumin and four cases of analbuminemia. We have previously characterized 16 point mutations, 3 C‐terminal mutants, and the genetic defects in two analbuminemic subjects. Here, we report the molecular defects of four alloalbumins that have been characterized by protein structural analysis. Of these, three represent new single‐point mutations: albumins Tregasio, Val122→ Glu, Bergamo, Asp314→ Gly, and Maddaloni, Va1533→ Met. The fourth, albumin Besana Brianza, has the same Asp494→Asn mutation that introduces a glycosylation site which has been previously reported in a variant from New Zealand, albumin Casebrook. However, in contrast to albumin Casebrook, albumin Besana Brianza is only partially glycosylated and the oligosaccharide is heterogeneous, consisting of a biantennary complex type N‐glycan with either two or one sialic acid residue(s) on the antennae. Both albumin Maddaloni and Besana Brianza represent mutations at hypermutable CpG dinucleotide sites; albumin Maddaloni is a mutant that does not involve a charged amino acid.
Loss of oestrogen receptor β, high PCNA and p53 expression and aneuploidy as markers of worse prognosis in ovarian granulosa cell tumours (2003)

Loss of ERbeta expression, high PCNA expression and aneuploidy, characterized a subgroup of OGCT with a worse outcome. The identification of a high-risk subclass of OGCT may be of primary importance in addressing appropriate therapeutic strategies, offering the chance to prevent relapses and metastases by using adjunctive, specifically targetted, more aggressive therapies.
A Simple General Method for the Acylation of Ethyl Indole-2-carboxylates (1980)

Reaction of ethyl indole-2-carboxylates(1) -with carboxylic acids in acetonitrile, using trifluoroacetic anhydride-phosphoric acid gave the ethyl 3-acylindole-2-carboxylates( 2 ) in satisfactory yields.The present method provides a simple general method for acylation of ethyl indole-2-carboxylates.Acylation reaction of indoles at their C-3 position is one of the important and fundamental reactions in the indole chemistry, and well documented1).On the other hand indole-2-carboxylic acids or their esters(l) are known2) to serve as stable synthon.However, acylation of thern(1) -has been little known except for
Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells (2004)

Botulinum neurotoxins (BoNTs) act as zinc-dependent endopeptidases that cleave proteins required for neurotransmitter release. To detect toxin activity, fragments of the toxin substrate proteins, synaptobrevin (Syb) or synaptosome-associated protein of 25 kDa (SNAP-25), were used to link cyan fluorescent protein (CFP) to yellow fluorescent protein (YFP). Cleavage of these fusion proteins by BoNTs abolished fluorescence resonance energy transfer between the CFP and YFP, providing a sensitive means to detect toxin activity in real-time in vitro. Furthermore, using full-length SNAP-25 and Syb as the linkers, we report two fluorescent biosensors that can detect toxin activity within living cells. Cleavage of the SNAP-25 fusion protein abolished fluorescence resonance energy transfer between CFP and YFP, and cleavage of Syb resulted in spatial redistribution of YFP fluorescence in cells. This approach provides a means to carry out cell-based screening of toxin inhibitors and to study toxin activity in situ. By using these biosensors, we found that the subcellular localizations of SNAP-25 and Syb are critical for efficient cleavage by BoNT/A and B, respectively.
Grating-Based Optical Fiber Interfaces for Silicon-on-Insulator Photonic Integrated Circuits (2010)

In this paper, we review our work on efficient interfaces between a silicon-on-insulator photonic IC and a single-mode optical fiber based on grating structures. Several device configurations are presented that provide high efficiency, polarization insensitive, and broadband optical coupling on a small footprint. The high alignment tolerance and the fact that the optical fiber interface is out-of-plane provide opportunities for easy packaging and wafer-scale testing of the photonic IC. Finally, an optical probe based on a grating structure defined on the fiber facet is described.
Heterosubtypic T-Cell Immunity to Influenza in Humans: Challenges for Universal T-Cell Influenza Vaccines (2016)

Influenza A virus (IAV) remains a significant global health issue causing annual epidemics, pandemics, and sporadic human infections with highly pathogenic avian or swine influenza viruses. Current inactivated and live vaccines are the mainstay of the public health response to influenza, although vaccine efficacy is lower against antigenically distinct viral strains. The first pandemic of the twenty-first century underlined the urgent need to develop new vaccines capable of protecting against a broad range of influenza strains. Such "universal" influenza vaccines are based on the idea of heterosubtypic immunity, wherein immune responses to epitopes conserved across IAV strains can confer protection against subsequent infection and disease. T-cells recognizing conserved antigens are a key contributor in reducing viral load and limiting disease severity during heterosubtypic infection in animal models. Recent studies undertaken during the 2009 H1N1 pandemic provided key insights into the role of cross-reactive T-cells in mediating heterosubtypic protection in humans. This review focuses on human influenza to discuss the epidemiological observations that underpin cross-protective immunity, the role of T-cells as key players in mediating heterosubtypic immunity including recent data from natural history cohort studies and the ongoing clinical development of T-cell-inducing universal influenza vaccines. The challenges and knowledge gaps for developing vaccines to generate long-lived protective T-cell responses is discussed.
Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. (2000)

Promoter hypermethylation is an important pathway for repression of gene transcription in cancer cells. We analyzed aberrant DNA methylation at four genes in primary tumors from 95 head and neck cancer patients and then used the presence of this methylation as a marker for cancer cell detection in serum DNA. These four genes were tested by methylation-specific PCR and included: p16 (CDKN2A), O6-methylguanine-DNA-methyltransferase, glutathione S-transferase P1, and death-associated protein kinase (DAP-kinase). Fifty-five % (52 of 95) of the primary tumors displayed promoter hypermethylation in at least one of the genes studied: 27% (26/95) at p16, 33% (31 of 95) at O6-methylguanine-DNA-methyltransferase; and 18% (17 of 92) at DAP-kinase. No promoter hypermethylation was observed at the glutathione S-transferase P1 gene promoter. We detected a statistically significant correlation between the presence of DAP-kinase gene promoter hypermethylation and lymph node involvement (P = 0.014) and advanced disease stage (P = 0.016). In 50 patients with paired serum available for epigenetic analysis, the same methylation pattern was detected in the corresponding serum DNA of 21 (42%) cases. Among the patients with methylated serum DNA, 5 developed distant metastasis compared with the occurrence of metastasis in only 1 patient negative for serum promoter hypermethylation (P = 0.056). Promoter hypermethylation of key genes in critical pathways is common in head and neck cancer and represents a promising serum marker for monitoring affected patients.
Common double- and single-stranded DNA binding factor for a sterol regulatory element. (1992)

A cis-acting element necessary for sterol regulation, SRE-1, has previously been identified in the promoters of the low density lipoprotein receptor, hydroxymethylglutaryl (HMG)-CoA reductase, and HMG-CoA synthase genes. In this report we describe a nuclear factor, SRE-BF, isolated from Chinese hamster ovary nuclear extracts, that binds to the SRE-1 octanucleotide sequence. In addition to sequence-specific binding to SRE-1, as indicated by competition analysis with double-stranded DNA fragments, single-stranded oligomer DNA sequences also compete for binding in a sequence-specific fashion. Photochemical cross-linking experiments suggest that a common protein factor, with apparent molecular mass of 45-49 kDa, recognizes both single-stranded and double-stranded SRE-1. The binding specificity of SRE-BF to single-stranded SRE-1 closely correlates with the reported in vivo ability of SRE-1 to direct sterol responsiveness of transcription.
[V-Y advancement of skin flap pedicled with upper limb lateral branch for small skin defect in the dorsal elbow]. (2012)

It is ideal to treat small skin defect in the dorsal elbow with V-Y advancement of skin flap pedicled with the upper limb lateral branch because of easier operation and less injury at donor site.
Therapeutic Roles of Peroxisome Proliferator–Activated Receptor Agonists (2005)

Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPARalpha and -gamma are currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPARalpha. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPARgamma, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPARgamma agonists are therefore used to treat type 2 diabetes. PPARalpha and -gamma agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPARalpha/gamma agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPARdelta, and its potential as a therapeutic target are currently under investigation.
Preparation and dienophilic reactions of nitrosyl cyanide (1980)

Nitrosyl chloride and silver cyanide react at low temperatures to give nitrosyl cyanide (ONCN) which undergoes 1,4-cycloaddition reactions with conjugated dienes to form the corresponding 2-cyano-3,6-dihydro-2H-1,2-oxazines. Thus, the alkaloid, thebaine (1), reacted with a limited quantity of nitrosyl cyanide to form a single adduct (2; R = H, X = CN) convertible into 14-cyanamidocodeinone (3); with an excess of nitrosyl cyanide the related N-cyanomethyl derivative (2; R = X = CN) was formed. Similarly, N-cyano-oxazines have been prepared from buts-1,3-diene and its 2,3-dimethyl, 1-methoxycarbonyl-4-methyl, 1-cyano-4-methyl, and 1,4-bisethoxycarbonyl derivatives. Base-induced rearrangements reactions leading to a pyridone (7), a pyrrolinone (11), and a mixture of dihydrofurans (14) are described.