gebhart/patrepeval huggingface dataset:
Overexpression of tumour‐ssociated carbohydrate antigen sialyl‐Tn in advanced bladder tumours (2013)

Little is known on the expression of the tumour-associated carbohydrate antigen sialyl-Tn (STn), in bladder cancer. We report here that 75% of the high-grade bladder tumours, presenting elevated proliferation rates and high risk of recurrence/progression expressed STn. However, it was mainly found in non-proliferative areas of the tumour, namely in cells invading the basal and muscle layers. STn was also found in tumour-adjacent mucosa, which suggests its dependence on a field effect of the tumour. Furthermore, it was not expressed by the normal urothelium, demonstrating the cancer-specific nature of this antigen. STn expression correlated with that of sialyltransferase ST6GalNAc.I, its major biosynthetic enzyme. The stable expression of ST6GalNAc.I in the bladder cancer cell line MCR induced STn expression and a concomitant increase of cell motility and invasive capability. Altogether, these results indicate for the first time a link between STn expression and malignancy in bladder cancer. Hence, therapies targeting STn may constitute new treatment approaches for these tumours.
Immunotherapy combination strategies (non-chemotherapy) in non-small cell lung cancer (2018)

Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors such as pembrolizumab have now received FDA approval in the first-line setting for patients with positive PD-L1 expression tumor types; however, only a portion of patients have shown objective and sustainable responses. To expand the number of patients with observed response to immunotherapeutic agents including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC.
DNA methylation and chromatin structure (1991)

Studies of the whole genome by molecular and cytogenetic methods have implicated DNA methylation in the formation of 'inactive chromatin'. This has been confirmed by analysis of specific endogenous sequences, and has been mimicked by introducing methylated and non-methylated sequences into cells. As well as affecting chromatin structure. DNA methylation also represses transcription. A protein (MeCP) which binds specifically to methylated DNA has been identified. The properties of MeCP could account for the effects of DNA methylation on both chromatin and transcription.
Nitrogen Fixation: The Mechanism of the Mo-Dependent Nitrogenase (2003)

This review focuses on recent developments elucidating the mechanism of the Mo-dependent nitrogenase. This enzyme, responsible for the majority of biological nitrogen fixation, is composed of two component proteins called the MoFe protein and the Fe protein. Recent progress in understanding the mechanism of this enzyme has focused on elucidating the structures of the active site metal clusters and of the proteins, understanding substrate interactions with the active site, defining the flow of electron transfer between the metal clusters, and defining the various roles of MgATP hydrolysis.
Separation of Semiconducting from Metallic Carbon Nanotubes by Selective Functionalization with Azomethine Ylides (2006)

A mild and efficient method for the functionalization of SWNTs by cycloaddition of azomethine ylides derived from trialkylamine-N-oxides is described. Selective reaction of semiconducting carbon nanotubes was achieved by preorganizing the starting N-oxides on the nanotube surface prior to generating the reactive ylides. Separation of met-SWNTs from functionalized sem-SWNTs was successfully accomplished by inducing solubilization of sem-SWNTs in the presence of lignoceric acid.
On the Adaptive Software-Defined LDPC-Coded Multidimensional Spatial-MIMO Multiband Generalized OFDM Enabling Beyond 10-Tb/s Optical Transport (2013)

Future Internet technologies will be affected by limited bandwidth of information infrastructure, high energy consumption, and heterogeneity of optical networks. In order to simultaneously solve these problems, we propose an adaptive multidimensional mode-multiplexed software-defined LDPC-coded modulation scheme suitable for few-mode-fiber-optic communications enabling beyond 10-Tb/s optical transport. This scheme employs the optimum multidimensional signal constellations and generalized OFDM operation principle. The proposed scheme significantly outperforms the corresponding scheme based on conventional polarization-division multiplexed QAM.
Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding (2008)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand BindingVijay M. Krishnamurthy, George K. Kaufman, Adam R. Urbach, Irina Gitlin, Katherine L. Gudiksen, Douglas B. Weibel, and George M. WhitesidesView Author Information Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138 Cite this: Chem. Rev. 2008, 108, 3, 946–1051Publication Date (Web):March 12, 2008Publication History Received13 December 2006Published online12 March 2008Published inissue 1 March 2008https://pubs.acs.org/doi/10.1021/cr050262phttps://doi.org/10.1021/cr050262presearch-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views11269Altmetric-Citations612LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Hydrophobicity,Inhibitors,Ligands,Peptides and proteins,Sulfones Get e-Alerts
Sendai virus‐based expression of HIV‐1 gp120: reinforcement by the V(−) version (1997)

SeV-based expression serves as a novel choice for producing large quantities of HIV-1 gp120 and will greatly facilitate biochemical, biological and immunological studies of this important glycoprotein.
Nephropathy in type 2 diabetes (1999)

End-stage renal failure (ESRF) in diabetic patients, mostly type 2, has become the most frequent cause of renal replacement therapy in western Europe. The majority of patients with type 2 diabetes and renal failure suffer from diabetic glomerulosclerosis, but nondiabetic renal disease and atypical presentations, e.g. as irreversible acute renal failure or ischaemic nephropathy, play an increasingly important role. Known risk factors for the onset of diabetic nephropathy include (1) genetic predisposition (indicated by a history of hypertension and cardiovascular events in first-degree relatives), (2) quality of glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in approximately 80%. In patients with established diabetic nephropathy, hypertension is the most important factor which promotes progression, and this is susceptible to intervention. Although less data are available for type 2 diabetes (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive agent of first choice, but monotherapy is rarely sufficient to achieve the blood pressure goal. Although, at least in principle, diabetic nephropathy is a preventable condition, currently only a minority of type 2 diabetic patients in western Europe receives adequate medical treatment to prevent onset or progression of diabetic nephropathy. Consequently, novel approaches to patient management and interdisciplinary interaction are necessary to fulfil the postulate of the St Vincent declaration concerning prevention of diabetic complications.
Total Chemical Synthesis of a D-Enzyme: The Enantiomers of HIV-1 Protease Show Reciprocal Chiral Substrate Specificity (1992)

The D and L forms of the enzyme HIV-1 protease have been prepared by total chemical synthesis. The two proteins had identical covalent structures. However, the folded protein-enzyme enantiomers showed reciprocal chiral specificity on peptide substrates. That is, each enzyme enantiomer cut only the corresponding substrate enantiomer. Reciprocal chiral specificity was also evident in the effect of enantiomeric inhibitors. These data imply that the folded forms of the chemically synthesized D- and L-enzyme molecules are mirror images of one another in all elements of the three-dimensional structure. Enantiomeric proteins are expected to display reciprocal chiral specificity in all aspects of their biochemical interactions.
THE PATTERNS OF NATURAL VARIATION IN HUMAN GENES (2005)

Currently, more than 10 million DNA sequence variations have been uncovered in the human genome. The most detailed variation discovery efforts have focused on candidate genes involved in cardiovascular disease or in susceptibilities associated with exposure to environmental agents. Here we provide an overview of natural genetic variation from the literature and in 510 human candidate genes resequenced for variation discovery. The average human gene contains 126 biallelic polymorphisms, 46 of which are common (> or =5% minor allele frequency) and 5 of which are found in coding regions. Using this complete picture of genetic diversity, we explore conservation, signatures of selection, and historical recombination to mine information useful for candidate gene association studies. In general, we find that the patterns of human gene variation suggest that no one approach will be appropriate for genetic association studies across all genes. Therefore, many different approaches may be required to identify the elusive genotypes associated with common human phenotypes.
Antidisialoganglioside/granulocyte macrophage–colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcγRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis (2002)

Polymorphonuclear leukocytes (PMNs) mediate antibody-dependent cellular cytotoxicity (ADCC), which is increased by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to determine whether PMN ADCC also would be increased by the addition of an antibody/GM-CSF fusion protein and whether this would be associated with the up-regulation and activation of Mac-1 (CD11b/CD18) and with azurophil granule exocytosis. ADCC against LA-N-1 human neuroblastoma cells was evaluated with 4-hour calcein acetoxymethyl ester (calcein-AM) microcytotoxicity assay, electron microscopy, and multi-parameter flow cytometry. With the calcein-AM assay, LA-N-1 cell survival was 10%, 55%, and 75% when PMN ADCC was mediated by the antidisialoganglioside (anti-GD2) immunocytokine hu14.18/GM-CSF, by monoclonal antibody (mAb) hu14.18 mixed with GM-CSF, and by hu14.18 alone. Function-blocking mAbs demonstrated that FcgammaRII and FcgammaRIII were required for ADCC with hu14.18 alone or mixed with GM-CSF, but that only FcgammaRII was required for ADCC with hu14.18/GM-CSF. ADCC mediated by hu14.18 and hu14.18/GM-CSF was Mac-1 dependent. Electron microscopy demonstrated the greatest PMN adhesion, spreading, and lysis of targets with hu14.18/GM-CSF. Monoclonal antibodies blocking Mac-1 function allowed the tethering of PMN to targets with hu14.18/GM-CSF but prevented adhesion, spreading, and cytolysis. Flow cytometry showed that hu14.18 with or without GM-CSF and hu14.18/GM-CSF all mediated Mac-1-dependent PMN-target cell conjugate formation but that GM-CSF was required for the highest expression and activation of Mac-1, as evidenced by the mAb24-defined beta(2)-integrin activation epitope. Hu14.18/GM-CSF induced the highest sustained azurophil granule exocytosis, almost exclusively in PMNs with activated Mac-1. Thus, hu14.18/GM-CSF facilitates PMN ADCC against neuroblastoma cells associated with FcgammaRII and Mac-1-dependent enhanced adhesion and degranulation.
Cooperative interaction between interleukin 10 and galectin-3 against liver ischemia-reperfusion injury. (2002)

These data suggest that IL-10 and galectin-3 cooperatively interact to protect cells from ischemia-reperfusion injury.
Expression of the ULBP ligands for NKG2D by B‐NHL cells plays an important role in determining their susceptibility to rituximab‐induced ADCC (2009)

Antibody-dependent cellular cytotoxicity (ADCC) is a major antitumor mechanism of action of therapeutic monoclonal antibodies (mAbs). The aim of this study was to identify tumor-associated factors which determine susceptibility to rituximab-induced ADCC. Thirty different CD20+ non-Hodgkin lymphoma cell lines were phenotyped for characteristics such as level of expression of NKG2D ligands, and the influence thereof on susceptibility to rituximab-induced ADCC was established. The present study demonstrated that tumor cell susceptibility to rituximab-induced ADCC was determined by 3 major tumor-associated factors: (i) the amount of the target molecule, CD20; (ii) the amount of the ligands for inhibitory killer Ig-like receptors, major histocompatibility complex class I; and (iii) the amounts of some of the NKG2D ligands, especially UL16-binding protein (ULBP) 1-3. The importance of the ULBPs was confirmed using antibody blockade. In conclusion, this is the first report to show the importance for rituximab-induced ADCC of ULBPs expressed on tumor cells. The ULBPs could be valuable diagnostic biological markers and significant targets for immunotherapy to improve efficacy not only of rituximab but also of other therapeutic mAbs.
Straightforward Synthesis of Axially Chiral 1,4-Naphthodiazepine Derivatives (2000)

Methyl 2,2'-dimethoxy-1,1'-binaphthalene-3-carboxylate reacts with 1,2-diamines to form 1 in excellent yields. The effects of the ester as well as the diamine structure were elucidated. The chirality of the starting binaphthalene derivative is retained.
Respiratory Syncytial Virus Is an Important Cause of Community-Acquired Lower Respiratory Infection among Hospitalized Adults (1996)

Respiratory syncytial virus (RSV), the most important cause of lower respiratory disease in infants and young children, is rarely considered among the causes for community-acquired lower respiratory infection in adults. All noninstitutionalized adults hospitalized with community-acquired pneumonia in two Ohio counties were evaluated between December 1990 and May 1992. Fifty-three (4.4%) of 1195 adults admitted during the RSV seasons and 4 (1.0%) of 390 in the off-season had serologic evidence of RSV infection, making RSV one of the four most common pathogens identified. RSV-infected patients had clinical features (e.g., wheezing and rhonchi) that distinguished them from all non-RSV-infected patients and other features (e.g., nonelevated white blood cell counts) that distinguished them from those infected with bacterial or atypical agents. However, RSV infection was not diagnosed during hospitalization for any of the 57 RSV-infected patients. RSV should be considered in the differential diagnosis for adults hospitalized between November and April with community-acquired lower respiratory infection.
Effect of Stationary Guiding Vanes on Improvement of the Washout Behind the Rotor in Centrifugal Blood Pumps (1992)

In centrifugal pumps, there always exists an area of stagnation between the rear of the rotor and the rear housing wall that promotes thrombus formation around the axle. Some current devices overcome the problem by using holes in the rotor plane, leading to increased hydrodynamic losses and shear stress. In this study, a simple apparatus was developed to overcome this problem. Guiding vanes were fixed to the rear housing wall. These vanes decrease the tangential velocity of the fluid and thus the centrifugal force, leading to an increased secondary flow toward the axle. The effect of such vanes was studied in videographic and ultrasound studies. An increase of washout and mixing between the flow layers could be demonstrated (stay time < 200 msec versus several seconds without vanes). In the first animal experiment using nonoptimized vanes, there was no thrombus at the back plane or the seal, and only a small thrombus at the transition between axle and rotor. Hemolysis was slightly elevated (3.2 mg/dl versus 2.5 mg/dl in control experiments). In conclusion, it is highly likely that this simple system will improve the flow characteristics in centrifugal pumps.
TAT-mediated Delivery of LAD Restores Pyruvate Dehydrogenase Complex Activity in the Mitochondria of Patients with LAD Deficiency (2008)

Modern medicine offers no cure for mitochondrial disorders such as lipoamide dehydrogenase (LAD) deficiency. LAD is the E3 subunit shared by alpha-ketoacid dehydrogenase complexes in the mitochondrial matrix, and these complexes are crucial for the metabolism of carbohydrates and amino acids. We propose a novel concept for restoring the activity of an immense multicomponent enzymatic complex by replacing one mutated component, the LAD subunit. Our approach entails the fusing of LAD with the transactivator of transcription (TAT) peptide, which is capable of rapidly crossing biological membranes, thereby allowing TAT-LAD to be delivered into cells and their mitochondria where it can replace the mutated endogenous enzyme. Our results show that TAT-LAD is indeed delivered into the cells and their mitochondria, where it is processed, restoring LAD activity to normal values and, most importantly, increasing the activity of pyruvate dehydrogenase complex. We report here, for the first time, that TAT-mediated replacement of one mutated component restores the activity of an essential mitochondrial multicomponent enzymatic complex in cells of patients with enzyme deficiencies. We believe that this approach involving TAT-mediated enzyme replacement therapy (ERT) can be applied to the treatment of LAD deficiency as well as to other mitochondrial and metabolic disorders.
Organic acid metabolism in cider and perry fermentations. II.—Non‐volatile organic acids of cider‐apple juices and sulphited ciders (1960)

Abstract The non‐volatile organic acids of cider‐apple juices and of ciders from sulphited fermentations have been separated using chromatographic methods, and identified. Several juice acids not previously detected were identified, namely mucic, benzoic, gluconic and 2‐methyl‐2,3‐dihydroxybutyric acid. During fermentation malic and gluconic acids often increased considerably in amount, appreciable quantities of succinic and lactic acids being formed together with small amounts of 2‐methyl‐, 3‐methyl‐, 2‐ethyl‐ and 3‐ethyl‐dihydroxy‐butyric acids, fumaric, α‐hydroxyglutaric and perhaps 2‐ketogluconic acids; pectic degradation gave rise to appreciable quantities of mono‐, di‐ and tri‐galacturonic acids.
Laser Synthesis of Low‐Agglomerated Submicrometer Silicon Nitride Powders from Chlorinated Silanes (1991)

The laser chemical vapor precipitation of Si 3 N 4 powder from mixtures of SiH 2 Cl 2 and NH 3 has been studied. The reactant gases were mixed at different heights with respect to the laser beam, thus preventing low‐temperature reactions and agglomeration of the produced particles. The morphology and the size of the particles formed are dependent on the injection height of NH 3 into the silicon reactant gas stream. Particle diameters are typically between 15 and 110 nm.
Osteosarcoma incidence and survival rates from 1973 to 2004 (2009)

This comprehensive, population-based description of osteosarcoma, identified important differences in incidence, survival, pathologic subtype, and anatomic site among age groups, and quantified the impact of osteosarcoma in patients with Paget disease or as a second cancer on incidence and mortality rates. These findings may have implications in understanding osteosarcoma biology and epidemiology.
Using Java reflection to automate extension language parsing (1999)

An extension language is an interpreted programming language designed to be embedded in a domain-specific framework. The addition of domain-specific primitive operations to an embedded extension language transforms that vanilla extension language into a domain-specific language. The LUxWORKS processor simulator and debugger from Lucent uses Tcl as its extension language. After an overview of extension language embedding and LUxWORKS experience, this paper looks at using Java reflection and related mechanisms to solve three limitations in extension language - domain framework interaction. The three limitations are gradual accumulation of ad hoc interface code connecting an extension language to a domain framework, over-coupling of a domain framework to a specific extension language, and inefficient command interpretation.
Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis (2017)

CSF and serum pNfH concentrations are elevated in patients with ALS and correlate with the disease progression rate. Moreover, CSF pNfH correlates with the burden of motor neuron dysfunction. Our findings encourage further pursuit of CSF and serum pNfH concentrations in the diagnostic pathway of patients suspected to have ALS.