gebhart/patrepeval huggingface dataset:
Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis (2009)

Multiple sclerosis (MS) is an inflammatory central nervous system (CNS) disorder characterized by T cell-mediated demyelination. In MS, prolonged T cell survival and increased T cell proliferation have been linked to disease relapse and progression. Recently, the autophagy-related gene 5 (Atg5) has been shown to modulate T cell survival. In this study, we examined the expression of Atg5 using both a mouse model of autoimmune demyelination as well as blood and brain tissues from MS cases. Quantitative real-time PCR analysis of RNA isolated from blood samples of experimental autoimmune encephalomyelitis (EAE) mice revealed a strong correlation between Atg5 expression and clinical disability.Analysis of protein extracted from these cells confirmed both upregulation and post-translational modification of Atg5, the latter of which was positively correlated with EAE severity. Analysis of RNA extracted from T cells isolated by negative selection indicated that Atg5 expression was significantly elevated in individuals with active relapsing-remitting MS compared to non-diseased controls. Brain tissue sections from relapsing-remitting MS cases examined by immunofluorescent histochemistry suggested that encephalitogenic T cells are a source of Atg5 expression in MS brain samples. Together these data suggest that increased T cell expression of Atg5 may contribute to inflammatory demyelination in MS.
Boron-Masking Strategy for the Selective Synthesis of Oligoarenes via Iterative Suzuki−Miyaura Coupling (2007)

The iterative synthesis of oligoarenes via an organoborane-based cross-coupling reaction (i.e., the Suzuki−Miyaura coupling) has been achieved by using a series of “masked” haloarylboronic acids as building blocks whose ordinarily reactive boronyl groups are temporarily protected by a new masking group derived from 1,8-diaminonaphthalene.
Stoichiometric model ofEscherichia coli metabolism: Incorporation of growth-rate dependent biomass composition and mechanistic energy requirements (1997)

A stoichiometric model of metabolism was developed to describe the balance of metabolic reactions during steady-state growth of Escherichia coli on glucose (or metabolic intermediates) and mineral salts. The model incorporates 153 reversible and 147 irreversible reactions and 289 metabolites from several metabolic data bases for the biosynthesis of the macromolecular precursors, coenzymes, and prosthetic groups necessary for synthesis of all cellular macromolecules. Correlations describing how the cellular composition changes with growth rate were developed from experimental data and were used to calculate the drain of precursors to macromolecules, coenzymes, and prosthetic groups from the metabolic network for the synthesis of those macromolecules at a specific growth rate. Energy requirements for macromolecular polymerization and proofreading, transport of metabolites, and maintenance of transmembrane gradients were included in the model rather than a lumped maintenance energy term. The underdetermined set of equations was solved using the Simplex algorithm, employing realistic objective functions and constraints; the drain of precursors, coenzymes, and prosthetic groups and the energy requirements for the synthesis of macromolecules served as the primary set of constraints. The model accurately predicted experimentally determined metabolic fluxes for aerobic growth on acetate or acetate plus glucose. In addition, the model predicted the genetic and metabolic regulation that must occur for growth under different conditions, such as the opening of the glyoxylate shunt during growth on acetate and the branching of the tricarboxylic acid cycle under anaerobic growth. Sensitivity analyses were performed to determine the flexibility of pathways and the effects of different rates and growth conditions on the distribution of fluxes. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 398-421, 1997.
Modulating immunometabolism of tumor specific mouse and human lymphocytes to enhance T cell based therapy for cancer (2015)

Meeting abstracts Tumor cells and tumor infiltrating lymphocytes (TIL) competes for glucose and other metabolites within the tumor microenvironment for their survival. Glucose consumption by tumors metabolically restricts T cell's ability to produce effector cytokines and therefore approaches to
Comparison of helix-stabilizing effects of α,α-dialkyl glycines with linear and cycloalkyl side chains (2000)

The ability of α,α-di-n-alkyl glycines with linear and cyclic alkyl side chains to stabilize helical conformations has been compared using a model heptapeptide sequence. The conformations of five synthetic heptapeptides (Boc–Val–Ala–Leu–Xxx–Val–Ala–Leu–OMe, Xxx = Ac8c, Ac7c, Aib, Dpg, and Deg, where Ac8c = 1-aminocyclooctane-1-carboxylic acid, Ac7c = 1-aminocycloheptane-1-carboxylic acid, Aib = α-aminoisobutyric acid, Dpg = α,α-di-n-propyl glycine, Deg = α,α-di-n-ethyl glycine) have been investigated. In crystals, helical conformations have been demonstrated by x-ray crystallography for the peptides, R–Val–Ala–Leu–Dpg–Val–Ala–Leu–OMe, (R = Boc and acetyl). Solution conformations of the five peptides have been studied by 1H-nmr. In the apolar solvent CDCl3, all five peptides favor helical conformations in which the NH groups of residues 3–7 are shielded from the solvent. Successive NiH ↔ Ni+1H nuclear Overhauser effects over the length of the sequence support a major population of continuous helical conformations. Solvent titration experiments in mixtures of CDCl3/DMSO provide evidence for solvent-dependent conformational transitions that are more pronounced for the Deg and Dpg peptides. Solvent-dependent chemical shift variations and temperature coefficients in DMSO suggest that the conformational distributions in the Deg/Dpg peptides are distinctly different from the Aib/Acnc peptides in a strongly solvating medium. Nuclear Overhauser effects provide additional evidence for the population of extended backbone conformations in the Dpg peptide, while a significant residual population of helical conformations is still detectable in the isomeric Ac7c peptide in DMSO. © 2000 John Wiley & Sons, Inc. Biopoly 53: 84–98, 2000
Conserved residues of the leader peptide are essential for cleavage by leader peptidase. (1985)

Gene 8 of bacteriophage M13 codes for procoat, the precursor of its major coat protein. Gene 8 has been cloned into a plasmid and mutagenized. We have isolated mutants of this gene in which procoat is synthesized but is not processed to coat protein. We now describe mutants in the leader region of procoat, at positions -6, -3, and -1 with respect to the leader peptidase cleavage site. These positions are quite conserved among the leader peptides of various pre-proteins. Each of these mutant procoats is synthesized at a normal rate and inserts correctly into the plasma membrane, as judged by its accessibility to protease in intact spheroplasts. Procoat accumulates, largely in its transmembrane form, and is not cleaved to coat. In detergent extracts, the mutant procoats are very poor substrates for added leader peptidase. We conclude that these 3 residues are not conserved for insertion across the membrane but are part of an essential recognition site for the leader peptidase.
Antioxidant Profile and Early Outcome in Stroke Patients (2000)

These results suggest that the majority of antioxidants are reduced immediately after an acute ischemic stroke, possibly as a consequence of increased oxidative stress. A specific antioxidant profile is associated with a poor early outcome.
Control versus Effort in Privacy Warnings for Webforms (2016)

Webforms are the primary way of collecting information online. However, some users may wish to limit the amount of personal information they provide and only fill out the minimum required for the transaction. With less than one third of websites marking fields as mandatory or optional, limiting disclosure can be a daunting task. This paper reports on a large behavioural online experiment on user reactions to warnings alerting them that they are about to submit non-mandatory information. Eight warning dialogues were tested between 4,620 participants. We found that warnings mentioning security or privacy threats both significantly reduced the disclosure of personal information in the webforms used (e.g., -27 percentage points for date of birth). The most actionable warning was not the one that minimised user effort but the one that left participants most in control. We consider our study useful to establish what kind of warning messages could help users manage their privacy. In order not to contribute to the ever increasing warning fatigue, a good real-world implementation of over-disclosure indicators would be for the browser to provide users with real-time information on mandatoriness/optionality when the webform loads, for example by highlighting optional fields.
In vitro analysis of interferon gamma (IFN-gamma) and interleukin-12 (IL-12) production and their effects in ileal Crohn's disease. (2003)

Crohn's disease is an inflammatory disease of the gut in which tumour necrosis factor (TNF) and T helper 1 (Th1) cytokines (interleukin (IL)-12, interferon (IFN)-gamma) are thought to play a major role. After the successes obtained with neutralisation of TNF, interest is now growing for therapy aiming at neutralisation of Th1-associated cytokines. Since cytokines are linked in a delicate network, in vitro cultures of ileal lamina propria mononuclear cells (LPMC) were set up for evaluation of a) IFN-gamma and IL-12 production, b) effects of rhIFN-gamma and rhIL-12 and c) effects of anti-IFN-gamma and anti-IL-12 on pro-inflammatory cytokines and IL-10 production. LPMC were isolated from surgical specimens of a total of 27 Crohn's disease and 17 caecum carcinoma (control) patients. Cells were stimulated with CD40L (which triggers myeloid CD40-expressing cells) or anti-CD3 +CD80 (which triggers T cells). LPMC from involved ileal, Crohn's disease produced, in both non-stimulated and stimulated conditions, more IFN-gamma and IL-12p70 than LPMC from non-involved tissue or from control patients. rhIFN-gamma significantly enhanced TNF production in both controls and in ileal Crohn's disease patients, while rhIL-12 enhanced IFN-gamma but not TNF production. LPMC from involved tissue were more sensitive to IL-12 than control LPMC. LP-T cell-dependent activation of monocytes was then studied by co-culture of anti-CD3/CD80-stimulated LPMC with fresh monocytes, which resulted in high IL-12, IFN-gamma, TNF and IL-10 production. The data show that neutralisation of either IL-12 or IFN-gamma with mAb in these cultures also affects secretion of the reciprocal cytokine and (in the case of anti-IL-12) also that of the anti-inflammatory cytokine IL-10. However, no effect of anti-IL-12 or anti-IFN-gamma on production of TNF, a cytokine with an important pathogenic role in Crohn's disease, could be found. Therapies aiming at neutralisation of IFN-gamma or IL-12 are therefore unlikely to replace anti-TNF, but they might provide an additive or synergistic effect.
Inhaled insulin (2007)

In Brief Get up to snuff on this new treatment so you can help patients with diabetes explore all their options. If your patient has diabetes, she may ask you about this exciting new option. Get the answers by reading this comprehensive report.
Ultrasound-guided single popliteal sciatic nerve block is an effective postoperative analgesia strategy for calcaneal fracture: a randomized clinical trial (2021)

ChiCTR, ChiCTR2100042340. Registered 19 January 2021, URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=66526 .
The synthesis of (±)-10a-homo-11a-carbathromboxane A1, a stable thromboxane A analogue (1984)

The thromboxane A1(TXA1) analogue (1), which retains the characteristic bridge oxygen atom of the TXA molecule, has been synthesized from the bicyclic ketone (2). Stereochemical control of alkylation of the bicyclic ketone (2) was achieved by the use of enamines.
A statistical model of the natural history of cervical carcinoma based on a prospective study of 557 cases. (1968)

The authors statistical model for the natural history of cervical dysplasia was developed through an investigation of smears obtained by aspiration from the external cervical os from 557 patients at the Medical College of Virginia in Charlottesville and the Columbia-Presbyterian Medical Center in New York City. No patient was admitted to the study without 3 abnormal smears. Follow-up was 1-4 months after admission diagnosis. Smears were classified according to a modification of the system presented by McKay et al. and Okagaki et al. The model assumes based on the data that a dysplastic lesion rarely spontaneously reverts to normal. The model further assumes that the probability of a lesion transiting from 1 stage to another is constant over time and that the behavior of a lesion during some time interval is independent of its behavior during a previous state. Transit (from 1 smear class to another) probabilities and rates (predicted mean times in months spent in each smear class having started in the given admission class before transit to the next higher smear class) are calculated. Thus the model seeks to provide predictive power to the physician presented with an abnormal smear. The predictions were consistent with the observed data and also with various studies of cervical dysplasia carcinoma in situ and invasive cervical carcinoma. The change from 1 stage in the natural history to another can be thought of as a process that is a function of 1) the probability of transition and 2) the induction time between the initiation of a stage and its ascertainment or transition to the next stage.
Facile Synthesis of 2,5-Diarylthiazoles via Palladium-Catalyzed Tandem C−H Substitutions. Design of Tunable Light Emission and Liquid Crystalline Characteristics (2003)

A mild and regioselective C-H substitution reaction of thiazole by the catalysis of the palladium/copper system is found to proceed in the presence of tetrabutylammonium fluoride under mild conditions. Applying the new reaction, we synthesized various 2,5-diarylthiazoles that exhibit light-emitting and liquid crystalline characteristics in good yields. The color of light emission is tunable by the introduction of the substituent. Differently substituted 2,5-diarylthiazoles are found to exhibit a stable liquid crystal phase in a wide temperature range.
Surgical diagnostics, guidance, and intervention using optical coherence tomography (1998)

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 1998.
Production of recombinant proteins using multiple‐copy gene integration in high‐cell‐density fermentations of Ralstonia eutropha (2003)

We have previously reported the development of a novel protein expression system based on Ralstonia eutropha. In this study we report on the influence of gene copynumber on recombinant protein expression in R. eutropha. We compare recombinant gene stability and expression levels of chromosomal integration with a plasmid-based expression system. Single, double, and triple copies of a gene encoding organophosphohydrolase (OPH), an enzyme prone to inclusion-body formation in E. coli, were integrated into the R. eutropha chromosome. A linear increase between the concentration of soluble, active OPH and gene copynumber was found. Using a triple-copy integrant, we were able to produce approximately 4.3 g/L of OPH in a high-cell-density fermentation. This represents the highest titer reported to date for this enzyme, and is approximately 30 times greater than expression levels reported in E. coli.
Clinical Management of Pain in Advanced Lung Cancer (2012)

Lung cancer is the most common cancer in the world and pain is its most common symptom. Pain can be brought about by several different causes including local effects of the tumor, regional or distant spread of the tumor, or from anti-cancer treatment. Patients with lung cancer experience more symptom distress than patients with other types of cancer. Symptoms such as pain may be associated with worsening of other symptoms and may affect quality of life. Pain management adheres to the principles set out by the World Health Organization's analgesic ladder along with adjuvant analgesics. As pain can be caused by multiple factors, its treatment requires pharmacological and non-pharmacological measures from a multidisciplinary team linked in with specialist palliative pain management. This review article examines pain management in lung cancer.
Differential binding of erythroid and myeloid progenitors to fibroblasts and fibronectin (1987)

Using a novel coverslip-transfer culture technique, we recently demonstrated that primitive erythroid burst-forming units (BFU-E) can migrate, proliferate, and differentiate in intimate association with stromal fibroblastoid cells in the presence of serum proteins and erythropoietin. No other exogenous hemopoietic growth factors are required. Most of the colonies that develop in this system are very large erythroid bursts, and very few granulocyte-macrophage (GM) colonies are observed. In this report, we present data indicating that the predominance of erythroid burst colonies in this culture system is due to preferential binding of primitive erythroid progenitors to the stromal fibroblastoid cells and not to differential stimulation of these erythroid progenitors by these cells. We next show that the binding of BFU-E to stromal cells is blocked by anti-fibronectin antibodies. Finally, we demonstrate the preferential binding of BFU-E to fibronectin by using glass coverslips or Petri dishes coated with purified human plasma fibronectin. The binding is blocked by a monoclonal antibody specific for the cell-binding domain of fibronectin. We conclude that: primitive erythroid progenitors bind strongly whereas G and/or M progenitors (CFU-G/M) bind only weakly to fibronectin; primitive erythroid progenitors bind to the cell-binding domain on the fibronectin molecule; and erythroid progenitors and precursors remain bound to fibronectin throughout differentiation.
Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). (1999)

HER2 is a ligand-less member of the human epidermal growth factor receptor or ErbB family of tyrosine kinases. In normal biological systems, HER2 functions as a co-receptor for a multitude of epidermal growth factor-like ligands that bind and activate other HER family members. HER2 overexpression is observed in a number of human adenocarcinomas and results in constitutive HER2 activation. Specific targeting of these tumors can be accomplished with antibodies directed against the extracellular domain of the HER2 protein. One of these antibodies, 4D5, has been fully humanized and is termed trastuzumab (Herceptin; Genentech, San Francisco, CA). Treatment of HER2-overexpressing breast cancer cell lines with trastuzumab results in induction of p27KIP1 and the Rb-related protein, p130, which in turn significantly reduces the number of cells undergoing S-phase. A number of other phenotypic changes are observed in vitro as a consequence of trastuzumab binding to HER2-overexpressing cells. These phenotypic changes include downmodulation of the HER2 receptor, inhibition of tumor cell growth, reversed cytokine resistance, restored E-cadherin expression levels, and reduced vascular endothelial growth factor production. Interaction of trastuzumab with the human immune system via its human immunoglobulin G1 Fc domain may potentiate its antitumor activities. In vitro studies demonstrate that trastuzumab is very effective in mediating antibody-dependent cell-mediated cytotoxicity against HER2-overexpressing tumor targets. Trastuzumab treatment of mouse xenograft models results in marked suppression of tumor growth. When given in combination with standard cytotoxic chemotherapeutic agents, trastuzumab treatment generally results in statistically superior antitumor efficacy compared with either agent given alone. Taken together, these studies suggest that the mechanism of action of trastuzumab includes antagonizing the constitutive growth-signaling properties of the HER2 system, enlisting immune cells to attack and kill the tumor target, and augmenting chemotherapy-induced cytotoxicity.
A High Conduction Composite Li Superionic Conductor (2013)

Abstract not Available.
Measuring phase shifts and energy dissipation with amplitude modulation atomic force microscopy (2006)

By recording the phase angle difference between the excitation force and the tip response in amplitude modulation AFM it is possible to image compositional variations in heterogeneous samples. In this contribution we address some of the experimental issues relevant to perform phase contrast imaging measurements. Specifically, we study the dependence of the phase shift on the tip-surface separation, interaction regime, cantilever parameters, free amplitude and tip-surface dissipative processes. We show that phase shift measurements can be converted into energy dissipation values. Energy dissipation curves show a maximum (∼10 eV/cycle) with the amplitude ratio. Furthermore, energy dissipation maps provide a robust method to image material properties because they do not depend directly on the tip-surface interaction regime. Compositional contrast images are illustrated by imaging conjugated molecular islands deposited on silicon surfaces.
An Intrabody Drug (rAAV6-INT41) Reduces the Binding of N-Terminal Huntingtin Fragment(s) to DNA to Basal Levels in PC12 Cells and Delays Cognitive Loss in the R6/2 Animal Model (2016)

Huntington's disease (HD) is a fatal progressive disease linked to expansion of glutamine repeats in the huntingtin protein and characterized by the progressive loss of cognitive and motor function. We show that expression of a mutant human huntingtin exon-1-GFP fusion construct results in nonspecific gene dysregulation that is significantly reduced by 50% due to coexpression of INT41, an intrabody specific for the proline-rich region of the huntingtin protein. Using stable PC12 cell lines expressing either inducible human mutant huntingtin (mHtt, Q73) or normal huntingtin (nHtt, Q23), we investigated the effect of rAAV6-INT41, an adeno-associated virus vector with the INT41 coding sequence, on the subcellular distribution of Htt. Compartmental fractionation 8 days after induction of Htt showed a 6-fold increased association of a dominate N-terminal mHtt fragment with DNA compared to N-terminal nHtt. Transduction with rAAV6-INT41 reduced DNA binding of N-terminal mHtt 6.5-fold in the nucleus and reduced nuclear translocation of the detected fragments. Subsequently, when rAAV6-INT41 is delivered to the striatum in the R6/2 mouse model, treated female mice exhibited executive function statistically indistinguishable from wild type, accompanied by reductions in Htt aggregates in the striatum, suggesting that rAAV6-INT41 is promising as a gene therapy for Huntington's disease.