gebhart/patrepeval huggingface dataset:
The inflammatory response in myocardial infarction (2002)

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
Arming Cytokine-induced Killer Cells With Chimeric Antigen Receptors: CD28 Outperforms Combined CD28–OX40 “Super-stimulation” (2013)

Cytokine-induced killer (CIK) cells raised interest for use in cellular antitumor therapy due to their capability to recognize and destroy autologous tumor cells in a HLA-independent fashion. The antitumor attack of CIK cells, predominantly consisting of terminally differentiated CD8(+)CD56(+) cells, can be improved by redirecting by a chimeric antigen receptor (CAR) that recognizes the tumor cell and triggers CIK cell activation. The requirements for CIK cell activation were, however, so far less explored and are likely to be different from those of "younger" T cells. We revealed that CD28 and OX40 CARs produced higher interferon- secretion as compared with the first-generation ζ-CAR; CD28-ζ and the third-generation CD28-ζ-OX40 CAR, however, performed similar in modulating most CIK cell effector functions. Compared with the CD28-ζ CAR, however, the CD28-ζ-OX40 CAR accelerated terminal maturation of CD56(+) CIK cells producing high frequencies in activation-induced cell death (AICD) and reduced antitumor efficiency in vivo. Consequently, CD28-ζ CAR CIK cells of CD56(-) phenotype were superior in redirected tumor cell elimination. CAR-mediated CIK cell activation also increased antigen-independent target cell lysis; the CD28-ζ CAR was more efficient than the CD28-ζ-OX40 CAR. Translated into therapeutic strategies, CAR-redirected CIK cells benefit from CD28 costimulation; "super-costimulation" by the CD28-ζ-OX40 CAR, however, performed less in antitumor efficacy due to increased AICD.
Characterization of MOCVD lateral epitaxial overgrown III-V semiconductor layers on GaAs substrates (2004)

We have studied the lateral epitaxial overgrowth by MOCVD of a variety of highly mismatched III-V semiconductors on GaAs substrates. For [001] substrates we determined the oxide stripe orientation that gives the maximum lateral growth rate to be /spl sim/ 25/sup o/ from [110]. We successfully achieved that lateral overgrowth of In/sub x/Ga/sub 1-x/As alloys on GaAs and found that the use of Bi as a surfactant led to an improvement in the morphology and luminescence uniformity. The studies have been extended to the lateral epitaxial overgrowth of InAs, GaP, and InP.
Flexible Management of Enzymatic Digestion Improves Human Islet Isolation Outcome from Sub‐Optimal Donor Pancreata (2003)

Worldwide growing interest in reproducing the result of the Edmonton protocol in islet transplantation trials poses the problem of paucity of donors to supply sufficient amount of islets for clinical use. Improved outcomes include finding better ways to obtain higher yields from every donor organ processed and the possibility of extending islet isolation processing to glands of suboptimal quality. In order to optimize enzymatic digestion of marginal donor organs, we have modified the technique of tissue collection following enzymatic digestion of human pancreatic organs, allowing for reduced time of exposure of free islets to warm Liberase trade mark solution. Our results indicate that better controlled exposure to enzyme yields: (i) higher islet numbers; (ii) complete dissociation of all parts of pancreatic tissue; (iii) successful islet harvest from organs otherwise excluded. We also show that by limiting the exposure of free islets to enzyme solution, islet fragmentation and loss of insulin content are reduced. We further support evidence that enzymatic digestion may contribute to impairment of insulin secretory capacity of the islets in vitro during culture.
FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer (2020)

On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan.
The antigenic index: a novel algorithm for predicting antigenic determinants (1988)

In this paper, we introduce a computer algorithm which can be used to predict the topological features of a protein directly from its primary amino acid sequence. The computer program generates values for surface accessibility parameters and combines these values with those obtained for regional backbone flexibility and predicted secondary structure. The output of this algorithm, the antigenic index, is used to create a linear surface contour profile of the protein. Because most, if not all, antigenic sites are located within surface exposed regions of a protein, the program offers a reliable means of predicting potential antigenic determinants. We have tested the ability of this program to generate accurate surface contour profiles and predict antigenic sites from the linear amino acid sequences of well-characterized proteins and found a strong correlation between the predictions of the antigenic index and known structural and biological data.
Extraction Procedure for TMS Carbohydrate Ethers (1970)

Journal Article Extraction Procedure for TMS Carbohydrate Ethers Get access R. D. Partridge, R. D. Partridge Search for other works by this author on: Oxford Academic PubMed Google Scholar A. H. Weiss A. H. Weiss Department of Chemical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts 01609 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Chromatographic Science, Volume 8, Issue 9, September 1970, Page 553, https://doi.org/10.1093/chromsci/8.9.553 Published: 01 September 1970 Article history Received: 16 October 1969 Published: 01 September 1970
Thermally Induced DNA·RNA Hybrid to G-Quadruplex Transitions:  Possible Implications for Telomere Synthesis by Telomerase (1996)

Telomerase is a specialized reverse transcriptase that contains its own RNA template for synthesis of telomeric DNA [Greider, C. W., & Blackburn, E. H. (1989) Nature 337, 331-337; Shippen-Lentz, D., & Blackburn, E. H. (1990) Science 247, 546-552]. The activity of this ribonucleoprotein enzyme has been associated with cancer cells [Kim et al. (1994) Science 266, 2011-2015] and is thus a potential target for anticancer chemotherapy. Telomeric DNA.RNA hybrids are important intermediates in telomerase function and form after extension of the growing telomere on the telomerase RNA template. Translocation is a critical step in telomerase function and consists of unwinding of the telomeric DNA.telomerase RNA hybrid followed by repositioning of the 3'-end of the extended telomere. A central question in telomerase function is how translocation of the extended telomere occurs in the absence of ATP or GTP. It has been hypothesized that unwinding of the telomeric hybrid may be facilitated by the formation of stable hairpins or G-quadruplexes by the telomere product (i.e., a hybrid to G-quadruplex transition) and that this may provide at least part of the driving force for translocation [Shippen-Lentz & Blackburn, 1990; Zahler et al. (1991) Nature 350, 718-720]. However, so far there has been no effort aimed at examining the possibility that a hybrid/G-quadruplex equilibrium can occur and to what extent this equilibrium depends on buffer and concentration conditions. Examination of these transitions may provide insight into telomerase function and may also provide clues for the development of anti-telomerase agents. Using a model system consisting of the DNA.RNA hybrid d(GGTTAGGGTTAG).r(cuaacccuaacc), we present evidence that a thermally induced transition of telomeric DNA.RNA hybrid to G-quadruplex can occur under certain conditions. These results provide support for the hypothesis that G-quadruplex formation by the telomere product may in fact regulate telomerase function at the translocation step (Zahler et al., 1991) and suggest an Achilles' heel for indirectly targeting telomerase. Thus, on the basis of the insight gained from the present studies and the results of Zahler et al. (1991), we propose that ligands that selectively bind or cleave G-quadruplex structures may modulate telomerase processivity.
Type II integral membrane protein, TM of J paramyxovirus promotes cell-to-cell fusion (2015)

Paramyxoviruses include many important animal and human pathogens. Most paramyxoviruses have two integral membrane proteins: fusion protein (F) and attachment proteins hemagglutinin, hemagglutinin-neuraminidase, or glycoprotein (G), which are critical for viral entry into cells. J paramyxovirus (JPV) encodes four integral membrane proteins: F, G, SH, and transmembrane (TM). The function of TM is not known. In this work, we have generated a viable JPV lacking TM (JPV∆TM). JPV∆TM formed opaque plaques compared with JPV. Quantitative syncytia assays showed that JPV∆TM was defective in promoting cell-to-cell fusion (i.e., syncytia formation) compared with JPV. Furthermore, cells separately expressing F, G, TM, or F plus G did not form syncytia whereas cells expressing F plus TM formed some syncytia. However, syncytia formation was much greater with coexpression of F, G, and TM. Biochemical analysis indicates that F, G, and TM interact with each other. A small hydrophobic region in the TM ectodomain from amino acid residues 118 to 132, the hydrophobic loop (HL), was important for syncytial promotion, suggesting that the TM HL region plays a critical role in cell-to-cell fusion.
Role of Excitatory Amino Acid Transporter‐2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics (2010)

Glutamate is an essential excitatory neurotransmitter regulating brain functions. Excitatory amino acid transporter (EAAT)-2 is one of the major glutamate transporters expressed predominantly in astroglial cells and is responsible for 90% of total glutamate uptake. Glutamate transporters tightly regulate glutamate concentration in the synaptic cleft. Dysfunction of EAAT2 and accumulation of excessive extracellular glutamate has been implicated in the development of several neurodegenerative diseases including Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Analysis of the 2.5 kb human EAAT2 promoter showed that NF-κB is an important regulator of EAAT2 expression in astrocytes. Screening of approximately 1,040 FDA-approved compounds and nutritionals led to the discovery that many β-lactam antibiotics are transcriptional activators of EAAT2 resulting in increased EAAT2 protein levels. Treatment of animals with ceftriaxone (CEF), a β-lactam antibiotic, led to an increase of EAAT2 expression and glutamate transport activity in the brain. CEF has neuroprotective effects in both in vitro and in vivo models based on its ability to inhibit neuronal cell death by preventing glutamate excitotoxicity. CEF increases EAAT2 transcription in primary human fetal astrocytes through the NF-κB signaling pathway. The NF-κB binding site at -272 position was critical in CEF-mediated EAAT2 protein induction. These studies emphasize the importance of transcriptional regulation in controlling glutamate levels in the brain. They also emphasize the potential utility of the EAAT2 promoter for developing both low and high throughput screening assays to identify novel small molecule regulators of glutamate transport with potential to ameliorate pathological changes occurring during and causing neurodegeneration.
Predictive interaction using the delphian desktop (2005)

This paper details the design and evaluation of the Delphian Desktop, a mechanism for online spatial prediction of cursor movements in a Windows-Icons-Menus-Pointers (WIMP) environment. Interaction with WIMP-based interfaces often becomes a spatially challenging task when the physical interaction mediators are the common mouse and a high resolution, physically large display screen. These spatial challenges are especially evident in overly crowded Windows desktops. The Delphian Desktop integrates simple yet effective predictive spatial tracking and selection paradigms into ordinary WIMP environments in order to simplify and ease pointing tasks. Predictions are calculated by tracking cursor movements and estimating spatial intentions using a computationally inexpensive online algorithm based on estimating the movement direction and peak velocity. In testing the Delphian Desktop effectively shortened pointing time to faraway icons, and reduced the overall physical distance the mouse (and user hand) had to mechanically traverse.
The ASAM principles of addiction medicine (2014)

In the midst of an addiction epidemic, this newly updated edition of The American Society of Addiction Medicine Principles of Addiction Medicine, 5th edition is the sought-after text every addiction researcher and care provider needs. This comprehensive reference text dedicates itself to both the science and treatment of addiction. You'll receive a thorough grounding in both the scientific principles behind the causes of addiction and the practical aspects of clinical care. Chapters are written by recognized experts, covering areas such as the basic science of addiction medicine; diagnosis, assessment and early intervention; pharmacologic and behavioral interventions; mutual help and twelve-step; and co-occurring addiction, medical and psychiatric disorders-backed by the latest research data and successful treatment methods. Features: numerous figures, tables and diagrams elucidate the text; chapters include case examples; list of data research reports provided at end of each chapter; new material on Prescription Drug Abuse, Club Drugs, Nursing Roles in Addressing Addiction, Conceptual and Treatment Issues in Behavioral Addictions, Rehabilitation Approaches to Pain Management, Comorbid Pain and Addiction, Pharmacotherapy for Adolescents with Substance Use Disorders, Preventing and Treating Substance Use Disorders in Military Personnel, and more. Now with the print edition, enjoy the bundled interactive eBook edition, offering tablet, smartphone, or online access to: complete content with enhanced navigation; a powerful search feature pulls results from your notes, everything in the book, and even the web; cross-linked pages, references, and more for easy navigation; ability to highlight text for easier reference of key content; ability to share notes with friends and colleagues; ability to save your favorite content for future, quick reference; and interactive question bank with more than 300 questions.
Digest Values for DOM (DOMHASH) (2000)

This memo defines a clear and unambiguous definition of digest (hash) values of the XML objects regardless of the surface string variation of XML. This definition can be used for XML digital signature as well efficient replication of XML objects.
Compact fiber-optic curvature sensor based on super-mode interference in a seven-core fiber (2015)

A compact, low loss, and highly sensitive optical fiber curvature sensor is presented. The device consists of a few-millimeter-long piece of seven-core fiber spliced between two single-mode fibers. When the optical fiber device is kept straight, a pronounced interference pattern appears in the transmission spectrum. However, when the device is bent, a spectral shift of the interference pattern is produced, and the visibility of the interference notches changes. This allows for using either visibility or spectral shift for sensor interrogation. The dynamic range of the device can be tailored through the proper selection of the length of the seven-core fiber. The effects of temperature and refractive index of the external medium on the response of the curvature sensor are also discussed. Linear sensitivity of about 3000 nm/mm(-1) for bending was observed experimentally.
Contrast-enhanced transcranial color-coded duplexsonography in stroke patients with limited bone windows. (2000)

In stroke-age patients with limited acoustic windows, contrast-enhancement with Levovist can markedly increase the sensitivity of TCCD and increase the detection of clinically relevant intracranial arterial disease.
The alpha-glucosidase inhibitor N-butyldeoxynojirimycin inhibits human immunodeficiency virus entry at the level of post-CD4 binding (1995)

The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is a potent inhibitor of human immunodeficiency virus (HIV) replication and syncytium formation in vitro. However, the exact mechanism of action of NB-DNJ remains to be determined. In this study we have examined the impairment of HIV infectivity mediated by NB-DNJ. By two independent HIV entry assays [PCR-based HIV entry assay and entry of Cocal(HIV) pseudotypes], the reduction in infectivity was found to be due to an impairment of viral entry. No effect of NB-DNJ treatment was seen on the kinetics of the interaction between gp120 and CD4 (surface plasmon resonance; BIAcore) or on the binding of virus particles to H9 cells (using radiolabeled virions). We therefore conclude that a major mechanism of action of NB-DNJ as an inhibitor of HIV replication is the impairment of viral entry at the level of post-CD4 binding, due to an effect on viral envelope components.
The Twitter of Babel: Mapping World Languages through Microblogging Platforms (2013)

Large scale analysis and statistics of socio-technical systems that just a few short years ago would have required the use of consistent economic and human resources can nowadays be conveniently performed by mining the enormous amount of digital data produced by human activities. Although a characterization of several aspects of our societies is emerging from the data revolution, a number of questions concerning the reliability and the biases inherent to the big data ''proxies'' of social life are still open. Here, we survey worldwide linguistic indicators and trends through the analysis of a large-scale dataset of microblogging posts. We show that available data allow for the study of language geography at scales ranging from country-level aggregation to specific city neighborhoods. The high resolution and coverage of the data allows us to investigate different indicators such as the linguistic homogeneity of different countries, the touristic seasonal patterns within countries and the geographical distribution of different languages in multilingual regions. This work highlights the potential of geolocalized studies of open data sources to improve current analysis and develop indicators for major social phenomena in specific communities.
Altered Glycosylation in Cancer: Sialic Acids and Sialyltransferases (2005)

Abnormal protein glycosylation, resulting in expression of altered carbohydrate determinants, is well associated with malignant transformation of the cell. One family of important molecules related to aberrant glycosylation is sialic acids (SAs) and their derivatives, which are ubiquitous at the terminal positions of the oligosaccharides of glycoproteins. Sialylation affects the half-lives of many circulating glycoproteins and plays roles in a variety of biologic processes such as cell-cell communication, cell-matrix interaction, adhesion, and protein targeting. The transfer of sialic acids from CMP-sialic acids to the acceptor carbohydrates is catalyzed by the sialyltransferase (ST) family, which includes 20 glycoprotein- and glycolipid-specific α2,3-, α2,6- and α2,8-linkage transferring enzymes described up to date. Cell surface SA levels are mainly correlated with the mRNA levels of ST genes. In human, STs are expressed in many tissues at different levels. Moreover, the level of ST expression is dramatically changed during cancer transformation and this alteration can be achieved transcriptionally through tissue-specific or cell type-specific promoters that lead to the production of mRNA species which diverge in the 5'-untranslated region. Evidence shows that altered ST expression have a significant correlation with oncogenesis, tumor progression, and lymph node metastases. Therefore, the functional roles of ST in cancer pathogenesis should be elucidated with the assistance of advanced molecular technology. In this paper, an overview of Sialylation changes in cancer is highlighted. Getting insights and understandings of altered glycosylation in cancers will offer a brand-new vision in modifying cancer behavior and treating these highly lethal diseases in the near future.