gebhart/patrepeval huggingface dataset:
Mesenchymal Stem Cells after Polytrauma: Actor and Target (2016)

Mesenchymal stem cells (MSCs) are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as "actors" in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent "targets" during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.
Secure Network Access Using Multiple Applications of AT&T's Smart Card (1994)

Fraud amounting annually to billions of dollars occurs due to the failure of conventional network access security systems, including data, voice, and credit card authorization networks. At the same time, consumers demand greater convenience in their daily lives, where a multitude of passwords and personal identification numbers, badges, keys, and other devices have become unmanageable. In response to the obviously conflicting needs, AT&T has developed a credit card sized device, the contactless AT&T Smart Card. By means of an internal microprocessor, the card provides the secure partitioning of authentication codes and data files, as well as encryption capabilities, using the data encryption standard. This paper provides a basic description of the card technology, and the overall architecture of securing access to multiple networks with the AT&T Smart Card.
DETERMINATION OF THE COMPARTMENT PRESSURE THRESHOLD OF MUSCLE ISCHEMIA IN A CANINE MODEL (1994)

A canine model was used to test the hypothesis that critical intracompartmental pressure leading to ischemic muscle necrosis is linked to diastolic blood pressure. Twenty adult dogs were subjected to an infusion of autologous plasma into the anterolateral muscle compartment of the left hindlimb to create an elevation in compartment pressure. There were four experimental groups of five dogs each. In group I, the compartment pressure (CP) was maintained at the animals' diastolic blood pressure (DBP); in group II, at 10 mm Hg less than the DBP; in group III, at 20 mm Hg less than the DBP; and in group IV, at 30 mm Hg. The pressure was measured continuously in the proximal, central, and distal segments of the compartment during an 8-hour period. Immediately postoperatively, and, on the first, fourth, seventh, and fourteenth days one animal from each group was killed. The tibialis cranialis muscle was then removed and analyzed using light and electron microscopy. The critical pressure threshold for ischemic muscle necrosis was found to be 20 mm Hg less than the diastolic blood pressure.
Representative cDNA Libraries and Their Utility in Gene Expression Profiling (1999)

An increasing interest in gene expression profiles in human diseases has led to the use of microdissected tumors and biopsies in gene discovery approaches. Since many of these clinical samples yield extremely small amounts of RNA, reproducible methods are needed to amplify this RNA while maintaining the original message profile. Using the SMART cDNA Synthesis Method, we show that high-, medium- and low-abundance transcripts can be amplified in a representative fashion and that the resulting cDNA can also be used as a complex probe to confirm gene expression differences identified by other techniques.
Cloning and Characterization of TRAIL-R3, a Novel Member of the Emerging TRAIL Receptor Family (1997)

TRAIL-R3, a new member of the TRAIL receptor family, has been cloned and characterized. TRAIL-R3 encodes a 299 amino acid protein with 58 and 54% overall identity to TRAIL-R1 and -R2, respectively. Transient expression and quantitative binding studies show TRAIL-R3 to be a plasma membrane-bound protein capable of high affinity interaction with the TRAIL ligand. The TRAIL-R3 gene maps to human chromosome 8p22-21, clustered with the genes encoding two other TRAIL receptors. In contrast to TRAIL-R1 and -R2, this receptor shows restricted expression, with transcripts detectable only in peripheral blood lymphocytes and spleen. The structure of TRAIL-R3 is unique when compared to the other TRAIL receptors in that it lacks a cytoplasmic domain and appears to be glycosyl-phosphatidylinositol-linked. Moreover, unlike TRAIL-R1 and -R2, in a transient overexpression system TRAIL-R3 does not induce apoptosis.
Configuring Radioligand Receptor Binding Assays for HTS Using Scintillation Proximity Assay Technology (2003)

Rapid progress in the fields of genomics, proteomics, and molecular biology has both increased the numbers of potential drug targets, and facilitated development of assays to screen these targets (1–5). In parallel with these changes, developments in robotics and combinatorial chemical synthesis have driven the production of very large numbers of compounds with potential for pharmacological activity (1–5). The need to screen these large libraries of drug candidates against multiple new targets has stimulated improvements in technology, instrumentation, and automation that have revolutionized the field of drug discovery, and evolved into the field of high throughput screening (HTS) (1,5–9). Radioligand binding assays have historically been the mainstay of drug discovery and drug development (6–8). In the era of HTS, incorporation of scintillation-proximity technology together with improved automation and radiometric-counting instrumentation have served to maintain radioligand receptor-binding as one of the premier tools of drug discovery (1,5,8,9). Radioligand binding assays are extremely versatile, easy to perform, can be automated to provide very high throughput (10–12). The quality of the data allows the determination of drug affinity, allosteric interactions, the existence of receptor subtypes, and estimates of receptor numbers (10–12). This chapter provides an overview of radioligand receptor-binding assays and discusses some of the issues associated with the conversion of traditional filtration assays to a homogeneous scintillating proximity assay (SPA) format that is more compatible with automation and HTS.
Antitumor and antiviral activity of synthetic .alpha.- and .beta.-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides (1989)

A novel and direct synthesis of the antiviral and antitumor agent 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine (ARPP, 8) and its alpha-anomer (11) has been developed. Treatment of 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine (1) with 2,3-O-isopropylidene-D-ribofuranosylamine gave an anomeric mixture of 2,4,6-trichloro-8-(2,3-O-isopropylidene-beta- and -alpha-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidines (3 and 4) in a ratio of 1.0:0.7. A nucleophilic displacement of the 4-chloro group of 3 and 4 with NH3 furnished 4-amino-2,6-dichloro-8-[(2,3-O-isopropylidene-beta-D-ribofuranosyl)amino ] pyrimido[5,4-d]pyrimidine (6) and its alpha-anomer (9), respectively. Catalytic hydrogenation of 6 and 9, followed by deisopropylidenation gave ARPP (8) and the alpha-anomer 11, respectively. Similarly, 3 and 4 have been transformed to 4-methoxy-8-(beta-D-ribofuranosylamino)pyrimido-[5,4-d]pyrimidine (MRPP, 14) and its alpha-anomer (17). Application of this procedure to 3 with NH2Me or NHMe2 resulted in the synthesis of 4-(methylamino)- and 4-(dimethylamino)-8-(beta-D-ribofuranosylamino)pyrimido [5,4-d]pyrimidine (24 and 27, respectively). A synthesis of 8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidin-4(3H)-one (21) has also been accomplished from 3 in three steps. Selective hydrogenation of 6 furnished 4-amino-6-chloro-8-[(2,3-O-isopropylidene-beta-D-ribofuranosyl)amino] pyrimido[5,4-d]pyrimidine (36), the structure of which was established by single-crystal X-ray diffraction analysis. Deisopropylidenation of 36 gave 6-chloro-ARPP (37). Extended treatment of 36 with NH3 furnished 4,6-diamino-8-[(2,3-O-isopropylidene-beta-D-ribofuranosyl)amino]pyrimido [5,4-d]pyrimidine (34), which on deisopropylidenation gave 6-amino-ARPP (35). An unambiguous synthesis of 34 and 36 has also been accomplished by the reaction of 4,6,8-trichloropyrimido[5,4-d]pyrimidine (28) with 2, followed by the treatment with NH3. Nucleophilic displacement studies with 1, 6, and 28 indicated the reactivity of the halogens in these compounds is in the order of 8 greater than 4 greater than 6 greater than 2. The structures of 3 and 9 have been assigned on the basis of 1H NMR data and further confirmed by single-crystal X-ray diffraction analysis. The exocyclic aminonucleosides synthesized during this study were tested for their activity against several RNA and DNA viruses in vitro and against L1210, WI-L2, and LoVo/L in cell culture. The effect of these compounds on the de novo nucleic acid biosynthesis has been studied. Compound 14 (MRPP) exhibited enhanced activity against L1210 in vivo, when compared to ARPP (8).
Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo (2009)

In addition to its immune suppressive function in T-regulatory cells, the nuclear transcription factor, FOXP3, has been identified as a tumor suppressor. To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated FOXP3 protein therapy of cancer, the Fv-FOXP3 fusion protein produced in Pichia pastoris was tested on breast, ovarian, and colon cancer cells in vitro, and with colon cancer cells in vivo in a mouse model of colon cancer metastasis to liver. Treatment with Fv-FOXP3 resulted in dose-dependent cell death of cancer cells in vitro. Apoptosis was established as a mechanism of cell death by demonstrating increased production of the p17 activated fragment of caspase-3 by cancer cells in response to Fv-FOXP3 and inhibition of cell killing by the caspase inhibitor, Z-VAD-FMK. Fv-FOXP3 treatment resulted in clinically significant reduction in tumor burden in a syngeneic model of colon cancer metastasis to liver in Balb/c mice. These results represent the first demonstration of effective full-length FOXP3 protein therapy and emphasize the clinical potential of mAb 3E10 as an intracellular and intranuclear delivery vehicle of FOXP3 for prevention and treatment of cancer metastasis.
Thiolation of symmetrical and unsymmetrical diketopiperazines (2011)

The introduction of sulfur units into a variety of symmetrical and unsymmetrical diketopiperazines (DKPs) is described. We investigated different thiolation methods utilizing several bases and electrophilic sulfur reagents, leading to monomethylthio-, bis(methylthio)-, and epithio-DKPs. Their formation proceeded diastereoselectively, facilitating the application in total syntheses of many thiodiketopiperazine (TDKP) natural products. Furthermore, possible side reactions as well as mechanistic studies and stereochemical structural assignments of the obtained products are given.
Activin A and Activin Receptors in the Human Thyroid: A Link to the Female Predominance of Goiter? (2000)

Activin A belongs to the TGF-beta family of growth factors involved in control of tissue formation by growth inhibition and to a family of hormones involved in human reproduction. Serum levels of dimeric activin A display a sexual dimorphism with significantly higher circulating hormone concentrations in men than in women after menopause. Since goiter is far more frequent in women than in men, we investigated the role of this sex-related growth factor in the human thyroid. Primary cultures were obtained from 3 patients with goiter, and 4 with recurrent goiter. Activin A significantly inhibited the proliferation of human thyroid follicular epithelial cells in vitro in concentrations between 0.5 and 50 ng/ml and was almost as potent as TGFbeta-1. Analysis in native tissues from 12 normal thyroids, 16 goiters, and 5 Graves thyroids demonstrated mRNA expression of the activin subunit betaA, TGFbeta-receptor type I and II, activin receptors type I receptors alk2 and alk4, and activin type II receptors actRII and actRIIb. Isoform analysis of the major functional type I activin receptor alk4 revealed the full-length transcript SKR2-1 and transcripts for the partially truncated proteins SKR2-2 and SKR2-3 in normal thyroids and goiters. Semi-quantitative RT-PCR revealed a significant 2.5-fold decrease of mRNA for alk4-1 type I activin receptors in goiter as compared to normal thyroid (p < 0.05), whereas expression of the type II receptor actRII was unchanged. These data identify a novel growth inhibitory pathway by activin in the human thyroid. Down-regulation of activin receptor type lb in goiter hints towards end-organ changes which could contribute to deficient growth inhibition. These data provide a mechanistic model how the sexually dimorphic hormone activin A may protect males from goitrogenesis.
CD8+T cells recognize an inclusion membrane-associated protein from the vacuolar pathogenChlamydia trachomatis (2001)

During infection with Chlamydia trachomatis, CD8(+) T cells are primed, even though the bacteria remain confined to a host cell vacuole throughout their developmental cycle. Because CD8(+) T cells recognize antigens processed from cytosolic proteins, the Chlamydia antigens recognized by these CD8(+) T cells very likely have access to the host cell cytoplasm during infection. The identity of these C. trachomatis proteins has remained elusive, even though their localization suggests they may play important roles in the biology of the organism. Here we use a retroviral expression system to identify Cap1, a 31-kDa protein from C. trachomatis recognized by protective CD8(+) T cells. Cap1 contains no strong homology to any known protein. Immunofluorescence microscopy by using Cap1-specific antibody demonstrates that this protein is localized to the vacuolar membrane. Cap1 is virtually identical among the human C. trachomatis serovars, suggesting that a vaccine incorporating Cap1 might enable the vaccine to protect against all C. trachomatis serovars. The identification of proteins such as Cap1 that associate with the inclusion membrane will be required to fully understand the interaction of C. trachomatis with its host cell.
Spray-drying as a preparation method of microparticulate drug delivery systems: an overview (1995)

La nebulisation est une technologie recemment utilisee pour la preparation de microparticules: microspheres et microcapsules. Differents procedes sont passes en revue, avec une attention particuliere pour les effets des parametres de fabrication sur les caracteristiques des microparticules et sur les differents materiaux (principe actif et polymere) utilises.
Increased apoptotic potential and dose‐enhancing effect of gold nanoparticles in combination with single‐dose clinical electron beams on tumor‐bearing mice (2008)

High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P = 0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P < 0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P < 0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy.
Putting people first (1994)

Communication is about people, not machines. But as firms and families alike spread out geographically, we rely increasingly on telecommunications tools to keep us “connected”. The challenge of such systems is to enable conversation between individuals without computational infrastructure getting in the way. This paper compares two speech-based communication systems, Phoneshell and Chatter, in how they deal with the keys to communication: proper names. Chatter, a conversational system using speech-recognition, improves upon the hierarchical nature of the touch-tone based Phoneshell by maintaining context and enabling use of anaphora. Proper names can present particular problems for speech recognizers, so an interface algorithm for reliable name specification by spelling is offered. Since individual letter recognition is non-robust, Chatter implicitly disambiguates strings of letters based on context. We hypothesize that the right interface can make faulty speech recognition as usable as TouchTones—even more so.
Polyethers. 1. Preparation of .omega.,.omega.'-bis(triphenylphosphine) polyethers (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyethers. 1. Preparation of .omega.,.omega.'-bis(triphenylphosphine) polyethersMasashi Tashiro, Tsuyoshi Sumida, and Gouki FukataCite this: J. Org. Chem. 1980, 45, 6, 1156–1158Publication Date (Print):March 1, 1980Publication History Published online1 May 2002Published inissue 1 March 1980https://pubs.acs.org/doi/10.1021/jo01294a048https://doi.org/10.1021/jo01294a048research-articleACS PublicationsRequest reuse permissionsArticle Views171Altmetric-Citations9LEARN 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 Get e-Alerts
Background Separation Encoding for Surveillance Purpose by using Stable Foreground Separation (2009)

An efficient encoding approach by separating background/foreground videos from a single video is proposed for surveillance applications. The required bit-rate becomes less than a half of that by a standard H.264 approach. The reduction comes from the employment of the low resolution background pictures with a low frame-rate. In addition, the foreground video is automatically handled so that the information amount becomes almost zero during the periods of no foreground objects. Therefore, storing videos or collecting multi-point surveillance videos at a surveillance center will save storage capacity or communications costs.
Noise subspace approach for interference cancellation (1989)

We propose an interference cancelling method using the noise subspace of a covariance matrix in which the desired signal is subtracted. A beamformer using the method can generate deep nulls even for the interferences correlated with the desired signal or located dose to the look-direction. In addition, we consider how the method can be computed efficiently by utilising the minimum eigenvector.
Antibody–Drug Conjugates in Triple Negative Breast Cancer (2018)

Triple negative breast cancer (TNBC) is a heterogeneous disease that comprises 15-20% of all breast cancers and is more frequently seen in younger women, African-Americans, and BRCA1 expression. Advanced TNBC carries aggressive features and is associated with overall poor outcomes. Unfortunately, there are no targeted therapies available for non-BRCA associated TNBC, which remains a high unmet therapeutic need. One emerging treatment modality includes antibody-drug conjugates which are highly selective monoclonal antibodies conjugated to cytotoxic agents, designed to deliver cytotoxic drugs to antigen-expressing tumor cells. This review will highlight three antibody-drug conjugates currently being evaluated in TNBC (CDX-011, SGN-LIV1a, IMMU-132), including one that has been given Breakthrough Therapy designation from the US FDA.
PP.01.37 (2015)

Objective: Shovelling snow is the biggest cause of exertion-related cardiac death, involving isometric and dynamic exercise. However, mechanisms underlying deleterious effects of cold air inhalation (CAH) during different exercise stressors are poorly understood. We measured haemodynamic responses to handgrip and cycling in coronary artery disease (CAD) patients, ± CAH, to assess the effect of CAH on afterload. Design and method: Eight subcritical CAD patients (62 ± 9 yrs) underwent randomized stressors: -15oC cold air (CAH) or room air (RAH) inhalation for 5 minutes, combined with handgrip (30% maximal voluntary contraction) or cycling with an incremental work load for 5 minutes. Carotid pulse wave analysis and echocardiography were performed at peak stress. Heart rate (HR), mean arterial pressure (MAP), and systemic vascular resistance (SVR) were calculated. P1, P2, augmentation pressure (AP) and Buckberg Index (BI) were derived using custom software. A lower BI ratio indicates increased risk of myocardial ischaemia. Data presented as mean ± SD. Results: CAH significantly reduced BI when combined with either handgrip or cycling. CAH, compared to RAH, increased afterload (MAP) when combined with handgrip (115.8 ± 22.4vs130.8 ± 26.7mmHg,p<0.001), but not when combined with cycling (117.2 ± 16.8vs119.5 ± 18.9mmHg,p = NS). P2 and AP, which are closely associated with myocardial contractility, increased with CAH during handgrip exercise but not during cycling. However CAH only caused a significant increase in HR when combined with cycling (130 ± 9.7vs140 ± 10.1bpm,p < 0.05). SVR decreased with cycling and increased with handgrip during RAH. CAH did not change SVR during handgrip or cycling. There were no significant differences between baseline measurements and RAH at rest.Conclusions: This study shows, for the first time, that CAH significantly increases myocardial oxygen demand and the risk of myocardial ischaemia during isometric or dynamic exercise. However the mechanisms appear to be distinct. CAH likely causes an increase in sympathetic drive, which when combined with isometric exercise results in steady state (afterload) and pulsatile increases in arterial pressure, the latter being driven by increases in myocardial contractility. Yet dynamic exercise results in a sufficient reduction in SVR to override any increased resistance caused by CAH, with the principal determinant for increased myocardial oxygen demand being an increase in HR.