gebhart/patrepeval huggingface dataset:
Constitutive Expression of CD40L by CAR-Modified Tumor Targeted T Cells Enhances Anti-Tumor Efficacy Both in Vitro and in Vivo (2012)

Abstract Abstract 4120 T cells can be genetically modified to target tumor antigens through the expression of a chimeric antigen receptor (CAR). Recent reports have demonstrated the effectiveness of CAR modified T cells in patients with relapsed or refractory malignancies. However, CAR modified T cells have yet to demonstrate the ability to recruit an endogenous anti-tumor response which would greatly enhance their therapeutic benefit. To overcome these limitations we have developed a bi-cistronic gamma-retroviral vector allowing for constitutive co-expression of a CD19-specific CAR (19–28z) and human CD40 ligand (CD40L; CD154). The CD40 ligand/CD40 system has been demonstrated to activate dendritic cells (DCs) and alter the phenotype of B cells (upregulation of co-stimulatory and adhesion molecules and secretion of pro-inflammatory cytokines) with subsequent stimulation of CD8+ T cell activation and proliferation. We now demonstrate T cells genetically modified to constitutively express CD40L undergo enhanced proliferation and up-regulated secretion of pro-inflammatory cytokines including GM-CSF and INF-g. Furthermore, T cells modified to constitutively express CD40L, upon co-culture, will alter the phenotype of CD40+ B cell tumor cell lines by enhancing the expression co-stimulatory molecules (CD80/CD86), adhesion molecules (CD54/CD58/CD70) and death receptors (CD95; Fas). These findings were similarly evident in primary patient tumor samples (e.g. CLL cells) when co-cultured with autologous T cells modified to constitutively express CD40L. We further demonstrate maturation of monocyte derived DCs with subsequent secretion of IL-12 following co-culture with autologous T cells modified to constitutively express CD40L. T cells transduced with the bi-cistronic 19–28z/CD40L vector showed enhanced in vitro cytotoxicity against a panel of CD19+ tumor cell lines. Furthermore, infusion of 19–28z/CD40L modified T cells enhances the survival of CD19+ tumor bearing immunodeficient mice (SCID/Beige) when compared to mice treated with T cells modified to express the anti-CD19 19–28z CAR alone. We conclude that further genetic modification of CAR targeted T cells to constitutively express the co-stimulatory CD40L may enhance the anti-tumor efficacy of this adoptive T cell therapy. Our data suggests this enhanced T cell efficacy may be due to both autocrine and paracrine mediated mechanisms. Disclosures: No relevant conflicts of interest to declare.
ChemInform Abstract: Synthesis of β‐Trifluoromethylated Enones: An Unexpected Reactivity of Trifluoromethylated Weinreb Enamides Towards Organolithium Species. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ENTREPRENEURIAL ORIENTATION AND FIRM PERFORMANCE: A DYNAMIC PERSPECTIVE (2011)

In this paper we help fill a gap in the literature on the relationship between entrepreneurial orientation (EO) and firm performance. Compared to prior studies our paper examines whether and to what extent the change in EO over time influence firm performance. In order to address this issue we draw on survey data where firms have been administered a questionnaire at two points in time matched with official firm register data about survival and exit in Norway. Regression analysis with control for selection bias is used to examine the relationship between EO and firm performance. Our results show that the firms initial EO at Time period 1, as well the change in EO over time, influence firm performance in Time period 2. Overall, this paper contributes to the literature by incorporating a dynamic perspective on the relationship between EO and firm performance.
In-vivo topography of structural alterations of the anterior cingulate gyrus in schizophrenia (2007)

Disturbances of metabolism and function of anterior cingulate cortex (ACC) have been repeatedly reported for patients with schizophrenia. In contrast, structural magnetic resonance imaging (MRI) studies of this region of interest (ROI) have been relatively few and the results inconsistent. The aim of the present study was to examine the hypothesis that different subregions of the ACC are differentially affected by the disease process of schizophrenia. We investigated ACC volumes in 50 male and right-handed patients with schizophrenia according to ICD-10 and DSM-IV. The patients were individually matched for age, sex, handedness and education with 50 control subjects. ACC was subdivided into four parts: precallosal, subgenual, precommissural and postcommissural regions. Measurements were performed with a 1.5 T magnetom vision apparatus. ROIs were defined on consecutive coronal MRI-slices. The software program BRAINS was used for volumetry and segmentation into gray and white matter. We detected that ACC gray matter volume of the right precallosal region and right total ACC was significantly reduced in schizophrenic patients compared with controls. In addition, left ACC gray matter was selectively reduced in the subgenual region. These results confirmed our hypothesis that different ACC regions are differentially affected by structural alterations in schizophrenia, a circumstance that might explain in part contradictory results of previous structural ACC studies.
Abstract 16024: High Frequency Driving Sites are Anchored by Fibrotic Regions in Chronic Atrial Fibrillation (2015)

Introduction: Stable high frequency sources and rotors have been described to drive episodes of atrial fibrillation (AF) but the mechanism for their stability is unknown. We used a chronic animal model of AF to test the hypothesis that fibrosis anchors sites of high frequency activation during AF, which may drive the arrhythmia.. Methods: Endocardial electrograms were measured with a Constellation catheter (Boston Scientific) placed in the left atrium (LA) of chronic AF dogs (n=6) (AF &gt; 12 months). An EnSite (St. Jude) geometric shell was then fused with a LA wall created by segmenting a high resolution T1 Mapping MRI. Regions with the lowest 10% T1 in the LA wall, used as a surrogate measure of fibrosis, were included on the LA wall segmentation. Fibrosis densities were calculated from histology and correlated with T1 Mapping MRI. Electrograms recorded during AF were processed to determine the dominant frequency (DFs) at each recording site. A probability map with the highest 10% DF value for each minute of AF at each of the sites was created to determine the stability of the DF during the 30 min AF episode. Results: Each AF animal had at least one site of high DF which was stable for at least 22.5 (75%) of a 30-minute AF episode and 82% of the high DF sites stabilized within 2 mm of a region of fibrosis (chi square test, p &lt; 0.05). The mean DF was 8.5±1.2 Hz and the highest DF sites showed an average DF of 10.3±1.1 Hz. The region of T1 Mapping MRI detected fibrosis of the LA wall had an average value of 283±32 ms whereas the rest of the LA had an average value of 463±79 ms. Histology confirmed that that T1 Mapping MRI detected fibrosis had more fibrosis than other LA regions. (25±1% vs. 13±2%). Conclusions: Fibrosis developed during chronic AF may provide a substrate that anchors sites of high DF. Cardiac T1 Mapping MRI provides a means to determine such fibrotic sites noninvasively. Ablating these sites may reduce the stability of these high frequency sources and eliminate the drivers of persistent AF.
Subcellular distribution of the soluble lytic transglycosylase in Escherichia coli (1991)

The localization of the major autolytic enzyme, the soluble lytic transglycosylase, in the different cell compartments of Escherichia coli was investigated by immunoelectron microscopy. Ultrathin sections were labeled with a specific antiserum against purified soluble lytic transglycosylase, and the antibody-enzyme complexes were visualized with colloidal protein A-gold. A preferential localization of the lytic transglycosylase in the envelope was observed, with only 20 to 30% of the enzyme left in the cytoplasm. Most of the enzyme associated with the cell wall was tightly bound to the murein sacculus. Sacculi prepared by boiling of cells in 4% sodium dodecyl sulfate could be immunolabeled with the specific antiserum, indicating a surprisingly strong interaction of the lytic transglycosylase with murein. The enzyme-substrate complex could be reconstituted in vitro by incubating pronase-treated, protein-free murein sacculi with purified lytic transglycosylase at 0 degrees C. Titration of sacculi with increasing amounts of enzyme indicated a limiting number of binding sites for about 1,000 molecules of enzyme per sacculus. Ruptured murein sacculi obtained after penicillin treatment revealed that the enzyme is exclusively bound to the outer surface of the sacculus. This finding is discussed in the light of recent evidence suggesting that the murein of E. coli might be a structure of more than one layer expanding by inside-to-outside growth of patches of murein.
Multi-Criteria Vertical Handover for Heterogonous Networks (2011)

In the next generation heterogeneous wireless networks, a user with a multi-interface terminal may have network access from different service providers using various technologies. Vertical Handover (VHO) is the capability to switch on-going connections from one Radio Access Network (RAN) to another. This switching is based on the discovered accesses, QoS constraints, operator policies, user preferences and available system capacity and utilization. Optimizing the VHO process is an important issue of research, which leads to reduction of network signaling and mobile device power loss and on the other hand improves network quality of service (QoS) and grade of service (GoS).
Generalization of Eshelby's Formula for a Single Ellipsoidal Elastic Inclusion to Poroelasticity and Thermoelasticity (1997)

Eshelby's formula gives the response of a single ellipsoidal elastic inclusion in an elastic whole space to a uniform strain imposed at infinity. Using a linear combination of results from two simple thought experiments, we show how this formula may be generalized to both poroelasticity and thermoelasticity. The resulting new formulas are important for applications to analysis of poroelastic and thermoelastic composites, including but not restricted to rocks.
Impurity analysis of heavy metal fluoride glass fibres using selectively excited photoluminescence (1986)

A technique based on selectively excited fibre impurity luminescence (SEFIL) has been developed and successfully applied to the quantitative analysis of Pr3+, Nd3+ and Fe3+ in heavy metal fluoride glass optical fibres. With fibre standards, SEFIL provides accurate analysis at impurity levels well below the requirements for long-distance fibre applications.
Toll-like receptors, inflammation, metabolism and obesity (2011)

Obesity is a highly prevalent health problem in Western countries that leads to many important diseases such as type 2 diabetes and metabolic syndrome being now considered an inflammatory chronic disease. Adipocytes are no longer considered passive cells storing fat since they are major producers of inflammatory cytokines during obesity. Adipocytes and macrophages share many biological properties including the synthesis of similar molecules regulating inflammation. Fatty acid levels are elevated in obesity and induce inflammatory pathways by yet a mostly unknown mechanism, leading to the development of insulin and leptin resistance. Recent studies suggest that these effects could be mediated through the activation of toll-like receptors (TLR). TLR signalling pathways might contribute to the development of obesity-associated insulin resistance, thus representing a connection between innate immunity and metabolism. Here, we summarize the recent evidence for the important role that TLRs play in adipose tissue, obesity and insulin resistance.
5-Amino-4-imidazolecarboxamide Riboside from Inosine. Ring-opening Reactions of Purine Nucleosides (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT5-Amino-4-imidazolecarboxamide Riboside from Inosine. Ring-opening Reactions of Purine NucleosidesElliott ShawCite this: J. Am. Chem. Soc. 1958, 80, 15, 3899–3902Publication Date (Print):August 1, 1958Publication History Published online1 May 2002Published inissue 1 August 1958https://pubs.acs.org/doi/10.1021/ja01548a025https://doi.org/10.1021/ja01548a025research-articleACS PublicationsRequest reuse permissionsArticle Views193Altmetric-Citations41LEARN 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
Multilocus Sequence Typing of Bacteria (2006)

Multilocus sequence typing (MLST) was proposed in 1998 as a portable, universal, and definitive method for characterizing bacteria, using the human pathogen Neisseria meningitidis as an example. In addition to providing a standardized approach to data collection, by examining the nucleotide sequences of multiple loci encoding housekeeping genes, or fragments of them, MLST data are made freely available over the Internet to ensure that a uniform nomenclature is readily available to all those interested in categorizing bacteria. At the time of writing, over thirty MLST schemes have been published and made available on the Internet, mostly for pathogenic bacteria, although there are schemes for pathogenic fungi and some nonpathogenic bacteria. MLST data have been employed in epidemiological investigations of various scales and in studies of the population biology, pathogenicity, and evolution of bacteria. The increasing speed and reduced cost of nucleotide sequence determination, together with improved web-based databases and analysis tools, present the prospect of increasingly wide application of MLST.
[Synthetic inhibitors of serine proteinases. Part 25: Inhibition of trypsin, plasmin and thrombin by amides of N alpha-substituted amidinophenylalanines and 3-amidinophenyl-3-aminopropionic acids (author's transl)]. (1981)

Amides of N alpha-substituted 3-amidinophenylalanine are potent inhibitors of the serine proteinases trypsin, plasmin and thrombin. They belong to the most potent inhibitors of these enzymes of the benzamidine type. In contrast, amides of 4-amidinophenylalanine possess weak inhibitory activity towards trypsin and plasmin. The cyclic amides of this group, however, are potent thrombin inhibitors. These derivatives are the first benzamidines with specific antithrombin activity. The isomeric compounds of 3-amidinophenyl-3-aminopropionic acids possess weak inhibitory effects on trypsin, plasmin and thrombin.
Determination of drug-plasma protein binding using human serum albumin chromatographic column and multiple linear regression model (1999)

Reversible attachment to serum proteins plays a significant role in pharmacokinetics and pharmacodynamics, and a clear understanding of this process is fundamental in the development of the rational use of many therapeutics agents. Over the last few years, it has been demonstrated that immobilized human serum albumin (HSA) could be used to estimate plasma protein binding. A series of 40 structurally unrelated pharmaceutical compounds were chromatographed on an immobilized HSA column in order to construct a protein binding 'calibration curve' and multiple linear regression system. When studying the relationship between the chromatographic retention and the percentage of binding determined in vitro, a good correlation can be observed (r(2) = 0.799) using a wide variety of compounds with different binding affinities (from 0 to 99% binding). Using a quantitative structure-retention relationships (QSRR) approach to analysing chromatographic data, the correlation was improved compared to the traditional approach (r(2) = 0.824).
Low-dose pancreatic polypeptide inhibits food intake in man (2007)

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to food ingestion and remains elevated for up to 6 h postprandially. Plasma levels are elevated in patients with pancreatic tumours. An intravenous infusion of PP has been reported to reduce food intake in man, suggesting that PP is a satiety hormone. We investigated whether a lower infusion rate of PP would induce significant alterations in energy intake. The study was randomised and double-blinded. Fourteen lean fasted volunteers (five men and nine women) received 90 min infusions of PP (5 pmol/kg per min) and saline on two separate days. The dose chosen was half that used in a previous human study which reported a decrease in appetite but at supra-physiological levels of PP. One hour after the end of the infusion, a buffet lunch was served and energy intake measured. PP infusion was associated with a significant 11 % reduction in energy intake compared with saline (2440 (se 200) v. 2730 (se 180) kJ; P<0 x 05). Preprandial hunger as assessed by a visual analogue score was decreased in the PP-treated group compared to saline. These effects were achieved with plasma levels of PP within the pathophysiological range of pancreatic tumours.
Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization (2008)

The use of phospholipid-coated microbubbles for medical applications is gaining considerable attention. However, the preparation of lipid-coated microbubble suspensions containing the ideal size and size distribution of bubbles still represents a considerable challenge. The most commonly used preparation methods of sonication and mechanical agitation result in the generation of polydisperse microbubbles with diameters ranging from less than 1 microm to greater than 50 microm. Efforts have been made via distinctly different techniques such as microfluidic and electrohydrodynamic bubbling to prepare lipid-coated microbubbles with diameters less than 10 microm and with a narrow size distribution, and recent results have been highly promising. In this paper, we describe a detailed investigation of the latter method that essentially combines liquid and air flow, and an applied electric field to generate microbubbles. A parametric plot was constructed between the air flow rate (Qg) and the lipid suspension flow rate (Ql) to identify suitable flow rate regimes for the preparation of phospholipid-coated microbubbles with a mean diameter of 6.6 microm and a standard deviation of 2.5 microm. The parametric plot has also helped in developing a scaling equation between the bubble diameter and the ratio Qg/Ql. At ambient temperature (22 degrees C), these bubbles were very stable with their size remaining almost unchanged for 160 min. The influence of higher temperatures such as the human body temperature (37 degrees C) on the size and stability of the microbubbles was also explored. It was found that the mean bubble diameter fell rapidly to begin with but then stabilized at 1-2 microm after 20 min.
The effect of chemical composition and roughness of titanium nickelide surface on proliferative properties of mesenchymal stem cells (2012)

The results of the investigation of the proliferation effect on a mesenchymal stem cell (MSC) culture and the estimates on cytotoxicity of surfaces of titanium nickelide specimens prepared using special mechanical and electrochemical methods and characterized by different morphology and roughness are presented. The specimens of the alloy based on titanium nickelide are shown not to exert any toxic action on the MSCs of rats. When cultivated in the presence of the tested materials or being on their surfaces, MSCs preserved their viability, adhesive and morphological properties, and the ability for in vitro proliferation. This was confirmed by the following methods: cell counting in a Goryaev chamber, MTT, flow cytometry, and light and fluorescent microscopy. It was revealed that the proliferation processes are weakly pronounced on the surface of TH1(B) specimens whose C10–11 class roughness was achieved by multistage mechanical grinding to “high luster” and subsequent electrolytic grinding. On the contrary, the C7 class roughness of the TH1(A) specimen surfaces achieved by chemical etching and subsequent electrolytic grinding is more optimal for MSC proliferation.
A Superfamily of DNA Transposons Targeting Multicopy Small RNA Genes (2013)

Target-specific integration of transposable elements for multicopy genes, such as ribosomal RNA and small nuclear RNA (snRNA) genes, is of great interest because of the relatively harmless nature, stable inheritance and possible application for targeted gene delivery of target-specific transposable elements. To date, such strict target specificity has been observed only among non-LTR retrotransposons. We here report a new superfamily of sequence-specific DNA transposons, designated Dada. Dada encodes a DDE-type transposase that shows a distant similarity to transposases encoded by eukaryotic MuDR, hAT, P and Kolobok transposons, as well as the prokaryotic IS256 insertion element. Dada generates 6-7 bp target site duplications upon insertion. One family of Dada DNA transposons targets a specific site inside the U6 snRNA genes and are found in various fish species, water flea, oyster and polycheate worm. Other target sequences of the Dada transposons are U1 snRNA genes and different tRNA genes. The targets are well conserved in multicopy genes, indicating that copy number and sequence conservation are the primary constraints on the target choice of Dada transposons. Dada also opens a new frontier for target-specific gene delivery application.