gebhart/patrepeval huggingface dataset:
Adipose-Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune Encephalomyelitis (2009)

Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSCs induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSCs (ASCs) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASCs preferentially home into lymphoid organs but also migrates inside the central nervous system (CNS). Most importantly, administration of ASCs in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASCs expresses activated alpha 4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that alpha 4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor, and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASCs have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuroregeneration by endogenous progenitors in animals with established disease. Overall, our data suggest that ASCs represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS.
Photovoltaic maximum power point tracking employing load parameters (2005)

Photovoltaic maximum power point tracking can be accomplished by monitoring the readings of the load parameters instead of the photovoltaic panel output parameters. It is demonstrated that load parameters based maximum power point tracking has advantages over conventional method in terms of tracking efficiency and simplicity of the hardware and software involved.
Androgen-induced recruitment of RNA polymerase II to a nuclear receptor–p160 coactivator complex (2003)

The androgen receptor, like other nuclear receptors, activates target genes by binding to hormone-responsive enhancers. Here we demonstrate that androgen induces robust recruitment of androgen receptor, members of the p160 coactivator family, and CREB-binding protein p300 specifically at the distant enhancer of prostate-specific antigen (PSA) gene. Unexpectedly, we found that RNA polymerase II (Pol II) is directly recruited to the enhancer in a hormone-dependent manner, independent of the proximal promoter, and that the isolated PSA enhancer can mediate efficient androgen induction of transcription. Inhibition of the Pol II carboxyl-terminal domain kinase activity with low concentrations of flavopiridol blocks Pol II transfer from the enhancer to the promoter and selectively abolishes PSA induction by androgen. Moreover, elevated levels of the p160 coactivator ACTR/AIB1 increase both androgen-dependent and -independent PSA expression, by facilitating Pol II recruitment to the enhancer. These results support a model in which nuclear receptors and their coactivators mediate hormone induction by serving as a staging platform for Pol II recruitment.
Highly Dispersed Catalytic Materials (1972)

Advances in machine learning have impacted myriad areas of materials science, such as the discovery of novel materials and the improvement of molecular simulations, with likely many more important developments to come. Given the rapid changes in this ...Read More
Identification of a new protein family which includes bovine protein kinase C inhibitor-1 (1994)

Correspondence| December 01 1994 Identification of a new protein family which includes bovine protein kinase C inhibitor-1 K Robinson; K Robinson Search for other works by this author on: This Site PubMed Google Scholar A Aitken A Aitken Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8728 Print ISSN: 0264-6021 © 1994 The Biochemical Society, London1994 Biochem J (1994) 304 (2): 662–664. https://doi.org/10.1042/bj3040662 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation K Robinson, A Aitken; Identification of a new protein family which includes bovine protein kinase C inhibitor-1. Biochem J 1 December 1994; 304 (2): 662–664. doi: https://doi.org/10.1042/bj3040662 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1994 The Biochemical Society, London1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Discovery and Preclinical Characterization of (+)-3-[4-(1- Piperidinoethoxy)phenyl]spiro[indene- 1,1‘-indane]-5,5‘-diol Hydrochloride:  A Promising Nonsteroidal Estrogen Receptor Agonist for Hot Flush (2003)

In our studies of the development of a novel class of selective estrogen receptor modulators, (+)-3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1'-indane]-5,5'-diol hydrochloride (1) was found to be an estrogen receptor ligand with beneficial effects in rat models for human hot flush. Moreover, 1 was found to have beneficial effects on lipid and bone metabolism while maintaining marginal effects on the uterus and breasts. These findings suggest that 1 would provide a new treatment for hot flush.
Improved GFR and renal plasma perfusion following remote ischaemic conditioning in a porcine kidney transplantation model (2012)

Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non-rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 × 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non-rIC (7.2 ml/min vs. 3.4 ml/min; ΔGFR = 3.7 ml/min, 95%-CI: 0.3-7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast-enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non-rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model.
Sequential Activation of Snail1 and N-Myc Modulates Sonic Hedgehog–Induced Transformation of Neural Cells (2011)

Activation of the Sonic hedgehog (Shh) pathway and increased expression of Gli1 play an important role in proliferation and transformation of granule cell progenitors (GCP) in the developing cerebellum. Medulloblastomas arising from cerebellar GCPs are frequently driven by Shh pathway-activating mutations; however, molecular mechanisms of Shh pathway dysregulation and transformation of neural progenitors remain poorly defined. We report that the transcription factor and oncogene Snail1 (Sna1) is directly induced by Shh pathway activity in GCPs, murine medulloblastomas, and human medulloblastoma cells. Enforced expression of Sna1 was sufficient to induce GCPs and medulloblastoma cell proliferation in the absence of Shh/Gli1 exposure. In addition, enforced expression of Sna1 increased transformation of medulloblastoma cells in vitro and in vivo. Analysis of potential Sna1 targets in neural cells revealed a novel Sna1 target, N-Myc, a transcription factor known to play a role in Shh-mediated GCP proliferation and medulloblastoma formation. We found that Sna1 directly induced transcription of N-Myc in human medulloblastoma cells and that depletion of N-Myc ablated the Sna1-induced proliferation and transformation. Taken together, these results provide further insight into the mechanism of Shh-induced transformation of neural progenitor cells and suggest that induction of Sna1 may serve to amplify the oncogenic potential of Shh pathway activation through N-Myc induction.
An Improved Synthesis of 5-Substituted Tetrazoles (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn Improved Synthesis of 5-Substituted TetrazolesWilliam G. Finnegan, Ronald A. Henry, and Robert LofquistCite this: J. Am. Chem. Soc. 1958, 80, 15, 3908–3911Publication Date (Print):August 1, 1958Publication History Published online1 May 2002Published inissue 1 August 1958https://pubs.acs.org/doi/10.1021/ja01548a028https://doi.org/10.1021/ja01548a028research-articleACS PublicationsRequest reuse permissionsArticle Views3467Altmetric-Citations360LEARN 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
Clinical pharmacokinetic studies of a human haemopoietic growth factor, GM‐CSF (1992)

The pharmacokinetics of glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied following intravenous (i.v.) and subcutaneous (s.c.) bolus injection of rhGM-CSF, 8 micrograms kg-1 employing a sensitive radioimmunoassay. After a single i.v. bolus injection, an initial high serum level of rhGM-CSF was observed, followed by a rapid decrease that occurred in two phases with a half-life (t1/2) alpha of 20.0 +/- 5 min and a t1/2 beta of 68.3 +/- 8 min. Following s.c. bolus injection the absorption was more prolonged. Peak serum concentrations did not occur until about 15-20 h, and were followed by a more protracted elimination than by the i.v. route. In all patients the single rhGM-CSF injection led to an increase in peripheral white blood cells (WBC), after a temporary drop of 2-5 h duration. The increase in WBC was of longer duration after s.c. than after i.v. bolus treatment. Since the subcutaneous administration leads to prolonged serum concentration of rhGM-CSF and prolonged increase in peripheral WBC, it seems preferable to i.v. bolus injection, and as effective as continuous i.v. infusion.
Practical all-fiber source of high-power, 120-fs pulses at 1 μm (2003)

Amplification of femtosecond pulses at 1.03 micrometre in a standard Yb-doped single-mode fiber is reported. A pulse energy of 8 nJ and an average power of 400 mW are obtained, limited by available pump power. To our knowledge these are the highest pulse energy and average power obtained from an integrated, single-mode fiber amplifier. After dechirping, 120-fs, 6-nJ pulses are obtained. A practical fiber-based source with performance comparable with that of a bulk solid-state laser is thus demonstrated, and scaling to substantially higher powers will be possible.
Persistent infection of normal mice with human immunodeficiency virus (1992)

In this article, we report the establishment of persistent HIV type 1 infection of normal Swiss mice after a single intraperitoneal injection with high-producing HIV-infected U937 cells. Anti-HIV antibodies were found more than 500 days after the original injection, and p24 antigenemia was detected in approximately 50% of the mice. By polymerase chain reaction (PCR) techniques, HIV-specific gag and env sequences were detected in DNA samples from peripheral blood mononuclear cells (PBMC) and peritoneal cells of seropositive mice 300 to 500 days after inoculation with HIV-infected cells. These DNA samples did not contain human DNA sequences, as determined by PCR analysis using primers and the probe for the HLA-DQ alpha gene. Low levels of p24 and detectable human reverse transcriptase activity were found in cultures of PBMC and peritoneal macrophages. Cocultivation of PBMC, peritoneal cells, and spleen cells with human uninfected U937 or CEM (a T lymphoma cell line) cells resulted in HIV infection of the target cells, as determined by PCR analysis and/or p24 assays. The intravenous injection of untreated Swiss mice with the PBMC from PCR-positive mice resulted in the development of an increasing antibody response to HIV in the recipient animals. Together these results indicate that cells from seropositive Swiss mice were persistently infected with HIV and were capable of producing infectious virus. The development of persistent HIV infection in an immunocompetent mouse may represent the starting point for further studies aimed at defining the host mechanisms involved in the restriction of virus replication, defining the pathogenesis of HIV infection, and testing antiviral compounds and vaccines.
2008 Update From the Collaborative Islet Transplant Registry (2008)

Clinical islet transplantation needs to be evaluated using the most clinically relevant endpoints such as glucose stabilization and severe hypoglycemia prevention. The cumulative results of the registry confirm the inarguably positive impact of islet transplantation on metabolic control in T1 diabetes.
Antiemetic efficacy of prochlorperazine, haloperidol, and droperidol in cisplatin-induced emesis. (1984)

The antiemetic efficacy of haloperidol, droperidol, and prochlorperazine in preventing cisplatin-induced emesis was evaluated. Twenty-seven patients receiving 51 courses of cisplatin chemotherapy randomly received antiemetic treatment with prochlorperazine (6 mg/sq m), droperidol (1 mg/sq m), or haloperidol (1 mg/sq m) in a double-blind crossover study. Antiemetics were given by intramuscular injection one hour before beginning cisplatin and every three hours thereafter for a total of six doses. The number of emetic episodes, volume of emesis, and duration of the emetic episodes were monitored by oncology nurses. There were no significant differences in the median number of emetic episodes among antiemetic treatments: 3.5 for prochlorperazine, 4.0 for haloperidol, and 3.0 for droperidol. There were also no significant differences among the antiemetics in the median volume of emesis or the median duration of the emetic episodes. At the doses used in this study, the antiemetic efficacy of prochlorperazine, droperidol, and haloperidol appear to be comparable for patients receiving cisplatin chemotherapy.
Autophagy and Cancer Therapy (2006)

Autophagy is a dynamic process of protein degradation, which is typically observed during nutrient deprivation. Recently, interest in autophagy has been renewed among oncologists, because different types of cancer cells undergo autophagy after various anticancer therapies. This type of nonapoptotic cell death has been documented mainly by observing morphological changes, e.g., numerous autophagic vacuoles in the cytoplasm of dying cells. Thus, autophagic cell death is considered programmed cell death type II, whereas apoptosis is programmed cell death type I. These two types of cell death are predominantly distinctive, but many studies demonstrate cross-talk between them. Whether autophagy in cancer cells causes death or protects cells is controversial. In multiple studies, autophagy has been inhibited pharmacologically or genetically, resulting in contrasting outcomes--survival or death--depending on the specific context. Interestingly, the regulatory pathways of autophagy share several molecules with the oncogenic pathways activated by tyrosine kinase receptors. Tumor suppressors such as Beclin 1, PTEN and p53 also play an important role in autophagy induction. Taken together, these accumulating data may lead to development of new cancer therapies that manipulate autophagy.
Changes in Drug Release Rate: Effect of Stress Storage Conditions on Film Coated Mini-Tablets (1991)

Film coated theophylline mini-tablets were exposed to stress storage conditions to investigate the effect of changes in temperature and relative humidity (RH) on drug release and the integrity of film coatings. The mini-tablets (3mm in diameter, weighing 20±1 mg) were film coated with polymers such as ethylcellulose with PEG (2:1), ethylcellulose with Eudragit L (2:1) and Eudragit RL. Samples were exposed isothermally at 28,35 and 45°C (constant RH ranging between 55 and 60%) for 21,90 and 180 days, as well as cyclically alternating them every 24h at 45°C, 55% RH; 28°C, 20% RH; and 5°C, 10% RH for 90 days. Dissolution profiles determined after storage were compared with those 24h after initial coating. All samples showed that the coating integrity was maintained. However, dissolution was significantly impeded to a degree directly proportional to temperature, whilst the effect of RH appeared insignificant.
The Ribavirin Analog ICN 17261 Demonstrates Reduced Toxicity and Antiviral Effects with Retention of both Immunomodulatory Activity and Reduction of Hepatitis-Induced Serum Alanine Aminotransferase Levels (2000)

The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.
Cell cycle state, response to hemopoietic growth factors and retroviral vector-mediated transduction of human hemopoietic stem cells. (1996)

A multi-parameter fluorometric analysis was applied to study in vitro proliferation and expansion of a candidate hemopoietic stem cell population, ie CD34brightLin cells. In primary hemopoietic cell samples the CD34brightLin population comprised on average, 1% of CD34+ cells from bone marrow (BM) or umbilical cord blood and 0.1% of mobilized peripheral blood CD34+ cells. The fraction of CD34brightLin cells engaged in the S+G2/M phases of the cell cycle was largest in regenerating BM (10.6% versus 1-2% in the other sources). Maintenance of CD34+ BM cells in hemopoietic growth factor supplemented liquid cultures resulted in a decrease of the CD34brightLin population in most samples. Cell cycle analysis showed the constant existence of proliferating CD34+ cells during the culture period. The fraction of cycling CD34brightLin cells was, however, very small and only occasionally exceeded input values. At all tested time-points during culture, BM CD34+ cells could be transduced by a single incubation with a recombinant retrovirus supernatant. CD34brightLin cells, however, were much more refractory to retroviral vector-mediated transduction. This could be explained only in part by quiescence of CD34brightLin cells. Hence, factors other than cell proliferation clearly influence the early stages of retroviral transduction of human hemopoietic stem cells.
Stability and Safety of an AAV Vector for Treating RPGR-ORF15 X-Linked Retinitis Pigmentosa (2015)

Our collaborative successful gene replacement therapy using AAV vectors expressing a variant of human RPGR-ORF15 in two canine models provided therapeutic proof of concept for translation into human treatment. The ORF15 sequence contained within this AAV vector, however, has ORF15 DNA sequence variations compared to the published sequence that are likely due to its unusual composition of repetitive purine nucleotides. This mutability is a concern for AAV vector production and safety when contemplating a human trial. In this study, we establish the safety profile of AAV-hIRBP-hRPGR and AAV-hGRK1-hRPGR vectors used in the initial canine proof-of-principle experiments by demonstrating hRPGR-ORF15 sequence stability during all phases of manipulation, from plasmid propagation to vector production to its stability in vivo after subretinal administration to animals. We also evaluate potential toxicity in vivo by investigating protein expression, retinal structure and function, and vector biodistribution. Expression of hRPGR is detected in the inner segments and synaptic terminals of photoreceptors and is restricted to the connecting cilium when the vector is further diluted. Treated eyes exhibit no toxicity as assessed by retinal histopathology, immunocytochemistry, optical coherence tomography, fundoscopy, electroretinogram, and vector biodistribution. Therefore, the hRPGR-ORF15 variant in our AAV vectors appears to be a more stable form than the endogenous hRPGR cDNA when propagated in vitro. Its safety profile presented here in combination with its proven efficacy supports future gene therapy clinical trials.
Mechanically and Light Induced Anchoring of Liquid Crystal on Polyimide Film (1999)

Abstract The interplay between the effects of mechanical rubbing and UV light induced deimidization on polyimide films has been studied. Exposure to depolarized UV light of rubbing PI film was found to suppress effective anchoring energy. Polarized light led to the alteration of the orientational distribution of PI molecules obtained by rubbing i.e to the change of both anchoring energy and easy axis direction. A simple model based on the selective UV light absorption with consequent deimidization of PI molecules describes the UV-initiated processes on the rubbed polyimide layers but contradicts the experimental data obtained for non-rubbed layers. The results obtained show that UV exposure can be effectively used to control anchoring parameters.