gebhart/patrepeval huggingface dataset:
IMMUNOPHARMACOLOGY OF RAPAMYCIN (1996)

The potent immunosuppressive drugs FK506 and rapamycin interfere with signal transduction pathways required for T cell activation and growth. The distinct inhibitory effects of these drugs on the T cell activation program are mediated through the formation of pharmacologically active complexes with members of a family of intracellular receptors termed the FK506 binding proteins (FKBPs). The FKBP12.FK506 complex specifically binds to and inhibits calcineurin, a signaling protein required for transcriptional activation of the interleukin (IL)-2 gene in response to T cell antigen receptor engagement. The FKBP12. rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin (mTOR). Accumulating data suggest that mTOR functions in a previously unrecognized signal transduction pathway required for the progression of IL-2-stimulated T cells from G1 into the S phase of the cell cycle. Here we review the immunopharmacology of rapamycin, with particular emphasis on the characterization of mTOR.
Phosphinimides as a Steric Equivalent to Cyclopentadienyl:  An Approach to Ethylene Polymerization Catalyst Design (1999)

Complexes of the form (Cp†)TiCl2(NPR3) and the analogous dimethyl derivatives (Cp†)TiMe2(NPR3) have been prepared. These species in the presence of MAO, B(C6F5)3, or [Ph3C][B(C6F5)4] are active catalysts for ethylene polymerization.
Bronchial hyperreactivity revisited. (1995)

Airway hyperresponsiveness can be found in many circumstances. Its relationship to symptom production and clinical course in any disease is not clear. Further studies are needed to elucidate the relationship between airways hyperreactivity, asthma, and other lung diseases and the factors that lead to increased bronchial reactivity.
Stacked Denoising Autoencoders: Learning Useful Representations in a Deep Network with a Local Denoising Criterion (2010)

We explore an original strategy for building deep networks, based on stacking layers of denoising autoencoders which are trained locally to denoise corrupted versions of their inputs. The resulting algorithm is a straightforward variation on the stacking of ordinary autoencoders. It is however shown on a benchmark of classification problems to yield significantly lower classification error, thus bridging the performance gap with deep belief networks (DBN), and in several cases surpassing it. Higher level representations learnt in this purely unsupervised fashion also help boost the performance of subsequent SVM classifiers. Qualitative experiments show that, contrary to ordinary autoencoders, denoising autoencoders are able to learn Gabor-like edge detectors from natural image patches and larger stroke detectors from digit images. This work clearly establishes the value of using a denoising criterion as a tractable unsupervised objective to guide the learning of useful higher level representations.
The Potential Use of Metabolic Cofactors in Treatment of NAFLD (2019)

Non-alcoholic fatty liver disease (NAFLD) is caused by the imbalance between lipid deposition and lipid removal from the liver, and its global prevalence continues to increase dramatically. NAFLD encompasses a spectrum of pathological conditions including simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Even though there is a multi-disciplinary effort for development of a treatment strategy for NAFLD, there is not an approved effective medication available. Single or combined metabolic cofactors can be supplemented to boost the metabolic processes altered in NAFLD. Here, we review the dosage and usage of metabolic cofactors including l-carnitine, Nicotinamide riboside (NR), l-serine, and <i>N</i>-acetyl-l-cysteine (NAC) in human clinical studies to improve the altered biological functions associated with different human diseases. We also discuss the potential use of these substances in treatment of NAFLD and other metabolic diseases including neurodegenerative and cardiovascular diseases of which pathogenesis is linked to mitochondrial dysfunction.
Mitotic transcription and waves of gene reactivation during mitotic exit (2017)

Although the genome is generally thought to be transcriptionally silent during mitosis, technical limitations have prevented sensitive mapping of transcription during mitosis and mitotic exit. Thus, the means by which the interphase expression pattern is transduced to daughter cells have been unclear. We used 5-ethynyluridine to pulse-label transcripts during mitosis and mitotic exit and found that many genes exhibit transcription during mitosis, as confirmed with fluorescein isothiocyanate-uridine 5'-triphosphate labeling, RNA fluorescence in situ hybridization, and quantitative reverse transcription polymerase chain reaction. The first round of transcription immediately after mitosis primarily activates genes involved in the growth and rebuilding of daughter cells, rather than cell type-specific functions. We propose that the cell's transcription pattern is largely retained at a low level through mitosis, whereas the amplitude of transcription observed in interphase is reestablished during mitotic exit.
Brain Cholesterol: Long Secret Life Behind a Barrier (2004)

Although an immense knowledge has accumulated concerning regulation of cholesterol homeostasis in the body, this does not include the brain, where details are just emerging. Approximately 25% of the total amount of the cholesterol present in humans is localized to this organ, most of it present in myelin. Almost all brain cholesterol is a product of local synthesis, with the blood-brain barrier efficiently protecting it from exchange with lipoprotein cholesterol in the circulation. Thus, there is a highly efficient apolipoprotein-dependent recycling of cholesterol in the brain, with minimal losses to the circulation. Under steady-state conditions, most of the de novo synthesis of cholesterol in the brain appears to be balanced by excretion of the cytochrome P-450-generated oxysterol 24S-hydroxycholesterol. This oxysterol is capable of escaping the recycling mechanism and traversing the blood-brain barrier. Cholesterol levels and cholesterol turnover are affected in neurodegenerating disorders, and the capacity for cholesterol transport and recycling in the brain seems to be of importance for the development of such diseases. The possibility has been discussed that administration of inhibitors of cholesterol synthesis may reduce the prevalence of Alzheimer disease. No firm conclusions can, however, be drawn from the studies presented thus far. In the present review, the most recent advances in our understanding of cholesterol turnover in the brain is discussed.
A 0.9V to 1.95V dynamic voltage-scalable and frequency-scalable 32b powerPC processor (2005)

A 32 b PowerPC/spl trade/ system-on-a-chip supporting dynamic voltage supply and dynamic frequency scaling operates from 366 MHz at 1.8 V and 600 mW down to 150 MHz at 1.0 V and 53 mW in a 0.18 /spl mu/m CMOS process. Maximum supply change without PLL relock is 10 mV//spl mu/s. Processor state save/restore enables a deep-sleep state.
Sensory representation abnormalities that parallel focal hand dystonia in a primate model (2002)

In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of microelectrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over 1 mm of cortex within 6 weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animal's ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as were found in cortical representations.
Pharmaceutical Cocrystals and Their Physicochemical Properties (2009)

This review article will highlight and discuss the advances made over the last 10 years pertaining to physical and chemical property improvements through pharmaceutical cocrystals and, hopefully, draw closer the fields of crystal engineering and pharmaceutical sciences.
Production of a Human Monoclonal Antibody to a Synthetic Peptide by Active In Vivo Immunization Using a SCID Mouse Grafted with Human Lymphocytes. (1993)

In order to meet the present increased demands, we have tried to improve the methods to produce human monoclonal antibodies by using a SCID mouse grafted with human mononuclear cells. Initially, we gave an anti-asialo GM1 antibody to a SCID mouse to suppress the NK activity, as a pretreatment. Then, fifty million human mononuclear cells (MNC) from a healthy volunteer were injected intraperitoneally to the SCID mouse so as to construct a human immune system in the mouse (PBL-SCID mouse). We immunized the mouse with a synthetic peptide (pep 190) conjugated with KLH four times. The spleen cells taken from the immunized PBL-SCID mouse were fused with (mouse x human) heteromyeloma cells. The hybridoma cells were selected in GIT medium containing HAT and IL-6. Among 68 hybridoma-growing wells, we obtained one hybridoma clone (#41-1-4) which secreted a specific antibody to pep 190. The reactivity of this monoclonal antibody was tested by ELISA and the specificity of this antibody was confirmed by an absorption test with different kinds of proteins. This paper is the first report of the successful production of peptide-specific human monoclonal antibody by active in vivo immunization using a PBL-SCID mouse. By this active in vivo immunization system using a PBL-SCID mouse, human monoclonal antibodies for any sort of peptide antigens may easily be made available.
Expanding Human T Regulatory Cells with the mTOR-Inhibitor Rapamycin (2011)

CD4(+)CD25(+)FOXP3(+) T regulatory (Treg) cells are pivotal for the induction and maintenance of peripheral tolerance in both mice and humans. The possibility to use Treg cells for the treatment of T-cell-mediated diseases has recently gained increasing momentum. However, given the limited amount of circulating FOXP3(+) Treg cells, efficient methods for their ex vivo expansion are highly desirable. Rapamycin allows for in vitro expansion of murine and human FOXP3(+) Treg cells, which maintain their regulatory phenotype and suppressive capacity. Here, we describe in detail the powerful methods for enriching human FOXP3(+) Treg cells starting from unfractionated CD4(+) T cells or for expanding CD25(+)-enriched Treg cells in the presence of rapamycin.
ATPS-52A PRE-CLINICAL COMBINATORIAL STRATEGY TO TARGET THE JAK/STAT AND EGFR PATHWAYS IN GBM (2015)

Glioblastoma multiforme (GBM), characterized by an aggressive clinical course, therapeutic resistance and striking molecular heterogeneity, remains incurable. A large number GBMs have EGFR alterations and, despite poor clinical translation to date, EGFR inhibition remains of therapeutic relevance. Recent evidence, from our group and others, indicates that JAK2/STAT3 pathway is an important mediator of tumor cell survival, growth, and invasion in GBM. Interestingly, EGFR inhibition leads to activation of survival-signalling pathways such as STAT3, diminishing effectiveness of EGFR inhibition. We investigated the efficacy of a novel JAK2 inhibitor, pacritinib, in brain tumour initiating cell (BTIC) lines to evaluate potential use in the treatment of GBM patients. In a Phase III study of patients with myelofibrosis, pacritinib demonstrated manageable toxicity and clinically and statistically improved patient spleen volume and patient reported outcomes. Pacritinib results in on-target JAK2/STAT3 inhibition at 1-2 µM and dramatically reduces BTIC proliferation, regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. Pacritinib in combination with temozolomide prolongs survival, over either drug alone, in orthopically xenografted NOD-SCID. We are testing the hypothesis that concurrent inhibition of JAK/STAT and EGFR signalling may be an effective, clinically relevant therapeutic, strategy for GBM. We examined the in vitro actions of pacritinib on BTICs, in combination with three clinically approved EGFR inhibitors, erlotinib, afatinib and lapatinib and are investigating other clinically relevant EGFR inhibitors for GBM. Combinatorial treatment with pacritinib and EGFR inhibitors shows striking responses, with lowered IC50s and BTIC viability. The combinatorial actions of EGFR and STAT3 inhibition were particularly effective in BTIC lines with EGFR activating vIII and missense point mutations. On target activity was demonstrated with reduced phospho-EGFR, phospho-STAT3 and effectors of both pathways. Current studies are aimed at investigating the combined actions of Pacritinib and EGFR inhibitors, over single agents, in orthotopic xenograft animal survival.
Common and Contrasting Themes of Plant and Animal Diseases (2001)

Recent studies in bacterial pathogenesis reveal common and contrasting mechanisms of pathogen virulence and host resistance in plant and animal diseases. This review presents recent developments in the study of plant and animal pathogenesis, with respect to bacterial colonization and the delivery of effector proteins to the host. Furthermore, host defense responses in both plants and animals are discussed in relation to mechanisms of pathogen recognition and defense signaling. Future studies will greatly add to our understanding of the molecular events defining host-pathogen interactions.
Red cell and platelet‐bound IgG penicillin antibodies in a patient with thrombocytopenia (1984)

A patient was found to have a positive direct antiglobulin test and thrombocytopenia while on a moderate dose of intravenous penicillin. Serological evaluation of the patient's red cells demonstrated that the positive antiglobulin test was due to antipenicillin antibody. This antibody also was demonstrated in the patient's serum. The patient's platelets had increased quantities of IgG; an eluate from her platelets gave positive test results with platelets treated with penicillin but not normal platelets. Her serum also reacted only with penicillin-treated platelets. Multiple absorptions of her serum with red cells treated with penicillin reduced reactivity against both fresh red cells and platelets treated with penicillin. This patient demonstrated the coexistence of drug-induced immune phenomena directed against both red cells and platelets.
A Novel Bioabsorbable Conduit Augments Healing of Avascular Meniscal Tears in a Dog Model (2007)

Clinical studies using the conduit in humans may be appropriate to determine the safety and efficacy of the device for cases of avascular and poorly vascularized meniscal tears, where the device can be successfully implanted from tear to meniscal rim, the tears can be surgically repaired, and patient compliance can be ensured.
Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation (2004)

The promise of human embryonic stem cells (hESCs) to provide an unlimited supply of cells for cell therapy and tissue engineering depends on the availability of a controllable bioprocess for their expansion and differentiation. We describe for the first time the formation of differentiating human embryoid bodies (hEBs) in rotating bioreactors to try and control their agglomeration. The efficacy of the dynamic process compared to static cultivation in Petri dishes was analyzed with respect to the yield of hEB formation and differentiation. Quantitative analyses of hEBs, DNA and protein contents, and viable cell concentration, as measures for culture cellularity and scale-up, revealed 3-fold enhancement in generation of hEBs compared to the static culture. Other metabolic indices such as glucose consumption, lactic acid production, and pH pointed to efficient cell expansion and differentiation in the dynamic cultures. The type of rotating vessel had a significant impact on the process of hEB formation and agglomeration. In the slow turning lateral vessel (STLV), hEBs were smaller in size and no large necrotic centers were seen, even after 1-month cultivation. In the high aspect rotating vessel (HARV), hEB agglomeration was massive. The appearance of representative tissues derived from the three germ layers as well as primitive neuronal tube organization, blood vessel formation, and specific-endocrine secretion indicated that the initial developmental events are not altered in the dynamically formed hEBs. Collectively, our study defines the culture conditions in which control over the aggregation of differentiating hESCs is obtained, thus enabling scaleable cell production for clinical and industrial applications.
Cleavage of deoxyoxanosine-containing oligodeoxyribonucleotides by bacterial endonuclease V (2004)

Oxanine (O) is a deamination product derived from guanine with the nitrogen at the N1 position substituted by oxygen. Cytosine, thymine, adenine, guanine as well as oxanine itself can be incorporated by Klenow Fragment to pair with oxanine in a DNA template with similar efficiency, indicating that oxanine in DNA may cause various mutations. As a nucleotide, deoxyoxanosine may substitute for deoxyguanosine to complete a primer extension reaction. Endonuclease V, an enzyme known for its enzymatic activity on uridine-, inosine- and xanthosine-containing DNA, can cleave oxanosine-containing DNA at the second phosphodiester bond 3' to the lesion. Mg2+ or Mn2+, and to a small extent Co2+ or Ni2+, support the oxanosine-containing DNA cleavage activity. All four oxanosine-containing base pairs (A/O, T/O, C/O and G/O) were cleaved with similar efficiency. The cleavage of double-stranded oxanosine-containing DNA was approximately 6-fold less efficient than that of double-stranded inosine-containing DNA. Single-stranded oxanosine-containing DNA was cleaved with a lower efficiency as compared with double-stranded oxanosine-containing DNA. A metal ion enhances the binding of endonuclease V to double-stranded and single-stranded oxanosine-containing DNA 6- and 4-fold, respectively. Hypothetic models of oxanine-containing base pairs and deaminated base recognition mechanism are presented.
Connective tissue diseases: advances in diagnosis and management. (1993)

Connective tissue diseases encompass a group of multisystem inflammatory syndromes whose pathogenesis is thought to be autoimmune. They are all associated with the production of autoantibodies that bind to predominantly intracellular antigens. We will describe recent advances that have led to improved classification and more accurate prognosis.
2-Amino-7-(.beta.-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one. Synthesis of ara-7-deazaguanosine via phase-transfer glycosylation (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Amino-7-(.beta.-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidin-4(3H)-one. Synthesis of ara-7-deazaguanosine via phase-transfer glycosylationFrank Seela and Heinz Dieter WinkelerCite this: J. Org. Chem. 1982, 47, 2, 226–230Publication Date (Print):January 1, 1982Publication History Published online1 May 2002Published inissue 1 January 1982https://pubs.acs.org/doi/10.1021/jo00341a009https://doi.org/10.1021/jo00341a009research-articleACS PublicationsRequest reuse permissionsArticle Views235Altmetric-Citations36LEARN 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
Cytogenetic analysis of 434 consecutively ascertained specimens of non‐Hodgkin's lymphoma: Correlations between recurrent aberrations, histology, and exposure to cytotoxic treatment (1991)

Cytogenetic abnormalities in non-Hodgkin's Lymphoma (NHL) provide a model system for the analysis of the role of multiple genomic aberrations in human malignancy. In order to define correlations with histology, tumor evolution, and the effects of genotoxic exposure, cytogenetic analysis was performed on 434 specimens of NHL derived from 423 patients consecutively ascertained over a 5-year period (1984-1989). Six recurring translocations (RT) were observed: t(14;18)(q32;q21), t(8;14)(q24;q32), t(11;14)(q13;q32), t(3;22)(q27;11), t(2;5)(p23;q35), and t(1;6)(q21;q25). No translocation was specific to a single histologic subtype. Other structural chromosome abnormalities were analyzed according to break site; groups of related breaks were considered together for statistical analysis. Recurring other structural and numerical aberrations (ROA) encountered in greater than 10% of specimens included rearrangements with breaks at bands 1p32-36, 1q21-23, 6q21-25, and trisomies of chromosomes 7 and 12. ROA with one of these breaks or numerical abnormalities were the sole abnormalities in at least two cases. Correlations were observed among ROA and between ROA and histologic subtypes. Trisomy 7, breaks at 1q21-23, 1p32-36, 6q21-25, and 7q32 were associated with t(14;18); trisomy 18 was associated with trisomy 3; and structural abnormalities of chromosome 17 were associated with breaks at 1p32-36 and 6q21-25. Trisomy 7 and trisomy 12 were more frequent in t(14;18)-bearing intermediate to high grade tumors compared to low grade tumors. Trisomy 12 and breaks at band 1p22 were associated with large cell diffuse lymphomas. Incidence rates of reciprocal translocations, ROA, and measures of karyotypic complexity, including number of breakpoints and marker chromosomes were compared in pretreatment and posttreatment samples. Karyotypic complexity was greater in the posttreatment samples, reflecting an increased frequency of nonrecurring and low incidence aberrations. These results better define the association of genomic aberrations and tumorigenesis, histologic transformation, and tumor progression.