gebhart/patrepeval huggingface dataset:
The Oral Fluid MEMS/NEMS Chip (OFMNC): Diagnostic & Translational Applications (2005)

The ability to monitor health status, disease onset and progression, and treatment outcome through non-invasive means is a most desirable goal in health-care promotion and delivery. There are three prerequisites for this goal to be realized: specific biomarkers associated with a health or disease state, a non-invasive approach to detect and monitor the biomarkers, and the technologies to discriminate between and among the biomarkers. We present a roadmap to achieve these goals using oral fluids as the diagnostic medium to scrutinize the health and/or disease status of individuals. This is an ideal opportunity to bridge state-of-the-art micro-/nano-electromechanical system (MEMS/NEMS) sensors to oral fluid for diagnostic applications. As the "mirror of body", oral fluid is a perfect medium to be explored for health and disease surveillance. The translational applications and opportunities are enormous.
The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. (1989)

FK506, a neutral macrolide with immunosuppressive properties, was shown to selectively and rapidly inhibit the accumulation of IL-2 mRNA, as well as the mRNAs of other early (E) phase T cell activation genes such as IL-3, IL-4, GM-CSF, TNF alpha, IFN-gamma, and c-myc in activated human peripheral blood T cells. The activity of FK506, when compared to Cyclosporin A, another immunosuppressant, was 10 to 100x more potent in its ability to inhibit IL-2 mRNA synthesis. FK506 inhibited IL-2 mRNA accumulation in Con A, Con A plus PMA, Ionomycin plus PMA, anti-CD3, and anti-CD3 plus PMA activated T cells. Transcripts from other T cell gene classes such as the immediate early (IE) phase gene, c-fos, the late phase (L) genes, transferrin receptor, IL-2R alpha-chain, and TNF-beta, and the constitutive class genes glyceraldehyde-3-phosphate dehydrogenase and class I MHC HLA-B7 were not affected by FK506. The macrolide Rapamycin, which is structurally related to FK506, had no inhibitory effect on IE, E, L, or constitutive class mRNAs, but it appeared to increase the levels of the E-phase transcripts that were inhibited in FK506 treated T cells. The effect of FK506 on inducible genes in non-T and non-lymphoid human cells was studied in LPS-induced monocytes and PMA or IL-1 activated synovial fibroblasts. FK506 did not affect expression of the mRNAs for IL-1 alpha or IL-1 beta in human monocytes, or of stromelysin, collagenase, or TIMP in synovial fibroblasts. Nuclear run-off transcription studies indicate that FK506 inhibits transcription of the IL-2 gene. These studies suggest that Cyclosporin A and FK506 may effect a common early event in the T cell activation pathway.
Detailed Analysis of Structures and Formulations of Cationic Lipids for Efficient Gene Transfer to the Lung (1996)

Cationic lipid-mediated gene transfer of cystic fibrosis transmembrane conductance regulator (CFTR) cDNA represents a promising approach for treatment of cystic fibrosis (CF). Here, we report on the structures of several novel cationic lipids that are effective for gene delivery to the lungs of mice. An amphiphile (#67) consisting of a cholesterol anchor linked to a spermine headgroup in a "T-shape" configuration was shown to be particularly efficacious. An optimized formulation of #67 and plasmid vector encoding chloramphenicol acetyl-transferase (CAT) was capable of generating up to 1 microgram of CAT enzyme/lung following intranasal instillation into BALB/c mice. This represents a 1,000-fold increase in expression above that obtained in animals instilled with naked pDNA alone and is greater than 100-fold more active than cationic lipids used previously for CFTR gene expression. When directly compared with adenovirus-based vectors containing similar transcription units, the number of molecules of gene product expressed using lipid-mediated transfer was equivalent to vector administration at multiplicities of infection ranging from 1 to 20. The level of transgene expression in the lungs of BALB/c mice peaked between days 1 and 4 post-instillation, followed by a rapid decline to approximately 20% of the maximal value by day 7. Undiminished levels of transgene expression in the lung could be obtained following repeated intranasal administration of #67:DOPE:pCF1-CAT in nude mice. Transfection of cells with formulations of #67:DOPE:pCF1-CFTR generated cAMP-stimulated CFTR chloride channel and fluid transport activities, two well-characterized defects associated with CF cells. Taken together, the data demonstrate that cationic lipid-mediated gene delivery and expression of CFTR in CF lungs is a viable and promising approach for treatment of the disease.
Analysis of Poly(carbon suboxide) by Small‐Angle X‐ray Scattering (2004)

Band substances: The polymerization of C3O2 (see picture left, at −10 °C) into a red-brown, solid polymer (right) having identical composition has been known for almost 100 years. However, the constitution of the polymer remained unknown. Small-angle X-ray scattering studies of the dissolved polymer show that it forms a stiff bandlike molecule with approximately 40 monomeric units, thus confirming the predicted bandlike structure with condensed α-pyrone rings.
Rimonabant Sanofi-Synthélabo. (2004)

Rimonabant, an antagonist of central cannabinoid type 1 (CB1) receptors, is being developed by Sanofi-Synthélabo for the potential treatment of obesity and as a potential smoking cessation agent. Phase III trials were initiated for obesity in August 2001 and were ongoing in September 2003. By September 2002, the compound had entered phase III trials for smoking cessation, and these trials were ongoing in September 2003.
On single-pass indexing with MapReduce (2009)

Indexing is an important Information Retrieval (IR) operation, which must be parallelised to support large-scale document corpora. We propose a novel adaptation of the state-of-the-art single-pass indexing algorithm in terms of the MapReduce programming model. We then experiment with this adaptation, in the context of the Hadoop MapReduce implementation. In particular, we explore the scale of improvements that can be achieved when using firstly more processing hardware and secondly larger corpora. Our results show that indexing speed increases in a close to linear fashion when scaling corpus size or number of processing machines. This suggests that the proposed indexing implementation is viable to support upcoming large-scale corpora.
CD4+Foxp3+ regulatory T cell therapy in transplantation (2011)

Regulatory T cells (Tregs) are long-lived cells that suppress immune responses in vivo in a dominant and antigen-specific manner. Therefore, therapeutic application of Tregs to control unwanted immune responses is an active area of investigation. Tregs can confer long-term protection against auto-inflammatory diseases in mouse models. They have also been shown to be effective in suppressing alloimmunity in models of graft-versus-host disease and organ transplantation. Building on extensive research in Treg biology and preclinical testing of therapeutic efficacy over the past decade, we are now at the point of evaluating the safety and efficacy of Treg therapy in humans. This review focuses on developing therapy for transplantation using CD4(+)Foxp3(+) Tregs, with an emphasis on the studies that have informed clinical approaches that aim to maximize the benefits while overcoming the challenges and risks of Treg cell therapy.
Mapping of the two overlapping genes for polypeptides NS1 and NS2 on RNA segment 8 of influenza virus genome. (1980)

RNA segment 8 of the influenza virus genome is unique in coding for two polypeptides, NS1 (Mr, approximately 25,000) and NS2 (Mr, approximately 11,000). These polypeptides are synthesized from separate mRNA species. By using cloned DNA derived from RNA segment 8 (NS DNA) the two mRNAs have been mapped on segment 8 by hybridization of mRNAs with restriction endonuclease fragments of the DNA and nuclease S1 digestion methods. These data indicate that the body of the NS1 mRNA (approximately 850 nucleotides) maps at 0.05-0.95 units of the cloned NS DNA and the body of the NS2 mRNA (approximately 340 nucleotides) maps at 0.59-0.95 unitssuggesting that the two mRNAs are 3' coterminal and share the same poly(A) addition site. These positions of the mRNAs on the viral genome segment were confirmed in hybrid-arrested translation experiments using fragments of the cloned NS DNA to inhibit the synthesis in vitro of NS1 or NS2 polypeptides. In addition, in these translation experiments the use of certain DNA fragments resulted in premature termination of the NS1 polypeptide. From these data, it could be estimated that the termination of translation of NS1 is at approximately 0.76 map unit. Thus, the coding regions of the two mRNAs overlap by approximately 144-159 nucleotides, the equivalent of approximately 48-53 amino acids. Peptide mapping experiments indicated that polypeptides NS1 and NS2 do not share methionine- or leucine-containing tryptic peptides. The results obtained indicate the translation of the NS2 mRNA occurs in a reading frame different from that used for NS1.
Endothelin‐1 and Neuregulin‐1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse (2005)

The cells that form the cardiac conduction system (CCS) are recruited from embryonic cardiomyocytes. Endothelin-1 (ET-1) and Neuregulin-1 (NRG-1) have been associated with this transition in the avian and murine systems, respectively. We established murine embryonic cardiomyocyte cultures induced or not with ET-1 and/or NRG-1 to compare the expression of cardiomyocyte and CCS-specific genes. Semiquantitative reverse transcription-polymerase chain reaction analysis showed that cardiomyogenesis and CCS-specific markers, such as Nkx2.5, GATA4, Irx4, Connexin 40, Connexin 45, HF-1b, and MinK, were up-regulated in the presence of either growth factor. Additionally, immunofluorescence analysis demonstrated that ET-1 or NRG-1 increased the number of cells expressing the Purkinje fiber-specific marker Connexin 40 in induced cultures but did not selectively increase their proliferation rate. Interestingly, additive effects were not observed in ET-1 and NRG-1 combination treatments. Among other possibilities, this observation suggests that these factors may interact to promote the differentiation of the murine CCS.
Assessment of the New Capacity and LOS of Transfer Facilities in the High-speed Railway Stations (2008)

The Design manual for adjusting the capacity and LOS of facilities has been shared in urban railways and high-speed railway stations. However, the pattern of urban railways users and those of high-speed railway users are different from each other. For an example, the high-speed railway users tend to carry voluminous luggages and the transportation disadvantaged such as children and the elderlies. Accordingly, we see that the scale of facilities and the station itself should be constructed differently. The transfer facilities in the high-speed railway stations are classified widely into walking assisting facilities and convenient facilities. We invented the concept of PME (Pedestrian Moving Equivalent) and PWE (Pedestrian Waiting Equivalent)for the spatial calculation of those who are with wheeled luggages, back packs, and children to reflect the uniqueness of users in high-speed railway stations. These equivalents have been applied to the design of the facilities to asses the new Capacity and LOS that are users' favored.
The development of oral vaccines against parasitic diseases utilizing live attenuatedSalmonella (1995)

Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.
Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1. (1983)

A guanosine analog, 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG), was found to inhibit herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, cytomegalovirus, and Epstein-Barr virus replication by greater than 50% at concentrations that do not inhibit cell growth in culture. The potency of the drug against all of these viruses is greater than that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir). DHPG was active against HSV-1 growth during the early phase of virus replication and had no activity when added at a later time after infection. Its antiviral activity was irreversible. Thymidine partially neutralized its action. The anti-HSV-1 activity of DHPG was dependent on the induction and the properties of virus-induced thymidine kinase. Virus variants that induced altered virus thymidine kinase and became resistant to acyclovir were still as sensitive to DHPG as the parental virus. DHPG is active against five different HSV variants with induced altered DNA polymerase and resistance to acyclovir.
Koordinierte Ablaufplanung auf mehreren Ebenen. (2001)

Bei der Planung der Produktion eines Betriebes mit mehreren Standorten (Multi-Site Scheduling) stellen sich Planungsprobleme auf unterschiedlichen Ebenen. Zusatzlich mussen die beteiligten Planungssysteme koordiniert werden. In diesem Papier wird ein Ansatz kooperierender Planungssysteme vorgestellt, die die Multi-Site Scheduling Problematik losen. In der globalen Ablaufplanung werden auf Basis von externen Auftragen Vorgaben fur die lokalen Betriebe in Form eines globalen Ablaufplans ermittelt, der dann in den lokalen Ablaufplanungssystemen fur die einzelnen Betriebe in konkrete maschinenbezogene Plane fur die einzelnen Zwischenprodukte umgesetzt werden muss. Auf beiden Ebenen sind pradiktive und reaktive Planungsaufgaben zu erfullen. Ein Gesamtkonzept fur das Multi-Site Scheduling Problem sowie mogliche Losungsansatze fur die enthaltenen Planungsaufgaben werden beschrieben.
Adenovirus-mediated thymidine kinase gene transduction in human epithelial ovarian cancer cell lines followed by exposure to ganciclovir. (1996)

In an effort to develop gene therapy for ovarian cancer efficacy and toxicity of adenovirus-mediated transfer of the HSV-TK gene followed by administration of ganciclovir were studied in two human epithelial ovarian cancer cell lines Ov-ca-2774 and Ov-ca-1225. 100% transduction was achieved in both cell lines at MOIs of 7 and 15 as demonstrated by X-Gal staining. No toxicity of virus alone was observed at MOIs up to 30. GCV was not toxic up to 200 micrograms/ml. Cell killing efficacy was shown to be dependent on MOI as well as GCV dose. The "bystander effect" of ADV/RSV-TK was quantified by mixing experiments and found to be dependent on the proportion of ADV/RSV-TK positive cells as well as the GCV dosage. Similar results were observed in both cell lines. ADV/RSV-TK mediated gene therapy may be a promising approach in ovarian cancer.
FISH detection of chromosome 14q32/IgH translocations: evaluation in follicular lymphoma (1998)

A FISH strategy capable of detecting chromosome 14q32 rearrangements involving the IgH locus, including in interphase nuclei, was developed using Ig variable and constant region cosmids from the extremities of the locus in a dual hybridization approach, using signal splitting as evidence of rearrangement. The large size of the locus (1.3 Mb) and the propensity for internal deletion due to physiological VDJ recombination and isotype switching complicate analysis of this locus. We used the Ig10 cosmid, which hybridizes to C epsilon and C alpha2 at the 3' end of the constant region, in order to minimize deletion and/or splitting of the constant region probe. Cos Ig10 and the IgV18 VH probes were compared with a specific IgH-BCL2 FISH dual hybridization approach in follicular lymphoma (FL). Both were capable of detecting the t(14;18) in interphase nuclei, including in cases with no apparent abnormality by classic karyotype analysis, although the sensitivity of the IgH approach was slightly lower. We have also successfully applied these probes to whole cell cytospin preparations, rendering analysis of cryopreserved material possible, although interpretation should be limited to frequent events, particularly following cell manipulation. Analysis of flow cytometric sorted bone marrow fractions from three FL patients by FISH and FICTION showed that the t(14;18) was present in a much lower proportion of CD34 positive than negative cells but that the higher level of background hybridization limits use of these techniques for the reliable quantification of rare events.
Prodrugs: effective solutions for solubility, permeability and targeting challenges. (2004)

This 2-day inaugural conference on prodrugs was presented by Pharmaceutical Education Associates and covered recent developments in prodrug techniques to solve delivery and targeting issues in drug discovery and development. The speakers were drawn from industry and academia, and the conference was attended mostly by researchers working in the pharmaceutical and biotechnology industries. A number of topics were presented at the conference, from basic prodrug design and functional group considerations to drug metabolism involving cytochrome P450 enzymes, from increasing water solubility, bioavailability, permeability and stability to tumor targeting, from the development of new anti-inflammatory agents to anti-HIV agents, and from the use of transporters and receptor-mediated endocytosis in prodrug delivery to the use of gene therapy for enzyme delivery to cancer cells and tissues. Several case studies were presented including improved pharmaceutical products in the clinic and at various stages of development.
Observation of viable alloskin vs xenoskin grafted onto subcutaneous tissue wounds after tangential excision in massive burns (2016)

From the clinical observations, fresh pigskin and cryopreserved alloskins could be used with equal effectiveness at an early stage (within 2 weeks post-operation) as temporary coverage on massive burns after TESGSTW. After engraftment, several cryopreserved alloskins or fresh pigskins could co-survive in a massive burn patient for an extended amount of time. The co-survival of alloskin and pigskin will provide clues for further research into skin transplantation.
Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. (1994)

Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable polyanhydride matrix for intracranial implantation and evaluated this formulation in a rat model of malignant glioma. Fischer 344 rats bearing intracranial 9L glioma tumors were treated with 10 mg poly[bis(p-carboxyphenoxy)propane-sebacic acid] (20:80) copolymer discs, containing 20-40% taxol by weight, 5 days after tumor implantation. The taxol-loaded polymers doubled (38 days, 40% taxol loading, P < 0.02) to tripled (61.5 days, 20% taxol loading, P < 0.001) the median survival of rats bearing tumor relative to control rats (19.5 days). Drug loadings of 20-40% taxol by weight released intact taxol for up to 1000 h in vitro. In rats followed up to 30 days postimplant, the polymer maintained a taxol concentration of 75-125 ng taxol/mg brain tissue (100-150 microM taxol) within a 1-3-mm radius of the disc. At points more distant from the disc (up to 8 mm away, the size limit of the rat brain), the polymer maintained a taxol concentration of greater than 4 ng taxol/mg brain tissue (5 microM). We conclude that taxol shows promise as a therapy for malignant glioma when delivered interstitially from a biodegradable polymer.
Novel therapeutic directions for the natriuretic peptides in cardiovascular diseases: what's on the horizon. (2006)

Remarkable advances have occurred since the discovery of ANP. The field of the natriuretic peptides has moved beyond their role as regulators of renal function. Growing evidence has now established the natriuretic peptides as regulators of myocardial structure and function as well as in cardiovascular regulation. Further, they emerge as being products not only of the cardiomyocyte but also of the cardiac fibroblast. Studies in vitro and in vivo have clearly established these cardiac hormones as antihypertrophic and antifibrotic. Further, indications such as cardioprotection for acute myocardial infarction, chronic therapy with oral BNP for hypertension and next generation peptides such as DNP-like peptides for acute heart failure may be in the near future. Novel therapeutic strategies to be tested in clinical trials in humans with cardiovascular disease are clearly on the horizon.
Acute Hemodynamic Effects of Nitroglycerin in Pulmonary Hypertension (1983)

Therapy of pulmonary hypertension is limited by the low potency and adverse effects of current pulmonary vasodilators. The hemodynamic effects of nitroglycerin in human pulmonary hypertension are not known. We administered nitroglycerin to nine patients with chronic pulmonary hypertension. Nitroglycerin increased cardiac index 40% (p less than 0.01), increased stroke volume 40% (p less than 0.01), decreased pulmonary vascular resistance 40% (p less than 0.01), and decreased mean pulmonary artery pressure 15% (p less than 0.01). Pulmonary vascular resistance decreased more than 25% in eight of the nine patients. In four patients the effects of intravenous nitroglycerin were reproduced by topical nitroglycerin preparations; cardiac index increased 50%, stroke volume increased 48%, pulmonary vascular resistance decreased 43%, and mean pulmonary artery pressure decreased 19%. Five of six patients treated with long-acting nitrates had substantial improvement of their symptoms. We conclude that therapy with nitroglycerin can be effective in patients with severe pulmonary hypertension.