gebhart/patrepeval huggingface dataset:
Induction of Chronic Myelogenous Leukemia in Mice by the P210 bcr/abl Gene of the Philadelphia Chromosome (1990)

In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
Aicardi syndrome: A report of five Indian cases (2006)

Five Indian cases of Aicardi syndrome, aged 1-13 years and all with the classic triad of infantile spasm, corpus callosal agenesis and chorioretinal lacunae, were presented. The purpose of this report was to demonstrate the clinical, electroencephalographic (EEG) and radiological spectrum and the treatment outcome of this disorder among the Indians. None of the patient had any family history of similar illness. All had profound psychomotor impairment with no meaningful speech development. There were microphthalmia in 2, optic disc coloboma in 1, interhemispheric cyst in 1, periventricular heterotopia in 2 and thoracolumbar kyphoscoliosis in 2 cases. They all had early onset epilepsy and there were multiple types of seizures. Two cases (40%) had the characteristic dissociated burst-suppression pattern in EEG. Two cases whose antiepileptic medications included vigabatrin had complete control of seizure.
Association of CD34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation (2002)

Although CD34 cell dose is known to influence outcome of peripheral stem cell- and/or T-cell-depleted transplantation, such data on unmanipulated marrow transplantation are scarce. To study the influence of CD34(+) cell dose on hematopoietic reconstitution and incidence of infections after bone marrow transplantation, we retrospectively analyzed 212 patients from January 1994 to August 1999 who received a transplant of an unmanipulated graft from an HLA-identical sibling donor. Median age was 31 years; 176 patients had hematologic malignancies. Acute graft-versus-host disease prophylaxis consisted mainly in cyclosporin associated with methotrexate (n = 174). Median number of bone marrow nucleated cells and CD34(+) cells infused were 2.4 x 10(8)/kg and 3.7 x 10(6)/kg, respectively. A CD34(+) cell dose of 3 x 10(6)/kg or more significantly influenced neutrophil (hazard ratio [HR] = 1.37, P =.04), monocyte (HR = 1.47, P =.02), lymphocyte (HR = 1.70, P =.003), erythrocyte (HR = 1.77, P =.0002), and platelet (HR = 1.98, P =.00008) recoveries. CD34(+) cell dose also influenced the incidence of secondary neutropenia (HR = 0.60, P =.05). Bacterial and viral infections were not influenced by CD34 cell dose, whereas it influenced the incidence of fungal infections (HR = 0.41, P =.008). Estimated 180-day transplantation-related mortality (TRM) and 5-year survival were 25% and 56%, respectively, and both were highly affected by CD34(+) cell dose (HR = 0.55, P =.006 and HR = 0.54, P =.03, respectively). Five-year survival and 180-day TRM were, respectively, 64% and 19% for patients receiving a CD34(+) cell dose of 3 x 10(6)/kg or more and 40% and 37% for the remainders. In conclusion a CD34(+) cell dose of 3 x 10(6)/kg or more improved all hematopoietic recoveries, decreased the incidence of fungal infections and TRM, and improved overall survival.
An Assessment of the Performance of Closed Cycles With and Without Heat Rejection at Cryogenic Temperatures (1996)

This paper presents optimized cycle performance that can be obtained with systems including a Closed Cycle Gas Turbine (CCGT). The influence of maximum temperature, minimum temperature and recuperator effectiveness on cycle performance is illustrated. Several power-plant arrangements are analyzed and compared based on: thermodynamic performance (thermal efficiency and specific work); enabling technologies (available at present); and developing technologies (available in the near term or future). The work includes the effects of utilization of high temperature ceramic heat exchangers and of coupling of CCGT systems with plants vaporizing Liquid Hydrogen (LH2) or Liquefied Natural Gas (LNG). Given the versatility of energy addition and rejection sources that can be utilized in closed gas-cycle systems, the thermodynamic performance of power plants shown in this paper indicate the remarkable capabilities and possibilities for closed gas-cycle systems.
Focal Adhesion Kinase: Targeting Adhesion Signaling Pathways for Therapeutic Intervention (2008)

The tumor microenvironment plays a central role in cancer progression and metastasis. Within this environment, cancer cells respond to a host of signals including growth factors and chemotactic factors, as well as signals from adjacent cells, cells in the surrounding stroma, and signals from the extracellular matrix. Targeting the pathways that mediate many of these signals has been a major goal in the effort to develop therapeutics.
Properties of ultrathin thermal nitrides in silicon Schottky barrier structures (1989)

Thermally grown silicon nitride layers ≤30 Å thick have been investigated as interfacial layers in silicon Schottky barrier structures. Current-voltage characteristics of these devices show modified barrier heights with near unity ideality factors, more ideal than those obtained using silicon dioxide films of the same thickness. By appropriate choice of metal or of nitride layer thickness barrier heights in any desired range can be produced. Barrier heights of different metals are ‘‘unpinned’’: they differ by a fixed constant, independent of the thickness, indicating that interface trap states are not present in sufficient quantity to affect the barrier height. The barrier height varies roughly linearly with nitride thickness, for both as-grown and etched films, suggesting the presence of a constant quantity of positive fixed charge located at the silicon-silicon nitride interface.
Pancreatic expression of human insulin gene in transgenic mice. (1986)

We have investigated the possibility of obtaining integration and expression of a native human gene in transgenic mice. An 11-kilobase (kb) human chromosomal DNA fragment including the insulin gene (1430 base pairs) was microinjected into fertilized mouse eggs. This fragment was present in the genomic DNA of several developing animals. One transgenic mouse and its progeny were analyzed for expression of the foreign gene. Synthesis and release of human insulin was revealed by detection of the human C-peptide in the plasma and urine. Human insulin mRNA was found in pancreas but not in other tissues. These findings indicate that the 11-kb human DNA fragment carries the sequences necessary for tissue-specific expression of the insulin gene and the human regulatory sequences react to homologous signals in the mouse.
95 PRODUCTION OF GENE-EDITED PIGS, CATTLE, AND LAMBS BY EMBRYO INJECTION OF TALENS OR ZFNs (2013)

Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) DNA editing technology enables site-directed engineering of the genome. To date, all gene-edited large animals have been produced by treatment of somatic cells and cloning to produce gene-edited offspring. Although effective, it does not take advantage of the ‘leave-no-trace' aspect of site-specific nucleases, and the derivation of food animals by cloning is negatively perceived by the public. Thus, we have investigated production of gene-edited pigs, cattle and sheep by direct injection of TALEN or ZFN mRNAs to develop loss-of-function alleles for disease resistance (RELA) or enhanced meat production (GDF8). In vitro studies demonstrated activity of TALENs by cytoplasmic injection of mRNAs from dosages of 2 to 20 ng mL–1 with an apparent increase in both editing frequency and toxicity at high dosage. Our first pregnancies were produced by transfer of pig embryos (in vivo produced) injected with 2 ng mL–1 RELA TALEN mRNA. Pregnancy was confirmed in 5 of 7 recipients 4 of which went full term giving rise to 39 piglets, 8 of which carried editing events (21%). In parallel, we injected ZFN mRNA (2 ng mL–1) targeted to a similar site of the RELA gene and 2 of 2 recipients became pregnant, resulting in the birth of 9 piglets, one of which was edited (11%). For cattle injections, we derived zygotes by ovum pickup from selected Nelore dams followed by in vitro maturation and fertilization with Nelore semen. Low (2 ng mL–1) and medium (5 ng mL–1) dosages of GDF8-targeted TALENs resulted in Day 7 development to morula/blastocyst stage in 40% (n = 18) and 10% (n = 66) of cultured embryos, respectively. A total of 20 morula/blastocysts were chosen for transfer to 11 recipients, resulting in two full-term pregnancies. One pregnancy produced two calves, both of which carried edited GDF8 alleles. Complications with parturition of the second pregnancy resulted in 2 stillborn calves, the genotypes of which are under investigation. Finally, 2 ng mL–1 of TALEN mRNA targeted to ovine GDF8 was injected into in vivo-produced sheep zygotes and transferred into nine recipients, 3 blastocysts each. The pregnancy rate, number of live-born animals, and gene editing frequency is under investigation and will be reported.
The Heart Metabolism: Pathophysiological Aspects in Ischaemia and Heart Failure (2009)

The morbidity and mortality of coronary heart disease and of heart failure remain unacceptably high despite major advances in their management. The main focus of treatment has been revascularisation for ischaemic heart disease and neuro-humoral modification for heart failure. There is an urgent need for new modalities of treatment to improve mortality and morbidity. Recently, there has been a great deal of interest in the role of disturbances in cardiac energetics and myocardial metabolism in the pathophysiology of both ischaemic heart disease and heart failure and of therapeutic potential of metabolic modulation. The myocardium is a metabolic omnivore, but mainly uses fatty acids and glucose for generation of Adenosine-5'-triphosphate (ATP). This review focuses on the key changes that occur to the metabolism of the heart in ischaemia and in heart failure and its effects on cardiac energetics.
Effect of intraperitoneally, intravenously and intralesionally administered monoclonal anti-beta-FGF antibodies on rat chondrosarcoma tumor vascularization and growth. (1997)

The growth and vascularization of many tumours has been reported to be associated with the overexpression of the potent mitogenic and angiogenic polypeptide basic fibroblast growth factor (beta-FGF). Consequently, it has been proposed that inhibition of beta-FGF action would prevent the growth of beta-FGF-dependent tumours. In this study, cell culture assays were established to assess the ability of mouse monoclonal DG-2 anti-beta-FGF antibodies to inhibit the mitogenic action of beta-FGF in vitro. Following in vitro characterisation, the monoclonal DG-2 antibodies were used to evaluate the role of beta-FGF in promoting the vascularization and growth of rat chondrosarcoma tumours. The effect the monoclonal anti-B-FGF antibodies had on tumour vascularization and growth in vivo were monitored using a 99m Technetium (99mTc)-labelled red blood cell procedure. The characterization studies confirmed that the DG-2 monoclonal antibody recognised beta-FGF and inhibited its mitogenic action on mouse Balb/c cells and bovine endothelial cells in vitro. When examined in vivo, intralesional administration of mouse monoclonal DG-2 antibody significantly inhibited rat chondrosarcoma growth and vascularization. However when the monoclonal DG-2 antibody was administered intraperitoneally or intravenously no attenuation of rat chondrosarcoma tumour vascularization or growth was observed. This report has confirmed the potential effectiveness of anti-beta-FGF antibodies in the regulation of tumour growth. It has also demonstrated that further studies on the pharmacokinetics of administered antibodies and their mode of delivery are required so that the effectiveness of such anti-growth factor immunotherapy can be assured.
Patent Update: Oncologic, Endocrine & Metabolic Small molecule inhibitors of tyrosine kinase activity (1995)

Inhibitors of tyrosine kinases may be effective in the treatment of certain cancers and chronic inflammatory conditions for which current therapy is either inadequate or lacking. As such, tyrosine kinase inhibitors are attractive targets for pharmaceutical research and may emerge as an important new class of therapeutic agents. Significant progress has been made during recent years towards the development of potent and highly selective tyrosine kinase inhibitors. In particular, recent discovery efforts at Zeneca have lead to the identification of very potent and selective inhibitors of EGF receptor tyrosine kinase. Likewise, a class of potent and selective inhibitors of PDGF receptor tyrosine kinase were described by Rhone-Poulenc Rorer and more recently by Ciba-Geigy. New inhibitors of p56lck and pp60src were also reported. This review focuses mainly on developments which appeared in the patent literature from 1993 to mid-1995. References to the primary literature are limited to studies which are relevant to the highlighted patents.
Aging-Shifted Prostaglandin Profile in Endothelium as a Factor in Cardiovascular Disorders (2012)

Age-associated endothelium dysfunction is a major risk factor for the development of cardiovascular diseases. Endothelium-synthesized prostaglandins and thromboxane are local hormones, which mediate vasodilation and vasoconstriction and critically maintain vascular homeostasis. Accumulating evidence indicates that the age-related changes in endothelial eicosanoids contribute to decline in endothelium function and are associated with pathological dysfunction. In this review we summarize currently available information on aging-shifted prostaglandin profiles in endothelium and how these shifts are associated with cardiovascular disorders, providing one molecular mechanism of age-associated endothelium dysfunction and cardiovascular diseases.
Use of MHC class II tetramers to investigate CD4+ T cell responses: Problems and solutions (2008)

MHC-class I tetramers technology enabled the characterization of peptide-specific T cells at the single cell level in a variety of studies. Several laboratories have also developed MHC-class II multimers to characterize Ag-specific CD4+ T cells. However, the generation and use of MHC-class II multimers seems more problematic than that of MHC-I multimers. We have generated HLA-DR*1101 tetramers in a versatile empty form, which can be loaded after purification with peptides of interest. We discuss the impact of critical biological and structural parameters for the optimal staining of Ag-specific CD4+ T cells using HLA-DR*1101 tetramers, such as: (i) activation state of CD4+ T cells; (ii) membrane trafficking in the target CD4+ T cells; (iii) binding characteristics of the loaded CD4 epitope. Our data indicate that reorganization of TCR on the plasma membrane upon CD4+ T cell activation, as well as an homogenous binding frame of the CD4 epitopes to the soluble HLA-DR monomer, are critical for a stable TCR/MHC-class II tetramer interaction. These factors, together with the low frequencies and affinities of specific CD4+ T cells, explain the need for in vitro expansion or ex vivo enrichment of specific T cells for the optimal visualization with MHC-class II tetramers.
New Approach to Virtualization Is a Lightweight (2006)

Virtualization is a hot topic in the technology world. The technology enables a single computer to run multiple operating systems simultaneously. It lets companies use a single server for multiple tasks that would normally have to run on multiple servers, each running a different OS. Now, vendors are releasing products based on two lightweight virtualization approaches that also let a single operating system run several instances of the same OS or different OSs. However, today's new virtualization approaches do not try to emulate an entire hardware environment, as traditional virtualization does. They thus require fewer CPU and memory resources, which is why the technology is called "lightweight" virtualization. However, lightweight virtualization still faces several barriers to widespread adoption.
Blood markers of early and late airway responses to allergen in asthmatic subjects. Relationship with functional findings (1997)

We evaluated the relationship between blood markers of mast-cell (plasma histamine and serum level of heat-stable neutrophil chemotactic activity [NCA]) and eosinophil (serum eosinophil cationic protein [ECP]) activation during early airway response (EAR) and late airway response (LAR) to allergen inhalation in 24 asthmatic subjects. After EAR, 14 subjects showed significant LAR (FEV1 fall: > or = 25%), while 10 subjects showed equivocal LAR (FEV1 fall: 15-20%). A significant increase from baseline value was observed in plasma histamine and in serum NCA during both EAR and LAR, while serum ECP significantly increased only during LAR. The sensitivity of different markers to detect significant FEV1 fall during EAR and LAR was low, except for NCA. Changes in blood mediators were similar in both groups with significant and equivocal LAR. There was a significant relationship between the increase in NCA during EAR and the severity of LAR. Stepwise regression between changes in different blood markers showed a significant relationship between histamine increase during EAR and ECP increase during LAR. Thus, serum NCA is a more sensitive marker of EAR and LAR than plasma histamine and serum ECP, and its increase during EAR seems predictive of the severity of the subsequent LAR.
Glucocorticoid receptors in bronchoalveolar cells from the patients with diffuse interstitial lung disease (1982)

In order to clarify the physiolosical and significance of glucocorticoid (GC) receptors in bronchoalveolar cell (BAC) fraction, we measured the content of GC receptors in BAC fraction obtained by segmental bronchoalveolar lavage from normal volunteers, control patients with localized lung cancer and pulmonary tuberculosis, and the patients with diffuse interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) . Segmental bronchoalveolar lavage was performed in a segment of right middle lobe or lingula, and was performed in the contralateral lung to the lesions in the control patients.In con'rol groups (normal volunteers and control patients), the BAC fraction consisted mainly of alveolar macrophages. The mean content of GC receptors in BAC fractions from normal volunteers was about 10, 000 sites per cell. This value might reflect that of alveolar macrophages and was significantly higher than those of monocytes, lymphocytes and polymorphonuclear leukocytes in peripheral blood.In the patient groups, the composition of BAG fraction was much changed compared with the control groups; increase of neutrophils in IPF and significant increase of lymphocytes in HP. In some patiets in this group, the contents of GC receptors in BAG fraction were decreased compared with control groups. The patients, who showed the same GC receptor content as control groups, responded well to glucocorticoids, but the patients, who showed lower GC receptor content, did not respond to glucocorticoids. These results suggested that the content of GC receptors in BAG fraction may be a parameter to glucocorticoid therapy in diffuse interstitial lung diseases.
The effect of food on serum concentrations of metopimazine. (1990)

1. Six healthy volunteers were given single oral doses of the antiemetic metopimazine (MPZ), starting with trial (a) 20 mg preprandially and followed by trial (b) 50 mg preprandially. In trials (c) and (d) the doses were similar to those in trials (a) and (b), but MPZ was given postprandially. To evaluate intra-individual variation in serum concentrations, trial (a) was repeated three times in four of the volunteers (trial (e)). 2. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite (AMPZ) were measured by h.p.l.c. 3. There was no evidence of dose-dependent kinetics at the dose levels studied. 4. Median AUC values were 22.6, 16.2, 52.4 and 35.2 (trials (a), (b), (c) and (d), ng ml-1 h). Food intake decreased the serum concentrations of MPZ, suggesting that MPZ should be taken preprandially.
EVIDENCE THAT PRODUCTION OF INTERLEUKIN 6 WITHIN THE REJECTING ALLOGRAFT COINCIDES WITH CYTOTOXIC T LYMPHOCYTE DEVELOPMENT (1991)

Current evidence suggests that the development of allosensitized cytotoxic T lymphocytes within sponge matrix allografts takes place primarily in situ and may be regulated by the secretory products of the cells infiltrating the graft. In vitro studies have implicated IL-2, IL-4, and IL-6 in CTL development. We have reported that TNF-alpha, macrophage colony-stimulating factor, IL-1, IFN-alpha, and IFN-beta are present in the allograft, but that IL-2 and IL-4 cannot be detected at any time using specific bioassays. In this study, we found significantly higher levels of IL-6 within the allografts compared with the syngeneic grafts. Peak IL-6 activity coincided with the appearance of allosensitized CTL in the allografts. IL-6 concentration in the serum of sponge allografted mice was less than 1% of that found in the graft. The sponge fluid exhibited both hybridoma growth factor and hepatocyte-stimulating factor activities in vitro, and both these activities were neutralized by antibody to murine IL-6 but not by antibody to murine IL-1-beta or TNF-alpha. Messenger RNA for murine IL-6 was detected in the graft-infiltrating cells. The high level of IL-6 found in the allograft coincident with the appearance of cellular immunity suggests that this cytokine might play some role in the development of allospecific CTL in vivo.
Simulation of a monolayer of alkyl thiol chains (1989)

Molecular dynamics simulations have been used to study the structure and dynamics of monolayers of long-chain molecules on a metallic substrate. The system consisted of 90 molecules held at a fixed surface density and periodically replicated in the plane of the surface. Two models have been studied as alternative representations of the admolecule–surface interactions in layers formed by the self-assembly of alkyl thiol [SH(CH2)15CH3] molecules onto a gold substrate. The principal difference between the two models is that in one, the S–C bond is required to lie nearly parallel to the substrate surface. After lengthy equilibration at room temperature, both models yield monolayers in which the chains are aligned and tilted with respect to the surface normal. Although the tilt angle is different for the two models, the thickness of the monolayers is the same and the influence of the ‘‘modified-headgroup’’ on the detailed structure of the film is confined to the region closest to the metal surface. There are striking differences in the chain rotational dynamics of the two models which are likely amenable to experimental verification.