gebhart/patrepeval huggingface dataset:
Phantom and animal tissues for modelling the electrical properties of human liver (2003)

The dielectric properties of human liver were characterized over the frequency range of 0.3-3 GHz for freshly excised tissue samples of primary hepatocellular carcinoma, metastatic colorectal carcinoma, and normal liver tissues resected from the tumour margin. On average, the dielectric constant (epsilon(r)) of freshly excised human liver tumour was 12% higher than that of surrounding normal liver, and the electrical conductivity (sigma) of tumour was 24% higher. In order to establish suitable tissue models for human liver, the electrical properties were compared to measurements of homogenous phantom mixtures, in vitro bovine liver, and in vivo canine and porcine liver tissues. The data demonstrate that there are several animal tissues that can be used to model the average dielectric properties of human liver reasonably accurately, and use of the most readily available bovine liver appears well-justified, even when stored for up to 10 days in a refrigerator. Additionally, the dielectric properties of in vitro liver remained stable over a large temperature range, with sigma rising only 1.1%/ degrees C in porcine liver (15-37 degrees C) and 2.0%/ degrees C in bovine liver (10-90 degrees C), and epsilon(r) decreasing < or =0.2%/ degrees C in both tissues. This effort identifies homogeneous solid and liquid phantom models and several heterogeneous in vitro tissues that adequately model the dielectric properties of human liver tumours for use in quantitative studies of microwave power deposition in liver.
Reducing Mass-Transport Limitations by Application of Special Pulsed Current Modes (2005)

Current pulsing, unlike potential pulsing, is generally considered ineffective in enhancing mass transport. However, we show here, that by properly selecting the pulsed current parameters, the depletion of the reactant at the electrode during cathodic reduction, or its excess during anodic dissolution, can be reduced compared to the corresponding dc current application, while still passing the same amount of charge in an identical amount of time. The advantageous pulsed current modes include a sequence of decreasing current density amplitudes, or pulsing the current at the same amplitude, but with increasing relaxation intervals. By comparison, it is also shown that applying a sequence of constant-amplitude square current pulses at constant time intervals leads to an identical concentration profile as in dc. The application to the battery-charging process is briefly discussed.
Controlled Surface Modification with Poly(ethylene)glycol Enhances Diffusion of PLGA Nanoparticles in Human Cervical Mucus (2008)

Drug delivery to mucosal epithelia is severely limited by the mucus gel, which is a physical diffusion barrier as well as an enzymatic barrier in some sites. Loading of drug into polymer particles can protect drugs from degradation and enhance their stability. To improve efficacy of nanoparticulate drug carriers, it has been speculated that polymers such as poly(ethylene)glycol (PEG) incorporated on the particle surface will enhance transport in mucus. In the present study, we demonstrate the direct influence of PEG on surface properties of poly(lactic-co-glycolic)acid (PLGA) nanoparticles (d = 170 +/- 57 nm). PEG of various molecular weights (MW = 2, 5, 10 kDa) were incorporated at a range of densities from 5-100% on the particle surface. Our results indicate PEG addition improves dispersion, neutralize charge, and enhance particle diffusion in cervical mucus in a manner strongly dependent on polymer MW and density. Diffusion of PEGylated particles was 3-10x higher than that of unmodified PLGA particles. These findings improve the understanding of, and confirm a possible direction for, the rational design of effective carriers for mucosal drug/vaccine delivery.
Comunicación 1940 - 1960: Positivismo lógico, teoría de los efectos y planificación (2002)

Existe una constante en la historia de la humanidad. El ser humano se asombra ante el mundo que lo rodea y quiere saber de el: quiere saber no solo que cosas hay en ese mundo, sino que son y por que estan ahi y ha llevado un registro detallado de las respuestas que se han dado a estas y otras preguntas. A este registro lo llamamos historia del conocimiento. Sin embargo el conocimiento no es unico. Depende no solo de las perspectivas historicas, sociales, politicas o culturales, en fin, de las visiones humanas que hacen que el mundo no sea uno solo para todos los hombres en todos los lugares y en todas las epocas, sino tambien del sentido y la causa por la que se formulan las preguntas o la forma en que ellas son formuladas; dando lugar a multiples respuestas que conviven en permanente debate y determinan la forma como vivimos.
Learning disability and advocacy: obstacles to client empowerment (1999)

Citizen advocacy, with its aim to empower, has the potential to transform the lives of people with learning disabilities, but an inevitable consequence of client empowerment is professional disempowerment. Professional workers are unlikely to relinquish power, control and influence without some resistance. As this paper seeks to show there are a number of ways for statutory agencies to neutralize the effect of citizen advocacy. If this challenge is to be met then a number of radical changes need to be made in the way advocacy programmes operate: the volunteering principle should be abandoned; full-time advocates should be appointed; generic rather than specialist advocacy services should be established; and, in order to protect the operational independence of advocacy programmes, funding should come from central and not local government sources. If the kind of fundamental changes, proposed in this paper, are not introduced then the credibility of advocacy services will be irretrievably damaged with the result that people with learning disabilities will continue to remain disadvantaged. If people with learning disabilities are to be empowered they need strong, independent, informed and expert representation.
Antisense Inhibition of Silica-induced Tumor Necrosis Factor in Alveolar Macrophages (1997)

Tumor necrosis factor-alpha (TNFalpha) has been shown to play an important role in the pathogenesis of silicotic fibrosis. In this study, antisense oligonucleotides targeted to TNFalpha mRNA were used to inhibit silica-induced TNFalpha gene expression in alveolar macrophages. To achieve macrophage-specific oligonucleotide delivery, a molecular conjugate consisting of mannosylated polylysine that exploits endocytosis via the macrophage mannose receptor was used. Complexes were formed between the mannosylated polylysine and oligonucleotides and added to the cells in the presence of silica. Enzyme-linked immunoadsorbent assay showed that the complex consisting of the conjugate and antisense oligomer effectively inhibited TNFalpha production, whereas the oligomer alone had much less effect. Reverse transcriptase-polymerase chain reaction analysis revealed that the reduction in TNFalpha secretion was associated with specific ablation of targeted TNFalpha mRNA. The conjugate alone or conjugate complexed with inverted or sense sequence oligonucleotide had no effect. The promoting effect of the conjugate on antisense activity was shown to be due to enhanced cellular uptake of the oligomer via mannose receptor-mediated endocytosis. Cells lacking mannose receptors showed no susceptibility to the conjugate treatment. These results indicate that effective and selective inhibition of macrophage TNFalpha expression can be achieved using the antisense mannosylated polylysine system.
The induction of virus-specific CTL as a function of increasing epitope expression: responses rise steadily until excessively high levels of epitope are attained. (1999)

The role of epitope expression levels in CD8+ T cell priming has been controversial. Yet this parameter is of great importance in the design of rational approaches to optimize CTL responses to a variety of pathogens. In this paper we examine the influence of epitope production on CD8+ T cell priming by exploiting a system that allows a 200-fold range of cell surface epitope expression in vitro with a fixed dose of vaccinia virus. Our results demonstrate that, with the exception of a notable decline at the highest level of epitope, the magnitude of the responding CTL population generated in vivo following equivalent viral infections is essentially proportional to epitope density.
A Phase I Study of 5‐Azacytidine (NSC‐102816) (1976)

5-Azacytidine was administered daily to 12 patients in a five-day schedule and to 15 patients in a weekly schedule as part of a phase I trial. The daily dose ranged from 50 mg/m2 to 158 mg/m2 and the weekly dose, from 200 mg/m2 to 633 mg/m2. The maximum total dose was 2000 mg in the daily schedule and 3775 mg in the weekly schedule. The major toxicity was gastrointestinal, with nausea and vomiting occurring in all patients in this study. Myelosuppression was less frequently encountered and appeared to be related to the increase in 5-azacytidine dose. Patients receiving 5-azacytidine in a weekly schedule of administration appeared to tolerate the drug better and to be more willing to continue their therapy.
A Novel Somatic Point Mutation of the RET Proto‐oncogene in Tumor Tissues of Small Cell Lung Cancer Patients (1995)

We examined whether the novel point mutation from GCC (Ala) to GAC (Asp) at codon 664 in exon 11 of RET proto-oncogene, which we had found in two small cell lung carcinoma (SCLC) cell lines, existed in genomic DNA of tumor tissues of the two SCLC patients from whom these SCLC cell lines were derived. Sequence analysis revealed that point mutation identical to that of the SCLC cell lines was present in amplified alleles of single-strand conformational variants in genomic DNA of the tumor tissues, whereas it was not detected in genomic DNA of non-tumor tissues of the patients. These results indicate that this mutation had initially occurred in the SCLC patients and was of somatic origin.
Decentralized deduplication in SAN cluster file systems (2009)

File systems hosting virtual machines typically contain many duplicated blocks of data resulting in wasted storage space and increased storage array cache footprint. Deduplication addresses these problems by storing a single instance of each unique data block and sharing it between all original sources of that data. While deduplication is well understood for file systems with a centralized component, we investigate it in a decentralized cluster file system, specifically in the context of VM storage. We propose DEDE, a block-level deduplication system for live cluster file systems that does not require any central coordination, tolerates host failures, and takes advantage of the block layout policies of an existing cluster file system. In DEDE, hosts keep summaries of their own writes to the cluster file system in shared on-disk logs. Each host periodically and independently processes the summaries of its locked files, merges them with a shared index of blocks, and reclaims any duplicate blocks. DEDE manipulates metadata using general file system interfaces without knowledge of the file system implementation. We present the design, implementation, and evaluation of our techniques in the context of VMware ESX Server. Our results show an 80 % reduction in space with minor performance overhead for realistic workloads. 1
Molecular Physiology of Low-Voltage-Activated T-type Calcium Channels (2003)

T-type Ca2+ channels were originally called low-voltage-activated (LVA) channels because they can be activated by small depolarizations of the plasma membrane. In many neurons Ca2+ influx through LVA channels triggers low-threshold spikes, which in turn triggers a burst of action potentials mediated by Na+ channels. Burst firing is thought to play an important role in the synchronized activity of the thalamus observed in absence epilepsy, but may also underlie a wider range of thalamocortical dysrhythmias. In addition to a pacemaker role, Ca2+ entry via T-type channels can directly regulate intracellular Ca2+ concentrations, which is an important second messenger for a variety of cellular processes. Molecular cloning revealed the existence of three T-type channel genes. The deduced amino acid sequence shows a similar four-repeat structure to that found in high-voltage-activated (HVA) Ca2+ channels, and Na+ channels, indicating that they are evolutionarily related. Hence, the alpha1-subunits of T-type channels are now designated Cav3. Although mRNAs for all three Cav3 subtypes are expressed in brain, they vary in terms of their peripheral expression, with Cav3.2 showing the widest expression. The electrophysiological activities of recombinant Cav3 channels are very similar to native T-type currents and can be differentiated from HVA channels by their activation at lower voltages, faster inactivation, slower deactivation, and smaller conductance of Ba2+. The Cav3 subtypes can be differentiated by their kinetics and sensitivity to block by Ni2+. The goal of this review is to provide a comprehensive description of T-type currents, their distribution, regulation, pharmacology, and cloning.
Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection (2006)

Abstract Helicobacter pylori infection is associated with gastritis, ulcers, and gastric cancer. The infection becomes chronic as the host response is unable to clear it. Gastric epithelial cells (GEC) play an important role during the host response, and their expression of class II MHC and costimulatory molecules such as CD80 and CD86 suggests their role in local Ag presentation. Although T cells are recruited to the infected gastric mucosa, they have been reported to be hyporesponsive. In this study, we detected the expression of B7-H1 (programmed death-1 ligand 1), a member of B7 family of proteins associated with T cell inhibition on GEC. Quantitative real-time RT-PCR revealed that B7-H1 expression increased significantly on GEC after H. pylori infection. Western blot analysis showed that B7-H1 expression was induced by various H. pylori strains and was independent of H. pylori virulence factors such as Cag, VacA, and Urease. The functional role of B7-H1 in the cross talk between GEC and T cells was assessed by coculturing GEC or H. pylori-infected GEC with CD4+ T cells isolated from peripheral blood. Using blocking Abs to B7-H1 revealed that B7-H1 was involved in the suppression of T cell proliferation and IL-2 synthesis, and thus suggested a role for B7-H1 on the epithelium as a contributor in the chronicity of H. pylori infection.
Epigenetic Properties and Identification of an Imprint Mark in the Nesp-Gnasxl Domain of the Mouse Gnas Imprinted Locus (2003)

The Gnas locus in the mouse is imprinted with a complex arrangement of alternative transcripts defined by promoters with different patterns of monoallelic expression. The Gnas transcript is subject to tissue-specific imprinted expression, Nesp is expressed only from the maternal allele, and Gnasxl is expressed only from the paternal allele. The mechanisms controlling these expression patterns are not known. To identify potential imprinting regulatory regions, particularly for the reciprocally expressed Nesp and Gnasxl promoters, we examined epigenetic properties of the locus in gametes, embryonic stem cells, and fetal and adult tissues. The Nesp and Gnasxl promoter regions are contained in extensive CpG islands with methylation of the paternal allele at Nesp and the maternal allele at Gnasxl. Parental allele-specific DNase I-hypersensitive sites were found at these regions, which correlate with hypomethylation rather than actual expression status. A germ line methylation mark was identified covering the promoters for Gnasxl and the antisense transcript Nespas. Prominent DNase I-hypersensitive sites present on paternal alleles in embryonic stem cells are contained within this mark. This is the second gametic mark identified at Gnas and suggests that the Nesp and Gnasxl promoters are under separate control from the Gnas promoter. We propose models to account for the regulation of imprinting at the locus.
Field-effect modulation of conductance in VO2 nanobeam transistors with HfO2 as the gate dielectric (2011)

We study field-effect transistors realized from VO2 nanobeams with HfO2 as the gate dielectric. When heated up from low to high temperatures, VO2 undergoes an insulator-to-metal transition. We observe a change in conductance (∼6%) of our devices induced by gate voltage when the system is in the insulating phase. The response is reversible and hysteretic, and the area of hysteresis loop becomes larger as the rate of gate sweep is slowed down. A phase lag exists between the response of the conductance and the gate voltage. This indicates the existence of a memory of the system and we discuss its possible origins.
Volunteering as Community (2009)

AimsThe recognition that volunteering constitutes the heart of community is not new. However, as government and non-government sectors become increasingly focussed on the potential of volunteerism for easing their service delivery and community support obligations, there is a tendency for volunteers and volunteering to be seen as a tool or strategy for maintaining community rather than as the essence of community itself. This has very practical consequences. It can result in a bureaucratic, formalised and reductionist approach to strategising, training, managing, theorising and researching volunteering. This paper draws on a whole of community study of rural volunteers to argue that strategies for recruitment, management, training , support and retention of rural volunteers need to be grounded in a deep understanding of the local. MethodA 12 month study of rural and regional volunteering, funded by Volunteering Tasmania and undertaken by the University Department of Rural Health, Tasmania involved in-depth interviews with a convenience sample of 67 rural volunteers across three rural/regional sites and a survey of 152 volunteer coordinators.ResultsThe study provides rich data on issues such as volunteer motivation, management, training, recruitment and ageing. Overlaying, and giving meaning, to all of this data is a strong sense of the importance and strength of local context - the entwining of local and personal history, culture and the social dynamics of time and place - in shaping the volunteer landscape and experience. The data reveal community volunteering as a delicate and finely balanced organism; a highly complex web of relationships, interactions and exchanges that delivers something more than the sum of its parts in terms of community well-being. The data suggest that while more formal regulatory, training and management requirements have an important place in maintaining the vitality and safety of rural volunteering, their successful translation into the local context requires great care and sensitivity based on a knowledge and understanding of local community. ConclusionsThe more bureaucratic and formal regulatory environment growing out of closer government focus on the role of volunteering in health and wellbeing service provision, is as inevitable as it is necessary. However, it could destroy the very thing it aims to nurture unless there is a sufficient recognition of the complexity and particularities of local volunteers and communities and the flexibility in application needed to adapt to this complexity.
A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain (2006)

The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180 degrees with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP-peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR-Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain.
A Novel Monoclonal Antibody for Detection of Folate Receptor Alpha in Paraffin-Embedded Tissues (2007)

Folate biochemical pathway components such as FR-alpha are determinants of response to novel antifolate drugs such as pemetrexed. Knowledge of their level of expression in tumors will enable their optimal use by identifying potentially responsive subgroups of patients. In spite of its importance in the diagnosis and treatment of cancer, monoclonal antibodies to FR-alpha suitable for immunohistochemical analysis of formalin-fixed and paraffin-embedded biopsy samples, or that can be used for Western blot analysis, are not available. The aim of this study was thus to generate a monoclonal antibody that could be used to detect specific expression of FR-alpha in paraffin-embedded tissues. A 189 amino acid region of the FR-alpha sequence was expressed as a recombinant fusion protein and used as antigen to generate monoclonal antibodies. Studies by ELISA and Western blot identified specific reactivity of the BN3.2 antibody to the recombinant protein and a single 40 kD protein in whole cell lysates from cell lines known to express FR-alpha. Immunohistochemical analysis of FR-alpha using hybridoma clone BN3.2 in a panel of normal tissues demonstrated expression limited to ovarian epithelia, placental trophoblasts, and proximal kidney tubules. Analysis of a panel of malignant and benign tissues demonstrated limited expression with variable intensities of staining and patterns of both membrane and cytoplasmic reactivity observed between cases. In the majority of malignant ovarian tumors, high intensity staining was observed, predominantly localized to the plasma membrane. Our results show that clone BN3.2 is a sensitive tool for detection of FR-alpha in paraffin-embedded tissues. This preliminary study also supports its use in immunohistochemical studies to determine the role of FR-alpha as a tumor prognostic marker and a possible therapeutic target.