gebhart/patrepeval huggingface dataset:
Electrically-Assisted Skin Permeation of Two Synthetic Capsaicin Derivatives, Sodium Nonivamide Acetate and Sodium Nonivamide Propionate, via Rate-Controlling Polyethylene Membranes (2005)

The objective of this study was to examine the transdermal delivery of sodium nonivamide acetate (SNA) using iontophoresis and electroporation with ultra high molecular weight polyethylene membranes (Solupor) to achieve controlled transdermal drug delivery. A derivative of SNA, sodium nonivamide propionate (SNP), was also used as a model drug in this investigation. Iontophoresis increased the transdermal permeation of SNA as compared to passive diffusion. Most Solupor membranes were rate-limiting for the iontophoretic permeation of SNA except for Solupor 8P07, which showed negligible resistance to SNA delivery. The tortuosity (Gurley number), pore size, and the current density-induced attachments on the surface of the Solupor membranes may have been important for their rate-controlling effect. The trends for inhibiting or controlling SNA permeation were similar for both iontophoretic and electroporation applications. The higher molecular size and lower hydrophilicity of SNP compared to SNA resulted in lower permeation of SNP using electrically-assisted methods. Moreover, the various types of Solupor membranes showed similar trends for both SNA and SNP. This present study indicates that Solupor membranes act as rate-limiting membranes for controlling the release and skin permeation of both SNA and SNP by electrically-assisted methods.
Concept, Discovery and Development of MMI Linkage: Story of a Novel Linkage: for Antisense Constructs (1997)

Abstract Methylene(methylimino) or MMI linkage is a novel backbone modification that has enormous potential in the oligonucleotide-based antisense therapeutics as a replacement for the natural phosphodiester linkage. This presentation synopsis covers the rationale, detailed SAR on the optimization process of this linkage vs. others, various synthetic strategies to construct MMI linkage and a brief discussion on the biological properties of the modified oligonucleotides.
Newer Antiepileptic Drugs and Cognitive Issues (2003)

Although the causes of cognitive impairment in patients with epilepsy have not been completely elucidated, three factors are clearly involved: the underlying etiology of epilepsy, the effects of seizures themselves, and the central nervous system effects of antiepileptic drugs (AEDs). All commonly used AEDS have some effect on cognitive function, and the effect may be substantial when crucial functions are involved, such as learning in children or driving ability in adults, or when already-vulnerable functions are involved, such as memory in elderly patients. The available evidence is insufficient to support definite conclusions about the cognitive effects of three of the newer AEDs, tiagabine, gabapentin, and levetiracetam. Better evidence is available for lamotrigine (LTG), topiramate (TPM), and, to a lesser degree, oxcarbazepine (OXC). OXC appears not to affect cognitive function in healthy volunteers or adults with newly diagnosed epilepsy, but its cognitive effects in children and adolescents have not been systematically studied. A relatively large number of studies are available for LTG, which has demonstrated a favorable cognitive profile overall, both in volunteers and in patients with epilepsy. Although dose and titration speed may be confounding factors in some of the studies of TPM, there is clear evidence that this agent does affect cognitive function, with specific effects on attention and verbal function. For LTG, attempts have been made to correlate cognitive effects with what is known of the drug's mechanism of action; this is an area of research that deserves further exploration with regard to other AEDs as well, especially TPM.
Sacral Neuromodulation: Does It Affect the Rectoanal Angle in Patients with Fecal Incontinence? (2010)

Rectoanal angle did not decrease significantly in patients with fecal incontinence during SNM.
The enigmatic protein kinase Cδ: complex roles in cell proliferation and survival (2004)

Protein kinase Cdelta (PKCdelta) has been implicated both as a tumor suppressor and a positive regulator of cell cycle progression. PKCdelta has also been reported to positively and negatively regulate apoptotic programs. This has led to conflicting hypotheses on the role of PKCdelta in the control of cell proliferation and survival. Surprisingly, PKCdelta mice develop normally and are fertile, indicating that PKCdelta is not critical for normal cell proliferation during development. However, PKCdelta may play important roles in neoplastic cell proliferation. In this review, we have summarized the apparent multifunctional properties of this enigmatic protein with regard to its role in the regulation of cell cycle progression and cell survival. It is proposed that PKCdelta has both tumor suppressor and proliferation capabilities that can be recruited as a backup kinase for both gatekeeper tumor suppression and as an activator of the Ras/Raf/MEK/MAP kinase signaling pathway in cell proliferation.
The arginine repressor of Escherichia coli (1994)

This review tells the story of the arginine repressor of Escherichia coli from the time of its discovery in the 1950s until the present. It describes how the research progressed through physiological, genetic, and biochemical phases and how the nature of the repressor and its interaction with its target sites were unraveled. The studies of the repression of arginine biosynthesis revealed unique features at every level of the investigations. In the early phase of the work they showed that the genes controlled by the arginine repressor were scattered over the linkage map and were not united, as in other cases, in a single operon. This led to the concept of the regulon as a physiological unit of regulation. It was also shown that different alleles of the arginine repressor could result in either inhibition of enzyme formation, as in E. coli K-12, or in stimulation of enzyme formation, as in E. coli B. Later it was shown that the arginine repressor is a hexamer, whereas other repressors of biosynthetic pathways are dimers. As a consequence the arginine repressor binds to two palindromic sites rather than to one. It was found that the arginine repressor not only acts in the repression of enzyme synthesis but also is required for the resolution of plasmid multimers to monomers, a completely unrelated function. Finally, the arginine repressor does not possess characteristic structural features seen in other prokaryotic repressors, such as a helix-turn-helix motif or an antiparallel beta-sheet motif. The unique features have sustained continuous interest in the arginine repressor and have made it a challenging subject of investigation.
Linoleic acid lowers LDL cholesterol without a proportionate displacement of saturated fatty acid. (1991)

We tested the specificity of the plasma cholesterol-lowering effect of linoleic acid in a comparison of linoleate-rich and saturated fatty acid-rich foods. Twelve mildly hypercholesterolemic men and women ate the two diets for three weeks each in a random cross-over design, after a two-week baseline period. A linoleic acid-rich supplement was added to the baseline diet so that the saturated and monounsaturated fatty acid content did not change significantly. Despite the consequent increase in total fat intake, the linoleate-rich diet (23 per cent energy from polyunsaturated fatty acids) significantly lowered plasma total and low-density lipoprotein (LDL) cholesterol (-8 per cent and -14 per cent respectively), while high-density lipoprotein (HDL) cholesterol rose 8 per cent. The direction of these changes was similar in all 12 subjects. Compared with a supplement that raised dietary saturated fatty acids to 30 per cent energy, the linoleate acid-rich diet gave lower total cholesterol (-14 per cent), LDL cholesterol (-18 per cent) and HDL cholesterol (-12 per cent) concentrations. Linoleic acid lowers LDL cholesterol even when saturated fatty acids are not significantly displaced and substantially more when there is such displacement.
A caged sperm‐activating peptide that has a photocleavable protecting group on the backbone amide (2002)

A backbone-caged sperm-activating peptide (caged speract) that has a 2-nitrobenzyl group at a backbone amide and a vastly reduced affinity for its receptor (IC50=950 nM) was synthesized. UV irradiation of caged speract photocleaves the 2-nitrobenzyl group (tau1/2=26 micros), restoring its affinity (IC50=0.67 nM) and ability to increase sperm intracellular pH and Ca2+, as intact speract. Backbone caging of the biological activity was more efficient than side chain caging, which adds a nitrobenzyl group on the peptide side chain. The backbone caging strategy described can be used as a general procedure to cage biologically active peptides, which have no side chain for introduction of a caging group.
Update on viral vaccines for fish. (2005)

A substantial amount of research has been done on fish viruses affecting species in aquaculture. This review will focus on the salmonid industry, as this is the most industrialised part of fish farming where vaccines are extensively used. In spite of the amount of research performed, both in commercial companies and in academic organisations, few viral vaccines are licensed. As of today, all fish virus vaccines for sale are based upon inactivated virus or recombinant proteins. No live attenuated or DNA vaccines are currently licensed, but one DNA vaccine against IHN is being tested in controlled field trials in Canada. Vaccines against infectious pancreatic necrosis (IPN) have been sold for many years in Norway and are now also available in Chile. Most of the research on these vaccines has been performed by pharmaceutical companies, and not much information is available as scientific publications. It has also been difficult to establish reproducible IPN challenge models suitable for vaccine testing and this probably explains the lack of scientific publications. Quite the reverse is the case for the fish rhabdoviruses viral hemorrhagic septicaemia virus (VHSV) and infectious haematopoietic necrosis virus (IHNV). The challenge models are reproducible, and both inactivated virus and DNA vaccines offer excellent protection. Recombinant subunit vaccines have so far shown unsatisfactory effect. Little information has been published regarding vaccine development against pancreas disease (PD) and infectious salmon anaemia (ISA). PD and ISA vaccines have been tested at the laboratory scale with good results, and two commercial ISA vaccines are currently available in Canada. Regarding nodaviruses, a few publications have shown effect of recombinant subunit formulations. However, nodaviruses cause disease early in the lifecycle of marine fish, and injection of these formulations into fish of a few grams is so far difficult on a commercial scale.
RoleNet: Movie Analysis from the Perspective of Social Networks (2009)

With the idea of social network analysis, we propose a novel way to analyze movie videos from the perspective of social relationships rather than audiovisual features. To appropriately describe role's relationships in movies, we devise a method to quantify relations and construct role's social networks, called RoleNet. Based on RoleNet, we are able to perform semantic analysis that goes beyond conventional feature-based approaches. In this work, social relations between roles are used to be the context information of video scenes, and leading roles and the corresponding communities can be automatically determined. The results of community identification provide new alternatives in media management and browsing. Moreover, by describing video scenes with role's context, social-relation-based story segmentation method is developed to pave a new way for this widely-studied topic. Experimental results show the effectiveness of leading role determination and community identification. We also demonstrate that the social-based story segmentation approach works much better than the conventional tempo-based method. Finally, we give extensive discussions and state that the proposed ideas provide insights into context-based video analysis.
Transparent run-time defense against stack smashing attacks (2000)

Permission is granted for noncommercial reproduction of the work for educational or research purposes.
Pathways of T‐cell regeneration in mice and humans: implications for bone marrow transplantation and immmunotherapy (1997)

Much of our understanding of the immunobiology of bone marrow transplantation (BMT) has come from studies in young adult mice reconstituted with T-cell-depleted bone marrow after lethal irradiation. Recent evidence indicates, however, that the applicability of conclusions drawn from this model to human BMT may be limited. While mice retain essentially normal thymic function well past sexual maturity, humans show significant age-related declines in thymic function relatively early in life. Therefore, thymic-deficient mice may provide a more accurate model for study of the immunobiology of BMT. T-cell regeneration in thymic-deficient mice occurs primarily via antigen-driven expansion of mature peripheral T cells resulting in limited immune competence due to quantitative deficiencies in T-cell number and severe restriction in the diversity of the regenerated T-cell receptor (TCR) repertoire. Similarly, immune reconstitution in adult humans after BMT is marked by quantitative T-cell deficiencies, especially in the CD4+ subset, and loss of TCR diversity. Taken together, prevailing evidence suggests that thymic function is suboptimal in most BMT recipients, and that thymic-independent pathways of T-cell regeneration are generally limited in their ability to restore host immune competence. New strategies to enhance thymic function in man after BMT would hold great therapeutic potential.
Dispersion by Pressure-Driven Flow in Serpentine Microfluidic Channels (2002)

Microfluidic hydrodynamic chromatography performed in serpentine microchannels etched on chips is analyzed in the limiting case of chips containing a large number of periodically arrayed turns. Comparison is made between these results and those for a straight channel of the same length as the curvilinear channel, all other things being equal. Explicitly, generalized Taylor−Aris dispersion (macrotransport) theory for spatially periodic systems is adapted to compute the chip-scale solute velocity Ū* and dispersivity D̄* for effectively point-size, physicochemically inert Brownian particles entrained in a low Reynolds number, pressure-driven solvent flow occurring within the curvilinear interstices of such serpentine devices. Attention is focused upon relatively thin channels of uniform cross section, enabling the various transport fields pertinent to the problem to be expressed as regular perturbation expansions with respect to a small dimensionless parameter ε, representing the ratio of channel half-width to curvilinear channel length per turn. The generic leading-order results obtained for Ū* and D̄*, valid for any sufficiently “thin” channel, formally demonstrate that the serpentine geometry results simply reproduce those for a straight channel, when account is taken of the channel's “tortuosity,” namely the square of the ratio of curvilinear serpentine length to rectilinear straight channel lengtha conclusion shown to accord with intuition.
A MultiPath Network for Object Detection (2016)

The recent COCO object detection dataset presents several new challenges for object detection. In particular, it contains objects at a broad range of scales, less prototypical images, and requires more precise localization. To address these challenges, we test three modifications to the standard Fast R-CNN object detector: (1) skip connections that give the detector access to features at multiple network layers, (2) a foveal structure to exploit object context at multiple object resolutions, and (3) an integral loss function and corresponding network adjustment that improve localization. The result of these modifications is that information can flow along multiple paths in our network, including through features from multiple network layers and from multiple object views. We refer to our modified classifier as a "MultiPath" network. We couple our MultiPath network with DeepMask object proposals, which are well suited for localization and small objects, and adapt our pipeline to predict segmentation masks in addition to bounding boxes. The combined system improves results over the baseline Fast R-CNN detector with Selective Search by 66% overall and by 4x on small objects. It placed second in both the COCO 2015 detection and segmentation challenges.
The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFα production and nuclear factor kappa B expression (2003)

These findings underscore the importance of incorporating biological parameters of inflammation in determining the clinical course of Crohn's disease.
In Vivo T Cell Costimulation Blockade with Abatacept for Acute Graft-versus-Host Disease Prevention: A First-in-Disease Trial (2013)

We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.
Genetic screening of LCA in Belgium: predominance of CEP290 and identification of potential modifier alleles in AHI1 of CEP290-related phenotypes (2010)

Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.
The Neurotrophins and Neuropoietic Cytokines: Two Families of Growth Factors Acting on Neural and Hematopoietic Cells (1998)

Recent progress has revealed similarities between the receptors and signaling systems used by neurotrophic factors as compared to other growth factors and cytokines. The neurotrophins use a family of receptor tyrosine kinases known as the Trk receptors, whereas ciliary neurotrophic factor (CNTF) uses a "cytokine receptor" system that shares receptor components with a number of distantly related cytokines. We have used a human embryonal carcinoma cell line and human leukemia cell lines to examine the actions of the neurotrophins and CNTF on cellular differentiation. Our findings demonstrate that specific combinations of neurotrophic factors are required to influence the neuronal progenitor cells to become postmitotic mature CNS neurons. Such synergistic interactions may play an important role in modulating the differentiation of a wide assortment of neuronal precursors in the developing nervous system. Furthermore, our studies with leukemia cells suggest that neurotrophic factors may play a similar role in hematopoietic differentiation and that these factors may have therapeutic application in leukemia differentiation.
美国退伍军人事务部／国防部成人脑卒中康复治疗管理临床实践指南（执行简写版） (2006)

背景专家委员会制定的卒中康复指南应用于退伍军人健康管理部门及国防部卫生保健系统。方法根据以前发表的指南，委员会利用美国预防服务特别工作组制定的标准。评价了截至到2002年发表的文献。指南根据临床随机化实验、非对照性研究等证据提出建议（如缺乏确定的数据则根据专家组的建议）。结果 Ⅰ级水平的建议包括：在多学科康复环境中或卒中单元中传递卒中治疗，通过NIHSS对卒中患者进行评价，早期启动康复治疗，对吞咽困难患者进行吞咽功能筛查，积极进行二级预防，预防深静脉血栓等。推荐应用标准化的评价上具制定适合每个患者的全面的治疗计划。强烈建议进行抗抑郁及情感波动方面的治疗。语言治疗师应评价患者的交流及认知障碍。并在需要时提供治疗。患者、家属及护理者是康复小组的重要成员，应当介入康复的全部疗程。这些建议在以下网站可查询：http：／／stroke．ahajournals．org／cgi／content／full／36／9／e100。并附有每项建议的全文证据表。结论这些建议应平等地应用于所有临床环境中的所有卒中康复患者，而不是仅针对联邦医疗系统的临床问题或资源。
Computational Approaches to Identify Promoters and cis-Regulatory Elements in Plant Genomes (2003)

The identification of promoters and their regulatory elements is one of the major challenges in bioinformatics and integrates comparative, structural, and functional genomics. Many different approaches have been developed to detect conserved motifs in a set of genes that are either coregulated or orthologous. However, although recent approaches seem promising, in general, unambiguous identification of regulatory elements is not straightforward. The delineation of promoters is even harder, due to its complex nature, and in silico promoter prediction is still in its infancy. Here, we review the different approaches that have been developed for identifying promoters and their regulatory elements. We discuss the detection of cis-acting regulatory elements using word-counting or probabilistic methods (so-called "search by signal" methods) and the delineation of promoters by considering both sequence content and structural features ("search by content" methods). As an example of search by content, we explored in greater detail the association of promoters with CpG islands. However, due to differences in sequence content, the parameters used to detect CpG islands in humans and other vertebrates cannot be used for plants. Therefore, a preliminary attempt was made to define parameters that could possibly define CpG and CpNpG islands in Arabidopsis, by exploring the compositional landscape around the transcriptional start site. To this end, a data set of more than 5,000 gene sequences was built, including the promoter region, the 5'-untranslated region, and the first introns and coding exons. Preliminary analysis shows that promoter location based on the detection of potential CpG/CpNpG islands in the Arabidopsis genome is not straightforward. Nevertheless, because the landscape of CpG/CpNpG islands differs considerably between promoters and introns on the one side and exons (whether coding or not) on the other, more sophisticated approaches can probably be developed for the successful detection of "putative" CpG and CpNpG islands in plants.