gebhart/patrepeval huggingface dataset:
Reperfusion-Induced Translocation of δPKC to Cardiac Mitochondria Prevents Pyruvate Dehydrogenase Reactivation (2005)

Cardiac ischemia and reperfusion are associated with loss in the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH). Pharmacological stimulation of PDH activity improves recovery in contractile function during reperfusion. Signaling mechanisms that control inhibition and reactivation of PDH during reperfusion were therefore investigated. Using an isolated rat heart model, we observed ischemia-induced PDH inhibition with only partial recovery evident on reperfusion. Translocation of the redox-sensitive delta-isoform of protein kinase C (PKC) to the mitochondria occurred during reperfusion. Inhibition of this process resulted in full recovery of PDH activity. Infusion of the deltaPKC activator H2O2 during normoxic perfusion, to mimic one aspect of cardiac reperfusion, resulted in loss in PDH activity that was largely attributable to translocation of deltaPKC to the mitochondria. Evidence indicates that reperfusion-induced translocation of deltaPKC is associated with phosphorylation of the alphaE1 subunit of PDH. A potential mechanism is provided by in vitro data demonstrating that deltaPKC specifically interacts with and phosphorylates pyruvate dehydrogenase kinase (PDK)2. Importantly, this results in activation of PDK2, an enzyme capable of phosphorylating and inhibiting PDH. Thus, translocation of deltaPKC to the mitochondria during reperfusion likely results in activation of PDK2 and phosphorylation-dependent inhibition of PDH.
Visualizing the Site and Dynamics of IgG Salvage by the MHC Class I-Related Receptor, FcRn (2004)

The MHC class I-related receptor, FcRn, plays a central role in regulating the serum levels of IgG. FcRn is expressed in endothelial cells, suggesting that these cells may be involved in maintaining IgG levels. We have used live cell imaging of FcRn-green fluorescent protein transfected human endothelial cells to analyze the intracellular events that control IgG homeostasis. We show that segregation of FcRn-IgG complexes from unbound IgG occurs in the sorting endosome. FcRn or FcRn-IgG complexes are gradually depleted from sorting endosomes to ultimately generate multivesicular bodies whose contents are destined for lysosomal degradation. In addition, the pathways taken by FcRn and the transferrin receptor overlap, despite distinct mechanisms of ligand uptake. The studies provide a dynamic view of the trafficking of FcRn and its ligand and have relevance to understanding how FcRn functions to maintain IgG homeostasis.
Functional interaction of VEGF‐C and VEGF‐D with neuropilin receptors (2006)

Lymphatic vascular development is regulated by vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by its ligands VEGF-C and VEGF-D. Neuropilin-2 (NP2), known to be involved in neuronal development, has also been implicated to play a role in lymphangiogenesis. We aimed to elucidate the mechanism by which NP2 is involved in lymphatic endothelial cell signaling. By in vitro binding studies we found that both VEGF-C and VEGF-D interact with NP2, VEGF-C in a heparin-independent and VEGF-D in a heparin-dependent manner. We also mapped the domains of VEGF-C and NP2 required for their binding. The functional importance of the interaction of NP2 with the lymphangiogenic growth factors was demonstrated by cointernalization of NP2 along with VEGFR-3 in endocytic vesicles of lymphatic endothelial cells upon stimulation with VEGF-C or VEGF-D. NP2 also interacted with VEGFR-3 in coprecipitation studies. Our results show that NP2 is directly involved in an active signaling complex with the key regulators of lymphangiogenesis and thus suggest a mechanism by which NP2 functions in the development of the lymphatic vasculature.
Culture and Growth Characteristics of Chondrocytes Encapsulated in Alginate Beads (1989)

Methodology is described for the culture of avian and mammalian chondrocytes in ionotrophically gelled "semi-solid" and "hollow" alginate beads. Chondrocytes grown in "semi-solid" gels exhibited a spherical shape as opposed to a fibroblastic morphology observed in monolayer culture. In the "semi-solid" beads, the cells grew as small clumps and as large aggregates. The aggregates were round or elliptical in appearance and surrounded by a dense Alcian Blue positive halo. Preliminary studies with collagen and chitosan matrixes encapsulated in "hollow" beads suggest that cell growth and morphology are profoundly influenced by the composition of the cellular environment. Chondrocyte structure and function in the "semi-solid" and "hollow" beads were partially characterized by light microscopy, histochemical and biochemical means. The encapsulation methodology is readily applicable for the culture of chondrocytes in single beads, in multiwell dishes, or mass culture.
Dissolution of cellulose with ionic liquids and its application: a mini-review (2006)

Dissolution of cellulose with ionic liquids allows the comprehensive utilization of cellulose by combining two major green chemistry principles: using environmentally preferable solvents and bio-renewable feed-stocks. In this paper, the dissolution of cellulose with ionic liquids and its application were reviewed. Cellulose can be dissolved, without derivation, in some hydrophilic ionic liquids, such as 1-butyl-3-methylimidazolium chloride (BMIMCl) and 1-allyl-3-methylimidazolium chloride (AMIMCl). Microwave heating significantly accelerates the dissolution process. Cellulose can be easily regenerated from its ionic liquid solutions by addition of water, ethanol or acetone. After its regeneration, the ionic liquids can be recovered and reused. Fractionation of lignocellulosic materials and preparation of cellulose derivatives and composites are two of its typical applications. Although some basic studies, such as economical syntheses of ionic liquids and studies of ionic liquid toxicology, are still much needed, commercialization of these processes has made great progress in recent years.
From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis (2011)

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.
Lipooligosaccharide biosynthesis in Neiseria gonorrhoeae: cloning, identification and characterization of the α1,5 heptosyltransferase I gene (rfaC) (1994)

The identical partial deep-core structure of Hep alpha 1-3Hep alpha 1-5KDO in Salmonella typhimurium LT2 LPS and Neisseria gonorrhoeae LOS enabled us to isolate a DNA fragment from N. gonorrhoeae that was able to complement the alpha 1,5 LOS heptosyltransferase defect in the S. typhimurium rfaC630 (SA1377) mutant. SDS-PAGE analysis confirmed the production of wild-type LPS in the transformant. Subcloning revealed that complementation was due to a 1.2 kb fragment. Sequence analysis revealed a complete open reading frame capable of encoding a 36-37 kDa peptide. In vitro transcription-translation analysis of the 1.2 kb clone confirmed that a 37 kDa protein was encoded by this DNA fragment. The DNA sequence-deduced protein had 36% identity and 58% similarity to S. typhimurium heptosyltransferase I (RfaC). Primer extension analysis indicated that transcription of the cloned gene in N. gonorrhoeae strain 1291 begins 144 bp upstream of the start codon at a G nucleotide. An isogenic mutant of N. gonorrhoeae strain 1291 with an m-Tn3 insertion inside the coding sequence expressed a single truncated LOS with a similar molecular mass to S. typhimurium rfaC LPS. We conclude that the 1.2 kb fragment encodes the alpha 1,5 LOS heptosyltransferase I (RfaC) in N. gonorrhoeae. Our studies also provide further evidence that the third KDO residue in S. typhimurium LPS is added after the core synthesis is completed.
Stimulation of peripheral cannabinoid receptor CB2 induces MCP‐1 and IL‐8 gene expression in human promyelocytic cell line HL60 (1999)

Using the recently developed methodology of nucleic acid microarrays spotted with specific cDNAs probes belonging to different gene families, we showed for the first time that nanomolar concentrations of the cannabinoid ligand CP-55940 upregulated the expression of two different members of the chemokine gene family: the alpha-chemokine interleukin-8 (IL-8) and the beta-chemokine monocyte chemotactic protein-1 (MCP-1), in the promyelocytic cell line HL60 transfected with peripheral cannabinoid receptors (CB2). These genomic modulations observed on large-scale cDNA arrays were first confirmed by Northern blot studies. Furthermore, ELISA evaluations in culture supernatants indicated that the cannabinoid-induced activation of these two chemokine genes was followed by enhanced expression and secretion of the corresponding proteins. These upregulations initially observed in transfected HL60 cells overexpressing CB2 receptors, also occurred in normal non-transfected HL60 cells. The enhancement of IL-8 and MCP-1 gene transcription and protein production was shown to be pertussis toxin sensitive attesting that this phenomenon was a Gi protein-coupled receptor-mediated process as expected for cannabinoid receptors. More specifically, the abolition of the cannabinoid-induced effect by the specific CB2 antagonist SR 144528 indicated a strict peripheral cannabinoid-mediated process. Altogether, our data highlight a possible new function of peripheral cannabinoid receptors in the modulation of immune and inflammatory responses.
Development of replication-competent viral vectors for HIV vaccine delivery (2013)

A variety of DNA and RNA viruses are being used to develop replication-competent viral vectors for HIV vaccine delivery. Multiple viral vector platforms have proven to be well tolerated and immunogenic with evidence of efficacy in macaques. Some of the more advanced HIV vaccine prototypes based on vesicular stomatitis virus, vaccinia virus, measles virus, and Sendai virus are in clinical trials.
Interaction of Shc with Grb2 Regulates Association of Grb2 with mSOS (1995)

The adapter protein Shc has been implicated in Ras signaling via many receptors, including the T-cell antigen receptor (TCR), B-cell antigen receptor, interleukin-2 receptor, interleukin-3 receptor, erythropoietin receptor, and insulin receptor. Moreover, transformation via polyomavirus middle T antigen is dependent on its interaction with Shc and Shc tyrosine phosphorylation. One of the mechanisms of TCR-mediated, tyrosine kinase-dependent Ras activation involves the simultaneous interaction of phosphorylated Shc with the TCR zeta chain and with a second adapter protein, Grb2. Grb2, in turn, interacts with the Ras guanine nucleotide exchange factor mSOS, thereby leading to Ras activation. Although it has been reported that in fibroblasts Grb2 and mSOS constitutively associate with each other and that growth factor stimulation does not alter the levels of Grb2:mSOS association, we show here that TCR stimulation leads to a significant increase in the levels of Grb2 associated with mSOS. This enhanced Grb2:mSOS association, which occurs through an SH3-proline-rich sequence interaction, is regulated through the SH2 domain of Grb2. The following observations support a role for Shc in regulating the Grb2:mSOS association: (i) a phosphopeptide corresponding to the sequence surrounding Tyr-317 of Shc, which displaces Shc from Grb2, abolished the enhanced association between Grb2 and mSOS; and (ii) addition of phosphorylated Shc to unactivated T cell lysates was sufficient to enhance the interaction of Grb2 with mSOS. Furthermore, using fusion proteins encoding different domains of Shc, we show that the collagen homology domain of Shc (which includes the Tyr-317 site) can mediate this effect. Thus, the Shc-mediated regulation of Grb2:mSOS association may provide a means for controlling the extent of Ras activation following receptor stimulation.
Microarray-Based Detection of Bacteria by On-Chip PCR (2006)

In this chapter, a protocol called on-chip polymerase chain reaction (PCR) is presented for the deoxyribonucleic acid (DNA) microarray-based detection of bacterial target sequences. On-chip PCR combines, in a single step, the conventional amplification of a target with a simultaneous, nested PCR round intended for target detection. While freely diffusible primers are deployed for amplification, the nested PCR is initiated by oligonucleotide primers bound to a solid phase. Thus, on-chip PCR allows the single-step amplification and characterization of a DNA sample as a result of separation in liquid- and solid-phase reactions. In contrast to conventional PCR, the reaction is performed directly on the flat surface of a glass slide that holds an array of covalently attached nested primers. The bacterial target DNA is amplified and probed using primers identifying either species-specific sequence regions of ribosomal DNA or unique bacterial target genes, such as virulence or resistance factors. The microarray is produced using standard spotting equipment with an array layout containing a high number of replicates. Fluorescence scanning of on-chip PCR slides allows the rapid detection of the target of interest. The protocol described herein will show how on-chip PCR can be used to detect and precisely identify DNA of bacterial origin.
Generation of Expression Plasmids for Angiostatin, Endostatin and Timp-2 for Cancer Gene Therapy (1999)

Antiangiogenic therapy may represent a promising approach to cancer treatment. Indeed, the efficacy of endogenous angiogenesis inhibitors, including angiostatin, endostatin and TIMPs, has been demonstrated in many types of solid tumors in animal models. In view of the possible problems associated with long-term administration of inhibitors as recombinant proteins, we propose their delivery as nucleic acids through a gene therapy approach. To this end, eukaryotic expression constructs for murine angiostatin and endostatin as well as human TIMP-2 were generated, and characterized in vitro. All constructs carry the relevant cDNAs under the control of the strong HCMV promoter/enhancer, and cleavable leader signals to allow protein secretion. Expression of the angiogenesis inhibitors was detected by in vitro transcription/translation experiments as well as transfection of 293T cells, followed by Western blotting (WB) or radioimmunoprecipitation analysis of both cell lysates and supernatants (SNs). These constructs might be used for in vivo intramuscular delivery of plasmid DNA and as a set of reagents for the development of retroviral as well as adeno-associated viral (AAV) vectors expressing angiogenesis inhibitors.
Synthesizing Images of Humans in Unseen Poses (2018)

We address the computational problem of novel human pose synthesis. Given an image of a person and a desired pose, we produce a depiction of that person in that pose, retaining the appearance of both the person and background. We present a modular generative neural network that synthesizes unseen poses using training pairs of images and poses taken from human action videos. Our network separates a scene into different body part and background layers, moves body parts to new locations and refines their appearances, and composites the new foreground with a hole-filled background. These subtasks, implemented with separate modules, are trained jointly using only a single target image as a supervised label. We use an adversarial discriminator to force our network to synthesize realistic details conditioned on pose. We demonstrate image synthesis results on three action classes: golf, yoga/workouts and tennis, and show that our method produces accurate results within action classes as well as across action classes. Given a sequence of desired poses, we also produce coherent videos of actions.
Regioselectively Nucleus and/or Side-Chain Fluorinated 2-(Phenanthryl)propionic Acids by an Effective Combination of Radical and Organometallic Chemistry (2004)

Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting beta-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110 degrees C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above alpha-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory overall yields.
Late Signals from CD27 Prevent Fas-Dependent Apoptosis of Primary CD8+ T Cells (2008)

The role of costimulation has previously been confined to the very early stages of the CD8+ T cell response. In this study, we demonstrate the requirement for CD27 costimulation during the later phase, but not programming of the primary CD8+ T cell response to influenza virus and reveal a novel mechanism of action for CD27 costimulation. CD27 signals, during the later phase of the primary CD8+ T cell response, prevent apoptosis of Ag-specific CD8+ T cells. Blocking CD27L (CD70) on days 6 and 8 after infection reduces the number of NP(366-374)-specific CD8+ T cells, increases their sensitivity to CD95/Fas-mediated apoptosis, and up-regulates FasL on CD4+ T cells. This reduction of NP(366-374)-specific CD8+ T cells requires the presence of CD4+ T cells and Fas signaling. Lack of CD27 signals also decreases the quality of memory CD8+ T cell responses. Memory CD8+ T cells, which express surface CD27 similar to naive cells, however, do not require CD27 costimulation during a secondary response. Thus, CD27 acts indirectly to regulate primary Ag-specific CD8+ T cell responses by preventing apoptosis of CD8+ T cells during the later phase of the primary response and is required for optimal quality of memory cells, but is not required during normally primed secondary CD8+ T cell responses.
Liver transplantation as a treatment option for three siblings with homozygous familial hypercholesterolemia (2011)

FH is a hereditary inherited disorder of cholesterol metabolism. Homozygous form of the disease associates severe form of atherosclerotic disease. Clinicians have been tried to inhibit the progression of the homozygous FH with medical and surgical treatment. We here present three siblings with homozygous FH who were successfully treated with liver transplantation.
Care Workers' Perceptions of Professionalism and Job Satisfaction (2013)

본 연구는 우리나라 노인요양시설의 주요 인력인 요양보호사들을 중심으로 그들의 전문성 인식수준이 어떠한가를 살펴보고, 이러한 전문성 인식수준이 그들의 직무만족에 어떠한 영향을 미치는가를 분석하여 요양보호사의 전문성을 향상시키는 데에 필요한 정책적 시사점을 제시하고자 하였다. 본 연구는 서울, 경기도, 부산의 노인요양시설에서 근무하는 요양보호사 440명을 대상으로 설문지를 활용한 우편조사를 통해 이루어졌으며 조사는 2012년 8월 13일에서 31일까지 실시하였다. 본 연구조사 결과, 요양보호사들의 전문성 인식수준은 5점 만점에 평균 3.38점, 직무만족은 3.41점으로 보통수준인 것으로 나타났고, 전문성 인식수준과 직무만족간의 상관관계 분석을 한 결과 상관관계 계수 r=.553으로 두 변수 간에 유의미한 높은 정적인 관계를 보이고 있어, 요양보호사가 자신의 전문 직업에 대한 인식이 높을수록 개인의 직무만족에 영향을 미치는 것으로 나타났다. 또한, 회귀분석을 통해 직무만족에 영향을 미치는 요인들을 타 변수들 간의 관련성을 통제하고 분석했을 때 직무만족에 영향을 줄 수 있는 유의미한 변수는 전문성 인식과 연령인 것으로 나타나, 노인요양시설에서 직접적으로 서비스를 제공하는 요양보호사들의 전문성 인식을 제고하기 위해 실무경력에 맞는 적절한 직위와 처우가 제공될 수 되는 경력개발 및 승급체계 등의 마련과, 요양보호사 스스로 심리적 변화를 촉진할 수 있는 계기를 마련하기 위한 교육과 지원이 요양보호사 초기교육에서부터, 현장에 투입되고 나서의 재교육에 이르기까지 지속적 정기적으로 도입되어야함을 제언하였다. This study aims to examine care workers' role perceptions of their occupation and job satisfaction with their work. They are core human resources in elderly care work practices and their perceptions of their occupation are likely to affect their work performance and job satisfaction. A mail survey is conducted targeting to 400 care workers who are at work in long-term care facilities located in Seoul, Gyeonggi and Pusan. Research findings are as follows: firstly, the perception level of care workers' professionalism is 3.38, and job satisfaction is 3.41. Secondly, the correlation analysis between perception level of professionalism and job satisfaction, coefficient is .553, which shows positive relations between two variables. Thirdly, the study shows that care workers' perceptions of professionalism significantly affects their job satisfaction. This study concludes that it is necessary to take a variety of measures in contribution to improve the quality of service through reinforcement of perception of professionalism higher than present level of care workers who supply direct service in long-term care facilities.