gebhart/patrepeval huggingface dataset:
Biological significance of essential fatty acids. (2006)

Essential fatty acids (EFAs)--linoleic acid (LA) and alpha-linolenic acid (ALA) are critical for human survival. EFAs are readily available in the diet. But, to derive their full benefit, EFAs need to be metabolized to their respective long-chain metabolites. EFAs not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs), resolvins, isoprostanes, and hydroxy- and hydroperoxyeicosatetraenoates. Certain PGs, TXs, and LTs have pro-inflammatory actions whereas LXs and resolvins are anti-inflammatory in nature. Furthermore, EFAs and their long-chain metabolites modulate the activities of angiotensin converting and HMG-CoA reductase enzymes, enhance acetylcholine levels in the brain, increase the synthesis of endothelial nitric oxide, augment diuresis, and enhance insulin action. Thus, EFAs and their metabolites may function as endogenous ACE and HMG-CoA reductase inhibitors, nitric oxide enhancers, beta-blockers, diuretics, anti-hypertensive, and anti-atherosclerotic molecules. In addition, EFAs and their long-chain metabolites react with nitric oxide (NO) to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). Thus, EFAs and their derivatives have varied biological actions that may have relevance to their involvement in several physiological and pathological processes.
SCARECROW Has a SHORT-ROOT-Independent Role in Modulating the Sugar Response (2012)

Sugar is essential for all cellular activities, but at high levels it inhibits growth and development. How plants balance the tradeoffs between the need for sugars and their growth inhibitory effects is poorly understood. SHORT-ROOT (SHR) and SCARECROW (SCR) are key regulators of stem cell renewal and radial patterning in the root of Arabidopsis (Arabidopsis thaliana). Recently, we identified direct targets of SHR at the genome scale. Intriguingly, among the top-ranked list, we found a number of genes that are involved in stress responses. By chromatin immunoprecipitation-polymerase chain reaction (PCR), we showed that SHR and SCR regulate a similar but not identical set of stress response genes. Consistent with this, scr and shr were found to be hypersensitive to abscisic acid (ABA). We further showed that both mutants were hypersensitive to high levels of glucose (Glc) but responded normally to high salinity and osmoticum. The endogenous levels of sucrose, Glc, and fructose were also elevated in shr and scr. Intriguingly, although shr had sugar content and developmental defects similar to those of scr, it was much less sensitive to Glc. Chromatin immunoprecipitation-PCR and reverse transcription-PCR assays as well as transgenic studies with an ABA-INSENSITIVE2 (ABI4)-β-glucuronidase reporter construct revealed that in root, SCR, but not SHR, repressed ABI4 and ABI5 directly and specifically in the apical meristem. When combined with abi4, scr became much more tolerant of high Glc. Finally, transgenic plants expressing ABI4 under the control of the SCR promoter manifested a short-root phenotype. These results together suggest that SCR has a SHR-independent role in mitigating the sugar response and that this role of SCR is important for root growth.
Generating statechart designs from scenarios (2000)

This paper presents an algorithm for automatically generating UML statecharts from a collection of UML sequence diagrams. Computer support for this transition between requirements and design is important for a successful application of UML's highly iterative, distributed software development process. There are three main issues which must be addressed when generating statecharts from sequence diagrams. Firstly, conflicts arising from the merging of independently developed sequence diagrams must be detected and resolved. Secondly, different sequence diagrams often contain identical or similar behaviors. For a true interleaving of the sequence diagrams, these behaviors must be recognized and merged. Finally, generated statecharts usually are only an approximation of the system and thus must be hand-modified and refined by designers. As such, the generated artifact should be highly structured and readable. In terms of statecharts, this corresponds to the introduction of hierarchy. Our algorithm successfully tackles all three of these aspects and will be illustrated in this paper with a well-known ATM example.
Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences (2011)

In eukaryotes, it is generally assumed that translation initiation occurs at the AUG codon closest to the messenger RNA 5' cap. However, in certain cases, initiation can occur at codons differing from AUG by a single nucleotide, especially the codons CUG, UUG, GUG, ACG, AUA and AUU. While non-AUG initiation has been experimentally verified for a handful of human genes, the full extent to which this phenomenon is utilized--both for increased coding capacity and potentially also for novel regulatory mechanisms--remains unclear. To address this issue, and hence to improve the quality of existing coding sequence annotations, we developed a methodology based on phylogenetic analysis of predicted 5' untranslated regions from orthologous genes. We use evolutionary signatures of protein-coding sequences as an indicator of translation initiation upstream of annotated coding sequences. Our search identified novel conserved potential non-AUG-initiated N-terminal extensions in 42 human genes including VANGL2, FGFR1, KCNN4, TRPV6, HDGF, CITED2, EIF4G3 and NTF3, and also affirmed the conservation of known non-AUG-initiated extensions in 17 other genes. In several instances, we have been able to obtain independent experimental evidence of the expression of non-AUG-initiated products from the previously published literature and ribosome profiling data.
Blue Light Differentially Modulates Cell Survival and Growth (2004)

Previous studies have reported that blue light (400-500 nm) inhibits cell mitochondrial activity. We investigated the hypothesis that cells with high energy consumption are most susceptible to blue-light-induced mitochondrial inhibition. We estimated cell energy consumption by population doubling time, and cell survival and growth by succinate dehydrogenase (SDH) activity. Six cell types were exposed to 5 or 60 J/cm(2) of blue light from quartz-tungsten-halogen (QTH), plasma-arc (PAC), or argon laser sources in monolayer culture. Post-light SDH activity correlated positively with population doubling time (R(2) = 0.91 for PAC, 0.76 for QTH, 0.68 for laser); SDH activity increased for cell types with the longest doubling times and was suppressed for cell types with shorter doubling times. Thus, light-induced exposure differentially affects SDH activity, cell survival, and growth, depending on cell energy consumption. Blue light may be useful as a therapeutic modulator of cell growth and survival.
On the expanding, then contracting scope of scientific publications (2009)

My great-grandfather was a professor of theology at the University of Bern and a prolific author of scientific papers and books in the late 19th and early 20th century. For his documentation, he used paper slips of 7 × 15.5 cm, which were specially manufactured according to his specifications. These papers might seem rather tiny, but they were large enough for his hand-written records of theological and historical documents. Obviously, the papers gave him enough space for capturing important biblical messages and divine inspiration. I did not know my great-grandfather personally as he died several years before I was born. But I inherited a large box of his paper slips and, although I have used lots of them over the past 50 years, plenty remain. I find them useful not for archiving purposes, but for momentarily jotting down facts, thoughts and ideas before I forget them.

Scientific documentation was an arduous task until the 1960s. It meant going to a library, finding journals and books, extracting the relevant information from these documents and writing it down on paper – be it on paper slips (like my great-grandfather did), on file cards or in notebooks. Photographic reproduction of documents was expensive and restricted to exceptional cases. Few scholars had direct access to good libraries and even fewer could count on secretarial help with copying and archiving information. As many scientific papers were published in …
Gas Storage in Nanoporous Materials (2008)

Gas storage in solids is becoming an ever more important technology, with applications and potential applications ranging from energy and the environment all the way to biology and medicine. Very highly porous materials, such as zeolites, carbon materials, polymers, and metal-organic frameworks, offer a wide variety of chemical composition and structural architectures that are suitable for the adsorption and storage of many different gases, including hydrogen, methane, nitric oxide, and carbon dioxide. However, the challenges associated with designing materials to have sufficient adsorption capacity, controllable delivery rates, suitable lifetimes, and recharging characteristics are not trivial in many instances. The different chemistry associated with the various gases of interest makes it necessary to carefully match the properties of the porous material to the required application.
Protein formulation and lyophilization cycle design: Prevention of damage due to freeze-concentration induced phase separation (1999)

Hemoglobin has been previously shown to unfold during freeze drying when lyophilized from formulations that undergo freeze-concentration induced phase separation (Heller et al. 1997. Biotechnol Prog 13:590-596). In this report, we show that such damage may be avoided using kinetic strategies to arrest the phase separation. By rapidly cooling samples during liquid nitrogen spray-freeze drying, the time that the formulation spends in temperature regimes (ca. -3 to -23 degrees C) in which phase separation is both thermodynamically favorable and kinetically realizable is minimized. Increased protein damage with decreasing cooling rates and/or longer annealing periods at -7 degrees C is observed by FTIR spectroscopy. Phase separation and concomitant protein damage may also be avoided by addition of mannitol at concentrations sufficient to cause crystallization. Mannitol crystals segregate the freeze concentrated solution into microscopic domains that block propagation and nucleation of phase separating events. Addition of noncrystallizing sugars, such as sucrose and trehalose, or nonionic surfactants, such as Tween 80 and Triton X-100, has little protective effect against phase separation induced damage during freezing drying.
Triazene: vielseitige Verbindungen für die organische Synthese (2002)

Triazene (RNNNR′R″) sind eine für die präparative Chemie außerordentlich vielversprechende Stoffklasse, da die Triazen-Einheit als funktionelle Gruppe einerseits beständig ist, andererseits dennoch in vielfältiger Weise modifiziert werden kann. Triazene haben sich nicht nur auf Gebieten wie Pharmakologie, Totalsynthese, Polymertechnologie oder bei der Konstruktion neuartiger Ringsysteme als nützlich erwiesen (um nur einige zu nennen), sondern überraschen den Chemiker durch erweiterte Anwendungsmöglichkeiten und durch neue Reaktionen. Dieser Aufsatz beschäftigt sich mit Fortschritten in der Chemie von Systemen dieser Art und ihrer Vielseitigkeit.
High IFN-γ Production of Individual CD8 T Lymphocytes Is Controlled by CD152 (CTLA-4) (2007)

CD8 T cell expansion and cytokine production is needed to generate an effective defense against viral invasion of the host. These features of CD8 T lymphocytes are regulated, especially during primary responses, by positive and negative costimulation. We show in this study that surface expression of CD152 is highly up-regulated on activated CD8 T lymphocytes during primary immune responses, suggesting a prominent regulatory role. Indeed, production of the proinflammatory cytokine IFN-gamma, but not TNF-alpha, by CD8 T cells was inhibited by CD152 engagement. The inhibition was regulated independent of proliferation and IL-2 production, but dependent on the quality of the TCR signaling. We show that signals induced by CD152 on activated CD8 T lymphocytes reduce the frequency of IFN-gamma(high)-expressing cells. Our data also show that in activated CD8 T cells, the CD152-mediated inhibition of cytokine production is more pronounced than inhibition of their proliferation.
Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype (2004)

Melanoma is the most lethal skin cancer. Most deaths from melanoma result from metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but the effects of semaphorins on tumor metastasis have not been documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human cell lines in vitro and in vivo, which suggested that it may be a metastasis inhibitor. Metastatic human melanoma cells were transfected with SEMA3F and implanted into mice; the resultant tumors did not metastasize. Rather, the primary tumors resembled benign nevi characterized by large areas of apoptosis, diminished vascularity, inhibition of hyperplasia in overlying epidermal cells, and encapsulated tumor borders delineated by thick layers of fibroblasts and collagen matrix. This phenotype is in stark contrast to highly invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The repulsive activity was abrogated by NRP2 RNA interference. Together these results indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and stromal cells and raise the possibility of SEMA3F having therapeutic potential.
Chemokine Receptor CCR1 Disruption in Bone Marrow Cells Enhances Atherosclerotic Lesion Development and Inflammation in Mice (2005)

Several chemokines or chemokine receptors are involved in atherogenesis. CCR1 is expressed by macrophages and lymphocytes, two major cell types involved in the progression of atherosclerosis, and binds to lesion-expressed ligands. We examined the direct role of the blood-borne chemokine receptor CCR1 in atherosclerosis by transplanting bone marrow cells from either CCR1+/+ or CCR1-/- mice into low-density lipoprotein-receptor (LDLr)-deficient mice. After exposure to an atherogenic diet for 8 weeks, no differences in fatty streak size or composition were detected between the 2 groups. After 12 weeks of atherogenic diet, however, an unexpected 70% increase in atherosclerotic lesion size in the thoracic aorta was detected in the CCR1-/- mice, accompanied by a 37% increase in the aortic sinus lesion area. CCR1-/- mice showed enhanced basal and concanavalin A-stimulated IFN-gamma production by spleen T cells and enhanced plaque inflammation. In conclusion, blood-borne CCR1 alters the immuno-inflammatory response in atherosclerosis and prevents excessive plaque growth and inflammation.
우리나라 대학의 균형성과표 도입효과 (2010)

본 연구는 우리나라 대학에 균형성과표가 새롭게 도입될 경우 어떠한 영향을 미치는 지를 알아보기 위하여 조직특성, 관리특성, 구성원인식특성이 균형성과표 요인에 어떠한 영향을 미치는지를 검증할 목적으로 수행되었다. 본 연구의 결과를 요약하고 그 시사점을 제시하면 다음과 같다. 첫째, 대학의 조직특성, 관리특성, 구성원 인식특성 요인이 균형성과표의 학습 및 성장성과에 미치는 영향을 검증한 결과, 관리특성 중 최고경영자 지원과 인식특성 중 사용용이성이 학습 및 성장성과에 미치는 영향은 기각되었으며, 다른 모든 요인은 학습 및 성장성과 요인에 정(+)의 영향을 미치는 것으로 나타났다. 이는 BSC 도입에 따라 대학조직이 의사소통과 업무표준화가 잘 이루어지고 구성원에 대한 교육훈련이 잘 이루어지며, BSC가 이용가치가 높다는 것을 인식시킴으로써 BSC의 학습 및 성장성과를 높일 수 있다는 것을 의미한다. 둘째, 대학의 조직특성, 관리특성, 구성원 인식특성 요인이 균형성과표의 내부프로세스성과 요인에 미치는 영향을 검증한 결과, 모두 정(+)의 영향을 미치는 것으로 나타났다. 이는 BSC의 도입에 따라 대학조직이 의사소통과 업무표준화가 잘 이루어지고, 구성원에 대한 교육훈련과 최고경영자로서 총장의 지원이 원활이 이루어지며, 균형성과표의 이용가치 및 사용용이성이 인식된다면 균형성과표의 내부프로세스성과는 높아질 것이라는 것을 의미한다. 셋째, 대학의 조직특성, 관리특성, 구성원 인식특성 요인이 균형성과표의 고객성과에 미치는 영향을 검증한 결과, 관리특성 중 최고경영자 지원과 인식특성 중 사용용이성이 고객성과에 미치는 영향은 기각되었으며, 다른 모든 요인은 학습 및 성장성과 요인에 정(+)의 영향을 미치는 것으로 나타났다. 이는 BSC의 도입에 따라 대학조직이 업무표준화가 잘 이루어지고 의사소통이 잘 이루어지며, 대학구성원에 대한 교육훈련이 잘 이루어져 균형성과표가 이용할 가치가 있다는 인식이 높아지면 균형성과표의 고객성과는 높아질 것이라는 것을 의미한다. 넷째, 대학의 조직특성, 관리특성, 구성원 인식특성 요인이 균형성과표의 재무성과에 미치는 영향을 검증한 결과, 모두 정(+)의 영향을 미치는 것으로 나타났다. 이는 BSC의 도입에 따라 대학조직이 의사소통과 업무표준화가 잘 이루어지고, 최고경영자의 지원과 구성원에 대한 교육훈련이 잘 이루어지며, 대학구성원이 균형성과표가 이용가치가 있고 사용이 용이하다는 인식이 확산되면 균형성과표의 재무성과가 높아진다는 것을 의미한다.
Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy (2016)

Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.
Intervention with bacterial adhesion by multivalent carbohydrates (2006)

Bacterial adhesion is often a prelude to infection. In many cases, this process is governed by protein-carbohydrate interactions. Intervention at this early stage of infection is a conceptually highly attractive alternative to conventional antibiotics that are increasingly prone to resistance. The lack of high-affinity inhibitors of adhesion has proven to be a hurdle for further exploitation of this concept; however, new developments indicate a positive change. Structure-based design at the monovalent level and also evaluation of glycodendrimers and glycopolymers have yielded structures of high affinity. In addition to the development of inhibitors, topics of this review include available structural information of adhesion proteins, carbohydrate specificities of the various pathogens and their adhesion proteins. Other new developments aimed at affecting bacterial adhesion and the use of the adhesins for bacterial detection are also discussed.
Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases (2009)

This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with the transplant centers' experience. These data support ongoing and planned phase III trials to evaluate the place of autologous hematopoietic stem cell transplantation in the treatment strategy for severe autoimmune diseases.
Interpersonal Influence among Public Health Leaders in the United States Department of Health and Human Services (2012)

Findings from this unique study provide a perspective on influence within a government agency that both helps to understand decision-making and also can serve to inform organizational efforts that allow for more effective structuring of leadership.
The trk Proto-Oncogene Product: a Signal Transducing Receptor for Nerve Growth Factor (1991)

The trk proto-oncogene encodes a 140-kilodalton, membrane-spanning protein tyrosine kinase (p140prototrk) that is expressed only in neural tissues. Nerve growth factor (NGF) stimulates phosphorylation of p140prototrk in neural cell lines and in embryonic dorsal root ganglia. Affinity cross-linking and equilibrium binding experiments with 125I-labeled NGF indicate that p140prototrk binds NGF specifically in cultured cells with a dissociation constant of 10(-9) molar. The identification of p140prototrk as an NGF receptor indicates that this protein participates in the primary signal transduction mechanism of NGF.
Free Energy Landscape of a DNA−Carbon Nanotube Hybrid Using Replica Exchange Molecular Dynamics (2009)

The DNA−carbon nanotube hybrid (DNA-CN) consists of a single-wall carbon nanotube (SWCN) coated with a self-assembled monolayer of single-stranded DNA (ssDNA). Recent experiments have demonstrated that this nanomaterial is ideal for numerous nanotechnological applications. Despite this importance, the structure of this material remains poorly understood. Molecular dynamics (MD) simulations have provided information about the self-assembly mechanisms and ssDNA conformations that characterize DNA-CN. However, MD simulations of biopolymers at low temperatures (T ∼ 300 K) result in kinetic trapping that limits conformational sampling. Here, we present results of a large-scale replica exchange molecular dynamics (REMD) simulation that provides extensive sampling of the entire ensemble of oligonucleotide conformations in a (GT)7-SWCN hybrid. We calculate the free energy landscape and find minima corresponding to six distinct conformations, with a nonhelical loop structure as the global minimum. The hybrid contains significant structural disorder, with desorbed bases as an important structural feature. These results expand our understanding of DNA-CN and indicate the relevance of REMD for explorations of the physical properties of organic−inorganic multifunctional nanomaterials.
Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis (1998)

Connective tissue growth factor (CTGF) is a newly described 38-kDa peptide mitogen for fibroblasts and a promoter of connective tissue deposition in the skin. The CTGF gene promotor contains a transforming growth factor-beta1 (TGF-beta1) response element. Because TGF-beta1 expression is upregulated in several models of fibroproliferative lung disease, we asked whether CTGF is also upregulated in a murine lung fibrosis model and whether CTGF could mediate some of the fibrogenic effects associated with TGF-beta1. A portion of the rat CTGF gene was cloned and used to show that primary isolates of both murine and human lung fibroblasts express CTGF mRNA in vitro. There was a greater than twofold increase in CTGF expression in both human and murine lung fibroblasts 2, 4, and 24 h after the addition of TGF-beta1 in vitro. A bleomycin-sensitive mouse strain (C57BL/6) and a bleomycin-resistant mouse strain (BALB/c) were given bleomycin, a known lung fibrogenic agent. CTGF mRNA expression was upregulated in the sensitive, but not in the resistant, mouse strain after administration of bleomycin. In vivo differences in the CTGF expression between the two mouse strains were not due to an inherent inability of BALB/c lung fibroblasts to respond to TGF-beta1 because fibroblasts from untreated BALB/c mouse lung upregulated their CTGF message when treated with TGF-beta1 in vitro. These data demonstrate that CTGF is expressed in lung fibroblasts and may play a role in the pathogenesis of lung fibrosis.