gebhart/patrepeval huggingface dataset:
Characterization of Membrane Transport Processes: Lessons from the Study of BSP, Bilirubin, and Fatty Acid Uptake (1996)

Recent efforts to identify plasma membrane transporters mediating the selective uptake of specific classes of organic anions have employed expression cloning techniques. The transporters identified by these procedures have, almost without exception, differed from putative transporters identified earlier by classical methods. In this review, the classical and molecular approaches to the identification of membrane transporters are examined and compared, with particular attention paid to the results obtained by each with respect to sulfobromophthalein, bilirubin, and fatty acid transport. The classical approach requires the initial identification and purification of a candidate transport protein, proof of its function as a transporter by antibody inhibition or liposome reconstitution studies, and following the cloning of its cDNA, genetic expression in transfected mammalian cells or in Xenopus laevis oocytes. Expression cloning affords more rapid identification of proteins which (by definition) influence uptake, avoids several potential artifacts (e.g., of conventional cDNA library screening techniques), and yields rapid access to sequence information and derived structural characteristics. However, it is ultimately necessary to express and purify the recombinant protein product, produce antibodies against synthetic peptides and/or the purified recombinant protein, use the antibodies to identify the subcellular location of the cloned protein, demonstrate that the protein binds the ligand of interest, and document that the protein mediates a facilitated process with the characteristics of the one under study. Hence, the two approaches ultimately require similar efforts. It is argued that the different putative BSP/bilirubin and fatty acid transporters identified by the two approaches may mediate different parallel transport pathways.
Patent Update Cardiovascular & Renal: Recent progress in modulators of purinergic activity (1995)

As knowledge of the molecular biology of purinergic receptors continues to evolve, the identification of novel compounds that mimic or block the actions of the purine nucleoside and its nucleotide, ATP, at P1 and P2 receptor subtypes, respectively, has continued to be an area of active interest in the pharmaceutical industry. Adenosine A1 receptor selective agonists with reduced cardiovascular liabilities have been recently described, as have novel A3 receptor selective agonists; both classes of agents showing potential as anti-ischaemic agents in animal models. A number of potent and receptor subtype selective agonists for P2 receptors have also been developed that are being used to characterise the functional role of this receptor class in various mammalian tissues. On the antagonist front, selective A1 receptor antagonists are being targeted as cognition enhancers while selective A2a receptor antagonists have been developed with potential use in Parkinson's disease therapy. Despite the clinical failure of Gensia's “site and event specific” adenosine potentiating agent, Acadesine™, there is continued interest in compounds that enhance the availability of endogenous adenosine, specifically novel inhibitors of adenosine transport and adenosine kinase.
Experiments on Automatic Web Page Categorization for IR system (1998)

This paper describes keyword-based Web page categorization. Our goal is to embed our categorization technique into information retrieval (IR) systems to facilitate the end-users&amp;apos; search task. In such systems, search results must be categorized faster, while keeping accuracy high. Our categorization system uses a knowledge base (KB) to assign categories to Web pages. The KB contains a set of characteristic keywords with weights by category, and is automatically generated from training texts. With the keyword-based approach, the algorithms to extract keywords and assign weights to them should be considered, because the algorithms affect strongly both categorization accuracy and processing speed. Furthermore, we must take two characteristics of Web pages into account: (1) the text length is very variable, which makes it harder to use statistics such as word frequency to calculate keyword weights, and (2) a huge number of distinct words are used, which makes the KB bigger and therefore pro...
Large-area graphene realizing ultrasensitive photothermal actuator with high transparency: new prototype robotic motions under infrared-light stimuli (2011)

As transparent flexible electronics have recently become an emerging technology, they present great demands on the development of transparent soft actuators in the construction of invisible soft robots that would satisfy our daily lives with artificial intelligence devices. However, the current methodologies in building traditional soft actuators have intrinsically hampered the realization of high transparency devices with ultrasensitive responses. Herein, the utilization of large-area graphene successfully realizes the construction of transparent soft actuators with ultrasensitive responses, thereby opening the door for the design of three-dimensional (3D) intelligent models of transparent humanoid robots and micro-/nano-machines. The multiple synergic advantages of large-area graphene, especially its excellent IR absorption ability and ultra-thin dimensions, successfully bring together the excellent actuating sensitivity and high transparency, with the fascinating advantages of remote control, excellent mechanical strength, high sensitivity and high energy conversion efficiency. The transparent actuator model then builds a new bridge between mechanical behavior and the photo-thermal conversion effect not yet realized in other systems. Using infrared-light as the driving energy to realize complex robotic motions not only represents new prototype soft robot models, but also offers novel prospects for highly efficient solar light utilization, as well as the design of novel intelligent soft robot models.
Specificity of Gene Expression in Adipocytes (1985)

During the differentiation of preadipose 3T3 cells into adipose cells, the mRNAs for three proteins increase strikingly in abundance. To determine the degree of cell-type specificity in the expression of these mRNAs, we estimated their abundances in several nonadipose tissues of the mouse. None of these mRNAs was strictly confined to adipocytes, but the ensemble of three mRNAs was rather specific to adipocytes. Insofar as is revealed by these three markers, the distinctive phenotype of adipocytes is the result of the enhanced expression of a number of genes, none of which is completely silent in all other cell types.
An improved analytical method to design CMUTs with square diaphragms (2013)

A highly accurate mathematical method has been presented for analytical characterization of capacitive micromachined ultrasonic transducers (CMUTs) built with square diaphragms. The method uses a new two-dimensional polynomial function to more accurately predict the deflection curve of a multilayer square diaphragm subject to both mechanical and electrostatic pressure and a new capacitance model that takes into account the contribution of the fringing field capacitances. Both of the models have been experimentally verified by comparing the models predicted values with measurement results and are found to be in excellent agreement with a maximum deviation of less than 2% for experimentally measured capacitance values. 3-D electromechanical finite element analysis (FEA) for a wide range of material properties, geometric specifications, and loading conditions show that the presented method is highly consistent in accuracy over the typical square-diaphragm CMUT design space.
Polymers grafted from solid surfaces (1998)

Abstract Monolayers of polymer molecules were generated at the surface of a solid substrate in situ by using self‐assembled monolayers of initiator molecules. The layers were characterized by IR‐spectroscopy, surface plasmon resonance measurements, ellipsometry, X‐ray reflectometry, AFM and neutron reflectometry. Several novel techniques for the photolithographic patterning of the attached films are described. As a potential application for the attached layers the control of adhesion of biological cells to solid substrates is studied.
Viral and bacterial aetiology of community‐acquired pneumonia in adults (2012)

In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.
Pathophysiology of fistula formation in Crohn's disease (2014)

Fistulae represent an important complication in patient suffering from Crohn's disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed to improve wound repair mechanisms since "conventional" wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase (MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti-fistula treatments.
Solution Structure of Human GABAA Receptor-associated Protein GABARAP (2002)

Control of neurotransmitter receptor expression and delivery to the postsynaptic membrane is of critical importance for neural signal transduction at synapses. The gamma-aminobutyric acid, type A (GABA(A)) receptor-associated protein GABARAP was reported to have an important role for movement and sorting of GABA(A) receptor molecules to the postsynaptic membrane. GABARAP not only binds to GABA(A) receptor gamma2-subunit but also to tubulin, gephyrin, and ULK1. We present for the first time the high resolution structure of human GABARAP determined by nuclear magnetic resonance in aqueous solution. One part of the molecule, despite being well ordered and rigid on a MHz time scale, exists in at least two different conformations that interchange with each other on a time scale slower than 25 Hz. An important feature of the solution structure is the observation that amino- and carboxyl-terminal ends of the protein directly interact with each other, which is not seen in recently reported crystal structures. The possible biological relevance of these observations for the regulation of GABARAP interactions and functions is discussed.
Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected (2015)

Our understanding of the role of myeloid-derived suppressor cells (MDSCs) in cancer is becoming increasingly complex. In addition to their eponymous role in suppressing immune responses, they directly support tumor growth, differentiation, and metastasis in a number of ways that are only now beginning to be appreciated. It is because of this increasingly complex role that these cells may become an important factor in the treatment of human cancer. In this Review, we discuss the most pertinent and controversial issues of MDSC biology and their role in promoting cancer progression and highlight how these cells may be used in the clinic, both as prognostic factors and as therapeutic targets.
Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro. (1998)

Angiogenesis is critical for tumor growth and inflammation. Shiunko is a Chinese herbal ointment used for the treatment of burns in Japan. Its main ingredient is the root of Lithospermum erythrorhizon, which had been used for treating tumors and inflammation in China since the 5th century. We report here that shikonin, the main chemical ingredient of L. erythrorhizon is a novel inhibitor of angiogenesis. It inhibited tumor necrosis factor-alpha-induced and B16 melanoma-induced angiogenesis in mice and normal developmental angiogenesis in the yolk-sac membranes of chick embryos. Shikonin also inhibited proliferation and migration of endothelial cells in culture and network formation by endothelial cells on Matrigel in vitro. The dose-responsive study suggests that the mechanism of this inhibitory effect on angiogenesis involves the prevention of network formation by endothelial cells via blocking integrin alpha v beta 3 expression.
원보 : 새로운 퀴놀론계 항생제 LB20304a 의 일반약리작용 (1996)

General pharmacological studies of LB20304a (a mesylate salt form of a new quinolone antibiotic LB20304) following oral administration of 300 ㎎/㎏ and 1000 ㎎/㎏, almost maximum tolerance dose in mice and rat, respectively, were performed in terms of effects on general behaviour, central nervous system, gastrointestinal system, and blood coagulation system in mice and rats. With regards to general behaviour of mice, at oral dose of 300 ㎎/㎏, LB20304a reduced muscle tone and locomotor activity. In terms of CNS, at oral treatment of 300 ㎎/㎏, LB20304a showed some analgesic effects in mice, and oral dose of 1000 ㎎/㎏ caused drop in normal, body temperature of rat, while it enhanced the pentylenetetrazole-induced clonic convulsion to tonic convulsion and/or death in mice at the doses of upto 300 ㎎/㎏. In addition, LB20304a increased hexobarbital-induced sleeping time two and three times in mice at oral doses of 20 ㎎/㎏ and 300 ㎎/㎏, respectively. Rota-rod and traction test in mice were not influenced by the dose of 300 ㎎/㎏ and 200 ㎎/㎏, respectively. LB20304a reduced gastric secretion of rat at dose of 1000 ㎎/㎏, and increased intestinal motility of mice at dose of 300 ㎎/㎏. In rats, blood coagulation index, such as PT (prothrombin time) and aPTT (activated partial thromboplastin time) were not affected by the treatment of upto 1000 ㎎/㎏ of LB 20304a.
Muscular Dystrophies—Diseases of the Dystrophin-Glycoprotein Complex (1995)

Defects in the gene for the muscle protein dystrophin cause many cases of muscular dystrophy. Worton discusses three new papers, one in this issue of Science (Noguchi et al ., p. 819 ) and two in the November issue of Nature Genetics , which report that defects in the sarcoglycans, transmembrane glycoproteins that associate with dystrophin, underlie certain other types of muscular dystrophy.
Ablation of bcl-2 gene expression decreases the numbers of oocytes and primordial follicles established in the post-natal female mouse gonad. (1995)

Oocyte loss, either directly through attrition (germ cell death) or indirectly through follicular atresia (somatic or granulosa cell death), is a fundamental event associated with defining the time of normal or premature reproductive senescence in females. Although apoptosis has been reported to function as the underlying mechanism responsible for death of both germ cells and somatic cells in the ovary, the final molecular steps which commit ovarian cells to death have not been fully elucidated. To examine if death repressor activity of the bcl-2 gene product is important for germ cell survival, we conducted studies using a Bcl-2 loss-of-function (bcl-2 -/-) transgenic mouse model. Histological analyses revealed that ovaries collected from bcl-2 -/- mice possessed numerous aberrantly formed primordial follicle-like structures containing a single layer of granulosa cells without an oocyte. Additionally, the total number of primordial follicles present which contained a healthy oocyte was markedly reduced in bcl-2 -/- mice as compared to heterozygote (bcl-2 -/+) or wild-type (bcl-2 +/+) mice, suggesting that expression of the bcl-2 death repressor gene is critical for endowment of a normal complement of germ cells and primordial follicles in the mammalian ovary.
Tailoring the Properties of Europium‐Doped Potassium Calcium Iodide Scintillators Through Defect Engineering (2017)

Codoping is an effective approach for precise control of point defects in many advanced materials, and can be used to optimize their function. This paper reports an effort toward tailoring the scintillation properties of metal halides through defect engineering. A study of aliovalent codoping of the KCaI 3 :Eu 2+ single‐crystalline scintillators is performed, through which it is discovered that a simultaneous suppression of X‐ray induced afterglow and improvement of gamma‐ray energy resolution can be successfully achieved via Zr 4+ codoping. The afterglow level is reduced by more than twofold with Zr 4+ codoping. The energy resolution of a 5 mm cubic KCaI 3 :Eu 2+ sample is improved from 3.25 to 2.7% at 662 keV, and 6.5 to 5.73% at 122 keV upon Zr 4+ codoping. Physical explanations for the improvements are revealed from our investigations into both the electronic structure and thermodynamics of the defects by using thermoluminescence techniques and density functional theory calculations. The codoped Zr 4+ ions prefer to form interstitials acting as shallow electron traps. The {Zr Ca +V Ca } complex can co‐exist with Zr i interstitials as shallow hole traps under certain condition, which are able to trap holes temporarily.
The A-Type Cyclin CYCA2;3 Is a Key Regulator of Ploidy Levels in Arabidopsis Endoreduplication (2006)

Plant cells frequently undergo endoreduplication, a process in which chromosomal DNA is successively duplicated in the absence of mitosis. It has been proposed that endoreduplication is regulated at its entry by mitotic cyclin-dependent kinase activity. However, the regulatory mechanisms for its termination remain unclear, although plants tightly control the ploidy level in each cell type. In the process of searching for regulatory factors of endoreduplication, the promoter of an Arabidopsis thaliana cyclin A gene, CYCA2;3, was revealed to be active in developing trichomes during the termination period of endoreduplication as well as in proliferating tissues. Taking advantage of the situation that plants encode highly redundant cyclin A genes, we were able to perform functional dissection of CYCA2;3 using null mutant alleles. Null mutations of CYCA2;3 semidominantly promoted endocycles and increased the ploidy levels achieved in mature organs, but they did not significantly affect the proportion of cells that underwent endoreduplication. Consistent with this result, expression of the CYCA2;3-green fluorescent protein fusion protein restrained endocycles in a dose-dependent manner. Moreover, a mutation in the destruction box of CYCA2;3 stabilized the fusion protein in the nuclei and enhanced the restraint. We conclude that CYCA2;3 negatively regulates endocycles and acts as a key regulator of ploidy levels in Arabidopsis endoreduplication.
Restored plasticity in a mouse model of neurofibromatosis type 1 via inhibition of hyperactive ERK and CREB (2007)

Patients with neurofibromatosis type 1 (NF1), resulting from neurofibromin gene mutations, frequently suffer from deficits in learning and spatial memory. Mice heterozygous for functional deletion of the NF1 gene (NF1(+/-) mice) also exhibit compromised spatial learning, and deficits in early-stage hippocampal long-term potentiation (LTP). Neurofibromin is a multifunctional protein which acts in part as an inhibitory constraint on Ras signalling, and the deficits in early-stage LTP and spatial learning have been linked to Ras hyperactivation. However, the downstream targets of Ras hyperactivation that lead to cognitive disruption are unknown. The levels of activity of signalling molecules potentially downstream of Ras were therefore studied in NF1(+/-) mice. Elevated phospho-ERK (pERK) levels were observed in the hippocampi from NF1(+/-) mice, while phospho-Akt/PKB (pAkt) and phospho-eIF4E (peIF4E) levels were unchanged relative to wild-type mice. Hippocampal levels of phospho-CREB (pCREB) were also increased, suggesting potential changes in late-phase LTP in NF1(+/-) mice. Indeed, LTP was found to be impaired for at least 4 h following induction in NF1(+/-) mice, linking neurofibromin function with the long-term maintenance of LTP. Remarkably, U0126, an inhibitor of ERK activation, at doses which reduced the hyperactive pERK levels in NF1(+/-) mice to the levels observed in control mice, caused a reduction in the deficits in early-phase LTP and completely rescued the long-term LTP deficits. In contrast to the abundant evidence that reductions in ERK activity lead to impaired plasticity, these data indicate that ERK hyperactivation in a partial model of type 1 neurofibromatosis leads to deficits in long-lasting hippocampal plasticity.
Time-lapse technology: evaluation of embryo quality and new markers for embryo selection (2012)

Current methods of embryo evaluation rely mainly on static observations of the embryo´s morphology. These observations are inevitably restricted to specific times and, considering that the development of the embryo is a dynamic process, several critical stages in between observations may go unnoticed. These methods are also very subjective, and variations between embryologists may affect critical decisions that will, in turn, affect the overall success of the IVF clinics. On the other hand, an increased number of multiple pregnancies calls for a reduction in the number of embryos transferred, making the selection procedure even more challenging for the embryologist. Therefore, new markers that may aid the selection of embryos with higher implantation probabilities are needed. This review details what is known about time-lapse imaging, its application in embryology and the possible use of this technology as a novel selection tool.
All translation elongation factors and the e, f, and h subunits of translation initiation factor 3 are encoded by 5′-terminal oligopyrimidine (TOP) mRNAs (2008)

Terminal oligopyrimidine (TOP) mRNAs (encoded by the TOP genes) are identified by a sequence of 6-12 pyrimidines at the 5' end and by a growth-associated translational regulation. All vertebrate genes for the 80 ribosomal proteins and some other genes involved, directly or indirectly, in translation, are TOP genes. Among the numerous translation factors, only eEF1A and eEF2 are known to be encoded by TOP genes, most of the others having not been analyzed. Here, we report a systematic analysis of the human genes for translation factors. Our results show that: (1) all five elongation factors are encoded by TOP genes; and (2) among the initiation and termination factors analyzed, only eIF3e, eIF3f, and eIF3h exhibit the characteristics of TOP genes. Interestingly, these three polypeptides have been recently shown to constitute a specific subgroup among eIF3 subunits. In fact, eIF3e, eIF3f, and eIF3h are the part of the functional core of eIF3 that is not conserved in Saccharomyces cerevisiae. It has been hypothesized that they are regulatory subunits, and the fact that they are encoded by TOP genes may be relevant for their function.