gebhart/patrepeval huggingface dataset:
Complexity in Language Learning and Treatment (2007)

The construct of complexity appears to be a general principle that is relevant to treating a range of language disorders in both children and adults. While challenging the long-standing clinical notion that treatment should begin with simple structures, mounting evidence points toward the facilitative effects of using more complex structures as a starting point for treatment.
Memristor PUFs: a new generation of memory-based physically unclonable functions (2013)

Memristors are emerging as a potential candidate for next-generation memory technologies, promising to deliver non-volatility at performance and density targets which were previously the domain of SRAM and DRAM. Silicon Physically Unclonable Functions (PUFs) have been introduced as a relatively new security primitive which exploit manufacturing variation resulting from the IC fabrication process to uniquely fingerprint a device instance or generate device-specific cryptographic key material. While silicon PUFs have been proposed which build on traditional memory structures, in particular SRAM, in this paper we present a memristor-based PUF which utilizes a weak-write mechanism to obtain cell behaviour which is influenced by process variation and hence usable as a PUF response. Using a model-based approach we evaluate memristor PUFs under random process variations and present results on the performance of this new PUF variant.
Identification of Two Additional Translation Products from the Matrix (M) Gene That Contribute to Vesicular Stomatitis Virus Cytopathology (2002)

The matrix (M) protein of vesicular stomatitis virus (VSV) is a multifunctional protein that is responsible for condensation of the ribonucleocapsid core during virus assembly and also plays a critical role in virus budding. The M protein is also responsible for most of the cytopathic effects (CPE) observed in infected cells. VSV CPE include inhibition of host gene expression, disablement of nucleocytoplasmic transport, and disruption of the host cytoskeleton, which results in rounding of infected cells. In this report, we show that the VSV M gene codes for two additional polypeptides, which we have named M2 and M3. These proteins are synthesized from downstream methionines in the same open reading frame as the M protein (which we refer to here as M1) and lack the first 32 (M2) or 50 (M3) amino acids of M1. Infection of cells with a recombinant virus that does not express M2 and M3 (M33,51A) resulted in a delay in cell rounding, but virus yield was not affected. Transient expression of M2 and M3 alone caused cell rounding similar to that with the full-length M1 protein, suggesting that the cell-rounding function of the M protein does not require the N-terminal 50 amino acids. To determine if M2 and M3 were sufficient for VSV-mediated CPE, both M2 and M3 were expressed from a separate cistron in a VSV mutant background that readily establishes persistent infections and that normally lacks CPE. Infection of cells with the recombinant virus that expressed M2 and M3 resulted in cell rounding indistinguishable from that with the wild-type recombinant virus. These results suggest that M2 and M3 are important for cell rounding and may play an important role in viral cytopathogenesis. To our knowledge, this is first report of the multiple coding capacities of a rhabdovirus matrix gene.
Characterization of the Neuroanatomical Distribution of Agouti-Related Protein Immunoreactivity in the Rhesus Monkey and the Rat* (1999)

Agouti-related protein (AGRP) is a recently described homolog of the skin agouti protein. AGRP is transcribed primarily in the adrenal and hypothalamus and is a high affinity antagonist of the neural melanocortin-3 and melanocortin-4 receptors. The perikarya expressing AGRP messenger RNA are found in the arcuate nucleus of the rat and rhesus monkey. Using a polyclonal antibody against the pharmacologically active domain of AGRP (amino acids 83-132), we have also characterized the distribution of AGRP-immunoreactive neurons in both species. The major fiber tracts are conserved in both species, with dense projections originating in the arcuate nucleus and proceeding along the third ventricle. Dense fiber bundles are also visible in the paraventricular, dorsomedial, and posterior nuclei in the hypothalamus, in the bed nucleus of the stria terminalis, and in the lateral septal nucleus of the septal region. AGRP-containing neurons are not visualized in a number of areas, including portions of the amygdala, thalamus, and brain stem, that express MC3-R and MC4-R messenger RNA and receive innervation from POMC neurons that serve as the source of melanocortin agonists. Thus, AGRP is most likely to be involved in modulating a conserved subset of the physiological functions of central melanocortin peptides. Based on the particular distribution of AGRP neurons, those functions are likely to include the central control of energy homeostasis.
Human in vitro immune reactions to animal filariids. (1987)

Infective third stage larvae of animal filariids Brugia pahangi and Breinlia booliati incubated in vitro in the presence of normal human peripheral leucocytes and sera from human filariasis subjects resulted in decrease in motility, cell adherence, and formation of precipitates around the larvae. Strongest immune reactions were seen with sera from amicrofilaraemic symptomatic subjects, normal exposed individuals, and patients with tropical pulmonary eosinophilia syndrome (TPE). Weaker reactions were observed with sera from patients with elephantiasis. In all cases, reactivity to B. pahangi larvae was considerably higher than against B. booliati. Sera from microfilaraemic patients and unexposed control subjects were nonreactive. The implication of these human in vitro immune reactions against filarial parasites of animal origin is discussed in the context of the hypothesis of "zooprophylaxis" previously suggested by other workers.
Posterior Lumbar Interbody Fusion via a Unilateral Approach (2006)

This study sought to determine the outcomes of posterior lumbar interbody fusion (PLIF), via a unilateral approach, in selected patients who presented with unilateral leg pain and segmental instability of the lumbar spine. Patients with a single level of a herniated disc disease in the lumbar spine, unilateral leg pain, chronic disabling lower back pain (LBP), and a failed conservative treatment, were considered for the procedure. A total of 41 patients underwent a single-level PLIF using two PEEK (Poly-Ether-Ether-Ketone) cages filled with iliac bone, via a unilateral approach. The patients comprised 21 women and 20 men with a mean age of 41 years (range: 22 to 63 years). Two cages were inserted using a unilateral medial facetectomy and a partial hemilaminectomy. At follow-up, the outcomes were assessed using the Prolo Scale. The success of the fusion was determined by dynamic lumbar radiography and/or computerized tomography scanning. All the patients safely underwent surgery without severe complications. During a mean follow-up period of 26 months, 1 patient underwent percutaneous pedicle screw fixation due to persistent LBP. A posterior displacement of the cage was found in one patient. At the last follow up, 90% of the patients demonstrated satisfactory results. An osseous fusion was present in 85% of the patients. A PLIF, via a unilateral approach, enables a solid union with satisfactory clinical results. This preserves part of the posterior elements of the lumbar spine in selected patients with single level instability and unilateral leg pain.
Local Temperature Determination of Optically Excited Nanoparticles and Nanodots (2011)

A thin film of Al(0.94)Ga(0.06)N embedded with Er(3+) ions is used as an optical temperature sensor to image the temperature profile around optically excited gold nanostructures of 40 nm gold nanoparticles and lithographically prepared gold nanodots. The sensor is calibrated to give the local temperature of a hot nanostructure by comparing the measured temperature change of a spherical 40 nm gold NP to the theoretical temperature change calculated from the absorption cross section. The calibration allows us to measure the temperature where a lithographically prepared gold nanodot melts, in agreement with the bulk melting point of gold, and the size of the nanodot, in agreement with SEM and AFM results. Also, we measure an enhancement in the Er(3+) photoluminescence due to an interaction of the NP and Er(3+). We use this enhancement to determine the laser intensity that melts the NP and find that there is a positive discontinuous temperature of 833 K. We use this discontinuous temperature to obtain an interface conductance of ∼10 MW/m(2)-K for the gold NP on our thermal sensor surface.
Mechanism of Uptake and Incorporation of the Non-human Sialic Acid N-Glycolylneuraminic Acid into Human Cells* (2004)

N-Glycolylneuraminic acid (Neu5Gc) is a widely expressed sialic acid in mammalian cells. Although humans are genetically deficient in producing Neu5Gc, small amounts are present in human cells in vivo. A dietary origin was suggested by human volunteer studies and by observing that free Neu5Gc is metabolically incorporated into cultured human carcinoma cells by unknown mechanisms. We now show that free Neu5Gc uptake also occurs in other human and mammalian cells. Inhibitors of certain non-clathrin-mediated endocytic pathways reduce Neu5Gc accumulation. Studies with human mutant cells show that the lysosomal sialic acid transporter is required for metabolic incorporation of free Neu5Gc. Incorporation of glycosidically bound Neu5Gc from exogenous glycoconjugates (relevant to human gut epithelial exposure to dietary Neu5Gc) requires the transporter as well as the lysosomal sialidase, which presumably acts to release free Neu5Gc. Thus, exogenous Neu5Gc reaches lysosomes via pinocytic/endocytic pathways and is exported in free form into the cytosol, becoming available for activation and transfer to glycoconjugates. In contrast, N-glycolylmannosamine (ManNGc) apparently traverses the plasma membrane by passive diffusion and becomes available for conversion to Neu5Gc in the cytosol. This mechanism can also explain the metabolic incorporation of chemically synthesized unnatural sialic acids, as reported by others. Finally, to our knowledge, this is the first example of delivery to the cytosol of an extracellular small molecule that cannot cross the plasma membrane, utilizing fluid pinocytosis and a specific lysosomal transporter. The approach could, thus, potentially be generalized to any small molecule that has a specific lysosomal transporter but not a plasma membrane transporter.
Reconstitution of an apicoplast‐localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum (2005)

In the malaria parasite Plasmodium falciparum isoprenoid precursors are synthesised inside a plastid-like organelle (apicoplast) by the mevalonate independent 1-deoxy-d-xylulose-5-phosphate (DOXP) pathway. The last reaction step of the DOXP pathway is catalysed by the LytB enzyme which contains a [4Fe-4S] cluster. In this study, LytB of P. falciparum was shown to be catalytically active in the presence of an NADPH dependent electron transfer system comprising ferredoxin and ferredoxin-NADP(+) reductase. LytB and ferredoxin were found to form a stable protein complex. These data suggest that the ferredoxin/ferredoxin-NADP(+) reductase redox system serves as the physiological electron donor for LytB in the apicoplast of P. falciparum.
조휴(蚤休)(중루(重樓), 칠엽일지화(七葉一枝花))의 독성에 관한 문헌적 고찰 (2011)

Paridis Rhizoma is in use in eastern medicine. The eastern medical doctors use Paridis Rhizoma for clearing away heat and eliminating toxin(淸熱解毒), etc. We investigated toxicity, poisoning symptoms, poisoning treatment and prevention against poisoning of Paridis Rhizoma. The results were summarized as follows: 1. The main ingredients of poisoning are pariphyllin, dioscin, etc. The ingredients of poisoning from Paridis Rhizoma mainly cause stimulating symptoms on gastrointestinal system, nervous system, etc. 2. The representative methods of poisoning treatment in eastern medicine take advantage of herbs, such as Glycyrrhizae Radix(甘草), Zingiberis Rhizoma Recens(生薑), etc. And eastern medical doctors should meet symptoms as patients call for attention. 3. The representative methods of poisoning treatment in western medicine are washing out the stomach, causing diarrhea, supplies of grape sugar, taking acetic acid and symptomatic treatment, etc. 4. In order to prevent against poisoning of Paridis Rhizoma, the patients should keep usage, dosage and notes.
Inhibitors of farnesylation of Ras from a microbial natural products screening program (2000)

Mutant ras oncogenes are associated with various human tumors such as pancreas, colon, lung, thyroid, bladder and several types of leukemia. Prenylation of Ras proteins plays a major role in cell proliferation of both normal and cancerous cells. Normal and oncogenic Ras proteins are posttranslationally modified by a farnesyl group that promotes membrane binding. Inhibitors of farnesyl protein transferase (FPTase), the enzyme that catalyzes the prenylation of Ras proteins, inhibit growth of tumor cells. In an effort to identify structurally diverse and unique inhibitors of FPTase, a program devoted to screening of natural products was initiated. This effort led to the identification of 10 different families of compounds, all of which selectively inhibit FPTase with a variety of mechanisms that are reviewed in this manuscript. These compounds originated from the fermentations of a number of microorganisms, either actinomycetes or fungi, isolated from different substrates collected in tropical and temperate areas. A chemotaxonomic discussion on the distribution of each compound among single or different types of microorganisms, either phylogenetically related or unrelated species, is included.
The Impact of Pharmacogenomics Research on Drug Development (2012)

Over the last two decades, identification of polymorphisms that influence human diseases has begun to have an impact on the provision of medical care. The promise of genetics lies in its ability to provide insight into an individual's susceptibility to disease, the likely nature of the disease and the most appropriate therapy. For much of its history, pharmacogenomics (PGx) has been limited to relatively simple phenotypes such as plasma drug levels. Progress in genetic technologies has broadened the scope of exploratory PGx and its implementation into safety and efficacy studies, impacting a broad spectrum of drug discovery and development activities. Recent PGx data show the ability of this approach to generate information that can be applied to target selection, dose selection, efficacy determination and safety issues. This in turn will lead to significant opportunities to influence the approaches to drug discovery, clinical development and the probability of success. In particular, adverse drug reactions are critical issues for pharmaceutical companies and for the patients who will benefit from these new medicines. In this review, we outline current progress in PGx, using examples to highlight the influence of polymorphisms, and discuss contemporary challenges for both researchers and clinicians.
A human cell-surface receptor for xenotropic and polytropic murine leukemia viruses: Possible role in G protein-coupled signal transduction (1999)

Although present in many copies in the mouse genome, xenotropic murine leukemia viruses cannot infect cells from laboratory mice because of the lack of a functional cell surface receptor required for virus entry. In contrast, cells from many nonmurine species, including human cells, are fully permissive. Using an expression library approach, we isolated a cDNA from HeLa cell RNA that conferred susceptibility to xenotropic envelope protein binding and virus infection when expressed in nonpermissive cells. The deduced product is a 696-aa multiple-membrane spanning molecule, is widely expressed in human tissues, and shares homology with nematode, fly, and plant proteins of unknown function as well as with the yeast SYG1 protein, which has been shown to interact with a G protein. This molecule also acts as a receptor for polytropic murine leukemia viruses, consistent with observed interference between xenotropic and polytropic viruses in some cell types. This xenotropic and polytropic retrovirus receptor (XPR1) is the fourth identified molecule having multiple membrane spanning domains among mammalian type C oncoretrovirus receptors and may play a role in G protein-coupled signal transduction, as do the chemokine receptors required for HIV entry.
Native and Heterologous Production of Bacteriocins from Gram-Positive Microorganisms (2011)

In nature, microorganisms can present several mechanisms for setting intercommunication and defense. One of these mechanisms is related to the production of bacteriocins, which are peptides with antimicrobial activity. Bacteriocins can be found in Gram-positive and Gram-negative bacteria. Nevertheless, bacteriocins produced by Gram-positive bacteria are of particular interest due to the industrial use of several strains that belong to this group, especially lactic acid bacteria (LAB), which have the status of generally recognized as safe (GRAS) microorganisms. In this work, we will review recent tendencies in the field of invention and state of art related to bacteriocin production by Gram-positive microorganism. Hundred-eight patents related to Gram-positive bacteriocin producers have been disclosed since 1965, from which 57% are related bacteriocins derived from Lactococcus, Lactobacillus, Streptococcus, and Pediococcus strains. Surprisingly, patents regarding heterologous bacteriocins production were mainly presented just in the last decade. Although the major application of bacteriocins is concerned to food industry to control spoilage and foodborne bacteria, during the last years bacteriocin applications have been displacing to the diagnosis and treatment of cancer, and plant disease resistance and growth promotion.
Pharmacodynamic Effects of Antibiotics: Studies on Bacterial Morphology, Initial Killing, Postantibiotic Effect and Effective Regrowth Time (1992)

Pharmacodynamics of antibiotics deals with time course of drug activity and mechanisms of action of drugs on bacteria. In this thesis pharmacodynamic parameters have been studied after brief exposure of gram-positive bacteria to daptomycin, imipenem or vancomycin and after short exposure of gram-negative bacteria to amikacin, ampicillin, aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, imipenem, mecillinam, or piperacillin. The studies have been focused on morphological alterations, initial killing, postantibiotic effect (PAE) and effective regrowth time (ERT) and a method, based on bioluminescence assay of intracellular ATP has been used. The basic principle behind this technique is that ATP in living cells is present in a relatively constant amount, and hence affords a measure of the number of microbial cells. The PAE describes the delayed regrowth of bacteria after brief exposure to antibiotics. The number of cells measured after this antibiotic exposure describes the initial killing and is also the start value for calculating the PAE. PAEs of 2-3 h were obtained by bioluminescence for gram-positive bacteria exposed to imipenem or vancomycin. This is in agreement with results obtained by viable count and is probably due to similar weak initial decrease in cell density when assayed by both methods. Long (greater than 3 h) concentration dependent PAEs and moderate (less than or equal to 1 log10) initial decrease in intracellular ATP were in general seen for gram-positive bacteria exposed to daptomycin and for gram-negative bacteria exposed to imipenem or amikacin when assayed by bioluminescence. These very long PAEs and rather weak initial killing have to be compared with the shorter PAEs and stronger initial killing reported by us and others using viable count. Furthermore, this study showed that there was a relatively good concordance between microscopy and bioluminescence, which are direct methods, in determining the initial killing and PAE of imipenem on Escherichia coli. The ERT, defined as the time for bacterial density to increase 1 log10 from the pre-exposure inoculum, was independent of the method used for measuring regrowth of E. coli after brief exposure to imipenem. The combination of mecillinam with ampicillin, aztreonam, ceftazidime or piperacillin and the combination of amikacin with ceftazidime, ceftriaxone or piperacillin induced longer PAEs on gram-negative bacteria than the sum of PAEs of the individual antibiotics. A strong initial killing in combination with a long PAE cause a long ERT and may allow the antibiotic concentration to stay below MIC during long periods of time without any regrowth. This may, in clinical practice, have implications for long dosing intervals.
Methotrexate analogs. 9. Synthesis and biological properties of some 8-alkyl-7,8-dihydro analogs (1977)

A series of 8-alkyl-7,8,-dihydromethotrexate analogues was prepared by direct alkylation of 7,8-dihydromethotrexate, after pilot studies were performed with simpler pteridines. These compounds are tested for in vitro inhibitory activity against Lactobacillus casei and as enzyme inhibitors against dihydrofolate reductase and thymidylate synthetase derived from this organism. All of the analogues were less inhibitory toward dihydrofolate reductase than was methotrexate but were more inhibitory toward thymidylate synthetase. The analogues were also evaluated for in vitro inhibitory activity against the CCRF-CEM human lymphoblastic leukemia cells. In vivo against the L-1210 leukemia in mice, several of the analogues exhibited some antileukemic activity.
Assembly of adenovirus type 2 fiber synthesized in cell-free translation system (1991)

Physicochemical and functional analyses of the translation products of fiber mRNA in rabbit reticulocyte lysate suggested that fiber polypeptide chains (monomers) were capable of self-assembling in vitro, forming trimeric fibers (trimers) without direct intervention of any other adenovirus-coded protein or cell nuclear matrix component. Kinetic studies showed that trimer formation occurred at a rate six times lower than that of fiber polypeptide synthesis. Fiber assembly was found to be relatively inefficient in vitro, with only 25-30% fiber polypeptides trimerized after 4-h translation reaction. The rate constant for fiber subunit assembly, extrapolated from the kinetic curves of trimer formation, was found to be in the order of magnitude of 10(5) M-1 s-1, with a t 1/2 of 1.3 h at 30 degrees C. A latence phase of approximately 40 min in the appearance of the first detectable trimers indicated that fiber assembly did not occur co-translationally, suggesting the existence of rate-limiting intermediate step(s) during assembly.