gebhart/patrepeval huggingface dataset:
Definition and Evaluation of Transient Ischemic Attack (2009)

This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging. Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD(2) score >or=3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.
Production of Polyunsaturated Fatty Acids by Polyketide Synthases in Both Prokaryotes and Eukaryotes (2001)

Polyunsaturated fatty acids (PUFAs) are essential membrane components in higher eukaryotes and are the precursors of many lipid-derived signaling molecules. Here, pathways for PUFA synthesis are described that do not require desaturation and elongation of saturated fatty acids. These pathways are catalyzed by polyketide synthases (PKSs) that are distinct from previously recognized PKSs in both structure and mechanism. Generation of cis double bonds probably involves position-specific isomerases; such enzymes might be useful in the production of new families of antibiotics. It is likely that PUFA synthesis in cold marine ecosystems is accomplished in part by these PKS enzymes.
Receptors for endogenous and heterogenous hydroxamate siderophores in Staphylococcus aureus B 471. (2005)

In Staphylococcus aureus B47 grown in iron-restricted medium, six new, iron-regulated proteins occurred in cytoplasmic membrane. Protein of 14kDa has bound two complexes of iron: Fe(III)-staphylobactin and Fe(III)-acinetoferrin. Complexes of Fe(llI)-ferrichrome and Fe(III)-rhodotorulic acid were not bound to any of new membrane protein. Iron of Fe(III)-staphylobactin and Fe(IIl)-acinetoferrin complexes was transported into the cells.
Preparation of an Insulin with Improved Pharmacokinetics Relative to Human Insulin through Consideration of Structural Homology with Insulin-Like Growth Factor I (1994)

The Diabetes Control and Complications Trial has emphasized the need for improved control of blood glucose as a means to diminish long-term complications of diabetes. LysPro-insulin is an analog of human insulin whose design was modeled on structural homology with insulin-like growth factor I. An analysis of the structural conformation of insulin suggested that an inversion of amino acids B28 and B29 in the C-terminus of the B chain could yield an insulin analog with a faster onset of biological action. This insulin analog has proved to be virtually identical to human insulin in action, with one important exception. LysPro-insulin has demonstrated an improved time course of action in control of a mealtime glucose elevation. This offers the opportunity for improved convenience and safety for patients with insulin-dependent diabetes mellitus.
Stroke Genomics: Approaches to Identify, Validate, and Understand Ischemic Stroke Gene Expression (2001)

Sequencing of the human genome is nearing completion and biologists, molecular biologists, and bioinformatics specialists have teamed up to develop global genomic technologies to help decipher the complex nature of pathophysiologic gene function. This review will focus on differential gene expression in ischemic stroke. It will discuss inheritance in the broader stroke population, how experimental models of spontaneous stroke might be applied to humans to identify chromosomal loci of increased risk and ischemic sensitivity, and also how the gene expression induced by stroke is related to the poststroke processes of brain injury, repair, and recovery. In addition, we discuss and summarise the literature of experimental stroke genomics and compare several approaches of differential gene expression analyzes. These include a comparison of representational difference analysis we have provided using an experimental stroke model that is representative of stroke evolution observed most often in man, and a summary of available data on stroke differential gene expression. Issues regarding validation of potential genes as stroke targets, the verification of message translation to protein products, the relevance of the expression of neuroprotective and neurodestructive genes and their specific timings, and the emerging problems of handling novel genes that may be discovered during differential gene expression analyses will also be addressed.
Bone incorporation of frozen femoral head allograft in revision total hip replacement. (1993)

Since 1983, 60 patients (60 joints) with acetabular bone loss underwent the total hip reconstruction using frozen femoral head allografts. Every 6 months, antero-posterior view radiographs of bilateral hip joints and sequential 99mTcMDP bone scintigrams were obtained. A CT scan of bilateral hip joints was taken to measure the volume of allograft. Bone incorporation was observed in 52 patients with an average time of 28.2 months. Bone scintigraphy also revealed that the uptake became normal 2-3 years after the revision. Differences in the time necessary for bone incorporation could be attributed to the size of allografts--the larger the volume, the longer the time required (p < 0.01). It was also found that on the side that received a transplant, the allograft was incorporated faster when there was more bone tissue surrounding the missing part of the acetabulum (p < 0.05).
Fibronectin modulates macrophage adhesion and FBGC formation: The role of RGD, PHSRN, and PRRARV domains (2001)

To probe the role of human plasma fibronectin in modulating human blood-derived macrophage adhesion and fusion to form multinucleated foreign-body giant cells (FBGC), a series of biomimetic oligopeptides based on the functional structure of fibronectin was designed and synthesized. Peptides incorporated the RGD and PHSRN integrin-binding sequences from FIII-10 and FIII-9 modules, respectively, and the PRRARV sequence from the C-terminal heparin-binding domain, either alone or in combination. Peptides were immobilized onto a polyethyleneglycol-based polymer substrate. The following conclusions were reached. Fibronectin modulated macrophage adhesion and the extent (i.e., size) of FBGC formation on control surfaces in the presence of serum proteins. Macrophages adhered to all substrates with relatively subtle differences between adhesion mediated by RGD, PHSRN, PRRARV, or combinations thereof. β1-integrin subunit was essential in macrophage adhesion to peptide-grafted networks in a receptor-peptide specific manner, whereas β3-integrin subunit was less important. Macrophage adhesion to PRRARV was mediated primarily by the direct interaction with integrins. RGD or PHSRN alone did not provide an adequate substrate for macrophage fusion to form FBGCs. However, the PHSRN synergistic site and the RGD site in a single oligopeptide provided a substrate for FBGC formation that was statistically comparable to that on the positive control material in the presence of serum proteins. This response was highly dependent upon the relative orientation between RGD and PHSRN. PRRARV did not support FBGC formation. These results demonstrate the importance of fibronectin and, specifically, the synergy between RGD and PHSRN domains, in supporting macrophage fusion to form FBGCs. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res 55: 79–88, 2001
Effect of TTP488 in patients with mild to moderate Alzheimer’s disease (2014)

Results of these analyses support further investigation of 5 mg/day in future Phase 3 trials in patients with mild AD.
High fluence deuteron bombardmemnt of silicon (1977)

Abstract A study has been made of d+ ion implantation in Si(111) at 100 K and 300 K. Deuterium depth profiles as a function of fluence were obtained using a method based on observing the energy spectra of the tritons and protons from the D(d, p)T reaction induced with a deuteron beam. Profiles at 300 K show two distinct regions in the target. For a fluence of 4 × 1015 d+/cm2 the surface region which extends over the first half of the deuteron range contains little deuterium (∼ 0.3 atomic %) while a relatively large amount (∼ 5 at. %) is retained in a buried layer. Typical scanning electron micrographs taken following implantation are presented. They show the deeper layers to be highly damaged. In striking contrast, the surface region shows little observable damage even for doses exceeding 1019d+/cm2. Deuterium diffusion coefficients are estimated for silicon under irradiation conditions.
Generation of a Monoclonal Antibody Agonist to Toll-Like Receptor 4 (2005)

Toll-Like Receptor 4 (TLR4) has recently been identified as the lipopolysaccharide (LPS) receptor. Upon stimulation of TLR4 with LPS, a Th1 type cytokine response is observed. This immune modulation is thought to have a potential benefit in anti-tumor therapy. We have generated a TLR4 antibody agonist (5D24.D4) that mimics the action of the natural ligand. 5D24.D4 and LPS stimulation of TLR4 leads to a similar response, including IL-8 secretion, activation of NF-kB-mediated transcription, and the induced expression of an overlapping set of target genes. 5D24.D4 may be beneficial as an adjuvant anti-tumor therapy.
Predicting coiled coils by use of pairwise residue correlations. (1995)

A method is presented that predicts coiled-coil domains in protein sequences by using pairwise residue correlations obtained from a (two-stranded) coiled-coil database of 58,217 amino acid residues. A program called PAIRCOIL implements this method and is significantly better than existing methods at distinguishing coiled coils from alpha-helices that are not coiled coils. The database of pairwise residue correlations suggests structural features that stabilize or destabilize coiled coils.
An optimized two-step camera calibration method (2002)

An optimized two-step camera calibration algorithm is developed. The proposed method starts with the well known linear calibration which approximates the transformation as a 3/spl times/4 matrix. Based on the results of the linear calibration and the camera model we construct the 4/spl times/4 homogeneous transformation matrix. Quaternion algebra is used to extract the optimum rotation matrix and this optimization is later extended to the other calibration parameters. Our calibration method includes nonlinear optimization which takes into consideration lens distortions. The convergence rate of the nonlinear optimization is accelerated by three more objective functions we introduced. To assess the accuracy of our proposed quaternion method, Euclidean norm of the error matrix between the original and computed homogeneous transformation matrices is calculated and compared to those of the existing methods. Simulations show that the quaternion method yields more accurate results both before and after the nonlinear optimization.
Multimodal recognition of personality traits in social interactions (2008)

This paper targets the automatic detection of personality traits in a meeting environment by means of audio and visual features; information about the relational context is captured by means of acoustic features designed to that purpose. Two personality traits are considered: Extraversion (from the Big Five) and the Locus of Control. The classification task is applied to thin slices of behaviour, in the form of 1-minute sequences. SVM were used to test the performances of several training and testing instance setups, including a restricted set of audio features obtained through feature selection. The outcomes improve considerably over existing results, provide evidence about the feasibility of the multimodal analysis of personality, the role of social context, and pave the way to further studies addressing different features setups and/or targeting different personality traits.
Anti‐inflammatory activity of cationic lipids (1997)

1. The effect of liposome phospholipid composition has been assumed to be relatively unimportant because of the presumed inert nature of phospholipids. 2. We have previously shown that cationic liposome formulations used for gene therapy inhibit, through their cationic component, the synthesis by activated macrophages of the pro-inflammatory mediators nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha). 3. In this study, we have evaluated the ability of different cationic lipids to reduce footpad inflammation induced by carrageenan and by sheep red blood cell challenge. 4. Parenteral (i.p. or s.c) or local injection of the positively charged lipids dimethyldioctadecylammomium bromide (DDAB), dioleyoltrimethylammonium propane (DOTAP), dimyristoyltrimethylammonium propane (DMTAP) or dimethylaminoethanecarbamoyl cholesterol (DC-Chol) significantly reduced the inflammation observed in both models in a dose-dependent manner (maximum inhibition: 70-95%). 5. Cationic lipids associated with dioleyol- or dipalmitoyl-phosphatidylethanolamine retained their anti-inflammatory activity while cationic lipids associated with dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylglycerol (DMPG) showed no anti-inflammatory activity, indicating that the release of cationic lipids into the macrophage cytoplasm is a necessary step for anti-inflammatory activity. The anti-inflammatory activity of cationic lipids was abrogated by the addition of dipalmitoylphosphatidylethanolamine-poly(ethylene)glycol-2000 (DPPE-PEG2000) which blocks the interaction of cationic lipids with macrophages. 6. Because of the significant role of protein kinase C (PKC) in the inflammatory process we have determined whether the cationic lipids used in this study inhibit PKC activity. The cationic lipids significantly inhibited the activity of PKC but not the activity of a non-related protein kinase, PKA. The synthesis of interleukin-6 (IL-6), which is not dependent on PKC activity for its induction in macrophages, was not modified in vitro or in situ by cationic lipids. The synthesis of NO and TNF-alpha in macrophages, both of which are PKC-dependent, was downregulated by cationic lipids. 7. These results demonstrate that cationic lipids can be considered as novel anti-inflammatory agents. The downregulation of pro-inflammatory mediators through interaction of cationic lipids with the PKC pathway may explain this anti-inflammatory activity. Furthermore, since cationic lipids have intrinsic anti-inflammatory activity, cationic liposomes should be used with caution to deliver nucleic acids for gene therapy in vivo.
Prediction of protein subcellular localization (2006)

Because the protein's function is usually related to its subcellular localization, the ability to predict subcellular localization directly from protein sequences will be useful for inferring protein functions. Recent years have seen a surging interest in the development of novel computational tools to predict subcellular localization. At present, these approaches, based on a wide range of algorithms, have achieved varying degrees of success for specific organisms and for certain localization categories. A number of authors have noticed that sequence similarity is useful in predicting subcellular localization. For example, Nair and Rost (Protein Sci 2002;11:2836-2847) have carried out extensive analysis of the relation between sequence similarity and identity in subcellular localization, and have found a close relationship between them above a certain similarity threshold. However, many existing benchmark data sets used for the prediction accuracy assessment contain highly homologous sequences-some data sets comprising sequences up to 80-90% sequence identity. Using these benchmark test data will surely lead to overestimation of the performance of the methods considered. Here, we develop an approach based on a two-level support vector machine (SVM) system: the first level comprises a number of SVM classifiers, each based on a specific type of feature vectors derived from sequences; the second level SVM classifier functions as the jury machine to generate the probability distribution of decisions for possible localizations. We compare our approach with a global sequence alignment approach and other existing approaches for two benchmark data sets-one comprising prokaryotic sequences and the other eukaryotic sequences. Furthermore, we carried out all-against-all sequence alignment for several data sets to investigate the relationship between sequence homology and subcellular localization. Our results, which are consistent with previous studies, indicate that the homology search approach performs well down to 30% sequence identity, although its performance deteriorates considerably for sequences sharing lower sequence identity. A data set of high homology levels will undoubtedly lead to biased assessment of the performances of the predictive approaches-especially those relying on homology search or sequence annotations. Our two-level classification system based on SVM does not rely on homology search; therefore, its performance remains relatively unaffected by sequence homology. When compared with other approaches, our approach performed significantly better. Furthermore, we also develop a practical hybrid method, which combines the two-level SVM classifier and the homology search method, as a general tool for the sequence annotation of subcellular localization.
Relationship between thyroid hormone transport and neutral amino acid transport in JAR human choriocarcinoma cells (1994)

The relationship between the transport of the thyroid hormone T3 and the transport of neutral amino acids was investigated in JAR human placental choriocarcinoma cells. The uptake of leucine, mediated by the amino acid transport system L, was inhibited by T3 and T4, and the nature of inhibition was competitive. Uptake of T3 into the cells was predominantly Na+ independent, and so was that of leucine. However, although an acidic extracellular pH stimulated leucine uptake, the uptake of T3 remained unaffected. In addition, leucine failed to inhibit T3 uptake. The aromatic amino acids phenylalanine and tryptophan were found to inhibit the uptake of T3, but these two amino acids were transported into the cells predominantly via system L. The amino acid transport system T, which is specific for aromatic amino acids, was not detectable in these cells. Treatment of the cells with the calmodulin antagonist CGS 9343 B stimulated the uptake of leucine and tryptophan, but inhibited the uptake of T3. Kinetic analysis of T3 uptake revealed the presence of a single saturable system for this hormone in these cells, and the Michaelis-Menten constant for this system was 0.77 +/- 0.06 microM. Metabolic poisons that interfere with the cellular generation of ATP had no effect on the uptake of T3. It is concluded that in placental choriocarcinoma cells, 1) T3 and T4 are high affinity competitive inhibitors of the amino acid transport system L, 2) uptake of T3 occurs via a specific Na(+)-independent, energy-independent, and saturable mechanism that is unrelated to the amino acid transport systems L and T, 3) the aromatic amino acids phenylalanine and tryptophan interact, although weakly, with the T3 uptake system, and 4) calmodulin-dependent processes participate in the regulation of the T3 uptake system.
Molecular Genetic Analysis of an Endotoxin Nonresponder Mutant Cell Line (2001)

Somatic cell mutagenesis is a powerful tool for characterizing receptor systems. We reported previously two complementation groups of mutant cell lines derived from CD14-transfected Chinese hamster ovary--K1 fibroblasts defective in responses to bacterial endotoxin. Both classes of mutants expressed a normal gene product for Toll-like receptor (TLR)4, and fully responded to stimulation by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 beta. We identified the lesion in one of the complementation groups in the gene for MD-2, a putative TLR4 coreceptor. The nonresponder phenotype of this mutant was reversed by transfection with MD-2. Cloning of MD-2 from the nonresponder cell line revealed a point mutation in a highly conserved region resulting in a C95Y amino acid exchange. Both forms of MD-2 colocalized with TLR4 on the cell surface after transfection, but only the wild-type cDNA reverted the lipopolysaccharide (LPS) nonresponder phenotype. Furthermore, soluble MD-2, but not soluble MD-2(C95Y), functioned to enable LPS responses in cells that expressed TLR4. Thus, MD-2 is a required component of the LPS signaling complex and can function as a soluble receptor for cells that do not otherwise express it. We hypothesize that MD-2 conformationally affects the extracellular domain of TLR4, perhaps resulting in a change in affinity for LPS or functioning as a portion of the true ligand for TLR4.
Gene Targeting of a Plasmid-Borne Sequence to a Double-Strand DNA Break in Drosophila melanogaster (1996)

We report an efficient and specific gene targeting method for transforming the germ line of Drosophila melanogaster. The targeting occurs during the repair of a double-strand DNA break that is induced at the white locus by the excision of a P transposable element. The break is repaired when homologous sequence is copied from a plasmid injected into the Drosophila embryo. The procedure efficiently integrates DNA into the targeted locus of the Drosophila genome. Heterologous sequence of up to 13 kbp in length can be inserted, permitting the intergration of entire genes into a common genomic site for further study.
Potential role of the growth hormone secretagogues in clinical practice (2007)

Growth hormone secretagogues (GHS) are synthetic molecules that promote secretion of growth hormone by activation of the GHS receptor (GHSR). Ghrelin is the endogenous ligand of this receptor, which was isolated from gastric mucosa. This peptide is widely expressed in different tissues and has a broad spectrum of effects. This review summarises: i) structure and pharmacokinetics of the more important GHS; ii) structure, distribution and subcellular pathways of ghrelin; iii) structure, distribution and signal transduction of the GHS receptors; and iv) effects of GHS in different tissues and organs and the potential therapeutic role of ghrelin and GHS. There are increasing evidences that GHS and ghrelin have a wide range of actions both in physiological and pathological conditions. Potential therapeutic applications of these GHS are constantly increasing and clinical trials are needed to establish usefulness of these compounds.
PE859, a Novel Tau Aggregation Inhibitor, Reduces Aggregated Tau and Prevents Onset and Progression of Neural Dysfunction In Vivo (2015)

In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.