gebhart/patrepeval huggingface dataset:
Peptides as drug candidates against Alzheimer's disease (2002)

Abstract Alzheimer's disease (AD) is the most common cause of dementia among people aged 65 and older. In fact, nearly 50% of all people aged 85 and older are thought to have AD. It is thus of high importance to develop therapies to combat the disease and alleviate the devastating outcome. The drugs currently available treat one of the disease symptoms, the decline in acetylcholine, by way of inhibiting the acetylcholinesterase pathway that leads to acetylcholine breakdown. However, this apparently slows the disease symptomology only for a limited time period. Here, neuropeptide/peptide involvement and potential therapy in AD will be approached at several different levels including (1) neuropeptides and AD; (2) amyloid precursor protein processing and toxic beta amyloid (A‐beta) accumulation; (3) peptide vaccination against toxic A‐beta aggregation; (4) peptides in the inhibition of tau phosphorylation and the formation of toxic neurofibrillary tangles; and most emphasis will be placed on (5) neuroprotective peptides, from vasoactive intestinal peptide (VIP) to activity‐dependent neuroprotective protein (ADNP), NAP and activity‐dependent neuroprotective factor (ADNF). Previous studies facilitated the characterization of a lead peptide termed NAP (Asn‐Ala‐Pro‐Val‐Ser‐Ile‐Pro‐Gln, single letter code, NAPVSIPQ). Preclinical experiments show that NAP protects neurons against numerous toxins and cellular stresses including the AD neurotoxin, excitotoxicity, the toxic envelope protein of HIV, electrical blockade, oxidative stress, dopamine toxicity, decreased glutathione, and tumor necrosis factor‐associated toxicity. NAP also has neuroprotective activity in a variety of animal models including the learning‐deficient apolipoprotein E knockout mice (a model related to AD), mouse paradigms of traumatic head injury (risk factor for AD) and fetal alcohol syndrome (oxidative stress), and rat models of cholinotoxicity and stroke. NAP has a short structure, is active at unprecedented low concentrations (femtomolar), is water soluble, bioavailable, easily delivered via intranasal inhalation, and is unusually stable. No NAP toxicity has been observed to date. Thus, NAP is poised to be developed as a novel Alzheimer's disease therapeutic. Drug Dev. Res. 56:475–481 2002. © 2002 Wiley‐Liss, Inc.
Nonlinear Learning using Local Coordinate Coding (2009)

This paper introduces a new method for semi-supervised learning on high dimensional nonlinear manifolds, which includes a phase of unsupervised basis learning and a phase of supervised function learning. The learned bases provide a set of anchor points to form a local coordinate system, such that each data point x on the manifold can be locally approximated by a linear combination of its nearby anchor points, and the linear weights become its local coordinate coding. We show that a high dimensional nonlinear function can be approximated by a global linear function with respect to this coding scheme, and the approximation quality is ensured by the locality of such coding. The method turns a difficult nonlinear learning problem into a simple global linear learning problem, which overcomes some drawbacks of traditional local learning methods. 1
Predicting future locations with hidden Markov models (2012)

The analysis of human location histories is currently getting an increasing attention, due to the widespread usage of geopositioning technologies such as the GPS, and also of online location-based services that allow users to share this information. Tasks such as the prediction of human movement can be addressed through the usage of these data, in turn offering support for more advanced applications, such as adaptive mobile services with proactive context-based functions. This paper presents an hybrid method for predicting human mobility on the basis of Hidden Markov Models (HMMs). The proposed approach clusters location histories according to their characteristics, and latter trains an HMM for each cluster. The usage of HMMs allows us to account with location characteristics as unobservable parameters, and also to account with the effects of each individual's previous actions. We report on a series of experiments with a real-world location history dataset from the GeoLife project, showing that a prediction accuracy of 13.85% can be achieved when considering regions of roughly 1280 squared meters.
Insight of Host Immune Evasion Mediated by Two Variants of Group A Streptococcus Mac Protein (2004)

Group A Streptococcus has evolved numerous mechanisms to evade the host immune system to survive, disseminate, and cause disease. Recently a secreted protein named Mac-1 was identified and shown to enhance survival of the pathogen. A new variant of Mac-1 (designated Mac-2) also was recently described and shown to differ from Mac-1 by approximately 50% amino acid sequence divergence in the middle one-third of the molecule. To gain new information about the role of Mac-1 and Mac-2 in host-pathogen interactions, solution binding experiments were performed using surface plasmon resonance and purified Mac proteins. Mac-1 bound the same lower hinge region of human IgG as Fc receptors with 2.5 microM affinity, which lead to proteolytic cleavage of the antibody. Similar Km (6.8-18.9 microM) and kcat (0.02-0.13 s(-1)) values of the Mac-1 endopeptidase activity were obtained for IgG1, IgG2, IgG3, and IgG4. Mac-2 variant, in contrast, bound human IgG poorly (KD = 16 mM) and had weak endopeptidase activity against IgG. Instead, Mac-2 bound FcgammaRII and FcgammaRIII with 5 and 75 microM affinity, respectively. This binding competitively blocked IgG from recognition by Fc receptors. Taken together, Mac proteins block immunoglobulin recognition by Fc receptors and degrade immunoglobulins, thereby enhancing survival of the pathogen through the inhibition of phagocytosis, endocytosis of IgG-opsonized particles, and antibody-dependent cell-mediated cytotoxicity. Consequently, these proteins may be potential therapeutic targets.
Preparation of purified erythropoietin by high performance liquid chromatography. (1984)

Highly purified erythropoietin was not available in quantities needed to carry out planned investigations and, therefore, the use of high performance liquid chromatography was explored. This technique permits the separation of proteins with high efficiency and resolution. Three types of chromatography were used. Size exclusion or gel permeation, reversed phase, and ion exchange columns were utilized with different solvent systems. The chromatographic fractions were assayed either by an exhypoxic polycythemic mouse assay or by the fetal liver cell assay. In addition, selected fractions were tested for their capability to stimulate CFU-E and BFU-E colony formation in methyl cellulose. The results of the techniques of size exclusion and ion exchange chromatography were found to be rapid and reproducible. Although reversed phase chromatography gave excellent resolution, the results were somewhat variable. Using different chromatographic combinations, erythropoietin with a specific bioactivity in the range of 50,000 u/mg protein was isolated. Although the erythropoietin gene has now been cloned and the hormone purified by utilizing monoclonal antibodies, high performance liquid chromatography may be useful in the removal of unwanted contaminants, as a tool in chemical characterization, and as a possible method for the hormone's identification and measurement in clinical laboratories.
Increasing rates of depression (1989)

Several recent, large epidemiologic and family studies suggest important temporal changes in the rates of major depression: an increase in the rates in the cohorts born after World War II; a decrease in the age of onset with an increase in the late teenaged and early adult years; an increase between 1960 and 1975 in the rates of depression for all ages; a persistent gender effect, with the risk of depression consistently two to three times higher among women than men across all adult ages; a persistent family effect, with the risk about two to three times higher in first-degree relatives as compared with controls; and the suggestion of a narrowing of the differential risk to men and women due to a greater increase in risk of depression among young men. These trends, drawn from studies using comparable methods and modern diagnostic criteria, are evident in the United States, Sweden, Germany, Canada, and New Zealand, but not in comparable studies conducted in Korea and Puerto Rico and of MexicanAmericans living in the United States. These cohort changes cannot be fully attributed to artifacts of reporting, recall, mortality, or labeling and have implications for understanding the etiology of depression and for clinical practice. (<i>JAMA</i>. 1989;261:2229-2235)
Matrix Profile XIV (2019)

The discovery of conserved (repeated) patterns in time series is arguably the most important primitive in time series data mining. Called time series motifs, these primitive patterns are useful in their own right, and are also used as inputs into classification, clustering, segmentation, visualization, and anomaly detection algorithms. Recently the Matrix Profile has emerged as a promising representation to allow the efficient exact computation of the top-k motifs in a time series. State-of-the-art algorithms for computing the Matrix Profile are fast enough for many tasks. However, in a handful of domains, including astronomy and seismology, there is an insatiable appetite to consider ever larger datasets. In this work we show that with several novel insights we can push the motif discovery envelope using a novel scalable framework in conjunction with a deployment to commercial GPU clusters in the cloud. We demonstrate the utility of our ideas with detailed case studies in seismology, demonstrating that the efficiency of our algorithm allows us to exhaustively consider datasets that are currently only approximately searchable, allowing us to find subtle precursor earthquakes that had previously escaped attention, and other novel seismic regularities.
Evidence for phosphorylation of yeast phosphofructokinase (1988)

Radioactively labelled material from yeast cells grown in the presence of [32P]phosphate was specifically recognized by antibodies raised against yeast phosphofructokinase. Purified yeast phosphofructokinase was phosphorylated in a cyclic AMP-independent manner by a protein kinase enriched from yeast extracts. This phosphorylation occurred specifically on the beta-subunit, and 0.56 mol of phosphate/mol of subunit was incorporated. The results indicate the phosphorylation of yeast phosphofructokinase both in vivo and in vitro. Phosphofructokinase phosphorylated in vitro was more stable against proteolytic degradation compared to the non-phosphorylated enzyme.
Microphase separation in RIM polyureas as studied by solid-state NMR (1998)

The microphase separation (MPS) in polyureas based on methylene diphenyl diisocyanate (MDI) hard segment, diethyltoluenediamine chain extender, and amino-terminated polypropylene glycol soft segment prepared by reaction injection molding (RIM) was studied by advanced solid-state NMR spectroscopy. Incomplete microphase separation leads to the presence of mobilized hard segments dispersed in the soft segment domains as well as immobilized soft segments residing in the hard domains. This is detected by 1H-NMR spectra recorded under spinning at the magic angle (MAS) as well as two-dimensional wide-line separation (WISE) NMR spectra. The sizes of the various domains as well as the interfaces between them are quantified by spin diffusion measurements. In this way the impact of annealing, method of polymerization, and hard segment content on MPS is studied. Whereas annealing at temperatures up to 170°C results in improving the MPS, major changes are observed after annealing at higher temperatures (190°C), where the system changes from “soft-in-hard” to “hard-in-soft” behavior. The MPS decreases with increasing hard segment content. The highest MPS is observed for solution polymerized samples. The various NMR experiments clearly reveal the nonequilibrium nature of RIM systems. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36: 693–703, 1998
Pulse Pressure: A Predictor of Cardiovascular Mortality Among Young Normotensive Subjects (2000)

Wide pulse pressure has been associated with increased cardiovascular disease events among hypertensive subjects. To test the hypothesis that this association also exists among normotensive subjects, data from the first National Health and Nutritional Examination Survey and the 1992 Epidemiological Follow-up Study were analyzed. The study group included 7346 participants, aged 25-74 years, with baseline blood pressure levels <140/90 mmHg and without a history of hypertension. Deaths from cardiovascular disease and all other causes were determined. At entry, mean age and blood pressure level were 43.4 years and 118/76 mmHg. During an average follow-up period of 17.4 years, there were 1443 (19.6%) deaths, 557 of them ascribed to cardiovascular disease. Age-race-adjusted cardiovascular mortality was significantly higher for those in the highest quartile of pulse pressure (> or = 50 mmHg). However, after stratification into age <55 years and > or = 55 years, and controlling for other cardiovascular risk factors, increased pulse pressure was associated with cardiovascular mortality only in younger men and women. In these subjects, men and women with pulse pressures > or = 48, and > or = 46 mmHg, respectively, had a relative risk (95% confidence in terval) of 2.35 (1.21-4.38) and 2.90 (1.34-4.98) for cardiovascular mortality with those with pulse pressures of less than 36 and 34 mmHg, respectively (p < 0.05) as reference. While systolic blood pressure by itself was a weaker predictor of cardiovascular mortality than pulse pressure, diastolic and mean arterial pressure were not predictive at all. No measure of blood pressure was related to mortality in those aged > or = 55 years. In conclusion, among young subjects, but not older normotensive persons, at very low risk of cardiovascular disease, a wide pulse pressure is associated with increased cardiovascular mortality.
Nanoscale Glassification of Gold Substrates for Surface Plasmon Resonance Analysis of Protein Toxins with Supported Lipid Membranes (2005)

Surface plasmon resonance (SPR) spectroscopy, a powerful tool for biosensing and protein interaction analysis, is currently confined to gold substrates and the relevant surface chemistries involving dextran and functional thiols. Drawbacks of using self-assembled monolayers (SAMs) for SPR-related surface modification include limited stability, pinhole defects, bioincompatibility, and nonspecific protein adsorption. Here we report the development of stable nanometer-scale glass (silicate) layers on gold substrates for SPR analysis of protein toxins. The nanoscale silicate layers were built up with layer-by-layer deposition of poly(allylamine hydrochloride) and sodium silicate, followed by calcination at high temperature. The resulting silicate films have a thickness ranging from 2 to 15 nm and demonstrate outstanding stability in flow cell conditions. The use of these surfaces as a platform to construct supported bilayer membranes (SBMs) is demonstrated, and improved performance against protein adsorption on SBM-coated surfaces is quantified by SPR measurements. SBMs can be formed reproducibly on the silicate surface via vesicle fusion and quantitatively removed using injection of 5% Triton X-100 solution, generating a fresh surface for each test. Membrane properties such as lateral diffusion of the SBMs on the silicate films are characterized with photobleaching methods. Studies of protein binding with biotin/avidin and ganglioside/cholera toxin systems show detection limits lower than 1 microg/mL (i.e., nanomolar range), and the response reproducibility is better than 7% RSD. The method reported here allows many assay techniques developed for glass surfaces to be transferred to label-free SPR analysis without the need for adaptation of protocols and time-consuming synthetic development of thiol-based materials and opens new avenues for developing novel bioanalytical technologies for protein analysis.
Pipecolic Acid, an Endogenous Mediator of Defense Amplification and Priming, Is a Critical Regulator of Inducible Plant Immunity (2012)

Metabolic signals orchestrate plant defenses against microbial pathogen invasion. Here, we report the identification of the non-protein amino acid pipecolic acid (Pip), a common Lys catabolite in plants and animals, as a critical regulator of inducible plant immunity. Following pathogen recognition, Pip accumulates in inoculated Arabidopsis thaliana leaves, in leaves distal from the site of inoculation, and, most specifically, in petiole exudates from inoculated leaves. Defects of mutants in AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) in systemic acquired resistance (SAR) and in basal, specific, and β-aminobutyric acid-induced resistance to bacterial infection are associated with a lack of Pip production. Exogenous Pip complements these resistance defects and increases pathogen resistance of wild-type plants. We conclude that Pip accumulation is critical for SAR and local resistance to bacterial pathogens. Our data indicate that biologically induced SAR conditions plants to more effectively synthesize the phytoalexin camalexin, Pip, and salicylic acid and primes plants for early defense gene expression. Biological priming is absent in the pipecolate-deficient ald1 mutants. Exogenous pipecolate induces SAR-related defense priming and partly restores priming responses in ald1. We conclude that Pip orchestrates defense amplification, positive regulation of salicylic acid biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR.
Mature‐stem expression of a silencing‐resistant sucrose isomerase gene drives isomaltulose accumulation to high levels in sugarcane (2013)

Isomaltulose (IM) is a natural isomer of sucrose. It is widely approved as a food with properties including slower digestion, lower glycaemic index and low cariogenicity, which can benefit consumers. Availability is currently limited by the cost of fermentative conversion from sucrose. Transgenic sugarcane plants with developmentally-controlled expression of a silencing-resistant gene encoding a vacuole-targeted IM synthase were tested under field conditions typical of commercial sugarcane cultivation. High yields of IM were obtained, up to 483 mm or 81% of total sugars in whole-cane juice from plants aged 13 months. Using promoters from sugarcane to drive expression preferentially in the sugarcane stem, IM levels were consistent between stalks and stools within a transgenic line and across consecutive vegetative field generations of tested high-isomer lines. Germination and early growth of plants from setts were unaffected by IM accumulation, up to the tested level around 500 mm in flanking stem internodes. These are the highest yields ever achieved of value-added materials through plant metabolic engineering. The sugarcane stem promoters are promising for strategies to achieve even higher IM levels and for other applications in sugarcane molecular improvement. Silencing-resistant transgenes are critical to deliver the potential of these promoters in practical sugarcane improvement. At the IM levels now achieved in field-grown sugarcane, direct production of IM in plants is feasible at a cost approaching that of sucrose, which should make the benefits of IM affordable on a much wider scale.
Bidirectional Database Storage and SQL Query Exploiting RRAM-Based Process-in-Memory Structure (2018)

With the coming of the “Big Data” era, a high-energy-efficiency database is demanded for the Internet of things (IoT) application scenarios. The emerging Resistive Random Access Memory (RRAM) has been considered as an energy-efficient replacement of DRAM for next-generation main memory. In this article, we propose an RRAM-based SQL query unit with process-in-memory (PIM) characteristics. A bidirectional storage structure for a database in RRAM crossbar array is proposed that avoids redundant data transfer to cache and reduces cache miss rate compared with the storage method in DRAM for an in-memory database. The proposed RRAM-based SQL query unit can support a representative subset of SQL queries in memory and thus can further reduce the data transfer cost. The corresponding query optimization method is proposed to fully utilize the PIM characteristics. Simulation results show that the energy efficiency of the proposed RRAM-based SQL query unit is increased by 4 to 6 orders of magnitudes compared with the traditional architecture.
Crossover and Self-Controlled Designs in Clinical Research (1984)

Crossover studies (clinical trials in which each patient receives two or more treatments in sequence) and self-controlled studies (in which each patient serves as his or her own control) can produce results that are statistically and clinically valid with far fewer patients than would otherwise be required. We investigated the use of the crossover design in the 13 crossover studies that appeared in the Journal during 1978 and 1979. We considered the following important features of design and analysis as they applied to these studies: the method by which patients were assigned to initial treatment (only 7 of 13 studies used random assignment); the determination of when to switch treatments (10 of the 13 used a time-dependent rule, and 3 a less appropriate disease-state-dependent rule); blinding of the crossover point (in only 3 of the 13 studies was the crossover point concealed, but in 4 of the remaining 10 concealment was impossible); assessment of the effects of the order of treatments (included in only 1 of the 13 studies); and the use of at least minimally acceptable statistical analysis (11 of the 13 studies had such an analysis). We also report briefly on 28 additional studies of a single treatment each, in which each patient served as his or her own control before or after treatment or both. The scientific issues were much the same as in crossover studies except that self-controlled comparisons of treatments tended to be less precisely designed and conducted and to focus on clinical problems and patient groups that are especially difficult to study.
Localization of factor VIII-procoagulant antigen: an immunohistological survey of the human body using monoclonal antibodies (1986)

Various organs, including liver, spleen, heart, lung, kidney, intestines, lymph nodes, pancreas, bone marrow, and thymus, were investigated for the presence of factor VIII-procoagulant antigen (VIIICAg) and factor VIII-related antigen (VIIIRAg), using a panel of monoclonal antibodies directed to factor VIII-von Willebrand factor in combination with a sensitive immunoperoxidase staining technique. In addition to hepatic sinusoidal endothelial cells, the presence of VIIICAg was demonstrated in mononuclear cells sporadically present in lymph nodes, in the alveolar septa of lung, and in the red pulp of spleen. The identity of these mononuclear cells could not be unequivocally determined. Based on morphological criteria, however, it is tentatively concluded that these cells are nonlymphoid and belong to the mononuclear phagocyte system. The presence of VIII-RAg was confined to vascular endothelial cells, hepatic sinusoidal endothelial cells, cells lining the venous sinuses of the red pulp of the spleen, cells lining renal glomeruli and lung capillaries, platelets, and megakaryocytes.