gebhart/patrepeval huggingface dataset:
Virus Replication and High-Titered Interferon Production in Human Leukocyte Cultures Inoculated with Newcastle Disease Virus (1966)

Wheelock, Frederick E. (Western Reserve University, Cleveland, Ohio). Virus replication and high-titered interferon production in human leukocyte cultures inoculated with Newcastle disease virus. J. Bacteriol. 92:1415-1421. 1966.-High titers of interferon (20,480 culture-protecting units per ml) are produced in freshly prepared human leukocyte cultures inoculated with a Newcastle disease virus (NDV)-cell multiplicity of 1:1. NDV replicates to low titers in these cultures. Incubation of leukocytes at 37 C for 24 hr prior to inoculation of NDV results in almost complete loss of detectable interferon production, but virus replicates to higher titers than in the freshly prepared cultures. In contrast, no diminution of interferon production in response to phytohemagglutinin (PHA) occurs on 24 hr of incubation of cultures prior to addition of PHA. Experiments with cultures of predominantly pure cell fractions of peripheral blood indicate that the lymphocyte fraction produces interferon in response to either NDV or PHA, and that polymorphonuclear leukocytes produce no interferon in response to these agents. These studies suggest a hitherto unsuspected ability of human lymphocytes to produce high titers of interferon in vivo.
On family-based genome-wide association studies with large pedigrees: observations and recommendations (2014)

Family based association studies are employed less often than case-control designs in the search for disease-predisposing genes. The optimal statistical genetic approach for complex pedigrees is unclear when evaluating both common and rare variants. We examined the empirical power and type I error rates of 2 common approaches, the measured genotype approach and family-based association testing, through simulations from a set of multigenerational pedigrees. Overall, these results suggest that much larger sample sizes will be required for family-based studies and that power was better using MGA compared to FBAT. Taking into account computational time and potential bias, a 2-step strategy is recommended with FBAT followed by MGA.
A new stopping sight distance model for use in highway geometric design (1998)

Stopping sight distance is an important design parameter in that it defines the minimum sight distance that must be provided at all points along the highway. Thus, it influences geometric design values, construction costs, and highway safety. Stopping sight distance is defined as the sum of two components - brake reaction distance and the braking distance. The basic model for calculating stopping sight distances was formalized in 1940, and the model's parameters have been altered to compensate for changes in eye height, object height, and driver behavior over the past 50 years. Recent studies, however, question whether the model's parameters and assumptions represent real-world conditions. This paper presents a new model for determining stopping sight distance requirements for geometric design of highways. The new model is based on parameters describing driver and vehicle capabilities that can be validated with field data and defended as safe driving behavior. More than 50 drivers, 3,000 braking maneuvers, 1,000 driver eye heights, and 1,000 accident narratives were used in developing the recommended parameter values for the new model. The recommended values are attainable by most drivers, vehicles, and roadways. The new model results in stopping sight distances, sag vertical curve lengths, and lateral clearances that are between the current minimum and desirable requirements, and crest vertical curve lengths that are shorter than current minimum requirements.
Variational Autoencoder for Deep Learning of Images, Labels and Captions (2016)

A novel variational autoencoder is developed to model images, as well as associated labels or captions. The Deep Generative Deconvolutional Network (DGDN) is used as a decoder of the latent image features, and a deep Convolutional Neural Network (CNN) is used as an image encoder; the CNN is used to approximate a distribution for the latent DGDN features/code. The latent code is also linked to generative models for labels (Bayesian support vector machine) or captions (recurrent neural network). When predicting a label/caption for a new image at test, averaging is performed across the distribution of latent codes; this is computationally efficient as a consequence of the learned CNN-based encoder. Since the framework is capable of modeling the image in the presence/absence of associated labels/captions, a new semi-supervised setting is manifested for CNN learning with images; the framework even allows unsupervised CNN learning, based on images alone.
The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between β-amyloid production and tau phosphorylation in Alzheimer disease (2006)

We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P < 0.05). Logistic regression analysis with age, sex and apolipoprotein E (APOE)-epsilon4 dose supported genetic risk of 17 markers, of which eight markers were linked to the SAMSN1, PRSS7, NCAM2, RUNX1, DYRK1A and KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.
Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viableBifidobacterium animalison the intestinal microflora during the first 4 months of life (2005)

Adding prebiotics or probiotics to infant formula to improve the intestinal flora of formula-fed infants is considered to be a major innovation. Several companies have brought relevant formulations onto the market. However, comparative data on the effects of pre- and probiotics on the intestinal microflora of infants are not available. The present study aimed to compare the effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the composition and metabolic activity of the intestinal microflora. Before birth, infants were randomised and double blindly allocated to one of three formulas. The prebiotic (GOS/FOS) group (n 19) received regular infant formula supplemented with a mixture of galacto-oligosaccharides and fructo-oligosaccharides (6 g/l). The probiotic (Bb-12) group (n 19) received the same formula supplemented with 6.0x10(10) viable cells of B. animalis per litre. The standard group (n 19) received non-supplemented regular formula. A group of sixty-three breast-fed infants was included as a reference group. Faecal samples were taken at postnatal day 5 and 10, and week 4, 8, 12 and 16. Compared with the groups fed Bb-12 and standard formula, the GOS/FOS formula group showed higher faecal acetate ratio (69.7 % (sem 2.7), 69.9 % (sem 3.9) and 82.2 % (sem 5.3); P<0.05) and lactate concentration (11.3 (sem 7.9), 3.1 (sem 2.3) and 34.7 (sem 10.7) mmol/kg faeces) and lower pH (6.6 (sem 0.2), 7.1 (sem 0.2) and 5.6 (sem 0.2); P<0.05) at 16 weeks. Differences in percentage of bifidobacteria between the GOS/FOS (59.2 % (sem 7.7)), Bb-12 (52.7 % (sem 8.0)) and the standard (51.8 % (sem 6.4)) groups were not statistically significant at 16 weeks. Feeding infants GOS/FOS formula resulted in a similar effect on metabolic activity of the flora as in breast-fed infants. In the Bb-12 group, composition and metabolic activity of the flora were more similar to those of the standard group.
A bifunctional fusion protein containing Fc-binding fragment B of staphylococcal protein A amino-terminal to antidigoxin single-chain Fv (1990)

A bifunctional molecule was genetically engineered which contained an amino-terminal effector domain that bound immunoglobulin Fc (fragment B of staphylococcal protein A) and a carboxyl-terminal domain that bound digoxin [a single-chain Fv (sFv)]. Effector and sFv binding properties were virtually identical with those of the parent molecules, despite the proximity of the FB to the sFv combining site. This finding is unprecedented since in all molecules of the natural immunoglobulin superfamily, the antigen binding domain is amino terminal to the effector domain. The FB-sFv sequence was encoded in a single synthetic gene and expressed as a 33,106 molecular weight protein in Escherichia coli. After purification, renaturation, and affinity isolation, yield of active fusion protein were 110 mg/L of fermented cells (18.5-g cell paste). Bifunctionality was confirmed by the ability of FB-sFv to cross-link IgG to digoxin-bovine serum albumin, as measured by plate assays and by Ouchterlony analysis. Analysis of the expressed fusion protein suggests that the sFv holds promise for the development of multifunctional, targetable single-chain proteins.
Resonant-energy-transfer-based biosensor for detection of multivalent proteins (1999)

We have developed a new fluorescence-based biosensor for sensitive detection of species involved in a multivslent interaction. The biosensor system utilizes specific interactions between proteins and cell surface receptors, which trigger a receptor aggregation process. Distance-dependent fluorescence self-quenching and resonant energy transfer mechanisms were coupled with a multivalent interaction to probe the receptor aggregation process, providing a sensitive and specific signal transduction method for such a binding event. The fluorescence change induced by the aggregation process can be monitored by different instrument platforms, e.g. fluorimetry and flow cytometry. In this article, a sensitive detection of pentavalent cholera toxin which recognizes ganglioside GM1 has been demonstrated through the resonant energy transfer scheme, which can achieve a double color change simultaneously. A detection sensitivity as high as 10 pM has been achieved within a few minutes (c.a. 5 minutes). The simultaneous double color change (an increase of acceptor fluorescence and a decrease of donor fluorescence intensity) of two similar fluorescent probes provides particularly high detection reliability owing to the fact that they act as each other's internal reference. Any external perturbation such as environmental temperature change causes no significant change in signal generation. Besides the application for biological sensing, the method also provides a useful tool for investigation of kinetics and thermodynamics of a multivalent interaction. Keywords: Biosensor, Fluorescence resonant energy transfer, Multivalent interaction, Cholera Toxin, Ganglioside GM1, Signal Transduction
تهیه و ارزیابی نانوپارتیکلهای کایتوزان حاوی توکسوئید دیفتری بعنوان حاملی جدید جهت آزادسازی واکسن داخل بینی در موش سوری (2006)

هدف از این تحقیق ارزیابی امکان تهیه و کاربرد نانوپارتیکلهای کایتوزان و مشتق شیمیایی با پلی اتیلن گلایکول (PEG) بعنوان حاملهای نوین در آزاد سازی داخل بینی واکسنها می باشد. برای این منظور توکسوئید دیفتری بعنوان یک مدل آنتی ژنی انتخاب گردید. آنتی ژن دیفتری با استفاده از روش کراس لینک یونی در درون نانوپارتیکلهای کایتوزان و کایتوزان با PEG محبوس گردیدند. نانوپارتیکلهای حاوی توکسوئید دیفتری پس تهیه از نظر اندازه، بار الکتریکی سطحی، کارآیی احتباس و رهایش آنتی ژن فعال در محیط برون تن مورد ارزیابی قرار گرفتند. به منظور بررسی کارآیی نانوپارتیکلها بعنوان حامل مناسب برای واکسن از طریق داخل بینی به موشهای هوشیار تجویز گردیدند. نتایج نشان داد که نانوپارتیکلهای بدست آمده براساس شرایط فرمولاسیون و مشتق سازی کایتوزان با PEG دارای اندازه ذره ای متغییر بین nm 100-500 می باشند. این ذرات همچنین دارای بار الکتریکی سطحی مثبت (حدوداً mV 40) بودند. انجام مشتق سازی بر روی کایتوزان با PEG سبب کاهش بار الکتریکی سطحی نانوپارتیکل تا حدود mV 10 می گردد. این ذرات همچنین (بر اساس شرایط فرمولاسیون) دارای کارآیی احتباس بین 50-100% برای توکسوئید دیفتری می باشند. نتایج آزاد سازی در برون تن نشان دهنده آزادسازی دو فازی می باشد که شدت آزادسازی اولیه برای نانوپارتیکلهای تهیه شده از مشتق PEG کایتوزان کمتر از کایتوزان معمولی می باشد. تجویز داخل بینی این نانوپارتیکلها سبب تحریک و افزایش سطح ایمنی هومورال (سطح IgG) نسبت به نمونه محلول توکسوئید گردید. همچنین پاسخ ایمنی مخاطی (سطح IgA)، 70 روز پس از اولین دز تجویز شده، بطور معنی داری برای نانوپارتیکلهای حاوی توکسوئید دیفتری بالاتر از نمونه محلول توکسوئید دیفتری بود. نتیجه جالب بدست آمده این بود که سطح پاسخ ایمنی بدست آمده تحت تاثیر وزن مولکولی کایتوزان قرار ندارد اما انجام مشتق سازی کایتوزان با PEG بشدت پاسخهای ایمنی را متاثر می نماید. از اینرو بنظر می رسد که کایتوزان و مشتق PEG آن حامل مناسبی برای ایمنی زاسیون داخل بینی باشد.
RNAi functions in cultured mammalian neurons (2002)

In a wide range of organisms, double-stranded RNA triggers posttranscriptional gene silencing or RNA interference (RNAi). Small interfering RNAs, the 21-nt double-stranded RNA intermediates of this natural pathway, have became a powerful tool to knock down specific gene expression in mammalian cell lines and potentially will be useful for the analysis of loss-of-function phenotypes. In mammalian primary neuronal cultures, where genetic manipulations are especially difficult, RNAi might be developed into a highly efficacious tool to study the roles of specific genes in neuron development and functioning. Neurons, however, have been considered the most resistant to RNAi. We report here an application of RNAi to postmitotic primary neuronal cultures. Synthetic siRNA can be readily introduced into neurons and effectively inhibit the expression of endogenous and transfected genes.
Titins: Giant Proteins in Charge of Muscle Ultrastructure and Elasticity (1995)

In addition to thick and thin filaments, vertebrate striated muscle contains a third filament system formed by the giant protein titin. Single titin molecules extend from Z discs to M lines and are longer than 1 micrometer. The titin filament contributes to muscle assembly and resting tension, but more details are not known because of the large size of the protein. The complete complementary DNA sequence of human cardiac titin was determined. The 82-kilobase complementary DNA predicts a 3-megadalton protein composed of 244 copies of immunoglobulin and fibronectin type III (FN3) domains. The architecture of sequences in the A band region of titin suggests why thick filament structure is conserved among vertebrates. In the I band region, comparison of titin sequences from muscles of different passive tension identifies two elements that correlate with tissue stiffness. This suggests that titin may act as two springs in series. The differential expression of the springs provides a molecular explanation for the diversity of sarcomere length and resting tension in vertebrate striated muscles.
Nucleic Acid-Functionalized Pt Nanoparticles:  Catalytic Labels for the Amplified Electrochemical Detection of Biomolecules (2006)

Nucleic acid-functionalized Pt nanoparticles (Pt-NPs) act as catalytic labels for the amplified electrochemical detection of DNA hybridization and aptamer/protein recognition. Hybridization of the nucleic acid-modified Pt-NPs with a sensing nucleic acid/analyte DNA complex associated with an electrode enables the amperometric, amplified, detection of the DNA by the Pt NP electrocatalyzed reduction of H2O2 (sensitivity limit, 1 x 10(-11) M). Similarly, the association of aptamer-functionalized Pt- NPs to a thrombin aptamer/thrombin complex associated with an electrode allowed the amplified, electrocatalytic detection of thrombin with a sensitivity limit corresponding to 1 x 10(-9) M.
Specific sequestering agents for the actinides. 16. Synthesis and initial biological testing of polydentate oxohydroxypyridinecarboxylate ligands (1988)

Chemical and biological similarities of plutonium(IV) and iron(III) suggested that octadentate ligands containing hydroxamate or catecholate functional groups, which are found in microbial iron chelating agents (siderophores), would be effective and relatively selective complexing agents for actinide(IV) ions. However, their usefulness for in vivo chelation of actinide(IV) is limited, because catechol and hydroxamate are such weak acids that the potential for octadentate binding of actinide(IV) cannot be achieved at physiological pH. The structurally similar monoprotic and more acidic 1-hydroxy-2(1H)-pyridinone (1,2-HOPO) group was, therefore, incorporated into multidentate ligands. Treatment of 1,2-dihydro-1-hydroxy-2-oxopyridine-6-carboxylic acid (5) with phosgene in THF solution gives the active ester poly[1,2-dihydro-1,2-dioxopyridine-6-carboxylate], which upon treatment with excess anhydrous dimethylamine gave a 60% yield of N,N-dimethyl-1,2-dihydro-1-hydroxy-2-oxopyridine-6-carboxamide (6). A similarly reactive intermediate was prepared from 5 and an equimolar amount of phosgene in N,N-dimethylacetamide. Combined in situ with 1,3-propanediamine, benzylamine, spermine, spermidine, 1,3,5-tris(aminomethyl)benzene, or desferrioxamine B and excess triethylamine, the latter intermediate gave the corresponding amides in isolated yields ranging from 16% to 60%. The free ligands, their Zn(II) complexes, and the ferric complex of 3,4,3-LIHOPO were administered to mice [30 mumol/kg intraperitoneally 1 h after Pu(IV)-238 citrate, kill at 24 h]. Net Pu removal [Pu excretion (treated)-PU excretion (control)], expressed as percent of injected Pu, was as follows: Na salts and Zn(II) complexes, respectively, of 3-LIHOPO (54, 56), 3,4-LIHOPO (58, 60), 3,4,3-LIHOPO (73, 76); Na salts of MEHOPO (46), DFO-HOPO (78); Fe(III) complex of 3,4,3-LIHOPO (79). DFO-HOPO and 3,4,3-LIHOPO and its Zn(II) and Fe(III) complexes promoted significantly more Pu excretion than CaNa3-DTPA (61% of injected Pu). Preliminary findings on the acute toxicity of the poly(HOPO) ligands and HOPO monomers are presented in an appendix. The biological data indicate strongly that the aqueous solubility and relatively high acidity of the octadentate HOPO ligands, 3,4,3-LIHOPO and DFO-HOPO allow them to form complete eight-coordinate complexes with Pu(IV) ion.
Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway (2007)

Numerous studies have now shown that the amyloid beta-protein (Abeta), the principal component of cerebral plaques in Alzheimer disease, rapidly and potently inhibits certain forms of synaptic plasticity. The amyloid (or Abeta) hypothesis proposes that the continuous disruption of normal synaptic physiology by Abeta contributes to the development of Alzheimer disease. However, there is little consensus about how Abeta mediates this inhibition at the molecular level. Using mouse primary hippocampal neurons, we observed that a brief treatment with cell-derived, soluble, human Abeta disrupted the activation of three kinases (Erk/MAPK, CaMKII, and the phosphatidylinositol 3-kinase-activated protein Akt/protein kinase B) that are required for long term potentiation, whereas two other kinases (protein kinase A and protein kinase C) were stimulated normally. An antagonist of the insulin receptor family of tyrosine kinases was found to mimic the pattern of Abeta-mediated kinase inhibition. We then found that soluble Abeta binds to the insulin receptor and interferes with its insulin-induced autophosphorylation. Taken together, these data demonstrate that physiologically relevant levels of naturally secreted Abeta interfere with insulin receptor function in hippocampal neurons and prevent the rapid activation of specific kinases required for long term potentiation.
An air-to-air Situationally Interactive Combat Model (SICM) (2002)

This paper discusses the Situationally Interactive Combat Model (SICM), a user-friendly air-to-air combat engagement model that is used to perform analyses of offensive and defensive tactics employment, changes to avionics suite components and aircraft capabilities, and changes of air-to-air armament systems. The inputs to the model are the performance parameters of the many disparate elements that comprise airborne weapon systems, and the outputs are various types of measures of engagement-level effectiveness. SICM supports the modeling of all sensor systems and the fusion of sensor data. The modeling techniques allow for rapid prototyping and for the very low cost method of evaluating new ideas and development strategies. Although originally designed for beyond visual range (BVR) engagements, improvements in graphical display of the engagements and maneuvering of aircraft have expanded SICM's capabilities to include the performance and display of close in combat (CIC). This model has supported the Advanced Tactical Fighter (ATF) Milestone I Cost and Operational Effectiveness Analysis (COEA), the Integrated Electronic Warfare System (INEWS) Milestone I COEA, the Mark XV Identification Friend or Foe (IFF) Milestone II COEA, and a number of marginal utility analyses for Wright Laboratory, WPAFB, Ohio. SICM is the model of choice for analysts due to its ease of use, user interactivity, speed of execution, sensor identification capabilities, and engagement modeling fidelity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>