gebhart/patrepeval huggingface dataset:
Cutting Edge: Transpresentation of IL-15 by Bone Marrow-Derived Cells Necessitates Expression of IL-15 and IL-15Rα by the Same Cells (2004)

IL-15 is critical for generation of multiple lymphoid subsets. Recent data have demonstrated a unique aspect of responses to IL-15, in that cells bearing the IL-15Ralpha chain can bind soluble IL-15 and "transpresent" the cytokine to other cells, allowing the latter to respond to IL-15. However, it is unclear whether IL-15 is normally secreted and then becomes bound to surface IL-15Ralpha on bystander cells, or whether transpresentation is mediated by the same cells which synthesize IL-15. Using mixed bone marrow chimeric mice, we present evidence for the latter model, showing that development of NK cells and memory phenotype CD8 T cells necessitates that both IL-15 and IL-15Ralpha be expressed by the same population of cells. These data argue that soluble forms of IL-15 are irrelevant for physiological responses to this cytokine, and the implications of this finding are discussed.
Photovoltaic effect in heterojunctions made of zinc and cadmium tellurides (1983)

A study of p-ZnTe--n-CdTe heterojunctions carried out in order to determine whether it is possible to construct converters from these functions and measure some of their photovoltaic characteristics is reported. (AIP)
A Magnetic Resonance Imaging-Compatible, Large-Scale Array for Trans-Skull Ultrasound Surgery and Therapy (2005)

The successful outcome of these experiments indicates that intensities high enough to destroy brain tissue can be produced without excessive heating of the surrounding areas and without producing large magnetic resonance noise and artifacts.
Reversal of Fortune for Drosophila Geneticists? (2000)

Although Drosophila is a wonderful model organism, there is one molecular arena where it lags far behind its yeast and mouse model counterparts. Reverse genetics, whereby a piece of DNA is integrated into a target gene such that the gene is disrupted or replaced, is not easy in Drosophila. As Engels explains in his provocative Perspective, this may be set to change with the description of a new method for reverse genetics in Drosophila (Rong and Golic). This new technique should ensure that Drosophila remains the darling of geneticists for many years to come.
Efficient secretion and purification of human insulin-like growth factor I with a gene fusion vector inStaphylococci (1985)

A novel approach for production of small polypeptides, using a staphylococcal protein A vector, is described. This system is used to express, secrete and purify human insulin-like growth factor I (IGF-I). A fusion protein consisting of protein A and IGF-I is recovered in high yield by passing the culture medium through an IgG affinity column. Using site-specific mutagenesis an acid labile asp-pro cleavage site was introduced at the fusion point between the two proteins. The protein A "tail" can thereby be removed from the affinity purified fusion protein by chemical cleavage releasing biologically active IGF-I molecules.
Pluripotency of cultured rabbit inner cell mass cells detected by isozyme analysis and eye pigmentation of fetuses following injection into blastocysts or morulae (1993)

Pluripotency of isolated rabbit inner cell masses (ICMs) and cultured (3 days) inner cell mass (ICM) cells was tested by injecting these donor cells into day 3.5 blastocysts (experiment 1) or day 3 morulae (experiment 2) to produce chimeric embryos. Injected (n = 107) and noninjected (n = 103) embryos were transferred to the opposite uterine horns of the same recipient females. Chimerism was determined by adenosine deaminase (ADA) isozyme analysis on fetal tissue and by eye pigmentation at midgestation. In experiment 1, 53% and 64%, respectively, of blastocysts injected with ICMs or cultured ICM cells developed to midgestation, compared with 52% and 48% for controls. Of these fetuses, four (31%) and one (6%), respectively, had ADA chimerism. In experiment 2, 38% and 62%, respectively, of the morulae injected with ICMs or cultured ICM cells developed to midgestation, compared with 46% and 56% for control morulae. Six (43%) chimeric fetuses from morulae injected with ICMs were detected by ADA analysis, but 12 (86%) chimeric fetuses were detected by eye pigmentation, indicating that eye pigmentation was a more sensitive marker for chimerism than our ADA assay. None of the 14 fetuses recovered after injecting morulae with cultured ICM cells were chimeric with either marker. No chimeras developed from control embryos. These studies demonstrate 1) that pregnancy rates are not compromised by injection of blastocysts or morulae with ICMs or cultured ICM cells, 2) that chimeric rabbit fetuses can be produced by injecting ICMs into either blastocysts or morulae, and 3) that cultured ICM cells can contribute to embryonic development when injected into blastocysts.
Design and synthesis of ortho-phthalaldehyde phosphoramidite for single-step, rapid, efficient and chemoselective coupling of DNA with proteins under physiological conditions (2018)

ortho-Phthalaldehyde (OPA) phosphoramidite with high reaction activity was designed and synthesized for labelling oligodeoxynucleotides (DNA). The DNA modified with OPA (OPA-DNA) can covalently couple with native proteins rapidly and efficiently via a condensation reaction with the formation of phthalimidines, which provides a highly efficient method for bioconjugation of DNA and native proteins under physiological conditions.
Transgenic Mice Lacking White Fat: Models for Understanding Human Lipoatrophic Diabetes (1999)

The human disease lipoatrophic (or lipodystrophic) diabetes is a rare syndrome in which a deficiency of adipose tissue is associated with Type 2 diabetes. This disease is an interesting contrast to the usual situation in which diabetes is associated with obesity, an excess of fat. Aside from obesity, patients with lipodystrophic diabetes have the other features associated with Metabolic Syndrome X, including hypertension and dyslipidemia. The contrast between diabetes with a lack of fat and diabetes with an excess of fat provides an opportunity to study the mechanisms causing Type 2 diabetes and its complications. Recently, three laboratories have produced transgenic mice that are deficient in white adipose tissue. These mice have insulin resistance and other features of lipoatrophic diabetes, and are a faithful model for the human disease. Here we review the different murine models of fat ablation and compare the murine and human diseases, addressing the questions: Is the lack of fat causative of the diabetes, and if so by what mechanism? How could the other clinical features be explained mechanistically? And finally, what can be gleaned about insight into treatment options?
Guselkumab 对使用优特克单抗疗效不佳的银屑病患者的有效性和安全性:随机、双盲 III 期 NAVIGATE 试验结果 (2018)

银屑病是一种慢性疾病,可导致发红以及鳞屑性皮损。当前治疗药物(尤其是生物制剂)经注射或静脉滴注 (IV) 给药,在治疗中度到重度的斑块状银屑病方面十分有效。但鉴于大部分患者希望痊愈,所以仍有改进的空间。优特克单抗是一种经批准的生物制剂,能够阻断人体的两种内蛋白质,即白介素 (IL)‐12 和 IL‐23。阻断这些蛋白质,人体就收不到引发银屑病炎症的信号。尽管优特克单抗对大部分患者有效,但患者大多无法痊愈。鉴于近期科学证据表明 IL‐23 在导致银屑病方面可能比 IL‐12 更重要,guselkumab 应时而生,这是一种专门针对 IL‐23 而非 IL‐12 研发的新型治疗方案,近期已经在美国获得批准,可用于治疗中度到重度的银屑病。在 NAVIGATE 试验中,871 位患有中度到重度斑块状银屑病的患者使用了优特克单抗。如果在 16 周后,患者未痊愈或几乎痊愈,则将被随机分配继续使用优特克单抗或开始使用 guselkumab 治疗,直到第 44 周为止。第 16 周至第 40 周,就患者实现痊愈或几乎痊愈的平均访视次数(最多 4 次)而言,使用 guselkumab 治疗的患者(1.5 次)显著高于使用优特克单抗治疗的患者(0.7 次)。此外第 28 周,使用 guselkumab 与使用优特克单抗治疗后痊愈或几乎痊愈的患者的比例相差一倍,分别是 31.1% 和 14.3%。在使用 guselkumab 或优特克单抗治疗的患者中,最常报告的不良反应是感染。作者得出结论,对于在使用优特克单抗治疗后未痊愈或几乎痊愈的患者,转用 guselkumab 可能是一种行之有效的治疗策略,并且不会引起安全问题。
Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. (1984)

We used a nuclear RNA transcript elongation assay to show that cAMP analogs and dexamethasone cause a selective increase of transcription of the P-enolpyruvate carboxykinase gene in H4IIE hepatoma cells. 8-(4-chlorophenylthio)-cAMP increased transcription within 5 min and the maximal rate, generally 10-15-fold above the basal rate, was attained by 30 min. This increase was of sufficient magnitude to account for the effect on mRNAPEPCK (for example, where PEPCK is phosphoenolpyruvate carboxykinase) accumulation. After the initial increase, and with continued presence of cAMP, transcription of this gene declined to a new steady-state level which was 2-3 times the basal value. The effect of cAMP analogs on P-enolpyruvate carboxykinase gene transcription was obtained in the absence of protein synthesis. This, and the rapidity of the response, indicates that the effect of cAMP is exerted directly on the P-enolpyruvate carboxykinase gene. Dexamethasone results in a specific, 6-fold increase of transcription, sufficient to account for the increase of mRNAPEPCK which follows treatment of H4IIE cells with this glucocorticoid. When 1 nM insulin was added to either untreated H4IIE cells, or cells first treated with a cAMP analog or dexamethasone, there was a marked reduction of cytoplasmic mRNAPEPCK. The inhibitory effect of insulin was readily reversible, as cells regained the basal level of mRNAPEPCK and full responsiveness to cAMP within 1 h after removing insulin. The transcript elongation assay was used to show that insulin inhibits transcription of the gene coding for mRNAPEPCK. The concentration of insulin required for 50% inhibition was 2-5 pM, whereas approximately 200 pM of proinsulin was required to achieve the same inhibition of transcription. This effect was specific, since insulin did not affect the synthesis of total RNA; it was rapid, as 5 nM insulin decreased the rate of P-enolpyruvate carboxykinase gene transcription by 50% within 15 min; and it also does not require ongoing protein synthesis. The magnitude and kinetics of the response suggest that the primary action of insulin in the regulation of P-enolpyruvate carboxykinase synthesis is exerted at the level of mRNAPEPCK transcription. The insulin-mediated inhibition of mRNAPEPCK transcription was noted in untreated cells and in cells first treated with 8-(4-chlorophenylthio)-cAMP, dexamethasone, or both of these agents. Hence, among these compounds, insulin is the dominant regulatory molecule.
The influence of silicide formation on the barrier height of Ti/Si MIS Schottky barriers (1986)

Ti/Si MIS diodes were made by evaporating Ti on a hot substrate at a temperature T,, which could be varied between room temperature and 760 degrees C. It was found that for T-s < 300 degrees C the Schottky barrier height phi B changed with T-s and also depended on the pre-metallisation treatment of the silicon surface. Between 300 degrees C and 500 degrees C, phi B remained independent of T-s. These results could be explained by the reaction wherein titanium converts the silicon oxide into titanium oxide and titanium silicide. Further support for this model was obtained from Auger measurements. Between 500 degrees C and 600 degrees C a complete conversion of both the interface layer and the Ti top layer into silicide occurred and oxide was no longer present at the interface. For T-s > 600 degrees C, a phi B typical for a titanium disilicide/Si contact was measured.
A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm (2010)

In natural systems, bacteria form complex, surface-attached communities known as biofilms. This lifestyle presents numerous advantages compared with unattached or planktonic life, such as exchange of nutrients, protection from environmental stresses and increased tolerance to biocides. Despite such benefits, dispersal also plays an important role in escaping deteriorating environments and in successfully colonizing favourable, unoccupied habitat patches. The α-proteobacterium Caulobacter crescentus produces a motile swarmer cell and a sessile stalked cell at each cell division. We show here that C. crescentus extracellular DNA (eDNA) inhibits the ability of its motile cell type to settle in a biofilm. eDNA binds to the polar holdfast, an adhesive structure required for permanent surface attachment and biofilm formation, thereby inhibiting cell attachment. Because stalked cells associate tightly with the biofilm through their holdfast, we hypothesize that this novel mechanism acts on swarmer cells born in a biofilm, where eDNA can accumulate to a sufficient concentration to inhibit their ability to settle. By targeting a specific cell type in a biofilm, this mechanism modulates biofilm development and promotes dispersal without causing a potentially undesirable dissolution of the existing biofilm.
Audio Encryption Using Fragile Watermarking (2006)

The main application area for digital watermarking is copyright protection. We propose a method that increases the robustness of copyright protection watermarks by persuading users not to try attacking the watermark. The method embeds two watermarks into media; a robust one and fragile one. Copy protection information is embedded into the robust watermark. The fragile watermark contains some application specific information that the user do not want to lose. The fragile watermark is constructed so that it is destroyed, if the robust watermark is attacked. The proposed method is demonstrated with a audio encryption scenario that uses the mobile phone to play protected audio files. The audio decryption keys are embedded into the fragile watermark
Observer-controller stabilization of a class of manipulators with a single flexible link (2002)

A nonlinear control strategy for a large class of multilink manipulators with one flexible link is proposed. The design is based on a transformation which almost linearizes the system. A nonlinear observer is proposed, and it is shown that combining this observer with the proposed nonlinear controller results in a system which is input/output stable in a local sense. >
GPCRDB information system for G protein-coupled receptors (2003)

The GPCRDB is a molecular class-specific information system that collects, combines, validates and disseminates heterogeneous data on G protein-coupled receptors (GPCRs). The database stores data on sequences, ligand binding constants and mutations. The system also provides computationally derived data such as sequence alignments, homology models, and a series of query and visualization tools. The GPCRDB is updated automatically once every 4-5 months and is freely accessible at http://www.gpcr.org/7tm/.
Identifying reusable functions using specification driven program slicing: a case study (2002)

We present the results of a case study in identifying and isolating reusable functions from C programs. The work exploits and specializes to programs written in C the theoretical framework of specification driven program slicing, a new program slicing process for isolating code fragments implementing functional abstractions. The specification of the function to be isolated, given in terms of a precondition and a postcondition, is used to identify a suitable slicing criterion. The preconditions for the execution of program statements and predicates are abstracted by using symbolic execution and compared with the conditions of the specification. The statements whose preconditions are equivalent to the pre and postconditions of the functional abstraction are candidates for entry and exit points of the slice implementing the abstraction. Once the slicing criterion has been identified, the slice can be isolated using algorithms based on control flow graphs and dependence graphs.
SeRLoc (2005)

Many distributed monitoring applications of Wireless Sensor Networks (WSNs) require the location information of a sensor node. In this article, we address the problem of enabling nodes of Wireless Sensor Networks to determine their location in an untrusted environment, known as the secure localization problem. We propose a novel range-independent localization algorithm called SeRLoc that is well suited to a resource constrained environment such as a WSN. SeRLoc is a distributed algorithm based on a two-tier network architecture that allows sensors to passively determine their location without interacting with other sensors. We show that SeRLoc is robust against known attacks on a WSNs such as the wormhole attack , the Sybil attack , and compromise of network entities and analytically compute the probability of success for each attack. We also compare the performance of SeRLoc with state-of-the-art range-independent localization schemes and show that SeRLoc has better performance.
Effects of total hydrophobicity and length of the hydrophobic domain of a signal peptide on in vitro translocation efficiency. (1992)

The hydrophobic domain of the signal peptide of OmpF-Lpp, a model secretory protein, was systematically engineered so as to be composed of different lengths of polyleucine residues or polymers with alternate leucine and alanine residues, and the effects of the length and nature of the hydrophobic stretch on the rate of in vitro translocation were studied using everted membrane vesicles of Escherichia coli. The translocation reaction exhibited high substrate specificity as to the number of hydrophobic residues. The results suggest that the hydrophobic domain is recognized specifically by a component(s) of the secretory machinery rather than nonspecifically by the hydrophobic region of the membrane. The in vitro translocation thus demonstrated required SecA and ATP and was markedly enhanced upon imposition of the proton motive force, as in the case of secretory proteins possessing a natural signal peptide. The highest translocation rate was obtained with the octamer in the case of polyleucine-containing signal peptides, whereas it was the decamer in the case of ones containing both leucine and alanine. These results suggest that the total hydrophobicity of the hydrophobic region of the signal peptides is an important determinant of the substrate specificity.
Laser‐assisted vasovasostomy (1989)

To find a less time-consuming alternative to conventional microsurgical vasovasostomy, we performed vasal anastomosis in four sterilized men by means of a Nd:YAG laser (wavelength 1,060 nm) under macroscopic conditions. After dissection of the vasal ends, the ends were approximated using 6-0 prolene sutures as intervasal stents. The apposed tissue edges were welded by laser pulses of 0.5 sec in duration and 10 W in power. Postoperative sperm counts proved normal in two patients; one of them reported a successful pregnancy in his wife 12 months after vasovasostomy. One patient had cryptospermia and one patient oligoasthenospermia. Laser-assisted vasovasostomy is a simple procedure and shortens the operative time. More patients still need to be studied to allow a favorable comparison with conventional suture techniques.
N-terminal pro-brain natriuretic peptide predicts cardiovascular events in patients with hypertension and left ventricular hypertrophy (2004)

Nt-proBNP, more than Nt-proANP, strongly predicts cardiovascular events in patients with hypertension and LV hypertrophy, especially in patients without diabetes or clinically overt cardiovascular disease.
Detecting and defending against third-party tracking on the web (2012)

While third-party tracking on the web has garnered much attention, its workings remain poorly understood. This poster describes our work from a recent paper [1], in which our goal is to dissect how mainstream web tracking occurs in the wild. We develop a client-side method for detecting and classifying five kinds of third-party trackers based on how they manipulate browser state. We run our detection system while browsing the web and observe a rich ecosystem, with over 500 unique trackers in our measurements alone. We find that most commercial pages are tracked by multiple parties, trackers vary widely in their coverage with a small number being widely deployed, and many trackers exhibit a combination of tracking behaviors. Based on web search traces taken from AOL data, we estimate that several trackers can each capture more than 20 % of a users browsing behavior. We further assess
Epitope Mapping Using Ribosome Display in a Reconstituted Cell-Free Protein Synthesis System (2009)

Ribosome display is a powerful technology for selecting ligand-binding peptides or proteins. We demonstrate here that the ribosome display using the reconstituted cell-free protein synthesis system can be applied for the epitope mapping of monoclonal antibodies (mAbs). Using this technology, we selected peptides that specifically bind to three mAbs from random peptide library. When selection was performed against the anti-FLAG M2 antibody, selected peptides contained previously characterized consensus epitope, indicating that the methodology can be applied for the epitope mapping. When the selection was carried out against two anti-beta-Catenin (anti-beta-Cat) mAbs, selected peptides had a homology for the partial peptide sequences of beta-Cat. Western blot analysis showed that these putative epitopes had affinity for the corresponding mAbs and beta-Cat mutants that lack these regions did not bind to the antibodies, indicating we correctly mapped the epitope for these mAbs. The study shown here provides a way for the quick identification of the epitope of mAbs.
Regioselective Acylation of Methyl 2‐Methyl‐4H‐thieno[3,2‐b]pyrrole‐5‐carboxylate. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Selectively Silencing GSK-3 Isoforms Reduces Plaques and Tangles in Mouse Models of Alzheimer's Disease (2012)

Glycogen synthase kinase-3 (GSK-3) is linked to the pathogenesis of Alzheimer's disease (AD), senile plaques (SPs), and neurofibrillary tangles (NFTs), but the specific contributions of each of the GSK-3 α and β isoforms to mechanisms of AD have not been clarified. In this study, we sought to elucidate the role of each GSK-3α and GSK-3β using novel viral and genetic approaches. First, we developed recombinant adeno-associated virus 2/1 short hairpin RNA constructs which specifically reduced expression and activity of GSK-3α or GSK-3β. These constructs were injected intraventricularly in newborn AD transgenic (tg) mouse models of SPs (PDAPP⁺/⁻), both SPs and NFTs (PDAPP⁺/⁻;PS19⁺/⁻), or wild-type controls. We found that knockdown (KD) of GSK-3α, but not GSK-3β, reduced SP formation in PDAPP⁺/⁻ and PS19⁺/⁻;PDAPP⁺/⁻ tg mice. Moreover, both GSK-3α and GSK-3β KD reduced tau phosphorylation and tau misfolding in PS19⁺/⁻;PDAPP⁺/⁻ mice. Next, we generated triple tg mice using the CaMKIIα-Cre (α-calcium/calmodulin-dependent protein kinase II-Cre) system to KD GSK-3α in PDAPP⁺/⁻ mice for further study of the effects of GSK-3α reduction on SP formation. GSK-3α KD showed a significant effect on reducing SPs and ameliorating memory deficits in PDAPP⁺/⁻ mice. Together, the data from both approaches suggest that GSK-3α contributes to both SP and NFT pathogenesis while GSK-3β only modulates NFT formation, suggesting common but also different targets for both isoforms. These findings highlight the potential importance of GSK-3α as a possible therapeutic target for ameliorating behavioral impairments linked to AD SPs and NFTs.