gebhart/patrepeval huggingface dataset:
Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers (2011)

A stressful event increases the risk of developing depression later in life, but the possible predisposing factors remain unknown. Our study aims to characterize latent vulnerability traits underlying the development of depressive disorders in adult animals. Four weeks after a priming stressful event, serum corticosterone concentration returned to control values in all animals, whereas the other biological parameters returned to basal level in only 58% of animals (called nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis, CA3 dendritic retraction and decrease in spine density, as well as amygdala neuron hypertrophy, constituting latent vulnerability traits to depression. In this group, called vulnerable, a subsequent mild stress evoked a rise of serum corticosterone levels and a "depressive" phenotype, in contrast to nonvulnerable animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a selective TrkB receptor agonist, dampened the development of the "depressive" phenotype. Our results thus characterize the presence of latent vulnerability traits that underlie the emergence of depression and identify the association of low BDNF with normal corticosterone serum concentrations as a predictive biomarker of vulnerability to depression.
Compass: Predicting Biological Activities from Molecular Surface Properties. Performance Comparisons on a Steroid Benchmark (1994)

We describe a new method, Compass, for predicting the biological activities of molecules based on the activities and three-dimensional structures of other molecules. The method improves on previous techniques by representing only the surface of molecules, by incorporating a nonlinear statistical method, and by automatically choosing conformations and alignments of molecules. We use a benchmark problem of steroid binding affinity prediction to compare the performance of the method with that of two previous systems: CoMFA and a molecular similarity method. Compass predicts steroid affinities substantially more accurately than the others, which represent the state of the art. We present experiments showing that the improved performance depends on each of the technical innovations.
An R5L τ mutation in a subject with a progressive supranuclear palsy phenotype (2002)

MAPT, the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation (R5L) was identified in a single progressive supranuclear palsy subject that was not in the other progressive supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters the ability of tau to promote microtubule assembly. Analysis of soluble tau from different brain regions indicates that the mutation does not affect the ratio of tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was predominantly four-repeat tau with no or one amino terminal insert (0N4R and 1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism.
Studies of Poly(ethylene glycol) Modification of HM-3 Polypeptides (2009)

An RGD modified endostatin-derived synthetic peptide, named HM-3, is a polypeptide angiogenesis inhibitor previously synthesized in our laboratory. Its robust inhibitory effects on endothelial cell migration and tumor growth have been demonstrated by in vivo and in vitro activity assays. The RGD integrin recognition sequence enables the selective binding of HM-3 and its specific targeting to tumor cells that express high levels of integrin. However, the drug has relatively short half-life in vivo, thus requiring administration twice a day to achieve its optimal in vivo antitumor efficacy. In the current study designed to prolong HM-3 half-life, we used methoxy-poly(ethylene glycol)-aldehyde (mPEG-ALD) to specifically modify its N terminus and optimized the reaction condition via monitoring the modification by reverse-phase high-performance liquid chromatograph (RP-HPLC) under varying stoichiometric ratios (n(mPEG10k-ALD):n(HM-3)), reaction times, and pH values. The maximal modification rate was achieved in a reaction when substrates mPEG10k-ALD and HM-3 were mixed at the molar ratio of 2:1 in a pH 6 phosphate buffer after 4 h incubation at room temperature. The reaction product of this optimal reaction was purified to 96% purity by RP-HPLC. Compared with HM-3, the newly modified PEG(10k)-HM-3 was shown to be more active in the inhibition of angiogenesis in the chorioallantoic membrane of chick embryos (CAM), its rate of in vitro degradation in serum was markedly reduced, and its in vivo half-life was prolonged by 5.86-fold relative to unmodified HM-3 after intravenous injection into male SD rats.
Chain Packing in Electro-Spun Poly(ethylene oxide) Visualized by Atomic Force Microscopy (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTChain Packing in Electro-Spun Poly(ethylene oxide) Visualized by Atomic Force MicroscopyR. Jaeger, H. Schönherr, and G. J. VancsoView Author Information Faculty of Chemical Technology, University of Twente, P.O. Box 217, NL - 7500 AE Enschede, The NetherlandsCite this: Macromolecules 1996, 29, 23, 7634–7636Publication Date (Web):November 4, 1996Publication History Received19 July 1996Revised3 September 1996Published online4 November 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ma9610673https://doi.org/10.1021/ma9610673rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1132Altmetric-Citations127LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Crystal structure,Crystallography,Fibers,Liquids,Solution chemistry Get e-Alerts
Sphingosine-1 Phosphate Prevents Monocyte/Endothelial Interactions in Type 1 Diabetic NOD Mice Through Activation of the S1P1 Receptor (2006)

Monocyte recruitment and adhesion to vascular endothelium are key early events in atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on modulating monocyte/endothelial interactions in the NOD/LtJ (NOD) mouse model of type 1 diabetes. Aortas from nondiabetic and diabetic NOD mice were incubated in the absence or presence of 100 nmol/L S1P. Fluorescently labeled monocytes were incubated with the aortas. Aortas from NOD diabetic mice bound 7-fold more monocytes than nondiabetic littermates (10+/-1 monocytes bound/field for nondiabetic mice vs 74+/-12 monocytes bound/field for diabetic mice, P<0.0001). Incubation of diabetic aortas with 100 nmol/L S1P reduced monocyte adhesion to endothelium by 90%. We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells. The S1P1 receptor-specific agonist SEW2871 inhibited monocyte adhesion to diabetic aortas. Studies in diabetic S1P3-deficient mice revealed that the S1P3 receptor did not play a pivotal role in this process. S1P reduced endothelial VCAM-1 induction in type 1 diabetic NOD mice, most likely through inhibition of nuclear factor kappaB translocation to the nucleus. Thus, S1P activation of the S1P1 receptor functions in an antiinflammatory manner in type 1 diabetic vascular endothelium to prevent monocyte/endothelial interactions. S1P may play an important role in the prevention of vascular complications of type 1 diabetes.
A 80-mV input, fast startup dual-mode boost converter with charge-pumped pulse generator for energy harvesting (2011)

A low startup-voltage and fast startup dual-mode boost converter for energy harvesting applications is developed in 65-nm CMOS. Comparing with the previous work [6], the startup-time, the minimum startup voltage, and the program time are greatly improved. (1) A startup by the boost converter instead of a charge pump reduced the startup-time to 4.8ms which is 1/56 of [6] and the shortest to date. (2) The proposed sub-1nW charge-pumped pulse generator (CPPG) enabled the lowest startup voltage of 80mV to date without mechanical switch. (3) The proposed threshold-voltage-tuned oscillator with hot-carrier injection (HCI) for CPPG to compensate for the die-to-die process variations reduced the program time to 3min which is 1/20 of [6], thereby reducing the test cost.
Controlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexes (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTControlled/"living" radical polymerization. atom transfer radical polymerization in the presence of transition-metal complexesJin-Shan Wang and Krzysztof MatyjaszewskiCite this: J. Am. Chem. Soc. 1995, 117, 20, 5614–5615Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/ja00125a035https://doi.org/10.1021/ja00125a035research-articleACS PublicationsRequest reuse permissionsArticle Views24748Altmetric-Citations4121LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
V2 vasopressin receptor dysfunction in nephrogenic diabetes insipidus caused by different molecular mechanisms (1998)

Loss-of-function mutations in the V2 vasopressin receptor (AVPR2) gene have been identified as a molecular basis for X-linked nephrogenic diabetes insipidus (NDI). Herein, we describe a novel deletion mutation at nucleotide position 102 (delG102) found in a Russian family resulting in a frameshift and a truncated receptor protein. Furthermore, we analyzed the AVPR2 gene of two other unrelated boys with NDI from our patient clientele. These patients showed previously described mutations (R137H, R181C). In-depth characterization of the three mutant AVPR2s by a combination of functional and immunological techniques permitted further insight into molecular mechanisms leading to receptor dysfunction. Premature truncation of the AVPR2 (delG102) led to a drastically reduced receptor protein expression in transfected COS-7 cells and, as expected, precluded specific AVPR2 functions. As indicated by different ELISA and binding studies, the R137H mutant was almost completely retained in the cell interior. In contrast to previous studies, the few mutant receptors in the plasma membrane displayed a low (2.3-fold above basal) but significant ability to stimulate the Gs/adenylyl cyclase system. In contrast to the latter mutation, the R181C mutant is properly delivered to the cell surface but the mutation interferes with high affinity vasopressin binding. Impaired ligand binding is reflected in an about 100-fold shift of the concentration-response curve toward higher vasopressin concentrations with only slightly reduced agonist potency.
Optimized siRNA-PEG Conjugates for Extended Blood Circulation and Reduced Urine Excretion in Mice (2013)

Some of the main concerns with in vivo application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol (PEG) with variable chain length affects siRNA pharmacokinetics and biodistribution. The PEG chains were conjugated to chemically stabilized siRNA at the 5' terminal end of the passenger strand using click chemistry. The siRNA conjugate remained functionally active and showed significantly prolonged circulation in the blood stream after intravenous injection. siRNA conjugated with 20kDa PEG (PEG20k-siRNA) was most persistent, approximately 50% PEG20k-siRNA remained 1h post-injection, while the uncoupled siRNA was rapidly removed >90% at 15min. In vivo fluorescent imaging of the living animal showed increased concentration of siRNA in peripheral tissue and delayed urine excretion when coupled to PEG 20k. Biodistribution studies by northern blotting revealed equal distribution of conjugated siRNA in liver, kidney, spleen and lung without significant degradation 24 h post-injection. Our study demonstrates that PEG conjugated siRNA can be applied as a delivery system to improve siRNA bioavailability in vivo and may potentially increase the efficiency of siRNA in therapeutic applications.
Asymmetric Hydrogenation of Olefins with Aprotic Oxygen Functionalities Catalyzed by BINAP-Ru(II) Complexes (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric Hydrogenation of Olefins with Aprotic Oxygen Functionalities Catalyzed by BINAP-Ru(II) ComplexesTetsuo Ohta, Tsutomu Miyake, Nobuo Seido, Hidenori Kumobayashi, and Hidemasa TakayaCite this: J. Org. Chem. 1995, 60, 2, 357–363Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://doi.org/10.1021/jo00107a014Request reuse permissionsArticle Views2611Altmetric-Citations161LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (912 KB) Get e-Alertsclose Get e-Alerts
Asymmetric Subunit Organization of Heterodimeric Rous Sarcoma Virus Reverse Transcriptase αβ: Localization of the Polymerase and RNase H Active Sites in the α Subunit (2000)

ABSTRACT The genes encoding the α (63-kDa) and β (95-kDa) subunits of Rous sarcoma virus (RSV) reverse transcriptase (RT) or the entire Pol polypeptide (99 kDa) were mutated in the conserved aspartic acid residue Asp 181 of the polymerase active site (YMDD) or in the conserved Asp 505 residue of the RNase H active site. We have analyzed heterodimeric recombinant RSV αβ and αPol RTs within which one subunit was selectively mutated. When αβ heterodimers contained the Asp 181→Asn mutation in their β subunits, about 42% of the wild-type polymerase activity was detected, whereas when the heterodimers contained the same mutation in their α subunits, only 7.5% of the wild-type polymerase activity was detected. Similar results were obtained when the conserved Asp 505 residue of the RNase H active site was mutated to Asn. RNase H activity was clearly detectable in αβ heterodimers mutated in the β subunit but was lost when the mutation was present in the α subunit. In summary, our data imply that the polymerase and RNase H active sites are located in the α subunit of the heterodimeric RSV RT αβ.
Characteristics of the m 2000 Automated Sample Preparation and Multiplex Real-Time PCR System for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae (2007)

We evaluated a new real-time PCR-based prototype assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae developed by Abbott Molecular Inc. This assay is designed to be performed on an Abbott m2000 real-time instrument system, which consists of an m2000sp instrument for sample preparation and an m2000rt instrument for real-time PCR amplification and detection. The limit of detection of this prototype assay was determined to be 20 copies of target DNA for both C. trachomatis and N. gonorrhoeae, using serially diluted linearized plasmids. No cross-reactivity could be detected when 55 nongonococcal Neisseria isolates and 3 non-C. trachomatis Chlamydia isolates were tested at 1 million genome equivalents per reaction. Concordance with the Roche Amplicor, BDProbeTec ET, and Gen-Probe APTIMA Combo 2 tests was assessed using unlinked/deidentified surplus clinical specimens previously analyzed with these tests. For C. trachomatis, concordance for positive results ranged from 93.7% to 100%, while concordance for negative results ranged from 98.2% to 100%. For N. gonorrhoeae, concordance for positive and negative results ranged from 91.4% to 100% and 99.3% to 100%, respectively. A workflow analysis of the prototype assay was conducted to obtain information on throughput under laboratory conditions. At 48 samples/run, the time to first result for both C. trachomatis and N. gonorrhoeae was 4.5 h. A total of 135 patient specimens could be analyzed in 8.9 h, with 75 min of hands-on time. This study demonstrated the technical and clinical feasibility of the new Abbott real-time PCR C. trachomatis/N. gonorrhoeae assay.
Object recognition in visually complex environments: an architecture for locating address blocks on mail pieces (2003)

A method of recognizing an object of interest in a complex visual environment is described. Motivated by the problem of finding the destination address block on a piece of mail, a general framework for coordinating a collection of specialized image analysis tools is described. The resulting system can deal with a wide range of environments: from those having a high degree of global spatial structure (e.g. mail envelopes which conform to specifications) to those with no structure (e.g. magazines with randomly pasted address labels). The problem-solving architecture accounts for uncertainty in the imaging environment by using the blackboard model. The system consists of several specialized tools and a control structure so that the tools are opportunistically invoked and coordinated. Its performance on an image database of difficult cases is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Live virtual machine migration techniques: Survey and research challenges (2013)

Cloud is an emerging technology in the world of information technology and is built on the key concept of virtualization. Virtualization separates hardware from software and has benefits of server consolidation and live migration. Live migration is a useful tool for migrating OS instances across distant physical of data centers and clusters. It facilitates load balancing, fault management, low-level system maintenance and reduction in energy consumption. In this paper, we survey the major issues of virtual machine live migration. We discuss how the key performance metrics e.g downtime, total migration time and transferred data are affected when a live virtual machine is migrated over WAN, with heavy workload or when VMs are migrated together. We classify the techniques and compare the various techniques in a particular class.
Adaptive algorithms for managing a distributed data processing workload (1997)

Workload management, a function of the OS/390™ operating system base control program, allows installations to define business objectives for a clustered environment (Parallel Sysplex™ in OS/390). This business policy is expressed in terms that relate to business goals and importance, rather than the internal controls used by the operating system. OS/390 ensures that system resources are assigned to achieve the specified business objectives. This paper presents algorithms developed to simplify performance management, dynamically adjust computing resources, and balance work across parallel systems. We examine the types of data the algorithms require and the measurements that were devised to assess how well work is achieving customer-set goals. Two examples demonstrate how the algorithms adjust system resource allocations to enable a smooth adaptation to changing processing conditions. To the customer, these algorithms provide a single-system image to manage competing workloads running across multiple systems.
A novel bispecific antibody recruits T cells to eradicate tumors in the “immunologically privileged” central nervous system (2013)

Bispecific T-cell engagers (BiTEs) may break multiple barriers that currently limit the use of immunotherapy in glioblastoma patients. We have recently described a novel BiTE specific for a mutated form of the epidermal growth factor receptor, EGFRvIII, that exerts potent antineoplastic effects against established invasive tumors of the brain.
Opioid-induced hyperalgesia: abnormal or normal pain? (2003)

Laboratoire Homéostasie-Allostasie-Pathologie, Université Victor-Ségalen Bordeaux 2, 33077 Bordeaux Cedex, France CACorresponding Author: [email protected]