gebhart/patrepeval huggingface dataset:
Targeted Hydrolysis of Beta-Amyloid with Engineered Antibody Fragments (2010)

Accumulation and deposition of beta amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's Disease (AD), and numerous approaches to control Abeta aggregation are being actively pursued. Brain Abeta levels are controlled by the action of several proteolytic enzymes such as neprilysin (NEP), insulin degrading enzyme (IDE) and plasmin. While up-regulation of these enzymes increased clearance of Abeta in transgenic mouse models of AD, these enzymes have other natural substrates and multiple cleavage sites in Abeta complicating their use for treating AD. Alternatively, immunotherapeutic approaches to clear Abeta are gaining interest. Active and passive immunization studies with Abeta can reduce plaque burden and memory loss, but clinical trials were stopped due to meningioencephalitis in some patients. Naturally occurring proteolytic antibodies have been shown to cleave Abeta, and their serum titers are increased in patients with AD reflecting a protective autoimmune response. These antibodies however cannot cross the blood brain barrier and depend entirely on peripheral clearance to clear Abeta. A potentially non-inflammatory approach to facilitate Abeta clearance and reduce toxicity is to promote hydrolysis of Abeta at its alpha-secretase site using affinity matured single chain antibody fragments (scFvs). Bispecific antibodies consisting of a proteolytic scFv and a targeting scFv can be engineered to selectively supplement and target extracellular alpha-secretase activity and to target toxic Abeta forms facilitating their degradation and clearance without generating an immune response. This strategy represents a suitable paradigm for treating other neurological diseases such as Parkinson's Disease, Lou Gehrig's Disease, and spongiform encephalopathies.
Using EM to Learn 3D Models of Indoor Environments with Mobile Robots (2001)

This paper describes an algorithm for generating compact 3D models of indoor environments with mobile robots. Our algorithm employs the expectation maximization algorithm to fit a lowcomplexity planar model to 3D data collected by range finders and a panoramic camera. The complexity of the model is determined during model fitting, by incrementally adding and removing surfaces. In a final post-processing step, measurements are converted into polygons and projected onto the surface model where possible. Empirical results obtained with a mobile robot illustrate that high-resolution models can be acquired in reasonable time. 1.
The boundary between privacy and utility in data publishing (2007)

We consider the privacy problem in data publishing: given a database instance containing sensitive information anonymize it to obtain a view such that, on one hand attackers cannot learn any sensitive information from the view, and on the other hand legitimate users can use it to compute useful statistics. These are conflicting goals. In this paper we prove an almost crisp separation of the case when a useful anonymization algorithm is possible from when it is not, based on the attacker's prior knowledge. Our definition of privacy is derived from existing literature and relates the attacker's prior belief for a given tuple t, with the posterior belief for the same tuple. Our definition of utility is based on the error bound on the estimates of counting queries. The main result has two parts. First we show that if the prior beliefs for some tuples are large then there exists no useful anonymization algorithm. Second, we show that when the prior is bounded for all tuples then there exists an anonymization algorithm that is both private and useful. The anonymization algorithm that forms our positive result is novel, and improves the privacy/utility tradeoff of previously known algorithms with privacy/utility guarantees such as FRAPP.
A Comparison of High-Resolution Melting Analysis With Denaturing High-Performance Liquid Chromatography for Mutation Scanning: Cystic Fibrosis Transmembrane Conductance Regulator Gene as a Model (2005)

High-resolution melting analysis (HRMA) was compared with denaturing high-performance liquid chromatography (dHPLC) for mutation scanning of common mutations in the cystic fibrosis transmembrane conductance regulator gene. We amplified (polymerase chain reaction under conditions optimized for melting analysis or dHPLC) 26 previously genotyped samples with mutations in exons 3, 4, 7, 9, 10, 11, 13, 17b, and 21, including 20 different genotypes. Heterozygous mutations were detected by a change in shape of the melting curve or dHPLC tracing. All 20 samples with heterozygous mutations studied by both techniques were identified correctly by melting (100% sensitivity), and 19 were identified by dHPLC (95% sensitivity). The specificity of both methods also was good, although the dHPLC traces of exon 7 consistently revealed 2 peaks for wild-type samples, risking false-positive interpretation. Homozygous mutations could not be detected using curve shape by either method. However, when the absolute temperatures of HRMA were considered, G542X but not F508del homozygotes could be distinguished from wild type. HRMA easily detected heterozygotes in all single nucleotide polymorphism (SNP) classes (including A/T SNPs) and 1- or 2-base-pair deletions. HRMA had better sensitivity and specificity than dHPLC with the added advantage that some homozygous sequence alterations could be identified. HRMA has great potential for rapid, closed-tube mutation scanning.
Disruption of GABAergic tone in the dorsomedial hypothalamus attenuates responses in a subset of serotonergic neurons in the dorsal raphe nucleus following lactate-induced panic (2008)

Panic patients are vulnerable to induction of panic attacks by sub-threshold interoceptive stimuli such as intravenous (i.v.) sodium lactate infusions. Facilitation of serotonergic signaling with selective serotonin reuptake inhibitors can suppress anxiety and panic-like responses, but the mechanisms involved are not clearly defined. We investigated the effects of i.v. 0.5 M sodium lactate or saline, in control and panic-prone rats on c-Fos expression in serotonergic neurons within subdivisions of the midbrain/pontine raphe nuclei. Rats were chronically infused with either the GABA synthesis inhibitor l-allylglycine into the dorsomedial hypo thalamus to make them panic-prone, or the enantiomer d-allylglycine (d-AG) in controls. Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats. The distribution of lactate-sensitive serotonergic neurons in d-AG-treated rats is virtually identical to previously defined pre-sympathomotor serotonergic neurons with multisynaptic projections to peripheral organs mediating 'fight-or-flight'-related autonomic and motor responses. We hypothesized that serotonergic neurons within the DRVL/VLPAG region represent a 'sympathomotor control system' that normally limits autonomic/behavioral responses to innocuous interoceptive and exteroceptive stimuli, and that dysfunction of this serotonergic system contributes to an anxiety-like state and increases vulnerability to panic in animals and humans.
Visualizing and querying software structures (1992)

Software engineering problems often involve large sets of objects and complex relationships among them. This report proposes that graphical visualization techniques can help engineers understanci and solve a class of these problems. To illustrate this, two problems are analyzed and recast using the graphical language GraphLog. The fwst problem is that of simplifying dependencies among components of a system, which translates into removing cycles from a graph. The second problem is that of designing an efficient code overlay structure, which is facilitat cd in several ways through graphical techniques.
Virus-like particles: flexible platforms for vaccine development (2007)

Virus-like particles (VLPs) consist of viral structural proteins that, when overexpressed, spontaneously self-assemble into particles that are antigenically indistinguishable from infectious virus or subviral particles. VLPs can be considered as dense, repetitive arrays of one or more protein subunits with properties that are highly advantageous for use as stand-alone vaccines or as vaccine platforms. This review discusses the development of VLP-based platform technologies for vaccines against pathogens, as well as nontraditional targets such as self-antigens involved in chronic diseases.
[Differentiation from human embryonic stem cells to hematopoietic cells and endothelial cells]. (2005)

Embryonic stem cells are pluripotent and their differentiation in vitro can serve as an experimental model to explore the molecular mechanisms of early embryonic development. To investigate the effect of stromal cell conditioned medium combined with cytokines (sccm + cys) on the differentiation from human embryonic stem cells to hematopoietic cells and endothelial cells, the mouse fibroblast feeder cells to make human embryonic stem cells grown into embryonic bodies (EBs) were initially deleted. After culture for 3 days, EB cells were trypsinized into single cells and induced for 8 days by sccm + cys. Then, the differentiated cells were cultured in the semisolid medium containing 0.9% methylcellulose and cytokines to study the colony forming and self-renewal ability of cells. Immunocytochemical staining was used to check the surface markers of the colony cells. During the induction, mRNA expression of flk-1, BMI-1, scl, and Zeta-globin genes was tested by RT-PCR. Surface markers, such as flk-1, CD34 were tested by the flow cytometry. The results demonstrated that: (1) cell clusters containing 20-30 cells were formed after culture for 8 - 14 days in the semisolid medium, replanting these cells resulted in similar cell cluster forming. In addition, CD45 positive in big cell colonies were also found in the semisolid medium; (2) attached cell colonies appeared after culture for 8 days in the semisolid medium and VIII factor, UEA and KDR could be detected as negative by immunocytochemical staining; (3) on the 4(th) day of induction, mRNAs of flk-1, BMI-1, scl and Zeta-globin were all expressed. On the 8(th) day of induction, all of the above genes except Zeta-globin were expressed, while ES cell and EB cells which served as controls did not express scl and Zeta-globin genes; (4) on the 8(th) day of induction, the proportions of flk-1(+) cells and CD34(+) cells among all the inducing population were 9.8% and 16.8%, respectively, while the corresponding positive populations were 0.36% and 1.16% in spontaneously differentiated 11(th) day's EB, and 0.04% and 0.16%, respectively, in ES cells. If is concluded that embryonic stem cells can differentiate into hematopoietic cells and endothelial cells in combinant culture system of this study.
Mendel’s dwarfing gene: cDNAs from the Le alleles and function of the expressed proteins (1997)

The major gibberellin (GA) controlling stem elongation in pea (Pisum sativum L.) is GA1, which is formed from GA20 by 3beta-hydroxylation. This step, which limits GA1 biosynthesis in pea, is controlled by the Le locus, one of the original Mendelian loci. Mutations in this locus result in dwarfism. We have isolated cDNAs encoding a GA 3beta-hydroxylase from lines of pea carrying the Le, le, le-3, and led alleles. The cDNA sequences from le and le-3 each contain a base substitution resulting in single amino acid changes relative to the sequence from Le. The cDNA sequence from led, a mutant derived from an le line, contains both the le "mutation" and a single-base deletion, which causes a shift in reading frame and presumably a null mutation. cDNAs from each line were expressed in Escherichia coli. The expression product for the clone from Le converted GA9 to GA4, and GA20 to GA1, with Km values of 1.5 microM and 13 microM, respectively. The amino acid substitution in the clone from le increased Km for GA9 100-fold and reduced conversion of GA20 to almost nil. Expression products from le and le-3 possessed similar levels of 3beta-hydroxylase activity, and the expression product from led was inactive. Our results suggest that the 3beta-hydroxylase cDNA is encoded by Le. Le transcript is expressed in roots, shoots, and cotyledons of germinating pea seedlings, in internodes and leaves of established seedlings, and in developing seeds.
The involvement of stromal derived factor 1alpha in homing and progression of multiple myeloma in the 5TMM model. (2006)

These data demonstrate that SDF1alpha/CXCR4 is involved in the homing and the expansion of MM cells. Blocking CXCR4 could be useful in synergy with other anti-neoplastic treatments targeting the bone marrow microenvironment.
The Ubiquitin-Proteasome Pathway and Pathogenesis of Human Diseases (1999)

The ubiquitin-proteasome pathway plays a pivotal role in the degradation of short-lived and regulatory proteins important in a variety of basic cellular processes, including regulation of the cell cycle, modulation of cell surface receptors and ion channels, and antigen presentation. The pathway involves an enzymatic cascade through which multiple ubiquitin molecules are covalently attached to the protein substrate, which is then degraded by the 26S proteasome complex. The pathway has been implicated in several forms of malignancy, in the pathogenesis of several genetic diseases (including cystic fibrosis, Angelman's syndrome, and Liddle syndrome), in immune surveillance/viral pathogenesis, and in the pathology of muscle wasting. The molecular mechanisms that underlie these processes are being unraveled at present.
Noninvasive real-time multipoint temperature control for ultrasound phased array treatments (1996)

A method for noninvasively estimating spatiotemporal temperature changes in samples using diagnostic ultrasound, and using these as inputs to a multipoint ultrasound phased array temperature controller, is presented in this paper. This method is based on a linear relationship between the apparent tissue echo pattern displacements and temperature, as seen along A-lines acquired with diagnostic ultrasound when the sample is heated by external heating fields. The proportionality constant between echo displacement and temperature is determined by the local change in speed of sound due to temperature and the linear coefficient of thermal expansion of the material. Accurate estimation of the displacements and proportionality constant yields accurate calibrated high-resolution (1 mm spatial, sub-/spl deg/C) noninvasive sample temperature estimates. These are used as inputs to a multipoint temperature controller, capable of controlling ultrasound phased array treatments in real-time. Phantom and in vitro results show that the noninvasively estimated temperature values can effectively be used to control ultrasound hyperthermia treatments, almost replacing invasive thermocouple measurements. The mathematical background and assumptions of the noninvasive temperature estimator and the controller are presented in this paper, together with experimental results showing estimator and controller performance and limitations. To the best of our knowledge, this paper presents the first demonstration of real-time treatment control based entirely on noninvasive temperature estimates.
Resting-State Neuroimaging Studies: A New Way of Identifying Differences and Similarities among the Anxiety Disorders? (2014)

This review examines recent functional neuroimaging research of resting-state regional connectivity between brain regions in anxiety disorders. Studies compiled in the PubMed- National Center for Biotechnology Information database targeting resting-state functional connectivity in anxiety disorders were reviewed. Diagnoses included posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), panic disorder (PD), and specific phobia (SP). Alterations to network connectivity were demonstrated in PTSD, GAD, SAD, OCD, and PD in several resting-state investigations. Differences from control subjects were primarily observed in the default mode network within PTSD, SAD, and OCD. Alterations within the salience network were observed primarily in PTSD, GAD, and SAD. Alterations in corticostriatal networks were uniquely observed in OCD. Finally, alterations within somatosensory networks were observed in SAD and PD investigations. Resting-state studies involving SPs as a primary diagnosis (with or without comorbidities) were not generated during the literature search. The emerging use of resting-state paradigms may be an effective method for understanding associations between anxiety disorders. Targeted studies of PD and SPs, meta-analyses of the studies conducted to date, and studies of the impact of specific comorbid presentations, are recommended future research directions.
Inhibition of biofilm formation and swarming of Bacillus subtilis by (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone (2002)

Natural furanone has potential for controlling the multicellular behaviour of Gram-positive bacteria.
Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells (1993)

The adenovirus penton base protein has a cell rounding activity and may lyse endosomes during virus entry into the cytoplasm. We found that penton base that was expressed in Escherichia coli also caused cell rounding and that cells adhered to polystyrene wells that were coated with the protein. Mutant analysis showed that both properties required an Arg-Gly-Asp (RGD) sequence at residues 340 to 342 of penton base. In flat adherent cells, virus mutants with amino acid substitutions in the RGD sequence were delayed in virus reproduction and in the onset of viral DNA synthesis. In nonadherent or poorly spread cells, the kinetics of mutant virus reproduction were similar to those of wild-type adenovirus type 2. Expression of the mutant phenotype exclusively in the flat cells that we tested supports a model in which penton base interacts with an RGD-directed cell adhesion molecule during adenovirus uptake or uncoating.
Cyclic Pull-Out Strength of Hamstring Tendon Graft Fixation with Soft Tissue Interference Screws (1999)

Blunt-threaded interference screws used for fixation of hamstring tendons in anterior cruciate ligament reconstructions provide aperture fixation and may provide a biomechanically more stable graft than a graft fixed further from the articular surface. It is unknown if soft tissue fixation strength using interference screws is affected by screw length. We compared the cyclic and time-zero pull-out forces of 7 x 25 mm and 7 x 40 mm blunt-threaded metal interference screws for hamstring graft tibial fixation in eight paired human cadaveric specimens. A four-stranded autologous hamstring tendon graft was secured by a blunt-threaded interference screw into a proximal tibial tunnel with a diameter corresponding to the graft width. Eight grafts were secured with a 25-mm length screw while the other eight paired grafts were secured with a 40-mm length screw. During cyclic testing, slippage of the graft occurred as the force of pull became greater with each cycle until the graft-screw complex ultimately failed. All grafts failed at the fixation site, with the tendon being pulled past the screw. There were no measurable differences in the mean cyclic failure strength, pull-out strength, or stiffness between the two sizes of screws. Although use of the longer screw would make removal technically easier should revision surgery be necessary, it did not provide stronger fixation strength than the shorter, standard screw as had been postulated.
ENZYMATIC OXYGEN FIXATION INTO ACETATE CONCOMITANT WITH THE ENZYMATIC DECARBOXYLATION OF L-LACTATE (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTENZYMATIC OXYGEN FIXATION INTO ACETATE CONCOMITANT WITH THE ENZYMATIC DECARBOXYLATION OF L-LACTATEOsamu Hayaishi and W. B. SuttonCite this: J. Am. Chem. Soc. 1957, 79, 17, 4809–4810Publication Date (Print):September 1, 1957Publication History Published online1 May 2002Published inissue 1 September 1957https://pubs.acs.org/doi/10.1021/ja01574a060https://doi.org/10.1021/ja01574a060research-articleACS PublicationsRequest reuse permissionsArticle Views141Altmetric-Citations38LEARN 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
Reflow of obstructed capillaries in the maculae of humans with diabetic retinopathy, observed by fluorescein angiography. (1988)

As diabetic retinopathy progresses, the non-perfused area in the retina gradually enlarges as the capillaries are obstructed. To elucidate the process of capillary obstruction we examined macular capillaries in 104 diabetics, using fluorescein angiography. The follow-up period was three to eight years. We found that some capillaries in the macular were obstructed, then became unobstructed. Reflow of blood into the macula after the obstruction was observed in nine patients (8.7%). The time between obstruction and reflow varied from two months to four years. There were four cases of simple, three of preproliferative, and two of proliferative retinopathy. Reflow in the capillaries was confirmed as occurring at the same position and in vessels with the same diameter as seen before the obstruction. There was no leakage of the fluorescein dye from the capillary where reflow took place. We tentatively conclude that one of the causes of this phenomenon is a functional obstruction.
Isolation of extracellular vesicles: Determining the correct approach (Review) (2015)

The discovery of extracellular vesicles (EVs) has revised the interpretation of intercellular communication. It is now well established that EVs play a significant role in coagulation, inflammation, cancer and stem cell renewal and expansion. Their release presents an intriguing, transporting/trafficking network of biologically active molecules, which are able to reach and modulate the function/behavior of the target cells in a variety of ways. Moreover, the presence of EVs in various body fluids points to their potential for use as biomarkers and prognostic indicators in the surveillance/monitoring of a variety of diseases. Although vast knowledge on the subject of EVs has accumulated over the years, there are still fundamental issues associated with the correct approach for their isolation. This review comprises the knowledge on EV isolation techniques that are currently available. The aim of this reveiw was to make both experienced researchers and newcomers to the field aware that different types of EVs require unique isolation approaches. The realization of this 'uniqueness' is the first step in the right direction for the complete assessment of EVs.