gebhart/patrepeval huggingface dataset:
LRRK2 phosphorylates membrane-bound Rabs and is activated by GTP-bound Rab7L1 to promote recruitment to the trans-Golgi network (2017)

Human genetic studies implicate LRRK2 and RAB7L1 in susceptibility to Parkinson disease (PD). These two genes function in the same pathway, as knockout of Rab7L1 results in phenotypes similar to LRRK2 knockout, and studies in cells and model organisms demonstrate LRRK2 and Rab7L1 interact in the endolysosomal system. Recently, a subset of Rab proteins have been identified as LRRK2 kinase substrates. Herein, we find that Rab8, Rab10, and Rab7L1 must be membrane and GTP-bound for LRRK2 phosphorylation. LRRK2 mutations that cause PD including R1441C, Y1699C, and G2019S all increase LRRK2 phosphorylation of Rab7L1 four-fold over wild-type LRRK2 in cells, resulting in the phosphorylation of nearly one-third the available Rab7L1 protein in cells. In contrast, the most common pathogenic LRRK2 mutation, G2019S, does not upregulate LRRK2-mediated phosphorylation of Rab8 or Rab10. LRRK2 interaction with membrane and GTP-bound Rab7L1, but not Rab8 or Rab10, results in the activation of LRRK2 autophosphorylation at the serine 1292 position, required for LRRK2 toxicity. Further, Rab7L1 controls the proportion of LRRK2 that is membrane-associated, and LRRK2 mutations enhance Rab7L1-mediated recruitment of LRRK2 to the trans-Golgi network. Interaction studies with the Rab8 and Rab10 GTPase-activating protein TBC1D4/AS160 demonstrate that LRRK2 phosphorylation may block membrane and GTP-bound Rab protein interaction with effectors. These results suggest reciprocal regulation between LRRK2 and Rab protein substrates, where Rab7L1-mediated upregulation of LRRK2 kinase activity results in the stabilization of membrane and GTP-bound Rab proteins that may be unable to interact with Rab effector proteins.
A matrix metalloproteinase 2 cleavable melittin/avidin conjugate specifically targets tumor cells in vitro and in vivo (2003)

Extracellular matrix breakdown as well as increased expression in cancer cells and tumor microvascular endothelial cells make matrix metalloproteinase 2 (MMP2) an attractive target for cancer treatment. By taking advantage of MMP2's properties, an MMP2 cleavable melittin/avidin conjugate was designed. Melittin alone is extremely toxic to cells and induces immediate cell lysis, but becomes inactive when coupled with avidin. The incorporation of the MMP2 target sequence into the peptide was used as a means for targeting tumor cells. In vitro, the melittin/avidin conjugate showed strong cytolytic activity against cancer cells with high MMP2 activity; DU 145 prostate cancer cells and SK-OV-3 ovarian cancer cells. The conjugate exhibited very little cytolytic activity against normal L-cells that displayed low MMP2 activity. These data demonstrate the MMP2 specificity of the melittin/avidin conjugate. In vivo, the size of tumors injected with the melittin/avidin conjugate was significantly smaller as compared to untreated tumors. Therefore, due to its tumor targeting capabilities as well as its cytolytic properties in vitro and in vivo, the melittin/avidin conjugate displays the potential for use in cancer therapy.
Antigenic Structure of Transmissible Gastroenteritis Virus. II. Domains in the Peplomer Glycoprotein (1986)

The antigenic structure of the peplomer glycoprotein E2 of the porcine transmissible gastroenteritis coronavirus (TGEV) was explored using a panel of 23 hybridoma antibodies (MAbs). The topography of the epitopes was established by means of a competition radioimmunoassay. Four main antigenic sites, termed A, B, C and D, were thus clearly delineated. Most of the neutralization-mediating determinants were found to cluster in the A-B area, which has been shown to be highly conserved among TGEV strains. Cooperative enhancement of binding to sites B and D was observed following attachment of MAbs relevant to site A. Additional epitopes were identified on E2 by MAbs that selectively recognized its intracellular precursor. Functional mapping was also performed using neutralization-resistant variants. Analysis of their reactivity confirmed part of the epitope linkages defined by the first approach. The overall lower frequency of such variants altered at site A suggested that some of the epitopes may play an essential function.
Amino acid substitutions in the poliovirus maturation cleavage site affect assembly and result in accumulation of provirions (1995)

The assembly of infectious poliovirus virions requires a proteolytic cleavage between an asparagine-serine amino acid pair (the maturation cleavage site) in VP0 after encapsidation of the genomic RNA. In this study, we have investigated the effects that mutations in the maturation cleavage site have on P1 polyprotein processing, assembly of subviral intermediates, and encapsidation of the viral genomic RNA. We have made mutations in the maturation cleavage site which change the asparagine-serine amino acid pair to either glutamine-glycine or threonine-serine. The mutations were created by site-directed mutagenesis of P1 cDNAs which were recombined into wild-type vaccinia virus to generate recombinant vaccinia viruses. The P1 polyproteins expressed from the recombinant vaccinia viruses were analyzed for proteolytic processing and assembly defects in cells coinfected with a recombinant vaccinia virus (VV-P3) that expresses the poliovirus 3CD protease. A trans complementation system using a defective poliovirus genome was utilized to assess the capacity of the mutant P1 proteins to encapsidate genomic RNA (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 67:3684-3690, 1993). The mutant P1 proteins containing the glutamine-glycine amino acid pair (VP4-QG) and the threonine-serine pair (VP4-TS) were processed by 3CD provided in trans from VV-P3. The processed capsid proteins VP0, VP3, and VP1 derived from the mutant precursor VP4-QG were unstable and failed to assemble into subviral structures in cells coinfected with VV-P3. However, the capsid proteins derived from VP4-QG did assemble into empty-capsid-like structures in the presence of the defective poliovirus genome. In contrast, the capsid proteins derived from processing of the VP4-TS mutant assembled into subviral intermediates both in the presence and in the absence of the defective genome RNA. By a sedimentation analysis, we determined that the capsid proteins derived from the VP4-TS precursor encapsidated the defective genome RNA. However, the cleavage of VP0 to VP4 and VP2 was delayed, resulting in the accumulation of provirions. The maturation cleavage of the VP0 protein containing the VP4-TS mutation was accelerated by incubation of the provirions at 37 degrees C. The results of these studies demonstrate that mutations in the maturation cleavage site have profound effects on the subsequent capability of the capsid proteins to assemble and provide evidence for the existence of the provirion as an assembly intermediate.
Cl-HCO3 exchange in choroid plexus: analysis by the DMO method for cell pH (1985)

[14C]DMO distribution was used to measure steady-state intracellular pH (pHi) and [HCO3]i in adult rat choroid plexus (CP) incubated in synthetic cerebrospinal fluid (CSF) for 30 min. In controls at 37 degrees C, mean pHi (6.95 at PCO2 = 30 mmHg) was close to corresponding in vivo values; and [HCO3]i/[HCO3]csf, i.e., rHCO3, was 0.37. At normal [HCO3]csf = 18 mM, cell HCO3 was accumulated threefold above electrochemical equilibrium (as estimated from Em = -50 mV). [HCO3]i decreased proportionally with [HCO3]csf, as the latter was altered from 47 to 9 mM; in severe extracellular acidosis [( HCO3]csf = 3.7 mM), [HCO3]i was not reduced further and so rHCO3 rose to 0.66. Except in low [HCO3]csf, acetazolamide and ouabain (10(-4) M) caused small depletion of cell HCO3. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid lowered [HCO3]i by 60%, thus decreasing rHCO3 (0.16) and rCl (0.25) to values close to estimated equilibrium distribution (0.15). Substitution of CSF Cl with isethionate resulted in marked alkalinization of pHi when [Cl]csf was depleted to 12 mM. Augmented PCO2 associated with temperature reduction to 15 degrees C elevated [HCO3]i, thereby increasing rHCO3 (to 0.66) as well as rCl. Anion distribution ratios indicate heteroanion exchange in mammalian CP.
Iejimalides Show Anti-Osteoclast Activity<i>via</i>V-ATPase Inhibition (2006)

Iejimalides (IEJLs), 24-membered macrolides, are potent antitumor compounds, but their molecular targets remain to be revealed. In the course of screening, we identified IEJLs as potent osteoclast inhibitors. Since it is known that osteoclasts are sensitive to vacuolar H(+)-ATPase (V-ATPase) inhibitor, we investigated the effect of IEJLs on V-ATPases. IEJLs inhibited the V-ATPases of both mammalian and yeast cells in situ, and of yeast V-ATPases in vitro. A bafilomycin-resistant yeast mutant conferred IEJL resistance, suggesting that IEJLs bind a site similar to the bafilomycins/concanamycins-binding site. These results indicate that IEJLs are novel V-ATPase inhibitors, and that antitumor and antiosteporotic activities are exerted via V-ATPase inhibition.
Tangible and modular input device for character articulation (2014)

Articulation of 3D characters requires control over many degrees of freedom: a difficult task with standard 2D interfaces. We present a tangible input device composed of interchangeable, hot-pluggable parts. Embedded sensors measure the device's pose at rates suitable for real-time editing and animation. Splitter parts allow branching to accommodate any skeletal tree. During assembly, the device recognizes topological changes as individual parts or pre-assembled subtrees are plugged and unplugged. A novel semi-automatic registration approach helps the user quickly map the device's degrees of freedom to a virtual skeleton inside the character. User studies report favorable comparisons to mouse and keyboard interfaces for the tasks of target acquisition and pose replication. Our device provides input for character rigging and automatic weight computation, direct skeletal deformation, interaction with physical simulations, and handle-based variational geometric modeling.
Standardized Full-Field Electroretinography in the Green Monkey (Chlorocebus sabaeus) (2014)

Full-field electroretinography is an objective measure of retinal function, serving as an important diagnostic clinical tool in ophthalmology for evaluating the integrity of the retina. Given the similarity between the anatomy and physiology of the human and Green Monkey eyes, this species has increasingly become a favorable non-human primate model for assessing ocular defects in humans. To test this model, we obtained full-field electroretinographic recordings (ERG) and normal values for standard responses required by the International Society for Clinical Electrophysiology of Vision (ISCEV). Photopic and scotopic ERG recordings were obtained by full-field stimulation over a range of 6 log units of intensity in dark-adapted or light-adapted eyes of adult Green Monkeys (Chlorocebus sabaeus). Intensity, duration, and interval of light stimuli were varied separately. Reproducible values of amplitude and latency were obtained for the a- and b-waves, under well-controlled adaptation and stimulus conditions; the i-wave was also easily identifiable and separated from the a-b-wave complex in the photopic ERG. The recordings obtained in the healthy Green Monkey matched very well with those in humans and other non-human primate species (Macaca mulatta and Macaca fascicularis). These results validate the Green Monkey as an excellent non-human primate model, with potential to serve for testing retinal function following various manipulations such as visual deprivation or drug evaluation.
Karyotype analysis and genetic variation of a mutant in Siraitia grosvenorii (2011)

This study analyzed the differences in karyotype and genetic variation between a mutant and wild-type Siraitia grosvenorii. Genetic variation included changes in genome and gene expression by SRAP molecular markers. Results showed that wild-type S. grosvenorii was diploid, with a chromosome number of 2n = 2x = 28, whereas the mutant was tetraploid with a chromosome number of 2n = 4x = 56. 4573 DNA bands were obtained using 189 different primer combinations, 577 of which were polymorphic, averaging 3.1 bands for each primer pair, while 1998 pairs were identical. There were no apparent differences on bands amplified by most primer pairs. After comparing the diploid and tetraploid strains, the data generally indicated that the polymorphism would be quite low. 2917 cDNA bands were generated using 133 primer combinations, and stable and clearly differential fragments were sorted out, cloned and sequenced. Ninety-two differentially expressed fragments were successfully sequenced. Sequence analysis showed that most fragments had significant homologous nucleotide sequences with resistant to stress and photosynthesis genes, including ribulose-1,5-bisphosphate carboxylase/oxygenase, phosphoenolpyruvate carboxykinase, pyruvate kinase, peroxisomal membrane transporter, NBS-LRR type resistance protein, protein phosphatase and others. The results revealed that the tetraploid strain has more resistant and photosynthesis ability than its diploid relatives, which providing reference information and resources for molecular breeding and seedless Luohanguo.
Plakoglobin: Role in Tumorigenesis and Metastasis (2012)

Plakoglobin (γ-catenin) is a member of the Armadillo family of proteins and a homolog of β-catenin. As a component of both the adherens junctions and desmosomes, plakoglobin plays a pivotal role in the regulation of cell-cell adhesion. Furthermore, similar to β-catenin, plakoglobin is capable of participating in cell signaling. However, unlike β-catenin that has well-documented oncogenic potential through its involvement in the Wnt signaling pathway, plakoglobin generally acts as a tumor/metastasis suppressor. The exact roles that plakoglobin plays during tumorigenesis and metastasis are not clear; however, recent evidence suggests that it may regulate gene expression, cell proliferation, apoptosis, invasion, and migration. In this paper, we describe plakoglobin, its discovery and characterization, its role in regulating cell-cell adhesion, and its signaling capabilities in regulation of tumorigenesis and metastasis.
Optical chiral metamaterials: a review of the fundamentals, fabrication methods and applications (2016)

Optical chiral metamaterials have recently attracted considerable attention because they offer new and exciting opportunities for fundamental research and practical applications. Through pragmatic designs, the chiroptical response of chiral metamaterials can be several orders of magnitude higher than that of natural chiral materials. Meanwhile, the local chiral fields can be enhanced by plasmonic resonances to drive a wide range of physical and chemical processes in both linear and nonlinear regimes. In this review, we will discuss the fundamental principles of chiral metamaterials, various optical chiral metamaterials realized by different nanofabrication approaches, and the applications and future prospects of this emerging field.
Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7) (2000)

Many matrix metalloproteinases (MMPs) are tightly bound to tissues; matrilysin (MMP-7), although the smallest of the MMPs, is one of the most tightly bound. The most likely docking molecules for MMP-7 are heparan sulfate proteoglycans on or around epithelial cells and in the underlying basement membrane. This is established by extraction experiments and confocal microscopy. The enzyme is extracted from homogenates of postpartum rat uterus by heparin/heparan sulfate and by heparinase III treatment. The enzyme is colocalized with heparan sulfate in the apical region of uterine glandular epithelial cells and can be released by heparinase digestion. Heparan sulfate and MMP-7 are expressed at similar stages of the rat estrous cycle. The strength of heparin binding by recombinant rat proMMP-7 was examined by affinity chromatography, affinity coelectrophoresis, and homogeneous enzyme-based binding assay; the K(D) is 5-10 nM. Zymographic measurement of MMP-7 activity is greatly enhanced by heparin. Two putative heparin-binding peptides have been identified near the C- and N-terminal regions of proMMP-7; however, molecular modeling suggests a more extensive binding track or cradle crossing multiple peptide strands. Evidence is also found for the binding of MMP-2, -9, and -13. Binding of MMP-7 and other MMPs to heparan sulfate in the extracellular space could prevent loss of secreted enzyme, provide a reservoir of latent enzyme, and facilitate cellular sensing and regulation of enzyme levels. Binding to the cell surface could position the enzyme for directed proteolytic attack, for activation of or by other MMPs and for regulation of other cell surface proteins. Dislodging MMPs by treatment with compounds such as heparin might be beneficial in attenuating excessive tissue breakdown such as occurs in cancer metastasis, arthritis, and angiogenesis.
Simultaneous determination of five sex hormones in human serum by radioimmunoassay after chromatography on Lipidex-5000. (1976)

We describe a method for determination of pregnenolone, progesterone, 17alpha-hydroxyprogesterone, testosterone, and 5alpha-dihydrotestosterone in 1-2 ml of serum from male or female. Using microcolumns of Lipidex-5000 (hydroxyalkoxypropyl Sephadex, 0.5 g) and light petroleum/chloroform (97/3) as the solvent during chromatography, we resolved these five steroids into four fractions, with pregnenolone and 5alpha-dihydrotestosterone eluting together. By use of selected antibodies, the latter two steroids were also determined specifically. Use of microcolumns allowed minimization of solvent volumes and sample transfers. Consequently, blank values for all the five steroids were negligible. Lowest measureable concentrations (in ng/liter) were: pregnenolone 100, progesterone 25, 17alpha-hydroxyprogesterone 50, testosterone 25, and 5alpha-dihydrotestosterone 25. Intra-assay and inter-assay coefficients of variation ranged from 5 to 9% and 10 to 15%, respectively, for the five steroids. Serum concentrations of these steroids are given for women in the follicular and luteal phases of the menstrual cycle and for women on oral contraceptives of the combination type, as well as for normal men.
Evaluation of preference for a novel durable insulin pen with memory function among patients with diabetes and health care professionals (2013)

NP5 was preferred to HPL by most participants. Significantly more patients with diabetes had more confidence for managing daily insulin injections when using NP5, the pen with a memory function.
전국체육대회 시범종목 경기장 시설에 대한 개선방향 -93회 전국체육대회 시범종목 지도자를 중심으로- (2013)

This study was to perform in order to offer basic data of current status about sports facilities for growing to developmental way aiming professional instructor who participated in exhibition sports fields such as Taekyeon, Dance sport, and mountain climbing on 93th national athletic competition. The results through the data analysis are drawn below. First of all, the satisfaction measurement was too negative about facilities of main and auxiliary stadium. So those stadium facilities are demanded to provide convenience for players as well as local residents`s participation. Second, the satisfaction measurement was comparatively negative about the safety matters and waiting times. So player`s waiting room should be provided to prepare competition and supervising department should pay attention to exhibition sports for not being discriminated with regular sports. Third, player`s waiting room and stadium stand are firstly and essentially demanded. Receiving positive evaluation about referee`s fairness is highly appreciated.
Using pseudo Kalman-filters in the presence of constraints application to sensing behaviors (1992)

A new generalization of the linear Kalman-Filter to non-linear equations is introduced. The deterministic interpretation of this mechanism is discussed. The proposed algorithm is an alternative to the well known Extended Kalman Filer. A small experimental illustration is given. An application to sensory-motor behaviors is proposed.
Quantitative Study of Fluoride Transport During Subsurface Dissolution of Dental Enamel (1989)

Previous studies using bovine dental enamel as a model have shown that surface and subsurface dissolution of enamel may be governed by micro-environmental solution conditions. We have now investigated the demineralization phenomenon more rigorously with the primary objective of developing a method for deducing solution species concentration profiles as a function of time from appropriate experimental data. More specifically, in this report, a model-independent method is described for determination of the pore solution fluoride gradients in bovine enamel during subsurface demineralization. Microradiography was used to determine the mineral density profiles, and an electron microprobe technique to determine total fluoride (F) profiles associated with the enamel. In each case, matched sections of bovine enamel were exposed to partially saturated acetate buffers at pH = 4.5 containing 0.5 ppm F for various periods of time (from six to 24 hours). The treated enamel was found to have an intact surface layer and subsurface demineralization. The extent of the demineralization and the depths of the lesions increased with time in all cases. The data were first used to calculate (a) the total F gradients in the enamel at various times, and (b) the local uptake rate of F as a function of time and position. Then, by manipulation of the equations describing the uptake and transport of F, we calculated the pore diffusion rate of F and the micro-environmental solution F concentration in the aqueous pores as a function of time and of distance from the enamel surface. It was also possible to calculate an intrinsic F diffusion coefficient in the pores, which was about 1.0 X 10(-5) cm2/sec, in good agreement with reported values. 14C-sucrose uptake and release experiments with identically prepared demineralized enamel sections were also conducted to provide an independent check on the assumed dependence of porosity on mineral density. The results of this investigation, especially the outcomes relative to this new method for determination of pore solution F gradients during acid attack of the dental enamel, should be valuable in future studies of the mechanism(s) of the action of F in inhibiting dental enamel demineralization.
First Synthesis of <i>N</i>-(3-Carboxylpropyl)-5-amino-2-hydroxy-3- tridecyl-1,4-benzoquinone, an Unusual Quinone Isolated from <i>Embelia </i><i>ribes</i> (2007)

The first synthesis of the unusual nitrogen-containing 3-alkyl-1,4-benzoquinone, N-(3-carboxylpropyl)-5-amino-2-hydroxy-3-tridecyl-1,4-benzoquinone, isolated from Embelia ribes, is reported. The key steps are a microwave-assisted combined Mitsunobu reaction-Claisen rearrangement to introduce the alkyl side chain into 2,5-dimethoxyphenol, followed by alkene reduction, oxidation to the quinone, and sequential displacement of the methoxy groups with hydroxide and GABA tert-butyl ester. Two other naturally occurring benzoquinones, O-methylrapanone and rapanone, were also prepared en route.
Revisiting the Efficiency of Malicious Two-Party Computation. (2006)

Abstract. In a recent paper Mohassel and Franklin study the efficiency of secure two-party computation in the presence of malicious behavior. Their aim is to make classical solutions to this problem, such as zero-knowledge compilation, more efficient. The authors provide several schemes which are the most efficient to date. We propose a modification to their main scheme using expanders. Our modification asymptotically improves at least one measure of efficiency of all known schemes. We also point out an error, and improve the analysis of one of their schemes.