6,809 research outputs found
A Different Approach to Jensen’s Alpha and Its Relationship with Returning Ranking
Based on Michael C. Jensen’s CAPM model (1968), this paper refines it with dummy variables included. It examines if fund manager’s skill is contributing to fund’s performance within a five-year span from June 2009 to June 2014, and if high total return ranking is related to outstanding Jensen’s Alpha. The findings coincide with Jensen’s research results
Neuropilin 1 is an entry factor that promotes EBV infection of nasopharyngeal epithelial cells
Epstein-Barr virus (EBV) is implicated as an aetiological factor in B lymphomas and nasopharyngeal carcinoma. The mechanisms of cell-free EBV infection of nasopharyngeal epithelial cells remain elusive. EBV glycoprotein B (gB) is the critical fusion protein for infection of both B and epithelial cells, and determines EBV susceptibility of non-B cells. Here we show that neuropilin 1 (NRP1) directly interacts with EBV gB 23-431. Either knockdown of NRP1 or pretreatment of EBV with soluble NRP1 suppresses EBV infection. Upregulation of NRP1 by overexpression or EGF treatment enhances EBV infection. However, NRP2, the homologue of NRP1, impairs EBV infection. EBV enters nasopharyngeal epithelial cells through NRP1-facilitated internalization and fusion, and through macropinocytosis and lipid raft-dependent endocytosis. NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. Taken together, NRP1 is identified as an EBV entry factor that cooperatively activates RTK signalling, which subsequently promotes EBV infection in nasopharyngeal epithelial cells. © 2014 Macmillan Publishers Limited. All rights reserved.published_or_final_versio
Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration
Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies
First direct observation of Dirac fermions in graphite
Originating from relativistic quantum field theory, Dirac fermions have been
recently applied to study various peculiar phenomena in condensed matter
physics, including the novel quantum Hall effect in graphene, magnetic field
driven metal-insulator-like transition in graphite, superfluid in 3He, and the
exotic pseudogap phase of high temperature superconductors. Although Dirac
fermions are proposed to play a key role in these systems, so far direct
experimental evidence of Dirac fermions has been limited. Here we report the
first direct observation of massless Dirac fermions with linear dispersion near
the Brillouin zone (BZ) corner H in graphite, coexisting with quasiparticles
with parabolic dispersion near another BZ corner K. In addition, we report a
large electron pocket which we attribute to defect-induced localized states.
Thus, graphite presents a novel system where massless Dirac fermions,
quasiparticles with finite effective mass, and defect states all contribute to
the low energy electronic dynamics.Comment: Nature Physics, in pres
NLO QCD Corrections to -to-Charmonium Form Factors
The meson to S-wave Charmonia transition form factors are
calculated in next-to-leading order(NLO) accuracy of Quantum
Chromodynamics(QCD). Our results indicate that the higher order corrections to
these form factors are remarkable, and hence are important to the
phenomenological study of the corresponding processes. For the convenience of
comparison and use, the relevant expressions in asymptotic form at the limit of
for the radiative corrections are presented
Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application
Background
The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A).
Results
The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection.
Conclusions
E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin
A compact statistical model of the song syntax in Bengalese finch
Songs of many songbird species consist of variable sequences of a finite
number of syllables. A common approach for characterizing the syntax of these
complex syllable sequences is to use transition probabilities between the
syllables. This is equivalent to the Markov model, in which each syllable is
associated with one state, and the transition probabilities between the states
do not depend on the state transition history. Here we analyze the song syntax
in a Bengalese finch. We show that the Markov model fails to capture the
statistical properties of the syllable sequences. Instead, a state transition
model that accurately describes the statistics of the syllable sequences
includes adaptation of the self-transition probabilities when states are
repeatedly revisited, and allows associations of more than one state to the
same syllable. Such a model does not increase the model complexity
significantly. Mathematically, the model is a partially observable Markov model
with adaptation (POMMA). The success of the POMMA supports the branching chain
network hypothesis of how syntax is controlled within the premotor song nucleus
HVC, and suggests that adaptation and many-to-one mapping from neural
substrates to syllables are important features of the neural control of complex
song syntax
Quantum Hall effect and Landau level crossing of Dirac fermions in trilayer graphene
We investigate electronic transport in high mobility (\textgreater 100,000
cm/Vs) trilayer graphene devices on hexagonal boron nitride, which
enables the observation of Shubnikov-de Haas oscillations and an unconventional
quantum Hall effect. The massless and massive characters of the TLG subbands
lead to a set of Landau level crossings, whose magnetic field and filling
factor coordinates enable the direct determination of the
Slonczewski-Weiss-McClure (SWMcC) parameters used to describe the peculiar
electronic structure of trilayer graphene. Moreover, at high magnetic fields,
the degenerate crossing points split into manifolds indicating the existence of
broken-symmetry quantum Hall states.Comment: Supplementary Information at
http://jarilloherrero.mit.edu/wp-content/uploads/2011/04/Supplementary_Taychatanapat.pd
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies
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