VisiStat: visualization-driven, interactive statistical analysis

Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light-and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, theyalso exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. in this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. the present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs. (C) 2014 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, São Paulo, SP, BrazilUniv Parma, Dept Biomed Biotechnol & Translat Sci, Microbiol & Virol Unit, I-43121 Parma, ItalyRecepta Biopharma, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, São Paulo, SP, BrazilFAPESP: 2010/51423-0Web of Scienc

Drag and jet quenching of heavy quarks in a strongly coupled N=2* plasma

The drag of a heavy quark and the jet quenching parameter are studied in the strongly coupled N=2* plasma using the AdS/CFT correspondence. Both increase in units of the spatial string tension as the theory departs from conformal invariance. The description of heavy quark dynamics using a Langevin equation is also considered. It is found that the difference between the velocity dependent factors of the transverse and longitudinal momentum broadening of the quark admit an interpretation in terms of relativistic effects, so the distribution is spherical in the quark rest frame. When conformal invariance is broken there is a broadening of the longitudinal momentum distribution. This effect may be useful in understanding the jet distribution observed in experiments.Comment: 30 pages, 5 figures, references added, minor corrections. To be published in JHE

Nuclear Alpha-Particle Condensates

The $\alpha$-particle condensate in nuclei is a novel state described by a product state of $\alpha$'s, all with their c.o.m. in the lowest 0S orbit. We demonstrate that a typical $\alpha$-particle condensate is the Hoyle state ($E_{x}=7.65$ MeV, $0^+_2$ state in $^{12}$C), which plays a crucial role for the synthesis of $^{12}$C in the universe. The influence of antisymmentrization in the Hoyle state on the bosonic character of the $\alpha$ particle is discussed in detail. It is shown to be weak. The bosonic aspects in the Hoyle state, therefore, are predominant. It is conjectured that $\alpha$-particle condensate states also exist in heavier $n\alpha$ nuclei, like $^{16}$O, $^{20}$Ne, etc. For instance the $0^+_6$ state of $^{16}$O at $E_{x}=15.1$ MeV is identified from a theoretical analysis as being a strong candidate of a $4\alpha$ condensate. The calculated small width (34 keV) of $0^+_6$, consistent with data, lends credit to the existence of heavier Hoyle-analogue states. In non-self-conjugated nuclei such as $^{11}$B and $^{13}$C, we discuss candidates for the product states of clusters, composed of $\alpha$'s, triton's, and neutrons etc. The relationship of $\alpha$-particle condensation in finite nuclei to quartetting in symmetric nuclear matter is investigated with the help of an in-medium modified four-nucleon equation. A nonlinear order parameter equation for quartet condensation is derived and solved for $\alpha$ particle condensation in infinite nuclear matter. The strong qualitative difference with the pairing case is pointed out.Comment: 71 pages, 41 figures, review article, to be published in "Cluster in Nuclei (Lecture Notes in Physics) - Vol.2 -", ed. by C. Beck, (Springer-Verlag, Berlin, 2011

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk

Two truncating variants in FANCC and breast cancer risk

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95% CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.Peer reviewe

Phase Behavior of Aqueous Na-K-Mg-Ca-CI-NO3 Mixtures: Isopiestic Measurements and Thermodynamic Modeling

A comprehensive model has been established for calculating thermodynamic properties of multicomponent aqueous systems containing the Na{sup +}, K{sup +}, Mg{sup 2+}, Ca{sup 2+}, Cl{sup -}, and NO{sub 3}{sup -} ions. The thermodynamic framework is based on a previously developed model for mixed-solvent electrolyte solutions. The framework has been designed to reproduce the properties of salt solutions at temperatures ranging from the freezing point to 300 C and concentrations ranging from infinite dilution to the fused salt limit. The model has been parameterized using a combination of an extensive literature database and new isopiestic measurements for thirteen salt mixtures at 140 C. The measurements have been performed using Oak Ridge National Laboratory's (ORNL) previously designed gravimetric isopiestic apparatus, which makes it possible to detect solid phase precipitation. Water activities are reported for mixtures with a fixed ratio of salts as a function of the total apparent salt mole fraction. The isopiestic measurements reported here simultaneously reflect two fundamental properties of the system, i.e., the activity of water as a function of solution concentration and the occurrence of solid-liquid transitions. The thermodynamic model accurately reproduces the new isopiestic data as well as literature data for binary, ternary and higher-order subsystems. Because of its high accuracy in calculating vapor-liquid and solid-liquid equilibria, the model is suitable for studying deliquescence behavior of multicomponent salt systems

Low pH and calcium effects on net Na+ and K+ fluxes in two catfish species from the Amazon River (Corydoras: Callichthyidae)

The present study analyzes Na+ and K+ disturbances caused by low pH in two catfish species from the Amazon River. Corydoras adolfoi inhabits ion-poor, black-stained, low pH (3.5-4.0) waters, while C. schwartzi is native to ion-rich waters at circumneutral pH. Fish were exposed to pH 3.5 Ca2+-free, and Ca2+-enriched (~500 µmol/l) water to determine the protective effects of calcium. Net Na+ and K+ fluxes were measured in the water collected from the fish experimental chambers. C. adolfoi was unable to control the Na+ efflux at low pH, exhibiting Na+ loss up to -594 ± 84 nmol g-1 h-1 during the first hour. After 3 and 6 h, net Na+ flux increased by 7- and 23-fold, respectively. In C. schwartzi, at pH 3.5, the initial high Na+ loss (-1,063 ± 73 nmol g-1 h-1) was gradually attenuated. A K+ loss occurred in both species, but remained relatively constant throughout exposure. High [Ca2+] affected ion losses in both species. C. adolfoi had 70% loss attenuation, indicating incapacity to control Na+ efflux. In C. schwartzi, elevated [Ca2+] completely prevented the Na+ losses caused by exposure to low pH. Rather different patterns were seen for K+ fluxes, with C. adolfoi showing no K+ disruption when exposed to low pH/high [Ca2+]. Thus, C. adolfoi loses Na+ during acid exposure, but has the ability to control K+ loss, while C. schwartzi controls diffusive Na+ loss but exhibits a slightly higher K+ loss. Ion balance was influenced by [Ca2+] at low pH in C. schwartzi but not in C. adolfoi