Large ptp_t enhancement from freeze out

Freeze out of particles across three dimensional space-time hypersurface is discussed in a simple kinetic model. The final momentum distribution of emitted particles, for freeze out surfaces with space-like normal, shows a non-exponential transverse momentum spectrum. The slope parameter of the $p_t$ distribution increases with increasing $p_t$, in agreement with recently measured SPS pion and $h^-$ spectra.Comment: 8 pages, 1 figure. Accepted for publication in Physics Letters

Impact of the Specific Mutation in KRAS Codon 12 Mutated Tumors on Treatment Efficacy in Patients with Metastatic Colorectal Cancer Receiving Cetuximab-Based First-Line Therapy: A Pooled Analysis of Three Trials

Purpose: This study investigated the impact of specific mutations in codon 12 of the Kirsten-ras (KRAS) gene on treatment efficacy in patients with metastatic colorectal cancer (mCRC). Patients: Overall, 119 patients bearing a KRAS mutation in codon 12 were evaluated. All patients received cetuximab-based first-line chemotherapy within the Central European Cooperative Oncology Group (CECOG), AIO KRK-0104 or AIO KRK-0306 trials. Results: Patients with KRAS codon 12 mutant mCRC showed a broad range of outcome when treated with cetuximab-based first-line regimens. Patients with tumors bearing a KRAS p.G12D mutation showed a strong trend to a more favorable outcome compared to other mutations (overall survival 23.3 vs. 14-18 months; hazard ratio 0.66, range 0.43-1.03). An interaction model illustrated that KRAS p.G12C was associated with unfavorable outcome when treated with oxaliplatin plus cetuximab. Conclusion: The present analysis suggests that KRAS codon 12 mutation may not represent a homogeneous entity in mCRC when treated with cetuximab-based first-line therapy. Copyright (C) 2012 S. Karger AG, Base

Massively parallel computing on an organic molecular layer

Current computers operate at enormous speeds of ~10^13 bits/s, but their principle of sequential logic operation has remained unchanged since the 1950s. Though our brain is much slower on a per-neuron base (~10^3 firings/s), it is capable of remarkable decision-making based on the collective operations of millions of neurons at a time in ever-evolving neural circuitry. Here we use molecular switches to build an assembly where each molecule communicates-like neurons-with many neighbors simultaneously. The assembly's ability to reconfigure itself spontaneously for a new problem allows us to realize conventional computing constructs like logic gates and Voronoi decompositions, as well as to reproduce two natural phenomena: heat diffusion and the mutation of normal cells to cancer cells. This is a shift from the current static computing paradigm of serial bit-processing to a regime in which a large number of bits are processed in parallel in dynamically changing hardware.Comment: 25 pages, 6 figure

Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams-Oliver Syndrome With Variable Cardiac Anomalies.

BACKGROUND: Adams-Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS. METHODS AND RESULTS: Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating NOTCH1 mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique NOTCH1 mutations, including 3 de novo amino acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of NOTCH1-positive probands and affected family members. In leukocyte-derived RNA from subjects harboring NOTCH1 extracellular domain mutations, we observed significant reduction of NOTCH1 expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized NOTCH1 missense constructs also revealed significant reduction in gene expression. Mutant NOTCH1 expression was associated with downregulation of the Notch target genes HEY1 and HES1, indicating that NOTCH1-related AOS arises through dysregulation of the Notch signaling pathway. CONCLUSIONS: These findings highlight a key role for NOTCH1 across a range of developmental anomalies that include cardiac defects and implicate NOTCH1 haploinsufficiency as a likely molecular mechanism for this group of disorders

An introduction to Graph Data Management

A graph database is a database where the data structures for the schema and/or instances are modeled as a (labeled)(directed) graph or generalizations of it, and where querying is expressed by graph-oriented operations and type constructors. In this article we present the basic notions of graph databases, give an historical overview of its main development, and study the main current systems that implement them

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents

Neural responses to others’ pain vary with psychopathic traits in healthy adult males

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid- and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affective-interpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population

The role of rigidity in adaptive and maladaptive families assessed by FACES IV: the points of view of adolescents

Previous studies using Olson’s Circumplex Model and FACES IV, the self-report assessing family functioning, did not clarify the role of rigidity, a dimension of this model. Rigidity emerged as ambiguous: it was considered either as a functional or as a dysfunctional dimension. Building upon the results of previous studies, we provided a contribution intended to disambiguate the role of rigidity considering adolescents’ perceptions and using a non-a priori classification analysis. 320 Italian adolescents (13–21 years) participated in this study and responded to a questionnaire containing scales of the study variables. A latent class analysis was performed to identify the association of rigidity with the other dimensions of Olson’s model and with indicators of adaptive family functioning in adolescence: parental monitoring and family satisfaction. We found six clusters corresponding to family typologies and having different levels of functioning. Rigidity emerged as adaptive in the typologies named rigidly balanced and flexibly oscillating; it was associated with positive dimensions of family functioning, i.e. flexibility, cohesion, parental monitoring, and high levels of family satisfaction. Differently, when rigidity was associated with disengagement, low cohesion and flexibility, and lack of parental supervision, emerged as maladaptive. This was the case of two typologies: the rigidly disengaged and the chaotically disengaged. Adolescents of these families reported the lowest levels of satisfaction. In the two last typologies, the flexibly chaotic and the cohesively disorganized, rigidity indicated a mid-range functionality as these families were characterized by emotional connectedness but lack of containment. Clinical implications are discussed

Anticipation of guilt for everyday moral transgressions : the role of the anterior insula and the influence of interpersonal psychopathic traits

Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in atypical affective/motivational processing, as opposed to an inability to judge the wrongness of an action. Guilt is a moral emotion believed to play a crucial role in adherence to moral and social norms, but the mechanisms by which guilt (or lack thereof) may influence behaviour in individuals with high levels of psychopathic traits are unclear. We measured neural responses during the anticipation of guilt about committing potential everyday moral transgressions, and tested the extent to which these varied with psychopathic traits. We found a significant interaction between the degree to which anticipated guilt was modulated in the anterior insula and interpersonal psychopathic traits: anterior insula modulation of anticipated guilt was weaker in individuals with higher levels of these traits. Data from a second sample confirmed that this pattern of findings was specific to the modulation of anticipated guilt and not related to the perceived wrongness of the transgression. These results suggest a central role for the anterior insula in coding the anticipation of guilt regarding potential moral transgressions and advance our understanding of the neurocognitive mechanisms that may underlie propensity to antisocial behaviour

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV