Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

"Dark energy" in the Local Void

The unexpected discovery of the accelerated cosmic expansion in 1998 has filled the Universe with the embarrassing presence of an unidentified "dark energy", or cosmological constant, devoid of any physical meaning. While this standard cosmology seems to work well at the global level, improved knowledge of the kinematics and other properties of our extragalactic neighborhood indicates the need for a better theory. We investigate whether the recently suggested repulsive-gravity scenario can account for some of the features that are unexplained by the standard model. Through simple dynamical considerations, we find that the Local Void could host an amount of antimatter ($\sim5\times10^{15}\,M_\odot$) roughly equivalent to the mass of a typical supercluster, thus restoring the matter-antimatter symmetry. The antigravity field produced by this "dark repulsor" can explain the anomalous motion of the Local Sheet away from the Local Void, as well as several other properties of nearby galaxies that seem to require void evacuation and structure formation much faster than expected from the standard model. At the global cosmological level, gravitational repulsion from antimatter hidden in voids can provide more than enough potential energy to drive both the cosmic expansion and its acceleration, with no need for an initial "explosion" and dark energy. Moreover, the discrete distribution of these dark repulsors, in contrast to the uniformly permeating dark energy, can also explain dark flows and other recently observed excessive inhomogeneities and anisotropies of the Universe.Comment: 6 pages, accepted as a Letter to the Editor by Astrophysics and Space Scienc

Not to normal order - Notes on the kinetic limit for weakly interacting quantum fluids

The derivation of the Nordheim-Boltzmann transport equation for weakly interacting quantum fluids is a longstanding problem in mathematical physics. Inspired by the method developed to handle classical dilute gases, a conventional approach is the use of the BBGKY hierarchy for the time-dependent reduced density matrices. In contrast, our contribution is motivated by the kinetic theory of the weakly nonlinear Schrodinger equation. The main observation is that the results obtained in the latter context carry over directly to weakly interacting quantum fluids provided one does not insist on normal order in the Duhamel expansion. We discuss the term by term convergence of the expansion and the equilibrium time correlation .Comment: 43 pages, corrected typos, updated assumptions in sec.

Some Consequences of Thermosolutal Convection: The Grain Structure of Castings

The essential principles of thermosolutal convection are outlined, and how convection provides a transport mechanism between the mushy region of a casting and the open bulk liquid is illustrated. The convective flow patterns which develop assist in heat exchange and macroscopic solute segregation during solidification; they also provide a mechanism for the transport of dendritic fragments from the mushy region into the bulk liquid. Surviving fragments become nuclei for equiaxed grains and so lead to blocking of the parental columnar, dendritic growth front from which they originated. The physical steps in such a sequence are considered and some experimental data are provided to support the argument

Thermal crop water stress index base line temperatures for sugarbeet in arid western U.S.

Sugarbeet is a deep-rooted crop in unrestricted soil profiles that can readily utilize stored soil water to reduce seasonal irrigation requirements. Utilization of soil water below 0.6 m is not commonly considered for irrigation scheduling due to the labor and expense of soil water monitoring at deeper depths and uncertainty in effective rooting depth and soil water holding capacity. Thermal-based crop water stress index (CWSI) irrigation scheduling for sugarbeet has the potential to overcome soil water monitoring limitations and facilitate utilization of stored soil water. The traditional canopy temperature based CWSI for monitoring plant water status has not been widely used for irrigated crops partly because of the need to know well-watered and non-transpiring canopy temperatures under identical environmental conditions. In this study, canopy temperature of irrigated sugarbeet under full irrigation (FIT) and 25%FIT in 2014, 2015, 2017 and 2018 in southcentral Idaho and FIT and 60%FIT in 2018 in northwestern Wyoming USA was monitored from full cover through harvest along with meteorological conditions and soil water content. Data driven models, multiple linear regression (MLR) and neural network (NN), were used to predict well-watered canopy temperature based on 15-min average values for solar radiation, air temperature, relative humidity, and wind speed collected within 2 hours of solar noon (13:00 – 16:00 MDT). The NN model had significantly less (p 0.6 m) soil water monitoring

Generalized Second Law of Thermodynamics in f(T)f(T) Gravity with Entropy Corrections

We study the generalized second law (GSL) of thermodynamics in $f(T)$ cosmology. We consider the universe as a closed bounded system filled with $n$ component fluids in the thermal equilibrium with the cosmological boundary. We use two different cosmic horizons: the future event horizon and the apparent horizon. We show the conditions under which the GSL will be valid in specific scenarios of the quintessence and the phantom energy dominated eras. Further we associate two different entropies with the cosmological horizons: with a logarithmic correction term and a power-law correction term. We also find the conditions for the GSL to be satisfied or violated by imposing constraints on model parameters.Comment: 17 pages, no figure, title changed, version accepted for publication in Astrophysics and Space Scienc

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review.

The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes