Gadd45 in stress signaling

Gadd45 genes have been implicated in stress signaling in response to physiological or environmental stressors, which results in cell cycle arrest, DNA repair, cell survival and senescence, or apoptosis. Evidence accumulated implies that Gadd45 proteins function as stress sensors is mediated by a complex interplay of physical interactions with other cellular proteins that are implicated in cell cycle regulation and the response of cells to stress. These include PCNA, p21, cdc2/cyclinB1, and the p38 and JNK stress response kinases. What deterministic factors dictate whether Gadd45 and partner proteins function in either cell survival or apoptosis remains to be determined. An attractive working model to consider is that the extent of cellular/DNA damage, in a given cell type, dictates the association of different Gadd45 proteins with particular partner proteins, which determines the outcome

Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia

Purpose: Aberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. Experimental design: We compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative. Results: Dual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2. Conclusions: Inhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes

Sampling Plans for Control-Inspection Schemes Under Independent and Dependent Sampling Designs With Applications to Photovoltaics

The evaluation of produced items at the time of delivery is, in practice, usually amended by at least one inspection at later time points. We extend the methodology of acceptance sampling for variables for arbitrary unknown distributions when additional sampling infor- mation is available to such settings. Based on appropriate approximations of the operating characteristic, we derive new acceptance sampling plans that control the overall operating characteristic. The results cover the case of independent sampling as well as the case of dependent sampling. In particular, we study a modified panel sampling design and the case of spatial batch sampling. The latter is advisable in photovoltaic field monitoring studies, since it allows to detect and analyze local clusters of degraded or damaged modules. Some finite sample properties are examined by a simulation study, focusing on the accuracy of estimation

Oral health-related impact profile of patients treated with fixed, removable, and telescopic dental prostheses in student courses — a prospective bicenter clinical trial

Objectives!#!To analyze the oral health-related impact profile in patients treated with three different types of dental prosthesis in student courses.!##!Materials and methods!#!This prospective bicenter clinical trial was conducted with 151 patients being treated with fixed (n = 70), removable (n = 61), or telescopic dental prostheses (n = 20) in clinical student courses of two German universities from October 2018 to October 2019. All patients completed three standardized German versions of the Oral Health Impact Profile (OHIP-G49/53) before prosthetic treatment (T0), at control after 1 week (T1), and after 3 months (T2), divided into five dimensions: (a) appearance, (b) oral function, (c) psychosocial impact, (d) linguistic limitations, and (e) orofacial pain. Data were analyzed with Kolmogorov-Smirnov, Wilcoxon signed-rank, Kruskal-Wallis, Mann-Whitney, and Cronbach's alpha tests.!##!Results!#!Within T0-T1 and T0-T2, greater improvements were determined for removable compared with fixed dental prostheses for the dimensions' oral function (p ≤ 0.014), linguistic limitations (p ≤ 0.016), and appearance (p ≤ 0.003). No significant differences were found between fixed and telescopic dental prostheses (p ≥ 0.104) or between removable (partial dental prosthesis with clasps and complete dental prosthesis) and telescopic dental prostheses (p ≥ 0.100). Within T1-T2, a significant improvement in orofacial pain could be determined (p = 0.007).!##!Conclusions!#!Restorations presented an improvement in oral health-related quality of life. Removable dental prostheses showed better improvement than fixed ones in various dimensions.!##!Clinical relevance!#!Knowledge about the influence of oral health-related quality of life on the three different types of prosthesis used in student courses can be of decisive help in dental consultations

Non-abelian Harmonic Oscillators and Chiral Theories

We show that a large class of physical theories which has been under intensive investigation recently, share the same geometric features in their Hamiltonian formulation. These dynamical systems range from harmonic oscillations to WZW-like models and to the KdV dynamics on $Diff_oS^1$. To the same class belong also the Hamiltonian systems on groups of maps. The common feature of these models are the 'chiral' equations of motion allowing for so-called chiral decomposition of the phase space.Comment: 1

Study of the acoustic signature of UHE neutrino interactions in water and ice

The production of acoustic signals from the interactions of ultra-high energy (UHE) cosmic ray neutrinos in water and ice has been studied. A new computationally fast and efficient method of deriving the signal is presented. This method allows the implementation of up to date parameterisations of acoustic attenuation in sea water and ice that now includes the effects of complex attenuation, where appropriate. The methods presented here have been used to compute and study the properties of the acoustic signals which would be expected from such interactions. A matrix method of parameterising the signals, which includes the expected fluctuations, is also presented. These methods are used to generate the expected signals that would be detected in acoustic UHE neutrino telescopes.Comment: 21 pages and 13 figure

Health screenings in college health centers: Variations in practice

Objective: The purpose of this study was to examine the routine screening of female students in college health centers for six priority health-related behaviors and experiences (tobacco use, alcohol use, eating disorders [EDs], obesity, anxiety and depression, intimate partner violence/sexual violence [IPV/SV]), and to identify variations in practice. Participants: A nationally representative sample of 1,221 healthcare providers (HCPs), including nurse practitioners, physicians, and physician assistants, from 471 U.S. college health centers. Methods: HCPs completed surveys (on-line or paper) and reported on routine screening of female college students. Results: HCPs reported consistently high rates (75–85%) of screening for tobacco use, alcohol use, and anxiety/depression. Rates of screening for IPV/SV, obesity and EDs were much lower. Nurse practitioners reported the highest IPV/SV screening rates. Conclusions: College health centers present unique opportunities for screening, case-finding and intervening to reduce long-term sequelae. Providers are well-positioned to lead initiatives to improve screening practices

Measuring velocity of sound with nuclear resonant inelastic x-ray scattering

Nuclear resonant inelastic x-ray scattering is used to measure the projected partial phonon density of states of materials. A relationship is derived between the low-energy part of this frequency distribution function and the sound velocity of materials. Our derivation is valid for harmonic solids with Debye-like low-frequency dynamics. This method of sound velocity determination is applied to elemental, composite, and impurity samples which are representative of a wide variety of both crystalline and noncrystalline materials. Advantages and limitations of this method are elucidated