Multi-parameter generalization of nonextensive statistical mechanics

We show that the stochastic interpretation of Tsallis' thermostatistics given recently by Beck [Phys. Rev. Lett {\bf 87}, 180601 (2001)] leads naturally to a multi-parameter generalization. The resulting class of distributions is able to fit experimental results which cannot be reproduced within the Boltzmann's or Tsallis' formalism.Comment: ReVTex 4.0, 4 eps figure

Generalized Interpolation Material Point Approach to High Melting Explosive with Cavities Under Shock

Criterion for contacting is critically important for the Generalized Interpolation Material Point(GIMP) method. We present an improved criterion by adding a switching function. With the method dynamical response of high melting explosive(HMX) with cavities under shock is investigated. The physical model used in the present work is an elastic-to-plastic and thermal-dynamical model with Mie-Gr\"uneissen equation of state. We mainly concern the influence of various parameters, including the impacting velocity $v$, cavity size $R$, etc, to the dynamical and thermodynamical behaviors of the material. For the colliding of two bodies with a cavity in each, a secondary impacting is observed. Correspondingly, the separation distance $D$ of the two bodies has a maximum value $D_{\max}$ in between the initial and second impacts. When the initial impacting velocity $v$ is not large enough, the cavity collapses in a nearly symmetric fashion, the maximum separation distance $D_{\max}$ increases with $v$. When the initial shock wave is strong enough to collapse the cavity asymmetrically along the shock direction, the variation of $D_{\max}$ with $v$ does not show monotonic behavior. Our numerical results show clear indication that the existence of cavities in explosive helps the creation of ``hot spots''.Comment: Figs.2,4,7,11 in JPG format; Accepted for publication in J. Phys. D: Applied Physic

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development. Statement of significance PDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors

Multi-disciplinary efforts to evaluate the therapeutic potential of CDK11, a novel transcription associated cyclin dependent kinase.

View full abstracthttps://openworks.mdanderson.org/leading-edge/1043/thumbnail.jp

IL-22BP controls the progression of liver metastasis in colorectal cancer

BackgroundThe immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown.MethodsWe used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages.ResultsOur data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice.ConclusionsWe here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC

The Seniors' outdoor survey : an observational tool for assessing outdoor environments at long-term care settings

Purpose of the Study: To describe the development and psychometric testing of the Seniors\u2019 Outdoor Survey (SOS), an instrument for evaluating how well the outdoor space in a long-term care setting supports the preferences and outdoor usage of residents. Design and Methods: Content validity of the main SOS items initially was based on relevant literature and preliminary studies in diverse long-term care settings. After conducting a multiregional pilot study with 152 outdoor spaces at 68 assisted living facilities, the instrument was substantially revised and tested for interrater and test\u2013retest reliability with 22 outdoor spaces at 12 long-term care settings, using 2 raters. Validity was examined using content analysis of resident survey responses (N = 1,128) from the multiregional study and specific item validation by subject matter experts (N = 53). Results: The final instrument contains 60 ratable items organized in 5 domains: access to nature (14 items), outdoor comfort and safety (15 items), walking and outdoor activities (14 items), indoor\u2013outdoor connection (11 items), and connection to the world (6 items). Intraclass correlation coefficient (ICC) estimates of interrater reliability were .91 for the overall instrument, ranging from .83 to .98 for the 5 domains. Interrater reliability (ICC) was above .70 for more than 79% of individual items. Test\u2013retest reliability (ICC) was .92, ranging from .81 to .98 for domains. Implications: The SOS tool fills a gap in the available environmental assessment instruments, providing a reliable way for researchers, providers, and designers to evaluate and compare the supportive potential of outdoor spaces for long-term care residents

Measurement invariance of core cognitive abilities in heterogenous neurological and community samples.

Confirmatory factor analysis of Australian adaptations of combined Wechsler Adult Intelligence Scale-Revised (WAIS-R) and Wechsler Memory Scale-Revised (WMS-R) scores was conducted in a sample of 277 participants undergoing investigation for neurological disorders. The best-fitting model was a six-factor model representing the latent abilities of Verbal Comprehension, Perceptual Organization, Working Memory, Verbal Memory, Visual Memory, and Processing Speed. Invariance of the measurement model was then examined in the mean and covariance structure with data from a recent Australian normative study of the WAIS-R and WMS-R. [Carstairs J.R. & Shores E.A.Aust Psychol 35 (2000) 36-40]. Results suggest that the measurement model underlying test scores displayed “strong” metric invariance [Widaman, K. F., & Reise, S. P. (1997). Exploring the measurement invariance of psychological instruments: Applications in the substance abuse domain. In K. J. Bryant & M. Windle (Eds.), The science of prevention: Methodological advance from alcohol and substance abuse research (pp. 281–324). Washington, DC: American Psychological Association] across clinical and community samples. These findings satisfy assumptions necessary for uncomplicated interpretation of validity correlations and differences in test scores across groups

Viscoelastic models for explosive binder materials

An improved model of the mechanical properties of the explosive contained in conventional munitions is needed to accurately simulate performance and accident scenarios in weapons storage facilities. A specific class of explosives can he idealized as a mixture of two components: energetic crystals randomly suspended in a polymeric matrix (binder). Strength characteristics of each component material are important in the macroscopic behavior of the composite (explosive). Of interest here is the determination of an appropriate constitutive law for a polyurethane binder material. This paper is a continuation of previous work in modeling polyurethane at moderately high strain rates and for large deformations. Simulation of a large deformation (strains in excess of 100%) Taylor Anvil experiment revealed numerical difficulties which have been addressed. Additional experimental data have been obtained including improved resolution Taylor Anvil data, and stress relaxation data at various strain rates. A thorough evaluation of the candidate viscoelastic constitutive model is made and possible improvements discussed