Fractal Properties of the Distribution of Earthquake Hypocenters

We investigate a recent suggestion that the spatial distribution of earthquake hypocenters makes a fractal set with a structure and fractal dimensionality close to those of the backbone of critical percolation clusters, by analyzing four different sets of data for the hypocenter distributions and calculating the dynamical properties of the geometrical distribution such as the spectral dimension $d_s$. We find that the value of $d_s$ is consistent with that of the backbone, thus supporting further the identification of the hypocenter distribution as having the structure of the percolation backbone.Comment: 11 pages, LaTeX, HLRZ 68/9

The Productivity Consequences of Two Ergonomic Interventions

Pre- and post-intervention data on health outcomes, absenteeism, and productivity from a longitudinal, quasi-experimental design field study of office workers was used to evaluate the economic consequences of two ergonomic interventions. Researchers assigned individuals in the study to three groups: a group that received an ergonomically designed chair and office ergonomics training; a group that received office ergonomics training only; and a control group. The results show that while training alone has neither a statistically significant effect on health nor productivity, the chair-with-training intervention substantially reduced pain and improved productivity. Neither intervention affected sick leave hours

Analysis of resistance gene-mediated defense responses in Arabidopsis thaliana plants carrying a mutation in CPR5

In resistant plants, pathogen attack often leads to rapid activation of defense responses that limit multiplication and spread of the pathogen. To investigate the signaling mechanisms underlying this process, we carried out a screen for mutants in the signaling pathway governing resistance in Arabidopsis thaliana to the bacterial pathogen Pseudomonas syringae. This involved screening for suppressor mutations that restored resistance to a susceptible line carrying a mutation in the RPS2 resistance gene. A mutant that conferred resistance by activating defense responses in the absence of pathogens was isolated. This mutant, which carries a mutation at the CPR5 locus and was thus designated cpr5-2, exhibited resistance to P. syringae, spontaneous development of necrotic lesions, elevated PR gene expression in the absence of pathogens, and abnormal trichomes. Resistance gene-mediated defenses, including the hypersensitive response, restriction of pathogen growth, and induction of defense-related gene expression, were functional in cpr5-2 mutant plants. Additionally, in cpr5-2 plants RPS2-mediated induction of PR-1 expression was enhanced, whereas RPM1-mediated induction of ELI3 was not. These findings suggest that CPR5 encodes a negative regulator of the RPS2 signal transduction pathway

Hypoxia Inactivates the VHL Tumor Suppressor through PIASy-Mediated SUMO Modification

The hypoxic microenvironment contributes to embryonic development and tumor progression through stabilization of the potent transcriptional factor HIFα. In normoxia, the tumor suppressor protein VHL acts as an E3 ubiquitin ligase to target HIFα for proteolytic destruction. Increasing evidence shows that VHL is a multifunctional adaptor involved in inhibition of HIFα-dependent and independent cellular processes. However, the molecular effect of hypoxic stress on VHL functions remains elusive. Here we report that PIASy, a SUMO E3 ligase upregulated in hypoxia, interacts with VHL and induces VHL SUMOylation on lysine residue 171. Moreover, PIASy-mediated SUMO1 modification induces VHL oligomerization and abrogates its inhibitory function on tumor cell growth, migration and clonogenicity. Knockdown of PIASy by small interfering RNA leads to reduction of VHL oligomerization and increases HIF1α degradation. These findings reveal a unique molecular strategy for inactivation of VHL under hypoxic stress

Undergraduate Rehabilitation Education and Accreditation: The Importance of Being Persistent

This article presents an overview of undergraduate rehabilitation education (URE) and the movement toward accreditation. Tracing the history of URE from the earliest days of rehabilitation education programs up to the present, this review discusses the purposes of URE, traditional URE program curricula, where URE graduates have been (and are being) employed, and the relationship between UREs and graduate rehabilitation counseling programs. The article also explains the development of URE curriculum and program standards, the development of a registry of qualified URE programs, and the transition to accreditation of URE programs in the United States. The purposes of accreditation are described, along with the advantages that accreditation offers to URE programs, their students, and to persons with disabilities

Pre‐pregnancy health of women with pre‐existing diabetes or previous gestational diabetes : analysis of pregnancy risk factors and behavioural data from a digital tool

Aims: To examine health behaviours and risk factors in women with pre‐existing diabetes or previous gestational diabetes mellitus who are planning pregnancy. Methods: Health behaviour, risk factor and demographic data obtained from a digital pregnancy planning advisory tool (Tommy's charity UK) were analysed. Descriptive statistical analysis was performed, stratified by diabetes type. Results: Data from 84,359 women, including 668 with type 1 diabetes, 707 with type 2 diabetes and 1785 with previous gestational diabetes obtained over a 12‐month period (September 2019–September 2020) were analysed. 65%, 95%CI (61,68%) of women with type 2 diabetes and 46%, 95%CI (43,48%) with previous gestational diabetes were obese (BMI ≥30 kg/m2), compared with 26%, 95%CI (26,26%) without diabetes. Use of folic acid supplements was low; 41%, 95%CI (40,41%) of women without diabetes and 42%, 95%CI (40,45%) with previous gestational diabetes reported taking folic acid (any dose) while 47%, 95%CI (43.50%) women with type 1 diabetes and 44%, 95%CI (40,47%) women with type 2 diabetes respectively reported taking the recommended dose (5 mg). More women with type 1 diabetes and type 2 diabetes reported smoking (20%, 95%CI [17,23%] and 23%, 95%CI [20,26%] respectively) and taking illicit/recreational drugs (7%, 95%CI [6,10%] and 9%, 95% CI [7,11%]) compared to women without diabetes (smoking 17%, 95% CI [16,17%], drug use 5%, 95%CI [5,5%]). Alcohol consumption, low levels of physical activity and of fruit and vegetable intake were also evident. Conclusions: This study highlights the potential of online pregnancy planning advisory tools to reach high‐risk women and emphasises the need to improve pre‐pregnancy care for women with pre‐existing diabetes and previous gestational diabetes, many of whom are actively seeking advice. It is also the first to describe pre‐pregnancy health behaviours in women with previous gestational diabetes

RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth

In B cells infected by the cancer-associated Epstein-Barr virus (EBV), RUNX3 and RUNX1 transcription is manipulated to control cell growth. The EBV-encoded EBNA2 transcription factor (TF) activates RUNX3 transcription leading to RUNX3-mediated repression of the RUNX1 promoter and the relief of RUNX1-directed growth repression. We show that EBNA2 activates RUNX3 through a specific element within a −97 kb super-enhancer in a manner dependent on the expression of the Notch DNA-binding partner RBP-J. We also reveal that the EBV TFs EBNA3B and EBNA3C contribute to RUNX3 activation in EBV-infected cells by targeting the same element. Uncovering a counter-regulatory feed-forward step, we demonstrate EBNA2 activation of a RUNX1 super-enhancer (−139 to −250 kb) that results in low-level RUNX1 expression in cells refractory to RUNX1-mediated growth inhibition. EBNA2 activation of the RUNX1 super-enhancer is also dependent on RBP-J. Consistent with the context-dependent roles of EBNA3B and EBNA3C as activators or repressors, we find that these proteins negatively regulate the RUNX1 super-enhancer, curbing EBNA2 activation. Taken together our results reveal cell-type-specific exploitation of RUNX gene super-enhancers by multiple EBV TFs via the Notch pathway to fine tune RUNX3 and RUNX1 expression and manipulate B-cell growth

A Bayesian view of murine seminal cytokine networks

It has long been established that active agents in seminal fluid are key to initiating and coordinating mating-induced immunomodulation. This is in part governed by the actions of a network of cytokine interactions which, to date, remain largely undefined, and whose interspecific evolutionary conservation is unknown. This study applied Bayesian methods to illustrate the interrelationships between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and vascular endothelial growth factor (VEGF) in a rat model. IL-2, IL-9, IL-12 (p70), IL-13, IL-18, eotaxin, IFN-gamma, IP-10, KC, leptin, MCP-1, MIP-1alpha and TNF-alpha were significantly higher in serum, whilst IL-1beta, IL-5, IL-6, IL-10, IL-17, G-CSF and GM-CSF were significantly higher in seminal fluid. When compared to mouse profiles, only G-CSF was present at significantly higher levels in the seminal fluid in both species. Bayesian modelling highlighted key shared features across mouse and rat networks, namely TNF-alpha as the terminal node in both serum and seminal plasma, and MCP-1 as a central coordinator of seminal cytokine networks through the intermediary of KC and RANTES. These findings reveal a marked interspecific conservation of seminal cytokine networks

Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis

The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. Purpose: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. Experimental Design: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. Results: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with ‘basal-like’ immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. Conclusions: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas

Seismic imaging in Long Valley, California, by surface and borehole techniques: An investigation of active tectonics

The search for silicic magma in the upper crust is converging on the Long Valley Caldera of eastern California, where several lines of geophysical evidence show that an active magma chamber exists at mid‐to lower‐crustal depths. There are also other strong indications that magma may be present at depths no greater than about 5 km below the surface. In this paper, we review the history of the search for magma at Long Valley. We also present the preliminary results from a coordinated suite of seismic experiments, conducted by a consortium of institutions in the summer and fall of 1984, that were designed to refine our knowledge of the upper extent of the magma chamber. Major funding for the experiments was provided by the Geothermal Research Program of the U.S. Geological Survey (USGS) and by the Magma Energy Technology Program of the U.S. Department of Energy (DOE), a program to develop the technology necessary to extract energy directly from crustal magma. Additional funding came from DOE's Office of Basic Energy Sciences and the National Science Foundation (NSF). Also, because extensive use was made of a 0.9‐km‐deep well lent to us by Santa Fe Geothermal, Inc., the project was conducted partly under the auspices of the Continental Scientific Drilling Program (CSDP). As an integrated seismic study of the crust within the caldera that involved the close cooperation of a large number of institutions, the project was moreover viewed as a prototype for future scientific experiments to be conducted under the Program for Array Seismic Studies of the Continental Lithosphere (PASSCAL). The experiment thus represented a unique blend of CSDP and PASSCAL methods, and achieved goals consistent with both programs