Constructive Fractional-Moment Criteria for Localization in Random Operators

We present a family of finite-volume criteria which cover the regime of exponential decay for the fractional moments of Green functions of operators with random potentials. Such decay is a technically convenient characterization of localization for it is known to imply spectral localization, absence of level repulsion, dynamical localization and a related condition which plays a significant role in the quantization of the Hall conductance in two-dimensional Fermi gases. The constructive criteria also preclude fast power-law decay of the Green functions at mobility edges.Comment: Announcement and summary of results whose proofs are given elsewhere. LaTex (10 pages), uses Elsevier "elsart" files (attached

Impaired DNA double-strand break repair contributes to chemoresistance in HIF-1α-deficient mouse embryonic fibroblasts

A mismatch between metabolic demand and oxygen delivery leads to microenvironmental changes in solid tumors. The resulting tumor hypoxia is associated with malignant progression, therapy resistance and poor prognosis. However, the molecular mechanisms underlying therapy resistance in hypoxic tumors are not fully understood. The hypoxia-inducible factor (HIF) is a master transcriptional activator of oxygen-regulated gene expression. Transformed mouse embryonic fibroblasts (MEFs) derived from HIF-1α-deficient mice are a popular model to study HIF function in tumor progression. We previously found increased chemotherapy and irradiation susceptibility in the absence of HIF-1α. Here, we show by single-cell electrophoresis, histone 2AX phosphorylation and nuclear foci formation of γH2AX and 53BP1, that the number of DNA double-strand breaks (DSB) is increased in untreated and etoposide-treated HIF-deficient MEFs. In etoposide-treated cells, cell cycle control and p53-dependent gene expression were not affected by the absence of HIF-1α. Using a candidate gene approach to screen 17 genes involved in DNA repair, messenger RNA (mRNA) and protein of three members of the DNA-dependent protein kinase complex were found to be decreased in HIF-deficient MEFs. Of note, residual HIF-1α protein in cancer cells with a partial HIF-1α mRNA knockdown was sufficient to confer chemoresistance. In summary, these data establish a novel molecular link between HIF and DNA DSB repair. We suggest that selection of early, non-hypoxic tumor cells expressing low levels of HIF-1α might contribute to HIF-dependent tumor therapy resistanc

HIF mediated and DNA damage independent histone H2AX phosphorylation in chronic hypoxia

The histone variant 2AX (H2AX) is phosphorylated at Serine 139 by the PI3K-like kinase family members ATM, ATR and DNA-PK. Genotoxic stress, such as tumor radio- and chemotherapy, is considered to be the main inducer of phosphorylated H2AX (γH2AX), which forms distinct foci at sites of DNA damage where DNA repair factors accumulate. γH2AX accumulation under severe hypoxic/anoxic (0.02% oxygen) conditions has recently been reported to follow replication fork stalling in the absence of detectable DNA damage. In this study, we found HIF-dependent accumulation of γH2AX in several cancer cell lines and mouse embryonic fibroblasts exposed to physiologically relevant chronic hypoxia (0.2% oxygen), which did not induce detectable levels of DNA strand breaks. The hypoxic accumulation of γH2AX was delayed by the RNAi-mediated knockdown of HIF-1α or HIF-2α and further decreased when both HIF-αs were absent. Conversely, basal phosphorylation of H2AX was increased in cells with constitutively stabilized HIF-2α. These results suggest that both HIF-1 and HIF-2 are involved in γH2AX accumulation by tumor hypoxia, which might increase a cancer cell's capacity to repair DNA damage, contributing to tumor therapy resistanc

Discourse and emotions in international relations

The field of International Relations (IR) has recently witnessed the emergence of a wide variety of different approaches to make sense of the many ways emotions work in and through discourse. This forum takes stock of and investigates this link based on two interrelated questions: Why study emotions through discourse? How can we study emotions through discourse? Concerning the first question, we argue that textual and verbal utterances provide us with a promising way to make emotions empirically accessible for researchers. Regarding the second question, we argue that it is essential to develop specific criteria for the study of emotions via speech acts. We propose three criteria that the study of emotion discourse must answer to, which revolve around theory (what is an emotion?), expression (how are emotions communicated?), and effects (what do emotions do?). In a step toward fostering engagement and dialogue on these questions, the contributors of this forum propose a variety of approaches to study emotion discourse in world politics. The idea is to explore the ways in which discourse evokes, reveals, and engages emotions and how these effects can speak to larger questions in IR. Precisely, the goal with this forum is to go beyond the “emotions matter” approach of the first wave of emotions scholarship in IR to offer more specific ways to integrate the consideration of emotion into existing research, particularly that of a constructivist vein

Effect of grain size of polycrystalline diamond on its heat spreading properties

Abstract The exceptionally high thermal conductivity of polycrystalline diamond (&gt;2000 W m−1 K−1) makes it a very attractive material for optimizing the thermal management of high-power devices. In this paper, the thermal conductivity of a diamond sample capturing grain size evolution from nucleation towards the growth surface is studied using an optimized 3ω technique. The thermal conductivity is found to decrease with decreasing grain size, which is in good agreement with theory. These results clearly reveal the minimum film thickness and polishing thickness from nucleation needed to achieve single-crystal diamond performance, and thus enable production of an optimal polycrystalline diamond for heat-spreading applications.</jats:p

The p38 MAPK pathway is essential for skeletogenesis and bone homeostasis in mice

Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member–encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteoblast differentiation. Among the MAPK kinase kinase (MAP3K) family, we identified TGF-β–activated kinase 1 (TAK1; also known as MAP3K7) as the critical activator upstream of p38 in osteoblasts. Osteoblast-specific deletion of Tak1 resulted in clavicular hypoplasia and delayed fontanelle fusion, a phenotype similar to the cleidocranial dysplasia observed in humans haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2). Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo. These results also suggest that selective p38β agonists may represent attractive therapeutic agents to prevent bone loss associated with osteoporosis and aging

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland

<p>Abstract</p> <p>Background</p> <p>Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic.</p> <p>Methods</p> <p>Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods.</p> <p>Results</p> <p>7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis.</p> <p>Conclusion</p> <p>Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.</p