Apparent Predation by Gray Jays, Perisoreus canadensis, on Long-toed Salamanders, Ambystoma macrodactylum, in the Oregon Cascade Range

We report observations of Gray Jays (Perisoreus canadensis) appearing to consume larval Long-toed Salamanders (Ambystoma macrodactylum) in a drying subalpine pond in Oregon, USA. Corvids are known to prey upon a variety of anuran amphibians, but to our knowledge, this is the first report of predation by any corvid on aquatic salamanders. Long-toed Salamanders appear palatable to Gray Jays, and may provide a food resource to Gray Jays when salamander larvae are concentrated in drying temporary ponds

Quantitative microstructure characterization of Ag nanoparticle sintered joints for power die attachment

The samples of sintered Ag joints for power die attachments were prepared using paste of Ag nanoparticles at 240 °C and 5 MPa for 3 to 17 minutes. Their microstructural features were quantitatively characterized with scanning elec-tronic microscopy, transmission electron microscopy, X-ray diffraction and image analysis method. The resulting nor-malized thickness, pore size and porosity decreased, and grain size increased with increasing the sintering time. A time dependence of the form t1/n with n close to 2 or 3 can be further derived for the kinetics of the thinning, densification and grain growth within the sintered Ag joints

Gene function in early mouse embryonic stem cell differentiation

BACKGROUND: Little is known about the genes that drive embryonic stem cell differentiation. However, such knowledge is necessary if we are to exploit the therapeutic potential of stem cells. To uncover the genetic determinants of mouse embryonic stem cell (mESC) differentiation, we have generated and analyzed 11-point time-series of DNA microarray data for three biologically equivalent but genetically distinct mESC lines (R1, J1, and V6.5) undergoing undirected differentiation into embryoid bodies (EBs) over a period of two weeks. RESULTS: We identified the initial 12 hour period as reflecting the early stages of mESC differentiation and studied probe sets showing consistent changes of gene expression in that period. Gene function analysis indicated significant up-regulation of genes related to regulation of transcription and mRNA splicing, and down-regulation of genes related to intracellular signaling. Phylogenetic analysis indicated that the genes showing the largest expression changes were more likely to have originated in metazoans. The probe sets with the most consistent gene changes in the three cell lines represented 24 down-regulated and 12 up-regulated genes, all with closely related human homologues. Whereas some of these genes are known to be involved in embryonic developmental processes (e.g. Klf4, Otx2, Smn1, Socs3, Tagln, Tdgf1), our analysis points to others (such as transcription factor Phf21a, extracellular matrix related Lama1 and Cyr61, or endoplasmic reticulum related Sc4mol and Scd2) that have not been previously related to mESC function. The majority of identified functions were related to transcriptional regulation, intracellular signaling, and cytoskeleton. Genes involved in other cellular functions important in ESC differentiation such as chromatin remodeling and transmembrane receptors were not observed in this set. CONCLUSION: Our analysis profiles for the first time gene expression at a very early stage of mESC differentiation, and identifies a functional and phylogenetic signature for the genes involved. The data generated constitute a valuable resource for further studies. All DNA microarray data used in this study are available in the StemBase database of stem cell gene expression data [1] and in the NCBI's GEO database

Results of a Rural Traffic Calming Event to Promote Physical Activity

This article describes how community need was addressed through a traffic calming pop-up event in rural Arkansas. The event was conducted on routes connecting a neighborhood, two schools, and a municipal park. A brief survey assessed safety concerns of parents and/or guardians related to children walking or biking to school. Prior to the event, parents/guardians reported it was not safe for their children to walk or bike to school; however, the majority agreed the event made the area safer. Small-scale traffic calming events can provide evidence to stakeholders that built environment changes are an important childhood obesity prevention strategy in rural Extension work

Responsibility Analysis by Abstract Interpretation

Given a behavior of interest in the program, statically determining the corresponding responsible entity is a task of critical importance, especially in program security. Classical static analysis techniques (e.g. dependency analysis, taint analysis, slicing, etc.) assist programmers in narrowing down the scope of responsibility, but none of them can explicitly identify the responsible entity. Meanwhile, the causality analysis is generally not pertinent for analyzing programs, and the structural equations model (SEM) of actual causality misses some information inherent in programs, making its analysis on programs imprecise. In this paper, a novel definition of responsibility based on the abstraction of event trace semantics is proposed, which can be applied in program security and other scientific fields. Briefly speaking, an entity ER is responsible for behavior B, if and only if ER is free to choose its input value, and such a choice is the first one that ensures the occurrence of B in the forthcoming execution. Compared to current analysis methods, the responsibility analysis is more precise. In addition, our definition of responsibility takes into account the cognizance of the observer, which, to the best of our knowledge, is a new innovative idea in program analysis.Comment: This is the extended version (33 pages) of a paper to be appeared in the Static Analysis Symposium (SAS) 201

Prevalence and Associations between Food Insecurity and Overweight/Obesity among Native Hawaiian and Pacific Islander Adolescents

Abstract Objective: This study estimates the prevalence of, and associations between, family food insecurity and overweight/obesity among Native Hawaiian and Pacific Islander (NHPI) adolescents and explores sociodemographic factors which might have a moderation effect on the association. Design: Cross-sectional study using 2014 NHPI-National Health Interview Survey (NHIS) data reported by a parent or guardian. Family-level food security was assessed by the United States (US) Department of Agriculture 10-item questionnaire. BMI for age and sex >=85th and 95th percentiles defined overweight and obesity, respectively, according to US Centers for Disease Control and Prevention criteria. Setting: The US, including all 50 states and the District of Columbia. Participants: 383 NHPI adolescents aged 12-17 in the US. Results: A third (33.5%) of NHPI adolescents aged 12-17 were overweight (19.1%) or obese (14.4%); 8.1% had low food security; and 8.5% had very low food security. Mean family food security score was 1.06, which corresponds to marginal food security. We found no association between family food insecurity and adolescent overweight/obesity or between any other covariates and overweight/obesity, except for family Supplemental Nutrition Assistance Program (SNAP) participation. Odds of being overweight/obese were 77% lower for adolescents in families participating in SNAP (OR: 0.23, 95% CI: 0.08-0.64, p=0.007). The association between SNAP participation and lower odds of overweight/obesity was particularly pronounced for adolescent girls in food insecure families. Conclusions: The association between SNAP participation and lower odds of overweight/obesity suggests potential benefit of research to determine whether interventions to increase SNAP enrollment would improve NHPI adolescents’ health outcomes

Antitumor activity in RAS-driven tumors by blocking AKT and MEK.

PURPOSE: KRAS is the most commonly mutated oncogene in human tumors. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. EXPERIMENTAL DESIGN: We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumors. Recommended dosing schedules were defined as MK-2206 at 135 mg weekly and selumetinib at 100 mg once daily. RESULTS: Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical antitumor activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. CONCLUSION: Responses in KRAS-mutant cancers were generally durable. Clinical cotargeting of MEK and AKT signaling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748).The Drug Development Unit of the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research is supported in part by a programme grant from Cancer Research UK (grant number: C347/A18077). Support was also provided by an Experimental Cancer Medicine Centre grant (no grant number) and the National Institute for Health Research Biomedical Research Centre (jointly to the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research) (grant numbers: A46/CCR - CCR4057 & CCR4058).This is the accepted manuscript of a paper published in Clinical Cancer Research, February 15, 2015 21; 739, doi: 10.1158/1078-0432.CCR-14-190

Crisis Standard of Care: Management of Infantile Spasms during COVID‐19

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/2/ana25792_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156180/1/ana25792.pd

The HSP90 Inhibitor NVP-AUY922 Radiosensitizes by Abrogation of Homologous Recombination Resulting in Mitotic Entry with Unresolved DNA Damage

Heat shock protein 90 (HSP90) is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001). NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2)/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line specific