Negative Poisson's Ratio Behavior Induced by an Elastic Instability

Negative Poisson's ratio behavior has been uncovered in cellular solids that comprise a solid matrix with a square array of circular voids. The simplicity of the fabrication implies robust behavior, which is relevant over a range of scales. The behavior results from an elastic instability, which induces a pattern transformation and excellent quantitative agreement is found between calculation and experiment.Engineering and Applied Science

Optical probing of ultrafast electronic decay in Bi and Sb with slow phonons

Illumination with laser sources leads to the creation of excited electronic states of particular symmetries, which can drive isosymmetric vibrations. Here, we use a combination of ultrafast stimulated and cw spontaneous Raman scattering to determine the lifetime of A(1g) and E-g electronic coherences in Bi and Sb. Our results both shed new light on the mechanisms of coherent phonon generation and represent a novel way to probe extremely fast electron decoherence rates. The E-g state, resulting from an unequal distribution of carriers in three equivalent band regions, is extremely short lived. Consistent with theory, the lifetime of its associated driving force reaches values as small as 2 (6) fs for Bi (Sb) at 300 K. DOI: 10.1103/PhysRevLett.110.04740

Time- and momentum-resolved probe of heat transport in photo-excited bismuth

We use time- and momentum-resolved x-ray scattering to study thermalization in a photo-excited thin single crystal bismuth film on sapphire. The time-resolved changes of the diffuse scattering show primarily a quasi-thermal phonon distribution that is established in less than or similar to 100 ps and that follows the time-scale of thermal transport. Ultrafast melting measurements under high laser excitation show that epitaxial regrowth of the liquid phase occurs on the time-scale of thermal transport across the bismuth-sapphire interface. (C) 2013 AIP Publishing LLC. (DOI: 10.1063/1.4804291

Task force on immigration and higher education in Central Massachusetts

In August 2007, the Colleges of Worcester Consortium, Inc. created a task force to examine the issue of immigration and higher education in Central Massachusetts. It has become increasingly clear from recent demographic and economic studies and projections that the population in the northeast, and certainly in Central Massachusetts, is showing minimal growth. There is evidence that a decline in the “native-born” population is caused by significant out-migration due to a number of factors, including the high cost of living, limited career opportunities and a declining birth rate. The limited population growth that is evident is due primarily to the recent influx of immigrants to this area, with the most significant numbers in Worcester coming from Ghana, Brazil, the Dominican Republic, Kenya, El Salvador, Albania and Liberia. It is also clear that the area’s economy is becoming more knowledge-based with an increasing percentage of all new jobs requiring some form of postsecondary education. According to the 2007 Massachusetts Department of Workforce Development’s Job Vacancy Survey, 38 percent of current job vacancies in Massachusetts require an associate’s degree or higher. This represents an increase from 30 percent in 2003. Consequently, the level of education that the immigrant population attains is of vital importance to everyone—not only to immigrant students and their families but also to the economic well-being of the entire region. The Task Force was charged with researching the barriers to higher education faced by this new wave of immigrants and suggesting recommendations to address those barriers. The 36-member Task Force was made up of representatives from Consortium member institutions; federal, state and local governments; community and faithbased organizations; the Worcester Public Schools; the Massachusetts Board of Higher Education; and the Massachusetts Immigrant and Refugee Advocacy (MIRA) Coalition. Meetings were held over six months, during which the Task Force identified three main barriers faced by immigrant communities in accessing higher education, and sub-committees were created to work on each of these. Speakers were invited to present on topics of interest. Two public hearings were held, the first of which was conducted at Worcester State College in October. It attracted community representatives, as well as college and high school faculty and administrators. The second hearing, held at the downtown branch of Quinsigamond Community College (QCC) in December, was attended by immigrants (English for Speakers of Other Languages – ESOL and GED) students as well as QCC staff.Published versio

Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut

Scientific Opportunities with an X-ray Free-Electron Laser Oscillator

An X-ray free-electron laser oscillator (XFELO) is a new type of hard X-ray source that would produce fully coherent pulses with meV bandwidth and stable intensity. The XFELO complements existing sources based on self-amplified spontaneous emission (SASE) from high-gain X-ray free-electron lasers (XFEL) that produce ultra-short pulses with broad-band chaotic spectra. This report is based on discussions of scientific opportunities enabled by an XFELO during a workshop held at SLAC on June 29 - July 1, 2016Comment: 21 pages, 12 figure

Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis

BACKGROUND: The Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations. RESULTS: We found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays. CONCLUSIONS: The greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1928-z) contains supplementary material, which is available to authorized users

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN