1,814 research outputs found
The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.
Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer
Outflows and Massive Stars in the protocluster IRAS 05358+3543
We present new near-IR H2, CO J=2-1, and CO J = 3-2 observations to study
outflows in the massive star forming region IRAS 05358+3543. The
Canada-France-Hawaii Telescope H2 images and James Clerk Maxwell Telescope CO
data cubes of the IRAS 05358 region reveal several new outflows, most of which
emerge from the dense cluster of sub-mm cores associated with the Sh 2-233IR NE
cluster to the northeast of IRAS 05358. We used Apache Point Observatory (APO)
JHK spectra to determine line of sight velocities of the outflowing material.
Analysis of archival VLA cm continuum data and previously published VLBI
observations reveal a massive star binary as a probable source of one or two of
the outflows. We have identified probable sources for 6 outflows and candidate
counterflows for 7 out of a total of 11 seen to be originating from the IRAS
05358 clusters. We classify the clumps within Sh 2-233IR NE as an early
protocluster and Sh 2-233IR SW as a young cluster, and conclude that the
outflow energy injection rate approximately matches the turbulent decay rate in
Sh 2-233IR NE.Comment: 15 figures, 42 pages, accepted for publication in the Astrophysical
Journal. Full size figures are included at
http://casa.colorado.edu/~ginsbura/iras05358.htm. Data can be accessed from
figshare: http://figshare.com/articles/IRAS_05358_3543_Data_Cubes/80631
Dark Matter in the Coming Decade: Complementary Paths to Discovery and Beyond
In this report we summarize the many dark matter searches currently being
pursued through four complementary approaches: direct detection, indirect
detection, collider experiments, and astrophysical probes. The essential
features of broad classes of experiments are described, each with their own
strengths and weaknesses. The complementarity of the different dark matter
searches is discussed qualitatively and illustrated quantitatively in two
simple theoretical frameworks. Our primary conclusion is that the diversity of
possible dark matter candidates requires a balanced program drawing from all
four approaches.Comment: Report prepared for the Community Summer Study (Snowmass) 2013, on
behalf of Cosmic Frontier Working Groups 1-4 (CF1: WIMP Dark Matter Direct
Detection, CF2: WIMP Dark Matter Indirect Detection, CF3: Non-WIMP Dark
Matter, and CF4: Dark Matter Complementarity); published versio
The reduction of intoxication and disorder in premises licensed to serve alcohol: An exploratory randomised controlled trial
Background: Licensed premises offer a valuable point of intervention to reduce alcohol-related harm. Objective: To describe the research design for an exploratory trial examining the feasibility and acceptability of a premises-level intervention designed to reduce severe intoxication and related disorder. The study also aims to assess the feasibility of a potential future large scale effectiveness trial and provide information on key trial design parameters including inclusion criteria, premises recruitment methods, strategies to implement the intervention and trial design, outcome measures, data collection methods and intra-cluster correlations. Design: A randomised controlled trial in licensed premises that had experienced at least one assault in the year preceding the intervention, documented in police or hospital Emergency Department (ED) records. Premises were recruited from four study areas by piloting four recruitment strategies of varying intensity. Thirty two licensed premises were grouped into matched pairs to reduce potential bias and randomly allocated to the control or intervention condition. The study included a nested process evaluation to provide information on intervention acceptability and implementation. Outcome measures included police-recorded violent incidents, assault-related attendances at each premises ’ local ED and patron Breath Alcohol Concentration assessed on exiting and entering study premises. Results: The most successful recruitment method involved local police licensing officers and yielded a 100% success rate. Police-records of violence provided the most appropriate source of data about disorder at the premises level. Conclusion: The methodology of an exploratory trial is presented and despite challenges presented by the study environment it is argued an exploratory trial is warranted. Initial investigations in recruitment methods suggest that study premises should be recruited with the assistance of police officers. Police data were of sufficient quality to identify disorder and street surveys are a feasible method for measuring intoxication at the individual level. Trial registration: UKCRN 7090; ISRCTN: 80875696. Funding: Medical Research Council (G0701758) to Simon Moore, Simon Murphy, Laurence Moore and Jonathan Shepherd.
Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes
Purpose
Chronic sugar-sweetened beverage (SSB) consumption is associated with obesity and type 2 diabetes mellitus (T2DM). Hyperglycaemia contributes to metabolic alterations observed in T2DM, such as reduced oxidative capacity and elevated glycolytic and lipogenic enzyme expressions in skeletal muscle tissue. We aimed to investigate the metabolic alterations induced by SSB supplementation in healthy individuals and to compare these with the effects of chronic hyperglycaemia on primary muscle cell cultures.
Methods
Lightly active, healthy, lean subjects (n = 11) with sporadic soft drink consumption underwent a 4-week SSB supplementation (140 ± 15 g/day, âŒ2 g glucose/kg body weight/day, glucose syrup). Before and after the intervention, body composition, respiratory exchange ratio (RER), insulin sensitivity, muscle metabolic gene and protein expression were assessed. Adaptive responses to hyperglycaemia (7 days, 15 mM) were tested in primary human myotubes.
Results
SSB supplementation increased fat mass (+1.0 kg, P < 0.05), fasting RER (+0.12, P < 0.05), fasting glucose (+0.3 mmol/L, P < 0.05) and muscle GAPDH mRNA expressions (+0.94 AU, P < 0.05). PGC1a mRNA was reduced (â0.20 AU, P < 0.05). Trends were found for insulin resistance (+0.16 mU/L, P = 0.09), and MondoA protein levels (+1.58 AU, P = 0.08). Primary myotubes showed elevations in GAPDH, ACC, MondoA and TXNIP protein expressions (P < 0.05).
Conclusion
Four weeks of SSB supplementation in healthy individuals shifted substrate metabolism towards carbohydrates, increasing glycolytic and lipogenic gene expression and reducing mitochondrial markers. Glucose-sensing protein MondoA might contribute to this shift, although further in vivo evidence is needed to corroborate this
HLâTWiM Empirical Model of HighâLatitude Upper Thermospheric Winds
We present an empirical model of thermospheric winds (Highâlatitude Thermospheric Wind Model [HLâTWiM]) that specifies F region highâlatitude horizontal neutral winds as a function of day of year, latitude, longitude, local time, and geomagnetic activity. HLâTWiM represents the largeâscale neutral wind circulation, in geomagnetic coordinates, for the given input conditions. The model synthesizes the most extensive collection to date of historical highâlatitude wind measurements; it is based on statistical analyses of several decades of F region thermospheric wind measurements from 21 groundâbased stations (FabryâPerot Interferometers and Scanning Doppler Imaging FabryâPerot Interferometers) located at various northern and southern high latitudes and two spaceâbased instruments (UARS WINDII and GOCE). The geomagnetic latitude and local time dependences in HLâTWiM are represented using vector spherical harmonics, day of year and longitude variations are represented using simple harmonic functions, and the geomagnetic activity dependence is represented using quadratic B splines. In this paper, we describe the HLâTWiM formulation and fitting procedures, and we verify the model against the neutral wind databases used in its formulation. HLâTWiM provides a necessary benchmark for validating new wind observations and tuning our physical understanding of complex wind behaviors. Results show stronger Universal Time variation in winds at southern than northern high latitudes. Modelâdata intraâannual comparisons in this study show semiannual oscillationâlike behavior of GOCE winds, rarely observed before in wind data.Key PointsWe developed a comprehensive empirical model of highâlatitude F region thermospheric winds (HLâTWiM)Universal Time variations in highâlatitude winds are stronger in the Southern than Northern HemisphereHLâTWiM provides a necessary benchmark for validating new highâlatitude wind observations and tuning first principal modelsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153588/1/jgra55363_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153588/2/jgra55363-sup-0001-Figure_SI-S01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153588/3/jgra55363.pd
Diverse protostellar evolutionary states in the young cluster AFGL961
We present arcsecond resolution mid-infrared and millimeter observations of
the center of the young stellar cluster AFGL961 in the Rosette molecular cloud.
Within 0.2 pc of each other, we find an early B star embedded in a dense core,
a neighboring star of similar luminosity with no millimeter counterpart, a
protostar that has cleared out a cavity in the circumcluster envelope, and two
massive, dense cores with no infrared counterparts. An outflow emanates from
one of these cores, indicating a deeply embedded protostar, but the other is
starless, bound, and appears to be collapsing. The diversity of states implies
either that protostellar evolution is faster in clusters than in isolation or
that clusters form via quasi-static rather than dynamic collapse. The existence
of a pre-stellar core at the cluster center shows that that some star formation
continues after and in close proximity to massive, ionizing stars.Comment: 22 pages, 7 figures, accepted for publication in Ap
Coordination risk and cost impacts on economic development in poor rural areas
This paper addresses issues relevant to a critical problem in economic development: how to get rapid pro-poor economic growth in poor rural areas in Africa and South Asia where most of the worldâs dollar a day poor live. It examines constraints to the development of coordinated exchange systems in poor rural areas, focusing on the core problem of thin markets and low density of economic activity in these areas. Transaction cost and risk analysis is integrated into a conventional neoclassical production economics framework to describe the existence of low level equilibrium traps in transactions and supply chains and to generate important insights for development policy
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