253 research outputs found
Resolution of conflicting views on thermodynamics of glass transition: a unified model
Classical description of thermodynamic properties during glass transition has been questioned by the entropy-loss model. The uncompensated loss of entropy at the glass transition temperature and zero residual entropy is at the heart of the controversy. Both the models are critically reviewed. A unified model is presented which incorporates features of both entropy loss and residual entropy. It implies two different types of contributions to the entropy of the supercooled liquid, one of which vanishes at the transition and the other which contributes to residual entropy. Entropy gain during spontaneous relaxation of glass, and the nature of heat capacity ‘hysteresis’ during cooling and heating through the glass transition range support the proposed model. Experiments are outlined for differentiating between the models
Prognostic factors for lymph node metastasis from upper gingival carcinomas
This study sought to identify tumor characteristics that associate with regional lymph node metastases in squamous cell carcinomas originating in the upper gingiva
Development of a roller quenching apparatus for the production of amorphous phases
The details of an apparatus designed to produce amorphous phases by rapid quenching from the melt are described. A drop of molten material is squeezed between two copper rollers rotating against each other at 5000 RPM and a thin foil of the material is produced. The system produces cooling rates of the order of 105 K/sec. Details of the development and construction are mentioned
Transcriptional Profiling of Peripheral Blood Mononuclear Cells in Pancreatic Cancer Patients Identifies Novel Genes with Potential Diagnostic Utility
Background: It is well known that many malignancies, including pancreatic cancer (PC), possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility. Methods and Findings: PBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK) cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%. Conclusions: In summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC. © 2011 Baine et al
Integrating indigenous and exogenous communication channels and capabilities through community-based armyworm forecasting
Many development interventions have failed to generate the desired
impact among African resource-poor farmers for reasons including the
centralised and top-down approach, lack of active community
participation, and over-reliance on external information and technology
delivery strategies and channels. The migrant African armyworm,
Spodoptera exempta, is among the major challenges threatening
livelihoods of millions of farmers in East and Southern Africa.
Outbreaks occur suddenly and can devastate crops and pasture. National
and regional forecasting services have been operational since the 1960s
to provide warning of potential outbreaks. This system relies on
information from armyworm moth traps usually operated at district
level. These centralised services have a number of difficulties and
limitations which include: delays in communicating trap catch data to
the forecaster; forecasts are not village specific; forecasts do not
reach many farmers; lack of responsibility and local ownership of
traps. An innovative approach called community-based armyworm
forecasting (CBAF) was developed as a response to these limitations.
The new approach has been piloted and tested in several East African
countries and found to be effective. CBAF establishes a system that
allows each village to have its own traps and trained forecasters who
collect and interpret data, and provide village specific forecasts. A
recent project on CBAF piloted the approach in 10, 5 and 39 villages of
Malawi, Zimbabwe and Tanzania, respectively, in the 1 st year, and in a
further 25 and 38 villages of Malawi and Tanzania in the 2 nd year.
Discussion with stakeholders, field observations and assessments
conducted by the authors indicate that the initiative has generated a
number of benefits. It built local capacity, and because of the
location specific early warning it enabled farmers to combat the pest
more effectively. It was noticed by the authors that local
communication channels and folk media play an important role in CBAF,
complementing and enhancing the effectiveness of exogenous channels.
This paper discusses how CBAF makes effective use of different
communication channels and capabilities, and highlights preliminary
results.Tant d\u2019interventions de d\ue9veloppement n\u2019ont pas pu
g\ue9n\ue9rer un impact satisfaisant parmi les fermiers africains
sans resources pour de raisons multiples, dont l\u2019utilisation de
l\u2019approche coercitive et centralis\ue9e, le manque d\u2019une
participation active de la communaut\ue9 et le fait d\u2019avoir
plus d\u2019attachement aux informations, aux strat\ue9gies et
guides externes de vulgarization de technologies. Spodoptera exempta,
une chenille aussi nomm\ue9e \u201cchenille africain
migratrice\u201d est parmi les contraintes majeures aux moyens de
subsistance de milliers de fermiers d\u2019Afrique orientale et
australe. Son \ue9ruption est soudaine et peut d\ue9vaster des
cultures ainsi que des pasturages. Les services nationaux et
r\ue9gionaux de pr\ue9diction \ue9taient op\ue9rationnels
depuis 1960 pour fournir des alertes sur des irruptions potentielles
sur base d\u2019informations collect\ue9es sur des pi\ue8ges
tendus aux chenilles au niveau du district. Ces services
centralis\ue9s pr\ue9sentent un bon nombre de difficult\ue9s et
limitations entre autre, le retard dans la communication des
donn\ue9es de pi\ue8ges au pr\ue9visioniste, le manqu\ue9 de
sp\ue9cificit\ue9 des pr\ue9visions, la lenteur dans la livraison
des pr\ue9visions aux fermiers, le manque de responsabilit\ue9 et
d\u2019appropriation locale de ces pi\ue8ges. En r\ue9ponse \ue0
ces limitations, une approche innovatrice appell\ue9e pr\ue9diction
des chenilles au niveau communautaire (CBAF) \ue9tait initi\ue9e et
test\ue9e dans plusieurs pays d\u2019Afrique de l\u2019Est. Cette
approche s\u2019\ue9tait av\ue9r\ue9e efficace \ue0 point
qu\u2019il avait permis \ue0 chaque village d\u2019avoir ses
propres pi\ue8ges et des pr\ue9visionistes form\ue9s pour la
collecte et l\u2019interpr\ue9tation des donn\ue9es ainsi que pour
fournir des pr\ue9visions sp\ue9cifiques aux villages.Un projet
recent sur CBAF avait ex\ue9cut\ue9 cette approche dans 10, 5 et 39
villages de Malawi, Zimbabwe et Tanzanie, respectivement, dans la
premi\ue8re ann\ue9e, et dans plus de 25 et 38 villages de Malawi
et Tanzanie au cours de la deuxi\ue8me ann\ue9e. Des r\ue9unions
avec des partenaires ainsi que des observations et \ue9valuations sur
terrain par des auteurs indiquent combien l\u2019initiative avait
\ue9t\ue9 b\ue9n\ue9fique. Le renforcement de capacit\ue9
locale avait \ue9t\ue9 realis\ue9 et les alertes localement
sp\ue9cifiques ont permis aux fermiers de combattre avec plus
d\u2019efficacit\ue9 la peste. Il \ue9tait remarqu\ue9 que les
cha\ueenes de communication locale ansi que les \u201cfolk
media\u201d jouent un role important dans CBAF par leur
compl\ue9mentarit\ue9 et la promotion de l\u2019efficacit\ue9
des cha\ueenes exog\ue8nes. Cet article discute comment CBAF fait
bon usage de diff\ue9rentes cha\ueenes de communication et
comp\ue9tences, et met en \ue9vidence les r\ue9sultats
pr\ue9liminaires
In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers
The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation
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Specific Targeting and Labeling of Colonic Polyps in CPC-APC Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (p-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in CPC-APC mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy
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