465 research outputs found
Possible Use of Light Alloys on Indian Railways
THE resources of the raw materials from which aluminium and magnesium are produced, are so abundant and widespread in India that one can hardly visualise conditions in which the users will at any time have difficulty in obtaining their full requirements, if these are fully exploited. This free availability in a world of shortages has, in itself, led numbers of manufacturers to abandon traditional
materials like steel, copper, lead, zinc, etc. in favour
of light alloys ; and many who were thus first attracted
will never wish to forego the advantages they have found in their use. Nevertheless Our main interest should be to further the development of light alloys in their natural and proper field--the field in which these materials stand supreme by reason of their unique characteristics and availability in India
Indigenous substitution of import ed materials on Indian Railways
THE psychology of import substitution is based on
the concept of dispensing with as much import as poss-
ible by providing alternative indigenous resources.
In a developing country like India, it is essential
to stress on research , development and trials through
different research laboratories/Institutes by suggesting
substitutes of imported materials for the avoidance of
use or conservation of the imported materials in our
country, particularly in the emergency which has high-lighted the necessity for intensifying efforts in this
direction
Solar Polar Fields During Cycles 21 --- 23: Correlation with Meridional Flows
We have examined polar magnetic fields for the last three solar cycles,
{}, cycles 21, 22 and 23 using NSO Kitt Peak synoptic magnetograms.
In addition, we have used SoHO/MDI magnetograms to derive the polar fields
during cycle 23. Both Kitt Peak and MDI data at high latitudes
(78--90) in both solar hemispheres show a significant
drop in the absolute value of polar fields from the late declining phase of the
solar cycle 22 to the maximum of the solar cycle 23. We find that long term
changes in the absolute value of the polar field, in cycle 23, is well
correlated with changes in meridional flow speeds that have been reported
recently. We discuss the implication of this in influencing the extremely
prolonged minimum experienced at the start of the current cycle 24 and in
forecasting the behaviour of future solar cycles.Comment: 4 Figures 11 pages; Revised version under review in Solar Physic
Nm23-H1 can induce cell cycle arrest and apoptosis in B cells
Nm23-H1 is a well-known tumor metastasis suppressor, which functions as a nucleoside-diphosphate kinase converting nucleoside diphosphates to nucleoside triphosphates with an expense of ATP. It regulates a variety of cellular activities, including proliferation, development, migration and differentiation known to be modulated by a series of complex signaling pathway. Few studies have addressed the mechanistic action of Nm23-H1 in the context of these cellular processes. To determine the downstream pathways modulated by Nm23-H1, we expressed Nm23-H1 in a Burkitt lymphoma derived B-cell line BJAB and performed pathway specific microarray analysis. The genes with significant changes in expression patterns were clustered in groups which are responsible for regulating cell cycle, p53 activities and apoptosis. We found a general reduction of cell cycle regulatory proteins including cyclins and cyclin dependent kinase inhibitors (anti proliferation), and upregulation of apoptotic genes which included caspase 3, 9 and Bcl-x. Nm23-H1 was also found to upregulate p53 and downregulate p21 expression. A number of these genes were validated by real time PCR and results from promoter assays indicated that Nm23-H1 expression downregulated cyclin D1 in a dose responsive manner. Further, we show that Nm23-H1 forms a complex with the cellular transcription factor AP1 to modulate cyclin D1 expression levels. BJAB cells expressing Nm23-H1 showed reduced proliferation rate and were susceptible to increased apoptosis which may in part be due to a direct interaction between Nm23-H1 and p53. These results suggest that Nm23-H1 may have a role in the regulation of cell cycle and apoptosis in human B-cells
Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management
INTRODUCTION:
Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs.
METHODS:
We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner.
RESULTS:
The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk.
CONCLUSION:
The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML
Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions
Models and Observations of Sunspot Penumbrae
The mysteries of sunspot penumbrae have been under an intense scrutiny for
the past 10 years. During this time, some models have been proposed and
refuted, while the surviving ones had to be modified, adapted and evolved to
explain the ever-increasing array of observational constraints. In this
contribution I will review two of the present models, emphasizing their
contributions to this field, but also pinpointing some of their inadequacies to
explain a number of recent observations at very high spatial resolution. To
help explaining these new observations I propose some modifications to each of
them. These modifications bring those two seemingly opposite models closer
together into a general picture that agrees well with recent 3D
magneto-hydrodynamic simulations.Comment: 9 pages, 1 color figure. Review talk to appear in the proceedings of
the International Workshop of 2008 Solar Total Eclipse: Solar Magnetism,
Corona and Space Weather--Chinese Space Solar Telescope Scienc
The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice
Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel
Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 1]
Background: Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses. Here we examine the importance of γc for myeloid dendritic cell (DC) function. Methods: We utilize a combination of in vitro DC/T-cell co-culture assays and a novel lipid bilayer system mimicking the T cell surface to delineate the role of DC-expressed γc during DC/T-cell interaction. Results: We observed that γc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Rα colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on DC γc expression. Neither recruitment of IL-15Rα nor IL-15 trans-signaling at the DC immune synapse (IS), required γc signaling in DC, suggesting that γc facilitates IL-15 transpresentation through induced intermolecular cis associations or cytoskeletal reorganization following MHCII ligation. Conclusions: These findings show that DC-expressed γc is required for effective antigen-induced CD4+ T cell activation. We reveal a novel mechanism for recruitment of DC IL-15/IL-15Rα complexes to the IS, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition
Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance
BACKGROUND: Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE PRESENTATION: During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery
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