BL-02: a versatile X-ray scattering and diffraction beamline for engineering applications at Indus-2 synchrotron source.

A hard X-ray engineering applications beamline (BL-02) was commissioned recently and started operation in March 2019 at the Indian synchrotron source, Indus-2. This bending-magnet-based beamline is capable of operating in various beam modes, viz. white, pink and monochromatic beam. The beamline utilizes the X-ray diffraction technique in energy-dispersive and angle-dispersive modes to carry out experiments mainly focused on engineering problems, viz. stress measurement, texture measurement and determination of elastic constants in a variety of bulk as well as thin-film samples. An open-cradle six-circle diffractometer with ∼12 kg load capacity allows accommodation of a wide variety of engineering samples and qualifies the beamline as a unique facility at Indus-2. The high-resolution mode of this beamline is suitably designed so as to carry out line profile analysis for characterization of micro- and nano-structures. In the present article the beamline is described starting from the beamline design, layout, optics involved, various operational modes and experimental stations. Experiments executed to validate the beamline design parameters and to demonstrate the capabilities of the beamline are also described. The future facilities to be incorporated to enhance the capabilities of the beamline are also discussed.

Implementation of prevention of mother-to-child transmission of HIV programme through private hospitals of Delhi--policy implications.

In India, programme for prevention of mother-to-child transmission (PMTCT) of HIV is primarily implemented through public health system. State AIDS Control Societies (SACSs) encourage private hospitals to set up integrated counselling and testing centres (ICTCs). However, private hospitals of Delhi did not set up ICTCs. Consequently, there is no information on PMTCT interventions in private hospitals of Delhi. This study was undertaken by Delhi SACS during March 2013 through September 2013 to assess status of implementation of PMTCT programme in various private hospitals of Delhi to assist programme managers in framing national policy to facilitate uniform implementation of National PMTCT guidelines. Out of total 575 private hospitals registered with Government of Delhi, 336 (58.4%) catering to pregnant women were identified. About 100 private hospitals with facility of antenatal care, vaginal/caesarean delivery and postnatal care and minimum 10 indoor beds were selected for study. Study sample comprised of large corporate hospitals (≥100 beds; n = 29), medium-sized hospitals (25 to <100 beds; n = 42) and small nursing homes (10 to <25 beds; n = 29). A pre-tested questionnaire was designed to obtain basic information about hospital in context to PMTCT programme. Interviews of heads of obstetrics and gynaecology and paediatric departments were conducted by trained interviewers. It was observed that in private hospitals in year 2012, out of 38,186 antenatal women tested, 52 (0.14%) were detected HIV-positive. However, against National Policy, HIV testing was done without pre/post-test counselling/or consent of women, no PMTCT protocol existed, delivery of HIV-positive women was not undertaken and no efforts were made to link HIV-positive women to antiretroviral treatment. Major intervention observed was medical termination of pregnancy, which indicates lack of awareness in private hospitals about available interventions under national programme. The role of private hospitals in management of HIV in pregnant women must be recognized and mainstreamed in HIV control efforts. There is an urgent need for capacity building of private health care providers to improve standards of practice. National AIDS Control Organization may consider establishing linkages or adopting model developed by some countries with generalized epidemic for delivering PMTCT services in private health sector.

A microfocus X-ray fluorescence beamline at Indus-2 synchrotron radiation facility.

A microfocus X-ray fluorescence spectroscopy beamline (BL-16) at the Indian synchrotron radiation facility Indus-2 has been constructed with an experimental emphasis on environmental, archaeological, biomedical and material science applications involving heavy metal speciation and their localization. The beamline offers a combination of different analytical probes, e.g. X-ray fluorescence mapping, X-ray microspectroscopy and total-external-reflection fluorescence characterization. The beamline is installed on a bending-magnet source with a working X-ray energy range of 4-20 keV, enabling it to excite K-edges of all elements from S to Nb and L-edges from Ag to U. The optics of the beamline comprises of a double-crystal monochromator with Si(111) symmetric and asymmetric crystals and a pair of Kirkpatrick-Baez focusing mirrors. This paper describes the performance of the beamline and its capabilities with examples of measured results.

Induction of murine adenosine A(2A) receptor expression by LPS: analysis of the 5' upstream promoter.

Non-activated macrophages express low levels of A(2A)Rs and lipopolysaccharides (LPS) upregulates A(2A)R expression in an NF-κB-dependent manner. The murine A(2A)R gene is encoded by three exons, m1, m2 and m3. Exons m2 and m3 are conserved, while m1 encodes the 5' untranslated UTR. Three m1 variants have been defined, m1A, m1B and m1C, with m1C being farthest from the transcriptional start site. LPS upregulates A(2A)Rs in primary murine peritoneal and bone-marrow-derived macrophages and RAW264.7 cells by selectively splicing m1C to m2, through a promoter located upstream of m1C. We have cloned ∼1.6 kb upstream of m1C into pGL4.16(luc2CP/Hygro) promoterless vector. This construct in RAW 264.7 cells responds to LPS, and adenosine receptor agonists augmented LPS responsiveness. The NF-κB inhibitors BAY-11 and triptolide inhibited LPS-dependent induction. Deletion of a key proximal NF-κB site (402-417) abrogated LPS responsiveness, while deletion of distal NF-κB and C/EBPß sites did not. Site-directed mutagenesis of CREB (309-320), STAT1 (526-531) and AP2 (566-569) sites had little effect on LPS and adenosine receptor agonist responsiveness; however, mutation of a second STAT1 site (582-588) abrogated this responsiveness. Further analysis of this promoter should provide valuable insights into regulation of A(2A)R expression in macrophages in response to inflammatory stimuli.

Prevalence of obesity in Indian women.

Comparison of two major studies conducted by National family health survey (NFHS-2) in 1998-1999 and NFHS-3 in 2005-2006 shows that prevalence of obesity among Indian women has elevated from 10.6% to 12.6% (increased by 24.52%). The prevalence is more profound in the women of age between 40-49 years (23.7%), residing in cities (23.5%), having high qualification (23.8%), belonging to Sikh community (31.6%) and households in the highest wealth quintile (30.5%). Highest percentage of obese women is found in Punjab (29.9%). Although this number seems small in the international perspective, it is significant because of the sheer size of population in India. While the problem of under-nutrition still exists in many parts of India, the additional burden of obesity due to increasing sedentary lifestyle, junk food habits in some urban and economically sound areas is really alarming. Prevention and control of this serious problem through awareness programmes to adopt diversified nutritional food and healthy lifestyle are strongly recommended.

Dose reduction to normal tissues as compared to the gross tumor by using intensity modulated radiotherapy in thoracic malignancies.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) is a powerful tool, which might go a long way in reducing radiation doses to critical structures and thereby reduce long term morbidities.The purpose of this paper is to evaluate the impact of IMRT in reducing the dose to the critical normal tissues while maintaining the desired dose to the volume of interest for thoracic malignancies. MATERIALS AND METHODS: During the period January 2002 to March 2004, 12 patients of various sites of malignancies in the thoracic region were treated using physical intensity modulator based IMRT. Plans of these patients treated with IMRT were analyzed using dose volume histograms. RESULTS: An average dose reduction of the mean values by 73% to the heart, 69% to the right lung and 74% to the left lung, with respect to the GTV could be achieved with IMRT.The 2 year disease free survival was 59% and 2 year overall survival was 59%. The average number of IMRT fields used was 6. CONCLUSION: IMRT with inverse planning enabled us to achieve desired dose distribution, due to its ability to provide sharp dose gradients at the junction of tumor and the adjacent critical organs.

Simian virus 40 large-T-antigen-specific rejection of mKSA tumor cells in BALB/c mice is critically dependent on both strictly tumor-associated, tumor-specific CD8(+) cytotoxic T lymphocytes and CD4(+) T helper cells.

Protective immunity of BALB/c mice immunized with simian virus 40 (SV40) large T antigen (TAg) against SV40-transformed, TAg-expressing mKSA tumor cells is critically dependent on both CD8(+) and CD4(+) T lymphocytes. By depleting mice of T-cell subsets at different times before and after tumor challenge, we found that at all times, CD4(+) and CD8(+) cells both were equally important in establishing and maintaining a protective immune response. CD4(+) cells do not contribute to tumor eradication by directly lysing mKSA cells. However, CD4(+) lymphocytes provide help to CD8(+) cells to proliferate and to mature into fully active cytotoxic T lymphocytes (CTL). Depletion of CD4(+) cells by a single injection of CD4-specific monoclonal antibody at any time from directly before injection of the vaccinating antigen to up to 7 days after tumor challenge inhibited the generation of cytolytic CD8(+) lymphocytes. T helper cells in this system secrete the typical Th-1 cytokines interleukin 2 (IL-2) and gamma interferon. Because in this system TAg-specific CD8(+) cells secrete only minute amounts of IL-2, it appears that T helper cells provide these cytokines for CD8(+) T cells. Moreover, this helper effect of CD4(+) T cells in mKSA tumor rejection in BALB/c mice does not simply improve the activity of TAg-specific CD8(+) CTL but actually enables them to mature into cytolytic effector cells. Beyond this activity, the presence of T helper cells is necessary even in the late phase of tumor cell rejection in order to maintain protective immunity. However, despite the support of CD4(+) T helper cells, the tumor-specific CTL response is so weak that only at the site of tumor cell inoculation and not in the spleen or in the regional lymph nodes can TAg-specific CTL be detected.

A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary gland.

The ductal carcinoma in situ (DCIS) of the mammary gland represents an early, pre-invasive stage in the development of invasive breast carcinoma and is increasingly diagnosed since the introduction of high-quality mammography screening. Uncertainties in the prognosis for patients with DCIS have caused a controversial discussion about adequate treatment, and it is suspected that most patients undergoing mastectomy may be overtreated. In order to improve treatment and treatment decision, it therefore is highly desirable to identify prognostic markers and therapeutic targets for DCIS. We here introduce a set of transgenic mice (WAP-T and WAP-T-NP lines) presenting with various morphological forms of DCIS-like lesions. In these mice the SV40 large tumor antigen is specifically induced in epithelial cells of the terminal duct lobular units (TDLU). As a consequence of continuous expression of the oncogene, the animals develop multifocal DCIS and consequently invasive carcinoma within strain specific periods of latency. DCIS lesions in transgenic mice exhibit distinct architectural and cytological features which closely resemble those commonly present in humans. We therefore propose these transgenic lines as an experimental model to study the underlying molecular events leading to DCIS and its progression to invasive disease.

Tail-specific antibodies that block return of 46,000 M(r) mannose 6-phosphate receptor to the trans-Golgi network.

Recycling of 46,000 M(r) mannose 6-phosphate receptor (MPR 46) was investigated by microinjection of Fab fragments against small epitopes within the cytoplasmic domain of the receptor. Fab fragments against the peptide 43-47 (Ala-Tyr-Arg-Gly-Val) efficiently blocked return of MPR 46 to the TGN. Antibody-induced redistribution resulted in accumulation of MPR 46 within an endosomal compartment, from which it recycled to the plasma membrane. Rab5 and rab7, markers for early and late endosomes, respectively, were not detectable in the compartment of redistributed MPR 46, suggesting that it represents a specialized endosomal subcompartment. The bulk of redistributed MPR 46 did not colocalize with endocytosed fluid-phase marker, suggesting that it accumulates at a site where MPR 46 has been segregated from endocytosed material, which is destined for transport to lysosomes. Peptide 43-47 contains a tyrosine (residue 44) which has been shown earlier to be part of an internalization signal for MPR 46 (Johnson, K. F., W. Chan, and S. Kornfeld. 1990. Proc. Natl. Acad. Sci. USA. 87:10010-10014). The role of tyrosine residue 44 as part of a putative multifunctional sorting signal is discussed.

A structure-activity relationship study on papaverine analogs.

The structure-activity relationship of papaverine analogs, the inhibitors of adenosine cyclic 3', 5'-monophosphate (c-AMP) phosphodiesterase, is discussed. The enzyme inhibition activity of these compounds are found to be dominantly controlled by hydrophobicity and steric factors. A significant quantitative correlation has been obtained between the inhibition activity and the van der Waals volume.