Determination of In-Situ Stress at Desilting Chamber of Punatsangchhu Hydroelectric Project (Bhutan), to Reconfirm Its Orientation Influenced by Topography — A Case Study

Punatsangchhu Hydroelectric Project stage-I was conceptualized in Wangdue- Phodrang district of Bhutan for harnessing the hydro-power potentiality of Punatsangchhu River. Regionally the project area is located within a part of a gneissic terrain of Tethyan Belt of Bhutan Himalayas. The project envisages construction of 195m high concrete gravity dam across the river Punatsangchhu. For Desilting chamber and Powerhouse, it is always desirable to carry out in-situ stress measurement in such huge underground openings for designing of the support types. The stability of the underground cavern gets enhanced if the long axis of the cavern is oriented along or sub-parallel to that of maximum principal stress. National Institute of Rock Mechanics, a premier Research Institute under Ministry of Mines, Government of India, carried out stress measurements at RD 100m and RD 150m inside an exploratory drift approaching towards desilting chamber with a rock cover of 100m. This test was required to freeze the orientation of desilting chamber vis. a vis. orientation of maximum compression (σH) which was found to be N 150°. As it was only 100 to 150 m away from the portal, a topography effect on the orientation of (σH) was not completely ruled out. So when the adit to Desilting chamber reached at RD 360m with a rock cover of 410m, it is necessary to carry out stress measurement at RD 360m to confirm the results of earlier tests at RD100m and RD 150m to find out the influence of topography on which the present paper is based was primarily for determination of in-situ stress measurements. The stress orientation as evaluated at RD 360m reconfirms the orientations revealed from earlier stress measurements at RD 100 and RD 150m.Thus it is recommended to freeze the direction of Desilting chamber along N 150°. It also confirms that the earlier stress measurement results do not suffer from topography related influence

Phase 4 Pharmacovigilance Trial of Paromomycin Injection for the Treatment of Visceral Leishmaniasis in India

Background. A phase 3 study demonstrated the safety and efficacy of paromomycin (paromomycin IM injection) for treatment of VL in an inpatient setting. Methods. This phase 4 study was conducted to assess the safety and efficacy of paromomycin in children and adults in an outpatient setting in Bihar, India. Results. This study enrolled 506 adult and pediatric patients. Of the 494 patients in the intent-to-treat (ITT) population, 98% received a full course of treatment. The overall study completion rate was 94% (462/494) for the ITT population and 96% (461/479) for the efficacy-evaluable (EE) population. Initial clinical cure was 99.6%, and final clinical cure 6 months after treatment was 94.2%. Grade 3 or 4 adverse events occurred in 5% of patients; events with a frequency of ≥1% were increases in alanine aminotransferase and aspartate aminotransferase. Conclusions. This study confirms the safety and efficacy of paromomycin to treat VL in an outpatient setting

Expression profiling of cervical cancers in I ndian women at different stages to identify gene signatures during progression of the disease

Cervical cancer is the second most common cancer among women worldwide, with developing countries accounting for >80% of the disease burden. Although in the West, active screening has been instrumental in reducing the incidence of cervical cancer, disease management is hampered due to lack of biomarkers for disease progression and defined therapeutic targets. Here we carried out gene expression profiling of 29 cervical cancer tissues from I ndian women, spanning International Federation of Gynaecology and Obstetrics ( FIGO ) stages of the disease from early lesion (IA and IIA) to progressive stages (IIB and IIIA–B), and identified distinct gene expression signatures. Overall, metabolic pathways, pathways in cancer and signaling pathways were found to be significantly upregulated, while focal adhesion, cytokine–cytokine receptor interaction and WNT signaling were downregulated. Additionally, we identified candidate biomarkers of disease progression such as SPP 1, proliferating cell nuclear antigen ( PCNA ), STK 17A, and DUSP 1 among others that were validated by quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ) in the samples used for microarray studies as well in an independent set of 34 additional samples. Integrative analysis of our results with other cervical cancer profiling studies could facilitate the development of multiplex diagnostic markers of cervical cancer progression. Cervical cancer is the leading cause of cancer deaths among women in I ndia, yet it remains poorly characterized at molecular level. This study provides one of the largest molecular profiling efforts from this region involving cervical cancer tissues from well‐defined clinical stages to identify molecular signatures of disease progression, as well as identify novel biomarkers distinguishing early and advanced disease. We expect this study to serve as a template for larger studies, including those based on high‐throughput sequencing, to help develop robust biomarkers of disease progression and potentially identify actionable therapeutic targets.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101800/1/cam4152.pd

Giant low frequency velocity fluctuations in a driven vortex lattice

The driven state of a well-ordered flux line lattice in a single crystal of 2H-NbSe2 in the time domain has revealed the presence of substantial fluctuations in velocity, with large and distinct time periods (~ seconds). A superposition of a periodic drive in the driven vortex lattice causes distinct changes in these fluctuations. We propose that prior to onset of the peak effect there exist hithertofore unexplored regime of coherent dynamics, with unexpected behaviour in velocity fluctuations.Comment: 16 pages, 3 figures. Accepted for publication in Physical Review Letters (http://prl.aps.org/accepted

Astrophysical S_{17}(0) factor from a measurement of d(7Be,8B)n reaction at E_{c.m.} = 4.5 MeV

Angular distribution measurements of $^2$H($^7$Be,$^7$Be)$^2$H and $^2$H($^7$Be,$^8$B)$n$ reactions at $E_{c.m.}\sim$~4.5 MeV were performed to extract the astrophysical $S_{17}(0)$ factor using the asymptotic normalization coefficient (ANC) method. For this purpose a pure, low emittance $^7$Be beam was separated from the primary $^7$Li beam by a recoil mass spectrometer operated in a novel mode. A beam stopper at 0$^{\circ}$ allowed the use of a higher $^7$Be beam intensity. Measurement of the elastic scattering in the entrance channel using kinematic coincidence, facilitated the determination of the optical model parameters needed for the analysis of the transfer data. The present measurement significantly reduces errors in the extracted $^7$Be(p,$\gamma$) cross section using the ANC method. We get $S_{17}$~(0)~=~20.7~$\pm$~2.4 eV~b.Comment: 15 pages including 3 eps figures, one figure removed and discussions updated. Version to appear in Physical Review

Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo.

PurposeWe tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.MethodsEighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. Gene therapy effects on corneal fibrosis and ocular safety were evaluated by slit-lamp microscope, stereo microscopes, quantitative real-time PCR, immunofluorescence, TUNEL, modified MacDonald-Shadduck scoring system, and Draize tests.ResultsPEI2-GNP-mediated BMP7+HGF gene therapy significantly decreased corneal fibrosis in live rabbits in vivo (Fantes scale was 0.6 in BMP7+HGF-treated eyes compared to 3.3 in -therapy group; P 104 gene copies per microgram DNA of BMP7 and HGF genes. The recombinant HGF rendered apoptosis in corneal myofibroblasts but not in fibroblasts. Localized topical BMP7+HGF therapy showed no ocular toxicity.ConclusionsLocalized topical BMP7+HGF gene therapy treats corneal fibrosis and restores transparency in vivo mitigating excessive healing and rendering selective apoptosis in myofibroblasts

‘It Takes Two Hands to Clap’: How Gaddi Shepherds in the Indian Himalayas Negotiate Access to Grazing

This article examines the effects of state intervention on the workings of informal institutions that coordinate the communal use and management of natural resources. Specifically it focuses on the case of the nomadic Gaddi shepherds and official attempts to regulate their access to grazing pastures in the Indian Himalayas. It is often predicted that the increased presence of the modern state critically undermines locally appropriate and community-based resource management arrangements. Drawing on the work of Pauline Peters and Francis Cleaver, I identify key instances of socially embedded ‘common’ management institutions and explain the evolution of these arrangements through dynamic interactions between individuals, communities and the agents of the state. Through describing the ‘living space’ of Gaddi shepherds across the annual cycle of nomadic migration with their flocks I explore the ways in which they have been able to creatively reinterpret external interventions, and suggest how contemporary arrangements for accessing pasture at different moments of the annual cycle involve complex combinations of the formal and the informal, the ‘traditional’ and the ‘modern’

Drug Susceptibility in Leishmania Isolates Following Miltefosine Treatment in Cases of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis

Resistance to antimonials has emerged as a major hurdle to the treatment and control of VL and led to the introduction of Miltefosine as first line treatment in the Indian subcontinent. MIL is an oral drug with a long half-life, and it is feared that resistance may emerge rapidly, threatening control efforts under the VL elimination program. There is an urgent need for monitoring treatment efficacy and emergence of drug resistance in the field. In a set of VL/PKDL cases recruited for MIL treatment, we observed comparable drug susceptibility in pre- and post-treatment isolates from cured VL patients while MIL susceptibility was significantly reduced in isolates from VL relapse and PKDL cases. The PKDL isolates showed higher tolerance to MIL as compared to VL isolates. Both VL and PKDL isolates were uniformly susceptible to PMM. MIL transporter genes LdMT/LdRos3 were previously reported as potential resistance markers in strains in which MIL resistance was experimentally induced. The point mutations and the down-regulated expression of these transporters observed in vitro could, however, not be verified in natural populations of parasites. LdMT/LdRos3 genes therefore, do not appear to be suitable markers so far for monitoring drug susceptibility in clinical leishmanial isolates