First passage time of N excluded volume particles on a line

Motivated by recent single molecule studies of proteins sliding on a DNA molecule, we explore the targeting dynamics of N particles ("proteins") sliding diffusively along a line ("DNA") in search of their target site (specific target sequence). At lower particle densities, one observes an expected reduction of the mean first passage time proportional to 1/N**2, with corrections at higher concentrations. We explicitly take adsorption and desorption effects, to and from the DNA, into account. For this general case, we also consider finite size effects, when the continuum approximation based on the number density of particles, breaks down. Moreover, we address the first passage time problem of a tagged particle diffusing among other particles.Comment: 9 pages, REVTeX, 6 eps figure

Contested governance of drinking water provisioning services in Nepal’s transboundary river basins

Governance and management of ecosystem services involve a diversity of institutional mechanisms and policy processes from voluntary to regulatory and collaborative approaches. The governance structures and policy processes are often contested, particularly when stakeholder concerns are insufficiently addressed, particularly of those who are most affected by policy decisions. This research examines how collaborative governance enables the ecosystem services approach to source water protection, thereby addressing contested governance problems and policy processes in transboundary river basins in central Nepal. The data were collected using key informant interviews, policy workshops, policy document review, and direct observation. Research results suggest that the state established collaborative governance institutions to improve already adversarial situations rather than in the co-management of water provisioning and other ecosystem services. We conclude that collaborative governance should focus on empowering vulnerable communities to speak for themselves and for the natural environment, particularly to maintain the sustainable flow of multiple ecosystem services for current and future generations

Role of Bharatiya Nirdeshak Dravya (BND®) in Development of Indian Reference Materials for Quality Assurance of Products

The benchmark of life and quality infrastructure of a nation is mainly dependent on the measurement system of country. The growth of nation in addition to its science & technology is highly influenced by measurement of any physical quantities or policies. The ancient as well as modern sciences predominantly rely on the measurement procedure and its accuracy. One can say that science starts from measurements hence it can be considered as one of the basic aspect of science and its growth. To perform these measurements which are basis of life, simple to sophisticated equipment's are used. The results from these instruments may be not accurate and precise if it is not calibrated. With calibration there is need of comparable measurement to attain the unbroken chain of measurements. Now Certified Reference Materials (CRMs) played critical role in calibration of instrument and to get the comparable measurements which are traceable to national or world-wide standards. The outcomes of sophisticated instruments may be wrong without its calibration. So now it is the time for the scientific and new innovations world to calibrate the sophisticated instruments using these certified reference standards. These CRMs are generally produced and maintained by "National Measurement Institute (NMI)" of the country. In India, Bharatiya Nirdeshak Dravya (BND®) division of National Physical Laboratory (NPL) is continuously working in developing the Indian Reference Materials (IRMs). Now these IRMs can be defined as those substances which are key factors for maintaining a healthy measurement system and to get very precise value. With this these are cost effective IRMs which will improve the quality of products and will help in economic growth of the country. In this article, we are discussing about that measurements which are attached to each steps of our life. But it is necessary that measurement should be accurate and precise and traceable to some true value. CSIR-NPL is continuously focused on the development of IRMs for calibration of instrument, improvement in quality of life, industrial production, global trade and to get accurate and precise measurements

Cytopathology Using High Resolution Digital Holographic Microscopy

We summarize a study involving simultaneous imaging of cervical cells from Pap-smear samples using bright-field and quantitative phase microscopy. The optimization approach to phase reconstruction used in our study enables full diffraction limited performance from single-shot holograms and is thus suitable for reducing cost of a quantitative phase microscope system. Over 48000 cervical cells from patient samples obtained from three clinical sites have been imaged in this study. The clinical sites used different sample preparation methodologies and the subjects represented a range of age groups and geographical diversity. Visual examination of quantitative phase images of cervical cell nuclei show distinct morphological features that we believe have not appeared in the prior literature. A PCA based analysis of numerical parameters derived from the bright-field and quantitative phase images of the cervical cells shows good separation of superficial, intermediate and abnormal cells. The distribution of phase based parameters of normal cells is also shown to be highly overlapping among different patients from the same clinical site, patients across different clinical sites and for two age groups (below and above 30 years), thus suggesting robustness and possibility of standardization of quantitative phase as an imaging modality for cell classification in future clinical usage

International Review and Advisory Committee

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Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

Adaptive transition for transformations to sustainability in developing countries

Adaptation and transition are two prominent sustainability science concepts. The former includes one facet of resilience, the capacity of socio-ecological systems to continually change and adapt within their critical thresholds with some exceptional transformability beyond thresholds. The latter concept entails niche experimentation of low-carbon systems and how niche-internal actors influence transformational changes, so-called sustainability transitions, and are influenced by incumbent socio-technical regime. Critics argue that neither adaptation literature nor transition literature sufficiently informs adaptive transition pathways that need to be responsive to already low-carbon subsistence production systems in many developing countries. Recognizing this gap, this paper, albeit in a modest way, develops a framework of adaptive transition integrating socio-ecological systems approaches to adaptation to change referred to as adaptive management, and socio-technical systems approaches to management of change referred to as transition management

Rethinking collaborative governance: contested legitimacy of the Melamchi inter-basin water transfer for municipal use in Nepal

Rapidly growing cities are constantly thirsty for water. The most common approach to meet growing demands is to extract water from rural areas. Whilst rural people and the environment bear the major risks of water extraction, urban municipal service providers and affluent urban consumers, for the most part, benefit from it, where the raw water is processed in treatment plants to generate added value in the form of clean and safe water. Although various governance approaches, from central economic planning to market mechanisms, are touted as effective mechanisms to govern natural resources, research evidence is equivocal on how the state and non-state stakeholders perceive the legitimacy of high modern water transfer. This research employs the contested legitimacy lens to generate nuances in the neoliberal cooption of consensus-based collaborative governance within the context of the Melamchi River diversion, which is Nepal’s largest inter-basin rural-to-urban water transfer for municipal use in the Kathmandu valley, the national capital region with over 3 million population. The research findings revealed that the liberal idea of justice as fairness in water transfer fails to appreciate the contested production of legitimacy in planning and implementation. This research concludes that the dominant narrative of industrialisation and economic growth leading to water crises in urban areas does not sufficiently legitimate the state-led decision to transfer water and other resources from already vulnerable rural areas. The legitimacy of inter-basin water transfer does not come from hierarchical decisions and market mechanisms alone but more importantly from social solidarity movements. The latter especially provides novel sources of legitimacy moving away from the consensus approach to water resource planning and implementation