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Publications (59)
We present a case of 42 year-old female, who presented with generalized tonic-clonic seizures with altered sensorium, not responding to antiepileptic medications. She was a diagnosed case of hypothyroidism since last three years and was on replacement therapy. Her systemic examination including the neurological examination did not point to any spec...
We present a case of 42 year-old female, who presented with generalized tonic-clonic seizures with altered sensorium, not responding to antiepileptic medications. She was a diagnosed case of hypothyroidism since last three years and was on replacement therapy. Her systemic examination including the neurological examination did not point to any spec...
Takayasu arteritis is an idiopathic, autoimmune, large vessel vasculitis, mainly affecting the young adults. Its exact etiopathogenesis is not known and it has varied clinical presentations. Acute stroke as initial presentation of Takayasu arteritis is uncommonly reported. Herein we present a case of a 24-year-old female who came to our hospital em...
Affinity optimization of monoclonal antibodies (mAbs) is essential for developing drug candidates with the highest likelihood of clinical success; however, a quantitative approach for setting affinity requirements is often lacking. In this study, we computationally analyzed the in vivo mAb-target binding kinetics to delineate general principles for...
We report a case of scrub typhus presenting with fever and thrombocytopenia highlighting the wide variation in clinical presentations leading to delayed diagnosis in dengue epidemic. Fever and thrombocytopenia are the most common clinical presentations in viral hemorrhagic fever but other diseases like malaria, typhoid, leptospira, rickettsial and...
Acute-phase response is the sum of the systemic and metabolic changes occurred by release of acute-phase proteins in response to an inflammatory stimulus. The most important ones of these acute-phase reactants are erythrocyte sedimentation rate, C-reactive protein, fibrinogen, procalcitonin and ferritin. The most widely used ones are ESR and CRP wh...
Bispecific antibodies (BAbs) are novel constructs that are under development and show promise as new therapeutic modalities for cancer and autoimmune disorders. The aim of this study is to develop a semi-mechanistic modeling approach to elucidate the disposition of BAbs in plasma and possible sites of action in humans. Here we present two case stud...
Prediction of human pharmacokinetics (PK) can be challenging for monoclonal antibodies (mAbs) exhibiting target-mediated drug disposition (TMDD). In this study, we performed a quantitative analysis of a diverse set of six mAbs exhibiting TMDD to explore translational rules that can be utilized to predict human PK. A TMDD model with rapid-binding ap...
TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD)...
Study the impact of CXCL13 neutralization on germinal center (GC) response in vivo, and build quantitative relationship between target coverage and pharmacological effects at the target tissue.
An anti-CXCL13 neutralizing monoclonal antibody was dosed in vivo in a T-dependent mouse immunization (TDI) model. A quantitative site-of-action (SoA) model...
TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD)...
Himalayan basins have considerable snow- and glacier-covered areas, which are an important source of water, particularly during summer season. In the Himalayan region, in general, the glacier melt season is considered to be from May to October. Changes in hydrological characteristics of the runoff over the melt season can be understood by studying...
SynonymsFiordDefinitionFjords are long, narrow, and over-deepened features with steep sides and are carved into bedrock by the glacial activity and flooded by melting water (Figure 1).Fjords, Figure 1Fjord as seen in Milford Sound, New Zealand. Photo courtesy Dr. Luke Copland.Fjords are erosional landforms that represent the movement of a glacier w...
Proglacial meltwater streams draining out of the Himalayan glaciers carry considerable amounts of suspended sediment, with a variety of particle sizes, because of the supraglacial, englacial, and subglacial debris, as well as formation of sediments from erosion by the movement of the ice. This paper examines particle size transported in the proglac...
This study investigates the relationships between hydrological and meteorological data collected near the snout of Gangotri Glacier, Indian Himalayas for the different ablation seasons (May -October). The complete analysis employs a hydro-meteorological data series for a period of 7 years (2000 -2006). The first 5 years data (2000 -2004) was used f...
Prostate Specific Antigen's (PSA) role as a biomarker for prostate cancer is well established but the physiological role of its serine protease activity in the pathobiology of normal prostate and prostate carcinogenesis remains largely unknown. In light of recent studies that implicate PSA's enzymatic activity in the initiation and/or progression o...
Prostate-specific antigen (PSA), a serine protease belonging to the human kallikrein family, is best known as a prostate cancer biomarker. Emerging evidence suggests that PSA may also play a salient role in prostate cancer development and progression. With large amounts of enzymatically active PSA continuously and selectively produced by all stages...
The hydrological cycle, a fundamental component of climate is likely to be altered in important ways due to climate change.
In this study, the historical daily runoff has been simulated for the Chenab River basin up to Salal gauging site using a
simple conceptual snowmelt model (SNOWMOD). The model has been used to study the impact of plausible hyp...
The standard hormonal therapy with currently available antiandrogens and the leutinizing hormone releasing hormone (LHRH) analogs is not effective in the hormone-refractory stage of prostate cancer due to changes in androgen receptor (AR) signaling axis. In this refractory stage, AR continues to play a significant role in the growth of cancer cells...
Seasonal and annual trends of changes in rainfall, rainy days, heaviest rain and relative humidity have been studied over the last century for nine different river basins in northwest and central India. The majority of river basins have shown increasing trends both in annual rainfall and relative humidity. The magnitude of increased rainfall for co...
Prostate cancer cells produce high (microgram to milligram/milliliter) levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the extracellular fluid surrounding prostate cancers but is found at 1,000- to 10,000-fold lower concentrations in the circulation, where it is inactivated due to binding to abundant se...
The understanding of the runoff generation processes is reviewed and simulation of daily streamflow is reported for the Gangotri Glacier basin (Central Himalayas) with area of ∼556 km, of which ∼286 km is occupied by the glaciers, and altitude of 4000 to 7000 m.a.s.l. A hydro-meteorological database was established by collecting meteorological and...
Estimates of trends of climatic changes at basin and state scales are required for developing adaptation strategies related to planning, development and management of water resources. In the present study, seasonal and annual trends of changes in maximum temperature (Tmax), minimum temperature (Tmin), mean temperature (Tmean), temperature range (Tr...
Molecular basis for secondary antiandrogen therapy in prostate cancer with mutant androgen receptors (ARs) is not fully elucidated.
Effects of steroidal and non-steroidal antiandrogens on transcriptional activities of wild-type and mutant (W741C, T877A, and W741C+T877A) ARs were measured. Crystal structure analysis and docking studies were performe...
The water balance approach was used to estimate the average contribution of snow- and glacier-melt runoff in the annual flow of the Beas River at Pandoh Dam. About 45% of the basin area is covered by snow during winter and about 15% remains covered by perpetual snow and glaciers. Snowand glacier-melt contribution was estimated by computing the othe...
Prostate Specific Antigen (PSA) is a biomarker used in the diagnosis of prostate cancer and to monitor therapeutic response. However, its precise role in prostate carcinogenesis and metastasis remains largely unknown. A number of studies arguing in the favor of an active role of PSA in prostate cancer development and progression have implicated thi...
Prostate cancer cells, like normal prostate epithelial cells, produce high levels of the differentiation marker and serine protease prostate-specific antigen (PSA). PSA is used extensively as a biomarker to screen for prostate cancer, to detect recurrence following local therapies, and to follow response to systemic therapies for metastatic disease...
In spite of the vital role of high altitude climatology in melting of snow and glaciers, retreat or advancement of glaciers, flash floods, erosion and sediment transport, etc., weather conditions are not much studied for the high altitude regions of Himalayas. In this study, a comprehensive meteorological analysis has been made for the Gangotri Met...
Prostate-specific membrane antigen (PSMA) is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types; however, it is not expressed by normal endothelial cells or other normal tissues. PSMA, therefore, represents an attractive candidate for selectively targeted therapies for prostate and/...
The Bhagirathi River, a proglacial melt water stream of the Gangotri Glacier, is the principal source of the Ganges river system. The upper part of the basin lies in the high altitude region of the Garhwal Himalayas and is extensively covered by glaciers. We provide hydro-meteorological insight into a severe storm that produced unusual high rains i...
The average distribution of precipitation provides essential input for understanding the hydrological process. The role of
complex topography in mountainous basins makes the spatial distribution of precipitation different than the plain areas. Besides
the rugged topography, the Himalayan basins also face the problem of limited physical accessibilit...
The present study describes the hydrological characteristics of the Gangotri Glacier (286 km2), which is one of the largest Himalayan Glaciers. The study involves collection and analysis of streamflow records near the snout of the Gangotri Glacier during four consecutive ablation seasons (May–October) (2000–2003). Discharge increases from May onwar...
The continuous increase in the emission of greenhouse gases has resulted in global warming, and substantial changes in the global climate are expected by the end of the current century. The reductions in mass, volume, area and length of glaciers on the global scale are considered as clear signals of a warmer climate. The increased rate of melting u...
To understand the sediment delivery variation for a Himalayan Glacier (Gangotri Glacier, Garhwal Himalayas) and to determine its relationship with discharge and air temperature, suspended sediment samples and discharge data were collected near the glacier snout (4000 m) for four melt seasons during the period 2000 2003. These data were used to esti...
Most of the Himalayan basins have considerable snow and glacier covered areas. The melt contribution in such rivers augments their flows in the lean season, thereby reducing the variation in water availability. Depending upon the prevailing climatic conditions, the runoff contribution from the glaciers in the Himalayan rivers starts in May after de...
IntroductionMethodologyStudy BasinStudy Period and Data UsedResults and DiscussionsApplicationsConclusions
References
Noncompetitive inhibitors of sarco- and endoplasmic reticulum calcium-ATPase (SERCA) have important therapeutic value in the treatment of cancer, due to their ability to induce apoptosis in cancer cells in a proliferation-independent manner. Thapsigargin (TG) and its analogues are one such class of inhibitors that bind to a hydrophobic pocket locat...
Diurnal variations in discharge and suspended sediment concentration (SSC), including runoff delaying characteristics, have been studied for the Gangotri Glacier, the largest glacier in the Garhwal Himalayas (glacierized area 286 km2; drainage area 556 km2). Hourly discharge and SSC data were collected near the snout of the glacier (∼4000 m) at an...
This study is carried out with the objective of examining the effect of altitude on water availability estimates for the various sub-basins of the Chenab river basin (mean elevation of the basin is 3600 m), which is a snow-fed Himalayan river basin located in the western Himalayas. This basin covers all three Himalayan ranges, i.e. outer, middle an...
Meteorological data collected near the snout of the Gangotri Glacier suggest that the study area receives less rainfall. The average seasonal rainfall is observed to be about 260 mm. The rainfall distribution does not show any monsoon impact. Amount of seasonal rainfall is highly variable (131.4-368.8 mm) from year to year, but, in general, August...
Abstract The impact of climate change is projected to have different effects within and between countries. Information about such change is required at global, regional and basin scales for a variety of purposes. An investigation was carried out to identify trends in temperature time series of 125 stations distributed over the whole of India. The n...
The impact of warmer climate on melt and evaporation was studied for rainfed, snowfed and glacierfed basins located in the western Himalayan region. Hydrological processes were simulated under current climatic conditions using a conceptual hydrological model, which accounts for the rainfall–runoff, evaporation losses, snow and glacier melt. After s...
The present study sets out to investigate the sensitivity of water availability to climate change for a large western Himalayan river (the Satluj River basin with an area of 22 275 km2 and elevation range of 500 to 7000 m), which receives contributions from rain, snow and glacier melt runoff. About 65% of the basin area is covered with snow during...
Storage and drainage characteristics of the Dokriani Glacier (9.66 km2) located in the Garhwal Himalayas have been studied. In order to understand these characteristics, clear weather (non-rainy) days data for three ablation seasons (1996–1998) are used because discharge is melt-driven on such days. Moreover, diurnal variations in the discharge on...
Assessment of soil erosion, sediment transport and deposition of sediment in the reservoirs, irrigation and hydropower systems are considered essential for the land and water management. The magnitude of sediment transported by rivers has become a serious concern for the water resources planning. In the present study, an assessment of sediment yiel...
The effect of warmer climate on the depletion of snow-covered area has been evaluated for the Satluj River basin located in the western Himalayan region in India. Snowmelt runoff contributes substantially to the annual streamflow of this river. In order to study the impact of three warming scenarios (T+1, T+2 and T+3°C), more than 160 new snow depl...
A conceptual snowmelt model, which accounts for both the snowmelt and rainfall runoff was developed and applied for daily streamflow simulation for the Satluj River basin located in the western Himalayan region. The model, designed primarily for mountainous basins, conceptualizes the basin as a number of elevation zones depending upon the topograph...
Sediment particles originating from erosion processes in the catchment are propagated along with the river flow. When the flow of a river is stored in a reservoir, the sediment settles in the reservoir and reduces its capacity. Reduction in the storage capacity of a reservoir beyond a limit hampers the purpose for which it was designed. Thus assess...
Streamflow in the Himalayan rivers is generated from rainfall, snow and ice. The distribution of runoff produced from these sources is such that the streamflow may be observed in these rivers throughout the year, i.e. they are perennial in nature. Snow and glacier melt runoff contributes substantially to the annual flows of these rivers and its est...
To assess the predictive significance of meteorologica l parameters for forecasting discharge from the Dokriani Glacier basin in the Himalayan region, discharge autocorrelation and correlations between discharge and meteorological factors were investigated on a monthly and a seasonal basis. Changes in correlations between discharge and meteorologic...
The present study deals with precipitation distribution with altitude for the Satluj and Beas basins in the western Himalayas. Rainfall increases linearly with elevation for both basins in the outer Himalayan range. The middle Himalayan range of the Beas basin has exceptionally heavy rainfall on the windward side and much less rain (less than half)...
The effect of climate change on snow water equivalent, snowmelt runoff, glacier melt runoff and total streamflow and their distribution is examined for the Spiti river. This is a high altitude Himalayan river located in the western Himalayan region. The total streamflow of this river has a significant contribution from snow and glacier melt runoff....
The contribution of snow and glacier-melt runoff to Himalayan rivers is significant and an estimation of the amount is necessary for the development, planning, and management of water resources. In this study, the average contribution of snow and glacier-melt runoff in the annual streamflow of the Chenab River at Akhnoor was estimated using a water...
Information on the snowmelt factor (SMF) is required for the estimation of snow and glacier melt runoff. In the present study, SMF is computed for a normal snowpack over a glacier at an altitude of about 4000 m in the Garhwal Himalayas. The effect of natural dusting on SMF is also examined. For this purpose, natural dust available at the site of th...
Observations of discharge, temperature and suspended sediment made at a gauging site established near the snout of the Dokriani glacier in the western Himalayan region are presented. These observations were made during a scientific expedition to this glacier over 21 days (23.8.1992-12.9.1992). Because of harsh weather conditions, obser vations cou...
