Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication.

Diabetes is associated with loss of functional pancreatic β-cells, and restoration of β-cells is a major goal for regenerative therapies. Endogenous regeneration of β-cells via β-cell replication has the potential to restore cellular mass; however, pharmacological agents that promote regeneration or expansion of endogenous β-cells have been elusive. The regenerative capacity of β-cells declines rapidly with age, due to accumulation of p16(INK4a), resulting in limited capacity for adult endocrine pancreas regeneration. Here, we show that transforming growth factor-β (TGF-β) signaling via Smad3 integrates with the trithorax complex to activate and maintain Ink4a expression to prevent β-cell replication. Importantly, inhibition of TGF-β signaling can result in repression of the Ink4a/Arf locus, resulting in increased β-cell replication in adult mice. Furthermore, small molecule inhibitors of the TGF-β pathway promote β-cell replication in human islets transplanted into NOD-scid IL-2Rg(null) mice. These data reveal a novel role for TGF-β signaling in the regulation of the Ink4a/Arf locus and highlight the potential of using small molecule inhibitors of TGF-β signaling to promote human β-cell replication

Experimental and Clinical Evaluation of Nootropic Activity of Bacopa monniera Linn. (Brahmi)

Bacopa monniera Linn. (Brahmi) is an annual creeper belonging to familyScrophulariaceae and growing all over the Indian sub-continent in marshy areas. It is a major Medhya Rasayana used in Ayurveda for treatment of memory disorders. Large number of saponins and glycosides has been isolated from the plant. Most of the experimental and clinical studies have been done with crude extracts or standardized preparation of the two active saponins Bacosides A and B.Extracts or saponin mixture facilitate learning, improve consolidation of learned behavior and delay extinction in several models of learnt behavior in normal rats and mice as well as in chemically induced or transgenic models of Alzheimer's disease. They also prevent or reverse amnesia produced by drugs, stress or ischemic hypoxia. Other CNS effects include anti-anxiety, anti-convulsant and analgesic activity. Several mechanisms have been proposed to explain the mechanism of these CNS effects.Extracts as well as the bacoside preparation have been found safe and well tolerated in healthy volunteers in single dose or chronic administration for several weeks in a number of double blind placebo controlled studies in India and abroad. Chronic administration significantly improved information processing, learning and memory consolidation. It was found more effective than caffeine in a comparative study.Double blind placebo controlled studies with bacoside preparation have demonstrated beneficial effects and safety in elderly patients with Age Related Memory Impairment and in children with Attention Deficit Memory Disorder. It has also been found useful in anxiety neurosis, epilepsy and sleep disturbances in post menopausal women.The standardized preparation is marketed as a prescription drug after having obtained the necessary regulatory approval in India, Australia, New Zealand and South Africa and as an OTC product in several other south east Asian and African countries.Bacopa monniera Linn. (Brahmi) is an annual creeper belonging to familyScrophulariaceae and growing all over the Indian sub-continent in marshy areas. It is amajor Medhya Rasayana used in Ayurveda for treatment of memory disorders. Largenumber of saponins and glycosides has been isolated from the plant. Most of theexperimental and clinical studies have been done with crude extracts or standardizedpreparation of the two active saponins Bacosides A and B.Extracts or saponin mixture facilitate learning, improve consolidation of learnedbehavior and delay extinction in several models of learnt behavior in normal rats andmice as well as in chemically induced or transgenic models of Alzheimer's disease.They also prevent or reverse amnesia produced by drugs, stress or ischemic hypoxia.Other CNS effects include anti-anxiety, anti-convulsant and analgesic activity. Severalmechanisms have been proposed to explain the mechanism of these CNS effects.Extracts as well as the bacoside preparation have been found safe and well tolerated inhealthy volunteers in single dose or chronic administration for several weeks in anumber of double blind placebo controlled studies in India and abroad. Chronicadministration significantly improved information processing, learning and memoryconsolidation. It was found more effective than caffeine in a comparative study.Double blind placebo controlled studies with bacoside preparation have demonstratedbeneficial effects and safety in elderly patients with Age Related Memory Impairmentand in children with Attention Deficit Memory Disorder. It has also been found usefulin anxiety neurosis, epilepsy and sleep disturbances in post menopausal women.The standardized preparation is marketed as a prescription drug after having obtainedthe necessary regulatory approval in India, Australia, New Zealand and South Africaand as an OTC product in several other south east Asian and African countries.Bacopa monniera Linn. (Brahmi) is an annual creeper belonging to familyScrophulariaceae and growing all over the Indian sub-continent in marshy areas. It is a major Medhya Rasayana used in Ayurveda for treatment of memory disorders. Large number of saponins and glycosides has been isolated from the plant. Most of the experimental and clinical studies have been done with crude extracts or standardized preparation of the two active saponins Bacosides A and B.Extracts or saponin mixture facilitate learning, improve consolidation of learned behavior and delay extinction in several models of learnt behavior in normal rats and mice as well as in chemically induced or transgenic models of Alzheimer's disease. They also prevent or reverse amnesia produced by drugs, stress or ischemic hypoxia. Other CNS effects include anti-anxiety, anti-convulsant and analgesic activity. Several mechanisms have been proposed to explain the mechanism of these CNS effects.Extracts as well as the bacoside preparation have been found safe and well tolerated in healthy volunteers in single dose or chronic administration for several weeks in a number of double blind placebo controlled studies in India and abroad. Chronic administration significantly improved information processing, learning and memory consolidation. It was found more effective than caffeine in a comparative study.Double blind placebo controlled studies with bacoside preparation have demonstrated beneficial effects and safety in elderly patients with Age Related Memory Impairment and in children with Attention Deficit Memory Disorder. It has also been found useful in anxiety neurosis, epilepsy and sleep disturbances in post menopausal women.The standardized preparation is marketed as a prescription drug after having obtained the necessary regulatory approval in India, Australia, New Zealand and South Africa and as an OTC product in several other south east Asian and African countries.Bacopa monniera Linn. (Brahmi) is an annual creeper belonging to familyScrophulariaceae and growing all over the Indian sub-continent in marshy areas. It is amajor Medhya Rasayana used in Ayurveda for treatment of memory disorders. Largenumber of saponins and glycosides has been isolated from the plant. Most of theexperimental and clinical studies have been done with crude extracts or standardizedpreparation of the two active saponins Bacosides A and B.Extracts or saponin mixture facilitate learning, improve consolidation of learnedbehavior and delay extinction in several models of learnt behavior in normal rats andmice as well as in chemically induced or transgenic models of Alzheimer's disease.They also prevent or reverse amnesia produced by drugs, stress or ischemic hypoxia.Other CNS effects include anti-anxiety, anti-convulsant and analgesic activity. Severalmechanisms have been proposed to explain the mechanism of these CNS effects.Extracts as well as the bacoside preparation have been found safe and well tolerated inhealthy volunteers in single dose or chronic administration for several weeks in anumber of double blind placebo controlled studies in India and abroad. Chronicadministration significantly improved information processing, learning and memoryconsolidation. It was found more effective than caffeine in a comparative study.Double blind placebo controlled studies with bacoside preparation have demonstratedbeneficial effects and safety in elderly patients with Age Related Memory Impairmentand in children with Attention Deficit Memory Disorder. It has also been found usefulin anxiety neurosis, epilepsy and sleep disturbances in post menopausal women.The standardized preparation is marketed as a prescription drug after having obtainedthe necessary regulatory approval in India, Australia, New Zealand and South Africaand as an OTC product in several other south east Asian and African countries

Understanding the agglomeration behavior of nickel laterite and gold ores using statistical design of experiments

pre-printThe drum agglomeration of nickel laterite and gold ores has been optimized through the design of experiments (DOE) using a Taguchi L16 (45) orthogonal array to determine the optimum conditions for maximizing average agglomerate size and minimizing the amount of fines. The effects of controllable operating factors including moisture content (nickel laterite ore: 34-37%; gold ore: 7-10%), retention time (2-3.5 min), drum speed (15-45% critical speed), drum load (nickel laterite ore: 8-32 %; gold ore: 6-22%) and acid concentration (150-600 g/L) on the performance of the agglomeration process were studied. For nickel laterite ore, maximum average agglomerate size and minimum percent fines (-1 mm) occurred under the following conditions: drum load (23.7%), moisture (36.5%), time (3 min), drum speed (30% critical speed) and acid concentration (150 g/L). Under the studied nickel laterite ore conditions, the most effective parameters for maximizing average agglomerate size and minimizing the amount of fines were found to be drum load and acid concentration, respectively. Drum speed had a statistically significant effect on minimizing the amount of fines. Maximum average agglomerate size and minimum percent fines (-1 mm) for gold ore occurred under the following conditions: drum load (19.3%), moisture (8.5%), time (2 min 15 s) and drum speed (40% critical). The most significant factors for maximizing average agglomerate size and minimizing the amount of fines for gold ore were found to be drum load, time and moisture

Guest Editorial to the Special Letters Issue on Emerging Technologies in Multiparameter Biomedical Optical Imaging and Image Analysis

The past two decades have witnessed revolutionary advances in biomedical imaging modalities capable of providing biological and physiological information from the cellular scale to the organ level. Recent advances have also been focused on cost-effective, noninvasive, portable, and molecularimaging technologies for imaging at microscopic, mesoscopic, and macroscopic levels. These technologies have significant potential to advance biomedical research and clinical practice. They can also provide a better understanding and monitoring of physiological and functional disorders, which could lead to mainstream diagnostic technologies of the future

On the role of magnetic reconnection in jet/accretion disk systems

The most accepted model for jet production is based on the magneto-centrifugal acceleration out off an accretion disk that surrounds the central source (Blandford & Payne, 1982). This scenario, however, does not explain, e.g., the quasi-periodic ejection phenomena often observed in different astrophysical jet classes. de Gouveia Dal Pino & Lazarian (2005) (hereafter GDPL) have proposed that the large scale superluminal ejections observed in microquasars during radio flare events could be produced by violent magnetic reconnection (MR) episodes. Here, we extend this model to other accretion disk systems, namely: active galactic nuclei (AGNs) and young stellar objects (YSOs), and also discuss its role on jet heating and particle acceleration.Comment: To be published in the IAU Highlights of Astronomy, Volume 15, XXVII IAU General Assembly, August 2009, Ian F. Corbett et al., eds., 201

Measurement of the analyzing power of proton-carbon elastic scattering in the CNI region at RHIC

The single transverse spin asymmetry, A_N, of the p-carbon elastic scattering process in the Coulomb Nuclear Interference (CNI) region was measured using an ultra thin carbon target and polarized proton beam in the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL). In 2004, data were collected to calibrate the p-carbon process at two RHIC energies (24 GeV, 100 GeV). A_N was obtained as a function of momentum transfer -t. The results were fit with theoretical models which allow us to assess the contribution from a hadronic spin flip amplitude.Comment: Contribution to the proceedings of the 16th International Spin Physics Symposium, spin2004 (Trieste

Constraining the Observer Angle of the Kilonova AT2017gfo Associated with GW170817: Implications for the Hubble Constant

There is a strong degeneracy between the luminosity distance (D L) and the observer viewing angle (θ obs; hereafter viewing angle) of the gravitational wave (GW) source with an electromagnetic counterpart, GW170817. Here, for the first time, we present independent constraints on IMG ALIGN="MIDDLE" ALT="${θ}_{\mathrm{obs}}={32.5}-{-9.7}^{^\circ +11.7}$" SRC="apjab5799ieqn1.gif"/from broadband photometry of the kilonova (kN) AT2017gfo associated with GW170817. These constraints are consistent with independent results presented in the literature using the associated gamma-ray burst GRB 170817A. Combining the constraints on θ obs with the GW data, we find an improvement of 24% on H 0. The observer angle constraints are insensitive to other model parameters, e.g., the ejecta mass, the half-opening angle of the lanthanide-rich region and the temperature. A broad wavelength coverage extending to the near-infrared is helpful to robustly constrain θ obs. While the improvement on H 0 presented here is smaller than the one from high angular resolution imaging of the radio counterpart of GW170817, kN observations are significantly more feasible at the typical distances of such events from current and future LIGO-Virgo collaboration observing runs (D L ∼ 100 Mpc). Our results are insensitive to the assumption of the peculiar velocity of the kN host galaxy. © 2020. The American Astronomical Society

Successful Auxiliary Liver Transplant Followed by Hematopoietic Stem Cell Transplantation in X-Linked Lymphoproliferative Disease Type 1

We described a five-year-old boy who presented with acute liver failure of indeterminate aetiology, requiring urgent liver transplant. Post-operative course was complicated by pancytopaenia, hypogammaglobulinaemia and cerebral lesions, histologically confirmed as EBV-driven post-transplant lymphoproliferative disease. Genetic testing showed XLP1 mutation, prompting matched-unrelated haematopoietic stem cell transplant to cure his primary immunodeficiency

Measurement of the analyzing power in pp elastic scattering in the peak CNI region at RHIC

We report the first measurements of the A_N absolute value and shape in the -t range from 0.0015 to 0.010GeV/c^2 with a precision better than 0.005 for each A_N data point using a polarized atomic hydrogen gas jet target and the 100 GeV RHIC proton beam.Comment: 4 pages, 5 figure