1,186 research outputs found
Bisphosphonates and Atypical Femoral Fractures
No full textComment on Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. [N Engl J Med. 2010
Identification and in vivo validation of a 9-mer peptide derived from FSHβ with FSHR antagonist activity
No full textFSH-FSHR interaction is critical for folliculogenesis, spermatogenesis and progression of several cancers. Therefore, FSHR is an attractive target for fertility regulation and cancer therapeutics. Based on homology and structural analysis of hFSH-FSHR(ECD) complex, a minimal continuous stretch within FSHβ seat-belt loop (FSHβ (89-97)) was identified to be crucial for FSHR interaction. The ability of FSHβ (89-97) peptide to neutralize FSHR activity was evaluated by a panel of in vitro and in vivo experiments. The synthetic peptide significantly inhibited binding of [125I]-FSH to rat Fshr as well as FSH-induced cAMP production. In immature rats, FSHβ (89-97) peptide administration reduced FSH-mediated increase in ovarian weight. The peptide inhibited transition of follicles from pre-antral to antral stage and hindered the cell cycle progression of granulosa cells beyond G0/G1 phase. In adult rats, administration of the peptide inhibited estradiol synthesis and significantly perturbed folliculogenesis
Central residues of FSHβ (89–97) peptide are not critical for FSHR binding: Implications for peptidomimetic design
No full textIn our previous study, we had identified a 9-mer peptide (FSHβ (89–97)) derived from seat belt loop of human FSHβ and demonstrated its ability to function as FSHR antagonist in vivo. Structure analysis revealed that the four central residues 91STDC94 within this peptide may not be critical for receptor binding. In the present study, 91STDC94 residues were substituted with alanine to generate ΔFSHβ 89–97(91STDC94/AAAA) peptide. Analogous to the parent peptide, ΔFSHβ 89–97(91STDC94/AAAA) peptide inhibited binding of iodinated FSH to rat FSHR and reduced FSH-induced cAMP production. The peptide could impede granulosa cell proliferation leading to reduction in FSH-mediated ovarian weight gain in immature female rats. In these rats, peptide administration further downregulated androgen receptor and estrogen receptor-alpha expression and upregulated estrogen receptor-beta expression. The results indicate that substitution of 91STDC94 with alanine did not significantly alter FSHR antagonist activity of FSHβ (89–97) peptide implying that these residues are not critical for FSH-FSHR interaction and can be replaced with non-peptidic moieties for development of more potent peptidomimetics
A verified compiler for Handel-C
No full textThe recent popularity of Field Programmable Gate Array (FPGA) technology has made the synthesis of Hardware Description Language (HDL) programs into FPGAs a very attractive topic for research. In particular, the correctness in the synthesis of an FPGA programming file from a source HDL program has gained significant relevance in the context of safety or mission-critical systems.
The results presented here are part of a research project aiming at producing a verified compiler for the Handel-C language. Handel-C is a high level HDL based on the syntax of the C language extended with constructs to deal with parallel behaviour and process communications based on
CSP.
Given the complexity of designing a provably correct compiler for a language like Handel-C, we have adopted the algebraic approach to compilation as it offers an elegant solution to this problem. The idea behind algebraic compilation is to create a sound reasoning framework in
which the a formal model of the source Handel-C program can be embedded and refined into a formal abstraction of the target hardware. As the algebraic rules used to compile the program are proven to preserve the semantics, the correctness of the entire compilation process (i.e., semantic equivalence between source and target programs) can be argued by construction, considering each programming construct in isolation, rather than trying to assert the correctness of the compilation in a single step.
Regarding hardware synthesis, the algebraic approach has already been applied to subsets of Occam and Verilog. Our work builds on some ideas from these works but focuses on the more complex timing model imposed by Handel-C. Moreover, our work covers features like shared variables, multi-way communications and priorities which, to our knowledge, have never been addressed within the framework of algebraic compilation.
Finally, one characteristic of the algebraic approach is that the basic reduction laws in the reasoning framework are postulated as axioms. As an invalid axiom would allow us to prove invalid results (up to the extent of being able to prove a false theorem) we are also concerned about
the consistency of the basic postulates in our theory. We addressed this by providing denotational semantics for Handel-C and its reasoning extensions in the context of the Unifying Theories of Programming (UTP). Our UTP denotational semantics not only provided a model for our theory (hence, proving its consistency) but also allowed us to prove all the axioms in the compilation framework
Particle Separation and Hydrologic Control by Cementitious Permeable Pavement
No full textCementitious permeable pavement (CPP) has the potential to provide in situ particulate, chemistry, and hydrologic control for storm water. The specific aspects of this control that have been the subject of significant interest and discussion are filtration, hydrologic control, and the potential for clogging. This study investigated the behavior of CPP subject to particle loadings for a constant particle size gradation, a sandy silt gradation. Recovered from an 1-75 Cincinnati, Ohio, site subject to runoff loadings, these CPP specimens had similar pore size distributions and effective porosities. The total mass removal efficiencies for the particles were significant, ranging from nearly total removal for medium and coarse sands to greater than 60% removal for fine silt-size particles. With an engineered surface matrix, total phosphorus reductions exceeded 80%. The commensurate turbidity reductions were significant, and the turbidity of the effluent was generally reduced from 50% to 90% of the influent values. In situ hydrologic restoration was significant, generating peak flow reductions and storage within the pore space that represented approximately 25% of the CPP volume, and the temporal aspects of the influent hydrograph were attenuated compared with that for conventional impervious pavement. The initial hydraulic conductivity was in the range of 10(-2) cm/s and followed a first-order exponential decline, and restoration of this hydraulic conductivity required some form of pavement cleaning approximately once every 6-month period. Cleaning by pavement vacuuming restored more than 95% of the initial hydraulic conductivity
Moonlighting glycolytic protein glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells
No full textProkaryotic pathogens establish infection in mammals by capturing the proteolytic enzyme plasminogen (Plg) onto their surface to digest host extracellular matrix (ECM). One of the bacterial surface Plg receptors is the multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In a defensive response, the host mounts an inflammatory response, which involves infiltration of leukocytes to sites of inflammation. This requires macrophage exit from the blood and migration across basement membranes, a phenomenon dependent on proteolytic remodeling of the ECM utilizing Plg. The ability of Plg to facilitate inflammatory cell recruitment critically depends on receptors on the surface of phagocyte cells. Utilizing a combination of biochemical, cellular, knockdown, and
approaches, we demonstrated that upon inflammation, macrophages recruit GAPDH onto their surface to carry out the same task of capturing Plg to digest ECM to aid rapid phagocyte migration and combat the invading pathogens. We propose that GAPDH is an ancient, evolutionarily conserved receptor that plays a key role in the Plg-dependent regulation of macrophage recruitment in the inflammatory response to microbial aggression, thus pitting prokaryotic GAPDH against mammalian GAPDH, with both involved in a conserved role of Plg activation on the surface of their respective cells, to conflicting ends.-Chauhan, A. S., Kumar, M., Chaudhary, S., Patidar, A., Dhiman, A., Sheokand, N., Malhotra, H., Raje, C. I., Raje, M. Moonlighting glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH): an evolutionarily conserved plasminogen receptor on mammalian cells
Review of Robson, S.; Sidomulyo, H. (2023) Kidung Pañji Margasmara: a Middle Javanese romance, by Kěmuling Rat Dyah Atapêng Raje
No full textAsian Studie
Determinants of Weekly Yields on Government Securities in India
No full textThis paper examines the determinants of the Government yields in India using weekly data from April 2001 through March 2009. The analysis covers Treasury Bills with residual maturity of 15-91 days and Government securities of residual maturity one, five and ten years respectively. The empirical estimates show that a long-run relationship exists between each of these interest rates and the policy rate, rate of growth of money supply, inflation, interest rate spread, foreign interest rate and forward premium. At the same time, the empirical results also show that the relative importance of the determinants varies across the maturity spectrum. The normalized generalized variance decompositions suggest that the policy rate and the rate of growth of high powered money are less important in explaining the proportion of variation in longer term interest rates. The weight of the forward premium also diminishes as we move towards higher maturity interest rates. The inflation rate is also relatively less important in explaining variations in the 10-year rate. The yield spread, on the other hand, is more important in explaining the longer term rates. The results also show that a large proportion of the variation in the rates on the 5-year and 10-year government securities is attributed to the interest rate itself suggesting that the unexplained variation may be a result of cyclical factors that are relatively more important for longer term rates but are not captured by the yield spread and are omitted from the estimations due to the high frequency of data employed.interest rate determination; government yields; cointegration and generalized variance decompositions
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