Transformation formula for exponential sums involving fourier coefficients of modular forms

In 1984 Jutila [5] obtained a transformation formula for certain exponential sums involving the Fourier coefficients of a holomorphic cusp form for the full modular group SL(2, Z). With the help of the transformation formula he obtained good estimates for the distance between consecutive zeros on the critical line of the Dirichlet series associated with the cusp form and for the order of the Dirichlet series on the critical line, [7]. In this paper we follow Jutila to obtain a transformation formula for exponential sums involving the Fourier coefficients of either holomorphic cusp forms or certain Maass forms for congruence subgroups of SL(2, Z) and prove similar estimates for the corresponding Dirichlet series.

Interaction of A beta peptide (1-40) with amino acid aluminium complexes: relevance to Alzheimer's disease

A beta (39-43 aminoacid residues) is the principal peptide component of amyloid deposits in Alzheimer's disease (AD). A beta peptide is derived from the amyloid precursor protein (APP) in which mutations give rise to many forms of familial AD. Aluminium is reported to play a key role in inducing conformational change in the synthetic beta-amyloid peptide (1-40)from alpha-helix to beta-pleated sheet, leading to aggregation and fibrillar formation. We have studied the interaction of amino acid-Al complexes such as D-Asp-Al and L-Glu-Al with A beta(1-40) in TFE/buffer (70% TFE and 30% H2O v/v pH 6.7) mixture using CD spectroscopy. The interaction of either of these amino acid complexes with A beta(1-40) results in loss of alpha-helical content and the peptide is more unstructured compared to free Al3+ in the solution. Our data strongly support the idea, that the Al3+ in the form of aminoacid-Al complexes is more effective in inducing random coil conformation in the A beta peptide than the free Al3+ present in the solution.

Real-time kinetic analysis of hCG-monoclonal antibody interaction using radiolabeled hCG probe: presence of two forms of Ag-mAb complex as revealed by solid phase dissociation studies

Real-time kinetics of ligand-ligate interaction has predominantly been studied by either fluorescence or surface plasmon resonance based methods. Almost all such studies are based on association between the ligand and the ligate. This paper reports our analysis of dissociation data of monoclonal antibody-antigen (hCG) system using radio-iodinated hCG as a probe and nitrocellulose as a solid support to immobilize mAb. The data was analyzed quantitatively for a one-step and a two-step model. The data fits well into the two-step model. We also found that a fraction of what is bound is non-dissociable (tight-binding portion (TBP)). The TBP was neither an artifact of immobilization nor does it interfere with analysis. It was present when the reaction was carried out in homogeneous solution in liquid phase. The rate constants obtained from the two methods were comparable. The work reported here shows that real-time kinetics of other ligand-ligate interaction can be studied using nitrocellulose as a solid support. (C) 2002 Elsevier Science B.V. All rights reserved.

Crystal structures of open and closed forms of D-serine deaminase from Salmonella typhimurium - implications on substrate specificity and catalysis

Metabolism of D-amino acids is of considerable interest due to their key importance in cell structure and function. Salmonella typhimurium D-serine deaminase (StDSD) is a pyridoxal 5' phosphate (PLP) dependent enzyme that catalyses degradation of D-Ser to pyruvate and ammonia. The first crystal structure of D-serine deaminase described here reveals a typical Foldtype II or tryptophan synthase beta subunit fold of PLP-dependent enzymes. Although holoenzyme was used for crystallization of both wild-type StDSD (WtDSD) and selenomethionine labelled StDSD (SeMetDSD), significant electron density was not observed for the cofactor, indicating that the enzyme has a low affinity for the cofactor under crystallization conditions. Interestingly, unexpected conformational differences were observed between the two structures. The WtDSD was in an open conformation while SeMetDSD, crystallized in the presence of isoserine, was in a closed conformation suggesting that the enzyme is likely to undergo conformational changes upon binding of substrate as observed in other Foldtype II PLP-dependent enzymes. Electron density corresponding to a plausible sodium ion was found near the active site of the closed but not in the open state of the enzyme. Examination of the active site and substrate modelling suggests that Thr166 may be involved in abstraction of proton from the C alpha atom of the substrate. Apart from the physiological reaction, StDSD catalyses a, b elimination of D-Thr, D-Allothr and L-Ser to the corresponding alpha-keto acids and ammonia. The structure of StDSD provides a molecular framework necessary for understanding differences in the rate of reaction with these substrates.

Preliminary X-ray crystallographic studies on acetate kinase (AckA) from Salmonella typhimurium in two crystal forms

Acetate kinase (AckA) catalyzes the reversible transfer of a phosphate group from acetyl phosphate to ADP, generating acetate and ATP, and plays a central role in carbon metabolism. In the present work, the gene corresponding to AckA from Salmonella typhimurium (StAckA) was cloned in the IPTG-inducible pRSET C vector, resulting in the attachment of a hexahistidine tag to the N-terminus of the expressed enzyme. The recombinant protein was overexpressed, purified and crystallized in two different crystal forms using the microbatch-under-oil method. Form I crystals diffracted to 2.70 angstrom resolution when examined using X-rays from a rotating-anode X-ray generator and belonged to the monoclinic space group C2, with unit-cell parameters a = 283.16, b = 62.17, c = 91.69 angstrom, beta = 93.57 degrees. Form II crystals, which diffracted to a higher resolution of 2.35 angstrom on the rotating-anode X-ray generator and to 1.90 angstrom on beamline BM14 of the ESRF, Grenoble, also belonged to space group C2 but with smaller unit-cell parameters (a = 151.01, b = 78.50, c = 97.48 angstrom, beta = 116.37 degrees). Calculation of Matthews coefficients for the two crystal forms suggested the presence of four and two protomers of StAckA in the asymmetric units of forms I and II, respectively. Initial phases for the form I diffraction data were obtained by molecular replacement using the coordinates of Thermotoga maritima AckA (TmAckA) as the search model. The form II structure was phased using a monomer of form I as the phasing model. Inspection of the initial electron-density maps suggests dramatic conformational differences between residues 230 and 300 of the two crystal forms and warrants further investigation.

Structures of new crystal forms of Mycobacterium tuberculosis peptidyl-tRNA hydrolase and functionally important plasticity of the molecule

The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase from M.similar to tuberculosis reported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure.

Comparison of tertiary structures of proteins in protein-protein complexes with unbound forms suggests prevalence of allostery in signalling proteins

Abstract: Background: Most signalling and regulatory proteins participate in transient protein-protein interactions during biological processes. They usually serve as key regulators of various cellular processes and are often stable in both protein-bound and unbound forms. Availability of high-resolution structures of their unbound and bound forms provides an opportunity to understand the molecular mechanisms involved. In this work, we have addressed the question "What is the nature, extent, location and functional significance of structural changes which are associated with formation of protein-protein complexes?" Results: A database of 76 non-redundant sets of high resolution 3-D structures of protein-protein complexes, representing diverse functions, and corresponding unbound forms, has been used in this analysis. Structural changes associated with protein-protein complexation have been investigated using structural measures and Protein Blocks description. Our study highlights that significant structural rearrangement occurs on binding at the interface as well as at regions away from the interface to form a highly specific, stable and functional complex. Notably, predominantly unaltered interfaces interact mainly with interfaces undergoing substantial structural alterations, revealing the presence of at least one structural regulatory component in every complex. Interestingly, about one-half of the number of complexes, comprising largely of signalling proteins, show substantial localized structural change at surfaces away from the interface. Normal mode analysis and available information on functions on some of these complexes suggests that many of these changes are allosteric. This change is largely manifest in the proteins whose interfaces are altered upon binding, implicating structural change as the possible trigger of allosteric effect. Although large-scale studies of allostery induced by small-molecule effectors are available in literature, this is, to our knowledge, the first study indicating the prevalence of allostery induced by protein effectors. Conclusions: The enrichment of allosteric sites in signalling proteins, whose mutations commonly lead to diseases such as cancer, provides support for the usage of allosteric modulators in combating these diseases.

Crystal Structures and Physicochemical Properties of Four New Lamotrigine Multicomponent Forms

In the present study, four new multicomponent forms of lamotrigine (LTG) with selected carboxylic acids, viz. acetic acid, propionic acid, sorbic acid, and glutaric acid, have been identified. Preliminary solid-state characterization was done by differential scanning calorimetry/thermogravimetric, infrared, and powder X-ray diffraction techniques. X-ray single-crystal structure analysis confirmed the proton transfer, stoichiometry, and the molecular composition, revealing all of these to be a new salt/salt-cocrystal/salt monosolvate monohydrate of LTG. All four compounds exhibited both the aminopyridine dimer of LTG (motif 4) and cation-anion dimers between protonated LTG and the carboxylate anion in their crystal structures. Further, these new crystal forms were subjected to solubility studies in water, powder dissolution studies in 0.1 N HCl, and stability studies under humid conditions in comparison with pure LTG base. The solubility of these compounds in water is significantly enhanced compared with that of pure base, which is attributed to the type of packing motifs present in their crystal structures as well as to the lowering of the pH by the acidic coformers. Solid residues of all forms remaining after solubility and dissolution experiments were also assessed for any transformation in water and acidic medium.

Comparison of North American universities with and without medical schools and their technology transfer initiatives

Empirical research available on technology transfer initiatives is either North American or European. Literature over the last two decades shows various research objectives such as identifying the variables to be measured and statistical methods to be used in the context of studying university based technology transfer initiatives. AUTM survey data from years 1996 to 2008 provides insightful patterns about the North American technology transfer initiatives, we use this data in our paper. This paper has three sections namely, a comparison of North American Universities with (n=1129) and without Medical Schools (n=786), an analysis of the top 75th percentile of these samples and a DEA analysis of these samples. We use 20 variables. Researchers have attempted to classify university based technology transfer initiative variables into multi-stages, namely, disclosures, patents and license agreements. Using the same approach, however with minor variations, three stages are defined in this paper. The first stage is to do with inputs from R&D expenditure and outputs namely, invention disclosures. The second stage is to do with invention disclosures being the input and patents issued being the output. The third stage is to do with patents issued as an input and technology transfers as outcomes.

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation I as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

New solid forms of the anti-HIV drug etravirine: salts, cocrystals, and solubility

Thirteen new solid forms of etravirine were realized in the process of polymorph and cocrystal/salt screening to improve the solubility of this anti-HIV drug. One anhydrous form, five salts (hydrochloride, mesylate, sulfate, besylate, and tosylate), two cocrystals (with adipic acid and 1,3,5-benzenetricarboxylic acid), and five solvates (formic acid, acetic acid, acetonitrile, and 2:1 and 1:1 methanolates) were obtained. The conformational flexibility of etravirine suggests that it can adopt four different conformations, and among these, two are sterically favorable. However, in all 13 solid forms, the active pharmaceutical ingredient (API) was found to adopt just one conformation. Due to the poor aqueous solubility of the API, the solubilities of the salts and cocrystals were measured in a 50% ethanol water mixture at neutral pH. Compared to the salts, the cocrystals were found to be stable and showed an improvement in solubility with time. All the salts were dissociated within an hour, except the tosylate, which showed 50% phase transformation after 1 h of the slurry experiment. A structure property relationship was examined to analyze the solubility behavior of the solid forms.

Synthesis of pure iron magnetic nanoparticles in large quantity

Free nanoparticles of iron (Fe) and their colloids with high saturation magnetization are in demand for medical and microfluidic applications. However, the oxide layer that forms during processing has made such synthesis a formidable challenge. Lowering the synthesis temperature decreases rate of oxidation and hence provides a new way of producing pure metallic nanoparticles prone to oxidation in bulk amount (large quantity). In this paper we have proposed a methodology that is designed with the knowledge of thermodynamic imperatives of oxidation to obtain almost oxygen-free iron nanoparticles, with or without any organic capping by controlled milling at low temperatures in a specially designed high-energy ball mill with the possibility of bulk production. The particles can be ultrasonicated to produce colloids and can be bio-capped to produce transparent solution. The magnetic properties of these nanoparticles confirm their superiority for possible biomedical and other applications.

ABOUT FORMS OF ELECTRONIC AND IONIC DEVICES WITH THERMIONIC CATHODES.

The miniaturization of electronic and ionic devices with thermionic cathodes and thc improvement of their vacuum properties are questions of very great interest to the electronic engineer. However there have bcen no proposals so far to analyse the problem of miniaturization of such devices In a fundamental way. The present work suggests a choice of the geometrical shape of the cathode, the anode and the envelope of the device, that may help towards such a fundamcnlal approach.It is shown that a design, in which the cathode and the envelope of the tube are made of thm prismatic shape and the anode coincides with the cnvclope, offers a slriknrg advantage over the conventional cylindrical design, in respect of over-all size. The use of the prismatic shape will lead to considerable economy in msterials and may facilitate simpler prodoct~ont echn~ques. I n respect of the miin criteria of vacuum, namely the grade of vacuum, the internal volume occupied by residual gases, the evolution of gases in the internal space and the diffusion of gases from outside into the devicc, it is shown that the prismatic form is at least as good as, if not somewhat superior lo, the cylindrical form.In the actual construction of thin prismatic tubes, manv practical problems will arise, the most important being the mechanical strength and stablity of the structure. But the changeover from the conventional cylindrical to the new prirmaiic form, with its basic advantages, is a development that merits close attention.