Stereochemical Analysis of Higher α,α-Dialkylglycine Containing Peptides. Characterization of Local Helical Conformations at Dipropylglycine Residues and Observation of a Novel Hydrated Multiple β-Turn Structure in Crystals of a Glycine Rich Peptide

The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the context of a poor helix promoting sequence. Single crystals of 1 were obtained in the space group P21/c with a = 13.716(2) Å, b = 12.960(2) Å, c = 22.266(4) Å, and β = 98.05(1)°; R = 6.3% for 3660 data with |Fo| > 4σ. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts φ, ψ values distorted from those expected for an ideal type II‘ β-turn (φGly(1) = +72.0°, ψGly(1) = −166.0°; φDpg(2) = −54.0°, ψDpg(2) = −46.0°) with an inserted water molecule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts φ, ψ values which lie broadly in the right handed helical region (φGly(3) = −78.0°, ψGly(3) = −9.0°; φGly(4) = −80.0°, ψGly(4) = −18.0°). There is a chiral reversal at Dpg(5) which takes up φ, ψ values in the left handed helical region. The Dpg(5)-Gly(6) segment closely resembles an ideal type I‘ β-turn (φDpg(5) = +56.0°, ψDpg(5) = +32.0°; φGly(6) = +85.0°, ψGly(6) = −3.0°). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminus forms a hydrated Schellman motif, with water insertion into the potential 6 → 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformation observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.

Thermal stresses in a finite hollow cylinder due to an axisymmetric temperature field at the end surface

A three-dimensional exact solution for determining the thermal stresses in a finite hollow cylinder subject to a steady state axisymmetric temperature field over one of its end surfaces has been given. Numerical results for a hollow cylinder, having lenght to outer diameter ratio equal to one and inner to outer diameter ratio equal to 0.75, subjected to a symmetric temperature variation over the end surfaces of the cylinder have been given.

Thermal stresses in a finite solid cylinder due to an axisymmetric temperature field at the end surface.

A three-dimensional rigorous solution for determining thermal stresses in a finite solid cylinder due to a steady state axisymmetric temperature field over one of its end surfaces is given. Numerical results for a solid cylinder having a length to diameter ratio equal to one and subjected to a symmetric temperature variation over half the radius of the cylinder at the end surfaces are included. These results have been compared with the results of the approximate solution given by W. Nowacki.

Assessment of Nanoscience and Nanotechnology Initiatives in India

Nanotechnology is a new technology which is generating a lot of interest among academicians, practitioners and scientists. Critical research is being carried out in this area all over the world.Governments are creating policy initiatives to promote developments it the nanoscale science and technology developments. Private investment is also seeing a rising trend. Large number of academic institutions and national laboratories has set up research centers that are workingon the multiple applications of nanotechnology. Wide ranges of applications are claimed for nanotechnology. This consists of materials, chemicals, textiles, semiconductors, to wonder drug delivery systems and diagnostics. Nanotechnology is considered to be a next big wave of technology after information technology and biotechnology. In fact, nanotechnology holds the promise of advances that exceed those achieved in recent decades in computers and biotechnology. Much interest in nanotechnology also could be because of the fact that enormous monetary benefits are expected from nanotechnology based products. According to NSF, revenues from nanotechnology could touch $ 1 trillion by 2015. However much of the benefits are projected ones. Realizing claimed benefits require successful development of nanoscience andv nanotechnology research efforts. That is the journey of invention to innovation has to be completed. For this to happen the technology has to flow from laboratory to market. Nanoscience and nanotechnology research efforts have to come out in the form of new products, new processes, and new platforms.India has also started its Nanoscience and Nanotechnology development program in under its 10(th) Five Year Plan and funds worth Rs. One billion have been allocated for Nanoscience and Nanotechnology Research and Development. The aim of the paper is to assess Nanoscience and Nanotechnology initiatives in India. We propose a conceptual model derived from theresource based view of the innovation. We have developed a structured questionnaire to measure the constructs in the conceptual model. Responses have been collected from 115 scientists and engineers working in the field of Nanoscience and Nanotechnology. The responses have been analyzed further by using Principal Component Analysis, Cluster Analysis and Regression Analysis.

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context

Multiple Perspectives on Networks: Conceptual Development, Application and Integration in an Entrepreneurial Context. The purpose of this thesis is to enhance cross-fertilization between three different approaches to network research. The business network approach may contribute in terms of how relationships are created, developed and how tie content changes within ties, not only between them. The social network approach adds to the discussion by offering concepts of structural change on a network level. The network approach in entrepreneurship contributes by emphasizing network content, governance and structure as a way of understanding and capturing networks. This is discussed in the conceptual articles, Articles 2 and 3. The ultimate purpose of this thesis is to develop a theoretical and empirical understanding of network development processes. This is fulfilled by presenting a theoretical framework, which offers multiple views on process as a developmental outcome. The framework implies that change ought to be captured both within and among relationships over time in the firm as well as in the network. Consequently, changes in structure and interaction taking place simultaneously need to be included when doing research on network development. The connection between micro and macro levels is also stressed. Therefore, the entrepreneur or firm level needs to be implemented together with the network level. The surrounding environment impacts firm and network development and vice versa and hence needs to be integrated. Further, it is necessary to view network development not only as a way forward but to include both progression and regression as inevitable parts of the process. Finally, both stability and change should be taken into account as part of network development. Empirical results in Article 1 show support for a positive impact of networks on SME internationalization. Article 4 compares networks of novice, serial and portfolio entrepreneurs but the empirical results show little support for differences in the networks by type of entrepreneur. The results demonstrate that network interaction and structure is not directly impacted by type of entrepreneur involved. It indicates instead that network structure and interaction is more impacted by the development phase of the firm. This in turn is in line with the theoretical implications, stating that the development of the network and the firm impacts each other, as they co-evolve.

The neuronal cell adhesion molecule ICAM-5

The neuronal cell adhesion molecule ICAM-5 ICAM-5 (telencephalin) belongs to the intercellular adhesion molecule (ICAM)-subgroup of the immunoglobulin superfamily (IgSF). ICAMs participate in leukocyte adhesion and adhesion-dependent functions in the central nervous system (CNS) through interacting with the leukocyte-specific b2 integrins. ICAM-5 is found in the mammalian forebrain, appears at the time of birth, and is located at the cell soma and neuronal dendrites. Recent studies also show that it is important for the regulation of immune functions in the brain and for the development and maturation of neuronal synapses. The clinical importance of ICAM-5 is still under investigation; it may have a role in the development of Alzheimer s disease (AD). In this study, the role of ICAM-5 in neuronal differentiation and its associations with a-actinin and N-methyl-D-aspartic acid (NMDA) receptors were examined. NMDA receptors (NMDARs) are known to be involved in many neuronal functions, including the passage of information from one neuron to another one, and thus it was thought important to study their role related to ICAM-5. The results suggested that ICAM-5 was able to induce dendritic outgrowth through homophilic adhesion (ICAM-5 monomer binds to another ICAM-5 monomer in the same or neighbouring cell), and the homophilic binding activity appeared to be regulated by monomer/multimer transition. Moreover, ICAM-5 binding to a-actinin was shown to be important for neuritic outgrowth. It was examined whether matrix metalloproteinases (MMPs) are the main enzymes involved in ICAM-5 ectodomain cleavage. The results showed that stimulation of NMDARs leads to MMP activation, cleavage of ICAM-5 and it is accompanied by dendritic spine maturation. These findings also indicated that ICAM-5 and NMDA receptor subunit 1 (NR1) compete for binding to a-actinin, and ICAM-5 may regulate the NR1 association with the actin cytoskeleton. Thus, it is concluded that ICAM-5 is a crucial cell adhesion molecule involved in the development of neuronal synapses, especially in the regulation of dendritic spine development, and its functions may also be involved with memory formation and learning.

Evaluation of the profitability of fast-growing tropical trees.

The profitability of fast-growing trees was investigated in the northeastern and eastern provinces of Thailand. The financial, economic, and tentative environmental-economic profitability was determined separately for three fast-growing plantation tree species and for three categories of plantation managers: the private industry, the state (the Royal Forest Department) and the farmers. Fast-growing tree crops were also compared with teak (Tectona grandis), a traditional medium or long rotation species, and Para rubber (Hevea brasiliensis) which presently is the most common cultivated tree in Thailand. The optimal rotation for Eucalyptus camaldulensis pulpwood production was eight years. This was the most profitable species in pulpwood production. In sawlog production Acacia mangium and Melia azedarach showed a better financial profitability. Para rubber was more profitable and teak less profitable than the three fast-growing species. The economic profitability was higher than the financial one, and the tentative environmental-economic profitability was slightly higher than the economic profitability. The profitability of tree growing is sensitive to plantation yields and labour cost changes and especially to wood prices. Management options which aim at pulpwood production are more sensitive to input or output changes than those options which include sawlog production. There is an urgent need to improve the growth and yield data and to study the environmental impacts of tree plantations for all species and plantation types.

On determining the elastic modulus of a cylindrical sample subjected to flexural excitation in a resonant column apparatus

For resonant column tests conducted in the flexure mode of excitation, a new methodology has been proposed to find the elastic modulus and associated axial strain of a cylindrical sample. The proposed method is an improvement over the existing one, and it does not require the assumption of either the mode shape or zero bending moment condition at the top of the sample. A stepwise procedure is given to perform the necessary calculations. From a number of resonant column experiments on aluminum bars and dry sand samples, it has been observed that the present method as compared with the one available in literature provides approximately (i) 5.9%-7.3% higher values of the elastic modulus and (ii) 6.5%-7.3% higher values of the associated axial strains.

Exact eigenstates of the Pariser-Parr-Pople model for anthracene

The pi-electronic structure of anthracene is discussed by combining exact solutions of the Pariser-Parr-Pople (PPP) model and semiempirical PM3 calculations. Symmetry adaptation of the 2.8 million singlet valence-bond (VB) diagrams is explicitly demonstrated for D2h and electron-hole symmetry. Standard PPP parameters provide a comprehensive fit to one- and two-photon anthracene spectra and intensities up to the strong 1 B-1(3u)-absorption at 5.24 eV, the 10th excited state in the dense correlated spectrum, and indicate a reassignment of two-photon absorptions. The singlet-triplet gap and fine-structure constants also agree with experiment. Fully-relaxed PM3 geometries are obtained for the anthracene ground state and for singlet, triplet, and charged bipolarons. The PM3 bond lengths correlate well with PPP bond orders for the idealized structure. Single-determinantal PM3 excitation and relaxation energies for bipolarons are consistent with exact PPP results and contrast all-valence electron with pi-electron calculations. Several correlation effects are noted in the rich pi-spectra of anthracene in connection with improved PPP modeling of conjugated molecules and polymers.

On The Temperature-Dependence of Regioselectivity in the Amination of Bromobenzotropones

The ipso/cine ratio in the amination of 5-bromo-2,3-benzo- or 2-bromo-4,5-benzotropone shows a dependence upon the temperature at which the reaction is conducted, changing in favour of the ipso-product when the temperature is maintained high, ruling out an aryne-type mechanism. A comparison of independent mechanisms envisaged for the formation of the two isomeric products suggests a two-part reason: (i) at a higher reaction temperature, C-protonation, a step necessary for the formation of the cine-product, could be retarded when a direct internal mode is interfered with by a less efficient external one, and (ii) reketonisation by elimination of bromide, needed to form the ipso-product, is likely to have a high temperature coefficient enabling the rate of its formation to overtake that of the cine-product.

Unwinding of heterologous DNA by RecA protein during the search for homologous sequences

The search for homologous sequences promoted by RecA protein in vitro involves a presynaptic filament and naked duplex DNA, the multiple contacts of which produce nucleoprotein networks or coaggregates. The single-stranded DNA within the presynaptic filaments, however, is extended to an axial spacing 1.5 times that of B-form DNA. To investigate this paradoxical difference between the spacing of bases in the RecA presynaptic filament versus the target duplex DNA, we explored the effect of heterologous contacts on the conformation of DNA, and vice versa. In the presence of wheat germ topoisomerase I, RecA presynaptic filaments induced a rapid, limited reduction in the linking number of heterologous circular duplex DNA. This limited unwinding of heterologous duplex DNA, termed heterologous unwinding, was detected within 30 seconds and reached a steady state within a few minutes. Presynaptic filaments that were formed in the presence of ATP?S and separated from free RecA protein by gel filtration also generated a ladder of topoisomers upon incubation with relaxed duplex DNA and topoisomerase. The inhibition of heterologous contacts by 60 mImage -NaCl or 5 mImage -ADP resulted in a corresponding decrease in heterologous unwinding. In reciprocal fashion, the stability or number of heterologous contacts with presynaptic filaments was inversely related to the linking number of circular duplex DNA. These observations show that heterologous contacts with the presynaptic filament cause a limited unwinding of the duplex DNA, and conversely that the ability of the DNA to unwind stabilizes transient heterologous contacts.

Nematogens with more flexible chains than aromatic rings in the core

Mesogens containing four rings in the main core can accommodate one terminal and two nearby lateral chains on each outside aromatic ring. These compounds containing six chains present an enantiotropic nematic range which is influenced by the rigidity of the links. The conformational behaviour of the first methyleneoxy group within the chains was investigated by one and two dimensional C-13 NMR. The sign of the jump in chemical shifts when entering the nematic phase indicates the folding of each lateral branch. Dipolar oscillations during cross-polarization contact provide the values of the bond order parameter. The two First lateral fragments do not behave in the same way, demonstrating the influence of the fragment along which the chain is back: folded.

Reproductive queue without overt conflict in the primitively eusocial wasp Ropalidia marginata

Colonies of the primitively eusocial wasp Ropalidia marginata consist of a single egg layer (queen) and a number of non-egg-laying workers. Although the queen is a docile individual, not at the top of the behavioral dominance hierarchy of the colony, she maintains complete reproductive monopoly. If the queen is lost or removed, one and only one of the workers potential queen (PQ)] becomes hyperaggressive and will become the next queen of the colony. The PQ is almost never challenged because she first becomes hyperaggressive and then gradually loses her aggression, develops her ovaries, and starts laying eggs. Although we are unable to identify the PQ when the queen is present, she appears to be a ``cryptic heir designate.'' Here, we show that there is not just one heir designate but a long reproductive queue and that PQs take over the role of egg-laying, successively, without overt conflict, as the queen or previous PQs are removed. The dominance rank of an individual is not a significant predictor of its position in the succession hierarchy. The age of an individual is a significant predictor, but it is not a perfect predictor because PQs often bypass older individuals to become successors. We suggest that such a predesignated reproductive queue that is implemented without overt conflict is adaptive in the tropics, where conspecific usurpers from outside the colony, which can take advantage of the anarchy prevailing in a queenless colony and invade it, are likely to be present throughout the year.

Multiple molecular alterations in phosphodegrons 1-3 within AAV2 capsid demonstrates higher hepatic gene transfer efficiency

The success of AAV2 mediated hepatic gene transfer in human trials for diseases such as hemophilia has been hampered by a combination of low transduction efficiency and a robust immune response directed against these vectors. We have previously shown that AAV2 is targeted for destruction in the cytoplasm by the host-cellular kinase/ubiquitination/proteasomal degradation machinery and modification of the serine(S)/threonine(T) kinase and lysine(K) targets on AAV capsid is beneficial. Thus targeted single mutations of S/T>A(S489A, S498A, T251A) and K>R (K532R) improved the efficiency of gene transfer in vivo as compared to wild type (WT)-AAV2 vectors (∼6-14 fold). In the present study, we evaluated if combined alteration of the phosphodegrons (PD), which are the phosphorylation sites recognized as degradation signals by ubiquitin ligases, improves further the gene transfer efficiency. Thus, we generated four multiple mutant vectors (PD: 1+3, S489A+K532R, PD: 1+3, S489A+K532R together with T251 residue which did not lie in any of the phosphodegrons but had shown increased transduction efficiency compared to the WT-AAV2 vector (∼6 fold) and was also conserved in 9 out of 10 AAV serotypes (AAV 1 to 10), PD: 1+3, S489A+K532R+S498A and a fourth combination of PD: 3, K532R+T251. We then evaluated them in vitro and in vivo and compared their gene transfer efficiency with either the WT-AAV2 or the best single mutant S489A-AAV2 vector. The novel multiple mutations on the AAV2 capsid did not affect the overall vector packaging efficiency. All the multiple AAV2 mutants showed superior transduction efficiency in HeLa cells in vitro when compared to either the WT (62-72% Vs 21%) or the single mutant S489A (62-72% Vs 50%) AAV2 vectors as demonstrated by FACS analysis (Fig. 1A). On hepatic gene transfer with 5x10^10 vgs per animal in C57BL/6 mice, all the multiple mutants showed increased transgene expression compared to either the WT-AAV2 (∼15-23 fold) or the S489A single mutant vector (∼2-3 fold) (Fig.1B and C). These novel multiple mutant AAV2 vectors also showed higher vector copy number in murine hepatocytes 4 weeks post transduction, as compared to the WT-AAV2 (∼5-6 Vs 1.4 vector copies/diploid genome) and further higher when compared to the single mutant S489A(∼5-6 fold Vs 3.8 fold) (Fig.1D). Further ongoing studies will demonstrate the therapeutic benefit of one or more of the multiple mutants vectors in preclinical models of hemophilia.

Multi-resistance states in the electrical switching behavior of amorphous Si15Te75Ge10 thin films: Possibility of multi-bit storage

Electrical switching studies on amorphous Si15Te75Ge10 thin film devices reveal the existence of two distinct, stable low-resistance, SET states, achieved by varying the electrical input to the device. The multiple resistance levels can be attributed to multi-stage crystallization, as observed from temperature dependant resistance studies. The devices are tested for their ability to be RESET with minimal resistance degradation; further, they exhibit a minimal drift in the SET resistance value even after several months of switching. (c) 2013 Elsevier B.V. All rights reserved.