Improved bounds on the radius and curvature of the K pi scalar form factor and implications to low-energy theorems

We obtain stringent bounds in the < r(2)>(K pi)(S)-c plane where these are the scalar radius and the curvature parameters of the scalar K pi form factor, respectively, using analyticity and dispersion relation constraints, the knowledge of the form factor from the well-known Callan-Treiman point m(K)(2)-m(pi)(2), as well as at m(pi)(2)-m(K)(2), which we call the second Callan-Treiman point. The central values of these parameters from a recent determination are accomodated in the allowed region provided the higher loop corrections to the value of th form factor at the second Callan-Treiman point reduce the one-loop result by about 3% with F-K/F-pi = 1.21. Such a variation in magnitude at the second Callan-Treiman point yields 0.12 fm(2) less than or similar to < r(2)>(K pi)(S) less than or similar to 0.21 fm(2) and 0.56 GeV-4 less than or similar to c less than or similar to 1.47 GeV-4 and a strong correlation between them. A smaller value of F-K/F-pi shifts both bounds to lower values.

New constraints on the pion EM form factor using Pi `(-Q(2))

We study the constraints arising on the expansion parameters c and d of the pion electromagnetic form factor from the inclusion of pure spacelike data and the phase of timelike data along with one spacelike datum, using as input the first derivative of the QCD polarization amplitude Pi'(-Q(2)). These constraints when combined with other analyses, provide a valuable check on a determination of c due to Guo et al. and on our previous work where pionic contribution to the (g - 2) of the muon was used as the input. This work further illustrates the power of analyticity techniques in form factor analysis.

Sequences that adopt non-B-DNA conformation in form V DNA as probed by enzymic methylation

pBR322 form V DNA is a highly torsionally strained molecule with a linking number of zero. We have used sequence- specific DNA methylases as probes for B-DNA in this molecule, exploiting the inability of methylases to methylate single-stranded DNA and Z-DNA, both of which are known to occur in form V DNA. Some sequences in form V DNA were shown to be totally in the B-form, others were totally in an altered, unmethylatable conformation, while still other sites appeared to exist partly in altered and partly in normal B-conformation. Some potential Z-forming sequences (alternating pyrimidine/purine) of less than seven base-pairs were not in the Z conformation in form V DNA, whereas others did adopt an altered structure, indicating a modulating influence of flanking sequences. Furthermore, regions of imperfect alternating pyrimidine/purine structure were sometimes capable of adopting an altered structure. In addition, some regions of altered structure had no apparent Z-forming sequences, nor were they in polypurine stretches, which have also been proposed to form left-handed DNA. These non-B-DNA conformations may represent novel left-handed helical structures or sequences that become single stranded under torsional strain. Long regions of either altered (unmethylatable) DNA or B-DNA were not always observed. In fact, one region showed three transitions between B-like DNA and altered structure within 26 base-pairs.

VEGF-C/VEGFR-3 and PDGF-B/PDGFR-b pathways in embryonic lymphangiogenesis

The circulatory system comprises the blood vascular system and the lymphatic vascular system. These two systems function in parallel. Blood vessels form a closed system that delivers oxygen and nutrients to the tissues and removes waste products from the tissues, while lymphatic vessels are blind-ended tubes that collect extravasated fluid and cells from the tissues and return them back to blood circulation. Development of blood and lymphatic vascular systems occurs in series. Blood vessels are formed via vasculogenesis and angiogenesis whereas lymphatic vessels develop via lymphangiogenesis, after the blood vascular system is already functional. Members of the vascular endothelial growth factor (VEGF) family are regulators of both angiogenesis and lymphangiogenesis, while members of the platelet-derived growth factor (PDGF) family are major mitogens for pericytes and smooth muscle cells and regulate formation of blood vessels. Vascular endothelial growth factor C (VEGF-C) is the major lymphatic growth factor and signaling through its receptor vascular endothelial growth factor receptor 3 (VEGFR-3) is sufficient for lymphangiogenesis in adults. We studied the role of VEGF-C in embryonic lymphangiogenesis and showed that VEGF-C is absolutely required for the formation of lymph sacs from embryonic veins. VEGFR-3 is also required for normal development of the blood vascular system during embryogenesis, as Vegfr3 knockout mice die at mid-gestation due to failure in remodeling of the blood vessels. We showed that sufficient VEGFR-3 signaling in the embryo proper is required for embryonic angiogenesis and in a dosage-sensitive manner for embryonic lymphangiogenesis. Importantly, mice deficient in both VEGFR-3 ligands, Vegfc and Vegfd, developed a normal blood vasculature, suggesting VEGF-C- and VEGF-D- independent functions for VEGFR-3 in the early embryo. Platelet-derived growth factor B (PDGF-B) signals via PDGFR-b and regulates formation of blood vessels by recruiting pericytes and smooth muscle cells around nascent endothelial tubes. We showed that PDGF-B fails to induce lymphangiogenesis when overexpressed in adult mouse skin using adenoviral vectors. However, mouse embryos lacking Pdgfb showed abnormal lymphatic vessels, suggesting that PDGF-B plays a role in lymphatic vessel maturation and separation from blood vessels during embryogenesis. Lymphatic vessels play a key role in immune surveillance, fat absorption and maintenance of fluid homeostasis in the body. However, lymphatic vessels are also involved in various diseases, such as lymphedema and tumor metastasis. These studies elucidate the basic mechanisms of embryonic lymphangiogenesis and add to the knowledge of lymphedema and tumor metastasis treatments by giving novel insights into how lymphatic vessel growth could be induced (in lymphedema) or inhibited (in tumor metastasis).

Structure of a new crystal form of 2- ([3-(trifluoromethyl)phenyl] amino)benzoic acid (flufenamic acid)

C14Ht0F3NO2, P2.Jc, a = 12.523 (4), b = 7.868(6), c = 12.874 (3)A, fl = 95.2 (2) ° , O,,, = 1.47 (4), D e = 1.47 Mg m -3, Z = 4. Final R = 0.074 for 2255 observed reflections. The carboxyl group and the phenyl ring bearing the carboxyl group are nearly coplanar whereas the two phenyl rings are inclined with respect to each other at 52.8 ° . The difference between the two polymorphs of flufenamic acid lies in the geometrical disposition of the [3-(trifluoromethyl)- phenyl]amino moiety with respect to the benzoic acid moiety. As in other fenamate structures, the carboxyl group and the imino N atom are connected through an intramolecular hydrogen bond; also, pairs of centrosymmetrically related molecules are connected through hydrogen bonds involving carboxyl groups.

Profiling ellagic acid content: The importance of form and ascorbic acid levels

As the importance of plant-based antioxidants to human health becomes clearer there is a rapidly expanding search for rich sources of these compounds. Much attention is currently focussed on the antioxidant potential of ellagic acid (EA). Making assessment difficult is that EA occurs in different forms: free EA, EA glycosides and polymeric ellagitannins. The overall structure of these forms has a pronounced effect on their antioxidant efficiency and is responsible for widely differing reactivity, solubility and hence bioavailability properties. Often associated with EA is vitamin C which also contributes to the plant foods total antioxidant activity. Previous studies have suggested that ascorbic acid may have protective effects on the polyphenol content of plants. With a view to gaining evidence that the bioactive forms of vitamin C influence EA content, several fruits with a range of EA and vitamin C contents were examined. To facilitate a more detailed assessment of the selected fruits antioxidant potential the relative proportions of EA forms were also determined. In strawberries and boysenberries EA content was predominantly in the polymeric form (21% and 12% free EA plus EA glycoside vs total EA levels for strawberry and boysenberry respectively), while in Kakadu plum it was mainly in the free form (70% of total EA). An increasing percentage of dehydroascorbic acid (9 to 14% of total vitamin C) indicating enhanced transformation of ascorbic acid to its oxidative degradation product together with stable free EA levels (≈ 950 mg/100 g DW) over the 4 month frozen storage period for the Kakadu plum samples are consistent with a possible protective effect of EA by ascorbic acid.

Structure of a new crystal form of 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid (flufenamic acid)

C14Ht0F3NO2, P2.Jc, a = 12.523 (4), b = 7.868(6), c = 12.874 (3)A, fl = 95.2 (2) ° , O,,, = 1.47 (4), D e = 1.47 Mg m -3, Z = 4. Final R = 0.074 for 2255 observed reflections. The carboxyl group and the phenyl ring bearing the carboxyl group are nearly coplanar whereas the two phenyl rings are inclined with respect to each other at 52.8 ° . The difference between the two polymorphs of flufenamic acid lies in the geometrical disposition of the [3-(trifluoromethyl)- phenyl]amino moiety with respect to the benzoic acid moiety. As in other fenamate structures, the carboxyl group and the imino N atom are connected through an intramolecular hydrogen bond; also, pairs of centrosymmetrically related molecules are connected through hydrogen bonds involving carboxyl groups.

Lymphatic vessels in health and disease: Role of the VEGF-C/VEGFR-3 pathway and the transcription factor FOXC2

The circulatory system consists of two vessel types, which act in concert but significantly differ from each other in several structural and functional aspects as well as in mechanisms governing their development. The blood vasculature transports oxygen, nutrients and cells to tissues whereas the lymphatic vessels collect extravasated fluid, macromolecules and cells of the immune system and return them back to the blood circulation. Understanding the molecular mechanisms behind the developmental and functional regulation of the lymphatic system long lagged behind that of the blood vasculature. Identification of several markers specific for the lymphatic endothelium, and the discovery of key factors controlling the development and function of the lymphatic vessels have greatly facilitated research in lymphatic biology over the past few years. Recognition of the crucial importance of lymphatic vessels in certain pathological conditions, most importantly in tumor metastasis, lymphedema and inflammation, has increased interest in this vessel type, for so long overshadowed by its blood vascular cousin. VEGF-C (Vascular Endothelial Growth Factor C) and its receptor VEGFR-3 are essential for the development and maintenance of embryonic lymphatic vasculature. Furthermore, VEGF-C has been shown to be upregulated in many tumors and its expression found to positively correlate with lymphatic metastasis. Mutations in the transcription factor FOXC2 result in lymphedema-distichiasis (LD), which suggests a role for FOXC2 in the regulation of lymphatic development or function. This study was undertaken to obtain more information about the role of the VEGF-C/VEGFR-3 pathway and FOXC2 in regulating lymphatic development, growth, function and survival in physiological as well as in pathological conditions. We found that the silk-like carboxyterminal propeptide is not necessary for the lymphangiogenic activity of VEGF-C, but enhances it, and that the aminoterminal propeptide mediates binding of VEGF-C to the neuropilin-2 coreceptor, which we suggest to be involved in VEGF-C signalling via VEGFR-3. Furthermore, we found that overexpression of VEGF-C increases tumor lymphangiogenesis and intralymphatic tumor growth, both of which could be inhibited by a soluble form of VEGFR-3. These results suggest that blocking VEGFR-3 signalling could be used for prevention of lymphatic tumor metastasis. This might prove to be a safe treatment method for human cancer patients, since inhibition of VEGFR-3 activity had no effect on the normal lymphatic vasculature in adult mice, though it did lead to regression of lymphatic vessels in the postnatal period. Interestingly, in contrast to VEGF-C, which induces lymphangiogenesis already during embryonic development, we found that the related VEGF-D promotes lymphatic vessel growth only after birth. These results suggest, that the lymphatic vasculature undergoes postnatal maturation, which renders it independent of ligand induced VEGFR-3 signalling for survival but responsive to VEGF-D for growth. Finally, we show that FOXC2 is necessary for the later stages of lymphatic development by regulating the morphogenesis of lymphatic valves, as well as interactions of the lymphatic endothelium with vascular mural cells, in which it cooperates with VEGFR-3. Furthermore, our study indicates that the absence of lymphatic valves, abnormal association of lymphatic capillaries with mural cells and an increased amount of basement membrane underlie the pathogenesis of LD. These findings have given new insight into the mechanisms of normal lymphatic development, as well as into the pathogenesis of diseases involving the lymphatic vasculature. They also reveal new therapeutic targets for the prevention and treatment of tumor metastasis and lymphatic vascular failure in certain forms of lymphedema. Several interesting questions were posed that still need to be addressed. Most importantly, the mechanism of VEGF-C promoted tumor metastasis and the molecular nature of the postnatal lymphatic vessel maturation remain to be elucidated.

Redox-linked proton transfer by cytochrome c oxidase

The respiratory chain is found in the inner mitochondrial membrane of higher organisms and in the plasma membrane of many bacteria. It consists of several membrane-spanning enzymes, which conserve the energy that is liberated from the degradation of food molecules as an electrochemical proton gradient across the membrane. The proton gradient can later be utilized by the cell for different energy requiring processes, e.g. ATP production, cellular motion or active transport of ions. The difference in proton concentration between the two sides of the membrane is a result of the translocation of protons by the enzymes of the respiratory chain, from the negatively charged (N-side) to the positively charged side (P-side) of the lipid bilayer, against the proton concentration gradient. The endergonic proton transfer is driven by the flow of electrons through the enzymes of the respiratory chain, from low redox-potential electron donors to acceptors of higher potential, and ultimately to oxygen. Cytochrome c oxidase is the last enzyme in the respiratory chain and catalyzes the reduction of dioxygen to water. The redox reaction is coupled to proton transport across the membrane by a yet unresolved mechanism. Cytochrome c oxidase has two proton-conducting pathways through which protons are taken up to the interior part of the enzyme from the N-side of the membrane. The K-pathway transfers merely substrate protons, which are consumed in the process of water formation at the catalytic site. The D-pathway transfers both substrate protons and protons that are pumped to the P-side of the membrane. This thesis focuses on the role of two conserved amino acids in proton translocation by cytochrome c oxidase, glutamate 278 and tryptophan 164. Glu278 is located at the end of the D-pathway and is thought to constitute the branching point for substrate and pumped protons. In this work, it was shown that although Glu278 has an important role in the proton transfer mechanism, its presence is not an obligatory requirement. Alternative structural solutions in the area around Glu278, much like the ones present in some distantly related heme-copper oxidases, could in the absence of Glu278 support the formation of a long hydrogen-bonded water chain through which proton transfer from the D-pathway to the catalytic site is possible. The other studied amino acid, Trp164, is hydrogen bonded to the ∆-propionate of heme a3 of the catalytic site. Mutation of this amino acid showed that it may be involved in regulation of proton access to a proton acceptor, a pump site, from which the proton later is expelled to the P-side of the membrane. The ion pair that is formed by the ∆-propionate of heme a3 and arginine 473 is likely to form a gate-like structure, which regulates proton mobility to the P-side of the membrane. The same gate may also be part of an exit path through which water molecules produced at the catalytically active site are removed towards the external side of the membrane. Time-resolved optical and electrometrical experiments with the Trp164 to phenylalanine mutant revealed a so far undetected step in the proton pumping mechanism. During the A to PR transition of the catalytic cycle, a proton is transferred from Glu278 to the pump site, located somewhere in the vicinity of the ∆-propionate of heme a3. A mechanism for proton pumping by cytochrome c oxidase is proposed on the basis of the presented results and the mechanism is discussed in relation to some relevant experimental data. A common proton pumping mechanism for all members of the heme-copper oxidase family is moreover considered.

A Generalized Approach to Multiresolution Complex SAR Signal Processing

Multiresolution synthetic aperture radar (SAR) image formation has been proven to be beneficial in a variety of applications such as improved imaging and target detection as well as speckle reduction. SAR signal processing traditionally carried out in the Fourier domain has inherent limitations in the context of image formation at hierarchical scales. We present a generalized approach to the formation of multiresolution SAR images using biorthogonal shift-invariant discrete wavelet transform (SIDWT) in both range and azimuth directions. Particularly in azimuth, the inherent subband decomposition property of wavelet packet transform is introduced to produce multiscale complex matched filtering without involving any approximations. This generalized approach also includes the formulation of multilook processing within the discrete wavelet transform (DWT) paradigm. The efficiency of the algorithm in parallel form of execution to generate hierarchical scale SAR images is shown. Analytical results and sample imagery of diffuse backscatter are presented to validate the method.

The curvature invariant for a class of homogeneous operators

For an operator T in the class B-n(), introduced by Cowen and Douglas, the simultaneous unitary equivalence class of the curvature and the covariant derivatives up to a certain order of the corresponding bundle E-T determine the unitary equivalence class of the operator T. In a subsequent paper, the authors ask if the simultaneous unitary equivalence class of the curvature and these covariant derivatives are necessary to determine the unitary equivalence class of the operator T is an element of B-n(). Here we show that some of the covariant derivatives are necessary. Our examples consist of homogeneous operators in B-n(). For homogeneous operators, the simultaneous unitary equivalence class of the curvature and all its covariant derivatives at any point w in the unit disc are determined from the simultaneous unitary equivalence class at 0. This shows that it is enough to calculate all the invariants and compare them at just one point, say 0. These calculations are then carried out in number of examples. One of our main results is that the curvature along with its covariant derivative of order (0, 1) at 0 determines the equivalence class of generic homogeneous Hermitian holomorphic vector bundles over the unit disc.

Effect of reinforcement form on the bearing capacity of square footings on sand

This paper presents the results of laboratory model loading tests and numerical studies carried out on square footings supported on geosynthetic reinforced sand beds. The relative performance of different forms of geosynthetic reinforcement (i.e. geocell, planar layers and randomly distributed mesh elements) in foundation beds is compared; using same quantity of reinforcement in each test. A biaxial geogrid and a geonet are used for reinforcing the sand beds. Geonet is used in two forms of reinforcement, viz. Planar layers and geocell, while the biaxial geogrid was used in three forms of reinforcement, viz. planar layers, geocell and randomly distributed mesh elements. Laboratory load tests on unreinforced and reinforced footings are simulated in a numerical model and the results are analyzed to understand the distribution of displacements and stresses below the footing better. Both the experimental and numerical studies demonstrated that the geocell is the most advantageous form of soil reinforcement technique of those investigated, provided there is no rupture of the material during loading. Geogrid used in the form of randomly distributed mesh elements is found to be inferior to the other two forms. Some significant observations on the difference in reinforcement mechanism for different forms of reinforcement are presented in this paper.

Crystal Structures of a New Polymorphic Form of Gabapentin Monohydrate and the E and Z Isomers of 4-Tertiarybutylgabapentin

Gabapentin, a widely used antiepileptic drug, crystallizes in multiple polymorphic forms. A new crystal form of gabapentin monohydrate in the space group Pbca is reported and the packing arrangement compared with that of a previously reported polymorph in the space group P2(1)/c [Ibers, J.A. (2001) Acta Crystallogr; C57:641]. Gabapentin polymorphs can also occur from a selection of one of the two distinct chair forms of the 1,1-disubstituted cyclohexane. Crystal structures of the E and Z isomers of 4-tert-butylgabapentin provide models for analyzing anticipated packing modes in the conformational isomers of gabapentin. The E isomer crystallized in the space group Pca2(1), while the Z isomer crystallized in the space group P2(1)/c. The crystal structure of E-4-tert-butylgabapentin provides the only example of a structure in a non-centrosymmetric space group. Crystal structures of the hydrochloride and hydrobromide salts of 4-tert-butyl derivatives are reported. The results suggest that for gabapentin, a large 'polymorph-space' may be anticipated, in view of the multiple conformational states that are accessible to the molecule.

Process-dependent magnetic properties of Co-doped ZnO in bulk and thin film form

Structural, optical and magnetic studies of Co-doped ZnO have been carried out for bulk as well as thin films. The magnetic studies revealed the superparamagnetic nature for low-temperature synthesized samples, indicating the presence of cobalt metallic clusters, and this is supported by the optical studies. For the high-temperature sintered samples one obtains paramagnetism. The optical studies reveal the presence of Co2+ ions in the tetrahedral sites indicating proper doping. Interestingly, the films deposited by laser ablation from the paramagnetic target showed room temperature ferromagnetism. It appears that the magnetic nature of this system is process dependent.

Structural Studies on the Second Mycobacterium smegmatis Dps: Invariant and Variable Features of Structure, Assembly and Function

A second DNA binding protein from stationary-phase cells of Mycobacterium smegmatis (MsDps2) has been identified from the bacterial genome. It was cloned, expressed and characterised and its crystal structure was determined. The core dodecameric structure of MsDps2 is the same as that of the Dps from the organism described earlier (MsDps1). However, MsDps2 possesses a long N-terminal tail instead of the C-terminal tail in MsDps1. This tail appears to be involved in DNA binding. It is also intimately involved in stabilizing the dodecamer. Partly on account of this factor, MsDps2 assembles straightway into the dodecamer, while MsDps1 does so on incubation after going through an intermediate trimeric stage. The ferroxidation centre is similar in the two proteins, while the pores leading to it exhibit some difference. The mode of sequestration of DNA in the crystalline array of molecules, as evidenced by the crystal structures, appears to be different in MsDps1 and MsDps2, highlighting the variability in the mode of Dps–DNA complexation. A sequence search led to the identification of 300 Dps molecules in bacteria with known genome sequences. Fifty bacteria contain two or more types of Dps molecules each, while 195 contain only one type. Some bacteria, notably some pathogenic ones, do not contain Dps. A sequence signature for Dps could also be derived from the analysis.