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Biomedical subjects

U Sen

Publications and source records attributed to U Sen.

17 recordsLinked to original sources

Distributed quantum dense coding.

We introduce the notion of distributed quantum dense coding, i.e., the generalization of quantum dense coding to more than one sender and more than one receiver. We show that global operations (as compared to local operations) of the senders do not increase the information transfer capacity, in the case of a single receiver. For the case of two receivers, using local operations and classical communication, a nontrivial upper bound for the capacity is derived. We propose a general classification scheme of quantum states according to their usefulness for dense coding. In the bipartite case (for any dimensions), bound entanglement is not useful for this task.

Journal Article↗

Purification and preliminary X-ray studies on hen serotransferrin in apo- and holo-forms.

Serum transferrins are monomeric glycoproteins with a molecular mass of around 80 kDa, that transport iron to cells via receptor-mediated endocytosis. Although both serum transferrins (STfs) and ovotransferrins (OTfs) are derived from the same gene in aves, the ovotransferrins do not transport iron in vivo. Crystal structures of OTf have been solved, in contrast no three-dimensional structure of avian STf have been determined as yet. Here we report the purification, crystallization, and preliminary crystallographic studies of the hen STf both in apo- (iron free) and holo- (iron loaded) forms. The hen STf has been purified to homogeneity by hydrophobic interaction chromatography. Both the apo- and holo-forms were crystallized by hanging drop vapor diffusion method at 277 K. The apo-crystals diffract to a resolution of 3.0 A and belong to the space group P4(3)2(1)2 with unit cell parameters a=b=90.5 and c=177.9 A. The holo-crystals diffract to a resolution of 2.8 A and belong to space group P2(1) with a=72.8, b=59.6, c=88.2 A, and beta=95.7 degrees.

Animals↗

Distinguishability of Bell states.

More than two multipartite orthogonal states cannot always be discriminated if only local operations and classical communication (LOCC) are allowed. We show that four Bell states cannot be discriminated by LOCC, even probabilistically, using the separability properties of a four-party unlockable bound entangled state. Using an existing inequality among the measures of entanglement, we show that any three Bell states cannot be discriminated with certainty by LOCC. Exploiting the inequality, we calculate the distillable entanglement of a certain class of 4 multiply sign in circle 4 mixed states.

Journal Article↗

Crystal structure of the von Willebrand factor modulator botrocetin.

The binding of von Willebrand factor (vWF) to the platelet receptor, glycoprotein (GP) Ib-IX-V complex, has a key role in the initiation of thrombus formation and is regulated by interactions with extracellular matrix components under the influence of hemodynamic forces. To a certain extent, these effects can be mimicked in vitro by two nonphysiologic modulators, ristocetin and botrocetin. The latter, isolated from the venom of the snake Bothrops jararaca, is a 31-kDa heterodimeric protein that forms a soluble complex with vWF. As an initial step toward understanding the mechanisms that regulate vWF function, we have solved the crystal structure of botrocetin at 1.8 A resolution. Botrocetin exhibits homology with other snake proteins, but contains only one metal binding site as compared to two in Factor IX binding protein and Factor IX/X binding protein and none in flavocetin. A distinctive feature of botrocetin is the presence of a negatively charged surface that may play a role in the association with the vWF A1 domain.

Amino Acid Sequence↗

Identification of maturation-inducing steroid in a freshwater perch Anabas testudineus and differential responses of intact follicles and denuded oocytes to cyclic AMP in oocyte maturation.

Postvitellogenic follicles of freshwater perch Anabas testudineus incubated with [(3)H]pregnenolone as exogenous precursor produced several metabolites, including 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (DHP) and 5 beta-pregnane-3 alpha, 17 alpha,20 beta-triol (5 beta-3 alpha,17 alpha,20 beta-P). These were identified by chromatography, microchemical reactions, and crystallization to constant specific activity. Following stimulation with fish (perch) pituitary extract (FPE) there was significant high production of DHP and 5 beta-3 alpha,17 alpha,20 beta-P, concomitant with a high percentage of germinal vesicle breakdown (GVBD). Inhibitor of steroidogenesis (trilostane) and inhibitors of protein synthesis (cycloheximide and actinomycin-D) completely blocked FPE-induced pregnenolone metabolism and oocyte maturation. The effectiveness of various C(21) steroids in inducing GVBD was examined. Results indicate that DHP was the most potent inducer of GVBD than other structurally related C(21) steroids. In intact follicles, FPE-stimulated production of DHP was shown to be mediated through the adenylate cyclase-cAMP pathway. Addition of IBMX or forskolin, which increases the endogenous cAMP level, as well as directly supplementing dbcAMP to the incubation medium, had no inhibitory effect on DHP-induced GVBD in the intact follicles. But all these agents were shown to inhibit GVBD in fully denuded oocytes. This study provides evidence that DHP, produced by postvitellogenic follicles through the adenylate cyclase-cAMP pathway, is the maturation-inducing steroid in freshwater perch and that the role played by cAMP in the induction of GVBD in intact follicles is different from that in the denuded oocytes. J. Exp. Zool. 287:294-303, 2000.

1-Methyl-3-isobutylxanthine↗

A transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in signal transduction.

BACKGROUND: Spo0F and Spo0B specifically exchange a phosphoryl group in a central step of the phosphorelay signal transduction system that controls sporulation in Bacilli. Spo0F belongs to the superfamily of response regulator proteins and is one of 34 such proteins in Bacillus subtilis. Spo0B is structurally similar to the phosphohistidine domain of histidine kinases, such as EnvZ, and exchanges a phosphoryl group between His30 and Asp54 on Spo0F. Information at the molecular level on the interaction between response regulators and phosphohistidine domains is necessary to develop a rationale for how phospho-signaling fidelity is maintained in two-component systems. RESULTS: Structural analysis of a co-crystal of the Spo0F response regulator interacting with the Spo0B phosphotransferase of the phosphorelay signal transduction system of B. subtilis was carried out using X-ray crystallographic techniques. The association of the two molecules brings the catalytic residues from both proteins into precise alignment for phosphoryltransfer. Upon complex formation, the Spo0B conformation remains unchanged. Spo0F also retains the overall conformation; however, two loops around the active site show significant deviations. CONCLUSIONS: The Spo0F-Spo0B interaction appears to be a prototype for response regulator-histidine kinase interactions. The primary contact surface between these two proteins is formed by hydrophobic regions in both proteins. The Spo0F residues making up the hydrophobic patch are very similar in all response regulators suggesting that the binding is initiated through the same residues in all interacting response regulator-kinase pairs. The bulk of the interactions outside this patch are through nonconserved residues. Recognition specificity is proposed to arise from interactions of the nonconserved residues, especially the hypervariable residues of the beta4-alpha4 loop.

Bacillus subtilis↗

Refined crystal structure (2.3 A) of a double-headed winged bean alpha-chymotrypsin inhibitor and location of its second reactive site.

The crystal structure of a double-headed alpha-chymotrypsin inhibitor, WCI, from winged bean seeds has now been refined at 2.3 A resolution to an R-factor of 18.7% for 9,897 reflections. The crystals belong to the hexagonal space group P6(1)22 with cell parameters a = b = 61.8 A and c = 212.8 A. The final model has a good stereochemistry and a root mean square deviation of 0.011 A and 1.14 degrees from ideality for bond length and bond angles, respectively. A total of 109 ordered solvent molecules were localized in the structure. This improved structure at 2.3 A led to an understanding of the mechanism of inhibition of the protein against alpha-chymotrypsin. An analysis of this higher resolution structure also helped us to predict the location of the second reactive site of the protein, about which no previous biochemical information was available. The inhibitor structure is spherical and has twelve anti-parallel beta-strands with connecting loops arranged in a characteristic beta-trefoil fold common to other homologous serine protease inhibitors in the Kunitz (STI) family as well as to some non homologous functionally unrelated proteins. A wide variation in the surface loop regions is seen in the latter ones.

Binding Sites↗

Cryocrystallography of a Kunitz-type serine protease inhibitor: the 90 K structure of winged bean chymotrypsin inhibitor (WCI) at 2.13 A resolution.

The crystal structure of a Kunitz-type double-headed alpha--chymotrypsin inhibitor from winged bean seeds has been refined at 2.13 A resolution using data collected from cryo-cooled (90 K) crystals which belong to the hexagonal space group P6(1)22 with unit-cell parameters a = b = 60.84, c = 207.91 A. The volume of the unit cell is reduced by 5.3% on cooling. The refinement converged to an R value of 20.0% (R(free) = 25.8%) for 11100 unique reflections and the model shows good stereochemistry, with r.m.s. deviations from ideal values for bond lengths and bond angles of 0.011 A and 1.4 degrees, respectively. The structural architecture of the protein consists of 12 antiparallel beta-strands joined in the form of a characteristic beta-trefoil fold, with the two reactive-site regions, Asn38-Leu43 and Gln63-Phe68, situated on two external loops. Although the overall protein fold is the same as that of the room-temperature model, some conformational changes are observed in the loop regions and in the side chains of a few surface residues. A total of 176 ordered water molecules and five sulfate ions are included in the model.

Binding Sites↗

Structure of a Kunitz-type chymotrypsin from winged bean seeds at 2.95 A resolution.

Thc crystal structure of an alpha-chymotrypsin inhibitor (P6(1)22; a = 61.4, c = 210.9 A) isolated from winged bean (Psophocarpus. tetragonolobus) seeds has been determined at 2.95 A resolution by the molecular-replacement method using the 2.6 A coordinates of Erythrina trypsin inhibitor (ETI) as the starting model (57% sequence homology). This protease inhibitor, WCI, belongs to the Kunitz (STI) family and is a single polypeptide chain with 183 amino-acid residues having a molecular weight of 20 244 Da. Structure refinement with RESTRAIN and X-PLOR has led to a crystallographic R factor of 19.1% for 3469 observed reflections (I > 2sigma) in the resolution range 8-2.95 A. A total of 56 water molecules have been incorporated in the refined model containing 181 amino-acid residues. In the refined structure the deviations of bond lengths and bond angles from ideal values are 0.015 A and 2.2 degrees, respectively. The inhibitor molecule is spherical and consists of 12 antiparallel beta-strands with connecting loops arranged in a characteristic folding (a six-stranded beta-barrel and a six-stranded lid on one hollow end of the barrel) common to other homologous serine protease inhibitors in the Kunitz (STI) family as well as to some non-homologous proteins like interleukin-lalpha and interleukin-lbeta. In the structure the conformation of the protruding reactive-site loop is stabilized through hydrogen bonds mainly formed by the side chain of Asnl4, which intrudes inside the cavity of the reactive-site loop, with the side-chain and main-chain atoms of some residues in the loop region. A pseudo threefold axis exists parallel to the barrel axis of the structure. Each of the three subdomains comprises of four beta-strands with connecting loops.

Journal Article↗

The role of alpha-difluoromethyl ornithine as an adjuvant to immunotherapy in mice bearing transplantable tumors.

alpha-Difluoromethyl ornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), depletes cellular polyamine levels which is significantly correlated to neoplastic transformation. DFMO was used to modulate the growth rate of Ehrlich ascites carcinoma in mice and attempts were made to use DFMO as an adjuvant to immunotherapy. The therapeutic efficacy was estimated by measurement of polyamine levels of blood and ODC activity. Significant changes were also observed in the survival of the treated groups of animals, the implications of which have been discussed.

Adjuvants, Immunologic↗

Study of acute mountain sickness during "rapid ascent" trekking to extreme altitude.

Acute mountain sickness (AMS) is an important cause of morbidity and mortality following acute exposure to high altitude. Several clinical variables were evaluated during the 1990 Trans-Kalindi Exploration to extreme altitude (5949 m) in 10 healthy adult lowlanders (age 31.7 +/- 6.4 yrs) who undertook a relatively rapid ascent from sea level to 5949 m with short periods of acclimatisation at 4393 m, 4898 m and 5700 m. 40% of the subjects had definite AMS. Only one subject had features of early cerebral oedema at 4393 m and had to be brought down temporarily to 3878 m. All subjects completed the trek without needing medication. Proper acclimatisation was characterised by absence of significant symptoms of AMS above 4500 m, absence of sustained tachycardia, fall in daily positive fluid balance from 1.7 +/- 0.9 (sea level) liters to 0.7 +/- 0.3 litres (at 5700 m) (p < 0.05), increase in 24 hours urinary sodium excretion from 174 +/- 78 mmol to 344 +/- 145 mmol (p < 0.01) and an increase in the ratio of urinary excretion of sodium and potassium from 3.1 (sea level) to 3.6 (5700 m). We conclude that the incidence of AMS at extreme altitude is similar to that at lower altitude. Reasonable acclimatisation is possible during the climb to extreme altitude.

Acclimatization↗

The role of glutathione in evaluating the efficacy of antimetabolites in transplanted tumors.

Levels of glutathione (GSH) in tumor cells play an important role in determining the clinical responses to certain anticancer agents. In the present work 5-fluorouracil and 5-fluorodeoxyuridine have been used as antineoplastic agents against transplanted Ehrlich ascites carcinoma. The glutathione levels in the tumor cells and liver tissues of the host animals have been studied by a specific histofluorescence method. Significant changes have been observed in the glutathione level of the host, tumor bearing and treated group of animals, the implications of which have been discussed.

Animals↗

The role of polyamines as a marker of tumor progression and regression in experimental tumors.

The pattern of changes in the polyamine spectrum has been studied under the stress of Sarcoma 180, a transplanted tumor growing in the peritoneal cavity of mice. Retinol, a known inhibitor of ornithine decarboxylase, was used to modulate tumor growth pattern and subsequent changes in the level of polyamines. The polyamine levels showed an increase during tumor proliferation. In the treated group, however, the enhanced levels exhibited a tendency to decrease, along with tumor inhibition, indicating that a positive correlation exists between the polyamine content in the red blood cells of mice and the tumor growth pattern.

Animals↗

Concanavalin A--horse radish peroxidase (Con A-HRP) labelling technique in detection and prognosis of cancer of uterine cervix.

The lectin binding capacity of the exfoliated epithelial cells of the uterine cervix was investigated with a modified concanavalin A - horse radish peroxidase labelling procedure. The normal healthy females exhibited a distinct rise in the percentage of labelled cells in comparison to those bearing squamous cell carcinoma. In the treated group, the responsive patients again exhibited a higher labelling percentage than the non-responsive patients - showing that the method is of both diagnostic and prognostic significance.

Adult↗

A study of the prognostic role of serum fucose and fucosyl transferase in cancer of the uterine cervix.

Serum fucose levels and fucosyl transferase activities have been designated as nonspecific markers of malignancy, and play an important role in the diagnosis of different types of malignancies. In the present study, attempts were made to determine the prognostic significance of these markers in patients with cancer of the uterine cervix after therapy. It was found that both serum fucose and fucosyl transferase, which were elevated in untreated patients declined significantly in patients responsive to therapy at different follow-up intervals, but not in patients unresponsive to therapy.

Adult↗

Serum fucosyl transferase activity and serum fucose levels as diagnostic tools in malignancy.

Glycoproteins play a significant role in neoplastic transformations. Both the levels of fucose and the activity of fucosyl transferase, which mediates the assembly of the oligosaccharide moieties of the glycoprotein chains, have been found to be elevated in neoplastic conditions. Since these elevations are common features of a variety of neoplastic cells, these two have been designated as non-specific markers of malignancy. In the present study, the fucose level and fucosyl transferase activity were determined in the sera of cancer patients and an attempt was made to establish a relationship between the two. It was found that both the fucose levels and fucosyl transferase activities showed considerable elevation in the five cancer groups studied, establishing them as useful diagnostic parameters. However, it was also observed that the rate of increased fucosyl transferase activity was not fully reflected in the resulting serum fucose levels in a few cases.

Carcinoma↗