Landau-Type Theory of Planar Crystal Plasticity.

We show that nonlinear continuum elasticity can be effective in modeling plastic flows in crystals if it is viewed as a Landau theory with an infinite number of equivalent energy wells whose configuration is dictated by the symmetry group GL(2,Z). Quasistatic loading can be then handled by athermal dynamics, while lattice-based discretization can play the role of regularization. As a proof of principle, we study dislocation nucleation in a homogeneously sheared 2D crystal and show that the global tensorial invariance of the elastic energy foments the development of complexity in the configuration of collectively nucleating defects. A crucial role in this process is played by the unstable higher symmetry crystallographic phases, typically thought to be unrelated to plastic flow.

Sea-level variations have influenced the demographic history of estuarine and freshwater fishes of the coastal plain of Paraná, Brazil.

This study surveyed the mitochondrial haplotype diversity of nine freshwater fish species and two estuarine-marine species from the coastal basins and drainages of the highland plateaus of Paraná, Brazil. Portions of the cytochrome b gene or the control region were sequenced. The demographic history of each species was inferred using the Bayesian skyline method, mismatch distribution analysis and statistical neutrality tests. Demographic reconstruction analyses revealed a single pattern of variation in the effective population size (Ne ) among species. No dramatic changes in Ne were detected in upland species. By contrast, evidence of population expansion over the past 200 000 years was detected in all coastal plain and estuarine species. These findings correspond to periods of low sea-level (regressions) followed by a rapid increase in the sea-level by >100 m. The resulting reconnections and subsequent fragmentation and isolation between the estuarine and freshwater bodies were putatively relevant to the historical demography of the fish species in these areas.

Inelastic rotations and pseudoturbulent plastic avalanches in crystals.

Plastic deformations in crystals produce microstructures with randomly oriented patches of unstressed lattice forming complex textures. We use a mesoscopic Landau-type tensorial model of crystal plasticity to show that in such textures rotations can originate from crystallographically exact microslips which self organize in the form of laminates of a pseudotwin type. The formation of such laminates can be viewed as an effective internal "wrinkling" of the crystal lattice. While such "wrinkling" disguises itself as an elastically neutral rotation, behind it is inherently dissipative, dislocation-mediated process. Our numerical experiments reveal pseudoturbulent effective rotations with power-law distributed spatial correlations which suggests that the process of dislocational self-organization is inherently unstable and points toward the necessity of a probabilistic description of crystal plasticity.

Molecular data reveal a diverse Astyanax species complex in the upper Iguaçu River.

Astyanax is among the most speciose genera in the Characidae. In this study, molecular markers were used to assess the extent to which some of the commonly recognized Astyanax species of the upper Iguaçu River correspond to natural groups. These results indicate that the diversity of Astyanax has been severely underestimated with several potential cryptic species.

Preparation and cytotoxicity toward cancer cells of mono(arylimino) derivatives of beta-lapachone.

A regio- and stereospecific synthesis of monoarylimino o-quinones derived from beta-lapachone (1) was achieved by treatment of the quinone with a slight excess of an arylamine in the presence of an excess of triethylamine/titanium tetrachloride 4:1. Imine formation occurred exclusively at position 6, giving the Z diastereomer, as determined by single-crystal X-ray analysis. In vitro tests for cytotoxicity in 55 human cancer cell cultures showed a substantial loss in activity for the p-nitrophenylimine (5), whereas the phenylimine (2), p-methylphenylimine (3), and p-methoxyphenylimine (4) retained (or bettered) most of the cytotoxicity and selectivity of the parent quinone. Preliminary in vivo testing in hollow fiber assays against a standard panel of 12 human tumor cell lines showed that although beta-lapachone failed, compounds 2 and 3 had good scores with net cell kills.

Bis(1,10-phenanthroline-N,N')(thiosulfato-O, S)nickel(II)-water-methanol (1/0.92/1.4) and bis(2,2'-bipyridyl-N, N')(thiosulfato-O,S)nickel(II)-water-methanol (1/2/0.55)

The title compounds, [Ni(S(2)O(3))(C(12)H(8)N(2))(2)].0.92H(2)O.1. 4CH(4)O and [Ni(S(2)O(3))(C(10)H(8)N(2))(2)].2H(2)O.0.55CH(4)O, are monomeric, containing nickel(II) in a distorted octahedral coordination environment provided by the four N atoms of two bidentate bipy or phen groups and one S and one O atom from a chelating thiosulfate anion. The crystals are highly unstable outside their mother liquors and are stabilized in solution by a not fully determined number of water and methanol solvate molecules. The phenanthroline structure includes two independent moieties related by a non-crystallographic inversion center. The thiosulfate anions display the usual S-O lengthening found when the anion acts in a bidentate mode.

Crystallographic, thermal and spectroscopic characterization of a ciprofloxacin saccharinate polymorph.

A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions.

Structure and magnetic properties of the hybrid system copper(II) mu2-2,2'-bipyridine-3-carboxylate-N,N':O-mu2-phosphate-O,O'.

The title compound [Cu(PO4H2)(C11H7N2O2)]n presents antiferromagnetic behavior. It has a polymeric one-dimensional structure in which the elemental links are tetranuclear units and the doubly protonated phosphates and the bipyridinemonocarboxylates act in a bridging mode. The magnetic behavior is described using an alternating chain model, with J = -3.32 cm (-1), alpha = 0.7, and g = 2.05.

trans-Diaqua(2,2'-biquinoline-N,N')(nitrato-O,O')nickel(II) nitrate hydrate.

The structure of the title compound, [Ni(NO(3))(C(18)H(12)N(2))(H(2)O)(2)]NO(3) x H(2)O, is composed of monomers with the nickel ion octahedrally coordinated to a bidentate biquinoline ligand, a bidentate nitrate anion and two water molecules, and is stabilized by a nitrate counter-ion and a hydrate water molecule. There is a fairly complex hydrogen-bonding scheme involving all the water H atoms and five different nitrate O atoms.

Bis(2,2':6',2"-terpyridine-kappa3N)manganese(II) tetrathionate trihydrate.

The structure of the title compound, [Mn(tpy)2](S4O6)*3H2O (tpy is 2,2':6',2"-terpyridine, C15H11N3), consists of monomeric [Mn(tpy)2]2+ units embedded in a complex anionic network made up of tetrathionate ions and hydration water molecules connected via a complex hydrogen-bonding scheme.

Comparative X-ray study of three nickel(II)-thiocyanate compounds.

Three cis nickel-dithiocyanate (SCN) complexes with different N,N'-bidentate bases have been prepared and their crystal structures determined: bis(2,2'-bipyridine-N,N')bis(-ato-N)nickel(II), [Ni(SCN)(2)(C(10)H(8)N(2))(2)], bis(1,10-phenanthroline-N,N')bis(thiocyanato-N)nickel(II), [Ni(SCN)(2)(C(12)H(8)N(2))(2)], and bis(2,9-dimethyl-1,10-phenanthroline-N,N')bis(thiocyanato-N)nickel(II) monohydrate, [Ni(SCN)(2)(C(12)H(8)N(2))(2)].H(2)O. Distortions due to ligand size are discussed.

From good substrates to good inhibitors: design of inhibitors for serine and thiol proteases.

Serine and thiol proteases react with peptide substrates to form an acyl-enzyme. We have synthesized inhibitors which are pseudo-substrates and react with the proteases to generate acyl-enzymes which hydrolize slowly. This is achieved by incorporating an electron-donating group near the carbonyl group of inhibitors I [Ac-Phe--C(O)NH--NH--C(O)X] and II [benzyl-O-C(O)-psiAla-Leu-ArgOMe]. The acyl-enzymes derived from the reaction of I with papain and II with chymotrypsin hydrolyze with t1/2 of 12 and 1 h, respectively. The increased electron density on the carbonyl group of the inhibitor also reduces the rate of acyl-enzyme formation. Components were incorporated into the inhibitor which interact with the leaving group binding site (S' subsite) and which accelerate the rate of reaction of inhibitor with enzyme. For inhibitor I, X = NH(CH3), k(on) < 0.13 M(-1) s(-1) for the reaction papain, but if X = psiLeu(CH3)2,k(on) =10(5) M(-1) s(-1). Similar results were obtained with II and chymotrypsin. Concomitant with acyl-enzyme formation, X is released and a slowly hydrolyzing acyl-enzyme remains.

Biochemical and functional profile of a newly developed potent and isozyme-selective arginase inhibitor.

An increase in arginase activity has been associated with the pathophysiology of a number of conditions, including an impairment in nonadrenergic and noncholinergic (NANC) nerve-mediated relaxation of the gastrointestinal smooth muscle. An arginase inhibitor may rectify this condition. We compared the effects of a newly designed arginase inhibitor, 2(S)-amino-6-boronohexanoic acid (ABH), with the currently available N(omega)-hydroxy-L-arginine (L-HO-Arg), on the NANC nerve-mediated internal anal sphincter (IAS) smooth-muscle relaxation and the arginase activity in the IAS and other tissues. Arginase caused an attenuation of the IAS smooth-muscle relaxations by NANC nerve stimulation that was restored by the arginase inhibitors. L-HO-Arg but not ABH caused dose-dependent and complete reversal of N(omega)-nitro-L-arginine-suppressed IAS relaxation that was similar to that seen with L-arginine. Both ABH and L-HO-Arg caused an augmentation of NANC nerve-mediated relaxation of the IAS. In the IAS, ABH was found to be approximately 250 times more potent than L-HO-Arg in inhibiting the arginase activity. L-HO-Arg was found to be 10 to 18 times more potent in inhibiting the arginase activity in the liver than in nonhepatic tissues. We conclude that arginase plays a significant role in the regulation of nitric oxide synthase-mediated NANC relaxation in the IAS. The advent of new and selective arginase inhibitors may play a significant role in the discrimination of arginase isozymes and have important pathophysiological and therapeutic implications in gastrointestinal motility disorders.

Safety and efficacy of high-purity concentrates in haemophiliac patients undergoing surgery by continuous infusion.

In this study we explore the feasibility of high-purity double-inactivated concentrates by continuous infusion for the treatment of haemophiliacs in a group of patients undergoing different surgical procedures. The patients were enrolled in the study on the basis of their transfusion history, which was well known due to their long-term follow up at our Haemophilia Center. We did not perform a pre-operative pharmacokinetic study because one of the aims of this study was to demonstrate that continuous infusion can become a first choice standard treatment in patients with haemophilia. Fourteen haemophilia A and one haemophilia B patients who needed at least 5 days of replacement therapy were monitored for haemostatic efficacy, post-operative factor VIII and factor IX levels and evaluated for safety and flexibility of the products. The infusion rate of 3 IU kg-1 h-1 was demonstrated to be sufficient to ensure haemostasis and patients did not need additional bolus infusion during the post-operative period. Our study demonstrates the safety and feasibility of high-purity concentrates in patients undergoing surgery by continuous infusion, also in the absence of a previous pharmacokinetic study.

Intra-articular rifamycin in haemophilic arthropathy.

Synoviorthesis is the intra-articular injection of chemical or radioactive substances able to produce fibrosis of hypertrophied synovium, which has proved effective in the treatment of chronic haemophilic synovitis. Between September 1999 and October 2001 we treated 28 outpatients (25 with haemophilia A, three with haemophilia B). Our treatment was focused on pain and functional limitation of joints. A schedule was adopted to treat each joint using intra-articular rifamycin once a week, repeated five times. Patients were covered with factor replacement on demand. Oral analgesia was offered as required because of acute but transient painful inflammatory reaction. Their median age was 34 years (range 15-60 years). The indication for synoviorthesis was chronic synovitis characterized by recurrent haemarthroses, persistent pain and limited range of motion (ROM). Thirty-five joints were treated with a total of 169 injections, including six joints (20%) in patients with inhibitors. In five patients two joints were treated in the same session. Thirty procedures were completed: 24 (80%) were considered effective (as excellent or good), while six were considered insufficient (20%). Pain was reduced in 96% of cases and in 70% the ROM was improved. In our experience intra-articular infiltration with rifamycin appears to be effective in reducing joint pain and in improving the ROM. The procedure presents a low risk of bleeding, can be used for patients with inhibitors and multiple joints can be treated without any additional cost.

Probing erectile function: S-(2-boronoethyl)-L-cysteine binds to arginase as a transition state analogue and enhances smooth muscle relaxation in human penile corpus cavernosum.

The boronic acid-based arginine analogue S-(2-boronoethyl)-L-cysteine (BEC) has been synthesized and assayed as a slow-binding competitive inhibitor of the binuclear manganese metalloenzyme arginase. Kinetic measurements indicate a K(I) value of 0.4-0.6 microM, which is in reasonable agreement with the dissociation constant of 2.22 microM measured by isothermal titration calorimetry. The X-ray crystal structure of the arginase-BEC complex has been determined at 2.3 A resolution from crystals perfectly twinned by hemihedry. The structure of the complex reveals that the boronic acid moiety undergoes nucleophilic attack by metal-bridging hydroxide ion to yield a tetrahedral boronate anion that bridges the binuclear manganese cluster, thereby mimicking the tetrahedral intermediate (and its flanking transition states) in the arginine hydrolysis reaction. Accordingly, the binding mode of BEC is consistent with the structure-based mechanism proposed for arginase as outlined in Cox et al. [Cox, J. D., Cama, E., Colleluori D. M., Pethe, S., Boucher, J. S., Mansuy, D., Ash, D. E., and Christianson, D. W. (2001) Biochemistry 40, 2689-2701.]. Since BEC does not inhibit nitric oxide synthase, BEC serves as a valuable reagent to probe the physiological relationship between arginase and nitric oxide (NO) synthase in regulating the NO-dependent smooth muscle relaxation in human penile corpus cavernosum tissue that is required for erection. Consequently, we demonstrate that arginase is present in human penile corpus cavernosum tissue, and that the arginase inhibitor BEC causes significant enhancement of NO-dependent smooth muscle relaxation in this tissue. Therefore, human penile arginase is a potential target for the treatment of sexual dysfunction in the male.