Nanohedra: Using symmetry to design self assembling protein cages, layers, crystals, and filaments

A general strategy is described for designing proteins that self assemble into large symmetrical nanomaterials, including molecular cages, filaments, layers, and porous materials. In this strategy, one molecule of protein A, which naturally forms a self-assembling oligomer, An, is fused rigidly to one molecule of protein B, which forms another self-assembling oligomer, Bm. The result is a fusion protein, A-B, which self assembles with other identical copies of itself into a designed nanohedral particle or material, (A-B)p. The strategy is demonstrated through the design, production, and characterization of two fusion proteins: a 49-kDa protein designed to assemble into a cage approximately 15 nm across, and a 44-kDa protein designed to assemble into long filaments approximately 4 nm wide. The strategy opens a way to create a wide variety of potentially useful protein-based materials, some of which share similar features with natural biological assemblies.

The impact of interindividual variation in NAT2 activity on benzidine urinary metabolites and urothelial DNA adducts in exposed workers.

Several epidemiologic studies indicate that NAT2-related slow N-acetylation increases bladder cancer risk among workers exposed to aromatic amines, presumably because N-acetylation is important for the detoxification of these compounds. Previously, we showed that NAT2 polymorphisms did not influence bladder cancer risk among Chinese workers exposed exclusively to benzidine (BZ), suggesting that NAT2 N-acetylation is not a critical detoxifying pathway for this aromatic amine. To evaluate the biologic plausibility of this finding, we carried out a cross-sectional study of 33 workers exposed to BZ and 15 unexposed controls in Ahmedabad, India, to evaluate the presence of BZ-related DNA adducts in exfoliated urothelial cells, the excretion pattern of BZ metabolites, and the impact of NAT2 activity on these outcomes. Four DNA adducts were significantly elevated in exposed workers compared to controls; of these, the predominant adduct cochromatographed with a synthetic N-(3'- phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine standard and was the only adduct that was significantly associated with total BZ urinary metabolites (r = 0.68, P < 0.0001). To our knowledge this is the first report to show that BZ forms DNA adducts in exfoliated urothelial cells of exposed humans and that the predominant adduct formed is N-acetylated, supporting the concept that monofunctional acetylation is an activation, rather than a detoxification, step for BZ. However, because almost all BZ-related metabolites measured in the urine of exposed workers were acetylated among slow, as well as rapid, acetylators (mean +/- SD 95 +/- 1.9% vs. 97 +/- 1.6%, respectively) and NAT2 activity did not affect the levels of any DNA adduct measured, it is unlikely that interindividual variation in NAT2 function is relevant for BZ-associated bladder carcinogenesis.

Nitrate reduction at Pt(1 0 0) single crystals and preferentially oriented nanoparticles in neutral media

The electroreduction of nitrate on Pt(1 0 0) electrodes in phosphate buffer neutral solution, pH 7.2, is reported. The sensitivity of the reaction to the crystallographic order of the surface is studied through the controlled introduction of defects by using stepped surfaces with (1 0 0) terraces of different length separated by monoatomic steps, either with (1 1 1) or (1 1 0) symmetry. The results of this study show that nitrate reduction occurs mainly on the well defined (1 0 0) terraces in the potential region where H adsorption starts to decrease, allowing the nitrate anion to access the surface. Adsorbed NO has been detected as a stable intermediate in this media. An oxidation process observed at 0.8 V has been identified as leading to the formation of adsorbed NO and being responsible for a secondary reduction process observed in the subsequent negative scan. Using in situ FTIRS, ammonium was found to be the main product of nitrate reduction. This species can be oxidized at high potentials resulting in adsorbed NO and nitrate (probably with nitrite as intermediate).

The pressure effect in selenium crystals and its relation to the light effect,

Thesis (Ph. D.)--University of Iowa, 1916.

Oxidation of magnesium single crystals and evaporated films.

"Contract no. Nonr-401 (31) Project No. NR036-035. Cornell University, Department of Engineering Physics."

Boylston medical prize dissertations for the years 1819 and 1821. Experiments and observations on the communication between the stomach and the urinary organs, and on the propriety of administering medicine by injection into the veins.

Dissertation I. On the question, Is there any communication from the stomach to the bladder, more direct than that through the circulating system and the kidneys? Which obtained the Boylston premium in 1819.--Dissertation II. On the question, Can medicinal substances be safely and advantageously introduced into animal bodies through the medium of the veins? Which obtained the Boylston premium in 1821.

Pubovaginal sling versus transurethral Macroplastique for stress urinary incontinence and intrinsic sphincter deficiency: a prospective randomised controlled trial

Objective To compare the pubovaginal sling and transurethral Macroplastique in the treatment of female stress urinary incontinence (SUI) and intrinsic sphincter deficiency (ISD). Design A prospective randomised controlled trial comparing two surgical treatments for SUI and ISD. Setting Tertiary referral urogynaecology unit in Australia. Population Women with SUI and ISD who were suitable for either surgical technique. Methods Forty-five women with SUI and ISD were randomly allocated the pubovaginal sling (n = 22) or transurethral Macroplastique (n = 23). Subjective and objective success rates, patient satisfaction and cost measurements at six months and one year following surgery were the primary outcome measures. A telephone questionnaire survey was performed at a mean follow up period of 62 months (43-71). Main outcome measure Comparison of success rates, complications and costs. Results The symptomatic and patient satisfaction success rates were similar following the sling and Macroplastique with the objective success rate being significantly greater (P < 0.001) following the sling (81% vs 9%). Macroplastique had significantly lower morbidity but was more expensive than the sling (P < 0.001). Response rate at 62 months follow up was 60% in both groups with the sling group reporting better continence success (69% vs 21%) and satisfaction rates (69% vs 29%, P = 0.057). Conclusions The pubovaginal sling was more effective and economical than transurethral Macroplastique for the treatment of SUI and ISD. However, transurethral Macroplastique remains an appropriate treatment in selected cases of SUI and ISD.

Study of the relation between the shape of lacosamide crystals and the composition of crystallization medium

Crystallization is the critical process used by pharmaceutical industries to achieve the desired size, size distribution, shape and polymorphism of a product material. Control of these properties presents a major challenge since they influence considerably downstream processing factors. Experimental work aimed at finding ways to control the crystal shape of Lacosamide, an active pharmaceutical ingredient developed by UCB Pharma, during crystallization was carried out. It was found that the crystal lattice displayed a very strong unidirectional double hydrogen bonding, which was at the origin of the needle shape of the Lacosamide crystals. Two main strategies were followed to hinder the hydrogen bonding and compete with the addition of a Lacosamide molecule along the crystal length axis: changing the crystallization medium or weakening the hydrogen bonding. Various solvents were tested to check whether the solvent used to crystallize Lacosamide had an influence on the final crystal shape. Solvent molecules seemed to slow down the growth in the length axis by hindering the unidirectional hydrogen bonding of Lacosamide crystals, but not enough to promote the crystal growth in the width axis. Additives were also tested. Certain additives have shown to compete in a more efficient way than solvent molecules with the hydrogen bonding of Lacosamide. The additive effect has also shown to be compatible with the solvent effect. In parallel, hydrogen atoms in Lacosamide were changed into deuterium atoms in order to weaken the hydrogen bonds strength. Weakening the hydrogen bonds of Lacosamide allowed to let the crystal grow in the width axis. Deuteration was found to be combinable with solvent effect while being in competition with the additive effect. The Lacosamide molecule was eventually deemed an absolute needle by the terms of Lovette and Doherty. The results of this dissertation are aimed at contributing to this classification.

Diketonylpyridinium cations as a support of new ionic liquid crystals and ion-conductive materials: analysis of counter-ion effects

Ionic liquid crystals (ILCs) allow the combination of the high ionic conductivity of ionic liquids (ILs) with the supramolecular organization of liquid crystals (LCs). ILCs salts were obtained by the assembly of long-chained diketonylpyridinium cations of the type [HOO^(R(n)pyH)] + and BF_(4)^(-) , ReO_(4)^(-), NO_(3)^(-), CF_(3)SO_(3)^(-), CuCl_(4)^(2-) counter-ions. We have studied the thermal behavior of five series of compounds by differential scanning calorimetry (DSC) and hot stage polarized light optical microscopy (POM). All materials show thermotropic mesomorphism as well as crystalline polymorphism. X-ray diffraction of the [HOO^(R(12)pyH)][ReO_(4)] crystal reveals a layered structure with alternating polar and apolar sublayers. The mesophases also exhibit a lamellar arrangement detected by variable temperature powder X-ray diffraction. The CuCl_(4)^(2-) salts exhibit the best LC properties followed by the ReO_(4)^(-) ones due to low melting temperature and wide range of existence. The conductivity was probed for the mesophases in one species each from the ReO_(4)^(-) , and CuCl_(4)^(2-) families, and for the solid phase in one of the non-mesomorphic Cl^(-) salts. The highest ionic conductivity was found for the smectic mesophase of the ReO_(4)^(-) containing salt, whereas the solid phases of all salts were dominated by electronic contributions. The ionic conductivity may be favored by the mesophase lamellar structure.

Temporal solitonic crystals and non-Hermitian informational lattices

Clusters of temporal optical solitons—stable self-localized light pulses preserving their form during propagation—exhibit properties characteristic of that encountered in crystals. Here, we introduce the concept of temporal solitonic information crystals formed by the lattices of optical pulses with variable phases. The proposed general idea offers new approaches to optical coherent transmission technology and can be generalized to dispersion-managed and dissipative solitons as well as scaled to a variety of physical platforms from fiber optics to silicon chips. We discuss the key properties of such dynamic temporal crystals that mathematically correspond to non-Hermitian lattices and examine the types of collective mode instabilities determining the lifetime of the soliton train. This transfer of techniques and concepts from solid state physics to information theory promises a new outlook on information storage and transmission.

Differences in pelvic floor morphology between continent, stress urinary incontinent, and mixed urinary incontinent elderly women : an MRI study

Aims To compare magnetic resonance imaging (MRI) of the pelvic floor musculature (PFM), bladder neck and urethral sphincter morphology under three conditions (rest, PFM maximal voluntary contraction (MVC), and straining) in older women with symptoms of stress (SUI) or mixed urinary incontinence (MUI) or without incontinence. Methods This 2008–2012 exploratory observational cohort study was conducted with community-dwelling women aged 60 and over. Sixty six women (22 per group), mean age of 67.7 ± 5.2 years, participated in the study. A 3 T MRI examination was conducted under three conditions: rest, PFM MVC, and straining. ANOVA or Kruskal–Wallis tests (data not normally distributed) were conducted, with Bonferroni correction, to compare anatomical measurements between groups. Results Women with MUI symptoms had a lower PFM resting position (M-Line P = 0.010 and PC/H-line angle P = 0.026) and lower pelvic organ support (urethrovesical junction height P = 0.013) than both continent and SUI women. Women with SUI symptoms were more likely to exhibit bladder neck funneling and a larger posterior urethrovesical angle at rest than both continent and MUI women (P = 0.026 and P = 0.008, respectively). There were no significant differences between groups on PFM MVC or straining. Conclusions Women with SUI and MUI symptoms present different morphological defects at rest. These observations emphasize the need to tailor UI interventions to specific pelvic floor defects and UI type in older women.

Conservative management for female urinary incontinence and pelvic organ prolapse review 2013 : summary of the 5th International Consultation on Incontinence

Aims The objective of the 5th International Consultation on Incontinence (ICI) chapter on Adult Conservative Management was to review and summarize the new evidence on conservative management of urinary incontinence (UI) and pelvic organ prolapse (POP) in order to compile a current reference source for clinicians, health researchers, and service planners. In this paper, we present the review highlights and new evidence on female conservative management. Methods Revision and updates of the 4th ICI Report using systematic review covering years 2008–2012. Results Each section begins with a brief definition and description of the intervention followed by a summary, where possible, of both the state and level of evidence for prevention and treatment, and ends with a “grade of recommendation.” The paper concludes with areas identified as requiring further research. Conclusions For UI, there are no prevention trials on lifestyle interventions. There are, however, few new intervention trials of lifestyle interventions involving weight loss and fluid intake with improved levels of evidence and grade of recommendation. Outside of pre- and post-natal pelvic floor muscle training (PFMT) trials for the prevention of female UI, there is a dearth of PFMT prevention trials for women with UI. PFMT remains the first-line treatment for female UI with high levels of evidence and grades of recommendation. Bladder training levels of evidence and grades of recommendation are maintained. For POP, new evidence supports the effectiveness of physiotherapy in the treatment of POP and there are now improved levels of evidence and grades of recommendation.

Differences in pelvic floor morphology between continent, stress urinary incontinent, and mixed urinary incontinent elderly women : an MRI study

Aims To compare magnetic resonance imaging (MRI) of the pelvic floor musculature (PFM), bladder neck and urethral sphincter morphology under three conditions (rest, PFM maximal voluntary contraction (MVC), and straining) in older women with symptoms of stress (SUI) or mixed urinary incontinence (MUI) or without incontinence. Methods This 2008–2012 exploratory observational cohort study was conducted with community-dwelling women aged 60 and over. Sixty six women (22 per group), mean age of 67.7 ± 5.2 years, participated in the study. A 3 T MRI examination was conducted under three conditions: rest, PFM MVC, and straining. ANOVA or Kruskal–Wallis tests (data not normally distributed) were conducted, with Bonferroni correction, to compare anatomical measurements between groups. Results Women with MUI symptoms had a lower PFM resting position (M-Line P = 0.010 and PC/H-line angle P = 0.026) and lower pelvic organ support (urethrovesical junction height P = 0.013) than both continent and SUI women. Women with SUI symptoms were more likely to exhibit bladder neck funneling and a larger posterior urethrovesical angle at rest than both continent and MUI women (P = 0.026 and P = 0.008, respectively). There were no significant differences between groups on PFM MVC or straining. Conclusions Women with SUI and MUI symptoms present different morphological defects at rest. These observations emphasize the need to tailor UI interventions to specific pelvic floor defects and UI type in older women.