Regio- and stereoselective synthesis of carbocyclic 2'',3''-dideoxy-3''-fluoro nucleosides as potential antiviral agents

OBJECTIVE: To determine the prevalence of the symptom of urinary incontinence during athletic endeavors among a group of nulliparous, elite college varsity female athletes. METHODS: All women currently participating in varsity athletics at a large state university were asked to fill out a questionnaire about the occurrence of urinary incontinence while participating in their sport and during activities of daily life. One hundred forty-four of 156 eligible women (92%) responded. RESULTS: The mean age was 19.9 years, and all women were nulliparous. Overall, 40 athletes (28%) reported urine loss while participating in their sport. The proportions in different sports were: gymnastics 67%, basketball 66%, tennis 50%, field hockey 42%, track 29%, swimming 10%, volleyball 9%, softball 6%, and golf 0%. Two-thirds of the women who noted urine loss during athletics were incontinent more often than rarely. There were no statistically significant relations between incontinence and amenorrhea, weight, hormonal therapy, or duration of athletic activity. Activities most likely to provoke incontinence included jumping, high-impact landings, and running. Forty percent and 17% of the women first noted incontinence during their sport while in high school and junior high school, respectively. CONCLUSIONS: Incontinence during physical stresses is common in young, highly fit, nulliparous women. This suggests that there is a continence threshold which, when exceeded, can result in urine loss, even in the absence of known risk factors for incontinence.     

Photochemical identification of transmembrane segment IVS6 as the binding region of semotiadil, a new modulator for the L-type voltage-dependent Ca2+ channel

To identify the binding domain of a new Ca2+ antagonist semotiadil on L-type Ca2+ channels from skeletal muscle, photolabeling was carried out by using an azidophenyl derivative of [3H]semotiadil. Photoincorporation was observed in several polypeptides of membrane triad preparations; the only specific photoincorporation was in the alpha1 subunit of the Ca2+ channel. After solubilization and purification, the photolabeled alpha1 subunit was subjected to proteolytic and CNBr cleavage followed by antibody mapping. Specific labeling was associated solely with the region of transmembrane segment S6 in repeat IV. Quantitative immunoprecipitation was found in the tryptic and the Lys-C/Glu-C fragments of 6.6 and 6.1 kDa, respectively. Further CNBr cleavage of the Lys-C digests produced two smaller fragments of 3.4 and 1.8 kDa that were included in the tryptic and Lys-C/Glu-C fragments. The smallest labeled fragments were: Tyr1350-Met1366 and Leu1367-Met1381 containing IVS6, a possible pore-forming region. The data suggest that semotiadil binds to a region that is overlapped with but not identical to those for phenylalkylamines, dihydropyridines and benzothiazepines. The present study also provides evidence that region IV represents an important component of a binding pocket for Ca2+ antagonists.     

Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase

In mice homozygous for the 'viable motheaten' (mev) mutation, numbers of macrophage progenitor cells, particularly monocytes, were markedly increased in the bone marrow and spleen. Increased mobilization of these precursor cells to peripheral tissues and their differentiation to macrophages were evidenced by striking increases in macrophage numbers. Immunohistochemical double staining of tissue sections and flow cytometry analyses of single cell suspensions from these mice demonstrated CD5 (Ly-1)-positive macrophages in the peritoneal cavity, spleen and other tissues. Ly-1-positive macrophage precursor cells were demonstrated in the peritoneal cavity of the mev mice and developed in the omental milky spots. The development of marginal metallophilic and marginal zone macrophages was poor in the splenic white pulp and related macrophage populations were absent in the other lymphoid tissues. The numbers of epidermal Langerhans cells in the skin and T cell-associated dendritic cells in the thymic medulla, lymph nodes, and the other peripheral lymphoid tissues were decreased. However, increased numbers of dendritic cells accumulated in the lungs, liver, and kidneys. These abnormalities in development and differentiation of macrophages and dendritic cells may be ascribed to the deficiency in haematopoietic cell SHP-1 tyrosine phosphatase or may be a secondary consequence of abnormal microenvironments, (either constitutive or in response to inflammatory stimuli) in the haematopoietic and lymphopoietic organs and tissues of these mice.     

Glibenclamide-sensitive mechanism is involved in helodermin-produced vasodilatation in rat mesenteric artery

Helodermin-caused vascular relaxation was simultaneously measured with intracellular Ca2+ concentration ([Ca2+]i) in rat mesenteric artery. Helodermin caused concentration-dependent relaxation in the mesenteric artery preconstricted with norepinephrine (NE). Helodermin-caused relaxation was accompanied by decrease in [Ca2+]i, D-cis-Diltiazem, a Ca2+ channel blocker, also lowered the [Ca2+]i and tension increased by NE. However, helodermin relaxed the artery more efficiently than D-cis-diltiazem, suggesting that the peptide decreased myofilament Ca2+ sensitivity. The vascular relaxation and the corresponding decrease in [Ca2+]i induced by helodermin were partly, but significantly attenuated by glibenclamide. Helodermin-induced vascular responses were mimicked by vasoactive intestinal polypeptide (VIP) or forskolin. Furthermore, helodermin increased cAMP contents in the mesenteric artery. These findings show that vasodilatation induced by helodermin is attributable to lowered [Ca2+]i of arterial smooth muscle partly through the activation of glibenclamide-sensitive K+ channels, and to decrease in the myofilament Ca2+ sensitivity. The increase in the cellular cAMP content probably plays a key role in the peptide-induced vasorelaxation.     

Hot drawing of partially miscible blends of polycarbonate and poly(butylene terephthalate)

Samples of PC-PBT blends over the entire composition range were drawn at 160°C to high extensions, 2.1–5.8, to study the mechanical reinforcement and the molecular structure development upon deformation. Elastic modulus E' increases with extension ratio for all compositions and temperatures. Blends with 25 and 40 wt% of PC show higher E' at low temperature than pure PBT blends do. Crystallinity increases with extension ratio and is relatively smaller with increasing PC content. The influence of the reversible α to β crystal form transformation was also studied. The second moment of the orientation function f for both crystal forms increases to high values > 0.9 at relatively low extensions. f decreases with PC content for α crystals but decreases for β crystals. The α fraction is high for PBT and decreases with PC content and extension ratio in the blends. Strain recovery experiments show that the α to β transformation is also elastic in nature at high extension ratios and that the reinforcing effect in high PBT content blends is not due to the α/β ratio. © 1996 John Wiley & Sons, Inc.     

Monte Carlo simulation of stress corrosion cracking on a smooth surface of sensitized stainless steel type 304

Stress corrosion cracking (SCC) on a smooth surface of structural metal materials occurs by initiation and coalescence of micro cracks, subcritical crack propagation and multiple large crack formation or final failure under combination of material, stress and corrosive environment. In this paper, a Monte Carlo simulation of the SCC process is proposed based on stochastic properties for micro crack initiation and concepts in fracture mechanics for crack coalescence and propagation. The procedure is as follows: The possible number of grain-sized micro cracks which can be initiated is set for a given space and initiation times for all cracks are assigned by random numbers based on exponential distribution. Sites and sizes of cracks are assigned by uniform random numbers and normal random numbers, respectively. Coalescence and propagation of cracks are determined based on fracture mechanics. The emphasis in the model is put on the influence of semi-elliptical surface cracks. Numerical simulations are carried out based on the results of creviced-bent-beam tests for sensitized stainless steel type 304 under high-temperature and high-purity water containing dissolved oxygen and the influence of micro crack initiation rate and coalescence condition on the simulation results is discussed.     

Performance evaluation of ozonation and an ozone/hydrogen peroxide process toward development of a new sewage treatment process—Focusing on organic compounds and emerging contaminants

Performance of ozonation and an ozone/hydrogen peroxide process under a new concept centering on ozonation and/or ozone/hydrogen peroxide processes in sewage treatment processes comprising only physical and chemical processes are discussed, with focus on the removal of matrix organic compounds and emerging contaminants. Matrix organic compounds of filtrated primary sewage effluents were removed to as low as 3.2 mgC/L in the ozone/hydrogen peroxide process at an ozone consumption of around 400 mg/L. Linear relationships between ozone consumption and removal amounts of organic compounds were observed, in which the amounts of ozone required to remove 1 mg of organic carbon were 9.5 and 8.3 mg (2.4 and 2.1 mol-O₃/mol-C) in ozonation and the ozone/hydrogen peroxide process, respectively. Ratios of hydroxyl radical exposure to ozone exposure were in the order of 10^–9 to 10^–8 for ozonation and 10^–7 to 10^–6 for the ozone/hydrogen peroxide process. Experiments and a kinetic evaluation showed that ozonation and/or the ozone/hydrogen peroxide process have high elimination capability for emerging contaminants, even in primary sewage effluent with the thorough removal of matrix organic compounds. Newly found reaction phenomena, the temporal increase and decrease of dissolved ozone and accumulation of hydrogen peroxide in the early stage of oxidation with the continuous feeding of hydrogen peroxide, were presented. Possible reaction mechanisms are also discussed.     

Thermally assisted recording of holographic gratings in semicrystalline azobenzene-containing polymers

We examine optically induced birefringence in semicrystalline azopolymer films that are held at glass-transition temperature Tg. The birefringence increases markedly after interception of the pump beam; the saturation value depends on exposure time. In addition, the induced birefringence is completely erased by irradiation with a circularly polarized beam at Tg. Using this thermally assisted method, we demonstrate the holographic recording of a test image. The intensity of the diffracted beam also increases after interception of the writing beams. Furthermore, the retrieved image is found to have a resolution of approximately 30 lp/mm. This resolution is comparable with that of the optical setup that is used. Accordingly, the thermally assisted recording by use of semicrystalline azopolymers is a promising method for reversible holographic storage.