Acoustic metasurfaces with Frieze symmetriesa).

Frieze patterns follow a set of tiling instructions including reflection, rotation, and translation, and tile the infinite strip. Many metamaterials function due to the underlying symmetry, and its strategic breaking, of their constituent sub-structures that allow tailoring of the dispersion of modes supported by the structure. We design, simulate, and experimentally characterize seven one-dimensional acoustic metasurfaces whose unit cells each belong to one of the distinct Frieze groups.

Structure-property relationships in non-epitaxial chalcogenide heterostructures: the role of interface density on charge exchange.

A homologous series of quasi-2D ([PbSe]1+δ)m(TiSe2)m nanolayered heterostructures are prepared via self-assembly of designed precursors with 1 ≤m≤ 4 and their structures and properties investigated. All heterostructures have the same global composition but vary in their interface density. X-ray diffraction and electron microscopy studies show that the structures consist of rock salt structured PbSe layers alternating with TiSe2 layers, and that grain size increases with m. The compounds are all metallic with upturns in resistivity at low temperature suggesting electron localization, with room temperature resistivity of 1-3 10(-5)Ω m, negative Hall coefficients and Seebeck coefficients between -50 and -100 µV K(-1). A decrease in the mobile carrier concentration with temperature is observed for all m and the rate increases with increasing low-dimensionality. Decreasing the interface density also decreases the average carrier concentration while increasing the electron mobility. The Seebeck coefficients systematically increase in magnitude as m is increased, but the net effect to the power factor is small due to a compensating increase in resistivity. The observed transport behavior is not described by the simple rigid band models with charge transfer between constituents used previously. Charge exchange between constituents stabilizes the intergrowth, but also introduces mobile carriers and interfacial band bending that must play a role in the transport behavior of the heterostructures. As chemical potentials equilibrate in high m heterostructures there is a decrease in total coulombic stabilization as there are fewer interfaces, so m = 1 is likely to be most stable. This rationalizes why the structurally similar misfit layer compounds with m = 1 are often the only intergrowths that can be prepared. Charge transfer and band bending at interfaces should occur in other heterostructures with similar type II broken-gap band alignments and are important considerations regarding both their stability and transport properties.

Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) single nucleotide polymorphisms: importance in ARDS in septic pediatric critically ill patients.

Accumulating evidence indicates that genetic background influences the outcome of sepsis, which despite medical advances continues to be a major cause of morbidity and mortality. This study aimed to evaluate the influence of SNPs LTA +252A>G, TNF-863C>A and TNF-308G>A on susceptibility to sepsis, acute respiratory distress syndrome (ARDS), septic shock and sepsis mortality. A prospective case-control study was carried out in a Brazilian pediatric intensive care unit and included 490 septic pediatric patients submitted to mechanical ventilation and 610 healthy children. No SNP association was found with respect to sepsis susceptibility. Nevertheless, a haplotype was identified that was protective against sepsis (+252A/-863A/-308G; OR=0.65; p=0.03). We further observed protection against ARDS in TNF-308 GA genotype carriers (OR=0.29; p=0.0006) and -308A allele carriers (OR=0.40; p=0.003). In addition, increased risk for ARDS was detectable with the TNF-863 CA genotype (OR=1.83; p=0.01) and the -863A carrier status (OR=1.82; p=0.01). After stratification according to age, this outcome remained significantly associated with the -308GA genotype in infants. Finally, protection against sepsis-associated mortality was found for the TNF-308 GA genotype (OR=0.22; p=0.04). Overall, our findings document a protective effect of the TNF-308 GA genotype for the ARDS and sepsis mortality outcomes, further providing evidence for an increased risk of ARDS associated with the TNF-863 CA genotype. Trial registration (www.clinicaltrials.gov): NCT00792883.

Republished review: The world through a lens: the vision of Sir Harold Ridley.

Sir Harold Ridley is recognised today as the inventor of intraocular lens implantation, one the most successful and common procedures in all of surgery. His story, however, is not largely one of triumph and public accolade. This paper reviews Ridley's invention of the intraocular lens and highlights the struggles he faced after his discovery.

The world through a lens: the vision of Sir Harold Ridley.

Sir Harold Ridley is recognised today as the inventor of intraocular lens implantation, one the most successful and common procedures in all of surgery. His story, however, is not largely one of triumph and public accolade. This paper reviews Ridley's invention of the intraocular lens and highlights the struggles he faced after his discovery.

Physical activity and incidence of postmenopausal breast cancer.

Whether physical activity reduces the risk of postmenopausal breast cancer is uncertain; few studies have addressed this issue. We examined the association of leisure physical activity with breast cancer incidence among 37,105 postmenopausal participants in the Iowa Women's Health Study. Women reporting the highest level of physical activity at baseline compared with women with the lowest level of activity had an age-adjusted relative risk of breast cancer of 0.92 (95% confidence interval = 0.80-1.05). Women reporting any regular leisure-time physical activity had a relative risk of 0.97 (95% confidence interval = 0.87-1.08) compared with those reporting no such regular physical activity. Adjustment for potential confounders did not appreciably alter the findings. There is little evidence from this study that physical activity later in life is associated to any appreciable extent with breast cancer incidence.

Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network.

The release of amyloidogenic amyloid-beta peptide (Abeta) from amyloid-beta precursor protein (APP) requires cleavage by beta- and gamma-secretases. In contrast, alpha-secretase cleaves APP within the Abeta sequence and precludes amyloidogenesis. Regulated and unregulated alpha-secretase activities have been reported, and the fraction of cellular alpha-secretase activity regulated by protein kinase C (PKC) has been attributed to the ADAM (a disintegrin and metalloprotease) family members TACE and ADAM-10. Although unregulated alpha-secretase cleavage of APP has been shown to occur at the cell surface, we sought to identify the intracellular site of PKC-regulated alpha-secretase APP cleavage. To accomplish this, we measured levels of secreted ectodomains and C-terminal fragments of APP generated by alpha-secretase (sAPPalpha) (C83) versus beta-secretase (sAPPbeta) (C99) and secreted Abeta in cultured cells treated with PKC and inhibitors of TACE/ADAM-10. We found that PKC stimulation increased sAPPalpha but decreased sAPPbeta levels by altering the competition between alpha- versus beta-secretase for APP within the same organelle rather than by perturbing APP trafficking. Moreover, data implicating the trans-Golgi network (TGN) as a major site for beta-secretase activity prompted us to hypothesize that PKC-regulated alpha-secretase(s) also reside in this organelle. To test this hypothesis, we performed studies demonstrating proteolytically mature TACE intracellularly, and we also showed that regulated alpha-secretase APP cleavage occurs in the TGN using an APP mutant construct targeted specifically to the TGN. By detecting regulated alpha-secretase APP cleavage in the TGN by TACE/ADAM-10, we reveal ADAM activity in a novel location. Finally, the competition between TACE/ADAM-10 and beta-secretase for intracellular APP cleavage may represent a novel target for the discovery of new therapeutic agents to treat Alzheimer's disease.

Neonatal ethanol exposure alters bcl-2 family mRNA levels in the rat cerebellar vermis.

BACKGROUND: The objective of the present work was to determine whether ethanol-induced cerebellar cell death during development is related to alterations in the expression of bcl-2 family genes. METHODS: Rats were exposed to ethanol or control conditions during the neonatal period and transcript levels of bcl-2 family members relative to cyclophilin were determined. Pups exposed in parallel were taken for cerebellar cell counts. RESULTS: Ethanol exposure during the first postnatal week significantly reduced Purkinje and granule cell numbers by postnatal day 21 (P21). Acute first postnatal week ethanol exposure up-regulated mRNA transcripts encoding the cell death-promoting molecules bax and bcl-xs as measured on P4. An additional day of exposure on P5 resulted in no further alterations in bcl-2 family transcripts, likely because Purkinje cell death was detectable as early as P5. To determine whether proapoptotic gene expression changes were specific to first postnatal week ethanol neurotoxicity, we examined bcl-2 family mRNA levels in rats exposed to ethanol during a developmental period of cerebellar insusceptibility, the second postnatal week. Exposure on P7 to P8 produced no change in cerebellar cell number, but also resulted in increased levels of bax, although only after 2-day ethanol exposure and not after acute exposure on P7. CONCLUSIONS: These data implicate altered expression of proapoptotic members of the bcl-2 gene family in acute ethanol-mediated cerebellar cell death during the first postnatal week. They also suggest that the differential survival of cerebellar neurons after ethanol exposure during more mature developmental stages may be related to more successful suppression of proapoptotic processes.

Ventricular asystole during vagus nerve stimulation for epilepsy in humans.

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.

Neurotrophic factors BDNF and GDNF protect embryonic chick spinal cord motoneurons from ethanol neurotoxicity in vivo.

Maternal consumption of ethanol is widely recognized as a leading cause of mental and physical deficits. Many populations of the central nervous system are affected by the teratogenic effects of ethanol. Neurotrophic factors (NTFs) have been shown to protect against ethanol neurotoxicity in culture, although there have been no demonstrations of such protection in vivo, in specific neuronal populations. Previous studies have demonstrated that ethanol is toxic to developing chick embryo motoneurons when administered from embryonic day 10 (E10) to E15. NTFs such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) have been shown to support developing spinal cord motoneurons, and when exogenously applied, decrease naturally occurring cell death, and protect against axotomy. The concurrent delivery of BDNF or GDNF with ethanol to the embryonic chick from E10 to E15 was designed to examine the capacity of these NTFs to provide in vivo neuroprotection for this ethanol-sensitive motoneuron population. Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels. This study represents the first demonstration of in vivo neuroprotection from ethanol toxicity with respect to specific neuronal populations.

Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity.

The developing nervous system is extremely sensitive to ethanol, and exposure often produces a condition known as the fetal alcohol syndrome. Although mechanisms underlying developmental ethanol toxicity have long been sought, they remain poorly understood. In this study, we examined the ability of the cell death repressor gene bcl-2 to protect against ethanol neurotoxicity. Transgenic mice overexpressing bcl-2 in neurons were exposed to ethanol vapor on postnatal days 4 and 5, which is the peak period of vulnerability of cerebellar Purkinje cells to ethanol. While exposure of wild-type animals to ethanol resulted in significant loss of Purkinje cells by P5, similar exposure of homozygous and heterozygous transgenics had no effect on the number of these neurons. This study suggests that bcl-2 can protect neurons from ethanol neurotoxicity and that modulation of cell death effector or repressor gene products may play a significant role in developmental ethanol neurotoxicity.

Determination of peroxygen species present in pulp fiber matrixes.

A new chromatographic method for the determination of oxidants, such as peroxyborates and peroxides, present in a pulp matrix has been developed. The new method is characterized by its high reproducibility, its low limit of detection, and its high selectivity. Thioanisole (methylphenyl sulfide) is shown to selectively and quantitatively react with oxidants that are present within a pulp matrix. The experimental protocol proposed requires an HPLC system with a normal-phase column. The method allows for the quantitative monitoring of the thioanisole starting material, as well as the products of oxidation, methylphenyl sulfoxide and methylphenyl sulfone. After a 2-day reaction period, the analysis time for a sample is less than 20 min. The detection limit is 2.7 × 10(-6) M for the sulfoxide and sulfone and less than 5.0 × 10(-7) M for the thioanisole. This novel approach for monitoring oxidants present on solid lignocellulosic matrixes may provide pulp and paper manufacturers with a new tool for the study of the long-term bleaching effectiveness of peroxy-containing chemical additives.

Prenatal ethanol exposure reduces parvalbumin-immunoreactive GABAergic neuronal number in the adult rat cingulate cortex.

The effect of prenatal ethanol exposure on the number of parvalbumin-immunoreactive (PA+) GABAergic neurons in the adult rat anterior cingulate cortex was determined. Pregnant Long-Evans rats were maintained on one of three diets throughout gestation: an ethanol-containing liquid diet, a similar, control liquid diet with the isocaloric substitution of sucrose for ethanol, or a lab chow control diet. Offspring were euthanized on postnatal day 60 and brains were prepared for parvalbumin immunocytochemistry. Rats exposed to the ethanol-containing diet contained 45% fewer PA+ neurons in the anterior cingulate cortex compared with sucrose and chow controls. This reduction occurred in the absence of changes in structure volume, and occurred in the absence of changes in PA+ neuronal size.

A comparative study of ethanol, hypoglycemia, hypoxia and neurotrophic factor interactions with fetal rat hippocampal neurons: a multi-factor in vitro model developmental ethanol effects.

Fetal alcohol syndrome (FAS) is characterized by numerous central nervous system anomalies, with the hippocampus being particularly vulnerable to developmental ethanol exposure. In addition to direct ethanol neurotoxicity, other conditions resulting from maternal ethanol consumption, such as hypoglycemia and hypoxia, may also contribute to FAS. The present study used a tissue culture system to model multiple conditions which may relate to in vivo FAS, and assessed their relative neurotoxicity with MTT assays. Gestational day 18 rat hippocampal cultures were exposed to varying ethanol concentrations, glucose withdrawal-induced hypoglycemic (gwHG, 16 h) or acute hypoxic (aHP, 2 h) conditions alone, as well as to co-treatments with ethanol and gwHG or aHP. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have previously been shown to ameliorate ethanol-, hypoglycemia- and hypoxia-induced neurotoxicity. Therefore, their neuroprotective potential, along with ciliary neurotrophic factor (CNTF), was examined. Neuronal viability was reduced dose-dependently by ethanol, alone or with hypoglycemia or hypoxia. Ethanol + gwHG or aHP was not uniformly additive. NGF treatment provided the most extensive neuroprotection, being effective against ethanol (200 and 400 mg/dl), gwHG, and aHP, alone and combined. BDNF afforded similar protection, but not against ethanol + gwHG. CNTF protected only against aHP. CNTF + BDNF, previously shown to act synergistically, protected against ethanol + aHP up to 800 mg/dl ethanol, but not, paradoxically, against ethanol alone, gwHG, or ethanol + gwHG, all conditions BDNF alone protected against. This study demonstrated that several neurotrophic factors are capable of mitigating neurotoxicity associated with ethanol, hypoglycemia and hypoxia.

Effects of neonatal ethanol exposure on cholinergic neurons of the rat medial septum.

The objective of this study was to determine the long-term effects of neonatal ethanol exposure on the cholinergic neurons in the medial septum (MS) of the rat. On postnatal day 4 (P4) pups were assigned to one of three groups: an ethanol-receiving, gastrostomized group (EtOH); a pair-fed, gastrostomized control group (GC); and a dam-reared suckle control group (SC). Gastrostomized pups were infused with ethanol-containing or control diet as a 9.1% v/v solution for two feedings on each day from P4 to P10. Choline acetyltransferase (ChAT) immunocytochemistry was analyzed at P60. Ethanol treatment resulted in long-lasting microencephaly in P60 EtOH animals. Ethanol exposure did not directly reduce ChAT-expressing (ChAT+) neuronal number, nor were changes noted in MS volume, mean area/section, or cell density as a result of ethanol treatment. Ethanol exposure reduced ChAT+ neuronal size in EtOH males compared with GC males but not SC males. No differences in ChAT+ neuronal size were noted in females. Thus, neonatal ethanol exposure, whereas producing long-lived microencephaly, has little effect on the cholinergic neurons of the adult rat MS.