Why do nanowires grow with their c-axis vertically-aligned in the absence of epitaxy?

Images of uniform and upright nanowires are fascinating, but often, they are quite puzzling, when the substrate is clearly not an epitaxial template. Here, we reveal the physics underlying one such hidden growth guidance mechanism through a specific example - the case of ZnO nanowires grown on silicon oxide. We show how electric fields exerted by the insulating substrate may be manipulated through the surface charge to define the orientation and polarity of the nanowires. Surface charge is ubiquitous on the surfaces of semiconductors and insulators, and as a result, substrate electric fields need always be considered. Our results suggest a new concept, according to which the growth of wurtzite semiconductors may often be described as a process of electric-charge-induced self-assembly, wherein the internal built-in field in the polar material tends to align in parallel to an external field exerted by the substrate to minimize the interfacial energy of the system.

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease.

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure. AIMS: To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP). METHODS: We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling. RESULTS: One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 µg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = -0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model. CONCLUSIONS: Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.

Behavioral rehabilitation of the eye closure reflex in senescent rats using a real-time biosignal acquisition system.

In this paper the replacement of a lost learning function of rats through a computer-based real-time recording and feedback system is shown. In an experiment two recording electrodes and one stimulation electrode were implanted in an anesthetized rat. During a classical-conditioning paradigm, which includes tone and airpuff stimulation, biosignals were recorded and the stimulation events detected. A computational model of the cerebellum acquired the association between the stimuli and gave feedback to the brain of the rat using deep brain stimulation in order to close the eyelid of the rat. The study shows that replacement of a lost brain function using a direct bidirectional interface to the brain is realizable and can inspire future research for brain rehabilitation.

Optical and electrical interfacing technologies for living cell bio-chips.

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by micro-system-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the micro-electronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

On-chip detection of cellular activity.

The use of on-chip cellular activity monitoring for biological/chemical sensing is promising for environmental, medical and pharmaceutical applications. The miniaturization revolution in microelectronics is harnessed to provide on-chip detection of cellular activity, opening new horizons for miniature, fast, low cost and portable screening and monitoring devices. In this chapter we survey different on-chip cellular activity detection technologies based on electrochemical, bio-impedance and optical detection. Both prokaryotic and eukaryotic cell-on-chip technologies are mentioned and reviewed.

Smoking attenuates the negative association between carotenoids consumption and colorectal cancer risk.

OBJECTIVES: Consumption of vegetables and fruits, physical activity, obesity and caloric intake are all strongly related to the risk of colorectal cancer (CRC). The association between dietary intake of carotenoids from vegetables/fruits and risk of CRC in the context of cigarette smoking was studied in a nutritionally diverse population. METHODS: The study included 1,817 age sex residence-matched case-control pairs from a population-based study in Northern Israel. Data were acquired by food-frequency questionnaire. Individual intake of carotenoid isomers was calculated using an Israeli food content database. Odds ratios (ORs) were calculated using conditional logistic regression models adjusted for known risk factors. RESULTS: Strong inverse associations were found with consumption of 9-cis-beta-carotene (OR = 0.35, 0.26-0.47), all-trans-beta-carotene (OR = 0.58, 0.44-0.76), cis-beta-cryptoxanthin (OR = 0.67, 0.50-0.90), all-trans-zeaxanthin (OR = 0.64, 0.48-0.86), and lutein (OR = 0.74, 0.57-0.96). Lycopene (OR = 2.22, 1.71-2.89) and all-trans-beta-cryptoxanthin (OR = 2.01, 1.48-2.73) were associated with increased risk of CRC. Inverse associations of most carotenoids with CRC, demonstrated in non-smokers, were much attenuated or reversed in past or current smokers with a highly significant interaction term. CONCLUSIONS: Consumption of most dietary carotenoids was found to be strongly associated with reduced risk of CRC. However, smoking significantly attenuated or reversed this observed protective effect on CRC occurrence. Smokers should be advised that smoking also hampers the potential health promoting effects of high fruit and vegetable consumption.

Improved quality of life with hyperbaric oxygen therapy in patients with persistent pelvic radiation-induced toxicity.

AIMS: We report the results of hyperbaric oxygen therapy (HBOT) used in the treatment of radiation-induced persistent side-effects after the irradiation of pelvic tumours. MATERIALS AND METHODS: Between January 2001 and December 2005, 13 women (median age 60.3 years) with radiation combined proctitis/cystitis (n=6), longstanding vaginal ulcers and fistulas (n=5) and longstanding skin injuries (n=2) underwent HBOT in a multiplace chamber for a median of 27 sessions (range 16-40). The treatment schedule was HBOT 100% oxygen, at 2 absolute atmospheres, for 90 min, once a day. For radiation-induced toxicity grading we used the National Cancer Institute Common Toxicity Criteria (CTC) grading system, before and after HBOT. RESULTS: Thirteen patients underwent an adequate number of HBOT sessions. The mean CTC grading score before HBOT was 3.3+/-0.75, whereas the mean CTC grading score after HBOT was 0.3+/-0.63. The scores showed a significant improvement after HBOT (P=0.001; exact Wilcoxon signed-rank test). Rectal bleeding ceased in five of six patients with proctitis and dysuria resolved in six of seven cystitis patients. Macroscopic haematuria stopped in seven of seven patients. Scar complications resolved in two of two patients. None reported HBOT-associated side-effects. CONCLUSION: HBOT is apparently safe and effective in managing radiation-induced late side-effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas.

Anthropometry of fetal vasculature in the chorionic plate.

Normal fetal development is dependent on adequate placental blood perfusion. The functional role of the placenta takes place mainly in the capillary system; however, ultrasound imaging of fetal blood flow is commonly performed on the umbilical artery, or on its first branches over the chorionic plate. The objective of this study was to evaluate the structural organization of the feto-placental vasculature of the chorionic plate. Casting of the placental vasculature was performed on 15 full-term placentas using a dental polymer mixed with colored ink. Observations of the cast models revealed that the branching architecture of the chorionic vessel is a combination of dichotomous and monopodial patterns, where the first two to three generations are always of a dichotomous nature. Analysis of the daughter-to-mother diameter ratios in the chorionic vessels provided a maximum in the range of 0.6-0.8 for the dichotomous branches, whereas in monopodial branches it was in the range of 0.1-0.3. Similar to previous studies, this study reveals that the vasculature architecture is mostly monopodial for the marginal cord insertion and mostly dichotomous for the central insertion. The more marginal the umbilical cord insertion is on the chorionic plate, the more monopodial branching patterns are created to compensate the dichotomous pattern deficiency to perfuse peripheral placental territories.

Noise squeezing in a nanomechanical Duffing resonator.

We study mechanical amplification and noise squeezing in a nonlinear nanomechanical resonator driven by an intense pump near its dynamical bifurcation point, namely, the onset of Duffing bistability. Phase sensitive amplification is achieved by a homodyne detection scheme, where the displacement detector's output, which has a correlated spectrum around the pump frequency, is down-converted by mixing with a local oscillator operating at the pump frequency with an adjustable phase. The down-converted signal at the mixer's output could be either amplified or deamplified, yielding noise squeezing, depending on the local oscillator phase.

Feto-feto-fetal transfusion syndrome in monozygotic monochorionic triamniotic triplets: vascular evaluation by a cast model.

A unique cast model of the placenta in a rare case of feto-feto-fetal triplet transfusion syndrome (FFFTTS) allowed the demonstration of why the transfusion syndrome developed in one fetus and not in the other two in that single placenta. The vasculature anatomy of a monochorionic triamniotic triplet placenta with FFFTTS of three healthy infants (one donor, two recipients) born in the 35th week of gestation was cast by means of dental casting materials. After the cast hardened, the tissue was corroded, revealing the cast blood vessels. The diameters and lengths of the chorionic blood and intraplacental vessels of the cast placenta were measured with a digital caliper. The cast revealed two artery-artery (A-A) anastomoses on the chorionic plate between the two recipients and the donor. Seven artery-vein (A-V) deep anastomoses connected only the arteries of the donor and the veins of the two recipients. The blood vessel connections among the fetuses allowed the evaluation of a pathologic case with its own control in a single placenta. From the vascular appearance, we speculate that the A-A anastomoses between the two fetuses protected them from developing blood transfusions, but that the A-V anastomoses contributed to their development.

Crystal structure of a deletion mutant of human thymidylate synthase Delta (7-29) and its ternary complex with Tomudex and dUMP.

The crystal structures of a deletion mutant of human thymidylate synthase (TS) and its ternary complex with dUMP and Tomudex have been determined at 2.0 A and 2.5 A resolution, respectively. The mutant TS, which lacks 23 residues near the amino terminus, is as active as the wild-type enzyme. The ternary complex is observed in the open conformation, similar to that of the free enzyme and to that of the ternary complex of rat TS with the same ligands. This is in contrast to Escherichia coli TS, where the ternary complex with Tomudex and dUMP is observed in the closed conformation. While the ligands interact with each other in identical fashion regardless of the enzyme conformation, they are displaced by about 1.0 A away from the catalytic cysteine in the open conformation. As a result, the covalent bond between the catalytic cysteine sulfhydryl and the base of dUMP, which is the first step in the reaction mechanism of TS and is observed in all ternary complexes of the E. coli enzyme, is not formed. This displacement results from differences in the interactions between Tomudex and the protein that are caused by differences in the environment of the glutamyl tail of the Tomudex molecule. Despite the absence of the closed conformation, Tomudex inhibits human TS ten-fold more strongly than E. coli TS. These results suggest that formation of a covalent bond between the catalytic cysteine and the substrate dUMP is not required for effective inhibition of human TS by cofactor analogs and could have implications for drug design by eliminating this as a condition for lead compounds.

Proband family uptake of familial-genetic counselling.

Familial-genetic counselling for breast/ovarian cancers is a process initiated by a proband, and designed for all her/his blood relatives. This study focused on family members' uptake of an invitation to participate in counselling as a function of proband and family determinants. Of 163 breast/ovarian syndrome families tested, 67 carrying one of the three known Jewish mutations were included. For both the proband and family members, demographic variables, cancer status, position in the family and type of referral (proband only) were examined. Eligible family members' uptake rate was 34%. Lower family uptake was associated with the proband having cancer, and/or being doctor-referred (vs self-referred). Individuals of either the proband's or older generations had lower uptake rates compared with family members of younger generations. Being a cancer patient or a first degree relative of either a cancer patient or the proband was related to higher uptake. The study results indicate that baseline information routinely gathered by counselling services can be useful in predicting uptake. Providing insight into complex barriers to genetic counselling, these results also suggest potential directions for interventions to improve uptake, thereby enhancing individuals' abilities to make informed decisions regarding issues such as genetic testing.

Prevalence of anti-hepatitis A antibodies, hepatitis B viral markers, and anti-hepatitis C antibodies among immigrants from the former USSR who arrived in Israel during 1990-1991.

The goal of this study was to assess the susceptibility of the sub-population of over 500,000 immigrants from the former USSR who came to Israel during 1989-94 to HAV infection, and to provide military physicians with estimates of the prevalence of HBV and HCV carriage in this sub-population. 987 males aged 17-49 and 195 females aged 17-19, reporting to military recruitment offices between December 1991 and March 1992 were tested. Anti-HAV, anti-HBV antibodies and hepatitis B surface antigen (HBsAg) were detected by using standard enzyme immunoassay (EIA) tests, and anti-HCV antibodies by a second-generation EIA and confirmed by a third-generation INNO-LIA test. It was found that in the 17-19-year age-group the prevalence of anti-HAV antibodies was 37%, anti-HBV was 12.8%, HBsAg was 3.0% and anti-HCV 1.3%. All markers were higher among males. The prevalence of anti-HAV and anti-HBs antibodies increased with age among males. That of HBsAg and anti-HCV antibodies increased with age overall. In the multiple logistic regression analysis, HAV and HBV seropositivity were significantly associated with the mother's education and republic of origin. It was concluded that the prevalence of anti-HAV antibodies is similar to that among the local population, which should not be considered at a higher risk of infection during military service. On the other hand, the higher prevalence of HBsAg and anti-HCV antibodies in this sub-population should heighten the awareness of the possibility of chronic liver pathology.

Immune status against diphtheria among immigrants from the former USSR who arrived in Israel during 1990-1991.

Large outbreaks of diphtheria occurred recently in the former USSR. Between 1989 and 1994, a total of about 600,000 Soviet immigrants arrived in Israel. The immune status against diphtheria in a sample of 992 men aged 17-49 and 195 women aged 17-19, who arrived in Israel during 1990-91, was studied in order to evaluate the need for vaccination. Participants completed a self-administered questionnaire and diphtheria antitoxin antibody levels were measured by means of ELISA. At age 17-19, the prevalence of antitoxin antibody levels below the protective level of 0.01 IU/ml was 4.8% in the men and 2.1% in the women. Among the men, the percentage lacking protection declined from 4.8% at age 17-19 years to 1.6% at age 20-24, and increased to 18.2% at age 35-49. In the oldest group, the prevalence of those lacking protection was considerably higher than for the general Israeli population. In the multivariate analysis, age, mother's education and republic of origin were significantly associated with the absence of protection. Immigrants from the former USSR appear to be more susceptible to diphtheria, thus increasing the possibility of clinical disease, and it is recommended that they receive booster doses of diphtheria toxoid.

The risk of postoperative haemorrhage in tonsillectomy as an outpatient procedure in children.

The safety of performing tonsillectomy as an outpatient procedure is still questionable. This study determined whether there was an increased risk of postoperative bleeding by performing tonsillectomy as an outpatient procedure. A six years' retrospective chart review was made of 363 children who underwent tonsillectomy. Out of 363 children, 43 had been selected as an inpatient group before the operation, 264 patients were discharged home 6 h after the operation and were the outpatient group, and 56 children had to be kept overnight because of complications that had occurred. We compared the haemorrhage rate in the outpatient and the inpatient groups. We found no increase in the postoperative haemorrhage rate in the outpatient group. No statistically significant correlations were found between the children's ages, indication for surgery, type of operation or intra-operative complications and the risk of postoperative haemorrhage. Only children who had haemorrhage in the recovery room were identified as a high risk subgroup for recurrent bleeding. On the basis of our findings we believe that tonsillectomy can be performed as an outpatient procedure regardless of age, indication for surgery, or type of procedure, as long as good recovery room supervision exists for 4 to 6 h.

Molecular packing of cord factor and its interaction with phosphatidylinositol in mixed monolayers.

Cord factor (trehalose 6,6'-dimycolate, CF) is a glycolipid located in the outer mycobacterial cell wall that is implicated in the pathogenesis of mycobacteria. Furthermore, CF is a convenient model for studying mycolic acid residues, the major lipid constituents of the mycobacterial cell wall that are believed to form a barrier against drug penetration. The surface properties of CF and its interactions with phosphatidylinositol (PI) have been investigated using the monolayer technique. During compression/expansion/recompression cycles, CF monolayers switch from a loosely packed to a more tightly packed structure. The change in surface properties suggests a molecular rearrangement, perhaps involving interdigitation of long and short chains of the CF molecules. In CF-PI monolayers, maximal lateral packing density occurs between 0.5 and 0.7 mole fraction CF, which is close to the relative composition of mycolic acid residues and shorter-chain lipids in the mycobacterial cell wall. Low concentrations of CF increase the order in PI monolayers, consistent with CF toxicity involving rigidification of cell membranes.