A chemist's overview of surface electron spins.
This review summarizes recent research progress in the measurement and tuning of the electron spins of alien atoms and molecules adsorbed on well-defined substrates. After a brief introduction to the main experimental techniques employed to study surface electron spins, some well-explored systems consisting of atomic and molecular spin-carriers at surfaces are overviewed from a chemist's viewpoint, focusing on the experimental measurements and chemical modifications of the electron spin states of the alien entities at the surfaces on the atomic/molecular level. Finally, personal perspectives have been provided, aiming at describing some of the remaining issues that need to be addressed in the future and proposing potential applications in surface chemistry.


Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles.
In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which the oocyte-specific Cre-recombinase induces the expression of constitutively active mutant PI3K during the formation of primordial follicles. The ovaries of neonatal transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which resulted in an excess number of follicles per ovary. Thus, the elevation of phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the survival of follicles during neonatal development. Despite the increase in AKT phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These primordial follicles containing a high level of nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the dominant factor in the maintenance of female reproductive lifespan through the regulation of primordial follicle recruitment. Although the oocytic PI3K activity and PTEN levels were elevated, the activation of primordial follicles and the subsequent accumulation of antral follicles with developmentally competent oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte complexes with developmentally competent oocytes in response to super-ovulation treatment, the anovulatory phenotype was not due to follicular defects but rather endocrine abnormalities, which were likely caused by the excess number of overgrown follicles. Our current study has elucidated the critical role of oocytic PI3K activity in follicular function, as well as the presence of a PTEN-mediated mechanism in the prevention of immature follicle activation.


Bleeding diathesis in canine multiple myeloma and prognostic implications: A cohort study in 156 dogs.
Multiple myeloma (MM) is a tumor of plasma cells representing approximately 1% of all canine tumors. Clinical evident bleeding is often referred to as the main finding. The aim of the study was to evaluate the occurrence of clinical bleedings in dogs with MM and its prognostic implications compared to a population of dogs not affected by MM. Two groups of dogs (# 78 each) individually matched for breed, age and gender were considered. Group-1 (exposed) was affected by MM and group-2 (unexposed) was affected by other diseases. They were compared for bleeding and mortality at 90 days after diagnosis (relative risk, RR; attributable risk, AR). Among group-1, bleeding patients (B) were compared with non-bleeding patients (NB) in terms of mortality at 90 days (RR, AR). Incident cases of MM were 78/57,694 (0.13%). Signs of bleeding up to 30 days before the referral presentation were found in 33 (42.3%) group-1 dogs in comparison to 6 (7.7%) group-2 dogs (RR, 5.50, CI 95% 2.55-12.3, p = 0.0001; AR, 0.34, CI 95% 0.22-0.47, p = 0.0001). Epistaxis was the most frequent sign of bleeding recorded. Nineteen dogs from group-1 (24.3%) and eight from group-2 (10.2%) were non-survivors (RR = 2.37, CI 95% 1.14-5.06, p = 0.01; AR = 0.14, CI 95% 0.02-0.26, p = 0.01). Among the group-1, the B dogs, 4/33 (12.1%) were non-survivors, while 15/45 NB dogs (33.3%) were non-survivors (RR = 2.75, CI 95% 1.08-7.44, p = 0.03; AR = 0.21, CI 95% 0.20-0.38, p = 0.03). Epistaxis at diagnosis was frequent in MM dogs, and signs of bleeding were associated with a more favorable 90-day prognosis.


An open prospective pilot study of a herbal combination "Relief" as a supportive dietetic measure during alcohol withdrawal.
A herbal combination (saffron extract, passion flower herb extract, cocoa seed extract, radish extract and black cumin extract) called "Relief" was designed as a supportive therapy of alcohol withdrawal syndrome (AWS). This combination was based on the scientific evidence of each constituent effect on AWS-like symptoms. In addition, our preclinical studies have shown the effectiveness of Relief on AWS detoxification. The rationale of the study was to document whether the oral intake of the designed content of Relief could have a positive effect on the course of alcohol detoxification by reducing some of the AWS in hospitalized patients. This pilot study was performed as non-interventional, open, single-armed, prospective on 32 hospitalized patients entered for detoxification of alcohol withdrawal syndrome. Each patient received daily three capsules of Relief for 15 days, and AWS parameters were monitored, in addition to serum liver enzymes and quality of life which was evaluated using the Befindlichkeits-Skala (Bf-SR) scaling system. Relief administration significantly reduced the percentage of patients with hyperhidrosis (r=0.815, p<0.001), reduced serum liver enzymes by ~50-80% (p<0.05), and increased normalization of appetite (r=0.777, p<0.001). Besides, before the treatment began the Bf-SR scale was 28.3±4.3, which was typical for neurological syndromes such as depression or insomnia, and during Relief administration the Bf-SR scale significantly dropped to 15.6±2.4 (p<0.001). As for the safety, four, but not serious, adverse events were observed; two of them may be product related. Finally, 84.4% of patients' assessed Relief treatment as good to excellent and 87.5% of the patients declared an interest in reusing Relief for the next detoxification period. Despite the limitations of the present study, the findings showed the potential of Relief for the improvement of the clinical situation of patients with symptoms of alcohol withdrawal and therefore, justify a full-scale well-controlled study design to be implemented.


P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities.
Human CD3-16+56+ natural killer (NK) cells have been shown to display a clonally distributed ability to recognize major histocompatibility complex (MHC) class I alleles. Opposite to T lymphocytes, in NK cells, specific recognition of MHC class I molecules appears to induce inhibition of cytolytic activity and, thus, to protect target cells. Since a precise correlation has been established between the expression of the NK-specific GL183 and EB6 surface molecules (belonging to the novel p58 molecular family) and the specificity of NK clones, we analyzed whether p58 molecules could function as receptors for MHC in human NK cells. NK clones displaying the previously defined "specificity 2" and characterized by the GL183+EB6+ phenotype, specifically recognize the Cw3 allele and thus fail to lyse the Fc gamma R+ P815 target cells transfected with Cw3. On the other hand, NK clones displaying "specificity 1" and expressing the GL183-EB6+ phenotype failed to lyse Cw4+ target cells. Addition of the F(ab')2 fragments of either GL183 or EB6 mAb as well as the XA141 mAb of IgM isotype (specific for the EB6 molecules) completely restored the lysis of Cw3-transfected P815 cells by the Cw3-specific NK clones EX2 and EX4. Similarly, both the entire EB6 mAb, its F(ab')2 fragment and the XA141 mAb reconstituted the lysis of C1R, a Fc gamma R- target cell expressing Cw4 as the only serologically detected class I antigen. Thus, it appears that masking of different members of p58 molecules prevents recognition of "protective" MHC class I alleles and thus the delivering of inhibitory signals. Further support to the concept that p58 molecules represent a NK receptor delivering a negative signal was provided by experiments in which the entire anti-p58 mAbs (of IgG isotype) could inhibit the lysis of unprotected Fc gamma R+ P815 target cells, thus mimicking the inhibitory effect of MHC class I molecules.


A comprehensive review of arsenic levels in the semiconductor manufacturing industry.
This paper presents a summary of arsenic level statistics from air and wipe samples taken from studies conducted in fabrication operations. The main objectives of this study were not only to describe arsenic measurement data but also, through a literature review, to categorize fabrication workers in accordance with observed arsenic levels. All airborne arsenic measurements reported were included in the summary statistics for analysis of the measurement data. The arithmetic mean was estimated assuming a lognormal distribution from the geometric mean and the geometric standard deviation or the range. In addition, weighted arithmetic means (WAMs) were calculated based on the number of measurements reported for each mean. Analysis of variance (ANOVA) was employed to compare arsenic levels classified according to several categories such as the year, sampling type, location sampled, operation type, and cleaning technique. Nine papers were found reporting airborne arsenic measurement data from maintenance workers or maintenance areas in semiconductor chip-making plants. A total of 40 statistical summaries from seven articles were identified that represented a total of 423 airborne arsenic measurements. Arsenic exposure levels taken during normal operating activities in implantation operations (WAM = 1.6 μg m⁻³, no. of samples = 77, no. of statistical summaries = 2) were found to be lower than exposure levels of engineers who were involved in maintenance works (7.7 μg m⁻³, no. of samples = 181, no. of statistical summaries = 19). The highest level (WAM = 218.6 μg m⁻³) was associated with various maintenance works performed inside an ion implantation chamber. ANOVA revealed no significant differences in the WAM arsenic levels among the categorizations based on operation and sampling characteristics. Arsenic levels (56.4 μg m⁻³) recorded during maintenance works performed in dry conditions were found to be much higher than those from maintenance works in wet conditions (0.6 μg m⁻³). Arsenic levels from wipe samples in process areas after maintenance activities ranged from non-detectable to 146 μg cm⁻², indicating the potential for dispersion into the air and hence inhalation. We conclude that workers who are regularly or occasionally involved in maintenance work have higher potential for occupational exposure than other employees who are in charge of routine production work. In addition, fabrication workers can be classified into two groups based on the reviewed arsenic exposure levels: operators with potential for low levels of exposure and maintenance engineers with high levels of exposure. These classifications could be used as a basis for a qualitative ordinal ranking of exposure in an epidemiological study.


In vivo microbiome and associated immune markers: New insights into the pathogenesis of vaginal dysbiosis.
The microbiota fulfils a key role in the training and function of the immune system, which contributes to the symbiosis between the host and complex microbial communities. In this study, we characterized the interplay between vaginal bacteria and local immune mediators during dysbiosis in selected women of reproductive age who were grouped according to Nugent's criteria. The abundance of Gardnerella vaginalis and Bifidobacterium breve was increased in the intermediate dysbiotic status, while the presence of a plethora of non-resident bacteria characterized the group with overt vaginosis. In response to these increases, the anti-inflammatory IL1ra and pro-inflammatory IL2 increased, while the embryo trophic factors FGFβ and GMCSF decreased compared to the healthy milieu. A specific pattern, including IL1α, IL1β, IL8, MIG, MIP1α and RANTES, distinguished the intermediate group from the vaginosis group, while IL5 and IL13, which are secreted by Th2 cells, were significantly associated with the perturbation of the commensals Lactobacilli, Gardnerella and Ureaplasma. Summarizing, we postulate that although the dysbiotic condition triggers a pro-inflammatory process, the presence of a steady state level of Th2 may influence clinical manifestations. These results raise clinically relevant questions regarding the use of vaginal immunological markers as efficacious tools to monitor microbial alterations.


Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.
Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants. Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.


Formulation: a multiperspective model.
This paper presents a model of formulation that can be used by psychiatrists and other mental health professionals. A review of the literature indicates a need for a more comprehensive approach that can accommodate a variety of perspectives, suggest treatment and can be easily recalled. These issues are addressed by the multiperspective grid presented in this paper.


Complex interactions between malaria and malnutrition: a systematic literature review.
Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition. Database searches were conducted in PubMed, Global Health and Cochrane Libraries and articles published in English, French or Spanish between Jan 1980 and Feb 2018 were accessed and screened. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale and the risk of bias across studies was assessed using the GRADE approach. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline were followed. Of 2945 articles screened from databases, a total of 33 articles were identified looking at the association between malnutrition and risk of malaria and/or the impact of malnutrition in antimalarial treatment efficacy. Large methodological heterogeneity of studies precluded conducting meaningful aggregated data meta-analysis. Divergent results were reported on the effect of malnutrition on malaria risk. While no consistent association between risk of malaria and acute malnutrition was found, chronic malnutrition was relatively consistently associated with severity of malaria such as high-density parasitemia and anaemia. Furthermore, there is little information on the effect of malnutrition on therapeutic responses to artemisinin combination therapies (ACTs) and their pharmacokinetic properties in malnourished children in published literature. The evidence on the effect of malnutrition on malaria risk remains inconclusive. Further analyses using individual patient data could provide an important opportunity to better understand the variability observed in publications by standardising both malaria and nutritional metrics. Our findings highlight the need to improve our understanding of the pharmacodynamics and pharmacokinetics of ACTs in malnourished children. Further clarification on malaria-malnutrition interactions would also serve as a basis for designing future trials and provide an opportunity to optimise antimalarial treatment for this large, vulnerable and neglected population. PROSPERO CRD42017056934 .


Patient selection for cardiac surgery in left ventricular power failure.
Nineteen patients in acute left ventricular power failure following acute myocardial infarction were given support with intraaortic balloon pumping and underwent cardiac catheterization. Hemodynamic response to disastolic augmentation, results of left ventriculography, and observations of selective coronary arteriography were evaluated to determine which patients could survive without operation, which would require operation to survive, and which could be predicted not to survive operation. Of ten patients who underwent operation, three were long-term survivors. Two patients predicted to have a good prognosis without surgery did survive. Of three patients who had been determined to require operation but not undergo it, two died in the hospital and one a month later. The four patients whose conditions were considered inoperable died in the hospital. The results indicate that current methods of predicting the need for corrective surgery are relatively accurate and that the rate of survival in surgically treated patients may be increased.


HDAC8 and STAT3 repress BMF gene activity in colon cancer cells.
Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein 3 (Sp3) transcription factor exchange and recruitment of p300. Treatment with a p300 inhibitor or transient overexpression of exogenous HDAC8 interfered with BMF induction, whereas RNAi-mediated silencing of STAT3 activated the target gene. This is the first report to identify a direct target gene of HDAC8 repression, namely, BMF. Interestingly, the repressive role of HDAC8 could be uncoupled from HDAC1 to trigger Bmf-mediated apoptosis. These findings have implications for the development of HDAC8-selective inhibitors as therapeutic agents, beyond the reported involvement of HDAC8 in childhood malignancy.


Preparation, characterization, and heck reaction of siloxane films derived from carbosilane dendrons with a bromophenyl group at the focal point and up to 27 SiCl3 groups at the periphery.
Multidentate organosiloxane thin films were prepared on SiO2/Si surfaces by solution phase deposition of carbosilane dendrons containing a bromophenyl group at the focal point and 3 (Br-G0), 9 (Br-G1), and 27 (Br-G2) SiCl3 groups at the periphery. The films were characterized by contact angle goniometry, ellipsometry, and X-ray photoelectron spectroscopy (XPS). The results indicated that about six Br-G0 molecules covered the same surface area as three Br-G1 molecules and one Br-G2 molecule. Hence, the density of the bromophenyl groups in the films could be defined by the size (generation) of the dendron adsorbates. We also demonstrated that the bromophenyl groups on the film surfaces could serve as a handle for attaching conjugated molecules via formation of C-C bonds. Thus, upon treatment of the films with 4-fluorostyrene under Heck reaction conditions, XPS analysis showed that about 90, 66, and 51% of the bromine atoms in the films prepared from Br-G0, Br-G1, and Br-G2 were consumed, and 94, 82, and 58% of the consumed bromine atoms were replaced by fluorostyryl groups. The remaining bromophenyl groups were probably not accessible to the reactants because of their unfavorable orientation. The overall yields for the surface Heck reaction were estimated to be 84, 54, and 30% for the films prepared from Br-G0, Br-G1, and Br-G2, respectively.


Impact of size, secondary structure, and counterions on the binding of small ribonucleic acids to layered double hydroxide nanoparticles.
Use of ribonucleic acid (RNA) interference to regulate protein expression has become an important research topic and gene therapy tool, and therefore, finding suitable vehicles for delivery of small RNAs into cells is of crucial importance. Layered double metal hydroxides such as hydrotalcite (HT) have shown great promise as nonviral vectors for transport of deoxyribose nucleic acid (DNA), proteins, and drugs into cells, but the adsorption of RNAs to these materials has been little explored. In this study, the binding of small RNAs with different lengths and levels of secondary structure to HT nanoparticles has been analyzed and compared to results obtained with small DNAs in concurrent experiments. Initial experiments established the spectrophotometric properties of HT in aqueous solutions and determined that HT particles could be readily sedimented with near 100% efficiencies. Use of RNA+HT cosedimentation experiments as well as electrophoretic mobility shift assays demonstrated strong adsorption of RNA 25mers to HT, with twofold greater binding of single-stranded RNAs relative to double-stranded molecules. Strong affinities were also observed with ssRNA and dsRNA 54mers and with more complex transfer RNA molecules. Competition binding and RNA displacement experiments indicated that RNA-HT associations were strong and were only modestly affected by the presence of high concentrations of inorganic anions.


Multilayer polarizing grating mirror used for the generation of radial polarization in Yb:YAG thin-disk lasers.
The design, fabrication and characterization of a multilayer polarizing grating mirror developed for an Yb:YAG thin-disk laser resonator are reported. The potential of the proposed solution is discussed together with the first demonstration of a radially polarized Yb:YAG thin-disk laser.


Tuning thermal transport in ultrathin silicon membranes by surface nanoscale engineering.
A detailed understanding of the connections of fabrication and processing to structural and thermal properties of low-dimensional nanostructures is essential to design materials and devices for phononics, nanoscale thermal management, and thermoelectric applications. Silicon provides an ideal platform to study the relations between structure and heat transport since its thermal conductivity can be tuned over 2 orders of magnitude by nanostructuring. Combining realistic atomistic modeling and experiments, we unravel the origin of the thermal conductivity reduction in ultrathin suspended silicon membranes, down to a thickness of 4 nm. Heat transport is mostly controlled by surface scattering: rough layers of native oxide at surfaces limit the mean free path of thermal phonons below 100 nm. Removing the oxide layers by chemical processing allows us to tune the thermal conductivity over 1 order of magnitude. Our results guide materials design for future phononic applications, setting the length scale at which nanostructuring affects thermal phonons most effectively.


Flaxseed oil attenuates nonalcoholic fatty liver of hyperlipidemic hamsters.
Hyperlipidemia of hamsters was induced by high-fat/cholesterol diets formulated by the addition of coconut oil (CO), butter (BU), and flaxseed oil (FX). Lower (p < 0.05) serum lipids, liver size, and hepatic cholesterol and triacylglycerol contents were observed in the FX group compared to both CO and BU groups. The liver damage indices [glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values] in the FX group were lower (p < 0.05) than those in the CO and BU groups, which may result from higher (p < 0.05) glutathione (GSH) levels and a tendency toward lower malondialdehyde (MDA) levels in livers. Besides, lower (p < 0.05) gene expression and activity of hepatic matrix metalloproteinases-9 (MMP-9) in the FX group were lower (p > 0.05) compared to those in the CO and BU groups; however, no (p > 0.05) differences in gene expression activities of hepatic MMP-2 were observed among treatments. Those beneficial effects could explain the attenuation of FX on nonalcoholic fatty liver (NAFL) induced by a high-fat/cholesterol dietary habit.


Pneumocephalus leading to the diagnosis of cerebrospinal fluid leak and esophageal perforation after cervical spine surgery.
Pneumocephalus is a collection of air within in the intracranial cavity, most commonly seen following traumatic injury or cranial surgeries. Esophageal injury and cerebrospinal fluid (CSF) leak are rare complications that may occur following anterior cervical discectomy and fusion (ACDF). We present a novel case of pneumocephalus arising from unrestricted leakage of CSF via coincident esophageal injury and durotomy in a patient who underwent an ACDF after trauma. A 21-year-old man presented to an outside hospital with C5/C6 subluxation, complete spinal cord injury, and quadriplegia from a motor vehicle accident. He underwent an ACDF, during which a CSF leak was observed. He was then transferred to our institution for rehabilitation and tracheostomy placement 1 week after the ACDF surgery. Following the tracheostomy, the patient developed intractable fevers and nonspecific symptoms. A CT scan demonstrated frontal pneumocephalus without mass effect. Air was found in the retropharyngeal space. There were no accumulations of CSF in the neck. Extravasation of contrast around instrumentation at C5/C6 on a cine esophagogram demonstrated an esophageal perforation at that level. Pneumocephalus may form when large volumes of CSF escape from the intracranial space and air is drawn into the space by the negative pressure. In this unusual case, the esophageal perforation promoted the formation of the pneumocephalus. Treatment included closure of both defects, disrupting the suspected communication between the intracranial space and the esophagus.


Site-specific saturation mutagenesis on residues 132 and 450 of Candida rugosa LIP2 enhances catalytic efficiency and alters substrate specificity in various chain lengths of triglycerides and esters.
The catalytic versatility of recombinant Candida rugosa LIP2 has been known to have potential applications in industry. In this study, site-specific saturation mutagenesis on residues L132 and G450 of recombinant LIP2 has been employed to investigate the impact of both residues on substrate specificity of LIP2. Point mutations on L132 and G450 were done separately using mutagenic degenerate primer sets containing 32 codons to generate two libraries of mutants in Pichia pastoris . Replacements of amino acid on these mutants were identified as L132A, L132I, G450S, and G450A. In lipase activity assay, L132A and L132I mutants showed a shift of preference from short- to medium-chain triglyceride, whereas G450S and G450A mutants retained preferences as compared to wild-type LIP2. Among mutants, G450A has the highest activity on tributyrin. However, hydrolysis of p-nitrophenyl (p-NP) esters with L132A, L132I, and G450S did not show differences of preferences over medium- to long-chain esters except in G450A, which prefers only medium-chain ester as compared to wild-type LIP2. All mutants showed an enhanced catalytic activity and higher optimal temperature and pH stability as compared to wild-type LIP2.


Scholar Plot: Design and Evaluation of an Information Interface for Faculty Research Performance.
The ability to objectively assess academic performance is critical to rewarding academic merit, charting academic policy, and promoting science. Quintessential to performing these functions is first the ability to collect valid and current data through increasingly automated online interfaces. Moreover, it is crucial to remove disciplinary and other biases from these data, presenting them in ways that support insightful analysis at various levels. Existing systems are lacking in some of these respects. Here we present Scholar Plot (SP), an interface that harvests bibliographic and research funding data from online sources. SP addresses systematic biases in the collected data through nominal and normalized metrics. Eventually, SP combines synergistically these metrics in a plot form for expert appraisal, and an iconic form for broader consumption. SP's plot and iconic forms are scalable, representing equally well individual scholars and their academic units, thus contributing to consistent ranking practices across the university organizational structure. In order to appreciate the design principles underlying SP, in particular the informativeness of nominal vs. normalized metrics, we also present the results of an evaluation survey taken by senior faculty (n = 28) with significant promotion and tenure assessment experience.


Phosphorus sources for aquatic weeds: water or sediments?
Nine common species of aquatic macrophytes took all their phosphorus from the sediments when grown in situ in both a mesotrophic and a mildly eutrophic bay. Even under hypertrophic conditions, the sediments contributed an average of 72 percent of all the phosphorus taken up during growth. These experiments unambiguously demonstrate for the first time that submergent macrophytes in nature over-whelmingly depend on the sediments for their phosphorus supply and characterize them as potential nutrient pumps to the open water.


Effects of Governance on Availability of Land for Agriculture and Conservation in Brazil.
The 2012 revision of the Brazilian Forest Act changed the relative importance of private and public governance for nature conservation and agricultural production. We present a spatially explicit land-use model for Brazilian agricultural production and nature conservation that considers the spatial distribution of agricultural land suitability, technological and management options, legal command, and control frameworks including the Atlantic Forest Law, the revised Forest Act, and the Amazonian land-titling, "Terra Legal," and also market-driven land use regulations. The model is used to analyze land use allocation under three scenarios with varying priorities among agricultural production and environmental protection objectives. In all scenarios, the legal command and control frameworks were the most important determinants of conservation outcomes, protecting at least 80% of the existing natural vegetation. Situations where such frameworks are not expected to be effective can be identified and targeted for additional conservation (beyond legal requirements) through voluntary actions or self-regulation in response to markets. All scenarios allow for a substantial increase in crop production, using an area 1.5-2.7 times the current cropland area, with much of new cropland occurring on current pastureland. Current public arrangements that promote conservation can, in conjunction with voluntary schemes on private lands where conversion to agriculture is favored, provide important additional nature conservation without conflicting with national agricultural production objectives.


Associations between intrusive thoughts, reality discrimination and hallucination-proneness in healthy young adults.
People who experience intrusive thoughts are at increased risk of developing hallucinatory experiences, as are people who have weak reality discrimination skills. No study has yet examined whether these two factors interact to make a person especially prone to hallucinatory experiences. The present study examined this question in a non-clinical sample. Participants were 160 students, who completed a reality discrimination task, as well as self-report measures of cannabis use, negative affect, intrusive thoughts and auditory hallucination-proneness. The possibility of an interaction between reality discrimination performance and level of intrusive thoughts was assessed using multiple regression. The number of reality discrimination errors and level of intrusive thoughts were independent predictors of hallucination-proneness. The reality discrimination errors × intrusive thoughts interaction term was significant, with participants who made many reality discrimination errors and reported high levels of intrusive thoughts being especially prone to hallucinatory experiences. Hallucinatory experiences are more likely to occur in people who report high levels of intrusive thoughts and have weak reality discrimination skills. If applicable to clinical samples, these findings suggest that improving patients' reality discrimination skills and reducing the number of intrusive thoughts they experience may reduce the frequency of hallucinatory experiences.


Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase.
Dendritic filopodia select synaptic partner axons by interviewing the cell surface of potential targets, but how filopodia decipher the complex pattern of adhesive and repulsive molecular cues to find appropriate contacts is unknown. Here, we demonstrate in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. Super-resolution and live-cell imaging reveals that EphB2 is located in the tips of filopodia and at nascent synaptic sites. Surprisingly, a genetically encoded indicator of EphB kinase activity, unbiased classification, and a photoactivatable EphB2 reveal that simple differences in the kinetics of EphB kinase signaling at the tips of filopodia mediate the choice between retraction and synaptogenesis. This may enable individual filopodia to choose targets based on differences in the activation rate of a single tyrosine kinase, greatly simplifying the process of partner selection and suggesting a general principle.


Fizeau-type multi-pass Shack-Hartmann-Test.
The stability of the Shack-Hartmann sensor against mechanical disturbances from the environment can advantageously be exploited in highly sensitive wave front tests of surfaces. Here, a Fizeau-type multiple beam test is investigated. The enhancement of the phase sensitivity in a Fizeau-resonator formed by two high reflecting mirror surfaces enables tests in reflected light which includes also opaque surfaces. The multiplication of the sensitivity with the number of passes through the Fizeau resonator provides a big margin against the rather limited repeatability of wave front measurements with such a wave front sensor. The method has been tested for planeness Fizeau measurements. It could also be exploited in spherical Fizeau tests. But in the latter case the two spherical surfaces forming the resonator should have radii which differ only by e.g. 1mm.


Identification of a novel system for boron transport: Atr1 is a main boron exporter in yeast.
Boron is a micronutrient in plants and animals, but its specific roles in cellular processes are not known. To understand boron transport and functions, we screened a yeast genomic DNA library for genes that confer resistance to the element in Saccharomyces cerevisiae. Thirty boron-resistant transformants were isolated, and they all contained the ATR1 (YML116w) gene. Atr1 is a multidrug resistance transport protein belonging to the major facilitator superfamily. C-terminal green fluorescent protein-tagged Atr1 localized to the cell membrane and vacuole, and ATR1 gene expression was upregulated by boron and several stress conditions. We found that atr1Delta mutants were highly sensitive to boron treatment, whereas cells overexpressing ATR1 were boron resistant. In addition, atr1Delta cells accumulated boron, whereas ATR1-overexpressing cells had low intracellular levels of the element. Furthermore, atr1Delta cells showed stronger boron-dependent phenotypes than mutants deficient in genes previously reported to be implicated in boron metabolism. ATR1 is widely distributed in bacteria, archaea, and lower eukaryotes. Our data suggest that Atr1 functions as a boron efflux pump and is required for boron tolerance.


Herpesvirus infection of the respiratory tract in patients with alcoholic hepatitis.
Respiratory herpesvirus infections have rarely been described in alcoholics. We report four cases of severe respiratory herpesvirus infections in patients with alcoholic liver disease. Two were related to Herpes Simplex Virus and two to Cytomegalovirus. Both chronic alcoholism and severe liver disease induce immunosuppression, which might account for these unusual herpesvirus infections of the respiratory tract. These cases suggest that infections with herpesviruses should be considered in patients with alcoholic liver disease and pulmonary or tracheobronchial disease unresponsive to standard antibiotic therapy. Bronchoscopy, viral culture, and serological tests appear warranted, particularly given the existence of specific therapy.


The effects of streptozotocin-induced diabetes and aldose reductase inhibition with sorbinil, on left and right atrial function in the rat.
Diabetes mellitus is frequently associated with the complications of cardiovascular disease. Activation of the aldose reductase (or polyol) pathway has long been implicated as an underlying factor for the development of many diabetic complications and indeed, treatment with aldose reductase inhibitors has been shown to prevent or reverse many of these diabetic complications. This study examines the effects of 14-day streptozotocin-induced diabetes on alpha1- and beta-adrenoceptor-mediated responses in rat isolated left and right atria. The effects of treatment with the aldose reductase inhibitor (ARI) sorbinil were also studied. A positive inotropic response was observed to both isoprenaline and phenylephrine in left atria. Diabetes of 14 days duration resulted in a supersensitivity of these tissues to the beta-adrenoceptor agonist in comparison with controls, while responses to the alpha1-adrenoceptor agonist were unaltered. Spontaneously beating right atria from diabetic rats was found to have a depressed resting rate compared with control tissues, although positive chronotropic beta-adrenoceptor-mediated responses were not affected by diabetes. Phenylephrine produced alpha1-adrenoceptor-mediated chronotropic responses in right atrial tissues, and these were found to be enhanced in rats with diabetes. Treatment of diabetic rats with the ARI sorbinil was successful in preventing only one of the observed diabetes-induced changes in atrial function, namely the supersensitivity of left atria to isoprenaline. Sorbinil treatment did, however, alter responses of control left and right atria in a manner similar to diabetes. In conclusion, streptozotocin-induced diabetes of 14 days duration was found to cause a number of alterations in the functioning of both left and right atria. ARI treatment with sorbinil failed to prevent all but one of these changes, and in addition altered responses of atria from control rats, having a similar effect to that produced by diabetes. These data suggest that sorbinil may have effects in addition to, and independent of, aldose reductase inhibition in the cardiovascular system.


Electrophysiological and hemodynamic effects of vernakalant and flecainide during cardiac resynchronization in dyssynchronous canine hearts.
Patients with heart failure and left bundle branch block (LBBB) are frequently treated with biventricular pacing (BiVP). Approximately one-third of them suffer from atrial fibrillation. Pharmacological conversion of atrial fibrillation is performed with drugs that slow ventricular conduction, but the effects of these drugs on the benefit of BiVP are poorly understood. Experiments were performed in dogs with chronic LBBB, investigating the effects of Vernakalant and Flecainide (n = 6 each) on hemodynamics and electrophysiology during epicardial (EPI) and endocardial BiVP. The degree of dyssynchrony and conduction slowing was quantified using QRS width and EPI electrical mapping. Compared with LBBB, EPI and endocardial BiVP reduced QRS duration by 7% ± 9% (P < 0.05 compared with LBBB) and 20% ± 13% (P < 0.05 compared with LBBB, P < 0.05 between modes), respectively. During BiVP, the administration of Vernakalant and Flecainide increased QRS duration by 20% ± 14% (P < 0.05 compared with predrug BiVP) and 34% ± 10% (P < 0.05 compared with predrug BiVP, P < 0.05 between drugs). left ventricular (LV) dP/dtmax decreased by 16% ± 8% (P < 0.05 compared with predrug BiVP) during Vernakalant and by 14% ± 15% (P < 0.05 compared with predrug BiVP) during Flecainide. The drugs did not affect the relative changes in QRS width and LV dP/dtmax induced by BiVP. Vernakalant and Flecainide decrease contractility, slow myocardial conduction velocity, and increase activation time. The electrical and hemodynamic benefits of BiVP are not altered by the drugs.


Predicting the Immunogenicity of T cell epitopes: From HIV to SARS-CoV-2.
We describe a physics-based learning model for predicting the immunogenicity of Cytotoxic T Lymphocyte (CTL) epitopes derived from diverse pathogens, given a Human Leukocyte Antigen (HLA) genotype. The model was trained and tested on experimental data on the relative immunodominance of CTL epitopes in Human Immunodeficiency Virus infection. The method is more accurate than publicly available models. Our model predicts that only a fraction of SARS-CoV-2 epitopes that have been predicted to bind to HLA molecules is immunogenic. The immunogenic CTL epitopes across all SARS-CoV-2 proteins are predicted to provide broad population coverage, but the immunogenic epitopes in the SARS-CoV-2 spike protein alone are unlikely to do so. Our model predicts that several immunogenic SARS-CoV-2 CTL epitopes are identical to those contained in low-pathogenicity coronaviruses circulating in the population. Thus, we suggest that some level of CTL immunity against COVID-19 may be present in some individuals prior to SARS-CoV-2 infection.


Effect of carbon source addition on toluene biodegradation by an Escherichia coli DH5alpha transconjugant harboring the TOL plasmid.
Horizontal gene transfer (HGT) of plasmids is a naturally occurring phenomenon which could be manipulated for bioremediation applications. Specifically, HGT may prove useful to enhance bioremediation through genetic bioaugmentation. However, because the transfer of a plasmid between donor and recipient cells does not always result in useful functional phenotypes, the conditions under which HGT events result in enhanced degradative capabilities must first be elucidated. The objective of this study was to determine if the addition of alternate carbon substrates could improve toluene degradation in Escherichia coli DH5alpha transconjugants. The addition of glucose (0.5-5 g/L) and Luria-Bertani (LB) broth (10-100%) resulted in enhanced toluene degradation. On average, the toluene degradation rate increased 14.1 (+/-2.1)-fold in the presence of glucose while the maximum increase was 18.4 (+/-1.7)-fold in the presence of 25% LB broth. Gene expression of xyl genes was upregulated in the presence of glucose but not LB broth, which implies different inducing mechanisms by the two types of alternate carbon source. The increased toluene degradation by the addition of glucose or LB broth was persistent over the short-term, suggesting the pulse amendment of an alternative carbon source may be helpful in bioremediation. While the effects of recipient genome GC content and other conditions must still be examined, our results suggest that changes in environmental conditions such as alternate substrate availability may significantly improve the functionality of the transferred phenotypes in HGT and therefore may be an important parameter for genetic bioaugmentation optimization.


A PER3 Polymorphism Interacts with Sleep Duration to Influence Transient Mood States in Women.
Expression of the clock family of genes in the suprachiasmatic nuclei (SCN) regulates the molecular control of circadian timing. Increasing evidence also implicates clock gene activity in the development of mood disorders. In particular, variation in the PER3 clock gene has been shown to influence diurnal preference and sleep homeostasis. However, there is not currently a clear association between PER3 polymorphisms and mood. This is possibly because the PER3 gene has been shown to influence homeostatic sleep drive, rather than circadian timing, and the PER3 gene may be behaviorally relevant only under chronic sleep loss conditions. To test the association between PER3 allele status and impaired mood, a total of 205 healthy women were genotyped for PER3 allele status and responded to previously-validated psychological questionnaires surveying self-reported sleep habits (MEQ, PSQI) and mood. Our mood measures included two measures of short-term, transient mood (state anxiety and mood disturbance) and two measures of longer term, ongoing mood (trait anxiety and depressive symptomology). The PER3 genotype distribution was 88 (42.9%) for PER3(4/4), 98 (47.8%) for PER3(4/5), and 19 (9.3%) for PER3(5/5). Our sleep duration x genotype interaction analyses showed that, relative to longer allele carriers, PER3(4/4) genotypes were at greater risk for transient psychological effects (mood and state anxiety) when they reported reduced sleep durations. Sleep duration plays a critical role in understanding the extent to which PER3 allele status relates to mood states.


High throughput screening based selection of phases for aqueous two-phase system-centrifugal partitioning chromatography of monoclonal antibodies.
Aqueous two-phase systems have been demonstrated to be a possible alternative to chromatographic separations during the industrial purification of proteins. While convenient high throughput screening methods were shown to drastically reduce experimental effort for the evaluations of ATPS as a unit operation, the selection of which phases to investigate is currently guided largely by prior knowledge. Correlations between protein descriptors and distribution were found, but the general applicability of such correlations especially under conditions of high protein load, is questionable, as currently no correlations take the saturation of the phases with protein into account. In this manuscript, we demonstrate how precipitation experiments using the phase forming components can guide the selection of both system type and tieline length for the purification of monoclonal antibodies. Phase selection and process development time can thus be significantly reduced, as all the necessary precipitation, binodal, and tieline experiments can be conducted within one day. Good qualitative correlations between precipitation data and both distribution and recovery of the target molecule were found. Most promising systems were selected for upscale to a 500mL CPC. Influence of operation condition on the column and on HCP clearance was investigated. An increase in HCP clearance of more than threefold compared to batch extractions was observed. The importance of load protein concentration underlined the value of using a screening approach that incorporated target protein solubility data.


Effects of 4 Weeks of High-Intensity Interval Training and β-Hydroxy-β-Methylbutyric Free Acid Supplementation on the Onset of Neuromuscular Fatigue.
This study investigated the effects of high-intensity interval training (HIIT) and β-hydroxy-β-methylbutyric free acid (HMB) supplementation on physical working capacity at the onset of neuromuscular fatigue threshold (PWC(FT)). Thirty-seven participants (22 men, 15 women; 22.8 ± 3.4 years) completed an incremental cycle ergometer test (graded exercise test [GXT]); electromyographic amplitude from the right vastus lateralis was recorded. Assessments occurred preceding (PRE) and after 4 weeks of supplementation (POST). Participants were randomly assigned to control (C, n = 9), placebo (P, n = 14), or supplementation (S, n = 14) groups. Both P and S completed 12 HIIT sessions, whereas C maintained normal diet and activity patterns. The PWC(FT) (W) was determined using the maximal perpendicular distance (D(MAX)) method. Electromyographic amplitude (μVrms) over time was used to generate a cubic regression. Onset of fatigue (TF) was the x-value of the point on the regression that was at D(MAX) from a line between the first and last data points. The PWC(FT) was estimated using TF and GXT power-output increments. The 2-way analysis of variance (ANOVA) (group × time) resulted in a significant interaction for PWC(FT) (F = 6.69, p = 0.004). Post hoc analysis with 1-way ANOVA resulted in no difference in PWC(FT) among groups at PRE (F = 0.87, p = 0.43); however, a difference in PWC(FT) was shown for POST (F = 5.46, p = 0.009). Post hoc analysis among POST values revealed significant differences between S and both P (p = 0.034) and C (p = 0.003). No differences (p = 0.226) were noted between P and C. Paired samples t-tests detected significant changes after HIIT for S (p < 0.001) and P (p = 0.016), but no change in C (p = 0.473). High-intensity interval training increased PWC(FT), but HMB with HIIT was more effective than HIIT alone. Furthermore, it seems that adding HMB supplementation with HIIT in untrained men and women may further improve endurance performance measures.


On the role of auditory feedback in robot-assisted movement training after stroke: review of the literature.
The goal of this paper is to address a topic that is rarely investigated in the literature of technology-assisted motor rehabilitation, that is, the integration of auditory feedback in the rehabilitation device. After a brief introduction on rehabilitation robotics, the main concepts of auditory feedback are presented, together with relevant approaches, techniques, and technologies available in this domain. Current uses of auditory feedback in the context of technology-assisted rehabilitation are then reviewed. In particular, a comparative quantitative analysis over a large corpus of the recent literature suggests that the potential of auditory feedback in rehabilitation systems is currently and largely underexploited. Finally, several scenarios are proposed in which the use of auditory feedback may contribute to overcome some of the main limitations of current rehabilitation systems, in terms of user engagement, development of acute-phase and home rehabilitation devices, learning of more complex motor tasks, and improving activities of daily living.


Evaluation of early and late-term infections after renal transplantation: Clinical experiences of Sanko University Medical Faculty Transplantation Center.
Infections play an important part in post-transplantation causes of morbidity and mortality. The purpose of this study is to evaluate short-, and long-term infections encountered in after renal transplantations. Two hundred and thirteen cases that consisted of both living and cadaver donors, who suffered from late period renal insufficiency and had renal transplant between June 2011 and January 2016 at the Transplantation Center of Sanko University School of Medicine were included in the study. In this study the short-, and long-term infections seen in post renal transplantation were examined retrospectively. Infection types, frequency and periods of infection, infection agents and predisposing factors were determined as the examination parameters. Of the 213 patients who received renal transplant, 139 were males (65.3%) and 74 were women (34.75%) and the mean age was 42±11,8 (range, 14-70) years. Twelve (5.6%) patients exited after renal transplantation. Post-transplant infections were seen in 49 patients (23.1%) within 1-6 months; in 13 patients (6.1%) within 6-12 months; and in 5 patients (2.4%) after the 12th month. The most common infections after renal transplantation were associated with urinary tract (70 patients, 34.3%). The most frequently isolated agents were E. coli (n=66; 30.9%), Kebsiella spp. (n=18; 8.4%) and Enterococci (n=18; 8.4%) respectively. The renal transplants from the cadavers were observed to contract infections 1.78 times more frequently compared to the living donors (OR=1.78, 95% CI=1.03-3.09). The most common complication after renal transplantation are infections. The majority of the infections are seen within the first year especially between 1-6 months. Post-transplant infections are often related to urinary system. E.coli is the most frequently isolated agent and it may be responsible for urosepsis in renal transplant patients. Infection more often seen in renal transplantations from cadavers.


A geometric framework for statistical analysis of trajectories with distinct temporal spans.
Analyzing data representing multifarious trajectories is central to the many fields in Science and Engineering; for example, trajectories representing a tennis serve, a gymnast's parallel bar routine, progression/remission of disease and so on. We present a novel geometric algorithm for performing statistical analysis of trajectories with distinct number of samples representing longitudinal (or temporal) data. A key feature of our proposal is that unlike existing schemes, our model is deployable in regimes where each participant provides a different number of acquisitions (trajectories have different number of sample points or temporal span). To achieve this, we develop a novel method involving the parallel transport of the tangent vectors along each given trajectory to the starting point of the respective trajectories and then use the span of the matrix whose columns consist of these vectors, to construct a linear subspace in R m . We then map these linear subspaces (possibly of distinct dimensions) of R m on to a single high dimensional hypersphere. This enables computing group statistics over trajectories by instead performing statistics on the hypersphere (equipped with a simpler geometry). Given a point on the hypersphere representing a trajectory, we also provide a "reverse mapping" algorithm to uniquely (under certain assumptions) reconstruct the subspace that corresponds to this point. Finally, by using existing algorithms for recursive Fréchet mean and exact principal geodesic analysis on the hypersphere, we present several experiments on synthetic and real (vision and medical) data sets showing how group testing on such diversely sampled longitudinal data is possible by analyzing the reconstructed data in the subspace spanned by the first few principal components.


Homogeneous hydroxyapatite/alginate composite hydrogel promotes calcified cartilage matrix deposition with potential for three-dimensional bioprinting.
Calcified cartilage regeneration plays an important role in successful osteochondral repair, since it provides a biological and mechanical transition from the unmineralized cartilage at the articulating surface to the underlying mineralized bone. To biomimic native calcified cartilage in engineered constructs, here we test the hypothesis that hydroxyapatite (HAP) stimulates chondrocytes to secrete the characteristic matrix of calcified cartilage. Sodium citrate (SC) was added as a dispersant of HAP within alginate (ALG), and homogeneous dispersal of HAP within ALG hydrogel was confirmed using sedimentation tests, electron microscopy, and energy dispersive spectroscopy. To examine the biological performance of ALG/HAP composites, chondrocyte survival and proliferation, extracellular matrix production, and mineralization potential were evaluated in the presence or absence of the HAP phase. Chondrocytes in ALG/HAP constructs survived well and proliferated, but also expressed higher levels of calcified cartilage markers compared to controls, including Collagen type X secretion, alkaline phosphatase (ALP) activity, and mineral deposition. Compared to controls, ALG/HAP constructs also showed an elevated level of mineralized matrix in vivo when implanted subcutaneously in mice. The printability of ALG/HAP composite hydrogel precursors was verified by 3D printing of ALG/HAP hydrogel scaffolds with a porous structure. In summary, these results confirm the hypothesis that HAP in ALG hydrogel stimulates chondrocytes to secrete calcified matrix in vitro and in vivo and reveal that ALG/HAP composites have the potential for 3D bioprinting and osteochondral regeneration.


Posterior calvarial distraction for complex craniosynostosis and cerebellar tonsillar herniation.
Children with syndromic, multisuture, and lambdoid craniosynostosis undergoing calvarial surgery often have Chiari malformation type I (CM-I) (or cerebellar tonsillar herniation). The optimal management of this patient group, including the surgical techniques and timing of surgery, remains uncertain. Posterior calvarial distraction (PCD) is an effective method to increase the supratentorial cranial volume and improve raised intracranial pressure in children with complex craniosynostosis. This study investigated the efficacy of PCD in posterior fossa (PF) volume expansion and treatment of CM-I and associated syringomyelia (syrinx) in this group of children. This retrospective study included patients who were surgically treated between 2006 and 2015. Over 10 years, 16 patients with multisuture synostosis, lambdoid synostosis, or craniosynostosis associated with a confirmed genetic syndrome, and a concurrent CM-I, were included. The mean age at the time of surgery was 5.1 years (range 8 months-18 years). Fourteen patients had pansynostosis and 2 had lambdoid synostosis. Eight had a confirmed syndromic diagnosis (Crouzon in 8, Apert in 4, Pfeiffer in 1, and Saethre-Chotzen in 1). Ten patients had raised intracranial pressure; 4 had syringomyelia. The average clinical follow-up was 50 months (range 9-116 months). Clinically, 9 patients improved, 7 remained stable, and none deteriorated. The average distraction distance was 23 mm (range 16-28 mm). The PF anterior-posterior (AP) distance/width ratio increased from 0.73 to 0.80 mm (p = 0.0004). Although an osteotomy extending inferior to the torcula (compared with superior) was associated with a larger absolute PF AP distance increase (13 vs 6 mm, p = 0.028), such a difference was not demonstrable when the PF AP distance/width ratio was calculated. Overall, the mean tonsillar herniation improved from 9.3 to 6.0 mm (p = 0.011). Syrinx dimensions also improved in the AP (from 7.9 to 3.1 mm) and superior-inferior (from 203 to 136 mm) dimensions. No patients required further foramen magnum decompression for CM. Of the 16 patients, 2 had subsequent frontoorbital advancement and remodeling, of which 1 was for volume expansion and 1 was for cosmetic purposes. Two patients required CSF shunt insertion after PCD. Following PCD, PF volume increased as well as supratentorial volume. This morphometric change was observed in osteotomies both inferior and superior to the torcula. The PF volume increase resulted in improvement of cerebellar tonsillar herniation and syrinx. PCD is an efficacious first-line, single-stage treatment for concurrent pansynostosis and lambdoid craniosynostosis, CM-I, and syrinx.


The kinetics of promonocytes and monocytes in the bone marrow.
The mononuclear phagocytes of the bone marrow can be classified into two cell types, promonocytes and monocytes. The present study was performed to establish whether the promonocytes are the progenitors of the monocytes and to determine the kinetic characteristics of the promonocytes and monocytes in the bone marrow compartment. Both in vitro labeling studies with thymidine-(3)H and determination of the relative amount of DNA in the nuclei of individual cells showed that under normal steady-state conditions the promonocytes are proliferating cells and the monocytes, nondividing cells. In vivo labeling studies provided further evidence that the promonocytes are the progenitor cells of the monocytes. During the first 24 hr after labeling, the promonocytes showed a constant high level of labeling (about 70%). The mean grain count of these cells decreased with time. The labeling index of the monocytes of the bone marrow increased during the first 24 hr after in vivo labeling, but during the same period the mean grain counts remained almost constant, with values amounting to about half those of the promonocytes during the first 6 hr of the experiment. The data concerning the labeling indices and the percentage distribution ratio of the promonocytes and monocytes in the bone marrow, and the labeling indices of the peripheral blood monocytes are used to construct a model population. The results lead to the conclusions that the promonocytes are multiplicative cells and that both daughter cells arising from the division of a promonocyte are monocytes. The DNA-synthesis time found for the promonocytes is 13.6 hr. From this value, the average generation time was computed to be 19.5 hr.


Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol.
The single most important prognostic determinant in childhood acute lymphoblastic leukaemia (ALL) is effective therapy and changes in therapy may influence the significance of other risk factors. The effect of intensified therapy on the importance of currently recognized phenotypic and genotypic determinants of outcome was assessed in 2090 children enrolled on the Medical Research Council United Kingdom acute lymphoblastic leukaemia XI (MRC UKALL XI) protocol. Treatment allocation was not determined by risk factors. Multivariate analysis confirmed the dominant influence on prognosis of age, sex and presenting white cell count (WCC). After allowing for these features, blast karyotype, d 8 marrow blast percentage and remission status at the end of induction therapy were the only remaining significant predictors of outcome. Organomegaly, haemoglobin concentration, French--American--British type, body mass index, presence of central nervous system disease at diagnosis, immunophenotype and presence of TEL/AML1 fusion gene (examined in a subset of 659 patients) either had no significant effect on outcome or were significant only in univariate analysis. Among karyotype abnormalities with an independent influence on prognosis, high hyperdiploidy (> 50 chromosomes) was shown to be favourable, whereas near haploidy (23--29 chromosomes), presence of the Philadelphia chromosome, t(4;11) and abnormalities affecting the short arm of chromosome 9 [abn (9p)] were adverse risk factors. Early responders to therapy, determined by residual marrow infiltration after 8 d of induction therapy, had a good outcome, while the small proportion of patients who did not achieve a complete remission by the end of induction therapy had a poor outcome. A third block of late intensification was shown to improve event-free survival by 8% at 5 years. The effect of these risk factors was not significantly different between those randomized to the third intensification block and those not randomized to a third block.


Incidence, predictors and management of left main coronary artery stent restenosis: a comprehensive review in the era of drug-eluting stents.
International guidelines recommend surgical revascularisation for unprotected left main (ULM) coronary artery disease. The introduction of drug-eluting stents (DES) as an emergency therapy has resulted in increasing numbers of patients having stents placed in ULM. As a consequence, important data on the safety and long-term outcome of PCI for ULM have progressively accumulated over recent years, derived mainly from registries rather than prospective randomised trials. These studies indicate that restenosis of the ULM still represents the main predictor of clinical events following stenting. However, the observed incidence is highly variable amongst the published studies and there is little data about the clinical management of restenosis of stents placed in the ULM. In the present paper we review the available literature regarding ULM restenosis, identify its predictors and suggest an algorithm for optimal management.


Molecular characterisation of Sarcocystis lutrae n. sp. and Toxoplasma gondii from the musculature of two Eurasian otters (Lutra lutra) in Norway.
Sarcocysts were detected in routinely processed histological sections of skeletal muscle, but not cardiac muscle, of two adult male otters (Lutra lutra; Mustelidae) from northern Norway following their post-mortem examination in 1999 and 2000. The sarcocysts were slender, spindle-shaped, up to 970 μm long and 35-70 μm in greatest diameter. The sarcocyst wall was thin (∼ 0.5 μm) and smooth with no visible protrusions. Portions of unfixed diaphragm of both animals were collected at the autopsies and kept frozen for about 14 years pending further examination. When the study was resumed in 2013, the thawed muscle samples were examined for sarcocysts under a stereo microscope, but none could be found. Genomic DNA was therefore extracted from a total of 36 small pieces of the diaphragm from both otters, and samples found to contain Sarcocystidae DNA were used selectively for PCR amplification and sequencing of the nuclear 18S and 28S ribosomal (r) RNA genes and internal transcribed spacer 1 (ITS1) region, as well as the mitochondrial cytochrome b (cytb) and cytochrome c oxidase subunit 1 (cox1) genes. Sequence comparisons revealed that both otters were infected by the same Sarcocystis sp. and that there was no genetic variation (100 % identity) among sequenced isolates at the 18S and 28S rRNA genes (six identical isolates at both loci) or at cox1 (13 identical isolates). PCR products comprising the ITS1 region, on the other hand, had to be cloned before sequencing due to intraspecific sequence variation. A total of 33 clones were sequenced, and the identities between them were 97.9-99.9 %. These sequences were most similar (93.7-96.0 % identity) to a sequence of Sarcocystis kalvikus from the wolverine in Canada, but the phylogenetic analyses placed all of them as a monophyletic sister group to S. kalvikus. Hence, they were considered to represent a novel species, which was named Sarcocystis lutrae. Sequence comparisons and phylogenetic analyses based on sequences of the 18S and 28S rRNA genes and cox1, for which little or no sequence data were available for S. kalvikus, revealed that S. lutrae otherwise was most closely related to various Sarcocystis spp. using birds or carnivores as intermediate hosts. The cox1 sequences of S. lutrae from the otters were identical to two sequences from an arctic fox, which in a previous study had been assigned to Sarcocystis arctica due to a high identity (99.4 %) with the latter species at this gene and a complete identity with S. arctica at three other loci when using the same DNA samples as templates for PCR reactions. Additional PCR amplifications and sequencing of cox1 (ten sequences) and the ITS1 region (four sequences) using four DNA samples from this fox as templates again generated cox1 sequences exclusively of S. lutrae, but ITS1 sequences of S. arctica, and thus confirmed that this arctic fox had acted as intermediate host for both S. arctica and S. lutrae. Based on the phylogenetic placement of S. lutrae, the geographical location of infected animals (otters, arctic fox) and the distribution of carnivores/raptors which may have interacted with them, the white-tailed eagle (Haliaeetus albicilla) seems to be a possible definitive host of S. lutrae. Some of the muscle samples from both otters were shown to harbour stages of Toxoplasma gondii through PCR amplification and sequencing of the entire ITS1 region (five isolates) and/or the partial cytb (eight isolates) and cox1 (one isolate). These sequences were identical to several previous sequences of T. gondii in GenBank. Thus, both otters had a dual infection with S. lutrae and T. gondii.


A health and wellbeing programme for preadolescents in underserved Australian communities: child and stakeholder perspectives.
Social inequities in childhood affect children's health and development. Active In-Betweens is a weekly, healthy lifestyle and outdoor activity after-school programme, tailor-made for preadolescent children (9-12 year olds), incorporating a strengths-based, trauma-informed, co-designed and place-based approach. This study evaluated the extent to which the programme strategies and activities met the anticipated short- to medium-term programme outcomes during its first year of operation in two socio-economically disadvantaged housing communities in New South Wales, Australia. A qualitative case study used data from semi-structured interviews with child participants (n = 11) and key stakeholders (n = 10). A broad range of positive outcomes were described. Children's feedback indicated they had experienced opportunities which facilitated the development of new physical activity skills; new healthy eating experiences and knowledge; positive relationships with peers and facilitators and new connections with neighbourhood programmes and outdoor environments. Stakeholders valued the programme for the positive outcomes they observed among the children and the strong organizational partnerships which resulted. The importance of skilled facilitators to deliver the programme, the engagement of local stakeholders and a long-term commitment to programme delivery, with secure funding to ensure continuity, were clearly identified as integral for effective, sustainable outcomes.


A meta-analysis of temporal changes of response in the placebo arm of surgical randomized controlled trials: an update.
Temporal changes in the placebo arm of randomized controlled trials (RCTs) have not been thoroughly investigated, despite the fact that results of RCTs depend on the comparison between arms. In this update of our earlier systematic review and meta-analysis, we set out to investigate the effect of assessment time and number of visits on the magnitude of change from baseline in the placebo arm of these trials. We used linear mixed-effects models to account for within-trial correlations. Across all 47 trials the magnitude of response in the placebo arm did not change with time (β = -0.0070, 95% CI -0.024, 0.010) or visit (β = -0.033, 95% CI -0.082, 0.017) and remained significantly different from baseline for at least 12 months or seven follow-up visits. Change in the placebo arm in trials with subjective outcomes was large (β0 = 0.68, 95% CI 0.53, 0.82) and relatively constant across time (β = -0.0042, 95% CI -0.024, 0.016) and visit (β = -0.029, 95% CI -0.089, 0.031), whereas in trials with objective outcomes the response was smaller (β0 = 0.28, 95% CI 0.11, 0.46) and diminished with time (β = -0.030, 95% CI -0.050, -0.010), but not with visit (β = -0.099, 95% CI -0.30, 0.11). For trials with assessed outcomes, there was no significant effect of time (β = -0.0071, 95% CI -0.026, 0.011) or visit (β = -0.032, 95% CI -0.33, 0.26); however, these results should be interpreted with caution due to the small number of studies, and high clinical heterogeneity between studies. In trials with pain as an outcome, the improvement was significant (β0 = 0.91, 95% CI 0.75, 1.07), but there was no effect of time (β = -0.013, 95% CI -0.06, 0.03) or visit (β = -0.045, 95% CI -0.16, 0.069), and pain ratings remained significantly different from baseline for 12 months or seven visits. These results are consistent with our previous findings. In trials with subjective outcomes response in the placebo arm remains large and relatively constant for at least a year, which is interesting considering that this is an effect of a single application of an invasive procedure. The lack of effect of time and visit number on subjective outcomes raises further questions regarding whether the observed response is the result of placebo effect or the result of bias.


Towards integrated pest management in red clover seed production.
The development of integrated pest management is hampered by lack of information on how insect pest abundances relate to yield losses, and how pests are affected by control measures. In this study, we develop integrated pest management tactics for Apion spp. weevils (Coleoptera: Brentidae) in seed production of red clover, Trifolium pratense L. We tested a method to forecast pest damage, quantified the relationship between pest abundance and yield, and evaluated chemical and biological pest control in 29 Swedish red clover fields in 2008 and 2011. Pest inflorescence abundance, which had a highly negative effect on yield, could be predicted with pan trap catches of adult pests. In 2008, chemical control with typically one application of pyrethroids was ineffective both in decreasing pest abundances and in increasing yields. In 2011, when chemical control included applications of the neonicotinoid thiacloprid, pest abundances decreased and yields increased considerably in treated field zones. A post hoc analysis indicated that using pyrethroids in addition to thiacloprid was largely redundant. Infestation rates by parasitoids was higher and reached average levels of around 40% in insecticide treated field zones in 2011, which is a level of interest for biological pest control. Based on the data presented, an economic threshold for chemical control is developed, and guidelines are provided on minimum effective chemical pest control.


[Investigation on the health-related quality of life among 411 patients with irritable bowel syndrome].
To evaluate and compare the health-related quality of life (HRQOL) on patients with irritable bowel syndrome (IBS). Following the Rome III Criteria, 411 IBS patients and 430 healthy people were selected as subjects,who were outpatients in Department of Gastroenterology, 2nd Hospital of Xi' an Jiaotong University and Shaanxi Provincial People's Hospital from July 2006 to April 2007. Using the 36-Item Short-Form Health Survey (SF-36). This study compared the SF-36 scale scores of IBS patients with the healthy people. On all of the 8 SF-36 scales, patients with IBS scored significantly lower than healthy people (P < 0.001). Decrements in HRQOL were most predominant in general health perception and role limitations caused by emotional health problem, with scores of 33.5 + 16.9, 40.8 +/- 25.1 respectively. The emotional well-being and energy/fatigue scale scores were also quite low (42.2 +/- 19.3,43.1 +/- 20.2,respectively). They also scored significantly lower on both physical summary. and mental summary scores (P < 0.001). IBS patients were classified into IBS with constipation,IBS with diarrhea, mixed IBS and unsubtyped IBS subgroups, with percentages as 25.3%, 50.1%, 11.2% and 13.4% respectively. IBS patients experienced great impairment in HRQOL. These data offered further insight into the impact of IBS on patient functional status and well-being.


Robotics and urologic reconstructive surgery.
Minimally invasive surgery has made a profound impact on how urologists approach the challenges in reconstruction of the urinary tract. The advent of laparoscopic approaches to reconstructive urology have demonstrated comparable outcomes to open surgery with improved morbidity. The recent adoption of robotic surgery has seen further advancements such as improved visibility and, freedom of movement, and an easier technical learning curve. With these advantages, more reconstructive urology procedures are being performed robotically. Herein, we review reconstructive urology procedures for which robotics have been applied.


The Effect of Housing First on Housing Stability for People with Mental Illness and Low Intellectual Functioning.
Housing First (HF) has been linked to increased tenure in housing for homeless people with mental illness, but the effect of HF on housing stability for people with borderline or lower intellectual functioning has not been examined. This study of homeless adults with mental illness in Toronto, Ontario assessed whether the association between housing stability and HF differed for adults with borderline or lower intellectual functioning, compared to adults with above borderline intellectual functioning. This study included 172 homeless adults with mental illness from the Toronto site of the At Home-Chez Soi randomized trial that compared receiving HF relative to treatment as usual. This sample was divided into two intellectual functioning groups: 1) adults with borderline or lower intellectual functioning (IQ < 85, 16%), and 2) adults with above borderline intellectual functioning (IQ ≥ 85, 84%). We compared these groups by modelling the percentage of days stably housed using a linear multivariable generalized estimating equation and included interaction between treatment and intellectual functioning. An interaction between treatment and time was also included. There were no overall differences in housing stability for individuals with borderline or lower intellectual functioning compared to people with higher than borderline intellectual functioning in either the HF or the treatment as usual groups. This study is the first to demonstrate that for homeless adults with mental illness, borderline or lower intellectual functioning did not significantly affect housing stability. This accentuates the need for more research and potentially wider consideration of their inclusion in housing interventions, such as HF.


Improving EEG Muscle Artifact Removal With an EMG Array.
Removal of artifacts induced by muscle activity is crucial for analysis of the electroencephalogram (EEG), and continues to be a challenge in experiments where the subject may speak, change facial expressions, or move. Ensemble empirical mode decomposition with canonical correlation analysis (EEMD-CCA) has been proven to be an efficient method for denoising of EEG contaminated with muscle artifacts. EEMD-CCA, likewise the majority of algorithms, does not incorporate any statistical information of the artifact, namely, electromyogram (EMG) recorded over the muscles actively contaminating the EEG. In this paper, we propose to extend EEMD-CCA in order to include an EMG array as information to aid the removal of artifacts, assessing the performance gain achieved when the number of EMG channels grow. By filtering adaptively (recursive least squares, EMG array as reference) each component resulting from CCA, we aim to ameliorate the distortion of brain signals induced by artifacts and denoising methods. We simulated several noise scenarios based on a linear contamination model, between real and synthetic EEG and EMG signals, and varied the number of EMG channels available to the filter. Our results exhibit a substantial improvement in the performance as the number of EMG electrodes increase from 2 to 16. Further increasing the number of EMG channels up to 128 did not have a significant impact on the performance. We conclude by recommending the use of EMG electrodes to filter components, as it is a computationally inexpensive enhancement that impacts significantly on performance using only a few electrodes.


An integrated, peptide-based approach to site-specific protein immobilization for detection of biomolecular interactions.
We have developed an integrated solution for the site-specific immobilization of proteins on a biosensor surface, which may be widely applicable for high throughput analytical purposes. The gold surface of a biosensor was coated with an anti-fouling layer of zwitterionic peptide molecules from which leucine zipper peptides protrude. Proteins of interest, the autoantigenic proteins La and U1A, were immobilized via a simple incubation procedure by using the complementary leucine zipper sequence as a genetically fused binding tag. This tag forms a strong coiled-coil interaction that is stable during multiple consecutive measurements and under common regeneration conditions. Visualization of the immobilized proteins of interest via antibody binding with multiplex surface plasmon resonance imaging demonstrated 2.5 times higher binding responses than when these proteins were randomly attached to the surface via the commonly applied activated ester-mediated coupling. The proteins could also be immobilized in a leucine zipper-dependent manner directly from complex mixtures like bacterial lysates, eliminating the need for laborious purification steps. This method allows the production of uniform functional protein arrays by control over immobilized protein orientation and geometry and is compatible with high-throughput procedures.


Reversible modulations of neuronal plasticity by VEGF.
Neurons, astrocytes, and blood vessels are organized in functional "neurovascular units" in which the vasculature can impact neuronal activity and, in turn, dynamically adjust to its change. Here we explored different mechanisms by which VEGF, a pleiotropic factor known to possess multiple activities vis-à-vis blood vessels and neurons, may affect adult neurogenesis and cognition. Conditional transgenic systems were used to reversibly overexpress VEGF or block endogenous VEGF in the hippocampus of adult mice. Importantly, this was done in settings that allowed the uncoupling of VEGF-promoted angiogenesis, neurogenesis, and memory. VEGF overexpression was found to augment all three processes, whereas VEGF blockade impaired memory without reducing hippocampal perfusion or neurogenesis. Pertinent to the general debate regarding the relative contribution of adult neurogenesis to memory, we found that memory gain by VEGF overexpression and memory impairment by VEGF blockade were already evident at early time points at which newly added neurons could not yet have become functional. Surprisingly, VEGF induction markedly increased in vivo long-term potentiation (LTP) responses in the dentate gyrus, and VEGF blockade completely abrogated LTP. Switching off ectopic VEGF production resulted in a return to a normal memory and LTP, indicating that ongoing VEGF is required to maintain increased plasticity. In summary, the study not only uncovered a surprising role for VEGF in neuronal plasticity, but also suggests that improved memory by VEGF is primarily a result of increasing plasticity of mature neurons rather than the contribution of newly added hippocampal neurons.


Complications Within 30 Days of Hand Surgery: An Analysis of 10,646 Patients.
The American College of Surgeons Surgical Quality Improvement Program database collects detailed and validated data on demographics, comorbidities, and 30-day postoperative outcomes of patients undergoing operations in most subspecialties. This dataset has been previously used to quantify complications and identify risk factors in other surgical subspecialties. We sought to determine the incidence of postoperative complications following hand surgery and to identify factors associated with increased risk of complications in order to focus preventive strategies. National Surgical Quality Improvement Program data from 2006 to 2011 were queried using 302 hand-specific Current Procedural Technology codes. Descriptive statistics were calculated for the population, and potential risk factors and patient characteristics were analyzed for their association with complications in the 30-day postoperative period using both univariate and multivariate analyses. There were 208 hand-specific Current Procedural Technology codes represented in the data, and of these, 84 were associated with at least 1 complication. The overall incidence of complications within 30 days of hand surgery was 2.5% (95% confidence interval, 2.2%-2.8%). In univariate analysis, older age, diabetes, chronic obstructive pulmonary disease, congestive heart failure, atherosclerosis, steroids, bleeding disorder, increasing American Society of Anesthesiologists class, increasing wound class, emergency procedure, longer operative time, and preoperative transfusion were associated with significantly higher risk of complications, and local anesthesia and outpatient surgery were associated with lower risk. In the multivariate model, male sex, increasing American Society of Anesthesiologists class, wound class 4, and preoperative transfusion were associated with significantly higher risk, and outpatient surgery was associated with significantly lower risk. The most common complication was surgical-site infection (1.2%). The incidence of complications was low, with overall health status being more important than specific comorbidities in predicting complication risk. This information may be valuable in counseling patients before surgery and in identifying patients at higher risk for complications following hand surgery. Therapeutic III.


Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site.
Mycobacterium tuberculosis is the cause of the world's most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.


Routine drainage of the operative bed following elective distal pancreatectomy does not reduce the occurrence of complications.
Routine drainage of the operative bed following elective pancreatectomy remains controversial. Data specific to distal pancreatectomy (DP) have not been examined in a multi-institutional collaborative. Data from the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project were utilized. The impact of drain placement on development of pancreatectomy-related and overall morbidity were analyzed. Propensity scores for drain placement were calculated, and nearest neighbor matching was used to create a matched cohort. Groups were compared using bivariate and logistic regression analyses. Over 14 months, 761 patients undergoing DP were accrued; 606 were drained. Propensity score matching was possible in 116 patients. Drain and no drain groups were not different with respect to multiple preoperative and operative variables. All pancreatic fistulas (p < 0.01) and overall morbidity (p < 0.05) were more common in patients who received a drain. The placement of a drain did not reduce the incidence of clinically relevant pancreatic fistula nor the need for postoperative procedures. Placement of drains following elective distal pancreatectomy was associated with a higher overall morbidity and pancreatic fistulas. Drains did not reduce intra-abdominal septic morbidity, clinically relevant pancreatic fistulas, nor the need for postoperative therapeutic intervention.


Guiding 3D cell migration in deformed synthetic hydrogel microstructures.
The ability of cells to navigate through the extracellular matrix, a network of biopolymers, is controlled by an interplay of cellular activity and mechanical network properties. Synthetic hydrogels with highly tuneable compositions and elastic properties are convenient model systems for the investigation of cell migration in 3D polymer networks. To study the impact of macroscopic deformations on single cell migration, we present a novel method to introduce uniaxial strain in matrices by microstructuring photo-polymerizable hydrogel strips with embedded cells in a channel slide. We find that such confined swelling results in a strained matrix in which cells exhibit an anisotropic migration response parallel to the strain direction. Surprisingly, however, the anisotropy of migration reaches a maximum at intermediate strain levels and decreases strongly at higher strains. We account for this non-monotonic response in the migration anisotropy with a computational model, in which we describe a cell performing durotactic and proteolytic migration in a deformable elastic meshwork. Our simulations reveal that the macroscopically applied strain induces a local geometric anisotropic stiffening of the matrix. This local anisotropic stiffening acts as a guidance cue for directed cell migration, resulting in a non-monotonic dependence on strain, as observed in our experiments. Our findings provide a mechanism for mechanical guidance that connects network properties on the cellular scale to cell migration behaviour.


Novel sol-gel precursors for thin mesoporous eu(3+)-doped silica coatings as efficient luminescent materials.
Europium(III) ions containing mesoporous silica coatings have been prepared via a solvent evaporation-induced self-assembly (EISA) approach of different single-source precursors (SSPs) in the presence of Pluronic P123 as a structure-directing agent, using the spin-coating process. A deliberate tailoring of the chemical composition of the porous coatings with various Si:Eu ratios was achieved by processing mixtures of tetraethylorthosilicate (TEOS) and Eu(3+)-coordinated SSPs. Small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses demonstrate that the thin metal oxide-doped silica coatings consist of a porous network with a short-range order of the pore structure, even at high europium(III) loadings. Furthermore, luminescence properties were investigated at different temperatures and different degrees of Eu(3+) contents. The photoluminescence spectra clearly show characteristic emission peaks corresponding to the (5)D0 → (7)FJ (J = 0-5) transitions resulting in a red luminescence visible by the eyes, although the films have a very low thickness (150-200 nm).


Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia.
Inflammation, and the subsequent proliferative activity of vascular smooth muscle cells (VSMCs), is one of the major pathophysiological mechanisms associated with neointimal hyperplasia following vascular injury. Although sulfasalazine (SSZ) has been used as an anti-inflammatory and immune-modulatory agent in various inflammatory diseases, its primary targets and therapeutic effects on vascular disease have not yet been determined. We investigated whether SSZ could suppress VSMC growth and prevent neointimal hyperplasia. SSZ was found to have pro-apoptotic and anti-proliferative activity in cultured VSMCs. Unexpectedly, these effects were not mediated by nuclear factor kappa B (NF-kappaB) inhibition, which has been suggested to be the anti-inflammatory mechanism associated with the effects of SSZ. Instead, cell-cycle arrest of the VSMCs was observed, which was mediated by induction of haem oxygenase-1 (HO-1) followed by an increased expression of p21(waf1/Cip1). The underlying mechanism for SSZ-induced HO-1 expression was by reactive oxygen species (ROS)-dependent nuclear translocation and activation of nuclear factor erythroid-2-related factor 2 (Nrf2). In a rat carotid artery balloon injury model, administration of SSZ significantly suppressed neointimal growth. In a series of reverse experiments, inhibition of HO-1 by shRNA, ROS by N-acetylcysteine (NAC) or Nrf2 by dominant-negative Nrf2 abrogated the beneficial effects of SSZ. Our data demonstrate that SSZ inhibits VSMC proliferation in vitro and in vivo through a novel signalling pathway and may be a promising therapeutic option for the treatment of proliferative vascular disease.


Role of Membrane Lipids in the Regulation of Erythrocytic Oxygen-Transport Function in Cardiovascular Diseases.
The composition and condition of membrane lipids, the morphology of erythrocytes, and hemoglobin distribution were explored with the help of laser interference microscopy (LIM) and Raman spectroscopy. It is shown that patients with cardiovascular diseases (CVD) have significant changes in the composition of their phospholipids and the fatty acids of membrane lipids. Furthermore, the microviscosity of the membranes and morphology of the erythrocytes are altered causing disordered oxygen transport by hemoglobin. Basic therapy carried out with the use of antiaggregants, statins, antianginals, beta-blockers, and calcium antagonists does not help to recover the morphofunctional properties of erythrocytes. Based on the results the authors assume that, for the relief of the ischemic crisis and further therapeutic treatment, it is necessary to include, in addition to cardiovascular disease medicines, medication that increases the ability of erythrocytes' hemoglobin to transport oxygen to the tissues. We assume that the use of LIM and Raman spectroscopy is advisable for early diagnosis of changes in the structure and functional state of erythrocytes when cardiovascular diseases develop.


EEG surveillance as a means of extending operability in high risk carotid endarterectomy.
Some patients who have transient ischemic attacks are denied operation because severe occlusive lesions in other extra-cranial arteries may be inappropriately interpreted as constituting an unacceptable surgical risk, or because the lesion is so distal as to make its removal hazardous. Failure of endarterectomy is usually due to incomplete removal of the lesion or to thrombosis upon the frayed intima. Such lesions require excellent visualization and meticulous surgical technique -- not always possible with a shunt. Among 130 consecutive carotid endarterectomies performed under general anesthesia, EEG changes consistent with cerebral ischemia appeared in only nine (7%). These patients required a shunt. In 11 patients normal EEG tracings were obtained during endarterectomy despite contralateral carotid occlusion. None of these patients had a neurological deficit. Continuous EEG monitoring is a reliable method of detecting changes in cerebral perfusion, permits a more meticulous endarterectomy in high-lying lesions without a shunt, and extends operability in high risk patients. Angiographical findings may be an unreliable predictor concerning risk of endarterectomy.


The physics of wind-blown sand and dust.
The transport of sand and dust by wind is a potent erosional force, creates sand dunes and ripples, and loads the atmosphere with suspended dust aerosols. This paper presents an extensive review of the physics of wind-blown sand and dust on Earth and Mars. Specifically, we review the physics of aeolian saltation, the formation and development of sand dunes and ripples, the physics of dust aerosol emission, the weather phenomena that trigger dust storms, and the lifting of dust by dust devils and other small-scale vortices. We also discuss the physics of wind-blown sand and dune formation on Venus and Titan.


Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype.
We and others have recently reported highly efficient liver gene transfer with adeno-associated virus 8 (AAV-8) pseudotypes, i.e., AAV-2 genomes packaged into AAV-8 capsids. Here we studied whether liver transduction could be further enhanced by using viral DNA packaging sequences (inverted terminal repeats [ITRs]) derived from AAV genotypes other than 2. To this end, we generated two sets of vector constructs carrying expression cassettes embedding a gfp gene or the human factor IX (hfIX) gene flanked by ITRs from AAV genotypes 1 through 6. Initial in vitro analyses of gfp vector DNA replication, encapsidation, and cell transduction revealed a surprisingly high degree of interchangeability among the six genotypes. For subsequent in vivo studies, we cross-packaged the six hfIX variants into AAV-8 and infused mice via the portal vein with doses of 5 x 10(10) to 1.8 x 10(12) particles. Notably, all vectors expressed comparably high plasma hFIX levels within a dose cohort over the following 6 months, concurrent with the finding of equivalent vector DNA copy numbers per cell. Partial hepatectomies resulted in approximately 80% drops of hFIX levels and vector DNA copy numbers in all groups, indicating genotype-independent persistence of predominantly episomal vector DNA. Southern blot analyses of total liver DNA in fact confirmed the presence of identical and mostly nonintegrated molecular vector forms for all genotypes. We conclude that, unlike serotypes, AAV genotypes are not critical for efficient hepatocyte transduction and can be freely substituted. This corroborates our current model for AAV vector persistence in the liver and provides useful information for the future design and application of recombinant AAV.