Computer prediction of human thermoregulatory and temperature responses to a wide range of environmental conditions.
A mathematical model for predicting human thermal and regulatory responses in cold, cool, neutral, warm, and hot environments has been developed and validated. The multi-segmental passive system, which models the dynamic heat transport within the body and the heat exchange between body parts and the environment, is discussed elsewhere. This paper is concerned with the development of the active system, which simulates the regulatory responses of shivering, sweating, and peripheral vasomotion of unacclimatised subjects. Following a comprehensive literature review, 26 independent experiments were selected that were designed to provoke each of these responses in different circumstances. Regression analysis revealed that skin and head core temperature affect regulatory responses in a nonlinear fashion. A further signal, i.e. the rate of change of the mean skin temperature weighted by the skin temperature error signal, was identified as governing the dynamics of thermoregulatory processes in the cold. Verification and validation work was carried out using experimental data obtained from 90 exposures covering a range of steady and transient ambient temperatures between 5 degrees C and 50 degrees C and exercise intensities between 46 W/m2 and 600 W/m2. Good general agreement with measured data was obtained for regulatory responses, internal temperatures, and the mean and local skin temperatures of unacclimatised humans for the whole spectrum of climatic conditions and for different activity levels.


A Systematic Study of Online Class Imbalance Learning With Concept Drift.
As an emerging research topic, online class imbalance learning often combines the challenges of both class imbalance and concept drift. It deals with data streams having very skewed class distributions, where concept drift may occur. It has recently received increased research attention; however, very little work addresses the combined problem where both class imbalance and concept drift coexist. As the first systematic study of handling concept drift in class-imbalanced data streams, this paper first provides a comprehensive review of current research progress in this field, including current research focuses and open challenges. Then, an in-depth experimental study is performed, with the goal of understanding how to best overcome concept drift in online learning with class imbalance.


Comparative acceptability of combined and progestin-only injectable contraceptives in Kenya.
We compared 12-month continuation rates, menstrual bleeding patterns and other aspects of acceptability between users of Cyclofem and users of Depo-Provera. The life-table method was used to calculate quarterly continuation rates. In all, 360 Kenyan women were randomly assigned to one of the two contraceptives. User-satisfaction questionnaires were administered at 6 and 12 months or at discontinuation, whichever occurred first. The 1-year continuation rate was 75.4% for Depo-Provera users versus 56.5% for Cyclofem users (p<.001). Main reasons for discontinuation included difficulty making clinic visits (45.1% for Cyclofem vs. 40% for Depo-Provera), menstrual changes (14.1% vs. 12.5%) and nonmenstrual problems (15.5% vs. 12.5%). None of the Depo-Provera users and 8.5% of the Cyclofem users claimed frequency of visits as the main reason for discontinuation. In all, 70.6% of the Depo-Provera users were amenorrheic after 12 months, as were 20.8% of the Cyclofem users. The 1-year continuation rate was higher for Depo-Provera than for Cyclofem. There was no important difference in discontinuation rates because of menstrual problems; the difference mainly reflected the frequency of visits required.


High transfusion ratios are not associated with increased complication rates in patients with severe extremity injuries.
High transfusion ratios of plasma to packed red blood cells (>1:2) have been associated with increased survival and increased complications in patients receiving massive transfusion (MT). We hypothesized that high ratio transfusion would be associated with no survival benefit and increased complications in combat victims with compressible hemorrhage. A retrospective analysis of soldiers injured in the current conflict during 5 years (n = 2,105) who received blood was performed on those with isolated extremity (abbreviated injury scale extremity score > or = 3 and abbreviated injury scale score 0-2 in all other regions) injury comparing those who received a MT with those who did not. Transfusion ratios in the first 24 hours were correlated with outcomes. Injury severity score (14.6 vs. 12.1; p < 0.05), international normalized ratio (1.65 vs. 1.28; p < 0.05), and base deficit (8.0 vs. 3.7; p < 0.05) were higher in the MT group. High transfusion ratios were associated with a trend toward decreased mortality (17.2% vs. 6.9%; p = 0.07) in MT patients and no increased complications (20.7% vs. 26.4%; p > 0.05). In those receiving a non-MT, high ratios were associated with similar mortality (4.8% vs. 3.9%; p > 0.05) and complications (12.4% vs. 9.2%; p > 0.05). Extremity injured patients receiving MT may benefit from high transfusion ratios and do not experience increased complications. No change in mortality or complications was observed in non-MT patients across transfusions ratios. High transfusion ratios are not associated with increased complications in patients with isolated extremity injury regardless of whether a MT is required.


Health risk assessment of electromagnetic fields: a conflict between the precautionary principle and environmental medicine methodology.
The purpose of the precautionary principle is that legal requirements are to be made to safeguard against the possible health risks that have not yet been scientifically established. That a risk is not established cannot, therefore, be used as an excuse for not applying the principle. Yet, that rationale is exactly what is happening in the case of the possible health risks from exposure to electromagnetic fields (EMF). The scientists, representing both the World Health Organization and the European Commission, do not have at all the precautionary principle in mind when they report on health risks. Their starting point is instead to determine whether new research findings have been scientifically established and thus cannot be the basis for an amendment to the existing exposure limits. Uncertain indications of risk are ignored or played down. This approach is in conflict with European Union (EU) law, which requires that the degree of scientific uncertainty should be presented correctly. A thorough examination of the state of research shows many serious indications of possible health risks from exposure very far below existing limits for EMF. Case law, for other types of exposure, also shows that the precautionary principle can be applied on the basis of weaker evidence than that. Our investigation shows that the precautionary principle is not being used for its intended purpose in relation to exposure to EMF. The reason for this position is that decision-makers are being misled by inaccurate risk assessments.


THE CHALLENGE OF DETECTING CLASSICAL SWINE FEVER VIRUS CIRCULATION IN WILD BOAR (SUS SCROFA): SIMULATION OF SAMPLING OPTIONS.
Classical swine fever (CSF) is one of the most important viral diseases of domestic pigs ( Sus scrofa domesticus) and wild boar ( Sus scrofa ). For at least 4 decades, several European Union member states were confronted with outbreaks among wild boar and, as it had been shown that infected wild boar populations can be a major cause of primary outbreaks in domestic pigs, strict control measures for both species were implemented. To guarantee early detection and to demonstrate freedom from disease, intensive surveillance is carried out based on a hunting bag sample. In this context, virologic investigations play a major role in the early detection of new introductions and in regions immunized with a conventional vaccine. The required financial resources and personnel for reliable testing are often large, and sufficient sample sizes to detect low virus prevalences are difficult to obtain. We conducted a simulation to model the possible impact of changes in sample size and sampling intervals on the probability of CSF virus detection based on a study area of 65 German hunting grounds. A 5-yr period with 4,652 virologic investigations was considered. Results suggest that low prevalences could not be detected with a justifiable effort. The simulation of increased sample sizes per sampling interval showed only a slightly better performance but would be unrealistic in practice, especially outside the main hunting season. Further studies on other approaches such as targeted or risk-based sampling for virus detection in connection with (marker) antibody surveillance are needed.


Cross-site evaluation of the Alliance to Reduce Disparities in Diabetes: clinical and patient-reported outcomes.
Alliance programs implemented multilevel, multicomponent programs inspired by the chronic care model and aimed at reducing health and health care disparities for program participants. A unique characteristic of the Alliance programs is that they did not use a fixed implementation strategy common to programs using the chronic care model but instead focused on strategies that met local community needs. Using data provided by the five programs involved in the Alliance, this evaluation shows that of the 1,827 participants for which baseline and follow-up data were available, the program participants experienced significant decreases in hemoglobin A1c and blood pressure compared with a comparison group. A significant time by study group interaction was observed for hemoglobin A1c as well. Over time, more program participants met quality indicators for hemoglobin A1c and blood pressure. Those participants who attended self-management classes and experienced more resources and support for self-management attained more benefit. In addition, program participants experienced more diabetes competence, increased quality of life, and improvements in diabetes self-care behaviors. The cost-effectiveness of programs ranged from $23,161 to $61,011 per quality-adjusted life year. In sum, the Alliance programs reduced disparities and health care disparities for program participants.


Applications of musculoskeletal ultrasonography in pediatric patients.
Ultrasonography is an excellent adjunct to other musculoskeletal imaging tools utilized in the pediatric population and in some instances offers advantages over CT and MRI. It permits dynamic examination of anatomic structures and assists in guiding minimally invasive procedures. In the lower extremity, ultrasonography assists in screening for such disorders as developmental dysplasia of the hip and in detecting slipped capital femoral epiphysis and femoral acetabular impingement. In the neonatal spine, ultrasonography can identify unossified vertebral arches. Among other applications in the upper extremity, ultrasonography may be used in the evaluation and examination of peripheral nerve injuries and is a preferred modality for imaging the shoulder in infants with neonatal brachial plexus palsy. It is also considered an optimal adjunct for administration of botulinum toxin-A in children with cerebral palsy. The portability, relative low cost, lack of radiation, and absence of known contraindications enhances the utility of ultrasonography in pediatric orthopaedics.


Combined use of intersubject and intrasubject controls to distinguish treatment versus patient effect in retrospective studies.
Clinical researchers seek to eliminate specific subject attributes from becoming confounding variables to distinguish a treatment effect from an underlying patient effect. In prospective studies, the random assignment of subjects into experimental groups results in the equal distribution of subject attributes, thereby eliminating them as confounding variables. Retrospective study designs, often used in prosthodontics research, preclude the random assignment of subjects. This article describes the application of a standard research design that combines the use of intersubject and intrasubject controls to compensate for the potential imbalance in subject attributes in retrospective clinical studies. This approach should help prevent clinical investigators from declaring differences between experimental groups when, in fact, no differences exist.


The initial stages of melting of graphene between 4000 K and 6000 K.
Graphene and its analogues have some of the highest predicted melting points of any materials. Previous work estimated the melting temperature for freestanding graphene to be a remarkable 4510 K. However, this work relied on theoretical methods that do not accurately account for the role of bond breaking or complex bonding configurations in the melting process. Furthermore, experiments to verify these high melting points have been challenging. Practical applications of graphene and carbon nanotubes at high temperatures will require a detailed understanding of the behavior of these materials under these conditions. Therefore, we have used reliable ab initio molecular dynamics calculations to study the initial stages of melting of freestanding graphene monolayers between 4000 and 6000 K. To accommodate large defects, and for improved accuracy, we used a large 10 × 10 periodic unit cell. We find that the system can be heated up to 4500 K for 18 ps without melting, and 3-rings and short lived broken bonds (10-rings) are observed. At 4500 K, the system appears to be in a quasi-2D liquid state. At 5000 K, the system is starting to melt. During the 20 ps simulation, diffusion events are observed, leading to the creation of a 5775 defect. We calculate accurate excitation energies for these configurations, and the pair correlation function is presented. The modified Lindemann criterion was calculated. Graphene and nanotubes together with other proposed high melting point materials would be interesting candidates for experimental tests of melting in the weightless environment of space.


Acupuncture for menopausal hot flashes: clinical evidence update and its relevance to decision making.
There is conflicting evidence on the efficacy and effectiveness of acupuncture for menopausal hot flashes. This article synthesizes the best available evidence for when women are considering whether acupuncture might be useful for menopausal hot flashes. We searched electronic databases to identify randomized controlled trials and systematic reviews of acupuncture for menopausal hot flushes. The overall evidence demonstrates that acupuncture is effective when compared with no treatment, but not efficacious compared with sham. Methodological challenges such as the complex nature of acupuncture treatment, the physiological effects from sham, and the significant efficacy of placebo therapy generally in treating hot flashes all impact on these considerations. Acupuncture improves menopausal hot flashes compared with no treatment; however, not compared with sham acupuncture. This is also consistent with the evidence that a range of placebo interventions improve menopausal symptoms. As clinicians play a vital role in assisting evidence-informed decisions, we need to ensure women understand the evidence and can integrate it with personal preferences. Some women may choose acupuncture for hot flashes, a potentially disabling condition without long-term adverse health consequences. Yet, women should do so understanding the evidence, and its strengths and weaknesses, around both effective medical therapies and acupuncture. Likewise, cost to the individual and the health system needs to be considered in the context of value-based health care.


3D absolute shape measurement of live rabbit hearts with a superfast two-frequency phase-shifting technique.
This paper presents a two-frequency binary phase-shifting technique to measure three-dimensional (3D) absolute shape of beating rabbit hearts. Due to the low contrast of the cardiac surface, the projector and the camera must remain focused, which poses challenges for any existing binary method where the measurement accuracy is low. To conquer this challenge, this paper proposes to utilize the optimal pulse width modulation (OPWM) technique to generate high-frequency fringe patterns, and the error-diffusion dithering technique to produce low-frequency fringe patterns. Furthermore, this paper will show that fringe patterns produced with blue light provide the best quality measurements compared to fringe patterns generated with red or green light; and the minimum data acquisition speed for high quality measurements is around 800 Hz for a rabbit heart beating at 180 beats per minute.


Effect of the Egyptian propolis on the hepatic antioxidant defense and pro-apoptotic p53 and anti-apoptotic bcl2 expressions in aflatoxin B1 treated male mice.
Aflatoxins are potent hepatotoxic due to their role in producing reactive oxygen species and consequently peroxidative damage. Propolis is a honey bee product known for its antioxidant capacity. The aim of this study was to verify the antioxidant effect of the Egyptian propolis extract (EPE) against aflatoxin B1 (AFB1)-induced hepatotoxicity in mice. Forty eight male mice were divided: first, second and third groups were used as control receiving saline, olive oil and EPE respectively, fourth was AFB1 group, fifth and sixth received EPE post or pre AFB1 treatment, respectively. EPE was given as (0.2mg/kg) 3 times a week. AFB1 was given as a single dose (0.25μg/kg). After 2 weeks, the mice were scarified and biochemical, histopathological and immunohistochemical investigations were assessed. EPE has a high content of total phenolics and alkaloids. The inhibitory concentration 50 (IC50) value for DPPH radical scavenging was 1353.8μg/mL. Pretreatment with EPE improved AFB1-induced hepatotoxicity represented in lowering alanine transaminase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, lipid peroxidation and pro-apoptotic p53 expression to 33.48±1.98 IU/ml, 53.00±2.37 IU/ml, 123.50±2.02 IU/ml, 76.50±2.66mg/dl, 54.00±3.03mg/dl, 2.22±0.14 nmol/g and 4.31±2.1 cells/field and raising the reduced glutathione, catalase, superoxide dismutase and anti-apoptotic bcl2 expression to 3.37±1.65 nmol/g, 4.92±0.25 nmol/g, 57±0.91UI/g and 39.7±5.9 cells/field which all had non-significant differences with the control, respectively. In conclusion, EPE can attenuate aflatoxin B1-induced hepatotoxicity in mice.


Honokiol Decreases Lung Cancer Metastasis through Inhibition of the STAT3 Signaling Pathway.
Lung cancer is the leading cause of cancer death in the United States. Metastasis to lymph nodes and distal organs, especially brain, leads to severe complications and death. Preventing lung cancer development and metastases is an important strategy to reduce lung cancer mortality. Honokiol (HNK), a natural compound present in the extracts of magnolia bark, has a favorable bioavailability profile and recently has been shown to readily cross the blood-brain barrier. In the current study, we evaluated the antimetastatic effects of HNK in both the lymph node and brain mouse models of lung tumor metastasis. We tested the efficacy of HNK in preventing 18 H2030-BrM3 cell (brain-seeking human lung tumor cells) migration to lymph node or brain. In an orthotopic mouse model, HNK significantly decreased lung tumor growth compared with the vehicle control group. HNK also significantly reduced the incidence of lymph node metastasis and the weight of mediastinal lymph nodes. In a brain metastasis model, HNK inhibits metastasis of lung cancer cells to the brain to approximately one third of that observed in control mice. We analyzed HNK's mechanism of action, which indicated that its effect is mediated primarily by inhibiting the STAT3 pathway. HNK specifically inhibits STAT3 phosphorylation irrespective of the mutation status of EGFR, and knockdown of STAT3 abrogated both the antiproliferative and the antimetastatic effects of HNK. These observations suggest that HNK could provide novel chemopreventive or therapeutic options for preventing both lung tumor progression and lung cancer metastasis. Cancer Prev Res; 10(2); 133-41. ©2016 AACR.


Aqueous Geochemical Controls on the Sestonic Microbial Community in Lakes Michigan and Superior.
Despite being the largest freshwater lake system in the world, relatively little is known about the sestonic microbial community structure in the Laurentian Great Lakes. The goal of this research was to better understand this ecosystem using high-throughput sequencing of microbial communities as a function of water depth at six locations in the westernmost Great Lakes of Superior and Michigan. The water column was characterized by gradients in temperature, dissolved oxygen (DO), pH, and other physicochemical parameters with depth. Mean nitrate concentrations were 32 μmol/L, with only slight variation within and between the lakes, and with depth. Mean available phosphorus was 0.07 μmol/L, resulting in relatively large N:P ratios (97:1) indicative of P limitation. Abundances of the phyla Actinobacteria, Bacteroidetes, Cyanobacteria, Thaumarchaeota, and Verrucomicrobia differed significantly among the Lakes. Candidatus Nitrosopumilus was present in greater abundance in Lake Superior compared to Lake Michigan, suggesting the importance of ammonia-oxidating archaea in water column N cycling in Lake Superior. The Shannon diversity index was negatively correlated with pH, temperature, and salinity, and positively correlated with DO, latitude, and N2 saturation. Results of this study suggest that DO, pH, temperature, and salinity were major drivers shaping the community composition in the Great Lakes.


The Effects of Twitter Sentiment on Stock Price Returns.
Social media are increasingly reflecting and influencing behavior of other complex systems. In this paper we investigate the relations between a well-known micro-blogging platform Twitter and financial markets. In particular, we consider, in a period of 15 months, the Twitter volume and sentiment about the 30 stock companies that form the Dow Jones Industrial Average (DJIA) index. We find a relatively low Pearson correlation and Granger causality between the corresponding time series over the entire time period. However, we find a significant dependence between the Twitter sentiment and abnormal returns during the peaks of Twitter volume. This is valid not only for the expected Twitter volume peaks (e.g., quarterly announcements), but also for peaks corresponding to less obvious events. We formalize the procedure by adapting the well-known "event study" from economics and finance to the analysis of Twitter data. The procedure allows to automatically identify events as Twitter volume peaks, to compute the prevailing sentiment (positive or negative) expressed in tweets at these peaks, and finally to apply the "event study" methodology to relate them to stock returns. We show that sentiment polarity of Twitter peaks implies the direction of cumulative abnormal returns. The amount of cumulative abnormal returns is relatively low (about 1-2%), but the dependence is statistically significant for several days after the events.


Results of percutaneous transluminal coronary angioplasty in unstable angina and non-Q-wave myocardial infarction. Observations from the TIMI IIIB Trial.
This report describes the results of percutaneous transluminal coronary angioplasty (PTCA) in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB Investigation. PTCA was performed before hospital discharge in 444 of 1473 patients with either unstable angina pectoris or non-Q-wave myocardial infarction (NQWMI) enrolled in TIMI IIIB. Angiographic success was observed in 96.1% of patients. For the entire cohort, the cumulative incidences of death and infarction at 1 year were 2.0% and 8.2%, respectively. The periprocedural incidence of myocardial infarction was 2.7%; emergency coronary bypass surgery, 1.4%; and death, 0.5%. By 1 year of follow-up, 122 patients (28.0%, Kaplan-Meier) had an additional revascularization procedure, 75 (61.5%) had PTCA only, 30 (24.6%) had coronary bypass surgery only, and 17 (13.9%) had both procedures. The results of PTCA were not improved by routine pretreatment with intravenous tissue plasminogen activator (TPA). Periprocedural myocardial infarction was more common among patients receiving TPA than placebo (odds ratio [OR], 2.19; P = .03) and among those with unstable angina than those with NQWMI (OR, 15.5; P = .007). No difference in outcome was observed when patients were analyzed according to age (OR, 1.06; P = .092) or sex (OR, 1.54; P = .51). Variables predictive of poor outcome were PTCA within the first 24 hours of enrollment, PTCA site being the left anterior descending coronary artery, and unsuccessful angiography. In TIMI IIIB, PTCA was performed for patients with unstable angina and NQWMI with a very high rate of angiographic success and a low incidence of complications. By 1 year, repeat revascularization was performed in 28.0% of patients. Routine pretreatment with thrombolysis did not enhance outcome.


BEES: Bayesian Ensemble Estimation from SAS.
Many biomolecular complexes exist in a flexible ensemble of states in solution that is necessary to perform their biological function. Small-angle scattering (SAS) measurements are a popular method for characterizing these flexible molecules because of their relative ease of use and their ability to simultaneously probe the full ensemble of states. However, SAS data is typically low dimensional and difficult to interpret without the assistance of additional structural models. In theory, experimental SAS curves can be reconstituted from a linear combination of theoretical models, although this procedure carries a significant risk of overfitting the inherently low-dimensional SAS data. Previously, we developed a Bayesian-based method for fitting ensembles of model structures to experimental SAS data that rigorously avoids overfitting. However, we have found that these methods can be difficult to incorporate into typical SAS modeling workflows, especially for users that are not experts in computational modeling. To this end, we present the Bayesian Ensemble Estimation from SAS (BEES) program. Two forks of BEES are available, the primary one existing as a module for the SASSIE web server and a developmental version that is a stand-alone Python program. BEES allows users to exhaustively sample ensemble models constructed from a library of theoretical states and to interactively analyze and compare each model's performance. The fitting routine also allows for secondary data sets to be supplied, thereby simultaneously fitting models to both SAS data as well as orthogonal information. The flexible ensemble of K63-linked ubiquitin trimers is presented as an example of BEES' capabilities.


Two terms--one meaning: the conundrum of contemporary nomenclature in autism.
Autism as a diagnostic construct in the last decade has undergone a process of rapid evolution in the way that it is operationalized. A by-product of the important conceptual shift is that we have been left with two terms, autistic disorder and Asperger's disorder, that point to the same thing. The existence of two terms that cannot be clearly delineated results in confusion and an added element in an already anxiety-laden mix for all those trying to come to terms with the concept of autism. This paper moves beyond contemporary arguments of whether autistic disorder and Asperger's disorder are different entities and uses a case study to consider the mechanism of the confusion caused, and highlight the importance of referent clarity. A review of sources in journals and texts related to the topic is included to complement the progressive review of the case study as the clients move through a 1-hour initial consult. The current diagnostic criteria are ambiguous posing the risk of confusion to parents, clinicians, and researchers. Nurses have an important role in assisting parents' construction of a unified concept of autism clinically, and through research. This paper moves beyond merely acknowledging the confusion that exists by considering the nature of the confusion, and through sharing the experience of one possible way of navigating it.


Uncovering a mitochondrial unfolded protein response in corals and its role in adapting to a changing world.
The Anthropocene will be characterized by increased environmental disturbances, leading to the survival of stress-tolerant organisms, particularly in the oceans, where novel marine diseases and elevated temperatures are re-shaping ecosystems. These environmental changes underscore the importance of identifying mechanisms which promote stress tolerance in ecologically important non-model species such as reef-building corals. Mitochondria are central regulators of cellular stress and have dedicated recovery pathways including the mitochondrial unfolded protein response, which increases the transcription of protective genes promoting protein homeostasis, free radical detoxification and innate immunity. In this investigation, we identify a mitochondrial unfolded protein response in the endangered Caribbean coral Orbicella faveolata, by performing in vivo functional replacement using a transcription factor (Of-ATF5) originating from a coral in the model organism Caenorhabditis elegans. In addition, we use RNA-seq network analysis and transcription factor-binding predictions to identify a transcriptional network of genes likely to be regulated by Of-ATF5 which is induced during the immune challenge and temperature stress. Overall, our findings uncover a conserved cellular pathway which may promote the ability of reef-building corals to survive increasing levels of environmental stress.


Comparative analysis of three hyperthermophilic GH1 and GH3 family members with industrial potential.
Beta-glucosidases (BGLs) are enzymes of great potential for several industrial processes, since they catalyze the cleavage of glucosidic bonds in cellobiose and other short cellooligosaccharides. However, features such as good stability to temperature, pH, ions and chemicals are required characteristics for industrial applications. This work aimed to provide a comparative biochemical analysis of three thermostable BGLs from Pyrococcus furiosus and Thermotoga petrophila. The genes PfBgl1 (GH1 from P. furiosus), TpBgl1 (GH1 from T. petrophila) and TpBgl3 (GH3 from T. petrophila) were cloned and proteins were expressed in Escherichia coli. The purified enzymes are hyperthermophilic, showing highest activity at temperatures above 80°C at acidic (TpBgl3 and PfBgl1) and neutral (TpBgl1) pHs. The BGLs showed greatest stability to temperature mainly at pH 6.0. Activities using a set of different substrates suggested that TpBgl3 (GH3) is more specific than GH1 family members. In addition, the influence of six monosaccharides on BGL catalysis was assayed. While PfBgl1 and TpBgl3 seemed to be weakly inhibited by monosaccharides, TpBgl1 was activated, with xylose showing the strongest activation. Under the conditions tested, TpBgl1 showed the highest inhibition constant (Ki=1100.00mM) when compared with several BGLs previously characterized. The BGLs studied have potential for industrial use, specifically the enzymes belonging to the GH1 family, due to its broad substrate specificity and weak inhibition by glucose and other saccharides.


Development and application of an instrument for the measurement of directional emittance of blackbody cavities.
A measurement technique for determining the directional spectral emittance of blackbody cavities was developed and subsequently applied to several specific cavity geometries. The emittance was deduced from cavity reflectance measurements performed with a laser energy source (10.6 micro) and an integrating hemi-ellipsoid. It was demonstrated that this technique is capable of providing highly precise emittance values with a resolution of five significant figures for high emittance cavities. The emittances of four specific cavity configurations were measured. One of these, an elongated off-axis cone with an entrance lip, gave emittances greater than 0.99999 when coated with nominally specularly reflecting or nominally diffusely reflecting black paints. The emittances of this cavity were on the order of 0.95 in the absence of a coating, the actual emittances of the cavity surfaces being approximately 0.05. Three other cavities with length-to-diameter ratios of three were also studied. These include a cylinder, cone, and off-axis cone having internal surfaces which were coated with black paints. Although the measured emittances were not so high as those for the 12.45-L/D off-axis cone, the level of blackness that was determined is sufficient for most engineering applications.


Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism.
The inflammasomes are intracellular complexes that have an important role in cytosolic innate immune sensing and pathogen defense. Inflammasome sensors detect a diversity of intracellular microbial ligands and endogenous danger signals and activate caspase-1, thus initiating maturation and release of the proinflammatory cytokines interleukin-1β and interleukin-18. These events, although crucial to the innate immune response, have also been linked to the pathology of several inflammatory and autoimmune disorders. The natural isothiocyanate sulforaphane, present in broccoli sprouts and available as a dietary supplement, has gained attention for its antioxidant, anti-inflammatory, and chemopreventive properties. We discovered that sulforaphane inhibits caspase-1 autoproteolytic activation and interleukin-1β maturation and secretion downstream of the nucleotide-binding oligomerization domain-like receptor leucine-rich repeat proteins NLRP1 and NLRP3, NLR family apoptosis inhibitory protein 5/NLR family caspase-1 recruitment domain-containing protein 4 (NAIP5/NLRC4), and absent in melanoma 2 (AIM2) inflammasome receptors. Sulforaphane does not inhibit the inflammasome by direct modification of active caspase-1 and its mechanism is not dependent on protein degradation by the proteasome or de novo protein synthesis. Furthermore, sulforaphane-mediated inhibition of the inflammasomes is independent of the transcription factor nuclear factor erythroid-derived 2-like factor 2 (Nrf2) and the antioxidant response-element pathway, to which many of the antioxidant and anti-inflammatory effects of sulforaphane have been attributed. Sulforaphane was also found to inhibit cell recruitment to the peritoneum and interleukin-1β secretion in an in vivo peritonitis model of acute gout and to reverse NLRP1-mediated murine resistance to Bacillus anthracis spore infection. These findings demonstrate that sulforaphane inhibits the inflammasomes through a novel mechanism and contributes to our understanding of the beneficial effects of sulforaphane.


Validation of "Signs of Inflammation in Children that Kill" (SICK) score for immediate non-invasive assessment of severity of illness.
To validate the SICK scoring system's ability to differentiate between individuals with higher and lower probabilities of death We performed a one year two-centre prospective evaluation of all children aged between one month and 12 years referred to the Paediatric team at St Stephens Hospital in Delhi and admitted to the Paediatric Department at West Middlesex University Hospital in London. We calculated SICK scores at presentation and correlated them with subsequent in-hospital mortality. We used discrimination by areas under receiver operating characteristic (ROC) curves to measure performance. We prospectively evaluated 3895 children in Delhi and 1473 children in London. The areas under the ROC curves were 84.8% in Delhi, 81.0% in London and 84.1% (95% CI 77.4-90.8%) for combined data. Hosmer-Lemeshow goodness of fit for the combined data was good (Hosmer-Lemeshow Chi-square=2.13 (p=0.345). We propose the SICK score as a useful triage tool at initial presentation and highlight its particular suitability for resource poor settings.


Flow profiles near receding three-phase contact lines: influence of surfactants.
The dynamics of wetting and dewetting is largely determined by the velocity field near the contact lines. For water drops it has been observed that adding surfactant decreases the dynamic receding contact angle even at a concentration much lower than the critical micelle concentration (CMC). To better understand why surfactants have such a drastic effect on drop dynamics, we constructed a dedicated setup on an inverted microscope, in which an aqueous drop is held stationary while the transparent substrate is moved horizontally. Using astigmatism particle tracking velocimetry, we track the 3D displacement of the tracer particles in the flow. We study how surfactants alter the flow dynamics near the receding contact line of a moving drop for capillary numbers in the order of 10-6. Even for surfactant concentrations c far below the critical micelle concentration (c ≪ CMC) Marangoni stresses change the flow drastically. We discuss our results first in a 2D model that considers advective and diffusive surfactant transport and deduce estimates of the magnitude and scaling of the Marangoni stress from this. Modeling and experiment agree that a tiny gradient in surface tension of a few μN m-1 is enough to alter the flow profile significantly. The variation of the Marangoni stress with the distance from the contact line suggests that the 2D advection-diffusion model has to be extended to a full 3D model. The effect is ubiquitous, since surfactant is present in many technical and natural dewetting processes either deliberately or as contamination.


Color-tuning method by filling porous alumina membrane using atomic layer deposition based on metal-dielectric-metal structure.
A novel and convenient color-tuning method by filling the porous alumina membrane (PAM) based on metal-dielectric-metal structure is proposed. The pore sizes of PAM as well as the thickness of TiO2 films, deposited by atomic layer deposition, causes various reflection colors due to multilayer interference effects. Overlapping films on top and within the PAM structure can be observed with a scanning electron microscope and will be used to show the change of the effective refractive index of the PAM composite layer. The color-tuning method resulting in changing the dynamics of the PAM layer can be widely applied in fields such as micro-optics, microstructures, nanomaterials, and micro/nanotechnology.


Azimuthal registration of image sequences affected by nonuniform rotation distortion.
Imaging modalities that use a mechanically rotated endoscopic probe to scan a tubular volume, such as an artery, often suffer from image degradation due to nonuniform rotation distortion (NURD). In this paper, we present a new method to align individual lines in a sequence of images. It is based on dynamic time warping, finding a continuous path through a cost matrix that measures the similarity between regions of two frames being aligned. The path represents the angular mismatch corresponding to the NURD. The prime advantage of this novel approach compared to earlier work is the line-to-line continuity, which accurately captures slow intraframe variations in rotational velocity of the probe. The algorithm is optimized using data from a clinically available intravascular optical coherence tomography (OCT) instrument in a realistic vessel phantom. Its efficacy is demonstrated on an in vivo recording, and compared with conventional global rotation block matching. Intravascular OCT is a particularly challenging modality for motion correction because, in clinical situations, the image is generally undersampled, and correlation between the speckle in different lines or frames is absent. The algorithm can be adapted to ingest data frame-by-frame, and can be implemented to work in real time.


Electromagnetic characterisation of MR RF coils using the transmission-line modelling method.
The Transmission-Line Modelling (TLM) method is applied to the electromagnetic characterisation of RF coils and samples for magnetic resonance imaging MRI. Theoretical verification was performed using a simple surface coil. Experimental verification was performed using Alderman-Grant and birdcage coils constructed for use on a 7 T micro-imaging system. The modelling method enabled electromagnetic characteristics of frequency response, electromagnetic field generation, energy stored and power loss to be determined. From these parameters, coil resonant modes, B1 field profiles, voltages, currents, quality factor (Q), pi/2 pulse length, and the equivalent lumped-element circuit components of resistance, inductance and capacitance were calculated. Equations are presented that enable a comprehensive electromagnetic characterisation of the RF coil and sample to be achieved based on the results of the TLM simulations. The use of the TLM method is extended to include the design of safe arbitrary multi-nuclear pulse sequences such that the specific absorption rate (SAR) of tissue, and RF coil component safety limits are not exceeded.


Brevetoxin-2 induces an inflammatory response in an alveolar macrophage cell line.
Brevetoxins, the algal toxins produced by Karenia brevis during red tide blooms, adversely impact health following ingestion or inhalation. Inhalation of brevetoxins results in a variety of acute symptoms including coughing, wheezing, and shortness of breath. Analysis of manatee lungs following death by purported brevetoxicosis has identified brevetoxin accumulation within macrophages, with pathological manifestions of lung congestion, inflammation, and edema. The goals of this work were to specifically examine effects of brevetoxin-2 on alveolar macrophages, a key cell in responding to toxins in the lung, as well as to determine if brevetoxin-2 results in an inflammatory response and/or direct cytotoxicity. Exposure of an alveolar macrophage cell line (MH-S) to an environmentally and physiologically relevant dose of brevetoxin-2 (0.5microg/ml) did not significantly alter cellular growth over a 24h time period. However, exposure of MH-S cells to brevetoxin-2 for 6h increased phagocytosis of latex beads, increased secretion of interleukin (IL)-2, IL-4, and tumor necrosis factor-alpha, and decreased secretion of IL-5. Very few changes were seen in gene expression following 3 or 6h exposure to brevetoxin-2. These results show that brevetoxin-2 induced an immune response indicative of inflammation in an alveolar macrophage cell line, indicating that inhalation of brevetoxin-2 may lead to lung inflammation through an alveolar macrophage-initiated pathway.


Fungal morphogenesis: cell wall construction in Mucor rouxii.
An autoradiographic study revealed two different patterns of cell wall constructioni associated with two types of morphogenesis in Mucor rouxii. In hyphae, the cell wall was preferentially synthesized in the apical region; these cylindrical walls seemed to be generated by a sharply descending gradient of wall synthesis radiating from the apex. In spherical cells (germinating spores, yeast cells), wall formation occurred largely, if not entirely, in uniformly dispersed fashion over the entire cell periphery.


Anxiety buffer disruption: Worldview threat, death thought accessibility, and worldview defense among low and high posttraumatic stress symptom samples.
Decades of research suggest that people are able to function effectively in the world and maintain mental health and well-being, at least in part, by relying on effective sociocultural anxiety buffer systems to shield against the awareness of death. However, according to anxiety buffer disruption theory, posttraumatic stress reflects anxiety buffer disruption, signaling that sociocultural belief systems have been rendered unable to buffer the individual against death awareness. As such, we would not expect to see the normal responses to death awareness meant to bolster and defend those belief systems in participants with posttraumatic stress. To test these hypotheses, we screened for posttraumatic stress in U.S. participants (n = 4,150) and recruited individuals with low (n = 193) and high (n = 205) posttraumatic stress symptoms. Each group was randomly assigned to a worldview-threat or -support condition, followed by a standardized measure of death-thought accessibility (DTA) and worldview defense. In the nonthreat (worldview-support) condition, individuals with high (vs. low) posttraumatic stress had elevated DTA. Further, among individuals with low posttraumatic stress, worldview threat (vs. -support) increased DTA, which in turn mediated an increase in worldview defense; however, among those with high posttraumatic stress, worldview threat did not increase DTA and its effect on worldview defense was substantially reduced. These findings supported the present hypotheses derived from anxiety buffer disruption theory, are important for understanding the existential dimension of posttraumatic stress, and may have implications for mental health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Supraicosahedral indenyl cobaltacarboranes.
13-vertex indenyl cobaltacarboranes with 4,1,6-, 4,1,10- and 4,1,2-CoC(2)B(10) architectures have been synthesised by reduction of the corresponding closo carborane and metallation with an {(eta-C(9)H(7))Co} fragment. Variants of the 4,1,6-isomer were prepared with no, one and two methyl groups on cage C atoms, whilst 4,1,2-species were obtained both with two methyl groups and a trimethylene tether on the cage C atoms. Thermolysis of the 4,1,6-isomers yielded the corresponding 4,1,8-isomers, which in turn were converted to 4,1,12-isomers by thermolysis at higher temperatures. Alternatively relatively mild heating of the 4,1,10-isomer led to the 4,1,12-isomer directly. Products were characterised by mass spectrometry, (1)H and (11)B NMR spectroscopies and, in most cases, elemental analysis, and nine compounds were studied crystallographically. The 4,1,6-, 4,1,8-, 4,1,10- and 4,1,12- species have docosahedral cages whilst the 4,1,2-species are henicosahedral. In the structural studies attention focused on the orientation of the indenyl ligand with respect to the carborane ligand since this affords experimental information on the metal-cage bonding through the structural indenyl effect. There is a general tendency for the indenyl ligand to adopt orientations in which the ring junction C atoms lie trans to cage B atoms. In cases where the orientation is not compromised by the presence of a non-H substituent on the face of the carborane there is generally good agreement between the experimental orientation and that computed by DFT calculations for the related naphthalene ferracarboranes (eta-C(10)H(8))FeC(2)B(10)H(12). The presence of C-methyl substituents in the indenyl cobaltacarboranes tends to override this preference except in the case of 1,6-Me(2)-4-(eta-C(9)H(7))-4,1,6-closo-CoC(2)B(10)H(10) where the indenyl ligand instead is forced to incline away from the cage methyl groups. In DCM solution the 4,1,6-, 4,1,8-, 4,1,10- and 4,1,12- isomers of (eta-C(9)H(7))CoC(2)B(10)H(12) exhibit two, stepwise, 1-electron reductions assigned to Co(III)/Co(II)/Co(I) couples at less negative potentials than those of the corresponding Cp compounds. Moreover these reductions are easier for those isomers (4,1,6- and 4,1,10-) in which there are two cage C atoms in the carborane face to which the metal atom is bound. By spectroelectrochemical and EPR measurements it is concluded that the reductions of these indenyl cobaltacarboranes are largely metal-based.


Novel approaches to the design of halftone masks for analog lithography.
We report novel approaches to the design of halftone masks for analog lithography. The approaches are derived from interferometric phase contrast. In a first step we show that the interferometric phase-contrast method with detour holograms can be reduced into a single binary mask. In a second step we introduce the interferometric phase-contrast method by interference of the object wavefront with the conjugate object wavefront. This method also allows for a design of a halftone mask. To use kinoform holograms as halftone phase masks, we show in a third step the combination of the zeroth-order phase-contrast technique with the interferometric phase-contrast method.


Associations between trichostrongylid worm egg count and productivity measures in Dorper lambs.
Two flocks of pure bred Dorper lambs were managed separately according to sex (283 ewe lambs and 212 ram lambs) in southern Western Australia. Faecal sample collection, weighing and body condition assessments were performed for each lamb on 2 occasions, specifically pre-weaning (approximately 14 weeks of age) and post-weaning (approximately 9 months of age). Body condition score (BCS) was assessed using a scale of 1 (very thin, emaciated) to 5 (excessively fat). Faecal worm egg counts (WECs) were measured using a modified McMaster technique and larval cultures were performed to identify trichostrongylid nematode genera present. Eye muscle and c-site fat depths were measured using ultrasound at post-weaning. Lambs received an abamectin anthelmintic treatment at weaning (18 weeks of age). Worm egg count data was assessed for normality of data distribution and homogeneity of variance. This data was transformed using log(10)(WEC+25) to stabilise variances between groups prior to statistical analyses and general linear models were used to assess relationships between WEC and productivity measures. Mean WECs were 564 eggs per gram of faeces (EPG) and 514 EPG at pre- and post-weaning in the ewe flock and 552 EPG and 480 EPG at pre- and post-weaning in the ram flock. Teladorsagia (Ostertagia) circumcincta, Trichostrongylus spp. and Oesophagostomum spp. larvae were identified. No lambs with WEC<500 EPG pre-weaning had WEC>1000 EPG post-weaning. Ewe and ram lambs with WEC>1000 EPG at pre-weaning were 42 (12-145 95% CI) and 37 (9-153) times more likely to have WEC>1000 EPG at post-weaning than lambs with WEC 501-1000 EPG at pre-weaning. There were no significant relationships between WEC and live weight in the ram flock, while relationships between WEC and live weight were inconsistent in the ewe lamb flock. There was no relationship between WEC and eye muscle or c-site fat depth. Significant negative relationships between WEC and BCS were identified at pre- and post-weaning for both flocks. Lambs with WEC<500 EPG had 0.19-0.61 higher mean BCS than lambs with WEC>1000 EPG at pre- and post-weaning. In conclusion, high WEC was associated with lower body condition in Dorper lambs, however the relationship between WEC and live weight was inconsistent and there was no effect on eye muscle depth.


Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling.
The glycoprotein VI (GPVI)-Fc receptor (FcR) gamma-chain complex, a key activatory receptor for collagen on platelet surface membranes, is constitutively associated with the Src family kinases Fyn and Lyn. Molecular cloning of GPVI has revealed the presence of a proline-rich domain in the sequence of GPVI cytoplasmic tail which has the consensus for interaction with the Src homology 3 (SH3) domains of Fyn and Lyn. A series of in vitro experiments demonstrated the ability of the SH3 domains of both Src kinases to bind the proline-rich domain of GPVI. Furthermore, depletion of the proline-rich domain in GPVI (Pro(-)-GPVI) prevented binding of Fyn and Lyn and markedly reduced phosphorylation of FcR gamma-chain in transiently transfected COS-7 cells, but did not affect the association of the gamma-chain with GPVI. Jurkat cells stably transfected with wild type GPVI show robust increases in tyrosine phosphorylation and intracellular Ca2+ in response to the snake venom convulxin that targets GPVI. Importantly, convulxin is not able to activate cells transfected with Pro(-)-GPVI, even though the association with the immunoreceptor tyrosine-based activation motif-containing chains is maintained. These findings demonstrate that the proline-rich domain of GPVI mediates the association with Fyn/Lyn via their SH3 domain and that this interaction initiates activation signals through GPVI.


Description of a novel technique for ultrasound-based planning for gynaecological 3D brachytherapy and comparison between plans of this technique and 2D with fluoroscopy.
With the purpose of implementing a way to obtain volumes from ultrasound axial images, a novel method for 3D gynaecologic brachytherapy was assessed, with a 3D-printed attachment for a commercial stepper (for prostate brachytherapy). It allowed the acquisition of a transabdominal axial image series by ultrasound; these images were uploaded to a treatment planning system where high-risk clinical tumour volume (HR-CTV) and risk organs were contoured. A dose administration plan was developed with orthogonal X-ray images (0° and 270° incidences), using International Commission on Radiation Units and Measurements (ICRU) 38 points. The same plan was applied in the ultrasound images' sequence and their respective volumes; differences were noted. In the 20 cases analysed, with a given point A dose, its corresponding dose delivered to 90% of HR-CTV percentage was highly variable (mean = 104.2, SD = 26.01). There is a significant variation of this percentage when point A falls outside the HR-CTV than when it falls inside (p < 0.00001). There is a significant correlation in terms of the bladder point dose ICRU 38 and the Maximum dose to 2cc of organ or target volume (D2cc) bladder (p = 0.021); however, there is no such correlation when we relate the rectum point dose ICRU 38 to the D2cc rectum (p = 0.327). There was a negative correlation between HR-CTV and D2cc bladder and D2cc rectum; both were statistically significant. There were significant differences comparing ICRU points and dose to prescription and organ at risk volumes, pointing out that there is room for optimisation of plans using the latter technique. So, it is proposed to further test this image modality and compare it to other imaging techniques that allow the creation of volumes, such as computed tomography or magnetic resonance imaging.


Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells.
The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial-mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 µM of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 µM. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 µM of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin.


Enhanced form birefringence of metal nanoparticles with anisotropic shell mediated by localized surface plasmon resonance.
We have prepared optically birefringence materials consisting of an isotropic core of metal nanoparticle and an anisotropic shell of amorphous oxide. The sample shows an enhanced optical birefringence in a wavelength-selective way. The sample was prepared by depositing amorphous iron oxide thin films on top of the silver nanoparticles using the oblique deposition technique. This results in ellipsoidal shell of amorphous iron oxide surrounding a silver nanoparticle. The form birefringence appears because of the anisotropic shape of shells; the refractive index for the light polarized parallel to the elongation direction of ellipsoid is different from that for the light polarized perpendicularly. Moreover, the rotation of polarization plane is significantly enhanced at around the wavelength of localized surface plasmon resonance (LSPR). The difference in refractive index between two optical axes is as large as 0.34 for a 600 nm light, which is more than twice of typical birefringence crystal calcite (0.14 for visible light). It is speculated that the anisotropic shell induces the dependence of LSPR wavelength on the polarization direction of the incident light, which causes the polarization dependence of refractive index through the Kramers-Kronig relation.


Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.
Equine hepacivirus (EqHV) in equids represents the closest homologue to hepatitis C virus (HCV) infecting humans. A majority of HCV infected patients develop a chronic course of infection leading to liver fibrosis, cirrhosis and liver failure. However, in horses mostly transient mild subclinical infections are reported for EqHV to date. EqHV can be involved in chronic liver diseases of horses. Biochemical parameters in serum samples were measured. Viral load was determined using qPCR. Next generation sequencing (NGS) of serum was performed. Liver tissue was stained with haematoxylin and eosin and analysed for viral RNA with fluorescent in situ-hybridization. The horse showed symptoms of severe hepatopathy and was chronically infected with EqHV. Viral RNA was detectable in the liver during disease. To rule out other infectious agents NGS was performed and showed the highest abundance for EqHV. The identified virus sequence was similar to other circulating equine hepaciviruses. EqHV can be associated with liver disease in horses. Whether it causes the disease or contributes in a multifactorial manner needs further investigation.


Pulse width shaping of passively mode-locked soliton fiber laser via polarization control in carbon nanotube saturable absorber.
We report the continuous control of the pulse width of a passively mode-locked fiber laser via polarization state adjustment in a single-walled carbon nanotube saturable absorber (SWCNT-SA). The SWCNT, coated on the side-polished fiber, was fabricated with optimized conditions and used for stable mode-locking of the fiber laser without Q-switching instabilities for any polarization state of the laser intra-cavity. The 3-dB spectral bandwidth of the mode-locked pulses can be continuously tuned from 1.8 nm to 8.5 nm with the polarization control for a given laser cavity length and applied pump power. A pulse duration varying from 470 fs to 1.6 ps was also observed with a change in the spectral bandwidth. The linear and the nonlinear transmission properties of the SA were analyzed, and found to exhibit different modulation depths depending on the input polarization state in the SA. The largest modulation depth of the SA was observed at the polarization state of the transverse electric mode that delivers shortest pulses at the laser output.


A unified model of the pathophysiology of bipolar disorder.
This work provides an overview of the most consistent alterations in bipolar disorder (BD), attempting to unify them in an internally coherent working model of the pathophysiology of BD. Data on immune-inflammatory changes, structural brain abnormalities (in gray and white matter), and functional brain alterations (from neurotransmitter signaling to intrinsic brain activity) in BD were reviewed. Based on the reported data, (1) we hypothesized that the core pathological alteration in BD is a damage of the limbic network that results in alterations of neurotransmitter signaling. Although heterogeneous conditions can lead to such damage, we supposed that the main pathophysiological mechanism is traceable to an immune/inflammatory-mediated alteration of white matter involving the limbic network connections, which destabilizes the neurotransmitter signaling, such as dopamine and serotonin signaling. Then, (2) we suggested that changes in such neurotransmitter signaling (potentially triggered by heterogeneous stressors onto a structurally-damaged limbic network) lead to phasic (and often recurrent) reconfigurations of intrinsic brain activity, from abnormal subcortical-cortical coupling to changes in network activity. We suggested that the resulting dysbalance between networks, such as sensorimotor networks, salience network, and default-mode network, clinically manifest in combined alterations of psychomotricity, affectivity, and thought during the manic and depressive phases of BD. Finally, (3) we supposed that an additional contribution of gray matter alterations and related cognitive deterioration characterize a clinical-biological subgroup of BD. This model may provide a general framework for integrating the current data on BD and suggests novel specific hypotheses, prompting for a better understanding of the pathophysiology of BD.


Role of the gut microbiota in the development of various neurological diseases.
In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.


Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney.
Reactive oxygen species (ROS) production induced by α,β-dicarbonyl compounds and advanced glycation end products causes renal dysfunction in patients with type 2 diabetes and metabolic syndrome. Hydrogen-rich water (HRW) increases the H2 level in blood and tissues, thus reducing oxidative stress in animals as well as humans. In this study, we investigated the effects of HRW on glucose- and α,β-dicarbonyl compound-induced ROS generation in vitro and in vivo. Kidney homogenates from Wistar rats were incubated in vitro with glucose and α,β-dicarbonyl compounds containing HRW, following which ROS levels were measured. In vivo animal models of metabolic syndrome, SHR.Cg-Leprcp/NDmcr rats, were treated with HRW for 16 weeks, following which renal ROS production and plasma and renal α,β-dicarbonyl compound levels were measured by liquid chromatograph mass spectrometer. HRW inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Furthermore, SHR.Cg-Leprcp/NDmcr rats treated with HRW showed a 34% decrease in ROS production. Moreover, their renal glyoxal, methylglyoxal, and 3-deoxyglucosone levels decreased by 81%, 77%, and 60%, respectively. Positive correlations were found between renal ROS levels and renal glyoxal (r = 0.659, p = 0.008) and methylglyoxal (r = 0.782, p = 0.001) levels. These results indicate that HRW inhibits the production of α,β-dicarbonyl compounds and ROS in the kidneys of SHR.Cg-Leprcp/NDmcr rats. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.


Paradoxical surrogate markers of dental injury-induced pain in the mouse.
Dental pain, including toothache, is one of the most prevalent types of orofacial pain, causing severe, persistent pain that has a significant negative effect on quality of life, including eating disturbances, mood changes, and sleep disruption. As the primary cause of toothache pain is injury to the uniquely innervated dental pulp, rodent models of this injury provide the opportunity to study neurobiological mechanisms of tissue injury-induced persistent pain. Here we evaluated behavioral changes in mice with a dental pulp injury (DPI) produced by mechanically exposing the pulp to the oral environment. We monitored the daily life behaviors of mice with DPI, including measures of eating, drinking, and movement. During the first 48 hours, the only parameter affected by DPI was locomotion, which was reduced. There was also a significant short-term decrease in the amount of weight gained by DPI animals that was not related to food consumption. As cold allodynia is frequently observed in individuals experiencing toothache pain, we tested whether mice with DPI demonstrate an aversion to drinking cold liquids using a cold-sucrose consumption test. Surprisingly, mice with DPI increased their consumption of sucrose solution, to over 150% of baseline, regardless of temperature. Both the weight loss and increased sucrose intake in the first 2 days of injury were reversed by administration of indomethacin. These findings indicate that enhanced sucrose consumption may be a reliable measure of orofacial pain in rodents, and suggest that alterations in energy expenditure and motivational behaviors are under-recognized outcomes of tooth injury.


Machine learning approaches to predict lupus disease activity from gene expression data.
The integration of gene expression data to predict systemic lupus erythematosus (SLE) disease activity is a significant challenge because of the high degree of heterogeneity among patients and study cohorts, especially those collected on different microarray platforms. Here we deployed machine learning approaches to integrate gene expression data from three SLE data sets and used it to classify patients as having active or inactive disease as characterized by standard clinical composite outcome measures. Both raw whole blood gene expression data and informative gene modules generated by Weighted Gene Co-expression Network Analysis from purified leukocyte populations were employed with various classification algorithms. Classifiers were evaluated by 10-fold cross-validation across three combined data sets or by training and testing in independent data sets, the latter of which amplified the effects of technical variation. A random forest classifier achieved a peak classification accuracy of 83 percent under 10-fold cross-validation, but its performance could be severely affected by technical variation among data sets. The use of gene modules rather than raw gene expression was more robust, achieving classification accuracies of approximately 70 percent regardless of how the training and testing sets were formed. Fine-tuning the algorithms and parameter sets may generate sufficient accuracy to be informative as a standalone estimate of disease activity.


Proteome analysis of cultured fibroblasts from type 1 diabetic patients and normal subjects.
Protein profiling of diabetic tissues could provide useful biomarkers for early diagnosis, therapeutic targets, and disease response markers. Cultured fibroblasts are a useful in vitro model for proteome analysis and study of the molecular mechanisms involved in diabetes. The objective of the study was to isolate and characterize the proteins of cultured fibroblasts, obtained by skin biopsy, from long-term type 1 diabetic patients without complications and age- and sex-matched normal subjects as controls. Proteins were separated by two-dimensional electrophoresis (2-DE), and the gel images were qualitatively and quantitatively analyzed. Protein identification was performed by matrix-assisted laser desorption/ionization mass spectrometry. Reproducible protein maps of fibroblasts from diabetic and healthy subjects were obtained. A total of 125 protein spots were isolated and identified, among them 27 proteins not previously reported in published human fibroblast 2-DE maps, including 20 proteins never reported previously in the literature in human skin fibroblasts. Quantitative analyses revealed six protein spots differentially expressed in the fibroblasts from the diabetic vs. the control subjects (P < 0.05), representing glycolytic enzymes and structural proteins. An increase of triosephosphate I isomerase of two splice isoforms of pyruvate kinase and alpha-actinin 4 and a decrease of tubulin-beta2 and splice isoform 2 of tropomyosin beta-chain were detected. We generated 2-DE reference maps of the proteome of human skin fibroblasts from both normal and uncomplicated type 1 diabetic patients. Differences in glycolytic enzymes and structural proteins were found. The functional implications of the identified proteins are discussed.


Face shields for infection control: A review.
Face shields are personal protective equipment devices that are used by many workers (e.g., medical, dental, veterinary) for protection of the facial area and associated mucous membranes (eyes, nose, mouth) from splashes, sprays, and spatter of body fluids. Face shields are generally not used alone, but in conjunction with other protective equipment and are therefore classified as adjunctive personal protective equipment. Although there are millions of potential users of face shields, guidelines for their use vary between governmental agencies and professional societies and little research is available regarding their efficacy.


Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin, on experimental reflux oesophagitis in rats.
Protective effect of quercetin and alpha-tocopherol on experimental reflux oesophagitis in rats was investigated. Rats received quercetin, (100 mg/kg), alpha-tocopherol (16 mg/kg), omeprazole (30 mg/kg) given at 1 h prior to surgery. Quercetin and alpha-tocopherol significantly inhibited the oesophagitis index to 1.33+/-0.12 (P<0.001) and 1.83+/-0.14 (P<0.001) respectively, as compare to control group 3.5+/-0.21. Further, acid and pepsin out put of gastric contents were significantly decreased in treated groups. Indeed, quercetin significantly inhibited the lipid peroxidation (from 0.69+/-0.05 to 0.43+/-0.04 nmol of malonyldialdehyde (MDA)/mg protein) (P<0.001) and increased in levels of catalase to 29.5+/-2.7 units of catalase activity/mg protein and superoxide dismutase (SOD) to 92.4+/-10.5 units/mg protein (P<0.001). The alpha-tocopherol and omperazole showed significant inhibition in lipid peroxidation (0.34+/-0.02 and 0.38+/-0.01) (P<0.01) and enhanced the activities of catalase (34.3+/-3.6 and 31.5+/-3.4) (P<0.01) and SOD (87.3+/-9.2 and 76.60+/-6.9) activity. Quercetin and alpha-tocopherol treated group significantly increased the glutathione level to 36.5+/-2.78 (P<0.01) and 32.1+/-2.34 (P<0.05) respectively. However, it altered the elevated levels of sialic acid and hexose contents in oesophageal tissue. Indeed, quercetin significantly decreased the elevated plasma histamine content (P<0.05). Quercetin and alpha-tocopherol significantly attenuated the elevated level of collagen in oesophageal tissue as of the omeprazole. The results suggest that antioxidants could attenuate the severity of reflux oesophagitis and prevent the oesophageal mucosal damage and validate its therapeutic use in gastroesophageal reflux disease.


Responses to air temperature and soil moisture of growth of four dominant species on sand dunes of central Inner Mongolia.
Little attention has been paid to how four dominant shrub species distributed in semi-arid areas respond to the combined effects of temperature and water supply. Seedlings of four species were grown in a glasshouse for eight weeks at air temperatures of 12.5/22.5, 15/25, 17.5/27.5, and 20/30 degrees C (night/day) and with water supplies of 37.5, 75, 112.5, and 150 mm per month. When temperatures were 17.5/27.5 and 20/30 degrees C relative growth rate (RGR) decreased for Artemisia ordosica, A. sphaerocephala, and Hedysarum laeve but not for Caragana korshinskii. RGR increased with increasing water availability for all four species and most treatments. In response to changing water availability, the RGR tended to correlate mainly with the physiological trait (net assimilation rate, NAR) and with dry matter allocation traits (below-ground to above-ground dry matter and leaf mass ratio). A higher ratio of below to above-ground dry matter for all four species under most treatments (0.3-1.7) and water-use efficiency (1.4-9.2 g kg(-1)) may explain how all four species survive drought. Higher temperatures may be harmful to A. ordosica and A. sphaerocephala, under current precipitation levels (average 75 mm per month from mid-June to mid-August). These findings support the proposal that A. ordosica mixed with C. korshinskii will prove optimal for re-vegetation of degraded areas of the Ordos plateau.


Nutritional control of growth and development in yeast.
Availability of key nutrients, such as sugars, amino acids, and nitrogen compounds, dictates the developmental programs and the growth rates of yeast cells. A number of overlapping signaling networks--those centered on Ras/protein kinase A, AMP-activated kinase, and target of rapamycin complex I, for instance--inform cells on nutrient availability and influence the cells' transcriptional, translational, posttranslational, and metabolic profiles as well as their developmental decisions. Here I review our current understanding of the structures of the networks responsible for assessing the quantity and quality of carbon and nitrogen sources. I review how these signaling pathways impinge on transcriptional, metabolic, and developmental programs to optimize survival of cells under different environmental conditions. I highlight the profound knowledge we have gained on the structure of these signaling networks but also emphasize the limits of our current understanding of the dynamics of these signaling networks. Moreover, the conservation of these pathways has allowed us to extrapolate our finding with yeast to address issues of lifespan, cancer metabolism, and growth control in more complex organisms.


Effects of valsartan and amlodipine on oxidative stress in type 2 diabetic patients with hypertension: a randomized, multicenter study.
Oxidative stress plays an important role in the pathogenesis and progression of diabetic complications and antagonists of renin-angiotensin system and amlodipine have been reported previously to reduce oxidative stress. In this study, we compared the changes in oxidative stress markers after valsartan and amlodipine treatment in type 2 diabetic patients with hypertension and compared the changes in metabolic parameters. Type 2 diabetic subjects with hypertension 30 to 80 years of age who were not taking antihypertensive drugs were randomized into either valsartan (n = 33) or amlodipine (n = 35) groups and treated for 24 weeks. We measured serum nitrotyrosine levels as an oxidative stress marker. Metabolic parameters including serum glucose, insulin, lipid profile, and urine albumin and creatinine were also measured. After 24 weeks of valsartan or amlodipine treatment, systolic and diastolic blood pressure decreased, with no significant difference between the groups. Both groups showed a decrease in serum nitrotyrosine (7.74 ± 7.30 nmol/L vs. 3.95 ± 4.07 nmol/L in the valsartan group and 8.37 ± 8.75 nmol/L vs. 2.68 ± 2.23 nmol/L in the amlodipine group) with no significant difference between the groups. Other parameters including glucose, lipid profile, albumin-to-creatinine ratio, and homeostasis model assessment of insulin resistance showed no significant differences before and after treatment in either group. Valsartan and amlodipine reduced the oxidative stress marker in type 2 diabetic patients with hypertension.


Efficient blue light emitting materials based on m-carborane-anthracene dyads. Structure, photophysics and bioimaging studies.
Efficient monosubstitution of the non-iodinated, mono-iodinated and di-iodinated m-carborane cluster at one Ccluster has led to the preparation of three single organic molecule-carborane dyads (4-6), which exhibited exceptional fluorescence properties with quantum yield values of 100% in solution, for all of them, with maxima around 415 nm, which correspond to the locally excited state (LE) emission. These results suggest that simply linking the m-carborane fragment to one anthracene unit through a CH2 spacer produces a significant enhancement of the fluorescence in the final fluorophore, probably due to the free rotation of the anthracene linked to the Ccluster. Besides, the presence of one or two iodine atoms linked to boron atoms does not cause any influence on the photophysical properties of the dyads, as it is confirmed by TD-DFT calculations. Notably, the three conjugates show good fluorescence efficiency in the aggregate state with quantum yields in the range of 19-23%, which could be ascribed to the presence of CH2, particularly for 4, and the iodine atoms in 5 and 6, which prevent π-π stacking. All these results indicate that our dyads are extremely good emitters in solution while maintaining the emission properties in the aggregate state. Crystal packing, fingerprint plot analysis, and TD-DFT calculations for the three compounds support these results. Confocal microscopy studies show that 6 is the best-internalized compound by HeLa cells via endocytosis, although 4 and 5 also presented a high fluorescence intensity emission. Moreover, due to the blue emission, this compound is an excellent candidate to be applied as a fluorescent dye in bioimaging studies.


Identification of platelet proteins that bind alloantibodies and autoantibodies.
We have used the techniques of radioimmunoprecipitation (RIP) and Western blot to identify the membrane proteins that bind certain alloantibodies. Anti-PlA1 sera precipitated two bands, corresponding to platelet glycoproteins IIb and III, whether or not calcium was present during the procedure. By Western blot, this antibody bound only glycoprotein III. Anti-PlA1 serum does not precipitate proteins from the platelets of a patient with Glanzmann's thrombasthenia. Two monoclonal antibodies reacting with lymphocyte HLA antigens, as well as sera from highly allosensitized patients, precipitated bands of 38,500 and 13,500 daltons. These bands correspond to the molecular weights of the two subunits of the HLA antigen, as it has been described for other cell types. The patients' sera also precipitated a protein of 72,000 daltons from some platelets. The sera of two patients with quinidine-induced thrombocytopenia precipitated a 138,000-dalton band (glycoprotein Ib-alpha) in the presence of quinidine. The purified IgG antibody from one patient did not require other plasma factors to bind to platelets in the presence of quinidine, while purified antibody from a second patient required plasma factors other than, or in addition to von Willebrand factor. Although several sera from patients with idiopathic thrombocytopenic purpura (ITP) were tested, only one precipitated membrane proteins by the RIP method; this serum identified binding proteins corresponding to glycoproteins IIb and III.


A comparison of total calcium, corrected calcium, and ionized calcium concentrations as indicators of calcium homeostasis among hypoalbuminemic dogs requiring intensive care.
(1) To evaluate whether total calcium (tCa) correlates with ionized calcium (iCa) in hypoalbuminemic dogs; (2) to evaluate whether calcium adjusted for albumin (Alb), or total protein (TP), or both accurately predict iCa concentrations and hence can be used to monitor calcium homeostasis in critically ill hypoalbuminemic dogs; and (3) to evaluate factors associated with any potential discrepancy in calcium classification between corrected total and ionized values. Prospective observational clinical study. Small animal intensive care unit in a veterinary medical teaching hospital. Twenty-eight client-owned dogs with hypoalbuminemia. None. iCa was determined using ion-specific electrode methodology, on heparinized plasma. The tCa concentration was adjusted for Alb and TP using published equations. In total 29% (8/28) of the hypoalbuminemic, critically ill dogs in this study were hypocalcemic at intensive care unit admission, as determined by iCa measurement. Corrected calcium values failed to accurately classify calcium status in 67.9% and 64.3% of cases, according to whether the Alb-adjusted or TP-adjusted values, respectively, were used. The sensitivity and specificity of the tCa to evaluate hypocalcemia was 100% and 47%, respectively. The sensitivity and specificity of the correction formulae were 37.5% and 79% for the Alb-adjusted values and 37.5% and 74% for TP-adjusted values. tCa overestimated the presence of hypocalcemia and underestimated the presence of normocalcemia, while corrected calcium values overestimated the presence of normocalcemia and underestimated the presence of hypocalcemia. Calcium homeostasis in hypoalbuminemic critically ill dogs should be evaluated by iCa concentrations rather than tCa or calcium adjusted for Alb or TP. Given that tCa has 100% sensitivity for detecting hypocalcemia in this population it is recommended that all hypoalbuminemic and critically ill patients with low tCa should be evaluated with an iCa measurement.


Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies.
The clinical outcome of hepatitis B virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure, depending on the success or failure of immune response to HBV. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.


Evidence that peptidoleukotriene is a prerequisite for antigen-dependent thromboxane synthesis in IgG1-passively sensitized guinea pig lungs.
Lungs from guinea pigs passively sensitized with an affinity-purified IgG1 antibody produce both leukotriene (LT)D4 and thromboxane (Tx)B2 upon ex vivo antigen challenge. This study was undertaken to determine the possibility of endogenously generated peptido-LTs being a prerequisite for Tx synthesis. In immunoglobulin G1-sensitized lungs, exogenous LTD4 induced TxB2 production with a median effective dose of 4.1 nM, whereas the response to LTE4, LTB4 or platelet-activating factor was relatively weak. Although LTC4 was as potent as LTD4 in stimulating TxB2 generation, LTC4's dose-response curve was shifted significantly to the right by AT-125, an irreversible gamma-glutamyl transpeptidase inhibitor, suggesting that at least a part of LTC4 sensitized lungs with antigen (0.01-30 micrograms/ml ovalbumin) for 20 min precipitated a significant amount of LTD4 production. The levels of LTD4 range from 8 to 26 nM (without taking LTD4 recovery into consideration). This level is 2- to 7-fold greater than the median effective dose value observed with exogenous LTD4. Moreover, pretreatment of sensitized lungs with ICI-198,615 a specific LTD4 antagonist, blocked equally both antigen (IC50 = 0.01 microM)- and LTD4 (IC50 = 0.017 microM)-induced TxB2 production. When sensitized lung fragments were treated with 5 mM AT-125, ICI-198,615 was effective in preventing not only antigen-but also LTC4-dependent production of TxB2 (IC50 = 0.018 and 0.021 microM, respectively). In contrast, neither WEB-2086, a platelet-activating factor antagonist, nor pyrilamine, a histamine antagonist, inhibited antigen and LTD4 responses (IC50 greater than 30 microM). Unlike its effect on antigen response, ICI-198,615 was unable to block Ca2+ ionophore-induced TxB2 production.2


Evaluation of Two Junctional Tourniquets Used on the Battlefield: Combat Ready Clamp® versus SAM® Junctional Tourniquet.
Junctional hemorrhage (i.e., between the trunk and limbs) are too proximal for a tourniquet and difficult to compress. These hemorrhages are responsible for 20% of preventable deaths by bleeding on the battlefield. The majority of these involve the groin area. Devices allowing a proximal compression for arterial axes have been recently developed. The purpose of this study was to compare the use of two junctional- tourniquet models, the Combat Ready Clamp (CRoC®) and the SAM® Junctional Tourniquet (SJT), in simulated out-of-hospital trauma care when tourniquets were ineffective to stop the arterial flow. During our clinical study, 84 healthy volunteers wearing battle dress performed a physical exercise to come approximate the operational context. The volunteers were randomly divided into two groups according to the device (the CRoC or SJT) used as supplement to a tourniquet self-applied to the root of the thigh. The primary study end point was the complete interruption of popliteal arterial flow, measured with Doppler auscultation. Time to effectiveness and subjective questionnaire data to evaluate the devices' application were also collected. Junctional device effectiveness was almost 90% for both the CRoC and the SJT, and did not differ between them, either used with a tourniquet (ρ = .36) or alone (ρ = .71). The time to effectiveness of the SJT was significantly shorter than that of the CRoC (ρ = .029). The SJT and the CRoC were equally effective. The SJT was faster to apply and preferred by the users. Our study provides objective evidence to the French Tactical Casualty Care Committee for improving junctional hemorrhage treatment.


Highly-controllable imprinted polymer nanoshell at the surface of silica nanoparticles based room-temperature phosphorescence probe for detection of 2,4-dichlorophenol.
This paper reports a facile and general method for preparing an imprinted polymer thin shell with Mn-doped ZnS quantum dots (QDs) at the surface of silica nanoparticles by stepwise precipitation polymerization to form the highly-controllable core-shell nanoparticles (MIPs@SiO2-ZnS:Mn QDs) and sensitively recognize the target 2,4-dichlorophenol (2,4-DCP). Acrylamide (AM) and ethyl glycol dimethacrylate (EGDMA) were used as the functional monomer and the cross-linker, respectively. The MIPs@SiO2-ZnS:Mn QDs had a controllable shell thickness and a high density of effective recognition sites, and the thickness of uniform core-shell 2,4-DCP-imprinted nanoparticles was controlled by the total amounts of monomers. The MIPs@SiO2-ZnS:Mn QDs with a shell thickness of 45 nm exhibited the largest quenching efficiency to 2,4-DCP by using the spectrofluorometer. After the experimental conditions were optimized, a linear relationship was obtained covering the linear range of 1.0-84 μmol L(-1) with a correlation coefficient of 0.9981 and the detection limit (3σ/k) was 0.15 μmol L(-1). The feasibility of the developed method was successfully evaluated through the determination of 2,4-DCP in real samples. This study provides a general strategy to fabricate highly-controllable core-shell imprinted polymer-contained QDs with highly selective recognition ability.


Combined removal of organic micropollutants and ammonium in reactive barriers developed for managed aquifer recharge.
Groundwater is an important drinking water resource. To ensure clean drinking water, managed aquifer recharge (MAR) could be an attractive solution when recharging with treated wastewater. The installation of reactive barriers, e.g. with compost or other organic materials at MAR facilities, may improve pollutant removal. To link pollutant transformation processes and microbiology in reactive barriers, we simulated infiltration through different sand-compost mixtures using laboratory columns with depth-specific sampling of water and barrier material. We also evaluated the effect of inoculation with activated sludge. Our focus was on the simultaneous removal of organic micropollutants and nitrogen species, with parallel monitoring of the development of microbial communities. During 17 weeks of operation, the columns were fed with synthetic wastewater containing five organic micropollutants (1-2 µg/L each) and ammonium (2 mg N/L). Unique communities developed in the columns in relation to barrier material, with high effects of compost addition and minor effect of inoculation. Removal of the micropollutant paracetamol (acetaminophen) occurred in all columns, while sulfamethoxazole was only removed in columns with 50% compost. By contrast, limited removal was observed for sulfadiazine, carbamazepine and diuron, with the latter two displaying transient removal, attributed sorption. Oxygen was depleted within the top few cm of the columns when compost was present, but this was sufficient to remove all ammonium through nitrification. The fate of accumulated nitrate at deeper layers depended on the fraction of compost, with more compost leading to removal of nitrate by denitrification, but also by dissimilatory nitrate reduction to ammonium, hampering the overall nitrogen removal efficiency. Introducing compost as reactive barrier in MAR facilities has a large effect on the microbial communities and processes, but whether it will provide overall cleaner water to the underlying aquifer is uncertain and will depend very much on the type of pollutant.


The roles of LSD1-mediated epigenetic modifications in maintaining the pluripotency of bladder cancer stem cells.
Bladder cancer stem cells (BCSCs) may be the source for tumorigenesis, recurrence, and resistance to treatment of bladder carcinoma. Lysine-specific demethylase 1 (LSD1) plays crucial roles in the pluripotency maintenance of embryonic and cancer stem cells through the epigenetical modification of the associated genes, such as the regulation of bivalent domain at regulatory region of the developmental genes. It has also been found that LSD1 expression is elevated in clinical bladder cancer tissues compared with in normal tissues, and LSD1 knock down could significantly result in the suppression of bladder cancer cell line proliferation. Furthermore, results from our unpublished study showed that elevated levels of LSD1 are highly associated with the grades of the cancers, and more interestingly, LSD1 was mainly presented in the basal layer of bladder carcinoma tissue, co-localizing with BCSCs. Thus we hypothesized that LSD1 is mainly expressed in BCSCs in bladder cancer tissues, and LSD1-mediated epigenetic modification of the developmental genes may play important roles in maintaining pluripotency of BCSCs. LSD1 may become a reliable prognostic indicator and could serve as a molecular target in bladder cancer therapy.


Efficacy of electro-acupuncture in chronic plantar fasciitis: a randomized controlled trial.
The aim of the study was to investigate the efficacy of electro-acupuncture coupled with conventional treatments and compare it with the efficacy of conventional treatments alone in patients with chronic plantar fasciitis. Thirty patients with chronic refractory plantar fasciitis were randomly assigned to two groups. Subjects in the control group received five weeks of conventional treatments, including stretching exercise, shoe modification and rescue analgesics. Subjects in the acupuncture group received the same treatments plus ten sessions of electro-acupuncture twice weekly. Endpoints included a success rate determined by a minimum of a 50% decrease in Visual Analog Scale (VAS) and Foot Function Index (FFI). At the end of treatment, VAS decreased significantly from 6.00 ± 1.69 to 1.89 ± 1.59 and from 6.27 ± 2.34 to 5.40 ± 2.26 in the acupuncture and control groups, respectively. FFI decreased significantly only in the acupuncture group (p < 0.05). Subjects in the acupuncture group obtained higher success rates than those in control group (80% and 13.3%, respectively). FFI in the acupuncture group was better than those in the control group (p < 0.001). At the sixth week follow-up, subjects in the acupuncture group showed a better FFI and success rate for pain during the day than those in the control group (p < 0.05). Electro-acupuncture coupled with conventional treatments provided a success rate of 80% in chronic planar fasciitis which was more effective than conventional treatments alone. The effects lasted for at least six weeks.


Characterizing DNA methylation alterations from The Cancer Genome Atlas.
The Cancer Genome Atlas (TCGA) Research Network is an ambitious multi-institutional consortium effort aimed at characterizing sequence, copy number, gene (mRNA) expression, microRNA expression, and DNA methylation alterations in 30 cancer types. TCGA data have become an extraordinary resource for basic, translational, and clinical researchers and have the potential to shape cancer diagnostic and treatment strategies. DNA methylation changes are integral to all aspects of cancer genomics and have been shown to have important associations with gene expression, sequence, and copy number changes. This Review highlights the knowledge gained from DNA methylation alterations in human cancers from TCGA.


Generalized approximate spin projection calculations of effective exchange integrals of the CaMn4O5 cluster in the S1 and S3 states of the oxygen evolving complex of photosystem II.
Full geometry optimizations followed by the vibrational analysis were performed for eight spin configurations of the CaMn4O4X(H2O)3Y (X = O, OH; Y = H2O, OH) cluster in the S1 and S3 states of the oxygen evolution complex (OEC) of photosystem II (PSII). The energy gaps among these configurations obtained by vertical, adiabatic and adiabatic plus zero-point-energy (ZPE) correction procedures have been used for computation of the effective exchange integrals (J) in the spin Hamiltonian model. The J values are calculated by the (1) analytical method and the (2) generalized approximate spin projection (AP) method that eliminates the spin contamination errors of UB3LYP solutions. Using J values derived from these methods, exact diagonalization of the spin Hamiltonian matrix was carried out, yielding excitation energies and spin densities of the ground and lower-excited states of the cluster. The obtained results for the right (R)- and left (L)-opened structures in the S1 and S3 states are found to be consistent with available optical and magnetic experimental results. Implications of the computational results are discussed in relation to (a) the necessity of the exact diagonalization for computations of reliable energy levels, (b) magneto-structural correlations in the CaMn4O5 cluster of the OEC of PSII, (c) structural symmetry breaking in the S1 and S3 states, and (d) the right- and left-handed scenarios for the O-O bond formation for water oxidation.


Lack of medial prefrontal cortex activation underlies the immediate extinction deficit.
We conducted a series of experiments to investigate the neural basis of the immediate extinction deficit, the lack of extinction when the interval between fear memory acquisition and extinction is short. In experiment 1, rats were given extinction training composed of 15 conditioned stimuli (CSs) either 15 min (immediate extinction: I-EXT) or 24 h (delayed extinction: D-EXT) after five tone-shock pairings. In the retention test performed 48 h after conditioning, I-EXT group exhibited significantly higher freezing than D-EXT group. In experiment 2, functional activation in the medial prefrontal cortex (mPFC) was detected using c-fos immunoreactivity. The number of Fos-positive neurons in the mPFC was significantly lower in I-EXT group than in D-EXT group. In experiment 3, rats received immediate extinction with microstimulation of the infralimbic region (IL) of the mPFC, either contingently paired or unpaired with the CS. In a subsequent retention test, the paired stimulation group exhibited decreased freezing relative to the unpaired stimulation group. Together, our results suggest that the immediate extinction deficit may be linked to the lack of neuronal activity in the IL.