bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Insular Cortex and Ventral Striatum Mediates the Effect of Incentive Memory on Choice Between Goal-Directed Actions
Authors: Parkes Shauna L. , Bradfield Laura A. , Balleine Bernard W.
Published: April 2015

The anterior insular cortex (IC) and the nucleus accumbens (NAc) core have been separately implicated in the selection and performance of actions based on the incentive value of the instrumental outcome. Here, we examined the role of connections between the IC and the NAc core in the performance of goal-directed actions. Rats were trained on two actions for distinct outcomes, after which one of the two outcomes was devalued by specific satiety immediately before a choice extinction test. We first confirmed the projection from the IC to the NAc core and then disconnected these structures via asymmetrical excitotoxic lesions before training. Contralateral, but not ipsilateral, disconnection of the IC and NAc core disrupted outcome devaluation. We hypothesized that communication between the IC and NAc core is necessary for the retrieval of incentive value at test. To test this, we infused the GABAAagonist muscimol into the IC and the μ-opioid receptor antagonist CTAP into the contralateral NAc before the choice extinction test. As expected, inactivation of the IC in one hemisphere and blocking μ-opioid receptors in the contralateral NAc core abolished outcome-selective devaluation. These results suggest that the IC and NAc core form part of a circuit mediating the retrieval of outcome values and the subsequent choice between goal-directed actions based on those values.
Costimulation of AMPA and Metabotropic Glutamate Receptors Underlies Phospholipase C Activation by Glutamate in Hippocampus
Authors: Kim Hye-Hyun , Lee Kyu-Hee , Lee Doyun , Han Young-Eun , Lee Suk-Ho , Sohn Jong-Woo , Ho Won-Kyung
Published: April 2015

Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca2+signals that are induced by AMPA-mediated depolarization and L-type Ca2+channel activation. Finally, we found that PLC and L-type Ca2+channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca2+influx via the L-type Ca2+channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus.
Injection of a Dopamine Type 2 Receptor Antagonist into the Dorsal Striatum Disrupts Choices Driven by Previous Outcomes, But Not Perceptual Inference
Authors: Lee Eunjeong , Seo Moonsang , Dal Monte Olga , Averbeck Bruno B.
Published: April 2015

Decisions are often driven by a combination of immediate perception and previous experience. In this study, we investigated how these two sources of information are integrated and the neural systems that mediate this process. Specifically, we injected a dopamine type 1 antagonist (D1A; SCH23390) or a dopamine type 2 antagonist (D2A; eticlopride) into the dorsal striatum while macaques performed a task in which their choices were driven by perceptual inference and/or reinforcement of past choices. We found that the D2A affected choices based on previous outcomes. However, there were no effects of the D2A on choices driven by perceptual inference. We found that the D1A did not affect perceptual inference or reinforcement learning. Finally, a Bayesian model applied to the results suggested that the D2A may be increasing noise in the striatal representation of value, perhaps by disrupting the striatal population that normally represents value.
Unit Activity of Hippocampal Interneurons before Spontaneous Seizures in an Animal Model of Temporal Lobe Epilepsy
Authors: Toyoda Izumi , Fujita Satoshi , Thamattoor Ajoy K. , Buckmaster Paul S.
Published: April 2015

Mechanisms of seizure initiation are unclear. To evaluate the possible roles of inhibitory neurons, unit recordings were obtained in the dentate gyrus, CA3, CA1, and subiculum of epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Most interneurons in the dentate gyrus, CA1, and subiculum increased their firing rate before seizures, and did so with significant consistency from seizure to seizure. Identification of CA1 interneuron subtypes based on firing characteristics during theta and sharp waves suggested that a parvalbumin-positive basket cell and putative bistratified cells, but not oriens lacunosum moleculare cells, were activated preictally. Preictal changes occurred much earlier than those described by most previousin vitrostudies. Preictal activation of interneurons began earliest (>4 min before seizure onset), increased most, was most prevalent in the subiculum, and was minimal in CA3. Preictal inactivation of interneurons was most common in CA1 (27% of interneurons) and included a putative ivy cell and parvalbumin-positive basket cell. Increased or decreased preictal activity correlated with whether interneurons fired faster or slower, respectively, during theta activity. Theta waves were more likely to occur before seizure onset, and increased preictal firing of subicular interneurons correlated with theta activity. Preictal changes by other hippocampal interneurons were largely independent of theta waves. Within seconds of seizure onset, many interneurons displayed a brief pause in firing and a later, longer drop that was associated with reduced action potential amplitude. These findings suggest that many interneurons inactivate during seizures, most increase their activity preictally, but some fail to do so at the critical time before seizure onset.
A Human Monoclonal IgG That Binds Aβ Assemblies and Diverse Amyloids Exhibits Anti-Amyloid ActivitiesIn VitroandIn Vivo
Authors: Levites Yona , O'Nuallain Brian , Puligedda Rama Devudu , Ondrejcak Tomas , Adekar Sharad P. , Chen Cindy , Cruz Pedro E. , Rosario Awilda M. , Macy Sallie , Mably Alexandra J. , Walsh Dominic M. , Vidal Ruben , Solomon Alan , Brown Daniel , Rowan Michael J. , Golde Todd E. , Dessain Scott K.
Published: April 2015

Alzheimer's disease (AD) and familial Danish dementia (FDD) are degenerative neurological diseases characterized by amyloid pathology. Normal human sera contain IgG antibodies that specifically bind diverse preamyloid and amyloid proteins and have shown therapeutic potentialin vitroandin vivo. We cloned one of these antibodies, 3H3, from memory B cells of a healthy individual using a hybridoma method. 3H3 is an affinity-matured IgG that binds a pan-amyloid epitope, recognizing both Aβ and λ Ig light chain (LC) amyloids, which are associated with AD and primary amyloidosis, respectively. The pan-amyloid-binding properties of 3H3 were demonstrated using ELISA, immunohistochemical studies, and competition binding assays. Functional studies showed that 3H3 inhibits both Aβ and LC amyloid formationin vitroand abrogates disruption of hippocampal synaptic plasticity by AD-patient-derived soluble Aβin vivo. A 3H3 single-chain variable fragment (scFv) retained the binding specificity of the 3H3 IgG and, when expressed in the brains of transgenic mice using an adeno-associated virus (AAV) vector, decreased parenchymal Aβ amyloid deposition in TgCRND8 mice and ADan (Danish Amyloid) cerebral amyloid angiopathy in the mouse model of FDD. These data indicate that naturally occurring human IgGs can recognize a conformational, amyloid-specific epitope and have potent anti-amyloid activities, providing a rationale to test their potential as antibody therapeutics for diverse neurological and other amyloid diseases.
The Complement Receptor C5aR Controls Acute Inflammation and Astrogliosis following Spinal Cord Injury
Authors: Brennan Faith H. , Gordon Richard , Lao Hong W. , Biggins Patrick J. , Taylor Stephen M. , Franklin Robin J.M. , Woodruff Trent M. , Ruitenberg Marc J.
Published: April 2015

This study investigated the role of the complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI).C5ar−/−mice, which lack the signaling receptor for C5a, displayed signs of improved locomotor recovery and reduced inflammation during the first week of SCI compared with wild-type mice. Intriguingly, the early signs of improved recovery inC5ar−/−mice deteriorated from day 14 onward, with absence of C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, reduced myelin content, and more widespread inflammation at 35 d SCI. Pharmacological blockade of C5aR with a selective antagonist (C5aR-A) during the first 7 d after SCI improved recovery compared with vehicle-treated mice, and this phenotype was sustained up to 35 d after injury. Consistent with observations made inC5ar−/−mice, these improvements were, however, lost if C5aR-A administration was continued into the more chronic phase of SCI. Signaling through the C5a-C5aR axis thus appears injurious in the acute period but serves a protective and/or reparative role in the post-acute phase of SCI. Further experiments in bone marrow chimeric mice suggested that the dual and opposing roles of C5aR on SCI outcomes primarily relate to its expression on CNS-resident cells and not infiltrating leukocytes. Additionalin vivoandin vitrostudies provided direct evidence that C5aR signaling is required during the postacute phase for astrocyte hyperplasia, hypertrophy, and glial scar formation. Collectively, these findings highlight the complexity of the inflammatory response to SCI and emphasize the importance of optimizing the timing of therapeutic interventions.
Hypoglycemia in everyday life after gastric bypass and duodenal switch
Authors: Abrahamsson Niclas , Edén Engström Britt , Sundbom Magnus , Karlsson F Anders
Published: April 2015

Design

Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life.

Methods

Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study.

Results

The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (<3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol,P<0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period.

Conclusion

Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.
Thyroid function, as assessed by TSH, and future risk of venous thromboembolism: the Tromsø study
Authors: Lerstad Gunhild , Enga Kristin F , Jorde Rolf , Brodin Ellen E , Svartberg Johan , Brækkan Sigrid K , Hansen John-Bjarne
Published: April 2015

Objective

The relationship between thyroid function and the risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the association between TSH levels and the risk of VTE in a general adult population.

Design

Population-based cohort study.

Methods

TSH was measured in 11 962 subjects aged 25–89 years who participated in Tromsø 4–6 starting in 1994–1995. Incident VTE events were recorded through 31st December 2010. Cox's regression models with TSH as a time-varying covariate were used to calculate hazard ratios (HRs) of VTE by TSH categories (low TSH: <0.05 mU/l; moderately reduced TSH: 0.05–0.19 mU/l; normal TSH: 0.20–4.00 mU/l; moderately elevated TSH: 4.01–5.00 mU/l; and high TSH: >5.00 mU/l) and within the normal range of TSH, modeling TSH as a continuous variable.

Results

There were 289 VTEs during 8.2 years of median follow-up. Subjects with low (prevalence: 0.22%) and high (3.01%) TSH had slightly higher risk estimates for VTE than did subjects with normal TSH (multivariable HRs: 2.16, 95% CI 0.69–6.76 and 1.55, 95% CI 0.87–2.77 respectively), but the CIs were wide. Moreover, there was no association between TSH within the normal range and VTE (HR per 1 mU/l increase: 0.95, 95% CI 0.82–1.11).

Conclusion

Serum levels of TSH within the normal range were not associated with a risk of VTE, whereas low and high TSH levels were rare and associated with a moderately higher risk of VTE. The present findings suggest that only a minor proportion of the VTE risk in the population can be attributed to thyroid dysfunction.
TFF3 is a valuable predictive biomarker of endocrine response in metastatic breast cancer
Authors: May Felicity E B , Westley Bruce R
Published: April 2015

The stratification of breast cancer patients for endocrine therapies by oestrogen or progesterone receptor expression is effective but imperfect. The present study aims were to validate microarray studies that demonstrate TFF3 regulation by oestrogen and its association with oestrogen receptors in breast cancer, to evaluate TFF3 as a biomarker of endocrine response, and to investigate TFF3 function. Microarray data were validated by quantitative RT-PCR and northern and western transfer analyses. TFF3 was induced by oestrogen, and its induction was inhibited by antioestrogens, tamoxifen, 4-hydroxytamoxifen and fulvestrant in oestrogen-responsive breast cancer cells. The expression of TFF3 mRNA was associated with oestrogen receptor mRNA in breast tumours (Pearson's coefficient=0.762,P=0.000). Monoclonal antibodies raised against the TFF3 protein detected TFF3 by immunohistochemistry in oesophageal submucosal glands, intestinal goblet and neuroendocrine cells, Barrett's metaplasia and intestinal metaplasia. TFF3 protein expression was associated with oestrogen receptor, progesterone receptor and TFF1 expression in malignant breast cells. TFF3 is a specific and sensitive predictive biomarker of response to endocrine therapy, degree of response and duration of response in unstratified metastatic breast cancer patients (P=0.000,P=0.002 andP=0.002 respectively). Multivariate binary logistic regression analysis demonstrated that TFF3 is an independent biomarker of endocrine response and degree of response, and this was confirmed in a validation cohort. TFF3 stimulated migration and invasion of breast cancer cells. In conclusion, TFF3 expression is associated with response to endocrine therapy, and outperforms oestrogen receptor, progesterone receptor and TFF1 as an independent biomarker, possibly because it mediates the malign effects of oestrogen on invasion and metastasis.
Uncertainty analysis: an evaluation metric for synthesis science
Authors: Harmon Mark E. , Fasth Becky , Halpern Charles B. , Lutz James A.
Published: April 2015

The methods for conducting reductionist ecological science are well known and widely used. In contrast, those used in the synthesis of ecological science (i.e., synthesis science) are still being developed, vary widely, and often lack the rigor of reductionist approaches. This is unfortunate because the synthesis of ecological parts into a greater whole is critical to understanding many of the environmental challenges faced by society. To help address this imbalance in approaches, we examine how the rigor of ecological synthesis science might be increased by using uncertainty as an evaluation metric—as a parallel to methods used in reductionist science. To estimate and understand uncertainty we propose that it be divided into four general classes: (1) measurement uncertainty (i.e., experimental error) as defined by precision and accuracy, (2) sampling uncertainty that reflects natural variation in space and time as quantified by classical statistical moments (e.g., mean and variance), (3) model prediction uncertainty which relates to the transformation of measurements into other variables of interest (e.g., plant dimensions to biomass), and (4) model selection uncertainty which relates to uncertainty about the form of the relationships used in models. Of these sources of uncertainty, model selection is the least understood and potentially, the most important, because it is integral to how components of a system are combined and it reflects imperfect knowledge about these relationships. To demonstrate uncertainty in synthesis science, we examine each source of uncertainty in an analysis that estimates the live tree biomass of a forest and how knowledge of each source can improve future estimates. By quantifying sources of uncertainty in synthesis science, it should be possible to make rigorous comparisons among results, to judge whether they differ within the bounds of measurement and knowledge, and to assess the degree to which scientific progress is being made. However, to be accepted as a standard method, best practices analogous to those used in reductionist science need to be developed and implemented.
Phylogenetics to help predict active metabolism
Authors: Guénard G. , Boisclair D. , Legendre P.
Published: April 2015

This paper shows how to build predictive models involving phylogenetic information to estimate metabolic traits such as active metabolic costs. Fish swimming cost is often estimated from body mass and swimming speed. The parameters of the relationships between these variables and swimming cost vary among species because each species has its own morphology and physiology. It is now widely recognized that traits are phylogenetically structured. Using new statistical approaches, it is possible to both correct swimming cost models for statistical phylogenetic non‐independence and use the inherent phylogenetic signal to improve models. With these models one can extend, to a larger set of species, empirical knowledge about traits that are difficult to obtain; swimming cost is one such trait.

Swimming cost accounts for a large and variable component of a fish energy budget, yet models have only been developed from observations performed on a few species, thereby constraining the scope of bioenergetic models. Here, we propose a method where body mass and swimming speed are used together with phylogeny to predict swimming cost. The resulting model explained a large proportion of the variation (90%) in the forced swimming cost of 16 fish species submitted to forced swimming experiments. We also compared phylogenetically‐explicit predictions for forced swimming experiments with experimental results of routine swimming for five species, among which one was not used to build the model. Results confirmed that forced swimming underestimates the cost of unsteady swimming. The phylogenetic modeling could be used to estimate other variables of interest in bioenergetic studies.
Transition Metal-free Epoxidation of Alkenes Based on the Existence of (2-
hydroxypropyl)-β-CD
Authors: Dongpo Shi , Xianqing Yin , Yancheng Zheng , wu Chen , Jiaxin Fu , Zhaohua Ren
Published: April 2015

A green, efficient epoxidation of alkenes with hydrogen peroxide (HO) and sodium bicarbonate (NaHCO3)
catalyzed by (2-hydroxypropyl)-β-cyclodextrin (2-hp-β-CD) in aqueous solution has been investigated in detail. A range
of alkenes were epoxidized at ambient temperature with high yields.
The Research and Application of MRF Magnetic Circuit Design
Authors: Shu Yuan , Hongjuan Ren , Yiping Luo
Published: April 2015

In this paper, the lord magnetic field of MRF and its circuit design are mainly expounded, according to the
loading ways of magnetic field and the magnetic circuit design plans of magneto-rheological fluid devices at present, the
general form and characteristics are summarized. In addition, a kind of magneto-rheological fluid dynamometer is
proposed in this paper, in terms of its magnetic circuit structure, a magnetic-field-lord test bench about magnetorheological
fluid is designed; a preliminary theoretical research is also given in order to improve the performance of
magneto-rheological fluid dynamometer.
The Auxiliary Problem Principle with Self-Adaptive Penalty Parameter for Multi-Area Economic Dispatch Problem
Authors: Ren Yaming , Fei Shumin
Published: April 2015

The auxiliary problem principle is a powerful tool for solving multi-area economic dispatch problem. One of the main drawbacks of the auxiliary problem principle method is that the convergence performance depends on the selection of penalty parameter. In this paper, we propose a self-adaptive strategy to adjust penalty parameter based on the iterative information, the proposed approach is verified by two given test systems. The corresponding simulation results demonstrate that the proposed self-adaptive auxiliary problem principle iterative scheme is robust in terms of the selection of penalty parameter and has better convergence rate compared with the traditional auxiliary problem principle method.
Enrichment of Druggable Conformations from Apo Protein Structures Using Cosolvent-Accelerated Molecular Dynamics
Authors: Kalenkiewicz Andrew , Grant Barry , Yang Chao-Yie
Published: April 2015

Here we describe the development of an improved workflow for utilizing experimental and simulated protein conformations in the structure-based design of inhibitors for anti-apoptotic Bcl-2 family proteins. Traditional structure-based approaches on similar targets are often constrained by the sparsity of available structures and difficulties in finding lead compounds that dock against flat, flexible protein-protein interaction surfaces. By employing computational docking of known small molecule inhibitors, we have demonstrated that structural ensembles derived from either accelerated MD (aMD) or MD in the presence of an organic cosolvent generally give better scores than those assessed from analogous conventional MD. Furthermore, conformations obtained from combined cosolvent aMD simulations started with the apo-Bcl-xL structure yielded better average and minimum docking scores for known binders than an ensemble of 72 experimental apo- and ligand-bound Bcl-xL structures. A detailed analysis of the simulated conformations indicates that the aMD effectively enhanced conformational sampling of the flexible helices flanking the main Bcl-xL binding groove, permitting the cosolvent acting as small ligands to penetrate more deeply into the binding pocket and shape ligand-bound conformations not evident in conventional simulations. We believe this approach could be useful for identifying inhibitors against other protein-protein interaction systems involving highly flexible binding sites, particularly for targets with less accumulated structural data.
Oxidative Stress in Aging Human Skin
Authors: Rinnerthaler Mark , Bischof Johannes , Streubel Maria , Trost Andrea , Richter Klaus
Published: April 2015

Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis.
Regulation of DNA Damage Response by Estrogen Receptor β-Mediated Inhibition of Breast Cancer Associated Gene 2
Authors: Lee Yuan-Hao , Sun Youping , Gerweck Leo , Glickman Randolph
Published: April 2015

Accumulating evidence suggests that ubiquitin E3 ligases are involved in cancer development as their mutations correlate with genomic instability and genetic susceptibility to cancer. Despite significant findings of cancer-driving mutations in the BRCA1 gene, estrogen receptor (ER)-positive breast cancers progress upon treatment with DNA damaging-cytotoxic therapies. In order to understand the underlying mechanism by which ER-positive breast cancer cells develop resistance to DNA damaging agents, we employed an estrogen receptor agonist, Erb-041, to increase the activity of ERβ and negatively regulate the expression and function of the estrogen receptor α (ERα) in MCF-7 breast cancer cells. Upon Erb-041-mediated ERα down-regulation, the transcription of an ERα downstream effector, BCA2 (Breast Cancer Associated gene 2), correspondingly decreased. The ubiquitination of chromatin-bound BCA2 was induced by ultraviolet C (UVC) irradiation but suppressed by Erb-041 pretreatment, resulting in a blunted DNA damage response. Upon BCA2 silencing, DNA double-stranded breaks increased with Rad51 up-regulation and ataxia telangiectasia mutated (ATM) activation. Mechanistically, UV-induced BCA2 ubiquitination and chromatin binding were found to promote DNA damage response and repair via the interaction of BCA2 with ATM, γH2AX and Rad51. Taken together, this study suggests that Erb-041 potentiates BCA2 dissociation from chromatin and co-localization with Rad51, resulting in inhibition of homologous recombination repair.
Cardiometabolic and Skeletal Risk Factors in Black Men with Prostate Cancer Starting Androgen Deprivation Therapy
Authors: Gunnarsson Orvar , Basaria Shehzad , Gignac Gretchen
Published: April 2015

Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with multiple metabolic complications, previously predominantly evaluated in the white population. Methods: A chart-based retrospective review was conducted on black patients with PCa, considered for ADT, from September 2007 to July 2010. Baseline data were collected on body mass index (BMI), vitamin-D status, bone mineral density (BMD), dyslipidemia and diabetes. Overweight and obesity were classified as BMI ≥ 25 and BMI ≥ 30, respectively. Vitamin-D sufficiency was defined as levels ≥30 ng/mL, insufficiency as <30 ng/mL and deficiency as ≤20 ng/mL. Osteopenia was defined as T scores between −1 to −2.5 and osteoporosis when T scores ≤−2.5. Results: Of the initial cohort of 130 black men, 111 (85.4%) patients underwent ADT. At baseline, average BMI was 28.1 ± 5.9 with 43.3% of men being overweight and 30.8% obese. More than one-third of the patients had pre-existing dyslipidemia while 28.8% were diabetics. 50% were vitamin-D deficient while 41% had low bone mass. Conclusions: Black men with PCa presenting for consideration of ADT have a high prevalence of existing metabolic risk factors. Close monitoring of this patient population is needed during ADT to prevent and treat metabolic complications.
Solid-Liquid Phase C-Alkylation of Active Methylene Containing Compounds under Microwave Conditions
Authors: Grün Alajos , Bálint Erika , Keglevich György
Published: April 2015

The solid–liquid phase C-alkylation of active methylene containing compounds with C=O or P=O functions under phase transfer catalysis or microwave conditions has been summarized in this minireview. The mono- and dialkylation of the methylene containing derivatives was investigated under microwave (MW) conditions. It was found that in many cases, there was no need to use phase transfer catalyst under MW conditions. Moreover, most of the reactions were carried out without any solvent. These results mean a serious green chemical advantage.
Information Geometry on Complexity and Stochastic Interaction
Authors: Ay Nihat
Published: April 2015

Interdependencies of stochastically interacting units are usually quantified by the Kullback-Leibler divergence of a stationary joint probability distribution on the set of all configurations from the corresponding factorized distribution. This is a spatial approach which does not describe the intrinsically temporal aspects of interaction. In the present paper, the setting is extended to a dynamical version where temporal interdependencies are also captured by using information geometry of Markov chain manifolds.
Justifying Objective Bayesianism on Predicate Languages
Authors: Landes Jürgen , Williamson Jon
Published: April 2015

Objective Bayesianism says that the strengths of one’s beliefs ought to be probabilities, calibrated to physical probabilities insofar as one has evidence of them, and otherwise sufficiently equivocal. These norms of belief are often explicated using the maximum entropy principle. In this paper we investigate the extent to which one can provide a unified justification of the objective Bayesian norms in the case in which the background language is a first-order predicate language, with a view to applying the resulting formalism to inductive logic. We show that the maximum entropy principle can be motivated largely in terms of minimising worst-case expected loss.
Thermodynamic Analysis of Double-Stage Compression Transcritical CO2 Refrigeration Cycles with an Expander
Authors: Zhang Zhenying , Tong Lirui , Wang Xingguo
Published: April 2015

Four different double-compression CO2 transcritical refrigeration cycles are studied: double-compression external intercooler cycle (DCEI), double-compression external intercooler cycle with an expander (DCEIE), double-compression flash intercooler cycle (DCFI), double-compression flash intercooler cycle with an expander (DCFIE). The results showed that the optimum gas cooler pressure and optimum intermediate pressure of the flash intercooler cycles are lower than that of the external intercooler cycle. The use of an expander in the DCEI cycle leads to a decrease of the optimum gas cooler pressure and little variation of the optimum intermediate pressure. However, the replacement of the throttle valve with an expander in the DCFI cycle results in little variation of the optimal gas cooler pressure and an increase of the optimum intermediate pressure. The DCFI cycle outperforms the DCEI cycle under all the chosen operating conditions. The DCEIE cycle outperforms the DCFIE cycle when the evaporating temperature exceeds 0 °C or the gas cooler outlet temperature surpasses 35 °C. When the gas cooler exit temperature varies from 32 °C to 48 °C, the DCEI cycle, DCEIE cycle, DCFI cycle and DCFIE cycle yield averaged 4.6%, 29.2%, 12.9% and 22.3% COP improvement, respectively, over the basic cycle.
The Impact of the Free Swimming Programme in a Local Community in the South East of England: Giving with One Hand, Taking Away with the Other
Authors: Kokolakakis Themis , Pappous Athanasios , Meadows Steve
Published: April 2015

The purpose of this study is to examine the impact of the introduction of the Free Swimming Programme (FSP) in a local community (not identified to preserve anonymity) in the South East of England. The question has been approached in a variety of ways: by using primary quantitative data from leisure centres and logistic regressions based on the Active People Survey (APS). Problems are identified related to the introduction of the FSP in this community and suggestions are made for future policy. A brief examination of swimming participation in England enables researchers to place this community into a national context. The problems and policies of sport organisation developed in this community are not dissimilar to a more general application reflecting the English experience; in this sense it is anticipated that the findings will enable managers of sport organisations, along with public health policy makers, to focus more effectively on raising sport participation. The unique selling points of this article are the examination of FSP for adult participants, the local analysis of junior and senior participation, and the overall assessment of the policy based on APS.
Chemical Bonding: The Orthogonal Valence-Bond View
Authors: Sax Alexander
Published: April 2015

Chemical bonding is the stabilization of a molecular system by charge- and spin-reorganization processes in chemical reactions. These processes are said to be local, because the number of atoms involved is very small. With multi-configurational self-consistent field (MCSCF) wave functions, these processes can be calculated, but the local information is hidden by the delocalized molecular orbitals (MO) used to construct the wave functions. The transformation of such wave functions into valence bond (VB) wave functions, which are based on localized orbitals, reveals the hidden information; this transformation is called a VB reading of MCSCF wave functions. The two-electron VB wave functions describing the Lewis electron pair that connects two atoms are frequently called covalent or neutral, suggesting that these wave functions describe an electronic situation where two electrons are never located at the same atom; such electronic situations and the wave functions describing them are called ionic. When the distance between two atoms decreases, however, every covalent VB wave function composed of non-orthogonal atomic orbitals changes its character from neutral to ionic. However, this change in the character of conventional VB wave functions is hidden by its mathematical form. Orthogonal VB wave functions composed of orthonormalized orbitals never change their character. When localized fragment orbitals are used instead of atomic orbitals, one can decide which local information is revealed and which remains hidden. In this paper, we analyze four chemical reactions by transforming the MCSCF wave functions into orthogonal VB wave functions; we show how the reactions are influenced by changing the atoms involved or by changing their local symmetry. Using orthogonal instead of non-orthogonal orbitals is not just a technical issue; it also changes the interpretation, revealing the properties of wave functions that remain otherwise undetected.
Novel Systems Modeling Methodology in Comparative Microbial Metabolomics: Identifying Key Enzymes and Metabolites Implicated in Autism Spectrum Disorders
Authors: Heberling Colin , Dhurjati Prasad
Published: April 2015

Autism spectrum disorders are a group of mental illnesses highly correlated with gastrointestinal dysfunction. Recent studies have shown that there may be one or more microbial “fingerprints” in terms of the composition characterizing individuals with autism, which could be used for diagnostic purposes. This paper proposes a computational approach whereby metagenomes characteristic of “healthy” and autistic individuals are artificially constructed via genomic information, analyzed for the enzymes coded within, and then these enzymes are compared in detail. This is a text mining application. A custom-designed online application was built and used for the comparative metabolomics study and made publically available. Several of the enzyme-catalyzing reactions involved with the amino acid glutamate were curiously missing from the “autism” microbiome and were coded within almost every organism included in the “control” microbiome. Interestingly, there exists a leading hypothesis regarding autism and glutamate involving a neurological excitation/inhibition imbalance; but the association with this study is unclear. The results included data on the transsulfuration and transmethylation pathways, involved with oxidative stress, also of importance to autism. The results from this study are in alignment with leading hypotheses in the field, which is impressive, considering the purely in silico nature of this study. The present study provides new insight into the complex metabolic interactions underlying autism, and this novel methodology has potential to be useful for developing new hypotheses. However, limitations include sparse genome data availability and conflicting literature experimental data. We believe our software tool and methodology has potential for having great utility as data become more available, comprehensive and reliable.
Analysis and Visualization for Hot Spot Based Route Recommendation Using Short-Dated Taxi GPS Traces
Authors: Shen Ying , Zhao Ligang , Fan Jing
Published: April 2015

Taxi GPS traces, which contain a great deal of valuable information as regards to human mobility and city traffic, can be extracted to improve the quality of our lives. Since the method of visualized analysis is believed to be an effective way to present information vividly, we develop our analysis and visualization method based on a city’s short-dated taxi GPS traces, which can provide recommendation to help cruising taxi drivers to find potential passengers with optimal routes. With our approach, hot spots for loading and unloading passenger(s) are extracted using an improved DBSCAN algorithm after data preprocessing including cleaning and filtering. Then, this paper describes the start-end point-based similar trajectory method to get coarse-level trajectories clusters, together with the density-based ε distance trajectory clustering algorithm to identify recommended potential routes. A weighted tree is defined including such factors as driving time, velocity, distance and endpoint attractiveness for optimal route evaluation from vacant to occupied hot spots. An example is presented to show the effectiveness of our visualization method.
Bioengineering and Stem Cell Technology in the Treatment of Congenital Heart Disease
Authors: Bosman Alexis , Edel Michael , Blue Gillian , Dilley Rodney , Harvey Richard , Winlaw David
Published: April 2015

Congenital heart disease places a significant burden on the individual, family and community despite significant advances in our understanding of aetiology and treatment. Early research in ischaemic heart disease has paved the way for stem cell technology and bioengineering, which promises to improve both structural and functional aspects of disease. Stem cell therapy has demonstrated significant improvements in cardiac function in adults with ischaemic heart disease. This finding, together with promising case studies in the paediatric setting, demonstrates the potential for this treatment in congenital heart disease. Furthermore, induced pluripotent stems cell technology, provides a unique opportunity to address aetiological, as well as therapeutic, aspects of disease.
Impact of Different Surface Ligands on the Optical Properties of PbS Quantum Dot Solids
Authors: Xu Fan , Gerlein Luis , Ma Xin , Haughn Chelsea , Doty Matthew , Cloutier Sylvain
Published: April 2015

The engineering of quantum dot solids with low defect concentrations and efficient carrier transport through a ligand strategy is crucial to achieve efficient quantum dot (QD) optoelectronic devices. Here, we study the consequences of various surface ligand treatments on the light emission properties of PbS quantum dot films using 1,3-benzenedithiol (1,3-BDT), 1,2-ethanedithiol (EDT), mercaptocarboxylic acids (MPA) and ammonium sulfide ((NH4)2S). We first investigate the influence of different ligand treatments on the inter-dot separation, which mainly determines the conductivity of the QD films. Then, through a combination of photoluminescence and transient photoluminescence characterization, we demonstrate that the radiative and non-radiative recombination mechanisms in the quantum dot films depend critically on the length and chemical structure of the surface ligands.
Setup of Extruded Cementitious Hollow Tubes as Containing/Releasing Devices in Self-Healing Systems
Authors: Formia Alessandra , Terranova Salvatore , Antonaci Paola , Pugno Nicola , Tulliani Jean
Published: April 2015

The aim of this research is to produce self-healing cementitious composites based on the use of cylindrical capsules containing a repairing agent. Cementitious hollow tubes (CHT) having two different internal diameters (of 2 mm and 7.5 mm) were produced by extrusion and used as containers and releasing devices for cement paste/mortar healing agents. Based on the results of preliminary mechanical tests, sodium silicate was selected as the healing agent. The morphological features of several mix designs used to manufacture the extruded hollow tubes, as well as the coatings applied to increase the durability of both core and shell materials are discussed. Three-point bending tests were performed on samples produced with the addition of the above-mentioned cementitious hollow tubes to verify the self-healing effectiveness of the proposed solution. Promising results were achieved, in particular when tubes with a bigger diameter were used. In this case, a substantial strength and stiffness recovery was observed, even in specimens presenting large cracks (>1 mm). The method is inexpensive and simple to scale up; however, further research is needed in view of a final optimization.
Gas Permeation Properties of Soluble Aromatic Polyimides Based on 4-Fluoro-4,4'-Diaminotriphenylmethane
Authors: Guzmán-Lucero Diego , Palomeque-Santiago Jorge , Camacho-Zúñiga Claudia , Ruiz-Treviño Francisco , Guzmán Javier , Galicia-Aguilar Alberto , Aguilar-Lugo Carla
Published: April 2015

A series of new organic polyimides were synthesized from 4-fluoro-4'4"-diaminotriphenylmethane and four different aromatic dianhydrides through a one-step, high-temperature, direct polycondensation in m-cresol at 180–200 °C, resulting in the formation of high-molecular-weight polyimides (inherent viscosities ~ 1.0–1.3 dL/g). All the resulting polyimides exhibited good thermal stability with initial decomposition temperatures above 434 °C, glass-transition temperatures between 285 and 316 °C, and good solubility in polar aprotic solvents. Wide-angle X-ray scattering data indicated that the polyimides were amorphous. Dense membranes were prepared by solution casting and solvent evaporation to evaluate their gas transport properties (permeability, diffusivity, and solubility coefficients) toward pure hydrogen, helium, oxygen, nitrogen, methane, and carbon dioxide gases. In general, the gas permeability was increased as both the fractional free volume and d-spacing were also increased. A good combination of permeability and selectivity was promoted efficiently by the bulky hexafluoroisopropylidene and 4-fluoro-phenyl groups introduced into the polyimides. The results indicate that the gas transport properties of these films depend on both the structure of the anhydride moiety, which controls the intrinsic intramolecular rigidity, and the 4-fluoro-phenyl pendant group, which disrupts the intermolecular packing.
Properties of Exchange Coupled All-garnet Magneto-Optic Thin Film Multilayer Structures
Authors: Nur-E-Alam Mohammad , Vasiliev Mikhail , Kotov Viacheslav , Balabanov Dmitry , Akimov Ilya , Alameh Kamal
Published: April 2015

The effects of exchange coupling on magnetic switching properties of all-garnet multilayer thin film structures are investigated. All-garnet structures are fabricated by sandwiching a magneto-soft material of composition type Bi1.8Lu1.2Fe3.6Al1.4O12 or Bi3Fe5O12:Dy2O3 in between two magneto-hard garnet material layers of composition type Bi2Dy1Fe4Ga1O12 or Bi2Dy1Fe4Ga1O12:Bi2O3. The fabricated RF magnetron sputtered exchange-coupled all-garnet multilayers demonstrate a very attractive combination of magnetic properties, and are of interest for emerging applications in optical sensors and isolators, ultrafast nanophotonics and magneto-plasmonics. An unconventional type of magnetic hysteresis behavior not observed previously in magnetic garnet thin films is reported and discussed.
The Fractional Orthogonal Derivative
Authors: Diekema Enno
Published: April 2015

This paper builds on the notion of the so-called orthogonal derivative, where an n-th order derivative is approximated by an integral involving an orthogonal polynomial of degree n. This notion was reviewed in great detail in a paper by the author and Koornwinder in 2012. Here, an approximation of the Weyl or Riemann–Liouville fractional derivative is considered by replacing the n-th derivative by its approximation in the formula for the fractional derivative. In the case of, for instance, Jacobi polynomials, an explicit formula for the kernel of this approximate fractional derivative can be given. Next, we consider the fractional derivative as a filter and compute the frequency response in the continuous case for the Jacobi polynomials and in the discrete case for the Hahn polynomials. The frequency response in this case is a confluent hypergeometric function. A different approach is discussed, which starts with this explicit frequency response and then obtains the approximate fractional derivative by taking the inverse Fourier transform.
Xyloketal B Suppresses Glioblastoma Cell Proliferation and Migration in Vitro through Inhibiting TRPM7-Regulated PI3K/Akt and MEK/ERK Signaling Pathways
Authors: Chen Wen-Liang , Turlova Ekaterina , Sun Christopher , Kim Ji-Sun , Huang Sammen , Zhong Xiao , Guan Yong-Yuan , Wang Guan-Lei , Rutka James , Feng Zhong-Ping , Sun Hong-Shuo
Published: April 2015

Glioblastoma, the most common and aggressive type of brain tumors, has devastatingly proliferative and invasive characteristics. The need for finding a novel and specific drug target is urgent as the current approaches have limited therapeutic effects in treating glioblastoma. Xyloketal B is a marine compound obtained from mangrove fungus Xylaria sp. (No. 2508) from the South China Sea, and has displayed antioxidant activity and protective effects on endothelial and neuronal oxidative injuries. In this study, we used a glioblastoma U251 cell line to (1) explore the effects of xyloketal B on cell viability, proliferation, and migration; and (2) investigate the underlying molecular mechanisms and signaling pathways. MTT assay, colony formation, wound healing, western blot, and patch clamp techniques were employed. We found that xyloketal B reduced cell viability, proliferation, and migration of U251 cells. In addition, xyloketal B decreased p-Akt and p-ERK1/2 protein expressions. Furthermore, xyloketal B blocked TRPM7 currents in HEK-293 cells overexpressing TRPM7. These effects were confirmed by using a TRPM7 inhibitor, carvacrol, in a parallel experiment. Our findings indicate that TRPM7-regulated PI3K/Akt and MEK/ERK signaling is involved in anti-proliferation and migration effects of xyloketal B on U251 cells, providing in vitro evidence for the marine compound xyloketal B to be a potential drug for treating glioblastoma.