bluuebunny/crossref_metadata_2025 huggingface dataset:
Mind Over Matter? The Role of Individual Perceptions in Understanding the Social Ecology of Housing Environments for Individuals with Psychiatric Disabilities
Authors: Townley Greg , Kloos Bret
Published: June 2014

There is a disagreement in place‐based research regarding whether objective indicators or individual perceptions of environments are better predictors of well‐being. This study assessed environmental influences on well‐being for 373 individuals with psychiatric disabilities living independently in 66 neighborhoods in the southeastern United States. Three questions were examined utilizing random effects models: (1) How much variance in personal and neighborhood well‐being can be explained by neighborhood membership? (2) What is the relationship between participant perceptions of neighborhood quality and researcher ratings of neighborhood quality? and (3) What is the relative influence of individual perceptions, perceptions aggregated by neighborhood, and researcher ratings of neighborhood quality in predicting personal and neighborhood well‐being? Results indicate that individual perceptions of neighborhood quality were more closely related to well‐being than either aggregated perceptions or researcher ratings. Thus, participants’ perceptions of their neighborhoods were more important indicators of their well‐being than objective ratings made by researchers. Findings have implications for measurement approaches and intervention design in placed‐based research.
Dorsal Fracture-Dislocations of the Proximal Interphalangeal Joint: Evaluation of Closed Reduction and Percutaneous Kirschner wire Pinning
Authors: Haseth Kristin B. de , Neuhaus Valentin , Mudgal Chaitanya S.
Published: June 2014

Background

The purpose of this study is to evaluate the outcome of closed reduction and percutaneous Kirschner wire pinning in acute dorsal fracture-dislocations of the proximal interphalangeal (PIP) joint.

Methods

Eight men and one woman were treated with closed reduction and percutaneous Kirschner wire pinning by one orthopaedic surgeon. The ring finger was injured in six patients, the small finger in two patients and the middle finger in one patient. The mean joint surface involvement was 36 % (range, 26–49 %). The Kirschner wires were removed after an average of 28 days (range, 24–37 days).

Results

All patients demonstrated a painless, but fusiform, swollen PIP joint after a mean follow-up of 6.5 months. The average flexion of the PIP joint was 106° (range, 80–110), and the average extension of the PIP joint was 4° short of full extension (range, 10 hyperextension–15 flexion contracture). All patients had a concentrically reduced PIP joint with a healed fracture on radiographs. Two patients had radiographic evidence of degenerative changes, but were asymptomatic. One patient developed a superficial pin track infection, which quickly resolved with a short course of antibiotics, and avascular necrosis affecting one of the condyles of the proximal phalanx.

Conclusions

In agreement with previous studies, closed reduction and percutaneous Kirschner wire pinning in dorsal fracture-dislocations of the PIP joint is a minimally invasive and simple technique which appears to give satisfactory outcomes in the short to intermediate term.
17β‐Estradiol Increases Liver and Serum Docosahexaenoic Acid in Mice Fed Varying Levels of α‐Linolenic Acid
Authors: Mason Julie K. , Kharotia Shikhil , Wiggins Ashleigh K. A. , Kitson Alex P. , Chen Jianmin , Bazinet Richard P. , Thompson Lilian U.
Published: June 2014

Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β‐estradiol (E2) appears to increase the conversion of α‐linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low‐ALA corn oil‐based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal‐based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow‐release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.
Fanconi-Bickel Syndrome - Mutation in SLC2A2 Gene
Authors: Kehar Mohit , Bijarnia Sunita , Ellard Sian , Houghton Jayne , Saxena Renu , Verma I. C. , Wadhwa Nishant
Published: June 2014

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. The defect in the GLUT 2 receptors in the hepatocytes, pancreas and renal tubules leads to symptoms secondary to glycogen storage, glucose metabolism and renal tubular dysfunction. Derangement in glucose metabolism is classical with fasting hypoglycemia and post-prandial hyperglycemia. The authors report a 4-year-old boy who presented with failure to thrive, motor delay, protuberant abdomen and was noted to have huge hepatomegaly with glycogen deposition in liver, and renal tubular acidosis. Gene sequencing revealed homozygous mutation, c.1330T > C in SLC2A2 gene, thus confirming the diagnosis of FBS. Only three mutations have been reported from India so far. The primary reason for referral to authors’ hospital was for liver transplantation, but an accurate diagnosis led to avoidance of the major surgery and streamlining of treatment with clinical benefit to the child and family.
Infinitely many new curves of the Fučík spectrum
Authors: Molle Riccardo , Passaseo Donato
Published: June 2014

In this paper we present some results on the Fučík spectrum for the Laplace operator, that give new information on its structure. In particular, these results show that, if

Ω

is a bounded domain of

\mathbb{R}^{N}

with

N > 1

, then the Fučík spectrum has infinitely many curves asymptotic to the lines

\{\lambda _{1}\} \times \mathbb{R}

and

\mathbb{R} \times \{\lambda _{1}\}

, where

\lambda _{1}

denotes the first eigenvalue of the operator

−Δ

in

H_{0}^{1}(\Omega )

. Notice that the situation is quite different in the case

N = 1

; in fact, in this case the Fučík spectrum may be obtained by direct computation and one can verify that it includes only two curves asymptotic to these lines.

Nous présentons des résultats qui donnent de nouvelles informations sur la structure du spectre de Fučík pour l'opérateur de Laplace. En particulier, ces résultats montrent que, si

Ω

est un domaine borné de

\mathbb{R}^{N}

avec

N > 1

, alors le spectre de Fučík a un nombre infini de courbes qui ont comme asymptotes les droites

\{\lambda _{1}\} \times \mathbb{R}

et

\mathbb{R} \times \{\lambda _{1}\}

, où

\lambda _{1}

est la première valeur propre de l'operateur

−Δ

in

H_{0}^{1}(\Omega )

. La situation est bien différente dans le cas

N = 1

; en effect, dans ce cas on peut vérifier qu'il y a seulement deux courbes dans le spectre de Fučík, qui ont ces droites comme asymptotes.
The polycomb group protein EZH2 inhibits lung cancer cell growth by repressing the transcription factor Nrf2
Authors: Li Ziming , Xu Ling , Tang Naiwang , Xu Yunhua , Ye Xiangyun , Shen Shengping , Niu Xiaomin , Lu Shun , Chen Zhiwei
Published: June 2014

EZH2 is a key component of the polycomb PRC2 complex and functions as a histone H3 Lys27 (H3K27) trimethyltransferase. Here we show that EZH2 is down‐regulated in human non‐small cell lung cancer and low EZH2 expression predicts poor survival. Further we demonstrate that EZH2 inhibits lung cancer cell proliferation and colony formation in vitro and growth in vivo. We found that EZH2 binds to the promoter of Nrf2, where it increases H3K27me3 and represses Nrf2 expression. Finally, Nrf2 seems to be essential for the hyper proliferation of lung cancer cells in the absence of EZH2.
Inhibition of constitutive TNF production is associated with PACAP‐mediated differentiation in PC12 cells
Authors: Manecka Destiny-Love , Lelièvre Vincent , Anouar Youssef
Published: June 2014

The pituitary adenylate cyclase‐activating polypeptide (PACAP) is a trophic neuropeptide that promotes cell survival and neuritogenesis in the central and peripheral nervous system. Our previous transcriptomic studies revealed the down‐regulation of the cytokine tumor necrosis factor (TNF) during PACAP‐induced PC12 cell differentiation. Here we show that TNF is constitutively expressed in PC12 cells in a manner dependent on NF‐κB transcription factor, and that PACAP rapidly inhibits TNF expression and secretion. The inhibition occurs through suppression of RelB subunit of NF‐κB, and is likely to prevent the deleterious effects of the cytokine on survival and neurite outgrowth during PC12 cell differentiation.
Nucleases in homologous recombination as targets for cancer therapy
Authors: Bartosova Zdenka , Krejci Lumir
Published: June 2014

Genomic DNA is constantly challenged from endogenous as well as exogenous sources. The DNA damage response (DDR) mechanism has evolved to combat these challenges and ensure genomic integrity. In this review, we will focus on repair of DNA double‐strand breaks (DSB) by homologous recombination and the role of several nucleases and other recombination factors as suitable targets for cancer therapy. Their inactivation as well as overexpression have been shown to sensitize cancer cells by increasing toxicity to DNA‐damaging agents and radiation or to be responsible for resistance of cancer cells. These factors can also be used in targeted cancer therapy by taking advantage of specific genetic abnormalities of cancer cells that are not present in normal cells and that result in cancer cell lethality.
Assay for characterizing the recovery of vertebrate cells for adhesion measurements by single‐cell force spectroscopy
Authors: Schubert Rajib , Strohmeyer Nico , Bharadwaj Mitasha , Ramanathan Subramanian P. , Krieg Michael , Friedrichs Jens , Franz Clemens M. , Muller Daniel J.
Published: June 2014

Single‐cell force spectroscopy (SCFS) is becoming a widely used method to quantify the adhesion of a living cell to a substrate, another cell or tissue. The high sensitivity of SCFS permits determining the contributions of individual cell adhesion molecules (CAMs) to the adhesion force of an entire cell. However, to prepare adherent cells for SCFS, they must first be detached from tissue‐culture flasks or plates. EDTA and trypsin are often applied for this purpose. Because cellular properties can be affected by this treatment, cells need to recover before being further characterized by SCFS. Here we introduce atomic force microscopy (AFM)‐based SCFS to measure the mechanical and adhesive properties of HeLa cells and mouse embryonic kidney fibroblasts while they are recovering after detachment from tissue‐culture. We find that mechanical and adhesive properties of both cell lines recover quickly (<10 min) after detachment using EDTA, while trypsin‐detached fibroblasts require >60 min to fully recover. Our assay introduced to characterize the recovery of mammalian cells after detachment can in future be used to estimate the recovery behavior of other adherent cell types.
Military‐related traumatic brain injury and neurodegeneration
Authors: McKee Ann C. , Robinson Meghan E.
Published: June 2014

Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long‐term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long‐term gray and white matter atrophy, precipitate or accelerate age‐related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early‐stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings.
Stress, PTSD, and dementia
Authors: Greenberg Mark S. , Tanev Kaloyan , Marin Marie‐France , Pitman Roger K.
Published: June 2014

The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later‐life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long‐term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well‐controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well‐controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals.
Smoking and increased Alzheimer's disease risk: A review of potential mechanisms
Authors: Durazzo Timothy C. , Mattsson Niklas , Weiner Michael W. ,   Alzheimer's Disease Neuroimaging Initiative
Published: June 2014

Background

Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians.

Methods

A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD‐related neuropathology was conducted. Original data from comparisons of smoking and never‐smoking cognitively normal elders on in vivo amyloid imaging are also presented.

Results

Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking‐related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD.

Conclusions

A reduction in the incidence of smoking will likely reduce the future prevalence of AD.
Lifestyle and health‐related risk factors and risk of cognitive aging among older veterans
Authors: Yaffe Kristine , Hoang Tina D. , Byers Amy L. , Barnes Deborah E. , Friedl Karl E.
Published: June 2014

Lifestyle and health‐related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health‐related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them.
Targeted polytherapy in small cell sarcoma and its association with doxorubicin
Authors: Dumont S.N. , Yang D. , Dumont A.G. , Reynoso D. , Blay J-Y. , Trent J.C.
Published: June 2014

A paradigm shift has occurred in the last decade from chemotherapy to targeted therapy for the management of many patients with advanced sarcoma. This work identifies a combination of targeted agents and doxorubicin that are effective against small cell sarcoma cell lines.

Three small cell sarcoma cell lines were studied: RD18 (rhabdomyosarcoma), A204 (undifferentiated sarcoma) and TC 71 (Ewing's sarcoma). Each cell line was exposed to increasing concentrations of vorinostat (HDAC inhibitor), 17‐DMAG (HSP90 inhibitor), abacavir (anti‐telomerase) or sorafenib (tyrosine kinase inhibitor) alone, combined with one another, or combined with doxorubicin. Cell viability, cell cycle analysis and apoptosis were assessed by MTS assay, propidium iodide‐Annexin V staining, and caspase 3/7 activity, respectively. The Chou and Talalay combination index (CI) was used to determine whether the effects were additive (CI = 1), synergistic (CI < 1) or antagonistic (CI > 1).

In monotherapy, targeted agents achieved 30–90% reductions in viability, with the exception of abacavir. Dual‐targeted combination therapies with vorinostat, sorafenib and 17‐DMAG demonstrated synergy. Abacavir was antagonistic with every other drug and was not further studied. Both vorinostat and 17‐DMAG synergized with doxorubicin, achieving 60% cell killing compared to 12% with doxorubicin alone. No synergy was observed for sorafenib with doxorubicin. The triple therapy vorinostat, 17‐DMAG and doxorubicin did not show synergy, but increased the subG1 population at 24H, from 30% to 70% compared to monotherapies with an increase in apoptosis.

This work provides evidence of synergy of combinations of vorinostat, 17‐DMAG and sorafenib in small cell sarcoma. In addition to doxorubicin, these combinations enhance doxorubicin cytotoxicity at therapeutically relevant concentrations.
Multi-solitons for nonlinear Klein–Gordon equations
Authors: CÔTE RAPHAËL , MUÑOZ CLAUDIO
Published: June 2014

In this paper, we consider the existence of multi-soliton structures for the nonlinear Klein–Gordon (NLKG) equation in $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\mathbb{R}^{1+d}$. We prove that, independently of the unstable character of NLKG solitons, it is possible to construct a $N$-soliton family of solutions to the NLKG equation, of dimension $2N$, globally well defined in the energy space $H^1\times L^2$ for all large positive times. The method of proof involves the generalization of previous works on supercritical Nonlinear Schrödinger (NLS) and generalized Korteweg–de Vries (gKdV) equations by Martel, Merle, and the first author [R. Côte, Y. Martel and F. Merle, Rev. Mat. Iberoam. 27 (1) (2011), 273–302] to the wave case, where we replace the unstable mode associated to the linear NLKG operator by two generalized directions that are controlled without appealing to modulation theory. As a byproduct, we generalize the linear theory described in Grillakis, Shatah, and Strauss [J. Funct. Anal. 74 (1) (1987), 160–197] and Duyckaerts and Merle [Int. Math. Res. Pap. IMRP (2008), Art ID rpn002] to the case of boosted solitons, and provide new solutions to be studied using the recent work of Nakanishi and Schlag [Zurich Lectures in Advanced Mathematics, vi+253 pp (European Mathematical Society (EMS), Zürich, 2011)] theory.
Spatiotemporal dynamics in two-dimensional Kolmogorov flow over large domains
Authors: Lucas Dan , Kerswell Rich
Published: June 2014

Kolmogorov flow in two dimensions – the two-dimensional (2D) Navier–Stokes equations with a sinusoidal body force – is considered over extended periodic domains to reveal localised spatiotemporal complexity. The flow response mimics the forcing at small forcing amplitudes but beyond a critical value develops a long wavelength instability. The ensuing state is described by a Cahn–Hilliard-type equation and as a result coarsening dynamics is observed for random initial data. After further bifurcations, this regime gives way to multiple attractors, some of which possess spatially localised time dependence. Co-existence of such attractors in a large domain gives rise to interesting collisional dynamics which is captured by a system of 5 (1-space and 1-time) partial differential equations (PDEs) based on a long wavelength limit. The coarsening regime reinstates itself at yet higher forcing amplitudes in the sense that only longest-wavelength solutions remain attractors. Eventually, there is one global longest-wavelength attractor which possesses two localised chaotic regions – a kink and antikink – which connect two steady one-dimensional (1D) flow regions of essentially half the domain width each. The wealth of spatiotemporal complexity uncovered presents a bountiful arena in which to study the existence of simple invariant localised solutions which presumably underpin all of the observed behaviour.
Compressible Taylor–Couette flow – instability mechanism and codimension 3 points
Authors: Welsh Stephanie , Kersalé Evy , Jones Chris A.
Published: June 2014

Taylor–Couette flow in a compressible perfect gas is studied. The onset of instability is examined as a function of the Reynolds numbers of the inner and outer cylinder, the Mach number of the flow and the Prandtl number of the gas. We focus on the case of a wide gap, with radius ratio 0.5. We find new modes of instability at high Prandtl number, which can allow oscillatory axisymmetric modes to onset first. We also find that onset can occur even when the angular momentum increases outwards, so that the classical Rayleigh criterion can be violated in the compressible case. We have also considered the case of counter-rotating cylinders, where the $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}m=0$ and $m=1$ modes can onset simultaneously to give a codimension 2 bifurcation, leading to the formation of complex flow patterns. In compressible flow we also find codimension 3 points. The Mach number and the critical inner and outer Reynolds numbers can be adjusted so that the two neutral curves for the $m=0$ and $m=1$ modes touch rather than cross. Complex codimension 3 points occur more readily in the compressible case than in the Boussinesq case, and they are expected to lead to a rich nonlinear behaviour.
Relation between understanding and agreeing in response to one-sentence assertion*
Authors: OZURU YASUHIRO , BOWIE DAVID , KAUFMAN GIULIA
Published: June 2014

abstract

Three quasi-experimental studies were conducted to investigate the relationship between the evaluative (i.e., agree/true) and the meta-cognitive (i.e., understand) response, and to determine which type of response people are more likely to provide when responding to one-sentence assertive statements. In Studies 1 and 2, participants performed two separate tasks in which they were asked to indicate the levels of: (i) understanding and (ii) agreement / perceived truthfulness of 126 one-sentence statements. The results indicated that participants were likely to provide a negative evaluative response (i.e., disagree/false) to a statement that they did not understand. In Study 3, participants were asked to evaluate the same 126 statements and choose between four response options: agree, disagree, understand, do not understand. The results indicated that people are more likely provide an evaluative response regardless of the understandability of a statement. The results of these studies are discussed in relation to (i) pragmatic perspective of how people infer speakers’ meaning, and (ii) cognitive processes underlying evaluative and meta-cognitive response.
NONINNER AUTOMORPHISMS OF ORDER IN FINITE -GROUPS OF COCLASS 2, WHEN
Authors: FOULADI S. , ORFI R.
Published: June 2014

It is shown that if $G$ is a finite $p$-group of coclass 2 with $p>2$, then $G$ has a noninner automorphism of order $p$.
Aristophanes vs. Socrates
Authors: ADAMS DON
Published: June 2014

In Plato’sApology, Socrates claims thatphthonosanddiabolēcaused Aristophanes to become one of his accusers. Either Socrates is blowing things out of proportion because Aristophanes was clearly just kidding around, or we are wrong to pass Aristophanes’ humour off as ‘just kidding around.’ In this paper, I defend the second alternative. I argue that Aristophanes is a specific kind of social conservative and that Socrates was the sort of social liberal that bothered Aristophanes. I conclude thatCloudsis not innocent, but is, as Socrates claimed, driven byphthonosanddiabolē.
Heat shock protein 90 as a potential drug target against surra
Authors: ROCHANI ANKIT K. , MITHRA CHANDAN , SINGH MEETALI , TATU UTPAL
Published: June 2014

Trypanosomiasis is caused by Trypanosoma species which affect both human and animal populations and pose a major threat to developing countries. The incidence of animal trypanosomiasis is on the rise. Surra is a type of animal trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority list B of significant diseases by the World Organization of Animal Health (OIE). Control of surra has been a challenge due to the lack of effective drugs and vaccines and emergence of resistance towards existing drugs. Our laboratory has previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a potential drug target and successfully demonstrated efficacy of an Hsp90 inhibitor in cell culture as well as a pre-clinical mouse model of trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life cycle and its potential as a drug target. It appears plausible that the repertoire of Hsp90 inhibitors available in academia and industry may have value for treatment of surra and other animal trypanosomiasis.
Précis onThe Cognitive-Emotional Brain
Authors: Pessoa Luiz
Published: June 2014

InThe Cognitive-Emotional Brain(Pessoa 2013), I describe the many ways that emotion and cognition interact and are integrated in the brain. The book summarizes five areas of research that support this integrative view and makes four arguments to organize each area. (1) Based on rodent and human data, I propose that the amygdala's functions go beyond emotion as traditionally conceived. Furthermore, the processing of emotion-laden information is capacity limited, thus not independent of attention and awareness. (2) Cognitive-emotional interactions in the human prefrontal cortex (PFC) assume diverse forms and are not limited to mutual suppression. Particularly, the lateral PFC is a focal point for cognitive-emotional interactions. (3) Interactions between motivation and cognition can be seen across a range of perceptual and cognitive tasks. Motivation shapes behavior in specific ways – for example, by reducing response conflict or via selective effects on working memory. Traditional accounts, by contrast, typically describe motivation as a global activation independent of particular control demands. (4) Perception and cognition are directly influenced by information with affective or motivational content in powerful ways. A dual competition model outlines a framework for such interactions at the perceptual and executive levels. A specific neural architecture is proposed that embeds emotional and motivational signals into perception and cognition through multiple channels. (5) A network perspective should supplant the strategy of understanding the brain in terms of individual regions. More broadly, in a network view of brain architecture, “emotion” and “cognition” may be used as labels of certain behaviors, but will not map cleanly into compartmentalized pieces of the brain.
Linear theory of quantum two-stream instability in a magnetized plasma with a transverse wiggler magnetic field
Authors: Hasanbeigi A. , Moghani S. , Mehdian H.
Published: June 2014

A fluid description is used to study the properties of two-stream instability due to interaction of a non-relativistic electron beam with quantum magnetized plasma and transverse wiggler magnetic field. It is assumed that the background plasma provides charge and current neutralization of the electron beam. The dispersion relation is obtained by solving and linearizing fluid-Maxwell equations. The resulting dispersion equation is analyzed numerically over a wide range of system parameters. The results of quantum and classical treatments are compared numerically, with including the effects of wiggler on the dispersion relation. It is found that the transverse wiggler magnetic field can strongly improve the instability of quantum plasma as well as classical plasma.
CAUSAL ANALYSIS AFTER HAAVELMO
Authors: Heckman James , Pinto Rodrigo
Published: June 2014

Haavelmo’s seminal 1943 and 1944 papers are the first rigorous treatment of causality. In them, he distinguished the definition of causal parameters from their identification. He showed that causal parameters are defined usinghypotheticalmodels that assign variation to some of the inputs determining outcomes while holding all other inputs fixed. He thus formalized and made operational Marshall’s (1890)ceteris paribusanalysis. We embed Haavelmo’s framework into the recursive framework of Directed Acyclic Graphs (DAGs) commonly used in the literature of causality (Pearl, 2000) and Bayesian nets (Lauritzen, 1996). We compare the analysis of causality based on a methodology inspired by Haavelmo’s ideas with other approaches used in the causal literature of DAGs. We discuss the limitations of methods that solely use the information expressed in DAGs for the identification of economic models. We extend our framework to consider models for simultaneous causality, a central contribution of Haavelmo.
TRYGVE HAAVELMO AND THE EMERGENCE OF CAUSAL CALCULUS
Authors: Pearl Judea
Published: June 2014

Haavelmo was the first to recognize the capacity of economic models to guide policies. This paper describes some of the barriers that Haavelmo’s ideas have had (and still have) to overcome and lays out a logical framework that has evolved from Haavelmo’s insight and matured into a coherent and comprehensive account of the relationships between theory, data, and policy questions. The mathematical tools that emerge from this framework now enable investigators to answer complex policy and counterfactual questions using simple routines, some by mere inspection of the model’s structure. Several such problems are illustrated by examples, including misspecification tests, nonparametric identification, mediation analysis, and introspection. Finally, we observe that economists are largely unaware of the benefits that Haavelmo’s ideas bestow upon them and, to close this gap, we identify concrete recent advances in causal analysis that economists can utilize in research and education.
What Future for Human Rights?
Authors: Nickel James W.
Published: June 2014

Like people born shortly after World War II, the international human rights movement recently had its sixty-fifth birthday. This could mean that retirement is at hand and that death will come in a few decades. After all, the formulations of human rights that activists, lawyers, and politicians use today mostly derive from the UN Universal Declaration of Human Rights, and the world in 1948 was very different from our world today: the cold war was about to break out, communism was a strong and optimistic political force in an expansionist phase, and Western Europe was still recovering from the war. The struggle against entrenched racism and sexism had only just begun, decolonization was in its early stages, and Asia was still poor (Japan was under military reconstruction, and Mao's heavy-handed revolution in China was still in the future). Labor unions were strong in the industrialized world, and the movement of women into work outside the home and farm was in its early stages. Farming was less technological and usually on a smaller scale, the environmental movement had not yet flowered, and human-caused climate change was present but unrecognized. Personal computers and social networking were decades away, and Earth's human population was well under three billion.
Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations
Authors: NAGEL-WOLFRUM KERSTIN , MÖLLER FABIAN , PENNER INESSA , WOLFRUM UWE
Published: June 2014

The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30–50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the potential of TRIDs as an alternative pharmacologic treatment strategy for treating nonsense mutation-based retinal disorders.
Impairments in facial affect recognition associated with autism spectrum disorders: A meta-analysis
Authors: Lozier Leah M. , Vanmeter John W. , Marsh Abigail A.
Published: June 2014

Autism spectrum disorders (ASDs) are characterized by social impairments, including inappropriate responses to affective stimuli and nonverbal cues, which may extend to poor face-emotion recognition. However, the results of empirical studies of face-emotion recognition in individuals with ASD have yielded inconsistent findings that occlude understanding the role of face-emotion recognition deficits in the development of ASD. The goal of this meta-analysis was to address three as-yet unanswered questions. Are ASDs associated with consistent face-emotion recognition deficits? Do deficits generalize across multiple emotional expressions or are they limited to specific emotions? Do age or cognitive intelligence affect the magnitude of identified deficits? The results indicate that ASDs are associated with face-emotion recognition deficits across multiple expressions and that the magnitude of these deficits increases with age and cannot be accounted for by intelligence. These findings suggest that, whereas neurodevelopmental processes and social experience produce improvements in general face-emotion recognition abilities over time during typical development, children with ASD may experience disruptions in these processes, which suggested distributed functional impairment in the neural architecture that subserves face-emotion processing, an effect with downstream developmental consequences.
Catechol-O-methyltransferase Val158Met genotype moderates the effect of disorganized attachment on social development in young children
Authors: Hygen Beate Wold , Guzey Ismail Cuneyt , Belsky Jay , Berg-Nielsen Turid Suzanne , Wichstrøm Lars
Published: June 2014

Children with histories of disorganized attachment exhibit diverse problems, possibly because disorganization takes at least two distinctive forms as children age: controlling–punitive and controlling–caregiving. This variation in the developmental legacy of disorganization has been attributed primarily to variations in children's rearing experiences. Here an alternative explanation of these divergent sequelae of disorganization is evaluated: one focused on genotype. Structural equation modeling was applied to data on 704 Norwegian children to test whether the catechol-O-methyltransferase Val158Met genotype moderates the effect of disorganized attachment, which was measured dimensionally at 4 years of age using the Manchester Child Attachment Story Task, on changes in aggressive behavior and social competence from ages 4 to 6. Children who scored high on disorganization and were homozygous for the valine allele displayed significantly greater increases in aggression and decreases in self-oriented social skills (e.g., self-regulation and assertiveness) over time than did their disorganized counterparts carrying the methionine allele, whereas disorganized children carrying the methionine allele increased their other-oriented social skill (e.g., cooperation and responsibility) scores more than did valine-homozygous children. These results are consistent with the controlling–punitive and controlling–caregiving behaviors observed in disorganized children, suggesting that the children's genotype contributed to variations in the social development of disorganized children.
Developmental trajectories of anxious and depressive problems during the transition from childhood to adolescence: Personality × Parenting interactions
Authors: Prinzie Peter , van Harten Leanthe V. , Deković Maja , van den Akker Alithe L. , Shiner Rebecca L.
Published: June 2014

This study examined separate developmental trajectories of anxious and depressive symptoms from childhood to adolescence (9–15 years) in a community-based sample (N= 290). At three measurement points, mothers and fathers reported on their children's anxious and depressive symptoms, and at Time 1 they reported on lower order child personality facets and on their parenting. By means of growth mixture modeling, three developmental trajectories were identified for anxious symptoms: steady low (82%), moderate increasing–decreasing (5.9%), and high declining groups (12.1%). For depressive symptoms, two developmental trajectories were found: steady low (94.1%) and moderate increasing groups (5.9%). Higher shyness, irritability, and altruism predicted membership in more problematic anxious and depressive groups. The personality facets energy, optimism, compliance, and anxiety were unique predictors for class membership for anxious symptoms, and the effects of shyness, irritability, and compliance were moderated by overreactive parenting. Shyness and irritability increased the probability of following the moderate increasing–decreasing anxiety trajectory, but only in the context of high or average levels of overreactive parenting. Compliance increased the probability of following the moderate increasing–decreasing and high decreasing trajectories in the context of high overreactive parenting. Our results indicate that childhood personality facets differentiate trajectories of anxious and depressive symptoms in theoretically compelling ways.
Social attribution skills of children born preterm at very low birth weight
Authors: Williamson Kathryn E. , Jakobson Lorna S.
Published: June 2014

Children born prematurely at very low birth weight (<1500 g) are at increased risk for impairments affecting social functioning, including autism spectrum disorders (e.g., Johnson et al., 2010). In the current study, we used the Happé–Frith animated triangles task (Abell, Happé, & Frith, 2000) to study social attribution skills in this population. In this task, typical viewers attribute intentionality and mental states to shapes, based on characteristics of their movements. Participants included 34 preterm children and 36 full-term controls, aged 8–11 years. Groups were comparable in terms of age at test, gender, handedness, and socioeconomic status; they also performed similarly on tests of selective attention/processing speed and verbal intelligence. Relative to full-term peers, preterm children's descriptions of the animations were less appropriate overall; they also overattributed intentionality/mental states to randomly moving shapes and underattributed intentionality/mental states to shapes that seemed to be interacting socially. Impairments in the ability to infer the putative mental states of triangles from movement cues alone were most evident in children displaying more “autistic-like” traits, and this may reflect atypical development of and/or functioning in, or atypical connections between, parts of the social brain.
Positional Goods
Authors: Hollis Martin
Published: June 2014

In days gone by, when we had something called Rapid Economic Growth, we used to worry about it. We worried especially about its social costs and its technical limits. If growth meant gearing people to efficient production, we would have to be geographically and socially mobile. That threatened our old ways of community life, with their neighbourhood values and extended families. There were more obvious costs too, like chemicals in the air and highways through the landscape. Furthermore, the cornucopia need not be bottomless. To sustain its effusions, nature might have to be pillaged until we ran out of trees or oil. Technology might hit bottlenecks so severe that costs began to outrun benefits. That would mean thwarting the new expectations which economic growth had aroused and which were its motivating force. But, for all that, our island race faced the horrors of affluence, abundance and goodies for all with a stiff upper lip.
Seasonal influence on dormancy alleviation inDodonaea viscosa(Sapindaceae) seeds
Authors: Jaganathan Ganesh K. , Liu Baolin
Published: June 2014

Seeds ofDodonaea viscosa(Sapindaceae) have a water-impermeable seed coat, i.e. physical dormancy (PY). Although mechanical scarification, dry heat, sulphuric acid and hot water treatment make seeds permeable under laboratory conditions, the mechanisms by which dormancy is alleviated in natural environments have not yet been understood completely. The present investigation aims to understand the pattern of dormancy alleviation inD. viscosaseeds using an artificial burial approach for 2 years. Freshly collected seeds held in hydrated soil at 10/20°C, 15/20°C, 15/30°C, 20/35°C and 25°C for 32 weeks germinated to less than 15%, irrespective of storage temperature. Dry storage of seeds at 15, 20, 25 and 30°C for 1 year did not break dormancy. Hot water treatment at 80 and 90°C for 30 s broke dormancy in 90% of the seeds. On the other hand, burying seeds at a depth of 3–5 cm in the natural environment for 2 years increased germination from 7 to 71%. In particular, seeds exhumed after summer in both years showed a significant increase in germination percentage(P< 0.05). However, seeds buried after summer did not germinate to a higher percentage when exhumed prior to summer. We suggest that a high summer temperature, rising above 60°C in the top soil layer of the tropics, is a likely factor breaking dormancy. Most seeds germinated during burial, which indicates that light is not a cue for germination. We conclude that germination ofD. viscosafollowing summer is an adaptive mechanism to tolerate summer droughts, which are common in the dry tropics.
Opt-Outs and Upgrades
Authors: STAMMERS TREVOR , JAMES MATT
Published: June 2014

We report on two areas in which UK law and ethics seem out of step with each
other. 2013 saw the passing of the Human Transplantation (Wales) Bill, which
will introduce an opt-out system of organ donation in Wales from 2015. In the
first section, we discuss the convoluted evolution of the Bill and some
potential problems that we consider may prevent it from achieving its intended
goal of increasing the number of organs transplanted. The prospect of being able
to enhance human cognition through cognitive-enhancing drugs (“smart
drugs”) also presents a nexus of questions associated with future
ambitions, hopes, and concerns as a society. How these drugs might affect the
future of work and employment is beginning to generate wide public engagement in
the UK and forms the focus of the second section.