bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the effects of serum iron levels on lacrimal gland secretion
Authors: Erdogan Firat , Eliaçık Mustafa , Senkal Evrim , Erdur Sevil Karaman , Kulak Kudret , Ipek Ilke Ozahi
Published: July 2015

In our study we aimed to demonstrate the relationship between the serum iron levels, and tears quality and quantity in term newborns. This study was conducted at a single institution between March 2013 and May 2013. A total of 46 newborns were prospectively enrolled. Serum iron levels were measured via the umbilical cord blood. Infants were divided into two groups according to their serum iron levels. Group A, serum iron level ≤70 μg/dL (n = 27) and Group B, serum iron level > 70 μg/dL (n = 19). The evaluation of the osmolarity was tested by using the TearLab Osmolarity System (TearLab Co, San Diego, CA, USA). The assessment of quantity was performed by using Schirmer I test. Osmolarity testing and Schirmer I test (with/without anesthesia) were performed bilaterally on the 1st day of life by an ophthalmologist. The outcomes of Schirmer I and tear osmolarity showed no statistically significant difference between right and left eyes of any infant in the groups. Moreover, there was no statistical difference between sexes in these two groups. Osmolarity was found to have a moderate negative correlation coefficient with serum iron level (r = −0.4, p < 0.01). Furthermore, there was a high positive correlation between Schirmer I with anesthesia and serum iron levels (r = 0.7, p < 0.01). We observed that the quality and quantity of the tears was lower in term newborns with lower serum iron levels than healthy newborns. These results indicate that low serum iron level could affect lacrimal gland functions.
“Back to the future?” Cuban—Russian relations under Raúl Castro
Authors: Bain Mervyn J.
Published: July 2015

Since Raúl Castro has become the President of Cuba relations between Moscow and Havana have displayed a number of reminiscence of the halcyon days of Soviet—Cuban relations, which has included Raúl Castro and Dmitry Medvedev traveling to Russia and Cuba twice, respectively and Vladimir Putin visiting the Cuban capital in July 2014. Correspondingly, this article will examine the relationship that is developing between the two countries with the aim to find out whether the bilateral relationship has “gone back to the future” since August 2006. Also it should conclude if a “Raúl” doctrine’ similar to the “Putin doctrine,” which has been vital for this relationship, has emerged within the realm of Cuban foreign policy.
Trauma and Adversity in the Lives of Children and Adolescents Attending a Mental Health Service
Authors: Reay Rebecca E. , Raphael Beverley , Aplin Velissa , McAndrew Virginia , Cubis Jeffery C. , Riordan Denise M. , Palfrey Nicola , Preston Wendy
Published: July 2015

Although childhood trauma and family adversity can increase vulnerability to serious mental health problems, uncertainty exists about the nature and prevalence in a clinical population. This embedded research aims to establish the prevalence of trauma and adversity in young people seeking help from Child and Adolescent Mental Health Services (CAMHS). All children, adolescents, and their parents/guardian attending their initial assessment at a CAMHS service were invited to participate in the ‘Stressful Life and Family Difficulties study’ and a clinical interview. 162 families participated in the study. It was more common for young people to experience multiple adversities (three or more) in the last 12 months than single events. Mothers self-reported a greater number of family adversities than fathers. According to clinicians, the most frequent adversities experienced by young people were having a parent with a mental illness (66%), being bullied (63%) and parental divorce or separation (43%). Overall, clinicians reported that 69% of CAMHS clients had experienced a potentially traumatic experience (any physical, emotional or sexual abuse, child neglect or traumatic event). Moreover, young people with trauma histories were significantly more likely to have a parent with a history of trauma.
Respiratory Outbreak Investigations: How Many Specimens Should Be Tested?
Authors: Schleihauf Emily , Fathima Sumana , Pettipas Janice , LeBlanc Jason J. , Hatchette Todd F. , Drews Steven J. , Haldane David
Published: July 2015

To determine the optimal number of specimens for virus detection in a respiratory outbreak, laboratory results from 2 Canadian public health laboratories were reviewed. The evidence suggests that 3 specimens are sufficient for detection of a virus in >95% of outbreaks, thereby reducing laboratory costs.

Infect. Control Hosp. Epidemiol. 2015;36(11): 1344–1347
Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice
Authors: Velez Eva M. M. , Maldonado Galdeano Carolina , Carmuega Esteban , Weill Ricardo , Bibas Bonet María E. , Perdigón Gabriela
Published: July 2015

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisation process. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treating allergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed with PFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-γ (IFN-γ), IL-4, IL-10 and total secretory IgA (S-IgA) were measured in the supernatants of macerated lungs or in the BALF. The levels of IgA+, CD4+and CD8+T lymphocytes and F4/80+cells were measured in the lungs by immunofluorescence. Inducible CD4+/CD25/Foxp3+regulatory T (Treg) cells were evaluated in the lungs. PFM shifted the T helper (Th)2 profile response towards a Th1 response that led to the production of IgG instead of IgE, with increasing levels of IL-10 and IFN-γ that play an important role in immunomodulation exerted by PFM administration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels of anti-OVA-specific IgG and total S-IgA. PFM did not influence Tregcells in treated mice. Consumption of PFM could be a promising strategy in the amelioration of airway allergies, considering that the effect is mediated by the production of IgG through the activation of Th1 instead of the direct activation of Th2 cells to produce IgE.
Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice
Authors: van den Elsen Lieke W. J. , van Esch Betty C. A. M. , Dingjan Gemma M. , Hofman Gerard A. , Garssen Johan , Willemsen Linette E. M.
Published: July 2015

Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 % soyabean oil diet before and during oral sensitisation with whey or whey hyperimmune serum transfer. Another group of mice received partial whey hydrolysate (pWH) while being fed the diets before oral sensitisation. The acute allergic skin response, serum Ig level, mouse mast cell protease-1 (mMCP-1) concentration and/or splenic T-cell percentages were determined upon whey challenge. When the diets were provided before and during oral sensitisation, the acute allergic skin response was increased in mice fed the 10 % soyabean oil diet compared with the 7 % soyabean oil diet. Whey IgE and IgG1 levels remained unaltered, whereas mMCP-1 levels increased in mice fed the 10 % soyabean oil diet. Furthermore, allergic symptoms were increased in naive mice fed the 10 % soyabean oil diet and sensitised with whey hyperimmune serum. In addition to enhancing the mast cell response, the 10 % soyabean oil diet increased the percentage of activated Th1 and Th2 cells as well as increased the ratios of Th2:regulatory T cells and Th2:Th1 when compared with the 7 % soyabean oil diet. Oral tolerance induction by pWH was abrogated in mice fed the 10 % soyabean oil diet compared with those fed the 7 % soyabean oil diet during pretreatment with pWH. In conclusion, increased intake of soyabean oil rich in n-6 PUFA suppresses tolerance induction by pWH and enhances the severity of the allergic effector response in whey-allergic mice. Dietary vegetable oils rich in n-6 PUFA may enhance the susceptibility to develop or sustain food allergy.
INFORMING DISINVESTMENT WITH LIMITED EVIDENCE: COBALAMIN DEFICIENCY IN THE FATIGUED
Authors: Mnatzaganian George , Karnon Jonathan , Moss John R. , Elshaug Adam G. , Metz Michael , Frank Oliver R. , Hiller Janet E.
Published: July 2015

Objectives:Health technology reassessment and disinvestment can be difficult due to uncertainties regarding available evidence. Pathology testing to investigate cobalamin (vitamin B12) deficiency is a strong case in point. We conducted a 3-month economic evaluation of five strategies for diagnosing and treating cobalamin deficiency in adult patients hypothetically presenting with new unexplained fatigue in the primary care setting. The first consultation per patient was considered. Screening tests other than serum cobalamin were not included.

Methods: A cost-effectiveness analysis was undertaken using a decision tree to represent the diagnostic / treatment pathways, with relevant cost and utility scores assigned to different stages in the evaluation process. Input parameter values were estimated from published evidence, supplemented by expert opinion, with sensitivity analysis undertaken to represent parameter uncertainty.

Results:Ordering serum vitamin B12to assess cobalamin deficiency among patients with unexplained fatigue was not cost-effective in any patient population, irrespective of pretest prevalence of this deficiency. For patients with a pretest prevalence above 1 percent, treating all with oral vitamin B12supplements without testing was most cost-effective, whereas watchful waiting with symptoms monitoring was most cost-effective for patients with lower pretest prevalence probabilities.

Conclusions:Substantial evidence gaps exist for parameter estimation: questionable cobalamin deficiency levels in the fatigued; debatable treatment methods; unknown natural history of the condition. Despite this, we reveal a robust path for disinvestment decision making in the face of a paradox between the evidence required to inform disinvestment compared with its paucity in informing initial funding decisions.
Why Food Safety Fails in China: The Politics of Scale
Authors: Yasuda John Kojiro
Published: July 2015

This article examines food safety failures in China to cast light on how scale has deeply affected its regulatory politics. Contrary to studies that view China's food safety challenges as primarily resulting from corruption, local obstructionism or weak state capacity, I argue that China's massive production system, unwieldy bureaucracy, and geographic size pose regulators with a more fundamental policy challenge. As they attempt to build an integrated national regulatory regime, regulators must make difficult trade-offs in cost, policy design and applicability that emphasize the interests of certain stakeholders over others, resulting in a contentious “politics of scale.” The article assesses four failed scale management initiatives: food safety coordination bodies, campaigns, model production zones, and regulatory segmentation. As China transitions to scientifically assessed, risk-based forms of regulation, its pervasive food safety problem suggests the adaptive limits of China's unitary regulatory structure to manage scale and its ensuing politics effectively in a complex multilevel context.
Neurologic state transitions in the eye and brain: Kinetics of loss
and recovery of vision and consciousness
Authors: WHINNERY TYP , FORSTER ESTRELLA M.
Published: July 2015

Visual alterations, peripheral light loss (PLL) and blackout (BO), are components
of acceleration (+Gz) induced loss of consciousness (LOC) and
recovery of consciousness (ROC). The kinetics of loss of vision (LOV) and
recovery of vision (ROV) were determined utilizing ocular pressure induced
retinal ischemia and compared to the kinetics of LOC and ROC resulting from
+Gz-induced cephalic nervous system (CPNS) ischemia. The time from
self-induced retinal ischemia in completely healthy subjects (N
= 104) to the onset of PLL and complete BO was measured. The time
from release of ocular pressure, with return of normal retinal circulation, to
the time for complete recovery of visual fields was also measured. The kinetics
of pressure induced LOV and ROV was compared with previously developed kinetics
of +Gz-induced LOC and ROC focusing on the rapid onset, vertical arm,
of the +Gz-induced LOC and ROC curves. The time from onset of
increased ocular pressure, immediately inducing retinal ischemia, to PLL was
5.04 s with the time to BO being 8.73 s. Complete recovery of the visual field
from BO following release of ocular pressure, immediately abolishing retinal
ischemia, was 2.74 s. These results confirm experimental findings that visual
loss is frequently not experienced prior to LOC during exposure to rapid onset,
high levels of +Gz-stress above tolerance. Offset of pressure induced
retinal ischemia to ROV was 2.74 s, while the time from offset of
+Gz-induced CPNS ischemia to ROC was 5.29 s. Recovery of retinal
function would be predicted to be complete before consciousness is regained
following +Gz-induced LOC. Ischemia onset time normalization in
neurologic tissues permits comparison between different stress-induced times to
altered function. The +Gz-time tolerance curves for LOV and LOC
provide comparison and integration of neurologic state transition kinetics in
the retina and CPNS.
Topographic organization of areas V3 and V4 and its relation to supra-areal organization of the primate visual system
Authors: ARCARO M.J. , KASTNER S.
Published: July 2015

Areas V3 and V4 are commonly thought of as individual entities in the primate visual system, based on definition criteria such as their representation of visual space, connectivity, functional response properties, and relative anatomical location in cortex. Yet, large-scale functional and anatomical organization patterns not only emphasize distinctions within each area, but also links across visual cortex. Specifically, the visuotopic organization of V3 and V4 appears to be part of a larger, supra-areal organization, clustering these areas with early visual areas V1 and V2. In addition, connectivity patterns across visual cortex appear to vary within these areas as a function of their supra-areal eccentricity organization. This complicates the traditional view of these regions as individual functional “areas.” Here, we will review the criteria for defining areas V3 and V4 and will discuss functional and anatomical studies in humans and monkeys that emphasize the integration of individual visual areas into broad, supra-areal clusters that work in concert for a common computational goal. Specifically, we propose that the visuotopic organization of V3 and V4, which provides the criteria for differentiating these areas, also unifies these areas into the supra-areal organization of early visual cortex. We propose that V3 and V4 play a critical role in this supra-areal organization by filtering information about the visual environment along parallel pathways across higher-order cortex.
The police and the urban ‘dangerous classes’: the culture and practice of public law and order in Milan after national unity
Authors: MORI SIMONA
Published: July 2015

The city of Milan during the second half of the nineteenth century is the field of observation for this study, which focuses on urban policing and social control in a situation that ultimately caused problems for the whole country. The case of Milan, which has not received enough attention in this regard, is particularly interesting, given its status as the northern metropolis. It was the second largest population centre in Italy and the most important economic one, a leader in the late struggle for political independence and an opponent at that time of the centralizing policies of the nation-state.1
SERMON AND STORY IN GEORGE MACDONALD
Authors: Dubois Martin
Published: July 2015

George MacDonald took to preachingearly in life. In his boyhood he once “rushed into the kitchen, jumped upon the clean-scrubbed table, and began a learned discourse, indicating Bell Mavor, the maid, as a reprobate past redemption”:

She flicked at him with her dish-clout, when he turned upon her in righteous anger, as he set straight the improvised bands about his neck: “Div ye no ken fan ye’re speakin’ til a meenister, Bell? Ye's no fleg [frighten] awa’ the Rev. Geordie MacDonald as gin he war a buzzin’ flee [fly]! Losh, woman, neist to Dr. Chaumers [Thomas Chalmers], he's the grandest preacher in a’ Scotland!” (Greville MacDonald 59)

Before long MacDonald would grow uneasy with the Calvinist beliefs from which this childhood frolic takes its bearings. He would later characterise the religion of his youth as one in which “hell is invariably the deepest truth, and the love of God is not so deep as hell” (Robert Falconer1: 152). Coming to feel “that the more perfect a theory about the infinite, the surer it is to be wrong” (qtd. in Greville MacDonald 155), MacDonald in maturity embraced a broad and undogmatic theology, and – at the urging of F. D. Maurice – eventually joined the Church of England. Yet the impulse to preach never left him. MacDonald is now principally remembered as a writer of fantasy and fairy tales, but his literary career was in one sense a stand-in for the pulpit. He briefly served as a Congregationalist minister in Arundel before being forced out for his unorthodox views on salvation. Unable to secure another appointment, and sustaining “a hand-to-mouth existence” with his family in Manchester, MacDonald came to prose fiction “through economic necessity” (Raeper 103, 125). Even once he had achieved literary fame, MacDonald continued to preach occasionally by invitation. Over the course of his lifetime he would also publish several volumes of sermons never delivered – not simply spiritual reflections, but, as the title of a series of his volumes has it,Unspoken Sermons(1867–1889).
QUANTUM TEAM LOGIC AND BELL’S INEQUALITIES
Authors: HYTTINEN TAPANI , PAOLINI GIANLUCA , VÄÄNÄNEN JOUKO
Published: July 2015

A logical approach to Bell’s Inequalities of quantum mechanics has been introduced by Abramsky and Hardy (Abramsky & Hardy, 2012). We point out that the logical Bell’s Inequalities of Abramsky & Hardy (2012) are provable in the probability logic of Fagin, Halpern and Megiddo (Fagin et al., 1990). Since it is now considered empirically established that quantum mechanics violates Bell’s Inequalities, we introduce a modified probability logic, that we call quantum team logic, in which Bell’s Inequalities are not provable, and prove a Completeness theorem for this logic. For this end we generalise the team semantics of dependence logic (Väänänen, 2007) first to probabilistic team semantics, and then to what we call quantum team semantics.
Commitment in Different Relationships Statuses: Validation Study of the Personal Commitment Scale
Authors: Monteiro Ana Pego , Costa-Ramalho Susana , Ribeiro Maria Teresa , Pinto Alexandra Marques
Published: July 2015

This study presents the validation process of the Portuguese version of the short-form Dedication Scale (Rhoades, Stanley, & Markman, 2006; Stanley, 1986), with a sample of 924 participants in different relationship statutes. With 14 items, this short version is recommended by the authors for its simple use, when wanting to measure commitment in romantic relationships. Confirmatory factor analysis showed that the instrument did not have a totally acceptable fit with the data so an exploratory factor analysis was conducted. This revealed a one-dimensional structure of the scale, and led to the exclusion of two items, which relate to a distinct meta-commitment dimension. In sum, the Portuguese version (ECP - Personal Commitment Scale) has 12 items, with good internal consistency (α = .82), correlations item-total between .36 and .60, and good criteria validity (p< .001). Its use for research is therefore appropriate. In a second study, significant differences were found between the participants' four relationship statuses (dating non-cohabiting and cohabiting relationships, formal unions and marriage) (p< .001; η2p= .03). Results showed that married participants were more committed than those in a formal union, even when controlling for several relational and socio-demographic variables. No differences were found between cohabiting and non-cohabiting dating participants. Men reported higher levels of commitment than women (p< .001; η2p= .02). Implications and suggestions for future research are discussed.
Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin
Authors: Escobar D , Hepp M I , Farkas C , Campos T , Sodir N M , Morales M , Álvarez C I , Swigart L , Evan G I , Gutiérrez J L , Nishinakamura R , Castro A F , Pincheira R
Published: July 2015

The Sall2 transcription factor is deregulated in several cancers; however, little is known about its cellular functions, including its target genes. Recently, we demonstrated that p53 directly regulates Sall2 expression under genotoxic stress. Here, we investigated the role of Sall2 in the context of cellular response to genotoxic stress. In addition, we further examined the Sall2-p53 relationship during genotoxic stress in primary mouse embryo fibroblasts (MEFs), which are derived fromSall2knockout mice separately, or in combination with thep53ERTAMknock-in mice. We found that the levels of Sall2 mRNA and protein are dynamically modulated in response to doxorubicin. At early times of stress, Sall2 is downregulated, but increases under extension of the stress in a p53-independent manner. Based on caspase-3/7 activities, expression of cleaved poly (ADP-ribose) polymerase, expression of cleaved caspase-3 and induction of proapoptotic proteins, Sall2 expression was correlated with cellular apoptosis. Consequently,Sall2−/−MEFs have decreased apoptosis, which relates with increased cell viability in response to doxorubicin. Importantly, Sall2 was required for apoptosis even in the presence of fully activated p53. Searching for putative Sall2 targets that could mediate its role in apoptosis, we identified proapoptoticNOXA/PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1). We demonstrated that Sall2 positively regulatesNoxapromoter activity. Conserved putative Sall2-binding sites at theNOXApromoter were validatedin vitroby electrophoretic mobility shift assay andin vivoby ChIP experiments, identifyingNOXAas a novel Sall2 target. In agreement, induction of Noxa protein and mRNA in response to doxorubicin was significantly decreased inSall2−/−MEFs. In addition, studies in leukemia Jurkat T cells support the existence of the Sall2/Noxa axis, and the significance of this axis on the apoptotic response to doxorubicin in cancer cells. Our study highlights the relevance of Sall2 in the apoptotic response to extended genotoxic stress, which is important for understanding its role in normal physiology and disease.
Targeting Mdmx to treat breast cancers with wild-type p53
Authors: Haupt S , Buckley D , Pang J-MB , Panimaya J , Paul P J , Gamell C , Takano E A , Ying Lee Y , Hiddingh S , Rogers T-M , Teunisse A F A S , Herold M J , Marine J-C , Fox S B , Jochemsen A , Haupt Y
Published: July 2015

The function of the tumor suppressor p53 is universally compromised in cancers. It is the most frequently mutated gene in human cancers (reviewed). In cases where p53 is not mutated, alternative regulatory pathways inactivate its tumor suppressive functions. This is primarily achieved through elevation in the expression of the key inhibitors of p53: Mdm2 or Mdmx (also called Mdm4) (reviewed). In breast cancer (BrCa), the frequency of p53 mutations varies markedly between the different subtypes, with basal-like BrCas bearing a high frequency of p53 mutations, whereas luminal BrCas generally express wild-type (wt) p53. Here we show that Mdmx is unexpectedly highly expressed in normal breast epithelial cells and its expression is further elevated in most luminal BrCas, whereas p53 expression is generally low, consistent with wt p53 status. Inducible knockdown (KD) of Mdmx in luminal BrCa MCF-7 cells impedes the growth of these cells in culture, in a p53-dependent manner. Importantly, KD of Mdmx in orthotopic xenograft transplants resulted in growth inhibition associated with prolonged survival, both in a preventative model and also in a treatment model. Growth impediment in response to Mdmx KD was associated with cellular senescence. The growth inhibitory capacity of Mdmx KD was recapitulated in an additional luminal BrCa cell line MPE600, which expresses wt p53. Further, the growth inhibitory capacity of Mdmx KD was also demonstrated in the wt p53 basal-like cell line SKBR7 line. These results identify Mdmx growth dependency in wt p53 expressing BrCas, across a range of subtypes. Based on our findings, we propose that Mdmx targeting is an attractive strategy for treating BrCas harboring wt p53.
AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment
Authors: Xu J , Wan P , Wang M , Zhang J , Gao X , Hu B , Han J , Chen L , Sun K , Wu J , Wu X , Huang X , Chen J
Published: July 2015

In mammals, spermatogonial stem cells (SSCs) arise from early germ cells called gonocytes, which are derived from primordial germ cells during embryogenesis and remain quiescent until birth. After birth, these germ cells migrate from the center of testicular cord, through Sertoli cells, and toward the basement membrane to form the SSC pool and establish the SSC niche architecture. However, molecular mechanisms underlying germ cell migration and niche establishment are largely unknown. Here, we show that the actin disassembly factor actin interacting protein 1 (AIP1) is required in both germ cells and Sertoli cells to regulate this process. Germ cell-specific or Sertoli cell-specific deletion of Aip1 gene each led to significant defects in germ cell migration after postnatal day 4 or 5, accompanied by elevated levels of actin filaments (F-actin) in the affected cells. Furthermore, our data demonstrated that interaction between germ cells and Sertoli cells, likely through E-cadherin-mediated cell adhesion, is critical for germ cells’ migration toward the basement membrane. At last, Aip1 deletion in Sertoli cells decreased SSC self-renewal, increased spermatogonial differentiation, but did not affect the expression and secretion levels of growth factors, suggesting that the disruption of SSC function results from architectural changes in the postnatal niche.
miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance
Authors: De Cola A , Volpe S , Budani M C , Ferracin M , Lattanzio R , Turdo A , D'Agostino D , Capone E , Stassi G , Todaro M , Di Ilio C , Sala G , Piantelli M , Negrini M , Veronese A , De Laurenzi V
Published: July 2015

The ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumulating evidences indicate that miR-205-5p is significantly downregulated in breast tumors compared with normal breast tissue and acts as a tumor suppressor directly targeting oncogenes such as Zeb1 and ErbB3. In this study, we report that miR-205-5p is highly expressed in BCSCs and represses directly ERBB2 and indirectly EGFR leading to resistance to targeted therapy. Furthermore, we show that miR-205-5p directly regulates the expression of p63 which is in turn involved in the EGFR expression suggesting a miR-205/p63/EGFR regulation.
Highly indistinguishable photons from deterministic quantum-dot microlenses utilizing three-dimensional in situ electron-beam lithography
Authors: Gschrey M. , Thoma A. , Schnauber P. , Seifried M. , Schmidt R. , Wohlfeil B. , Krüger L. , Schulze J. -H. , Heindel T. , Burger S. , Schmidt F. , Strittmatter A. , Rodt S. , Reitzenstein S.
Published: July 2015

The success of advanced quantum communication relies crucially on non-classical light sources emitting single indistinguishable photons at high flux rates and purity. We report on deterministically fabricated microlenses with single quantum dots inside which fulfil these requirements in a flexible and robust quantum device approach. In our concept we combine cathodoluminescence spectroscopy with advanced in situ three-dimensional electron-beam lithography at cryogenic temperatures to pattern monolithic microlenses precisely aligned to pre-selected single quantum dots above a distributed Bragg reflector. We demonstrate that the resulting deterministic quantum-dot microlenses enhance the photon-extraction efficiency to (23±3)%. Furthermore we prove that such microlenses assure close to pure emission of triggered single photons with a high degree of photon indistinguishability up to (80±7)% at saturation. As a unique feature, both single-photon purity and photon indistinguishability are preserved at high excitation power and pulsed excitation, even above saturation of the quantum emitter.
High-quality EuO thin films the easy way via topotactic transformation
Authors: Mairoser Thomas , Mundy Julia A. , Melville Alexander , Hodash Daniel , Cueva Paul , Held Rainer , Glavic Artur , Schubert Jürgen , Muller David A. , Schlom Darrell G. , Schmehl Andreas
Published: July 2015

Epitaxy is widely employed to create highly oriented crystalline films. A less appreciated, but nonetheless powerful means of creating such films is via topotactic transformation, in which a chemical reaction transforms a single crystal of one phase into a single crystal of a different phase, which inherits its orientation from the original crystal. Topotactic reactions may be applied to epitactic films to substitute, add or remove ions to yield epitactic films of different phases. Here we exploit a topotactic reduction reaction to provide a non-ultra-high vacuum (UHV) means of growing highly oriented single crystalline thin films of the easily over-oxidized half-metallic semiconductor europium monoxide (EuO) with a perfection rivalling that of the best films of the same material grown by molecular-beam epitaxy or UHV pulsed-laser deposition. As the technique only requires high-vacuum deposition equipment, it has the potential to drastically improve the accessibility of high-quality single crystalline films of EuO as well as other difficult-to-synthesize compounds.
A spectrally tunable all-graphene-based flexible field-effect light-emitting device
Authors: Wang Xiaomu , Tian He , Mohammad Mohammad Ali , Li Cheng , Wu Can , Yang Yi , Ren Tian-Ling
Published: July 2015

The continuous tuning of the emission spectrum of a single light-emitting diode (LED) by an external electrical bias is of great technological significance as a crucial property in high-quality displays, yet this capability has not been demonstrated in existing LEDs. Graphene, a tunable optical platform, is a promising medium to achieve this goal. Here we demonstrate a bright spectrally tunable electroluminescence from blue (∼450 nm) to red (∼750 nm) at the graphene oxide/reduced-graphene oxide interface. We explain the electroluminescence results from the recombination of Poole–Frenkel emission ionized electrons at the localized energy levels arising from semi-reduced graphene oxide, and holes from the top of the π band. Tuning of the emission wavelength is achieved by gate modulation of the participating localized energy levels. Our demonstration of current-driven tunable LEDs not only represents a method for emission wavelength tuning but also may find applications in high-quality displays.
Locking GTPases covalently in their functional states
Authors: Wiegandt David , Vieweg Sophie , Hofmann Frank , Koch Daniel , Li Fu , Wu Yao-Wen , Itzen Aymelt , Müller Matthias P. , Goody Roger S.
Published: July 2015

GTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase–acryl–nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.
Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice
Authors: Aoki Shiho , Iwai Atsushi , Kawata Koji , Muramatsu Daisuke , Uchiyama Hirofumi , Okabe Mitsuyasu , Ikesue Masahiro , Maeda Naoyoshi , Uede Toshimitsu
Published: July 2015

Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD).
Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study
Authors: Yuan Zhongshang , Zhao Meng , Zhang Bingchang , Zhang Haiqing , Zhang Xu , Guan Qingbo , Ning Guang , Gao Ling , Xue Fuzhong , Zhao Jiajun
Published: July 2015

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708) and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.
Efficient search for a face by chimpanzees (Pan troglodytes)
Authors: Tomonaga Masaki , Imura Tomoko
Published: July 2015

The face is quite an important stimulus category for human and nonhuman primates in their social lives. Recent advances in comparative-cognitive research clearly indicate that chimpanzees and humans process faces in a special manner; that is, using holistic or configural processing. Both species exhibit the face-inversion effect in which the inverted presentation of a face deteriorates their perception and recognition. Furthermore, recent studies have shown that humans detect human faces among non-facial objects rapidly. We report that chimpanzees detected chimpanzee faces among non-facial objects quite efficiently. This efficient search was not limited to own-species faces. They also found human adult and baby faces-but not monkey faces-efficiently. Additional testing showed that a front-view face was more readily detected than a profile, suggesting the important role of eye-to-eye contact. Chimpanzees also detected a photograph of a banana as efficiently as a face, but a further examination clearly indicated that the banana was detected mainly due to a low-level feature (i.e., color). Efficient face detection was hampered by an inverted presentation, suggesting that configural processing of faces is a critical element of efficient face detection in both species. This conclusion was supported by a simple simulation experiment using the saliency model.
Visual measurement of the evaporation process of a sessile droplet by dual-channel simultaneous phase-shifting interferometry
Authors: Sun Peng , Zhong Liyun , Luo Chunshu , Niu Wenhu , Lu Xiaoxu
Published: July 2015

To perform the visual measurement of the evaporation process of a sessile droplet, a dual-channel simultaneous phase-shifting interferometry (DCSPSI) method is proposed. Based on polarization components to simultaneously generate a pair of orthogonal interferograms with the phase shifts of π/2, the real-time phase of a dynamic process can be retrieved with two-step phase-shifting algorithm. Using this proposed DCSPSI system, the transient mass (TM) of the evaporation process of a sessile droplet with different initial mass were presented through measuring the real-time 3D shape of a droplet. Moreover, the mass flux density (MFD) of the evaporating droplet and its regional distribution were also calculated and analyzed. The experimental results show that the proposed DCSPSI will supply a visual, accurate, noncontact, nondestructive, global tool for the real-time multi-parameter measurement of the droplet evaporation.
Geometric diffusion of quantum trajectories
Authors: Yang Fan , Liu Ren-Bao
Published: July 2015

A quantum object can acquire a geometric phase (such as Berry phases and Aharonov–Bohm phases) when evolving along a path in a parameter space with non-trivial gauge structures. Inherent to quantum evolutions of wavepackets, quantum diffusion occurs along quantum trajectories. Here we show that quantum diffusion can also be geometric as characterized by the imaginary part of a geometric phase. The geometric quantum diffusion results from interference between different instantaneous eigenstate pathways which have different geometric phases during the adiabatic evolution. As a specific example, we study the quantum trajectories of optically excited electron-hole pairs in time-reversal symmetric insulators, driven by an elliptically polarized terahertz field. The imaginary geometric phase manifests itself as elliptical polarization in the terahertz sideband generation. The geometric quantum diffusion adds a new dimension to geometric phases and may have applications in many fields of physics, e.g., transport in topological insulators and novel electro-optical effects.
Zbtb16 (PLZF) is stably suppressed and not inducible in non-innate T cells via T cell receptor-mediated signaling
Authors: Zhang Sai , Laouar Amale , Denzin Lisa K. , Sant’Angelo Derek B.
Published: July 2015

The transcription factor PLZF (promyelocytic leukemia zinc finger; zbtb16) is essential for nearly all of the unique characteristics of NKT cells including their rapid and potent response to antigen. In the immune system, zbtb16 expression is only found in innate cells. Conventional T cells that ectopically express PLZF spontaneously acquire an activated, effector phenotype. Activation induced expression of lineage defining transcription factors such as T-bet, FoxP3, RORγt, GATA3 and others is essential for naïve T cell differentiation into effector T cells. In this study, we used sensitive genetic-based approaches to assess the induction of PLZF expression in non-innate T cells by T cell receptor (TCR)-mediated activation. Surprisingly, we found that PLZF was stably repressed in non-innate T cells and that TCR-mediated signaling was not sufficient to induce PLZF in conventional T cells. The inactivated state of PLZF was stably maintained in mature T cells, even under inflammatory conditions imposed by bacterial infection. Collectively, our data show that, in contrast to multiple recent reports, PLZF expression is highly specific to innate T cells and cannot be induced in conventional T cells via TCR-mediated activation or inflammatory challenge.
Regioselective Halogenation of 1,4-Benzodiazepinones via CH Activation
Authors: Abdelkafi Hajer , Cintrat Jean-Christophe
Published: July 2015

This article reports an efficient CH activation process for regioselective halogenation of 1,4-benzodiazepinones. Direct halogenation with NXS (X = Br, I) affords halogenated benzodiazepinones on the central aromatic ring whereas catalyst (Pd(OAc)2) controlled CH activation furnishes regioselectively ortho halogenated benzodiazepinones on the phenyl side chain.
Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders
Authors: Lu Wenjie , Xu Youzhi , Shao Xiaoni , Gao Fabao , Li Yan , Hu Jing , Zuo Zeping , Shao Xue , Zhou Liangxue , Zhao Yinglan , Cen Xiaobo
Published: July 2015

Epidemiological studies have shown that an elevated uric acid (UA) level predicts the development of metabolic syndrome and diabetes; however, there is no direct evidence of this and the underlying mechanism remains unclear. Here, we showed that a high-UA diet triggered the expression of pro-inflammatory cytokines, activated the NF-κB pathway and increased gliosis in the hypothalamus. Intracerebroventricular injection of UA induced hypothalamic inflammation and reactive gliosis, whereas these effects were markedly ameliorated by the inhibition of NF-κB. Moreover, magnetic resonance imaging confirmed that hyperuricemia in rodents and humans was associated with gliosis in the mediobasal hypothalamus. Importantly, the rats administered UA exhibited dyslipidemia and glucose intolerance, which were probably mediated by hypothalamic inflammation and hypothalamic neuroendocrine alterations. These results suggest that UA can cause hypothalamic inflammation via NF-κB signaling. Our findings provide a potential therapeutic strategy for UA-induced metabolic disorders.
Homo sapiens exhibit a distinct pattern of CNV genes regulation: an important role of miRNAs and SNPs in expression plasticity
Authors: Dweep Harsh , Kubikova Nada , Gretz Norbert , Voskarides Konstantinos , Felekkis Kyriacos
Published: July 2015

Gene expression regulation is a complex and highly organized process involving a variety of genomic factors. It is widely accepted that differences in gene expression can contribute to the phenotypic variability between species and that their interpretation can aid in the understanding of the physiologic variability. CNVs and miRNAs are two major players in the regulation of expression plasticity and may be responsible for the unique phenotypic characteristics observed in different lineages. We have previously demonstrated that a close interaction between these two genomic elements may have contributed to the regulation of gene expression during evolution. This work presents the molecular interactions between CNV and non CNV genes with miRNAs and other genomic elements in eight different species. A comprehensive analysis of these interactions indicates a unique nature of human CNV genes regulation as compared to other species. By using genes with short 3′ UTR that abolish the “canonical” miRNA-dependent regulation, as a model, we demonstrate a distinct and tight regulation of human genes that might explain some of the unique features of human physiology. In addition, comparison of gene expression regulation between species indicated that there is a significant difference between humans and mice possibly questioning the effectiveness of the latest as experimental models of human diseases.
Reformation Capability of Short-Range Order and Their Medium-Range Connections Regulates Deformability of Bulk Metallic Glasses
Authors: Li Congling , Wei Yujie , Shi Xinghua
Published: July 2015

Metallic glasses (MGs) typically have high yield strength while low ductility and the latter is commonly considered as the Achilles’ heel of MGs. Elucidate the mechanism for such low ductility becomes the research focus of this field. With molecular level simulations, we show the degree of short-range order (SRO) of atomic structure for brittle Fe-based glass decreases dramatically during the stretch, while mild change occurs in ductile Zr-based glass. The reformation capability for SRO and their medium-range connections is found to be the primary characteristics to differentiate the deformability between the two metallic glasses. We suspect that, in addition to the strength of networks formed by SRO structure, the reformation capability to reform SRO networks also plays the key role in regulating the ductility in metallic glasses. Our study provides important insights into the understanding about the mechanisms accounting for ductility or brittleness of bulk metallic glasses.