bluuebunny/crossref_metadata_2025 huggingface dataset:
The endocranial anatomy of maba 1
Authors: Wu Xiu‐jie , Bruner Emiliano
Published: March 2016

Objectives

Maba 1, a partial cranium from Guandong Province (China) tentatively dated between 300 and 130 ka, has been suggested to display a mosaic of archaic and derived features, including facial affinities with Neandertals. This study aims to evaluate whether Maba 1 shows a derived endocranial phenotype, or if it displays a plesiomorphic braincase morphology.

Materials and methods

We analyzed a set of metric variables on fossil and modern human endocasts using bivariate correlation, principal component analysis, and cluster analyses, to evaluate the morphological affinities of the Maba 1 endocast.

Results

The cranial capacity, estimated at around 1300 cc, and the endocranial proportions of Maba 1 are within the ranges of modern humans, Neandertals and Homo heidelbergensis. However, the frontal lobes are narrow and the parietal areas are short and flattened, as in H. heidelbergensis and H. erectus. Nonetheless, the position of the frontal lobes relative to the orbits, the morphology of the frontal sinus and the curve of the frontal squama are more derived, being similar to Neandertals and modern humans.

Conclusions

The endocast displays a general archaic morphology, although with some derived features associated with the spatial relationships with the face. A similar admixture was described for other Middle Pleistocene samples, like Sima de los Huesos. Future phylogenetic studies must re‐evaluate the facial skeleton to consider whether its features can be considered as related to the Neandertal lineage. Alternatively, they should be interpreted as the result of homoplasy and parallelism within the genus Homo, and may reflect a predominantly Asian variation. Am J Phys Anthropol 160:633–643, 2016. © 2016 Wiley Periodicals, Inc.
GSK3ß‐dependent dysregulation of neurodevelopment in SPG11‐patient induced pluripotent stem cell model
Authors: Mishra Himanshu K. , Prots Iryna , Havlicek Steven , Kohl Zacharias , Perez‐Branguli Francesc , Boerstler Tom , Anneser Lukas , Minakaki Georgia , Wend Holger , Hampl Martin , Leone Marina , Brückner Martina , Klucken Jochen , Reis Andre , Boyer Leah , Schuierer Gerhard , Behrens Jürgen , Lampert Angelika , Engel Felix B. , Gage Fred H. , Winkler Jürgen , Winner Beate
Published: March 2016

Objective

Mutations in the spastic paraplegia gene 11 (SPG11), encoding spatacsin, cause the most frequent form of autosomal‐recessive complex hereditary spastic paraplegia (HSP) and juvenile‐onset amyotrophic lateral sclerosis (ALS5). When SPG11 is mutated, patients frequently present with spastic paraparesis, a thin corpus callosum, and cognitive impairment. We previously delineated a neurodegenerative phenotype in neurons of these patients. In the current study, we recapitulated early developmental phenotypes of SPG11 and outlined their cellular and molecular mechanisms in patient‐specific induced pluripotent stem cell (iPSC)‐derived cortical neural progenitor cells (NPCs).

Methods

We generated and characterized iPSC‐derived NPCs and neurons from 3 SPG11 patients and 2 age‐matched controls.

Results

Gene expression profiling of SPG11‐NPCs revealed widespread transcriptional alterations in neurodevelopmental pathways. These include changes in cell‐cycle, neurogenesis, cortical development pathways, in addition to autophagic deficits. More important, the GSK3ß‐signaling pathway was found to be dysregulated in SPG11‐NPCs. Impaired proliferation of SPG11‐NPCs resulted in a significant diminution in the number of neural cells. The decrease in mitotically active SPG11‐NPCs was rescued by GSK3 modulation.

Interpretation

This iPSC‐derived NPC model provides the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ß as a potential novel target to reverse the disease phenotype. Ann Neurol 2016;79:826–840
Unconventional Luminescent Centers in Metastable Phases Created by Topochemical Reduction Reactions
Authors: Liu Bo‐Mei , Zhang Zhi‐Gang , Zhang Kai , Kuroiwa Yoshihiro , Moriyoshi Chikako , Yu Hui‐Mei , Li Chao , Zheng Li‐Rong , Li Li‐Na , Yang Guang , Zhou Yang , Fang Yong‐Zheng , Hou Jing‐Shan , Matsushita Yoshitaka , Sun Hong‐Tao
Published: March 2016

A low‐temperature topochemical reduction strategy is used herein to prepare unconventional phosphors with luminescence covering the biological and/or telecommunications optical windows. This approach is demonstrated by using BiIII‐doped Y2O3 (Y2−xBixO3) as a model system. Experimental results suggest that topochemical treatment of Y2−xBixO3 using CaH2 creates randomly distributed oxygen vacancies in the matrix, resulting in the change of the oxidation states of Bi to lower oxidation states. The change of the Bi coordination environments from the [BiO6] octahedra in Y2−xBixO3 to the oxygen‐deficient [BiO6−z] polyhedra in reduced phases leads to a shift of the emission maximum from the visible to the near‐infrared region. The generality of this approach was further demonstrated with other phosphors. Our findings suggest that this strategy can be used to explore Bi‐doped or other classes of luminescent systems, thus opening up new avenues to develop novel optical materials.
Chemoenzymatic Synthesis of a Phosphorylated Glycoprotein
Authors: Priyanka Pragya , Parsons Thomas B. , Miller Antonia , Platt Frances M. , Fairbanks Antony J.
Published: March 2016

The majority of lysosomal enzymes are targeted to the lysosome by post‐translational tagging with N‐glycans terminating in mannose‐6‐phosphate (M6P) residues. Some current enzyme replacement therapies (ERTs) for lysosomal storage disorders are limited in their efficacy by the extent to which the recombinant enzymes bear the M6P‐terminated glycans required for effective trafficking. Chemical synthesis was combined with endo‐β‐N‐acetylglucosaminidase (ENGase) catalysis to allow the convergent synthesis of glycosyl amino acids bearing M6P residues. This approach can be extended to the remodeling of proteins, as exemplified by RNase. The powerful synergy of chemical synthesis and ENGase‐mediated biocatalysis enabled the first synthesis of a glycoprotein bearing M6P‐terminated N‐glycans in which the glycans are attached to the peptide backbone by entirely natural linkages.
Review: Translational GTPases
Authors: Maracci Cristina , Rodnina Marina V.
Published: March 2016

Translational GTPases (trGTPases) play key roles in facilitating protein synthesis on the ribosome. Despite the high degree of evolutionary conservation in the sequences of their GTP‐binding domains, the rates of GTP hydrolysis and nucleotide exchange vary broadly between different trGTPases. EF‐Tu, one of the best‐characterized model G proteins, evolved an exceptionally rapid and tightly regulated GTPase activity, which ensures rapid and accurate incorporation of amino acids into the nascent chain. Other trGTPases instead use the energy of GTP hydrolysis to promote movement or to ensure the forward commitment of translation reactions. Recent data suggest the GTPase mechanism of EF‐Tu and provide an insight in the catalysis of GTP hydrolysis by its unusual activator, the ribosome. Here we summarize these advances in understanding the functional cycle and the regulation of trGTPases, stimulated by the elucidation of their structures on the ribosome and the progress in dissecting the reaction mechanism of GTPases. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 463–475, 2016.
Invited review: Small GTPases and their GAPs
Authors: Mishra Ashwini K. , Lambright David G.
Published: March 2016

Widespread utilization of small GTPases as major regulatory hubs in many different biological systems derives from a conserved conformational switch mechanism that facilitates cycling between GTP‐bound active and GDP‐bound inactive states under control of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), which accelerate slow intrinsic rates of activation by nucleotide exchange and deactivation by GTP hydrolysis, respectively. Here we review developments leading to current understanding of intrinsic and GAP catalyzed GTP hydrolytic reactions in small GTPases from structural, molecular and chemical mechanistic perspectives. Despite the apparent simplicity of the GTPase cycle, the structural bases underlying the hallmark hydrolytic reaction and catalytic acceleration by GAPs are considerably more diverse than originally anticipated. Even the most fundamental aspects of the reaction mechanism have been challenging to decipher. Through a combination of experimental and in silico approaches, the outlines of a consensus view have begun to emerge for the best studied paradigms. Nevertheless, recent observations indicate that there is still much to be learned. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 431–448, 2016.
TALEored Epigenetics: A DNA‐Binding Scaffold for Programmable Epigenome Editing and Analysis
Authors: Kubik Grzegorz , Summerer Daniel
Published: March 2016

Epigenetic modification of the cytosine 5‐position is an important regulator of gene expression with essential roles in genome stability, development, and disease. In addition to 5‐methylcytosine (mC), the oxidized mC derivatives 5‐hydroxymethyl‐, 5‐formyl‐, and 5‐carboxylcytosine (hmC, fC, and caC) have recently been discovered. These are intermediates of an active demethylation pathway but might also represent new epigenetic marks with individual biological roles. This increase in chemical complexity of DNA‐encoded information has created a pressing need for new approaches that allow reading and editing of this information. Transcription‐activator‐like effectors (TALEs) are DNA‐binding domains with programmable sequence selectivity that enable the direct reading of epigenetic cytosine modifications but can also guide enzymatic editing domains to genomic loci of choice. Here, we review recent advances in employing TALEs for these applications.
Severe case of staphylococcal scalded skin syndrome in a 5‐year‐old child – case report
Authors: Aydin Dogu , Alsbjørn Bjarne
Published: March 2016

Key Clinical Message

Benign impetigo can progress into a potential fatal staphylococcal scalded skin syndrome (SSSS) if prompt diagnosis and correct therapy is not established rapidly. Local and systematic antibiotics as well as Lactulose are crucial in order to stop SSSS from progressing. Burns units should be involved when skin lesions are extensive.
Carbon‐Coated Hematite Electrodes with Enhanced Photoelectrochemical Performance Obtained through an Electrodeposition Method with a Citric Acid Additive
Authors: Wang TsingHai , Chen Yi‐Nuo , Chiang Chia‐Che , Hsieh Yi‐Kong , Li Po‐Chieh , Wang Chu‐Fang
Published: March 2016

In this study, carbon‐coated hematite electrodes exhibiting high photoelectrochemical (PEC) performance with a photocurrent density of 2.1 mA cm−2 at 0.4 V versus SCE were obtained by using a simple electrodeposition method with an electrolyte containing citric acid additives. This achievement is attributed to the high affinity of citric acid to iron oxide, which allows the bound citric acid residing in the porous hematite films to develop a carbon layer in the subsequent sintering process. The passivation effect resulting from the surface carbon layer is likely responsible for the observed high PEC performance. Importantly, the oxidation of the surface carbon layer would, on the other hand, reduce the surface of hematite to FeOOH, which deteriorates the photocurrent density by approximately one order of magnitude. Accordingly, the manipulation of a good carbon layer on the surface of hematite would be an important issue to further improve the PEC performance of hematite electrodes.
σ‐Hole Opposite to a Lone Pair: Unconventional Pnicogen Bonding Interactions between ZF3 (Z=N, P, As, and Sb) Compounds and Several Donors
Authors: Bauzá Antonio , Mooibroek Tiddo J. , Frontera Antonio
Published: March 2016

The ability of several pnicogen sp3 derivatives ZF3 (Z=N, P, As, Sb) to interact with electron‐rich entities by means of the opposite face to the lone pair (lp) is investigated at the RI‐MP2/aug‐cc‐pVQZ level of theory. The strength of the interaction ranges from −1 to −87 kJ mol−1, proving its favorable nature, especially when the lp is coordinated to a metal center, whereby the strength of the interaction is significantly enhanced. NBO analysis showed that orbital effects are modest contributors to the global stabilization of the pnicogen σ‐hole bonded complexes studied. Finally, a selection of Cambridge Structural Database examples are shown that demonstrate the impact of this counterintuitive binding mode in the solid state.
Should Therapeutic Drug Monitoring for Monoclonal Antibodies Remain the Exception or Become the Norm?
Authors: Stroh M , Lum BL
Published: March 2016

Therapeutic drug monitoring (TDM) aims to maintain circulating drug concentrations at a desired level to optimize clinical outcome. The vast majority of marketed drugs do not require TDM, suggesting the clinical benefit of TDM has not been sufficiently demonstrated in most cases. With the continued emergence and prominence of monoclonal antibodies (mAbs) as drugs, especially in inflammation and cancer therapeutic areas, we are at a juncture to consider applicability of TDM for mAbs.
An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells
Authors: Tone Kiyoshi , Kojima Keiko , Hoshiai Keita , Kumagai Naoya , Kijima Hiroshi , Kurose Akira
Published: March 2016

Background

The essential of urine cytology for the diagnosis and the follow‐up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination.

Methods

Using Papanicolaou‐stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4′,6‐diamidino‐2‐phenylindole for detection of the nuclei and the nucleoli. Z‐stack method was performed to analyze.

Results

When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P <0.001). In the verification test using the nucleolar/nuclear ratio (%), four of the seven cases were concordant with the final diagnosis.

Conclusion

This study analyzed the nuclear and nucleolar volume to establish an index for discrimination of benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483–491. © 2016 Wiley Periodicals, Inc.
High‐resolution investigation of memory‐specific reinstatement in the hippocampus and perirhinal cortex
Authors: Tompary Alexa , Duncan Katherine , Davachi Lila
Published: March 2016

Episodic memory involves remembering the details that characterize a prior experience. Successful memory recovery has been associated with the reinstatement of brain activity patterns in a number of sensory regions across the cortex. However, how the hippocampus and surrounding medial temporal lobe (MTL) cortex contribute to this process is less clear. Models of episodic memory posit that hippocampal pattern reinstatement, also referred to as pattern completion, may mediate cortical reinstatement during retrieval. Empirical evidence of this process, however, remains elusive. Here, we use high‐resolution fMRI and encoding‐retrieval multi‐voxel pattern similarity analyses to demonstrate for the first time that the hippocampus, particularly right hippocampal subfield CA1, shows evidence of reinstating individual episodic memories. Furthermore, reinstatement in perirhinal cortex (PrC) is also evident. Critically, we identify distinct factors that may mediate the cortical reinstatement in PrC. First, we find that encoding activation in PrC is related to later reinstatement in this region, consistent with the theory that encoding strength in the regions that process the memoranda is important for later reinstatement. Conversely, retrieval activation in right CA1 was correlated with reinstatement in PrC, consistent with models of pattern completion. This dissociation is discussed in the context of the flow of information into and out of the hippocampus during encoding and retrieval, respectively. © 2016 Wiley Periodicals, Inc.
Age‐related changes in Egr1 transcription and DNA methylation within the hippocampus
Authors: Penner M.R. , Parrish R.R. , Hoang L.T. , Roth T.L. , Lubin F.D. , Barnes C.A.
Published: March 2016

Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate‐early genes (IEGs), including Egr1, is necessary for processes such as long‐term potentiation and memory consolidation. Here, we show an age‐related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging‐related changes is an age‐associated, CpG site‐specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc.
Bidirectional Contrast agent leakage correction of dynamic susceptibility contrast (DSC)‐MRI improves cerebral blood volume estimation and survival prediction in recurrent glioblastoma treated with bevacizumab
Authors: Leu Kevin , Boxerman Jerrold L. , Lai Albert , Nghiemphu Phioanh L. , Pope Whitney B. , Cloughesy Timothy F. , Ellingson Benjamin M.
Published: March 2016

Purpose

To evaluate a leakage correction algorithm for T1 and
artifacts arising from contrast agent extravasation in dynamic susceptibility contrast magnetic resonance imaging (DSC‐MRI) that accounts for bidirectional contrast agent flux and compare relative cerebral blood volume (CBV) estimates and overall survival (OS) stratification from this model to those made with the unidirectional and uncorrected models in patients with recurrent glioblastoma (GBM).

Materials and Methods

We determined median rCBV within contrast‐enhancing tumor before and after bevacizumab treatment in patients (75 scans on 1.5T, 19 scans on 3.0T) with recurrent GBM without leakage correction and with application of the unidirectional and bidirectional leakage correction algorithms to determine whether rCBV stratifies OS.

Results

Decreased post‐bevacizumab rCBV from baseline using the bidirectional leakage correction algorithm significantly correlated with longer OS (Cox, P = 0.01), whereas rCBV change using the unidirectional model (P = 0.43) or the uncorrected rCBV values (P = 0.28) did not. Estimates of rCBV computed with the two leakage correction algorithms differed on average by 14.9%.

Conclusion

Accounting for T1 and
leakage contamination in DSC‐MRI using a two‐compartment, bidirectional rather than unidirectional exchange model might improve post‐bevacizumab survival stratification in patients with recurrent GBM. J. Magn. Reson. Imaging 2016;44:1229–1237.
Improved cortical bone specificity in UTE MR Imaging
Authors: Johnson Ethan M. , Vyas Urvi , Ghanouni Pejman , Pauly Kim Butts , Pauly John M.
Published: March 2016

Purpose

Methods for direct visualization of compact bone using MRI have application in several “MR‐informed” technologies, such as MR‐guided focused ultrasound, MR‐PET reconstruction and MR‐guided radiation therapy. The specificity of bone imaging can be improved by manipulating image sensitivity to Bloch relaxation phenomena, facilitating distinction of bone from other tissues detected by MRI.

Methods

From Bloch equation dynamics, excitation pulses suitable for creating specific sensitivity to short‐T2 magnetization from cortical bone are identified. These pulses are used with UTE subtraction demonstrate feasibility of MR imaging of compact bone with positive contrast.

Results

MR images of bone structures are acquired with contrast similar to that observed in x‐ray CT images. Through comparison of MR signal intensities with CT Hounsfield units of the skull, the similarity of contrast is quantified. The MR technique is also demonstrated in other regions of the body that are relevant for interventional procedures, such as the shoulder, pelvis and leg.

Conclusion

Matching RF excitation pulses to relaxation rates improves the specificity to bone of short‐T2 contrast. It is demonstrated with a UTE sequence to acquire images of cortical bone with positive contrast, and the contrast is verified by comparison with x‐ray CT. Magn Reson Med 77:684–695, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Synthesis of graphene oxide–epoxy resin encapsulated urea–formaldehyde microcapsule by in situ polymerization process
Authors: Sarkar Sourav , Kim Byungki
Published: March 2016

A new type of microcapsule has been prepared with urea–formaldehyde (UF) as shell material and graphene oxide (GO)–epoxy resin with acetone as standard solvent between them as the core material. In situ polymerization procedure was used, employing aqueous condition for the synthesis step. The chemical structures of the microcapsules were analyzed using Fourier‐transform infrared (FTIR). The morphology of the microcapsules was observed through scanning electron microscopy (SEM). The effects of various amounts of emulsifier and stirring rates on the sizes and agglomeration properties of the microcapsules were closely studied. The storage stability of the microcapsules over various time limits was also investigated. Thermal stability was evaluated using thermogravimetric analysis (TGA) procedure. The results showed that the successful encapsulation of GO–epoxy polymer complex in the presence of acetone could be done under a controlled environment. Also, the rough outer surface of the microcapsules was composed mainly of urea and formaldehyde. The surface morphology and the sizes of the prepared microcapsules could be controlled by varying many process parameters. The microcapsules showed greater amounts of thermal stability with increasing amounts of GO percentage in the core material. POLYM. COMPOS., 39:636–644, 2018. © 2016 Society of Plastics Engineers
Universal features of fluctuations in globular proteins
Authors: Erman Burak
Published: March 2016

Using data from 2000 non‐homologous protein crystal structures, we show that the distribution of residue B factors of proteins collapses onto a single master curve. We show by maximum entropy arguments that this curve is a Gamma function whose order and dispersion are obtained from experimental data. The distribution for any given specific protein can be generated from the master curve by a linear transformation. Any perturbation of the B factor distribution of a protein, imposed at constant energy, causes a decrease in the entropy of the protein relative to that of the reference state. Proteins 2016; 84:721–725. © 2016 Wiley Periodicals, Inc.
Kras is Required for Adult Hematopoiesis
Authors: Damnernsawad Alisa , Kong Guangyao , Wen Zhi , Liu Yangang , Rajagopalan Adhithi , You Xiaona , Wang Jinyong , Zhou Yun , Ranheim Erik A. , Luo Hongbo R. , Chang Qiang , Zhang Jing
Published: March 2016

Previous studies indicate that Kras is dispensable for fetal liver hematopoiesis, but its role in adult hematopoiesis remains unclear. Here, we generated a Kras conditional knockout allele to address this question. Deletion of Kras in adult bone marrow (BM) is mediated by Vav-Cre or inducible Mx1-Cre. We find that loss of Kras leads to greatly reduced thrombopoietin (TPO) signaling in hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), while stem cell factor-evoked ERK1/2 activation is not affected. The compromised TPO signaling is associated with reduced long term- and intermediate-term HSC compartments and a bias toward myeloid differentiation in MPPs. Although granulocyte macrophage colony-stimulating factor (GM-CSF)-evoked ERK1/2 activation is only moderately decreased in Kras-/- myeloid progenitors, it is blunted in neutrophils and neutrophil survival is significantly reduced in vitro. At 9-12 months old, Kras conditional knockout mice develop profound hematopoietic defects, including splenomegaly, an expanded neutrophil compartment, and reduced B cell number. In a serial transplantation assay, the reconstitution potential of Kras-/- BM cells is greatly compromised, which is attributable to defects in the self-renewal of Kras-/- HSCs and defects in differentiated hematopoietic cells. Our results demonstrate that Kras is a major regulator of TPO and GM-CSF signaling in specific populations of hematopoietic cells and its function is required for adult hematopoiesis.
Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience
Authors: Jaeger Bregje , Bosch Annet M.
Published: March 2016

Introduction

Riboflavin (vitamin B2) is absorbed in the small intestine by the human riboflavin transporters RFVT1 and RFVT3. A third riboflavin transporter (RFVT2) is expressed in the brain. In 2010 it was demonstrated that mutations in the riboflavin transporter genes SLC52A2 (coding for RFVT2) and SLC52A3 (coding for RFVT3) cause a neurodegenerative disorder formerly known as Brown‐Vialetto‐Van Laere (BVVL) syndrome, now renamed to riboflavin transporter deficiency. Five years after the diagnosis of the first patient we performed a review of the literature to study the presentation, treatment and outcome of patients with a molecularly confirmed diagnosis of a riboflavin transporter deficiency.

Method

A search was performed in Medline, Pubmed using the search terms ‘Brown‐Vialetto‐Van Laere syndrome’ and ‘riboflavin transporter’ and articles were screened for case reports of patients with a molecular diagnosis of a riboflavin transporter deficiency.

Results

Reports on a total of 70 patients with a molecular diagnosis of a RFVT2 or RTVT3 deficiency were retrieved. The riboflavin transporter deficiencies present with weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties and respiratory difficulties which are caused by a sensorimotor axonal neuropathy and cranial neuropathy. Biochemical abnormalities may be absent and the diagnosis can only be made or rejected by molecular analysis of all genes. Treatment with oral supplementation of riboflavin is lifesaving. Therefore, if a riboflavin transporter deficiency is suspected, treatment must be started immediately without first awaiting the results of molecular diagnostics.
Does worry moderate the relation between aggression and depression in adolescent girls?☆
Authors: Blain‐Arcaro Christine , Vaillancourt Tracy
Published: March 2016

Aggressive girls, more so than aggressive boys, are at an increased risk for depression. Despite disconcerting outcomes, few researchers have examined factors that may attenuate or exacerbate the relation between aggression and depression. Competing hypotheses for explaining the role of worry in the relation between aggressive behaviour and depressive symptoms, commonly co‐occurring problems in girls, have been proposed. In the present study, we examined worry as a possible moderator in the relation between girls nominated as aggressive by their peers and self‐reported depressive symptoms in a sample of 226 girls aged 13 (M = 12.92, SD = 1.28) at Time 1. We found that worry exacerbated the risk of depressive symptoms concurrently and one year later for physically aggressive girls, but not relationally aggressive girls. These results suggest that worry plays an important role in the prediction of depression for aggressive girls, which varies by the form aggression takes.
Arnica montana effects on gene expression in a human macrophage cell line. Evaluation by quantitative Real-Time PCR
Authors: Marzotto Marta , Bonafini Clara , Brizzi Maurizio , Bellavite Paolo , Olioso Debora
Published: March 2016

Background: Arnica montana is a popular traditional remedy widely used in complementary medicine, also for its wound healing properties. Despite its acknowledged action in clinical settings at various doses, the molecular aspects relating to how A. montana promotes wound healing remain to be elucidated. To fill this gap, we evaluated the whole plant extract, in a wide range of dilutions, in THP-1 human cells, differentiated into mature macrophages and into an alternative IL-4-activated phenotype involved in tissue remodelling and healing.

Methods: Real-time quantitative Reverse Transcription Polymerase Chain Reaction (PCR) analysis was used to study the changes in the expression of a customized panel of key genes, mainly cytokines, receptors and transcription factors.

Results: On macrophages differentiated towards the wound healing phenotype, A. montana affected the expression of several genes. In particular CXC chemokine ligand 1 (CXCL1), coding for an chief chemokine, exhibited the most consistent increase of expression, while also CXC chemokine ligand 2 (CXCL2), Interleukin8 (IL8) and bone morphogenetic protein (BMP2) were slightly up-regulated, suggesting a positive influence of A. montana on neutrophil recruitment and on angiogenesis. MMP1, coding for a metalloproteinase capable of cleaving extracellular matrix substrates, was down-regulated. Most results showed non-linearity of the dose-effect relationship.

Conclusions This exploratory study provides new insights into the cellular and molecular mechanisms of action of A. montana as a promoter of healing, since some of the genes it modifies are key regulators of tissue remodelling, inflammation and chemotaxis.
Rational Benefit Assessment for an Irrational World: Toward a Behavioral Transfer Test
Authors: Kip Viscusi W. , Gayer Ted
Published: March 2016

Behavioral economists have identified certain biases in decision making that lead people to make decisions that harm themselves, but there is insufficient guidance for estimating benefits in the presence of such behavioral failures. This gap in principles and standards for benefit-cost analysis has led government agencies at times to adopt arbitrary and excessive benefit valuations. This article describes an approach to incorporating behavioral market failures into benefit estimation, first by advocating a behavioral transfer test to use before applying behavioral findings from narrow contexts to broader populations subject to regulation, and then by comparing the outcomes from the self-harming behavior to a policy reference point in which people are assumed to be fully informed and to act fully rationally in their own self-interest. This approach, which is grounded on systematic, well-documented, and context-specific findings of behavioral failings, would reduce instances of agencies assuming that behavioral findings in some contexts provide sufficient rationale for overriding consumer preferences in other contexts. It would also establish a consistent approach to government policy by, for example, creating symmetry between advancing policies that seek to discourage consumption of products for which consumers underestimate the health risks and fostering accurate risk beliefs to address erroneous individual choices based on risk overestimation.
Feedback control of unstable flows: a direct modelling approach using the Eigensystem Realisation Algorithm
Authors: Flinois Thibault L. B. , Morgans Aimee S.
Published: March 2016

Obtaining low-order models for unstable flows in a systematic and computationally tractable manner has been a long-standing challenge. In this study, we show that the Eigensystem Realisation Algorithm (ERA) can be applied directly to unstable flows, and that the resulting models can be used to design robust stabilising feedback controllers. We consider the unstable flow around a D-shaped body, equipped with body-mounted actuators, and sensors located either in the wake or on the base of the body. A linear model is first obtained using approximate balanced truncation. It is then shown that it is straightforward and justified to obtain models for unstable flows by directly applying the ERA to the open-loop impulse response. We show that such models can also be obtained from the response of the nonlinear flow to a small impulse. Using robust control tools, the models are used to design and implement both proportional and $\mathscr{H}_{\infty }$ loop-shaping controllers. The designed controllers were found to be robust enough to stabilise the wake, even from the nonlinear vortex shedding state and in some cases at off-design Reynolds numbers.
Mach-number scaling of individual azimuthal modes of subsonic co-flowing jets
Authors: Sandberg R. D. , Tester B. J.
Published: March 2016

The Mach-number scaling of the individual azimuthal modes of jet mixing noise was studied for jets in flight conditions, i.e. with co-flow. The data were obtained via a series of direct numerical simulations (DNS), performed of fully turbulent jets with a target Reynolds number, based on nozzle diameter, of $Re_{jet}=8000$. The DNS included a pipe 25 diameters in length in order to ensure that the flow developed to a fully turbulent state before exiting into a laminar co-flow, and to account for all possible noise generation mechanisms. To allow for a detailed study of the jet mixing noise component of the combined pipe–jet configuration, acoustic liner boundary conditions on the inside of the pipe and a modification to the synthetic turbulent inlet boundary condition of the pipe were applied to minimize internal noise in the pipe. Despite these measures, the use of a phased-array source breakdown technique was essential in order to isolate the sources associated with jet noise mechanisms from additional noise sources that could be attributed to internal noise or unsteady flow past the nozzle lip, in particular for the axisymmetric mode. Decomposing the sound radiation from the pipe–jet configuration into its azimuthal Fourier modes, and accounting for the co-flow effects, it was found that at $90^{\circ }$ the individual azimuthal Fourier modes of far-field pressure for the jet mixing noise component exhibit the same $M^{8}$ scaling with the centreline jet Mach number as that experimentally documented for the overall noise field. Applying the phased-array source breakdown code to the DNS data at smaller angles to the jet axis, an increase of the velocity exponent of the jet noise source was found, approaching 10 at $30^{\circ }$. At this smaller angle the higher azimuthal modes again showed the same behaviour as the axisymmetric mode.
Recent retreat of the Elbrus glacier system
Authors: HOLOBÂCĂ IULIAN-HORIA
Published: March 2016

The glacier system covering Europe's highest mountain, Elbrus, has exhibited an accelerated retreat since 1980. Some studies have related this retreat to a significant summer temperature increasing trend. Relief- and aspect-related parameters for the glacierized area have an important impact on glacier changes. In this paper, the changes in glacier area are identified, quantified and correlated with relief parameters for the period 1985–2007. Spatial analysis was performed using the GLAM-CD (Glacier Mapper – Change Detector) algorithm. The input data for this algorithm were Landsat 5 images, the Aster Global Digital Elevation and the glacier outlines from the GLIMS project (Global Land Ice Measurements from Space). Regression analyses between glacier area losses and relief-related parameters indicate a significant positive relation with the altitude and a significant negative relation with the glacier surface area. In this context, we used a correlated component regression to model these relations. The model explains >50% of the total variation.
Evidence for the Continued Use of Medieval Medical Prescriptions in the Sixteenth Century: A Fifteenth-Century Remedy Book and its Later Owner
Authors: Connolly Margaret
Published: March 2016

This article examines a fifteenth-century remedy book, Oxford, Bodleian Library, Rawlinson c. 299, and describes its collection of 314 medieval medical prescriptions. The recipes are organised broadly from head to toe, and often several remedies are offered for the same complaint. Some individual recipes are transcribed with modern English translations. The few non-recipe texts are also noted. The difference between a remedy book and a leechbook is explained, and this manuscript is situated in relation to other known examples of late medieval medical anthologies. The particular feature that distinguishes Oxford, Bodleian Library, Rawlinson c. 299 from other similar volumes is the evidence that it continued to be used during the sixteenth century. This usage was of two kinds. Firstly, the London lawyer who owned it not only inscribed his name but annotated the original recipe collection in various ways, providing finding-aids that made it much more user-friendly. Secondly, he, and other members of his family, added another forty-three recipes to the original collection (some examples of these are also transcribed). These two layers of engagement with the manuscript are interrogated in detail in order to reveal what ailments may have troubled this family most, and to judge how much faith they placed in the old remedies contained in this old book. It is argued that the knowledge preserved in medieval books enjoyed a longevity that extended beyond the period of the manuscript book, and that manuscripts were read and valued long after the advent of printing.
Hybridising Medicine: Illness, Healing and the Dynamics of Reciprocal Exchange on the Upper Guinea Coast (West Africa)
Authors: Havik Philip J.
Published: March 2016

The present article seeks to fill a number of lacunae with regard to the study of the circulation and assimilation of different bodies of medical knowledge in an important cultural contact zone, that is the Upper Guinea Coast. Building upon ongoing research on trade and cultural brokerage in the area, it focuses upon shifting attitudes and practices with regard to health and healing as a result of cultural interaction and hybridisation against the background of growing intra-African and Afro-Atlantic interaction from the fifteenth to the late seventeenth century. Largely based upon travel accounts, missionary reports and documents produced by the Portuguese Inquisition, it shows how forms of medical knowledge shifted and circulated between littoral areas and their hinterland, as well as between the coast, the Atlantic and beyond. It shows that the changing patterns of trade, migration and settlement associated with Mandé influence and Afro-Atlantic exchange had a decisive impact on changing notions of illness and therapeutic trajectories. Over the centuries, cross-cultural, reciprocal borrowing contributed to the development of healing kits employed by Africans and non-African outsiders alike, which were used and brokered by local communities in different locations in the region.
Black Hole Mass Estimation: How Good is the Virial Estimate?
Authors: Yong Suk Yee , Webster Rachel L. , King Anthea L.
Published: March 2016

Black hole mass is a key factor in determining how a black hole interacts with its environment. However, the determination of black hole masses at high redshifts depends on secondary mass estimators, which are based on empirical relationships and broad approximations. A dynamical disk wind broad line region model (BLR) of active galactic nuclei is built in order to test the impact of different BLR geometries and inclination angles on the black hole mass estimation. Monte Carlo simulations of two disk wind models are constructed to recover the virial scale factor, f, at various inclination angles. The resulting f values strongly correlate with inclination angle, with large f values associated with small inclination angles (close to face-on) and small f values with large inclination angles (close to edge-on). The recovered f factors are consistent with previously determined f values, found from empirical relationships. Setting f as a constant may introduce a bias into virial black hole mass estimates for a large sample of active galactic nuclei. However, the extent of the bias depends on the line width characterisation (e.g. full width at half maximum or line dispersion). Masses estimated using $f_{\text{FWHM}}$ tend to be biased towards larger masses, but this can generally be corrected by calibrating for the width or shape of the emission line.
RECTIFICATION VERSUS INTERPRETATION: THE NATURE AND SCOPE OF THE EQUITABLE JURISDICTION
Authors: Davies Paul S.
Published: March 2016

This article argues that mistakes in written contracts should be corrected under the equitable doctrine of rectification rather than the common law of interpretation. But rectification on the basis of a common mistake should only be granted where both parties are actually mistaken. Any other approach is inconsistent with the nature of the equitable jurisdiction, and blurs the boundary between common mistake and unilateral mistake rectification.
RIGHTS AND FUNDAMENTAL RIGHTS IN ENGLISH LAW
Authors: Sales Philip
Published: March 2016

This paper examines the role of rights and fundamental rights in English public law and private law in recent times. It argues that the idea of fundamental rights has been more significant in the filed of public law and seeks to explain why. It compares the operation of domestic fundamental rights with the rights in the European Convention of Human Rights and suggests a methodology for identifying the existence and scope of the former. The paper considers the possible legal effects which might follow from repeal of the Human Rights Act 1998.
NEGLIGENCE LIABILITY FOR OMISSIONS AND THE POLICE
Authors: Tofaris Stelios , Steel Sandy
Published: March 2016

The police do not owe a duty of care to protect victims from the criminal acts of a third party when investigating or suppressing crime save in exceptional circumstances. This is justified as an application of the omissions principle and on several other grounds. The article argues that most of these justifications are unconvincing and it sets outs a positive rationale for the imposition on the police of a duty of care in respect of sufficiently proximate victims of a negligent omission. The scope of this duty can be coherently delimited by re-adjusting the existing framework of negligence liability of public authorities.
RATIONALISING ANTICIPATORY BREACH IN EXECUTED CONTRACTS
Authors: Goh Yihan , Yip Man
Published: March 2016

RATIONALISING the doctrine of anticipatory breach is notoriously difficult. This may explain the complete lack of attempt by the UK Supreme Court to address its conceptual difficulties in its recent judgment in Bunge SA v Nidera BV [2015] UKSC 43; [2015] 3 All E.R. 1082. It is therefore of interest that the Singapore Court of Appeal in The “STX Mumbai” [2015] SGCA 35; [2015] 5 S.L.R. 1 explained why the doctrine of anticipatory breach can be applied to executed contracts (in the sense of being fully executed by the innocent party). Whilst anticipatory breach applies similarly under English law, the English courts have never considered the underlying justification, save to say in a case with a partially executed contract that “it would be very strange and hardly unworkable” if the innocent party had to wait until the time for performance (Moschi v Lep Air Services Ltd. [1973] A.C. 331, 356, per Lord Simon).
ESTOPPEL AND THE LAND REGISTRATION ACT 2002
Authors: Sampson Joe
Published: March 2016

WISHART v Credit and Mercantile Plc [2015] EWCA Civ 655 is an unusual priorities case. At its heart is an informal business partnership between two close friends: S and W. Together, the pair undertook a series of property developments. In all their ventures, S took the lead on financial matters. With the approaching sale of a particularly lucrative development, S and W considered how to spend their gains. W indicated that he would like to purchase a residential property for himself and his family, and entrusted the arrangements for the acquisition to S. W removed himself entirely from the process, failing even to look at the contract of sale. As such, he did not realise that S had inserted himself as the purchaser of the property. Upon sale, W and his family moved into the property, oblivious to the subterfuge. S then secured a loan of £500,000 on the property by way of a legal mortgage in favour of C&M. The sum was promptly gambled away, and S, now declared bankrupt, disappeared. C&M obtained possession of the property and sold it for £1.1 million, using just under £700,000 of the proceeds to recoup their loan and expenses. It was at this point that W re-entered the narrative, appearing before the court to argue that, by virtue of an overriding interest, he was entitled to the proceeds of the sale over C&M.
THE RIGHT TO VOTE AS AN EU FUNDAMENTAL RIGHT AND THE EXPANDING SCOPE OF APPLICATION OF THE EU CHARTER OF FUNDAMENTAL RIGHTS
Authors: Kornezov Alexander
Published: March 2016

IS the right to vote in European Parliament elections a matter for EU law? Until recently, the answer to this query seemed to be a clear “no”. Indeed, while Article 223(1) of the TFEU does confer on the European Union the competence to lay down a uniform procedure for the election of Members of the European Parliament (“MEPs”), this competence has not been exercised so far. Consequently, Article 8 of the Act concerning the election of the MEPs by direct universal suffrage, annexed to Council Decision 76/787/ECSC, EEC, Euratom (OJ 1976 L 278 p. 1, henceforth “the 1976 Act”), provides that the “electoral procedure shall be governed in each Member State by its national provisions”. Apart from the general principles of “direct universal suffrage in a free and secret ballot” and of non-discrimination on the ground of nationality, enshrined respectively in Article 14(3) of the TEU, Article 1(3) of the 1976 Act, and Article 20(2)(b) of the TFEU, there is nothing in EU law that governs specifically the eligibility to vote in EP elections.
PROMOTION OF LATERAL ROOT GROWTH AND LEAF QUALITY OF FLUE-CURED TOBACCO BY THE COMBINED APPLICATION OF HUMIC ACIDS AND NPK CHEMICAL FERTILIZERS
Authors: SHEN HONG , SHEN JUN ZHANG , LI YUE , LAI YONG LIN , JIA ZHI HONG , YI JIAN HUA
Published: March 2016

In this study, the effects of HA combined with NPK fertilizer (HANPK) on root growth and leaf quality of tobacco plants were investigated in tobacco fields. Results indicated that the application of HA alone did not enhance the growth of tobacco obviously, while HANPK increased tobacco biomass by 36.9% and stimulated the growth of lateral roots significantly. The number of the second-order lateral roots was increased by 89.3% compared with the control. Furthermore, HANPK raised the ratio of root biomass in 0–20 cm soil layer over the whole soil layer and increased the proportion of fine roots over the total roots. Tobacco leaf yield, output value, and benefit of HANPK were 12.2%, 29.4% and 35.5% higher than those of the control, respectively. The above results suggest that the combined application of HA and NPK chemical fertilizer is an economical pattern for improving tobacco growth.