bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyramidal tract activation due to subthalamic deep brain stimulation in Parkinson's disease
Authors: Mahlknecht Philipp , Akram Harith , Georgiev Dejan , Tripoliti Elina , Candelario Joseph , Zacharia Andre , Zrinzo Ludvic , Hyam Jonathan , Hariz Marwan , Foltynie Thomas , Rothwell John C. , Limousin Patricia
Published: June 2017

Background: Subthalamic deep brain stimulation (STN‐DBS) is an effective treatment for Parkinson's disease (PD), but can have side effects caused by stimulus spread to structures outside the target volume such as the pyramidal tract.

Objectives: To assess the relevance of pyramidal tract activation with STN‐DBS in PD.

Methods: In a multimodal, blinded study in 20 STN‐DBS patients, we measured stimulation thresholds for evoking electromyographic activity in orbicularis oris and first dorsal interosseous muscles at each of 150 electrode sites. We also modeled the electric field spread and calculated its overlap with the estimated anatomical location of corticospinal and corticobulbar tracts from primary motor cortex using 3 Tesla MRI probabilistic tractography.

Results: Mean resting motor thresholds were significantly lower for the contralateral orbicularis oris (3.5 ± 1.0 mA) compared with ipsilaterally (4.1 ± 1.1 mA) and with the contralateral first dorsal interosseous (4.0 ± 1.2 mA). The modeled volumes of corticobulbar and corticospinal tract activated correlated inversely with the resting motor threshold of the contralateral orbicularis oris and first dorsal interosseous, respectively. Active motor thresholds were significantly lower compared with resting motor thresholds by around 30% to 35% and correlated with the clinically used stimulation amplitude. Backward multiple regression in 12 individuals with a “lateral‐type” speech showed that stimulation amplitude, levodopa equivalent dose reduction postsurgery, preoperative speech intelligibility, and first dorsal interosseous resting motor thresholds explained 79.9% of the variance in postoperative speech intelligibility.

Conclusions: Direct pyramidal tract activation can occur at stimulation thresholds that are within the range used in clinical routine. This spread of current compromises increase in stimulation strengths and is related to the development of side effects such as speech disturbances with chronic stimulation. © 2017 International Parkinson and Movement Disorder Society
Seventy years of pallidotomy for movement disorders
Authors: Cif Laura , Hariz Marwan
Published: June 2017

The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid‐1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa‐induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience. © 2017 International Parkinson and Movement Disorder Society
Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes
Authors: Zhang Jing , Lu Shaohua , Zhou Ye , Meng Kun , Chen Zhipeng , Cui Yizhi , Shi Yunfeng , Wang Tong , He Qing‐Yu
Published: June 2017

Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super‐SILAC‐based MS analysis on the exosomes secreted by three human HCC cell lines, including the non‐motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism‐centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism‐associated proteins via exosomes that differentiate them from non‐motile HCC cells.
KCTD12 modulation of GABA(B) receptor function
Authors: Li Melody , Milligan Carol J. , Wang Haiyan , Walker Andrew , Churilov Leonid , Lawrence Andrew J. , Reid Christopher A. , Hopkins Seth C. , Petrou Steven
Published: June 2017

The molecular composition and functional diversity of native GABAB receptors (GABABR) are still poorly understood, thus hindering development of selective GABABR ligands. Potassium channel tetramerization domain‐containing protein (KCTD) 12 is a GABABR auxiliary subunit and mouse KCTD12 can alter GABABR function. In this study, we sought to characterize the effects of human KCTD12 on GABABR kinetics and pharmacology, using an automated electrophysiological assay. Seizure susceptibility and ethanol consumption were also investigated in a KCTD12 knockout mouse model. Human KCTD12 co‐expression altered the kinetics of GABABR‐mediated GIRK channels, speeding rates of both activation and desensitization. Analysis of concentration‐response curves showed that KCTD12 coexpression did not alter effects of the agonists GABA or baclofen on GABABR. KCTD12 coexpression enhanced the potentiating effects of the positive allosteric modulator CGP7930, and its effects on GABABR activation and desensitization. The function of KCTD12 in vivo was examined, using the KCTD12 knockout mouse model. The knockout mice were more resistant to a pentylenetetrazole proconvulsant challenge suggesting reduced seizure susceptibility. In the two bottle preference test, KCTD12 knockout mice demonstrated a reduced consumption at high ethanol concentrations. In summary, human KCTD12 accelerated the kinetics of GABABR in vitro, in a manner possibly sensitive to allosteric pharmacological modulation. This study also provides novel in vivo evidence that the interaction between KCTD12 and GABABR is of physiological significance, and may be a mechanism to more selectively modulate GABABR.
Geographic variation in parity progression in Australia
Authors: Gray Edith , Evans Ann
Published: June 2017

Australia has moderately high fertility compared to many Western‐industrialized countries. The current total fertility rate is around 1.88, but fertility levels are not uniform across the country. There is a distinct geographic pattern with the total fertility rate about 0.5 higher in remote and very remote Australia (2.33) compared to major cities (1.82). In this paper, we examine 2 explanations for this pattern: the compositional hypothesis and the contextual hypothesis. Using event‐history methods with joint modelling to investigate parity progression, we find that after taking into account differences in age, country of birth, indigenous status, relationship status, education levels, and economic activity, women living in smaller towns in regional Australia are more likely to have a first, second, and third birth. Further, there is lower propensity to have a first child in inner or middle city areas that are characterized by smaller and more expensive housing than suburban or regional areas.
Etching SiC‐slurry and diamond wire‐sawn silicon wafers with HF‐HCl‐Cl2 mixtures: Parameter influences on etch rates and surface structures
Authors: Stapf André , Nattrodt Peter , Gondek Christoph , Kroke Edwin
Published: June 2017

Solutions for the wet chemical treatment of silicon wafer surfaces were investigated using mixtures which are based on hydrofluoric acid (HF), hydrochloric acid (HCl), and chlorine (Cl2). We used a DoE‐test plan (Design of Experiments) to evaluate the effects of five selected parameters: concentrations of HF and HCl, gas flow rate of Cl2, stirring, and saw type of the wafer material. High etch rates of up to 0.63 μm min−1 were observed at room temperature, which are comparable to the etch rates of KOH‐IPA solutions. The silicon surface was investigated by reflectivity measurements and scanning electron microscopy (SEM), indicating pyramidal textured and polished surfaces for diamond wire‐ and SiC‐slurry‐sawn wafers. Using an optimized parameter set, random inverted pyramidal surface structures are formed. These random inverted structures show a significant increase in light absorption compared to standard random upright pyramid textures, for example produced by KOH‐IPA solutions.
Photoluminescence associated with {113} defects in oxygen‐implanted silicon
Authors: Sobolev N. A. , Kalyadin A. E. , Shek E. I. , Shtel‘makh K. F. , Vdovin V. I. , Gutakovskii A. K. , Fedina L. I.
Published: June 2017

The dependences of photoluminescence (PL) and the structure of {113} defects induced in n‐Cz‐Si (100) wafers by implantation of 350 keV O+ ions at a dose of 3.7 × 1014 cm−2 on the annealing time at 700 °C for 0.5–2.0 h in a chlorine‐containing atmosphere have been studied in detail. Extended defects were examined by high‐resolution transmission electron microscopy (HRTEM) on cross‐sectional samples. HRTEM evidences that {113} defects dominate in all the samples under study. A shift of the PL band from 920 to 903 meV (“903” line, R‐line, or 1370 nm line) was observed with increasing annealing time, which suggests a strong change of the {113} defect structure. According to the Geometrical Phase Method used for the measurements of lattice deformations around the {113} defects observed by HRTEM, this change is related to a transformation of a vacancy‐type {113} defect to an interstitial one. The effect of the measurement temperature on the main parameters of R‐line has been studied, too. A sample annealed for 1 h has some characteristic features of the temperature dependence of the PL intensity: it increases with activation energy of 19.1 meV at low temperatures and decreases with deactivation energies of 32.2 and 175.5 meV at higher temperatures. With the increasing temperature, the luminescence peak shifts by the same energy as the forbidden gap width, while the FWHM of the line grows linearly.
Gas‐phase fragmentation of 1‐adamantylbisimidazolium salts and their complexes with cucurbit[7]uril studied using selectively 2H‐labeled guest molecules
Authors: Čablová Andrea , Rouchal Michal , Hanulíková Barbora , Vícha Jan , Dastychová Lenka , Prucková Zdeňka , Vícha Robert
Published: June 2017

Rationale

Bisimidazolium salts (BIMs) represent an interesting family of ditopic ligands that are used in the construction of supramolecular systems with hosts based on cyclodextrins or cucurbit[n]urils. Understanding the fragmentation mechanism of individual BIMs and how this mechanism changes after complexation with cucurbit[n]urils can bring new insight into the intrinsic host‐guest relationship, thereby allowing utilization of mass spectrometry to describe binding behavior.

Methods

Selectively 2H‐labeled bisimidazolium salts were prepared and fully characterized by spectroscopic methods. All MSn experiments were conducted in the positive‐ion mode using an electrospray ionization (ESI) ion‐trap mass spectrometer. The structures of the proposed fragments were supported by theoretical optimizations performed at the B3LYP/6‐31G(d) level of density functional theory (DFT) using the Spartan'14 program.

Results

Using selectively deuterium‐labeled isotopologues of two adamantylated bisimidazolium salts and DFT calculations, we describe the fragmentation pathways of bisimidazolium salts. The release of two important adamantane moieties, [C11H17]+ and C11H16, from M2+ was determined, although the former was strongly preferred. In contrast, when M2+ was complexed with CB7, the neutral loss of the C11H16 fragment was favored. The fragmentation pattern strongly depended on the steric hindrance of the M2+ guest against slippage of the CB7 unit over the guest molecular axle.

Conclusions

The structures of two adamantane‐based fragments and the mechanisms of their formation were rationalized. Two distinct geometric arrangements for the adamantane cage inside the CB7 cavity were hypothesized to explain the differences in the fragmentation patterns for guests with minimal, moderate, and high steric hindrance. This finding brings new insight into the understanding of intrinsic behavior of the adamantane‐based guests inside the CB7 cavity.
Challenges of soil mixing using catalyzed hydrogen peroxide with rotating dual axis blending technology
Authors: Kakarla Prasad , Symmes Frederick , Temple Michael , Dello Russo Vincent , Hall Erik , Caldicott William , Hoffman Andrew
Published: June 2017

Although known to be one of the most effective oxidants for treatment of organic contaminants, catalyzed hydrogen peroxide (CHP) is typically not used for soil mixing applications because of health and safety concerns related to vapor generation and very rapid rates of reaction in open excavations. In likely the first large‐scale in situ CHP soil mixing application, an enhanced CHP, modified Fenton's reagent (MFR), was applied during soil mixing at the Kearsarge Metallurgical Superfund Site in New Hampshire. An innovative rotating dual‐axis blender (DAB) technology was used to safely mix the MFR into low‐plasticity silt and clay soils to remediate residual 1,1,1‐trichloroethane (111TCA); 1,1‐dichloroethene (11DCE); and 1,4‐dioxane (14D). It was expected that the aggressive treatment approach using relatively “greener” hydrogen peroxide (HP) chemistry would effectively treat Site contaminants without significant byproduct impacts to groundwater or the adjacent pond. The remediation program was designed to treat approximately 3,000 cubic yards of residual source area soil in situ by aggressively mixing MFR into the soils. The subsurface interval treated was from 7 to 15 feet below ground surface. To accurately track the soil mixing process and MFR addition, the Site was divided into 109 10‐foot square treatment cells that were precisely located, dosed, and mixed using the DAB equipped with an on‐board GPS system. The use of stabilizing agents along with careful calculation of the peroxide dose helped to ensure vapor‐free conditions in the vicinity of the soil mixing operation. Real‐time sampling and monitoring were critical in identifying any posttreatment exceedences of the cleanup goals. This allowed retreatment and supplemental testing to occur without impacting the soil mixing/in situ chemical oxidation (ISCO) schedule. Posttreatment 24‐hr soil samples were collected from 56 random locations after ensuring that the HP had been completely consumed. The posttreatment test results showed that 111TCA and 11DCE concentrations were reduced to nondetect (ND) or below the cleanup goals of 150 μg/kg for 111TCA and 60 μg/kg for 11DCE. Supplemental posttreatment soil samples, collected six months after treatment, showed 100 percent compliance with the soil treatment goals. Groundwater samples collected one year after the MFR soil mixing treatment program showed either ND or low concentrations for 111TCA, 11DCE, and 14D. Successful stabilization and site restoration was performed after overcoming considerable challenges associated with loss of soil structure, high liquid content, and reduced bearing capacity of the blended soils.
BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints
Authors: Zhou Heng , Lee J. Jack , Yuan Ying
Published: June 2017

We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co‐primary) endpoints under a unified framework. We use a Dirichlet‐multinomial model to accommodate different types of endpoints. At each interim, the go/no‐go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd.
One‐Pot Preparation of Macroporous Organic‐Silica Monolith for the Organics‐/Oil‐Water Separation
Authors: Liu Zhongshan , Ou Junjie , Wang Hongwei , Chen Lianfang , Xu Junwen , Ye Mingliang
Published: June 2017

Three‐dimensional porous monoliths have been considered as attractive candidates for the organics‐/oil‐water separation due to their high porosity, low density and hydrophobic/oleophilic property. To simplify the preparation process, one‐pot method based on thiol‐methacrylate click polymerization was developed to fabricate macroporous organic‐silica monolith by using octakis(3‐mercaptopropyl)octasilsesquioxane, ethylene glycol dimethacrylate and heptadecafluorodecyl methacrylate as starting monomers. The rapid click polymerization was carried out at room temperature under air atmosphere, which made it possible for preparation of monolith with desired scale and geometry. The hybrid monolith with good thermal stability and compressibility generated through‐pores with diameter ranging from several microns to tens of microns. As a result of the flexible organic linkages and fluorocarbon groups, the hybrid monolith showed hydrophobic feature, and could be fast swollen in organic liquids. Particularly, a cylindrical hybrid monolith (15 mm in diameter × 11 mm in height) supported by a modified syringe, which exhibited excellent recyclability and swelling‐squeezing performance, has been applied to selectively absorb organic liquids located on the upper or under water layer.
Unraveling the Hydrogen Evolution Reaction Active Sites in N‐Functionalized Interconnected Graphene Quantum Dots
Authors: Kundu Sumana , Malik Bibhudatta , Pattanayak Deepak K. , Pitchai Ragupathy , Pillai Vijayamohanan K.
Published: June 2017

Herein, we report for the first time, a unique three‐ dimensionally (3‐D) interconnected and surface N functionalized (25%) graphene quantum dots (c‐GQDs), which has been designed by a simple hydrazine hydrate treatment of GQDs in acidic condition at low temperature followed by a heat treatment that has remarkably enhanced electrocatalytic activity. A comparable exchange current density (i0: 0.8×10−3 A/cm2) with respect to the Pt/C and a low overpotential (220 mV; η10mA/cm2) has been observed for c‐GQDs. The improved performance of the material is attributed to the unique structure of the N‐interlinkage among the individual GQDs where the pyridinic‐N‐oxide develops electron rich active sites in the carbon framework for favourable H+ adsorption and desorption. We hope that our study may build up a new platform to the graphene based materials for various energy applications.
Synthesis of 5,6‐Di(2‐fluoro‐2,2‐dinitro ethoxy)‐2,3‐Dicyanopyrazine by One–step Nucleophilic Substitution and Its Energetic Properties
Authors: Ma Qing , Gu Hao , Lu Huanchang , Liao Longyu , Huang Jinglun , Fan Guijuan , Li Jinshan , Liu Dabin
Published: June 2017

5,6‐di(2‐fluoro‐2,2,–dinitroethoxy)‐2,3‐dicyanopyrazine was synthesized in a one‐pot process starting from 5,6‐dichloro‐2,3‐dicyanopyrazine. Its structure was fully characterized by 1H, 13C, 15N and 19F NMR, mass spectroscopy, infrared spectrum as well as elementary analysis. Low‐temperature X‐ray diffraction was employed for analyzing its crystal structure. It exhibits excellent thermal stability (onset m.p. 203 oC, onset dec. 222 oC) which is comparable to those of 1,3,5‐trinitroperhydro‐1,3,5‐triazine (RDX). Different from RDX, it shows good safety properties (IS>60 J, FS=160 N). Its detonation performance exceed those of 2,4,6‐trinitrotoluene (TNT). The above‐mentioned energetic performance show that it is insensitive and worth further potential applications.
Structural and Phase Transformations in Internally Nitrided Corrosion‐Resistant Steel during Severe Plastic Deformation and Subsequent Annealings
Authors: Rogachev Stanislav O. , Nikulin Sergey A. , Khatkevich Vladimir M.
Published: June 2017

The effect of severe plastic deformation (SPD) by high‐pressure torsion (HPT) and subsequent annealings on structural and phase transformations in 0.08C–18Cr–0.5Ti steel, which is preliminarily hardened by high‐temperature internal nitriding (the microhardness is 3.2 GPa), has been studied. The HPT results in the formation of nanostructure with an average structural‐element size of 55 nm and the refining and in part dissolution of Cr2N particles. After HPT, the microhardness of steel increases by 2.7 times (to 8.6 GPa at the midradius of samples), which is substantially higher than the microhardness of non‐nitrided steel after HPT. The hardening of the material remains during heating to a temperature of no less than 450 °С at the expense of precipitation of disperse Cr2N particles and despite of coarsening structural elements. HPT of nitrided steel leads to a shift of phase transformations, namely the temperature of chromium nitride precipitation decreases.
Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases
Authors: Volkman Rotem , Offen Daniel
Published: June 2017

Stem cell-based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hold great potential for cell therapy as they can be efficiently derived from adult tissue, ex vivo expanded in culture and safely transplanted autologously. MSCs were also shown to be able to differentiate toward neural fates and to secrete a broad range of factors able to promote nervous tissue maintenance and repair. Moreover, upon transplantation, MSCs were shown capable of homing toward lesioned areas, implying their potential use as vehicles for therapeutic agents administration. Indeed, various advantageous effects were reported following human MSCs transplantation into rodent models of neurodegenerative diseases, such as neurotrophic factor-mediated protection, enhanced neurogenesis, modulation of inflammation, and abnormal protein aggregate clearance. Recent studies have also used ex vivo manipulation for enhanced expression of potentially favorable factors, by so exploiting the homing capacity of MSCs for effective expression at the lesion site. Here, we will summarize current advancements in MSCs-based therapies for neurodegenerative diseases. We will examine the roles of central mechanisms suggested to mediate the beneficial effects of MSCs-based therapy and consider the augmentation of these mechanisms for superior clinical outcomes in rodent models of neurodegeneration as well as in clinical trials.
Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function
Authors: Sun Congshan , De Mello Vanessa , Mohamed Abdalla , Ortuste Quiroga Huascar P. , Garcia-Munoz Amaya , Al Bloshi Abdullah , Tremblay Annie M. , von Kriegsheim Alexander , Collie-Duguid Elaina , Vargesson Neil , Matallanas David , Wackerhage Henning , Zammit Peter S.
Published: June 2017

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene Wwtr1–/–) knockout mice, there were no overt effects on regeneration. Conversely, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+: Yapfl°x/fl°x:Rosa26Lacz mice produced a regeneration deficit. To identify potential mechanisms, microarray analysis showed many common TAZ/YAP target genes, but TAZ also regulates some genes independently of YAP, including myogenic genes such as Pax7, Myf5, and Myod1 (ArrayExpress–E-MTAB-5395). Proteomic analysis revealed many novel binding partners of TAZ/YAP in myogenic cells, but TAZ also interacts with proteins distinct from YAP that are often involved in myogenesis and aspects of cytoskeleton organization (ProteomeXchange–PXD005751). Neither TAZ nor YAP bind members of the Wnt destruction complex but both regulated expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to enhance myogenic differentiation.
Chimeric RNAs in cancer and normal physiology
Authors: Chwalenia Katarzyna , Facemire Loryn , Li Hui
Published: June 2017

Traditionally, chimeric RNAs were considered to be exclusive to cancer cells. When occasionally observed in normal samples, they were usually considered to be transcriptional ‘noises,’ or artifacts due to template switching during the reverse transcription and/or Polymerase chain reaction (PCR) steps of experimentation. However, with the advances being made in next generation sequencing technologies and software tools, as well as the accumulation of new experimental evidences, increasing numbers of chimeric transcripts are being identified in noncancerous tissues and cells. Recent studies have also demonstrated functional relevance, for at least a subset of chimeric RNAs in normal physiology. The advances have resulted in an influx of knowledge; this knowledge indicates that chimeric RNAs are a component of basic biology, and thus challenging traditional dogma. In addition to chromosomal rearrangement, chimeric RNAs can also be formed via different molecular mechanisms including cis‐splicing of adjacent genes (cis‐SAGe) and trans‐splicing, as well as others. Little is known about the details of these noncanonical splicing processes. However, research in this new field promises to not only advance our basic understanding of the human genome and gene regulation, but also lead to improvements in clinical practice, especially in the areas of cancer diagnostics and treatment. WIREs RNA 2017, 8:e1427. doi: 10.1002/wrna.1427

This article is categorized under:

RNA Processing > Splicing Regulation/Alternative Splicing

RNA in Disease and Development > RNA in Disease
Structure Elucidation and Characterization of the High‐Pressure Nickel Borate Hydroxide NiB3O5(OH)
Authors: Schmitt Martin K. , Janka Oliver , Pöttgen Rainer , Huppertz Hubert
Published: June 2017

The high‐pressure nickel borate hydroxide NiB3O5(OH) was synthesized in a high‐temperature/high‐pressure reaction at 4 GPa and 1023 K using a Walker‐type multianvil apparatus. Single‐crystal X‐ray diffraction was used to determine the structure of NiB3O5(OH). It crystallizes in the monoclinic space group P21/c (no. 14) with a = 4.3222(1), b = 9.5888(2), c = 8.5067(3) Å, and β = 90.50(1)°. Furthermore, the compound was characterized by powder X‐ray diffraction, vibrational spectroscopy, and magnetic measurements. The effective magnetic moment is μeff = 3.30(1) μB and the Weiss constant θP = –28.3(1) K indicates antiferromagnetic interactions in the paramagnetic regime.
Modified Inflatable Penile Prosthesis Reservoir Placement Into Space of Retzius: Comparing Outcomes in Men with or Without Prior Pelvic Surgery
Authors: Capoccia Edward M. , Phelps Jessica N. , Levine Laurence A.
Published: June 2017

Background

Traditional inflatable penile prosthesis (IPP) reservoir placement has rare but potentially serious complications including damage to local structures, and Levine and Hoeh (J Sex Med 2012;9:2759–2769) described a modified technique designed to avoid these complications.

Aim

To determine whether the modified Jorgenson scissors technique is safe and effective in patients who have had prior pelvic surgery.

Methods

A retrospective chart review was performed on all patients who had a three-piece IPP placed by a single urologist from 2011 to 2015. Complication rates between the prior pelvic surgery group and the virgin pelvis group were compared using χ2 test. Differences between the two groups were considered statistically significant at a P value less than .05.

Outcomes

Reservoir-related complication rate and rate of converting to ectopic placement.

Results

A total of 246 procedures were included, with 174 having no prior pelvic surgery and 72 with prior pelvic surgery. The reservoir-related complication rates were 2.8% (2 of 72) in the prior pelvic surgery group and 3.4% (6 of 174) in the virgin pelvis group. This difference was not statistically significant (P = .79). The two complications from the prior pelvic surgery cohort were inguinal hernias requiring surgical repair, which occurred in the same patient. In the virgin pelvis cohort, there were five inguinal hernias and one autoinflation. There were 16 patients who required ectopic placement of the reservoir owing to difficulty in entering the space of Retzius (SOR), 14 of whom had prior pelvic surgery.

Clinical Implications

We believe this modified technique for IPP reservoir placement into the SOR is a safe alternative because the Jorgenson scissors allow perforation into the SOR away from vital structures.

Strengths and Limitations

The study is limited by the fact that it is a retrospective, single-center, chart review of a non-randomized surgical procedure with variable follow-up in a limited number of patients. Its strength is its applicability to provide surgeons a modified technique that can be used routinely for IPP reservoir placement that appears to be safe and effective, even in men who have had prior pelvic surgery.

Conclusion

In our experience, the modified Jorgenson scissors technique allows for safe entry into the SOR through a transverse scrotal incision and is a viable alternative to the standard SOR placement and the ectopic approach.
Mastering Single Best Answer Questions for the Part 2 MRCOG Examination
Authors: Elkady Adel , Dawlatly Bashir , Ahmed Mustafa Hassan , Rees Alexandra
Published: June 2017

This comprehensive question-and-answer resource covers all aspects of the curriculum for the Part 2 MRCOG examination. Candidates are given the opportunity to practise the Single Best Answer question style, to cover the content they will encounter in the examination and to assess their knowledge. As consultants actively engaged in the writing of the Part 2 Single Best Answers, the authors and editor have provided directly applicable questions. Candidates to review the syllabus in an organised, systematic manner, with comprehensive explanations for each answer. This title also includes new sections on ethics, training, audit and clinical governance. Mock exams are also available online to familiarise candidates with the real-life examination. The detailed answers, evidence and comprehensive list of references offer an excellent training and reading source for all candidates preparing for the Part 2 MRCOG examination.
Living with the Enemy
Authors: Ott Sandra
Published: June 2017

In post-liberation France, the French courts judged the cases of more than one hundred thousand people accused of aiding and abetting the enemy during the Second World War. In this fascinating book, Sandra Ott uncovers the hidden history of collaboration in the Pyrenean borderlands of the Basques and the Béarnais in southwestern France through nine stories of human folly, uncertainty, ambiguity, ambivalence, desire, vengeance, duplicity, greed, self-interest, opportunism and betrayal. Covering both the occupation and liberation periods, she reveals how the book's characters became involved with the occupiers for a variety of reasons, ranging from a desire to settle scores and to gain access to power, money and material rewards, to love, friendship, fear and desperation. These wartime lives and subsequent postwar reckonings provide us with a new lens through which to understand human behavior under the difficult conditions of occupation, and the subsequent search for retribution and justice.
A survey of front-line paramedics examining the professional relationship between paramedics and physician medical oversight
Authors: Foerster Christopher R. , Tavares Walter , Virkkunen Ilkka , Kämäräinen Antti
Published: June 2017

Objective

Paramedicine is often dependent on physician medical directors and their associated programs for direction and oversight. A positive relationship between paramedics and their oversight physicians promotes safety and quality care while a strained or ineffective one may threaten these goals. The objective of this study was to explore and understand the professional relationship between paramedics and physician medical oversight as viewed by front-line paramedics.

Methods

All active front-line paramedics from four municipal paramedic services involving three medical oversight groups in Ontario were invited to complete an online survey.

Results

Five hundred and four paramedics were invited to participate in the study, with 242 completing the survey (48% response rate); 66% male, 76% primary care paramedics with an average of 13 (SD=9) years of experience. Paramedics had neutral or positive perceptions regarding their autonomy, opportunities to interact with their medical director, and medical director understanding of the prehospital setting. Paramedics perceived medical directives as rigid and ambiguous. A significant amount of respondents reported a perception of having provided suboptimal patient care due to fear of legal or disciplinary consequences. Issues of a lack of support for critical thinking and a lack of trust between paramedics and medical oversight groups were often raised.

Conclusions

Paramedic perceptions of physician medical oversight were mixed. Concerning areas identified were perceptions of ambiguous written directives and concerns related to the level of trust and support for critical thinking. These perceptions may have implications for the system of care and should be explored further.
Infection dynamics of Caryophyllaeid tapeworm, Adenoscolex oreini Fotedar, 1958 and impacts of intra-lake pollution gradient on intermediate host (copepods) and health attributes of Schizothorax spp.
Authors: ZARGAR U. R. , CHISHTI M. Z. , RATHER M. I. , KHANDAY S.A.
Published: June 2017

This study is an attempt to unravel the infection pattern of the Caryophyllaeid tapeworm, Adenoscolex oreini and its association with water quality, planktonic copepods and health traits of fish in a highly stressed lake. Prevalence differed significantly (P < 0·05) among different fish species with highest infection recorded in Schizothorax niger (% = 36·74) compared to Schizothorax esocinus (% = 15·7). Within-lake trophic gradient affected the infection pattern as prevalence of A. oreini was significantly higher (44·62%, P = 0·0001) at hypereutrophic site as compared to least eutrophic site (8·01%). The data suggest that spatial variation in the intensity of A. oreini corresponded to the variation in the abundance of planktonic copepods. The density of Cyclops scutifer was positively correlated with the prevalence of tapeworm. Results indicate that the health condition, which was reflected by condition factor and gonadosomatic index, was lower in parasitized fish, and there seems to be synergistic effect of eutrophication and parasitism on fish health. Linear regression coefficients showed that the health indices were significantly (P < 0·05) predicted by infection intensity. It is concluded from the results that within-lake pollution gradient affects the infection pattern, density of intermediate host and health attributes of fish, and therefore these finding will lead us to elucidate the predictors responsible for decline of health of fish in highly stressed water bodies.
THE NATIVE VILLAGE DEBATE IN PIETERMARITZBURG, 1848–1925: REVISITING THE ‘SANITATION SYNDROME’
Authors: EPPRECHT MARC
Published: June 2017

This article examines the history of debates around the creation of a ‘native village’ in Pietermaritzburg culminating in the construction of the city's first formal township. This, and the decision to locate the new township next to the city's main dump, have commonly been interpreted to corroborate Maynard Swanson's influential concept of the ‘sanitation syndrome’. Swanson first coined that term to explain the origins of racial segregation in Durban, but it struck a chord very widely, not only because it problematized science as metaphorical, but also because it shifted responsibility for the antecedents of apartheid onto urban, self-styled progressive English-speaking officials and voters. From the Pietermaritzburg evidence, however, I argue that the concept ‘sanitation syndrome’ now unhelpfully elides or oversimplifies a complex history. I thus question its continued utility as a critique of cultural racism within liberal or modernization discourses in the wider contemporary regional context.
Book lists from the Cairo Genizah: a window on the production of texts in the middle ages
Authors: Frenkel Miriam
Published: June 2017

The historicity of books – their role as a force in history – has been addressed in post-war literary studies from different perspectives and across various disciplines. Nevertheless, the scholarship on the history of the book in medieval Islam is still relatively sparse, even though this society underwent a thorough process of textualization. But even authors who do consider the social and cultural role of books in medieval Islam look only at the production and consumption of Arabic books within the boundaries of Muslim society, relying on Islamic sources which reflect mainly the courtly milieu of scribes and secretariats. None discuss books produced and consumed by the religious minorities that were an indispensable part of this society, and none have made use of the abundant Genizah documents as source material. In the present programmatic article, I call attention to the many book lists found in the Cairo Genizah and to their potential as significant tools for developing a better understanding of the cultural and social history of the medieval Islamicate world.
BANDIT STRATEGIES EVALUATED IN THE CONTEXT OF CLINICAL TRIALS IN RARE LIFE-THREATENING DISEASES
Authors: Villar Sofía S.
Published: June 2017

In a rare life-threatening disease setting the number of patients in the trial is a high proportion of all patients with the condition (if not all of them). Further, this number is usually not enough to guarantee the required statistical power to detect a treatment effect of a meaningful size. In such a context, the idea of prioritizing patient benefit over hypothesis testing as the goal of the trial can lead to a trial design that produces useful information to guide treatment, even if it does not do so with the standard levels of statistical confidence. The idealized model to consider such an optimal design of a clinical trial is known as aclassicmulti-armed bandit problem with a finite patient horizon and a patient benefit objective function. Such a design maximizes patient benefit by balancing the learning and earning goals as data accumulates and given the patient horizon. On the other hand, optimally solving such a model has a very high computational cost (many times prohibitive) and more importantly, a cumbersome implementation, even for populations as small as a hundred patients. Several computationally feasible heuristic rules to address this problem have been proposed over the last 40 years in the literature. In this paper, we study a novel heuristic approach to solve it based on the reformulation of the problem as a Restless bandit problem and the derivation of its corresponding Whittle Index (WI) rule. Such rule was recently proposed in the context of a clinical trial in Villar, Bowden, and Wason [16]. We perform extensive computational studies to compare through both exact value calculations and simulated values the performance of this rule, other index rules and simpler heuristics previously proposed in the literature. Our results suggest that for the two and three-armed case and a patient horizon less or equal than a hundred patients, all index rules area prioripractically identical in terms of the expected proportion of success attained when all arms start with a uniform prior. However, we find thata posteriori, for specific values of the parameters of interest, the index policies outperform the simpler rules in every instance and specially so in the case of many arms and a larger, though still relatively small, total number of patients with the diseases. The very good performance of bandit rules in terms of patient benefit (i.e., expected number of successes and mean number of patients allocated to the best arm, if it exists) makes them very appealing in context of the challenge posed by drug development and treatment for rare life-threatening diseases.
Results of survey on hedging practices
Authors: Cadman J. M. , Bhatia R. , Dissanayake N. A. , Mageed S. , Rogers I. J. , Zavadlal G.
Published: June 2017

The hedging practices survey took place towards the end of 2015 in the final few months prior to Solvency II regulations coming into force. At the point of completing the survey we would expect that companies would have largely transitioned their hedging approaches to work in a Solvency II environment. There may be some cases where further changes were planned but not implemented at the point of completing the survey. Further, as familiarity with working under the new regulations increases, approaches are expected to continue to develop over time. The working party hopes that this report is useful in summarising industry attitudes at this point in time and as a comparator in future years. Before launching the survey we did have several conjectures of what we may expect to see in the results. Some proved true, for some it was difficult to glean any strong conclusion from the data, and there were one or two where results countered what we expected to see.
Mycelium-mediated transfer of water and nutrients stimulates bacterial activity in dry and oligotrophic environments
Authors: Worrich Anja , Stryhanyuk Hryhoriy , Musat Niculina , König Sara , Banitz Thomas , Centler Florian , Frank Karin , Thullner Martin , Harms Hauke , Richnow Hans-Hermann , Miltner Anja , Kästner Matthias , Wick Lukas Y.
Published: June 2017

Fungal–bacterial interactions are highly diverse and contribute to many ecosystem processes. Their emergence under common environmental stress scenarios however, remains elusive. Here we use a synthetic microbial ecosystem based on the germination of Bacillus subtilis spores to examine whether fungal and fungal-like (oomycete) mycelia reduce bacterial water and nutrient stress in an otherwise dry and nutrient-poor microhabitat. We find that the presence of mycelia enables the germination and subsequent growth of bacterial spores near the hyphae. Using a combination of time of flight- and nanoscale secondary ion mass spectrometry (ToF- and nanoSIMS) coupled with stable isotope labelling, we link spore germination to hyphal transfer of water, carbon and nitrogen. Our study provides direct experimental evidence for the stimulation of bacterial activity by mycelial supply of scarce resources in dry and nutrient-free environments. We propose that mycelia may stimulate bacterial activity and thus contribute to sustaining ecosystem functioning in stressed habitats.
Towards colloidal spintronics through Rashba spin-orbit interaction in lead sulphide nanosheets
Authors: Ramin Moayed Mohammad Mehdi , Bielewicz Thomas , Zöllner Martin Sebastian , Herrmann Carmen , Klinke Christian
Published: June 2017

Employing the spin degree of freedom of charge carriers offers the possibility to extend the functionality of conventional electronic devices, while colloidal chemistry can be used to synthesize inexpensive and tunable nanomaterials. Here, in order to benefit from both concepts, we investigate Rashba spin–orbit interaction in colloidal lead sulphide nanosheets by electrical measurements on the circular photo-galvanic effect. Lead sulphide nanosheets possess rock salt crystal structure, which is centrosymmetric. The symmetry can be broken by quantum confinement, asymmetric vertical interfaces and a gate electric field leading to Rashba-type band splitting in momentum space at the M points, which results in an unconventional selection mechanism for the excitation of the carriers. The effect, which is supported by simulations of the band structure using density functional theory, can be tuned by the gate electric field and by the thickness of the sheets. Spin-related electrical transport phenomena in colloidal materials open a promising pathway towards future inexpensive spintronic devices.
Flexible integration of free-standing nanowires into silicon photonics
Authors: Chen Bigeng , Wu Hao , Xin Chenguang , Dai Daoxin , Tong Limin
Published: June 2017

Silicon photonics has been developed successfully with a top-down fabrication technique to enable large-scale photonic integrated circuits with high reproducibility, but is limited intrinsically by the material capability for active or nonlinear applications. On the other hand, free-standing nanowires synthesized via a bottom-up growth present great material diversity and structural uniformity, but precisely assembling free-standing nanowires for on-demand photonic functionality remains a great challenge. Here we report hybrid integration of free-standing nanowires into silicon photonics with high flexibility by coupling free-standing nanowires onto target silicon waveguides that are simultaneously used for precise positioning. Coupling efficiency between a free-standing nanowire and a silicon waveguide is up to ~97% in the telecommunication band. A hybrid nonlinear-free-standing nanowires–silicon waveguides Mach–Zehnder interferometer and a racetrack resonator for significantly enhanced optical modulation are experimentally demonstrated, as well as hybrid active-free-standing nanowires–silicon waveguides circuits for light generation. These results suggest an alternative approach to flexible multifunctional on-chip nanophotonic devices.