bluuebunny/crossref_metadata_2025_split huggingface dataset:
Notable Carrier Risks for Individuals Having Two Copies of SMN1 in Spinal Muscular Atrophy Families with 2‐copy Alleles: Estimation Based on Chinese Meta‐analysis Data
Authors: Wei Xianda , Tan Hu , Yang Pu , Zhang Rui , Tan Bo , Zhang Yue , Mei Libin , Liang Desheng , Wu Lingqian 
Published: July 2016

AbstractSpinal muscular atrophy is an autosomal recessive neuromuscular disease mainly caused by homozygous deletion of SMN1. The 2‐copy SMN1 allele may present in the families of SMA patients with homozygous deletion of SMN1, one of whose parents has two SMN1 copies. In such families, individuals having two SMN1 copies still have a chance to be “2 + 0” carriers. In this study, the risks for the parents, fetuses and other siblings having two SMN1 copies to be “2 + 0” carriers were estimated based on Chinese meta‐analysis data and turned out to be rather striking. Our findings would help to optimize genetic counseling regarding spinal muscular atrophy.
Family Studies for Classification of Variants of Uncertain Classification: Current Laboratory Clinical Practice and a New Web‐Based Educational Tool
Authors: Garrett Lauren T. , Hickman Nathan , Jacobson Angela , Bennett Robin L. , Amendola Laura M. , Rosenthal Elisabeth A. , Shirts Brian H. 
Published: July 2016

AbstractMulti‐gene cancer panels often identify variants of uncertain clinical significance (VUS) that pose a challenge to health care providers in managing a patient's cancer risk. Family segregation analysis can yield powerful data to re‐classify a VUS (as either benign or pathogenic). However, financial and personnel resources to coordinate these studies are limited. In an informal assessment we found that family studies for variant classification are done by most clinical genetics laboratories that offer hereditary cancer panel testing. The process for family studies differs substantially across laboratories. One near universal limitation is that families usually have too few individuals for an informative co‐segregation analysis. A unique and potential resource‐saving approach is to engage patients and their families in expanding their own pedigrees for segregation analysis of their VUS. We describe a novel public educational tool (FindMyVariant.org) designed to inform patients and genetic counselors about strategies to improve the probability of variant classification using familial segregation. While the web tool is designed to be useful for any gene, the project was primarily focused on VUS's returned in cancer risk genes. FindMyVariant.org is a resource for genetic providers to offer motivated families who are willing to gather information about their family relationships and history. Working alongside clinical or research genetic laboratories, the information they collect may help reclassify their VUS using segregation analysis.
Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats
Authors: Perez‐Pouchoulen Miguel , Miquel Marta , Saft Paul , Brug Brenda , Toledo Rebeca , Hernandez Maria Elena , Manzo Jorge 
Published: July 2016

AbstractValproic acid (VPA) is an anti‐epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600 mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points. Testosterone has been linked to autism and plays an important role during brain development. Therefore, we identified and analyzed the androgen receptor (AR) by immunohistochemistry and densitometry, respectively. We found VPA decreases AR density in the superficial Purkinje layer only in cerebellar lobule 8 at PN7, but increased it at PN14 compared to control in males. In females, VPA decreased AR density in the superficial Purkinje layer in cerebellar lobule 6 at PN14, but increased it in lobule 9 at the same time point. No differences were found in the deep Purkinje layer of any cerebellar lobule in terms of AR density neither in males nor females. We additionally found a particular AR density decreasing in both superficial and deep regions across development in the majority of cerebellar lobules in males, but in all cerebellar lobules in females. Thus, our results indicate that VPA disrupts the AR ontogeny in the developing cerebellum in an age and region specific manner in male and female rats. Future epigenetic studies including the evaluation of histone deacetylases (HDAC's) might shed light these results as HDAC's are expressed by Purkinje neurons, interact with the AR and are VPA targets. This work contributes to the understanding of the cerebellar development and it might help to understand the role of the cerebellum in neurodevelopmental disorders such as autism.
The self medication use among adolescents aged between 13–18 years old; Prevalence and behavior, Riyadh – Kingdom of Saudi Arabia, from 2014–2015
Authors: Albatti Turki Homod , Alawwad Shahd , Aldueb Roqaih , Alhoqail Razan , Almutairi Rawan 
Published: July 2016

Background and objectives:
In Saudi Arabia, people have easy access to medication and can purchase prescribed medications, such as anti-acne medications and antibiotics, over the counter without the need for a prescription from a physician.
Our research is focused on estimating the prevalence of self-medication and understanding the reason for self-medication because previous studies have shown an increase in the practice of self-medication globally and locally.
The aim of this study is to estimate the prevalence of self-medication among adolescents aged 13–18 years of both genders in Riyadh, Saudi Arabia. In addition, we aim to identify the indications and external and internal factors behind self-medication, including the effects of gender, peer influence and parental supervision on the decision of adolescents to self-medicate.

Patients and Methods:
An observational and cross-sectional adolescent-based study was performed to estimate the degree of self-medication among 400 intermediate and high school students in private and governmental schools living in Riyadh between 2014 and 2015 using a multistage random sampling technique. A validated self-administered questionnaire was used for data collection, and data were tabulated and analyzed with the SPSS version 21 computer program.

Results:
We found that the rate of self-medication among adolescents was high (94.5%). Analgesics were the most common medication used (87.3%), and the least common medication used was hormones (5%). A majority of the students reported that headache was the reason for using analgesics. The sources of the medications included the pharmacy (51.64%), followed by parents (34.33%). The results showed that self-medication was significantly associated with the type of school that the adolescents attended (P < 0.011) and the health status of the adolescents (P -value <0.035).

Conclusion:
Self-medication is highly prevalent in Riyadh, particularly among adolescents. Easy access to pharmacies was found to be the leading cause for self-medication. The use of these drugs was associated with inappropriate drug use and the deterioration of health status. Self-medication should be closely monitored and awareness should be increased with educational programs among students.
Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer's disease
Authors: Gispert Juan Domingo , Suárez‐Calvet Marc , Monté Gemma C. , Tucholka Alan , Falcon Carles , Rojas Santiago , Rami Lorena , Sánchez‐Valle Raquel , Lladó Albert , Kleinberger Gernot , Haass Christian , Molinuevo José Luis 
Published: July 2016

AbstractIntroductionTREM2 is involved in the regulation of inflammatory response and phagocytosis. A soluble fragment (sTREM2) is often found abnormally increased in cerebrospinal fluid (CSF) in Alzheimer's disease (AD).MethodsOne hundred fourteen participants (45 control, 19 preclinical, 27 mild cognitive impairment [MCI], and 23 AD) underwent CSF sTREM2 determination and magnetic resonance imaging (MRI). We studied the association between CSF sTREM2, gray matter volume, and water motion diffusivity and anisotropy across groups.ResultsIn MCI patients, a positive correlation between CSF sTREM2 and gray matter volume was found in the bilateral inferior and middle temporal cortices, precuneus, the supramarginal, and angular gyri, after controlling by age, sex, and p‐tau. A negative correlation with mean diffusivity was detected in overlapping regions, among others.DiscussionIn early AD, augmented CSF sTREM2 levels correspond with cerebral MRI features typical of brain swelling, supporting a role for TREM2 in the regulation of the neuroinflammatory response to early neurodegeneration.
The role of evaluation mode on the unit effect
Authors: Schley Dan R. , Lembregts Christophe , Peters Ellen 
Published: July 2016

AbstractRecent research on the unit effect has suggested that consumers tend to ignore relevant unit information and over‐rely on numeric magnitudes in judgments (e.g., perceiving the difference between 700 and 900 on a 1000‐point quality scale to be larger than the difference between 7 and 9 on a 10‐point scale). The current work investigates the nature of the unit effect by studying the role of different modes of evaluation, and types of information processing, on the unit effect. Specifically, three studies demonstrate that the unit effect occurs when options are evaluated simultaneously and attenuated when options are evaluated sequentially. The current article builds on research concerning comparative versus selective information processing. It demonstrates that, when information is processed in a comparative rather than selective manner, common elements in the decision (i.e., units) are more likely to be edited out, resulting in the unit effect.
Characterization of a re‐engineered, mesothelin‐targetedPseudomonasexotoxin fusion protein for lung cancer therapy
Authors: Bauss Frieder , Lechmann Martin , Krippendorff Ben-Fillippo , Staack Roland , Herting Frank , Festag Matthias , Imhof-Jung Sabine , Hesse Friederike , Pompiati Marc , Kollmorgen Gwendlyn , da Silva Mateus Seidl Rita , Bossenmaier Birgit , Lau Wilma , Schantz Christian , Stracke Jan O. , Brinkmann Ulrich , Onda Masanori , Pastan Ira , Bosslet Klaus , Niederfellner Gerhard 
Published: July 2016

Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin‐targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non‐specific toxicity. To overcome both obstacles we developed RG7787, a de‐immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B‐cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). Reactivity of RG7787 with sera from immunotoxin‐treated patients was >1000 fold reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with picomolar potency. The pharmacokinetic properties of RG7787 in rodents were comparable to SS1P, yet it was tolerated up to 10 fold better without causing severe vascular leak syndrome or hepatotoxicity. A pharmacokinetic/pharmacodynamic model developed based on NCI‐H596 xenograft studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies closely correlate. At optimal doses of 2–3 mg/kg RG7787 is more efficacious than SS1P. Even large, well established tumors (600 mm3) underwent remission during three treatment cycles with RG7787. Also in two patient‐derived lung cancer xenograft models, Lu7336 and Lu7187, RG7787 showed anti‐tumor efficacy. In monotherapy two treatment cycles were moderately efficacious in the Lu7336 model but showed good anti‐tumor activity in the KRAS mutant Lu7187 model (26% and 80% tumor growth inhibition, respectively). Combination of RG7787 with standard chemotherapies further enhanced efficacy in both models achieving near complete eradication of Lu7187 tumors.
NPT088 reduces both amyloid‐β and tau pathologies in transgenic mice
Authors: Levenson Jonathan M. , Schroeter Sally , Carroll Jenna C. , Cullen Valerie , Asp Eva , Proschitsky Ming , Chung Charlotte H.‐Y. , Gilead Sharon , Nadeem Muhammad , Dodiya Hemraj B. , Shoaga Shadiyat , Mufson Elliott J. , Tsubery Haim , Krishnan Rajaraman , Wright Jason , Solomon Beka , Fisher Richard , Gannon Kimberley S. 
Published: July 2016

AbstractIntroductionAlzheimer's disease (AD) is characterized by appearance of both extracellular senile plaques and intracellular neurofibrillary tangles, comprised of aggregates of misfolded amyloid‐β (Aβ) and hyper‐phosphorylated tau, respectively. In a previous study, we demonstrated that g3p, a capsid protein from bacteriophage M13, binds to and remodels misfolded aggregates of proteins that assume an amyloid conformation. We engineered a fusion protein (“NPT088”) consisting of the active fragment of g3p and human‐IgG1‐Fc.MethodsAged Tg2576 mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or functional motor endpoints were monitored during dosing. Pathology was quantified biochemically and immunohistochemically.ResultsNPT088‐lowered Aβ plaque and improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced phospho‐tau pathology, reduced brain atrophy, and improved cognition in rTg4510 mice.DiscussionThese observations establish NPT088 as a novel therapeutic approach and potential drug class that targets both Aβ and tau, the hallmark pathologies of AD.
Large deflection analysis of cantilever beams of symmetrical cross-section subjected to a rotational distributed loading including the effect of material nonlinearity
Authors: Nageswara Rao B. , Venkateswara Rao G. 
Published: July 2016

AbstractCombined effects of geometrical and material non-linearities on a cantilever beam having symmetrical cross-section about its central axis with a rotational distributed loading are studied. It is assumed that the stress-strain relation in compression is identical to that in tension. Due to this, the neutral axis coincides with the central axis of the beam. The problem is formulated by means of an integral equation which is suitably converted to a system of nonlinear ordinary differential equations which are solved using a simple and accurate numerical method. Details of the load deflection characteristics for an I-beam and for a beam of rectangular cross-section are presented.
Modelling of aircraft program motion with application to circular loop simulation
Authors: Blajer W. 
Published: July 2016

SummaryThe objective of this paper is to present the principles of a mathematical model of aircraft prescribed motion. Requirements imposed on the aircraft motion are treated as program constraints on the system and both the transient dynamic solution of motion equations and the control ensuring the exact realisation of the prescribed motion are obtained as a result. The approach used is equivalent to the Lagrange multiplier method, generalised for the purpose of this paper. It consists of the solution of the set of differential/algebraic equations of index exceeding three. The presented mathematical model has been applied to the simulation of aircraft prescribed motion in a loop. The flight along an ideal circle and the flight with additionally demanded constant velocity are described. Some results of numerical calculations are demonstrated.
An appraisal of ‘flat plate’ closure for the approximate solution of boundary layer problems
Authors: Poll D. I. A. , Hellon C. M. 
Published: July 2016

SummaryThe usefulness of zero pressure gradient, flat plate closure relations in providing approximate solutions for the boundary layer momentum and energy integral equations is examined. Expressions are obtained for skin friction, surface heat transfer rate and local Reynolds analogy factor under general compressible flow conditions. For laminar flows the predictions are compared with well known similarity solutions, with some exact solutions for non-similar flows and with experimental heat transfer data for high speed flow over a blunt cone. Consideration is also given to situations in which the surface temperature is a function of position. For turbulent flow situations comparisons are made with experimental data obtained from two-dimensional and axi-symmetric tests. Conditions vary from low Mach number incompressible flows through to high Mach number compressible flows with highly cooled walls. Some comparisons are also made with other prediction techniques.
The dynamic response of an aircraft wheel to variations in runway friction
Authors: Wattling A. G. 
Published: July 2016

Experimental and analytical techniques are presented for the determination of the response characteristics of a scale-model aircraft wheel to changes in runway friction. Results obtained from tests using these techniques are given. The wheel spin-up acceleration is shown to be proportional to wheel load and to the magnitude of the surface friction coefficient after surface change. It is also found to be inversely proportional to brake torque, but is largely independent of speed. An increase of speed is shown to increase the distance required for spin-up of a locked wheel as it encounters surfaces of higher friction coefficient. Good correlation of these trends is obtained analytically.The effects of tyre flexibility are indicated by the results of both the experimental tests and the analytical simulations. These effects may degrade the performance of aircraft antiskid braking systems. It is recommended, therefore, that simulations used in the development of such systems take proper account of tyre flexibility when modelling the dynamics of the wheel and tyre.
The longitudinal dynamic stability and control of a large receiver aircraft during air-to-air refuelling
Authors: Bloy A. W. , Ali K. A. M. , Trochalidis V. 
Published: July 2016

SummaryThe longitudinal stability and control of a large receiver aircraft was considered during air-to-air refuelling. A simple horseshoe vortex was used to model the tanker wake and approximate expressions were derived for the additional aerodynamic derivatives due to the position and attitude of the receiver aircraft within the downwash field. These derivatives were shown to depend on the mean variation of downwash with vertical displacement at the receiver wing and tailplane. The mean downwash gradients, in turn, depend mainly on the vertical separation between the tanker and receiver aircraft and the ratio of the tanker-to-receiver aircraft wing spans. Solutions of the linearised equations of motion were obtained for a range of values of the downwash gradients. The large receiver aircraft, considered in the paper, typically exhibits two divergent modes which appear to be controlled in flight by frequent alternate movement of the elevators and engine throttle.
Project Management—A Science, an Art, or an Organisation Problem?
Authors: Harland R. E. W. 
Published: July 2016

Modern weapons are very powerful. They may be very spectacular. They make news.They are also very complex. They cost a lot of money. This, too, makes news.Doing something complex and expensive usually takes a long time. This is not news. It only becomes news, then, if something sudden or unexpected happens—like a crash or a cancellation.Sometimes it seems that, for such projects, the press look on no news as bad news; and bad news is good news for a reporter.The art of project management is to ensure that nothing is entirely unexpected. This may not be newsworthy, but it should be economic.
Simulators for the Lunar Mission
Authors: McGowan James 
Published: July 2016

This is the Age of Space Flight. Satellites orbiting the earth are the heralds of more spectacular demonstrations to come. “Man in earth orbit” is the prologue to manned missions in the alien environment of lunar space.Basically, the objectives of the US space programme are to:1.Expand human knowledge of atmosphere and space.2.Improve the use, speed, performance, safety and efficiency of aeronautical and space vehicles.3.Develop and operate vehicles capable of carrying instruments, equipment, supplies and living organisms through space.4.Study the potential benefits of space activities for peaceful and scientific purposes.5.Preserve the role of the US as a leader in aeronautical and space science and technology, and in the application thereof to peaceful activities.
Dr. A. A. Griffith, CBE, FRS
Authors: Eyre Donald 
Published: July 2016

From June 1937, I had been working on advanced project design schemes with a small group located at the Rolls-Royce guest house. An ideal spot for quiet concentration, in extensive private grounds by the river Derwent and on the outskirts of the village of Duffield.Early in 1939, we were informed that Dr. A. A. Griffith would be occupying a room at the guest house. E. W. Hives (later Lord Hives) had invited Griffith to join Rolls-Royce and to work on the initiation of aero engine research, in particular the gas turbine and its applications.We were naturally interested to learn more about him but all that I could gather from my associates was that he was “tall, thin and had a hell of a brain”.
Modern Solutions to Coupling and Transmission Problems of Aircraft Engines
Authors: Bruyère Marcel 
Published: July 2016

SummaryAfter a brief review of the classification of the couplings from the kinematic and mechanical points of view, the problem of aircraft engine Interconnection is introduced, together with some solutions which have made it possible to overcome the difficulty presented by the joint, at the expense, however, of some other mechanical requirements. The troubles experienced with couplings are to be blamed on the following three aspects of the conventional coupling designs: the use of gear-tooth couplings, sliding splined shaft arrangements, and the use of couplings of excessive weight. Possible improvements in the conventional designs using splined shafts are described, also the correct means of ensuring lubrication and the possibility of avoiding the need of lubrication by use of elastic distortion. Some Information is given about the effect of materials to be used for joint faces. The author then deals with coupling systems which are essentially based on the elastic property of materials. Three systems are investigated: flexible shafts, diaphragms and flexible couplings. Although flexible shafts are excellent for small misalignments, they do not permit axial movements of which diaphragms and flexible couplings are capable. The author then deals with sliding motions by recirculation of rollers which considerably extend the possibilities of axial movement. While couplings are devices normally intended to (ink up adjacent units, they become transmissions when units are some distance apart, and the typical feature of transmissions is that they require to be supported on one or more bearings. Straight and curved transmissions are presented, together with a brief survey of the following problems:Torsional and bending strength, critical speeds, bearings, damping, loads on attachment points, effect of high and low temperatures, selection of materials, end couplings.Typical test results are given, including those for the Breguet 941 curved transmission which has been run for 17 000 hours, that is 3.6 X 1010 revolutions, with only one relubrication at 10 000 hours. A short length instructional film showed the operation of a flexible bearing under critical speed conditions (this bearing is a part of the Breguet 941 curved transmission), and also demonstrated the endurance of the joints using sliding-type flexible couplings.