bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis
Authors: Howells James , Matamala José Manuel , Park Susanna B. , Garg Nidhi , Vucic Steve , Bostock Hugh , Burke David , Kiernan Matthew C. 
Published: September 2018

Key points
The progressive loss of motor units in amyotrophic lateral sclerosis (ALS) is initially compensated for by the reinnervation of denervated muscle fibres by surviving motor axons.
A disruption in protein homeostasis is thought to play a critical role in the pathogenesis of ALS.
The changes in surviving motor neurons were studied by comparing the nerve excitability properties of moderately and severely affected single motor axons from patients with ALS with those from single motor axons in control subjects.
A mathematical model indicated that approximately 99% of the differences between the ALS and control units could be explained by a non‐selective reduction in the expression of all ion channels.
These changes in ALS patients are best explained by a failure in the supply of ion channel and other membrane proteins from the diseased motor neuron.
AbstractAmyotrophic lateral sclerosis (ALS) is characterised by a progressive loss of motor units and the reinnervation of denervated muscle fibres by surviving motor axons. This reinnervation preserves muscle function until symptom onset, when some 60–80% of motor units have been lost. We have studied the changes in surviving motor neurons by comparing the nerve excitability properties of 31 single motor axons from patients with ALS with those from 21 single motor axons in control subjects. ALS motor axons were classified as coming from moderately or severely affected muscles according to the compound muscle action potential amplitude of the parent muscle. Compared with control units, thresholds were increased, and there was reduced inward and outward rectification and greater superexcitability following a conditioning impulse. These abnormalities were greater in axons from severely affected muscles, and were correlated with loss of fine motor skills. A mathematical model indicated that 99.1% of the differences between the moderately affected ALS and control units could be explained by a reduction in the expression of all ion channels. For the severely affected units, modelling required, in addition, an increase in the current leak through and under the myelin sheath. This might be expected if the anchoring proteins responsible for the paranodal seal were reduced. We conclude that changes in axonal excitability identified in ALS patients are best explained by a failure in the supply of ion channel and other membrane proteins from the diseased motor neuron, a conclusion consistent with recent animal and in vitro human data.
Feedforward‐ and motor effort‐dependent increase in prefrontal oxygenation during voluntary one‐armed cranking
Authors: Ishii Kei , Liang Nan , Asahara Ryota , Takahashi Makoto , Matsukawa Kanji 
Published: September 2018

Key points
Some cortical areas are believed to transmit a descending signal in association with motor intention and/or effort that regulates the cardiovascular system during exercise (termed central command). However, there was no evidence for the specific cortical area responding prior to arbitrary motor execution and in proportion to the motor effort.
Using a multichannel near‐infrared spectroscopy system, we found that the oxygenation of the dorsolateral and ventrolateral prefrontal cortices on the right side increases in a feedforward‐ and motor effort‐dependent manner during voluntary one‐armed cranking with the right arm.
This finding may suggest a role of the dorsolateral and ventrolateral prefrontal cortices in triggering off central command and may help us to understand impaired regulation of the cardiovascular system in association with lesion of the prefrontal cortex.
AbstractOutput from higher brain centres (termed central command) regulates the cardiovascular system during exercise in a feedforward‐ and motor effort‐dependent manner. This study aimed to determine a cortical area responding prior to arbitrarily started exercise and in proportion to the effort during exercise. The oxygenation responses in the frontal and frontoparietal areas during one‐armed cranking with the right arm were measured using multichannel near‐infrared spectroscopy, as indexes of regional blood flow responses, in 20 subjects. The intensity of voluntary exercise was 30% and 60% of the maximal voluntary effort (MVE). At the start period of both voluntary cranking tasks, the oxygenation increased (P < 0.05) only in the lateral and dorsal part of the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and sensorimotor cortices. Then, the oxygenation increased gradually in all cortical areas during cranking at 60% MVE, while oxygenation increased only in the frontoparietal area and some of the frontal area during cranking at 30% MVE. The rating of perceived exertion to the cranking tasks correlated (P < 0.05) with the oxygenation responses on the right side of the lateral‐DLPFC (r = 0.46) and VLPFC (r = 0.48) and the frontopolar areas (r = 0.47–0.49). Motor‐driven passive one‐armed cranking decreased the oxygenation in most cortical areas, except the contralateral frontoparietal areas. Accordingly, the lateral‐DLPFC and VLPFC on the right side would respond in a feedforward‐ and motor effort‐dependent manner during voluntary exercise with the right arm. Afferent inputs from mechanosensitive afferents may decrease the cortical oxygenation.
Endwall
Film Cooling Performance for a First-Stage Guide Vane With Upstream Combustor Walls and Inlet
Injection
Authors: Yang Xing , Liu Zhao , Liu Zhansheng , Simon Terrence , Feng Zhenping 
Published: September 2018

Abstract
Effects of an upstream combustor wall on turbine nozzle endwall film cooling performance are numerically examined in a linear cascade in this paper. Film cooling is by two rows of cooling holes at 20% of the axial chord length upstream of the vane leading edge (LE) plane. The combustor walls are modeled as flat plates with square trailing edges (TE) positioned upstream of the endwall film cooling holes. A combustor wall is in line with the LE of every second vane. The influence of the combustor wall, when shifted in the axial and tangential directions, is investigated to determine effects on passage endwall cooling for three representative film cooling blowing ratios. The results show how shed vortices from the combustor wall greatly alter the flow field near the cooling holes and inside the vane passage. Film cooling distribution patterns, particularly in the entry region and along the pressure side of the passage, are affected. The combustor wall leads to an imbalance in film cooling distribution over the endwalls for adjacent vane passages. Results show a larger effect of tangential shift of the combustor wall on endwall cooling effectiveness than the effect of an equal axial shift. The study provides guidance regarding design of combustor-to-turbine transition ducts.
Evaluation of a Diffusion Coefficient Based on Proper Solution Space
Authors: Wang Yuanlong , Hamad Abdalkaleg , Tadi Mohsen 
Published: September 2018

Abstract
This note is concerned with the evaluation of the unknown diffusion coefficient in a steady-state heat conduction problem. The proposed method is iterative and, starting with an initial guess, updates the assumed value at every iteration. The updating stage is achieved by generating a set of functions that satisfy some of the required boundary conditions. The correction to the assumed value is then computed by imposing the remaining boundary conditions. Numerical examples are used to study the applicability of this method.
Numerical Optimization, Characterization, and Experimental Investigation of Additively Manufactured Communicating Microchannels
Authors: Kirsch Kathryn L. , Thole Karen A. 
Published: September 2018

The degree of complexity in internal cooling designs is tied to the capabilities of the manufacturing process. Additive manufacturing grants designers increased freedom while offering adequate reproducibility of micro-sized, unconventional features that can be used to cool the skin of gas turbine components. One such desirable feature can be sourced from nature; a common characteristic of natural transport systems is a network of communicating channels.
In an effort to create an engineered design that utilizes the benefits of those natural systems, the current study presents wavy microchannels that were connected using branches. Two different wavelength baseline configurations were designed, then each were numerically optimized using a commercial adjoint-based method. Three objective functions were posed to (1) minimize pressure loss, (2) maximize heat transfer, and (3) maximize the ratio of heat transfer to pressure loss. All baseline and optimized microchannels were manufactured using Laser Powder Bed Fusion for experimental investigation; pressure loss and heat transfer data were collected over a range of Reynolds numbers.
The additive manufacturing process reproduced the desired optimized geometries faithfully. Surface roughness, however, strongly influenced the experimental results; successful replication of the intended flow and heat transfer performance was tied to the optimized design intent. Even still, certain test coupons yielded performances that correlated well with the simulation results.
A Reduced Order Model for Predicting Hot-Gas Ingestion Into the Wheelspace of Gas Turbines
Authors: Pardeshi Irsha , Liu Jason , Shih Tom I-P. 
Published: September 2018

In gas turbines, pressure variations induced by the rotor’s rotation and created by the stator and rotor-stator interactions cause hot gas to enter into the wheelspace (i.e., the region between the stator and rotor disks). Purge flow is used to prevent the hot gas from entering, and rim seals are used to minimize the amount of purge flow needed. Preventing hot-gas ingestion is essential to protect the structural integrity of the rotor and stator disks.
In this study, a reduced-order model is developed to predict hot-gas ingestion for a given purge flow and for an axial and a radial rim seal and to guide the design of rim seals. The model developed is semi-empirical — utilizing available data in the literature and recognizing certain trends and universal properties in the data if proper dimensionless parameters are used. The model has the advantage of only requiring the following inputs to make predictions: rotor’s rotation speed, flow rate in the turbine’s hot-gas path, purge flow rate, and dimensions of the seal and the wheelspace. Thus, this model differs from existing models in that an experimental input on parameters such as discharge coefficient, minimum sealing flow rate, or mixing length across the rim seal are not needed.
The model developed was assessed by using it to predict hot-gas ingestion for a range of purge flow rates (0 to minimum needed to prevent ingestion), rotor speeds (2,000 to 3,500 rpm), and dimensions of the seal geometries (amount of overlap in the seal and width of the flow path through the seal) and then comparing the prediction with experimental data not used in the creation of the model.
Adiabatic Film Cooling Effectiveness of a LAM Fabricated Porous Leading Edge Segment of a Turbine Blade
Authors: Calderon Luisana , Curbelo Andres , Gupta Gaurav , Kapat Jayanta S. 
Published: September 2018

Laser additive manufacturing (LAM) is an emerging technology that builds parts in a layer-by-layer process by selectively melting metal powders. This additive manufacturing technique among others can produce very complex geometries, which are not possible using conventional methods. A mock segment of the leading edge of a turbine blade, designed with both internal and external cooling features fabricated by LAM of Inconel powder, is investigated. This design consists of an internal impingement cooling array and an engineered-porous structure. This porous region consists of a lattice of intersecting cylinders that simulates the effect of a transpiration cooled segment or permeable wall with a designed porosity of 0.57.
Transpiration cooling is a promising external cooling technique capable of reducing thermal gradients at the surface of the blade by providing a more uniform film than conventional discrete film cooling holes. In this current study, adiabatic film cooling effectiveness is experimentally investigated using pressure sensitive paint (PSP) for blowing ratios ranging between 0.03 and 0.15. Using air as the mainstream, and CO2 as the coolant source, a density ratio of 1.5 is obtained. Steady state simulations using RANS are analyzed and used to compare against experimental results. All cases result in an increase in effectiveness values with increasing blowing ratio. Highest effectiveness values are associated with high pressure drop. Coolant uniformity is observed downstream the porous region and mixing becomes more significant as blowing ratio is increased.
Transfer of Knowledge in Urology: A Case Study of Jacob Eduard Polak (1818–1891) and the Introduction of Contemporary Techniques of Lithotomy and Lithotripsy from Vienna to Persia in the Mid-19th Century: A New Analysis of Scientific Papers from the 19th Century
Authors: Gächter Afsaneh , Halling Thorsten , Shariat Shahrokh F. , Moll Friedrich H. 
Published: September 2018

The middle of the 19th century marks the beginning of a global process of science and knowledge transfer from ­Europe to the rest of the world. During the phase of globali­zation, Austrian physician and ethnographer Jacob E. Polak (1818–1891) played a key role in the transmission of practical and scientific reasoning, leading to the development of medical science and clinical care in Persia. In 1851, Polak was commissioned by the Persian court to work as an academic teacher at the first secular institution of higher learning in Teheran, the Dār al-Fonūn. After 4 years of teaching and working as a doctor and surgeon, Polak was appointed personal physician to the Qājār king, Nāṣer-ad-Dīn Shāh (r. 1848–1896). During Polak’s 9 year stay in Persia, he performed numerous surgical operations with specific focus on lithotomies on men and women of all ages. He documented each operation and collected samples of bladder calculi for the purpose of chemical analysis. After his return to Austria, he published a detailed report on his practice of lithotomy in Persia. This extensive documentation is, we believe, the only known historical evidence that currently exists of the introduction of modern urology to Persia. This study will present Polak’s role as a pioneer of modern medicine and lithotomy, and will examine how he introduced the latest achievements of Viennese medicine in the field of operative urology to Persia.
Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers
Authors: Shinfuku Aya , Shimazaki Toshiharu , Fujiwara Masanori , Sato Fumihiko , Watase Hirotaka , Numazaki Takumi , Kawakita Yasunori , Mutoh Masaru , Yamasaki Hironori , Takayama Noriko , Kato Sota , Sugimoto Tomohiro , Maruyama Jinsei 
Published: September 2018

<b><i>Background:</i></b> TP0463518 is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor developed to aid in the treatment of anemia associated with chronic kidney disease (CKD) and is expected to increase erythropoietin (EPO) derived from liver. Two phase I studies were conducted in healthy volunteers (HV) and CKD patients undergoing hemodialysis (i.e., HD patients) or those not undergoing dialysis (i.e., ND patients). <b><i>Methods:</i></b> Pharmacokinetics, pharmacodynamics, and safety profiles of TP0463518 were assessed. Forty HV received single oral doses of TP0463518 at 3, 6, 11, 20, and 36 mg or placebo. Twenty ND patients received single doses of TP0463518 at 1, 6, and 11 mg and 9 HD patients received TP0463518 at 1 and 11 mg doses. To identify the source organ of EPO, glycosylation patterns were determined using percentage migrated isoform (PMI) values. <b><i>Results:</i></b> Declining renal function slowed elimination of TP0463518 and increased the mean AUC<sub>0–∞</sub>. ∆E<sub>max</sub> of serum EPO in 11-mg groups of HV, ND patients, and HD patients were 24.37 ± 11.37, 201.57 ± 130.34, and 1,324.76 ± 1,189.24 mIU/mL respectively. A strong correlation was ­observed between logarithm conversions of ∆E<sub>max</sub> and AUC<sub>0–∞</sub> with correlation coefficients of 0.945. PMI values of blood after TP0463518 administration were elevated to similar or higher levels in comparison with those of umbilical cord blood, which mainly contains liver-derived EPO. <b><i>Conclusions:</i></b> TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.
Formal modeling of a complex adaptive air traffic control system
Authors: Jarrar Abdessamad , Balouki Youssef 
Published: September 2018

AbstractAir traffic control system in airports is one of the most complex systems in the context of air traffic management due to the huge number of requirements. In order to help engineers to develop such complex system we propose a predefined model that includes the essence of air traffic control and the standard requirements. We develop this model using the Event-B formal method which is based on set theory and allows theorems proving. Event-B is also hinged on refinement which means starting with an abstract model and then enriching it in successive steps. Event-B has been successfully applied in several transportation systems and shows no bugs. This encourages us to use it in this critical system to guarantee a strong assurance of bugs’ absence and to ensure model correctness. Our approach provides a standard model to start with in order to model any airport control system, which allows engineers to focus on more typical requirements that are not developed here.
Re-visiting the ATA 2015 sonographic guidelines - who are we missing?: A retrospective review
Authors: Chan D. S. , Gong K. , Roskies M. G. , Forest V. I. , Hier M. P. , Payne R. J. 
Published: September 2018

Background The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm. Methods Patients ( n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1–1.49 cm ( n = 155). Results 45% ( n = 70) of patients with nodules between 1 and 1.49 cm were “low suspicion” nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% ( n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% ( n = 16) were associated with regional metastases. Conclusions Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.
Shared decision making and decisional conflict in the Management of Vestibular Schwannoma: A prospective cohort study
Authors: Graham M. Elise , Westerberg Brian D. , Lea Jane , Hong Paul , Walling Simon , Morris David P. , Hebb Andrea L. O. , Galleto Rochelle , Papsin Emily , Mulroy Maeve , Foggin Hannah , Bance Manohar 
Published: September 2018

Background Patients with vestibular schwannomas (VS) are faced with complex management decisions. Watchful waiting, surgical resection, and radiation are all viable options with associated risks and benefits. We sought to determine if patients with VS experience decisional conflict when deciding between surgery or non-surgical management, and factors influencing the degree of decisional conflict. Methods A prospective cohort study in two tertiary ambulatory skull-base clinics was performed. Patients with newly diagnosed or newly growing vestibular schwannomas were recruited. Patients were given a demographic form and the decisional conflict scale (DCS), a validated measure to assess the degree of uncertainty when making medical decisions. The degree of shared decision making (SDM) experienced by the patient and physician were assessed via the SDM-Q-10 and SDM-Q-Doc questionnaires, respectively. Non-parametric statistics were used. Questionnaires and demographic information were correlated with DCS using Spearman correlation coefficient and Mann-Whitney U. Logistic regression was performed to determine factors independently associated with DCS scores. Results Seventy-seven patients participated (55% female, aged 37–81 years); VS ranged in size from 2 mm–50 mm. Significant decisional conflict (DCS score 25 or greater) was experienced by 17 (22%) patients. Patients reported an average SDM-Q-10 score of 86, indicating highly perceived level of SDM. Physician and patient SDM scores were weakly correlated ( p = 0.045, Spearman correlation coefficient 0.234). DCS scores were significantly negatively correlated with a decision to pursue surgery, presence of a trainee, and higher SDM-Q-10 score. DCS was higher with female gender. Using logistic regression, the SDM-Q-10 score was the only variable associated with significantly reduced DCS. Conclusions About one fifth of patients deciding how to manage their vestibular schwannoma experienced a significant degree of decisional conflict. Involving the patients in the process through shared decision-making significantly reduced the degree of uncertainty patients experienced.