bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease Modification in Parkinson's Disease: Current Approaches, Challenges, and Future Considerations
Authors: Lang Anthony E. , Espay Alberto J. 
Published: April 2018

ABSTRACTThe greatest unmet therapeutic need in Parkinson's disease is the development of treatment that slows the relentless progression of the neurodegenerative process. The concept of “disease modification” encompasses intervention types ranging from those designed to slow the underlying degeneration to treatments directed at regenerating or replacing lost neurons. To date all attempts to develop effective disease‐modifying therapy have failed. Many reasons have been proposed for these failures including our rudimentary understanding of disease pathogenesis and the assumption that each targeted mechanisms of disease apply to most patients with the same clinical diagnosis. Here we review all aspects of this broad field including general concepts and past challenges followed by a discussion of treatment approaches under the following 4 categories: (1) α‐synuclein, (2) pathogenic mechanisms distinct from α‐synuclein (most also potentially triggered by α‐synuclein toxicity), (3) non‐SNCA genetic subtypes of “PD,” and (4) possible disease‐modifying interventions not directly influencing the underlying PD pathobiology. We emphasize treatments that are currently under active clinical development and highlight a wide range of important outstanding questions and concerns that will need to be considered to advance the field of disease modification in PD. Critically, it is unknown whether the dysfunctional molecular pathways/organelles amenable to modification occur in a sequential fashion across most clinically affected individuals or manifest differentially in independent molecular subtypes of PD. It is possible that there is no “order of disruption” applicable to most patients but, rather, “type of disruption” applicable to subtypes dependent on unknown factors, including genetic variability and other causes for heterogeneity in PD. Knowing when (early vs late), which (eg, synaptic transmission, endosomal sorting and maturation, lysosomal degradation, mitochondrial biogenesis), and in whom (PD subtype) specific disrupted cell pathways are truly pathogenic versus compensatory or even protective, will be important in considering the use of single or combined (“cocktails”) putative disease‐modifying therapies to selectively target these processes. Beyond the current phase 2 or 3 studies underway evaluating treatments directed at oxidative stress (inosine), cytosolic Ca2+ (isradipine), iron (deferiprone), and extracellular α‐synuclein (passive immunization), and upcoming trials of interventions affecting c‐Abl, glucagon‐like peptide‐1, and glucocerebrosidase, it might be argued that further trials in populations not enriched for the targeted pathogenic process are doomed to repeat the failures of the past. © 2018 International Parkinson and Movement Disorder Society
Studies on the local structures for the trigonal Ni3+ centers in cathode materials LiAlyCo1–yO2 (y = 0, 0.1, 0.5, and 0.8)
Authors: Ding Chang‐Chun , Wu Shao‐Yi , Xu Yong‐Qiang , Zhang Li‐Juan 
Published: April 2018

The local angular distortions Δθ are theoretically studied for the various Ni3+ centers in LiAlyCo1–yO2 at different Al concentrations (y = 0, 0.1, 0.5, and 0.8) based on the perturbation calculations of electron paramagnetic resonance g factors for a trigonally distorted octahedral 3d7 cluster with low spin (S = 1/2). Due to the Jahn–Teller effect, the [NiO6]9– clusters are found to experience the local angular distortions (Δθ ≈ 5°–9°) along the C3 axis. The variation trend of Δθ with y is in accordance with that of anisotropy (Δg = g|| − g⊥). As the substitutions can weaken bond strengths between transition metal and oxygen and the structural stability plays an important role in cathode performances, detailed investigations on the structural properties of the cathode materials LiAlyCo1–yO2 can be practically helpful to understand the performances of these materials. The oxy‐redox properties of LiAlyCo1–yO2 systems are comprehensible in the framework of Ni3+/Ni4+ couples, and the trigonally compressed octahedral [NiO6]9– clusters are applicable to the clarification of the electrochemical properties of lithium nickel oxide batteries. It appears that LiAl0.8Co0.2O2 with the largest Al concentration may correspond to the smallest distortion among the mixing systems.
Experimental butchery study investigating the influence of timing of access and butcher expertise on cut mark variables
Authors: Pobiner Briana L. , Higson Charles P. , Kovarovic Kris , Kaplan Robert S. , Rogers Jacklyn , Schindler William 
Published: April 2018

AbstractCut marks on fossils from Plio‐Pleistocene faunal assemblages can elucidate the timing and nature of hominin procurement of animal tissues. Although butchery experiments have great potential to enhance our ability to understand hominin butchery behaviours, studies that model variation in the timing of access to carcasses and butcher expertise have either yielded conflicting results or have not yet been undertaken. We conducted butchery experiments on 8 pig limbs with replicated Oldowan flake tools that varied the amount of flesh removed prior to butchery (simulating early or late carcass access) and butcher expertise. These experiments investigated the effects of these variables on resultant cut mark count, length, and number of tool strokes. The relationship between the number of tool strokes as a measure of butchery intensity and the number of cut marks produced was also explored. We also compared the length of experimental cut marks with those on 1.5‐million‐year‐old fossil bones from Koobi Fora, Kenya. Although the bones that were partially defleshed prior to butchery had a higher number and longer cut marks on average than fleshed bones, and the expert butcher created fewer and shorter cut marks than the novice butcher, none of these relationships were statistically significant. We found no relationship between the number of tool strokes and the amount of flesh removed prior to butchery or the number of cut marks produced during butchery, although the expert butcher used fewer tool strokes. Although not statistically significant, the length of cut marks created by the novice butcher is much more variable than those created by the expert butcher and the fossil cut marks, and fossil cut marks are much shorter than those created by both modern butchers. More work needs to be undertaken to identify cut mark attributes that may be influenced by behavioural or ecological variables that can be measured and manipulated during butchery experiments.
Prevalence of mental disorders and psychosocial distress in German adolescent and young adult cancer patients (AYA)
Authors: Geue Kristina , Brähler Elmar , Faller Hermann , Härter Martin , Schulz Holger , Weis Joachim , Koch Uwe , Wittchen Hans‐Ulrich , Mehnert Anja 
Published: April 2018

AbstractObjectiveThis study provides prevalence data of mental disorders (4‐week, 1‐year, lifetime) and psychological distress in Adolescent and Young Adult (AYAs) with cancer.MethodsWe included an AYA subsample (15 to 39 year olds; diagnosed within the last 5 years) extracted from a larger sample (4.020 cancer patients) who had been recruited for an epidemiological study across all major tumor entities. Participants were assessed with a depression screener (PHQ‐9). Following that, 50% of the participants who scored below the cutoff of 9 and all patients who scored above were assessed using the Composite International Diagnostic Interview for Oncology (CIDI‐O). Patients also completed an anxiety screener (GAD‐7).ResultsA total of 302 AYA (167 completed CIDI‐O) were identified. With regard to psychological distress, 29.5% of the AYA had increased depression symptoms (PHQ‐9), and 20.8% had increased anxiety symptoms (GAD‐7). Gender and age were associated with psychological distress, with women and older AYA being found to have higher distress. The 4‐week prevalence of mental disorders of any kind was 46.7% (95%‐CI:39%‐55%). Anxiety (24.4%; 95%‐CI:20%‐36%) and adjustment disorders (14.1%; 95%‐CI:9%‐19%) had the highest prevalence rates. The lowest prevalence rates were reported for alcohol dependence (0.8%; 95%‐CI:0%‐2%) and somatoform disorders (3.7%; 95%‐CI:1%‐7%). The 1‐year‐prevalence was 55.4% (CI:47.36‐62.64), and the lifetime‐prevalence was 69.5% (CI: 62.29‐77.06).ConclusionOur findings may sensitize clinicians to the possible presence of mental disorders in AYA. The results indicate that there is a strong need for psycho‐oncological interventions designed to improve mental health in AYAs with cancer at all stages of medical care.
Maternal perceptions of BRCA genetic counseling communication processes about disclosing cancer risk information to children and adult relatives
Authors: Hamilton Jada G. , Peshkin Beth N. , Mays Darren , DeMarco Tiffani A. , Patenaude Andrea Farkas , Tercyak Kenneth P. 
Published: April 2018

AbstractObjectivesUsing a novel measure, examine maternal perceptions of the process by which issues pertaining to family communication of BRCA test results are addressed during cancer genetic counseling.MethodsAfter receiving BRCA results, mothers (N = 211) of minor‐age children reported on their counseling experiences with providers using a communication process measure as well as other psychosocial variables.ResultsThe novel Genetic Counseling Communication Process measure demonstrated good internal consistency of its 2 factors: patient‐led communication (Cronbach's α = 0.73) and provider‐led communication (Cronbach's α = 0.82). Participants most often reported that discussions about family communication of BRCA test results to children and adult relatives were led only by their providers (38.2%‐39.2%), as opposed to being led by the patient, both parties, or neither party. Providers were most likely to lead these discussions when mothers had stronger family histories of cancer and expressed more confidence about making a decision to talk to their children about BRCA. However, mothers typically led such discussions if they were raising older children and held more positive attitudes about pediatric BRCA testing.ConclusionsWhen the assessment of BRCA genetic counseling outcomes includes family communication to potentially at‐risk relatives, we learned that most but not all sessions addressed this topic. Cancer family history, child age, and maternal attitudes are important co‐factors in these patient‐provider communication exchanges. Providers delivering BRCA genetic counseling should be attentive to mothers' information and support needs regarding communicating cancer genetic test results to at‐risk relatives, including children.
Investigating the dynamics and polyanion binding sites of fibroblast growth factor‐1 using hydrogen‐deuterium exchange mass spectrometry
Authors: Angalakurthi Siva K. , Tenorio Connie A. , Blaber Michael , Middaugh Charles Russell 
Published: April 2018

AbstractIn this study, we examined the local dynamics of acidic fibroblast growth factor (FGF‐1) as well as the binding sites of various polyanions including poly‐sulfates (heparin and low MW heparin) and poly‐phosphates (phytic acid and ATP) using hydrogen‐deuterium exchange mass spectrometry (HX‐MS). For local dynamics, results are analyzed at the peptide level as well as in terms of buried amides employing crystallographic B‐factors and compared with a residue level heat map generated from HX‐MS results. Results show that strand 4 and 5 and the turn between them to be the most flexible regions as was previously seen by NMR. On the other hand, the C‐terminal strands 8, 9, and 10 appear to be more rigid which is also consistent with crystallographic B‐factors as well as local dynamics studies conducted by NMR. Crystal structures of FGF‐1 in complex with heparin have shown that heparin binds to N‐terminal Asn18 and to C‐terminal Lys105, Tryp107, Lys112, Lys113, Arg119, Pro121, Arg122, Gln127, and Lys128 indicating electrostatic forces as dominant interactions. Heparin binding as determined by HX‐MS is consistent with crystallography data. Previous studies have also shown that other polyanions including low MW heparin, phytic acid and ATP dramatically increase the thermal stability of FGF‐1. Using HX‐MS, we find other poly anions tested bind in a similar manner to heparin, primarily targeting the turns in the lysine rich C‐terminal region of FGF‐1 along with two distinct N‐terminal regions that contains lysines and arginines/histidines. This confirms the interactions between FGF‐1 and polyanions are primary directed by electrostatics.
Airfoil optimization for wind turbine application
Authors: Hansen T. H. 
Published: April 2018

AbstractAn airfoil optimization method for wind turbine applications that controls the loss in performance due to leading edge contamination is developed and tested. The method uses the class‐shape‐transformation technique to parametrize the airfoil geometry and uses an adjusted version of the panel code XFOIL to calculate the aerodynamic performance. To find optimal airfoil shapes, the derivative‐free Covariance Matrix Adaptation Evolution Strategy is used in combination with an adaptive penalty function. The method is tested for the design of airfoils for the outer part of a megawatt‐class wind turbine rotor blade, and the results are compared with airfoils from Delft University. It is found that the method is able to automatically create airfoils with equal or improved performance compared with the Delft designs. For the tested application, the adjustments performed to the XFOIL code improve the maximum lift, post stall, and the overall drag predictions.
Modulus D-term inflation
Authors: Kadota Kenji , Kobayashi Tatsuo , Saga Ikumi , Sumita Keigo 
Published: April 2018

AbstractWe propose a new model of single-field D-term inflation in supergravity, where the inflation is driven by a single modulus field which transforms non-linearly under the U(1) gauge symmetry. One of the notable features of our modulus D-term inflation scenario is that the global U(1) remains unbroken in the vacuum and hence our model is not plagued by the cosmic string problem which can exclude most of the conventional D-term inflation models proposed so far due to the CMB observations.
Dispersion of group velocities of Rayleigh and Love waves and anisotropic properties of the Asian continent
Authors: Seredkina A.I. , Kozhevnikov V.M. , Solovei O.A. 
Published: April 2018

Abstract
We have studied the structures of the Earth’s crust and upper mantle of the Asian continent using a representative sample of dispersion curves of group velocities of fundamental-mode Rayleigh and Love waves for more than 3200 seismic paths. Maps of distributions of variations in group velocities with periods of 10 to 250 s over a spherical surface were calculated by the 2D tomography method. The maps reflect the deep structure of the Earth’s crust and upper mantle of the study area and give a tentative idea of the horizontal distribution of the anisotropic properties of the mantle matter. The obtained data are confirmed by the calculations of the velocity profiles of SV- and SH-waves for the entire Asian continent and for its regions. Vertically, anisotropy is observed to the depths of ~250 km, with its maximum in the depth range from the bottom of the crust to 150 km.
Thermodynamic model of formation of carbonates and uranium mineral phases in lakes Namshi-Nur and Tsagan-Tyrm (Cisbaikalia)
Authors: Strakhovenko V.D. , Gas’kova O.L. 
Published: April 2018

Abstract
The Tazheran lakes are located compactly in the small Tazheran steppe area. Their bottom sediments are predominantly various calcite–dolomite carbonates, and their waters are rich in uranium. The studies have shown that the main process in these lakes is chemogenic carbonate precipitation with the participation of carbon dioxide formed through the bacterial destruction of organic matter. For thermodynamic modeling of the composition of bottom sediments, we chose two lakes with different basic parameters. Calculations were made for the 15-component heterogeneous system H2O–Na–Ca–Mg–K–Sr–Ba–Si–Al–Cl–C–S–Fe–U–Mn including particles in the solution, minerals, and gases at 25 °C and 1 bar. As starting information, we used the obtained analytical data on the natural composition of waters and bottom sediments. The results show that calcite–dolomite carbonates are predominant in the bottom sediments and the destruction of organic matter results in reducing conditions. This confirms the hypothesis of the formation of mineral phases of U(IV) during diagenetic processes in the bottom sediments of the studied lakes.
Structure of the basement surface and sediments in the Kochkor basin (Tien Shan): geological and geophysical evidence
Authors: Przhiyalgovskii E.S. , Lavrushina E.V. , Batalev V.Yu. , Bataleva E.A. , Leonov M.G. , Rybin A.K. 
Published: April 2018

Abstract
The basement surface and sediments of the Kochkor basin have been studied by structural geological and geophysical methods. The work included high-resolution mapping of the southern basin margin, with a focus on Cenozoic basin stratigraphy, structural unconformities, basement/sediment contacts, and latest deformation (folds, fractures, and faults). Magnetotelluric (MT) soundings provided insights into basin and basement structure, especially important in the poorly exposed eastern flank of the basin margin. The sections across the southern margin of the basin based on geological and geophysical data reveal deformation in both the basement and the sediments. Deformation in sediments shows up as folding, conformal peneplain surfaces, large faults, low-angle detachment faults, and related thrust-fold belts. Thrusting in sediments is inferred to result from cataclastic flow and mass redistribution in disintegrated basement granites. With this mechanism, the total amount of thrusting in the central part of the basin can exceed the convergence of the basin sides.
ON THE DISTRIBUTION OF THE EXCEDENTS OF FUNDS WITH ASSETS AND LIABILITIES IN PRESENCE OF SOLVENCY AND RECOVERY REQUIREMENTS
Authors: Avanzi Benjamin , Henriksen Lars Frederik Brandt , Wong Bernard 
Published: April 2018

AbstractWe consider a profitable, risky setting with two separate, correlated asset and liability processes (first introduced by Gerber and Shiu, 2003). The company that is considered is allowed to distribute excess profits (traditionally referred to as dividends in the literature), but is regulated and is subject to particular regulatory (solvency) constraints. Because of the bivariate nature of the surplus formulation, such distributions of excess profits can take two alternative forms. These can originate from a reduction of assets (and hence a payment to owners), but also from an increase of liabilities (when these represent the wealth of owners, such as in pension funds). The latter is particularly relevant if distributions of assets do not make sense because of the context, such as in regulated pension funds where assets are locked until retirement. In this paper, we extend the model of Gerber and Shiu (2003) and consider recovery requirements for the distribution of excess funds. Such recovery requirements are an extension of the plain vanilla solvency constraints considered in Paulsen (2003), and require funds to reach a higher level of funding than the solvency level (if and after it is triggered) before excess funds can be distributed again. We obtain closed-form expressions for the expected present value of distributions (asset decrements or liability increments) when a distribution barrier is used.
Large-sample neutron activation analysis in mass balance and nutritional studies
Authors: Van de Wiel Albert , Blaauw Menno 
Published: April 2018

AbstractLow concentrations of elements in food can be measured with various techniques, mostly in small samples (mg). These techniques provide only reliable data when the element is distributed homogeneously in the material to be analysed either naturally or after a homogenisation procedure. When this is not the case or homogenisation fails, a technique should be applied that is able to measure in samples up to grams and even kilograms and regardless of the distribution of the element. An adaptation of neutron activation analysis (NAA), called large-sample NAA, has been developed and proven accurate and may be an attractive alternative in food research and mass balance studies. Like standard NAA, large-sample NAA can be used to measure both toxic and trace elements relevant for nutrition.
The presence of children in households was associated with dietary intake among Japanese married women: the POTATO study
Authors: Saito Aki , Matsumoto Mai , Hyakutake Aiko , Saito Masafumi , Okamoto Naoko 
Published: April 2018

AbstractA growing body of evidence from Western countries shows that the presence of children in households is associated with the dietary intake of adults, but little is known about this relationship in non-Western countries with different food cultures. Our aim was to examine whether dietary intake was different with respect to the presence of young children in the home among Japanese married women. Subjects were Japanese married women (aged 23–44 years) living with children aged less than 5 years (n73) and married women who did not have children (n85). Data regarding habitual dietary intake were obtained using a validated, self-administered diet history questionnaire. A cross-sectional comparison between women with young children and women without children was conducted using ANCOVA adjusted for potential confounding factors. Women with young children had a significantly greater intake of protein, carbohydrates, Na, Zn and Cu than did women without children. Intake of cereals, pulses and sugar was significantly higher among mothers than among non-mothers. Intake of both alcoholic and non-alcoholic beverages was significantly higher among non-mothers than among mothers. Thus, the presence of young children at home might influence women's intake of macronutrients and some minerals, especially Na, and beverages among Japanese married women. Our findings suggest that effective dietary interventions among Japanese mothers with young children may differ from those of married women without children.
Directly dating postglacial Greenlandic land-surface emergence at high resolution using in situ10Be
Authors: Bierman Paul R. , Rood Dylan H. , Shakun Jeremy D. , Portenga Eric W. , Corbett Lee B. 
Published: April 2018

AbstractPostglacial emergence curves are used to infer mantle rheology, delimit ice extent, and test models of the solid Earth response to changing ice and water loads. Such curves are rarely produced by direct dating of land emergence; rather, most rely on the presence of radiocarbon-datable organic material and inferences made between the age of sedimentary deposits and landforms indicative of former sea level. Here, we demonstrate a new approach,10Be dating, to determine rates of postglacial land emergence in two different settings. In southern Greenland (Narsarsuaq/Igaliku), we date directly the exposure, as relative sea level fell, of gravel beaches and rocky outcrops allowing determination of rapid, post–Younger Dryas emergence. In western Greenland (Kangerlussuaq), we constrain Holocene isostatic response by dating the sequential stripping of terrace sediment driven by land-surface uplift, relative sea-level fall, and resulting fluvial incision. The technique we employ provides high temporal and elevation resolution important for quantifying rapid emergence immediately after deglaciation and less rapid uplift during the middle Holocene.10Be-constrained emergence curves can improve knowledge of relative sea-level change by dating land emergence along rocky coasts, at elevations and locations where radiocarbon-datable sediments are not present, and without the lag time needed for organic material to accumulate.