bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐linked hemoglobin bis‐tetramers from bioorthogonal coupling do not induce vasoconstriction in the circulation
Authors: Wang Aizhou , Singh Serena , Yu Binglan , Bloch Donald B. , Zapol Warren M. , Kluger Ronald 
Published: November 2018

BACKGROUNDHemoglobin‐based oxygen carriers (HBOCs) are potential alternatives to red blood cells in transfusions. Clinical trials using early versions of HBOCs noted adverse effects that appeared to result from removal of the vasodilator nitric oxide (NO). Previous reports suggest that size‐enlarged HBOCs may avoid NO‐rich regions along the vasculature and therefore not cause vasoconstriction and hypertension.STUDY DESIGN AND METHODSHemoglobin (Hb) bis‐tetramers (bis‐tetramers of hemoglobin that are prepared using CuAAC chemistry [BT‐Hb] and bis‐tetramers of hemoglobin that are specifically acetylated and prepared using CuAAC chemistry [BT‐acHb]) can be reliably produced by a bio‐orthogonal cyclo‐addition approach. We considered that an HBOC derived from chemical coupling of two Hbs would be sufficiently large to avoid NO scavenging and related side effects. The ability of intravenously infused BT‐Hb and BT‐acHb to remain in the circulation without causing hypertension were determined in wild‐type (WT) and diabetic (db/db) mouse models.RESULTSIn WT mice, the coupled oxygen‐carrying proteins retained their function over several hours after administration. No significant changes in systolic blood pressure from baseline were observed after intravenous infusion of BT‐Hb or BT‐acHb in awake WT and db/db mice. In contrast, infusion of native Hb or cross‐linked Hb tetramers in both animal models induced systemic hypertension.CONCLUSIONThe results of this study indicate that bis‐tetrameric HBOCs derived from the bio‐orthogonal cyclo‐addition process are likely to overcome clinical issues that arise from NO scavenging by Hb derivatives.
Women's experiences of induced abortion resulting from unplanned pregnancy: a qualitative systematic review protocol
Authors: Marques Patrícia Figueiredo , Coelho Edmeia de Almeida Cardoso , Bertolozzi Maria Rita , Hoga Luiza Akiko Komura , Fonseca Jamile Guerra , Rodrigues Isadora Reis 
Published: November 2018

Review question/objective:
The objective of this review is to synthesize qualitative evidence on the experiences of women undergoing an induced abortion resulting from an unplanned pregnancy.
More specifically, the review question is: how do women experience induced abortions resulting from an unplanned pregnancy?
Endocrine regulation of gut function – a role for glucagon‐like peptide‐1 in the pathophysiology of irritable bowel syndrome
Authors: O'Malley Dervla 
Published: November 2018

New Findings
What is the topic of this review?
Pathophysiological changes linked to irritable bowel syndrome (IBS) include stress and immune activation, changes in gastrointestinal microbial and bile acid profiles and sensitization of extrinsic and intrinsic gut neurons. This review explores the potential role for L‐cells in these pathophysiological changes.

What advances does it highlight?
L‐cells, which secrete glucagon‐like peptide‐1 in response to nutrients, microbial factors, bile acids and short‐chain fatty acids, may sense IBS‐related changes in the luminal environment. Glucagon‐like peptide‐1 can act as a hormone, a paracrine factor or a neuromodulatory factor and, through its actions on central or peripheral neurons, may play a role in gastrointestinal dysfunction.

AbstractThe prevalent and debilitating functional bowel disorder, irritable bowel syndrome (IBS), is characterized by symptoms that include abdominal pain, bloating, diarrhoea and/or constipation. The heterogeneity of IBS underscores a complex multifactorial pathophysiology, which is not completely understood but involves dysfunction of the bi‐directional signalling axis between the brain and the gut. This axis incorporates efferent and afferent branches of the autonomic nervous system, circulating endocrine hormones and immune factors, local paracrine and neurocrine factors and microbial metabolites. L‐cells, which are electrically excitable biosensors embedded in the gastrointestinal epithelium, secrete glucagon‐like peptide‐1 (GLP‐1) in response to nutrients in the small intestine. However, they appear to function in a different manner more distally in the gastrointestinal tract, where they are activated by luminal factors including short‐chain fatty acids, bile acids and microbial metabolic products, all of which are altered in IBS patients. Glucagon‐like peptide‐1 can also interact with the hypothalamic–pituitary–adrenal stress axis and the immune system, both of which are activated in IBS. Given that a GLP‐1 mimetic has been found to alleviate acute pain symptoms in IBS patients, GLP‐1 might be important in the manifestation of IBS symptoms. This review assesses the current knowledge about the role of GLP‐1 in IBS pathophysiology and its potential role as a signal transducer in the microbiome–gut–brain signalling axis.
HAMR Emulation Using Plasmonic SERS Sensor As Near Field Transducer
Authors: Yanagisawa M. , Kunimoto M. , Saito M. , Homma T. 
Published: November 2018

A plasmonic Surface-enhanced Raman Spectroscopy (SERS) sensor has been used for emulation of Near Field Transducer (NFT) in Heat-Assisted Magnetic Recording (HAMR). Laser heating mechanism by the sensor is the same as that by NFT with electro-magnetic near-field or plasmonic field, which is different from far field heating.
Heating behavior for a lubricant film on a carbon overcoat for a hard disk medium was observed using Surface-enhanced Raman Spectroscopy with the plasmonic SERS sensor. Spectral change of lube films in laser heating with a continuous power changer was measured with heating temperature, calculated by anti-Stokes/Stokes intensity ratio in Raman spectra. As a result, it is found that the lubricant film composed of a tetraol perfluoro-polyether (PFPE) is evaporated above 290°C, which shows good agreement with that by TGA (Thermogravimetric Analysis).
The evaporation occurs in wide range of spacing between the lubricant film and the SERS sensor from 0 (contact) to 50nm, and more. After laser heating, lubricant film with free surface in a large gap area, i.e. spacing of 3nm, is recovered with elapsed time. However it is difficult to be recovered in confined (contact) area, because lubricant mobility is small. Lost lubricant can be recovered in head flying by surface diffusion or centrifugal force during disk rotation.
Preliminary Assessment of Morphing Winglet and Flap Tabs Influence on the Aeroelastic Stability of Next Generation Regional Aircraft
Authors: Noviello Maria Chiara , Dimino Ignazio , Amoroso Francesco , Concilio Antonio , Pecora Rosario 
Published: November 2018

Future aircraft wing technology is rapidly moving toward flexible and morphing wing concepts capable to enhance aircraft wing performance in off-design conditions and to reduce operative maneuver and gust loads. However, due to the reduced stiffness, increased mass, and increased degree of freedom (DOF), such mechanical systems require advanced aeroelastic assessments since the early design phases; this appears crucial to properly drive the design of the underlying mechanisms since the conceptual phase by mitigating their impact on the whole aircraft aeroelastic stability.
Preliminary investigations have shown that the combined use of adaptive flap tabs and morphing winglets significantly improves aircraft aerodynamic performance in climb and cruise conditions by the order of 6%. Additionally, by adapting span-wise lift distributions to reduce gust solicitations and alleviate wing root bending moment at critical flight conditions, significant weight savings can also be achieved.
Within the scope of Clean Sky 2 Airgreen 2 project, flutter and divergence characteristics of a morphing wing design integrating adaptive winglets and flap tabs are discussed. Multi-parametric flutter analyses are carried out in compliance with CS-25 airworthiness requirements (paragraph 25.629, parts (a), (b), (c) and (d)) to investigate static and dynamic aeroelastic stability behavior of the aircraft. The proposed kinematic systems are characterized by movable surfaces, each with its own domain authority, sustained by a structural skeleton and completely integrated with EMA-based actuation systems. For that purpose, a sensitivity analysis was performed taking into account variations of the stiffness and inertial properties of the referred architectures. Such layouts were reduced to a stick-equivalent model which properties were evaluated through MSC-NASTRAN-based computations. The proprietary code SANDY 4.0 was used to generate the aero-structural model and to solve the aeroelastic stability equations by means of theoretical modes association in frequency domain. Analyses showed the presence of critical modal coupling mechanisms in nominal operative conditions as well as in case of system malfunctioning or failure. Design solutions to assure clearance from instabilities were then investigated. Trade-off flutter and divergence analyses were finally carried out to assess the robustness of the morphing architectures in terms of movable parts layout, mass balancing and actuators damping.
Comparison of Critical Speed and D′ Derived From 2 or 3 Maximal Tests
Authors: Kordi Mehdi , Menzies Campbell , Galbraith Andy 
Published: November 2018

Purpose: The hyperbolic distance–time relationship can be used to profile running performance and establish critical speed (CS) and D′ (the curvature constant of the speed–time relationship). Typically, to establish these parameters, multiple (3+) performance trials are required, which can be highly fatiguing and limit the usability of such protocols in a single training session. This study aimed to compare CS and D′ calculated from a 2-trial (2-point model) and a 3-trial (3-point model) method. Methods: A total of 14 male distance runners completed 3 fixed-distance (3600, 2400, and 1200 m) time trials on a 400-m outdoor running track, separated by 30-min recoveries. Participants completed the protocol 9 times across a 12-mo period, with approximately 42 d between tests. CS and D′ were calculated using all 3 distances (3-point model) and also using the 3600- and 1200-m distances only (2-point model). Results: Mean (SD) CS for both 3-point and 2-point models was 4.94 (0.32) m·s−1, whereas the values for D′ were 123.3 (57.70) and 127.4 (57.34) m for the 3-point and 2-point models, respectively. Overall bias for both CS and D′ between 3-point and 2-point model was classed as trivial. Conclusion: A 2-point time-trial model can be used to calculate CS and D′ as proficiently as a 3-point model, making it a less fatiguing, inexpensive, and applicable method for coaches, practitioners, and athletes for monitoring running performance in 1 training session.
Joint-Level Analyses of the Back Squat With and Without Intraset Rest
Authors: Stone Jason D. , King Adam C. , Goto Shiho , Mata John D. , Hannon Joseph , Garrison James C. , Bothwell James , Jagim Andrew R. , Jones Margaret T. , Oliver Jonathan M. 
Published: November 2018

Purpose: To provide a joint-level analysis of traditional (TS) and cluster (CS) set structure during the back-squat exercise. Methods: Eight men (24 [3] y, 177.3 [7.9] cm, 82.7 [11.0] kg, 11.9 [3.5] % body fat, and 150.3 [23.0] kg 1-repetition maximum [1RM]) performed the back-squat exercise (80%1RM) using TS (4 × 6, 2-min interset rest) and CS (4 × [2 × 3], 30-s intraset rest, 90-s interset rest), randomly. Lower-limb kinematics were collected by motion capture, as well as kinetic data by bilateral force platforms. Results: CS attenuated the loss in mean power (TS −21.6% [3.9%]; CS −12.4% [7.5%]; P = .042), although no differences in gross movement pattern (sagittal-plane joint angles) within and between conditions were observed (P ≥ .05). However, joint power produced at the hip increased from repetition (REP) 1 through REP 6 during TS, while a decrease was noted at the knee. A similar pattern was observed in the CS condition but was limited to the hip. Joint power produced at the hip increased from REP 1 through REP 3 but returned to REP 1 values before a similar increase through REP 6, resulting in differences between conditions (REP 4, P = .018; REP 5, P = .022). Conclusions: Sagittal-plane joint angles did not change in either condition, although CS elicited greater power. Differing joint power contributions (hip and knee) suggest potential central mechanism that may contribute to enhanced power output during CS and warrant further study. Practitioners should consider incorporating CS into training to promote greater power adaptations and to mitigate fatigue.
Influence of persistent buried ice on late glacial landscape development in part of Wisconsin’s Northern Highlands
Authors: Attig John W. , Rawling J. Elmo 
Published: November 2018

ABSTRACT
Landscape features that formed when buried ice melted and overlying sediment collapsed are abundant and widespread in the part of Wisconsin’s Northern Highland region glaciated by the Wisconsin Valley Lobe and the western part of the Langlade Lobe. Stagnation and burial of ice of the Wisconsin Valley Lobe are documented by broad tracts of hummocky moraine topography that record the position of the maximum extent of the lobe, and by extensive pitted and collapsed heads-of-outwash and outwash plains deposited during recession. Recession of the Wisconsin Valley Lobe was characterized by episodes of stagnation interspersed with episodes of readvance, documented by small west-east–trending heads-of-outwash. Advances of the western margin of the Langlade Lobe deposited large northwest-southeast–trending heads-of-outwash characterized by extensive areas of pitted and collapsed outwash plains with obscure but recognizable ice-contact faces. Following recession of the Wisconsin Valley and Langlade Lobes, the Ontonagon Lobe advanced out of the Superior Basin and over sediment containing abundant buried ice. Permafrost and debris cover combined to delay the melting of buried ice and the formation of the postglacial landscape. Regional correlation of ice-margin positions, combined with geomorphic and stratigraphic relationships, indicates that ice buried in north-central Wisconsin persisted in some places for up to 5000 yr or more following the recession of active ice.
Minimum age of the Mapleton, Tully, and Labrador Hollow moraines indicates correlation with the Port Huron Phase in central New York State
Authors: Kozlowski Andrew L. , Bird Brian C. , Lowell Thomas V. , Smith Colby A. , Feranec Robert S. , Graham Brandon Lars 
Published: November 2018

ABSTRACT
The glaciated terrain along the northern edge of the Appalachian Plateau in the eastern Finger Lakes of central New York has long been recognized as an important location for meltwater routing and for proglacial lake development in the Great Lakes region. Despite recognition of multiple ice margins formed by the Ontario Lobe of the Laurentide ice sheet during the late Wisconsinan, numerical age control of several margins has been elusive, particularly in regard to regional readvances of the Port Bruce (ca. 16,980–18,000 cal [calibrated] yr B.P.) and Port Huron (ca. 14,300– 16,000 cal yr B.P.) Phases. Utilizing light detection and ranging (LiDAR) terrain models in the eastern Finger Lakes area, we identified and described the Mapleton, Tully, and Labrador Hollow moraines. Associated ice-marginal landforms include push moraines, fans, and hummocky topography. In places, these features intrude into the northern heads of through valleys. Coring of three basins directly associated with these landforms yielded more than 20 samples of boreal tree needles and twigs, and Dryas leaves. Accelerated mass spectrometry (AMS) radiocarbon assay results indicate that poststadial lacustrine sedimentation began at ca. 15,000 cal yr B.P., consistent with ages of the Port Huron Phase.
Styles of underplating in the Marin Headlands terrane, Franciscan complex, California
Authors: Regalla Christine A. , Rowe Christie D. , Harrichhausen Nicolas , Tarling Matthew S. , Singh Jyotsana 
Published: November 2018

ABSTRACT
Geophysical images and structural cross sections of accretionary wedges are usually aligned orthogonal to the subduction trench axis. These sections often reveal underplated duplexes of subducted oceanic sediment and igneous crust that record trench-normal shortening and wedge thickening facilitated by down-stepping of the décollement. However, this approach may underrecognize trench-parallel strain and the effects of faulting associated with flexure of the downgoing plate. New mapping of a recently exposed transect across a portion of the Marin Headlands terrane, California, United States, documents evidence for structural complexity over short spatio-temporal scales within an underplated system. We documented the geometry, kinematics, vergence, and internal architecture of faults and folds along ~2.5 km of section, and we identified six previously unmapped intraformational imbricate thrusts and 13 high-angle faults that accommodate shortening and flattening of the underthrust section. Thrust faults occur within nearly every lithology without clear preference for any stratigraphic horizon, and fold vergence varies between imbricate sheets by ~10°–40°. In our map area, imbricate bounding thrusts have relatively narrow damage zones (≤5–10 m) and sharp, discrete fault cores and lack veining, in contrast to the wide, highly veined fault zones previously documented in the Marin Headlands terrane. The spacing of imbricate thrusts, combined with paleoconvergence rates, indicates relatively rapid generation of new fault surfaces on ~10–100 k.y. time scales, a process that may contribute to strain hardening and locking within the seismogenic zone. The structural and kinematic complexity documented in the Marin Headlands is an example of the short spatial and temporal scales of heterogeneity that may characterize regions of active underplating. Such features are smaller than the typical spatial resolution of geophysical data from active subduction thrusts and may not be readily resolved, thus highlighting the need for cross-comparison of geophysical data with field analogues when evaluating the kinematic and mechanical processes of underplating.
Firing properties of muscle spindles supplying the intrinsic foot muscles of humans in unloaded and freestanding conditions
Authors: Knellwolf T. P. , Burton A. R. , Hammam E. , Macefield V. G. 
Published: November 2018

We recently developed an approach for recording from muscle spindles in the intrinsic muscles of the foot in freestanding humans by inserting a tungsten microelectrode into the posterior tibial nerve behind the medial malleolus of the ankle. Here we characterize the behavior of muscle spindles in the small muscles of the foot in 1) seated subjects with the leg horizontal and the foot naturally plantarflexed and 2) standing subjects. In the first study, recordings were made from 26 muscle spindle afferents located within flexor digiti minimi brevis ( n = 4), abductor digiti minimi ( n = 3), quadratus plantae ( n = 3), plantar interossei ( n = 4), flexor digitorum brevis ( n = 3), dorsal interossei ( n = 2), and lumbricals ( n = 2), with one each supplying abductor hallucis, adductor hallucis, and flexor hallucis brevis. The identity of another two muscle afferents was unknown. The majority of the units were silent at rest, only seven (27%) being spontaneously active. Because of the anatomic constraints of the foot, some spindles supplying muscles acting on the toes responded to movements of one or more digits. In the second study, 12 muscle spindle afferents were examined during standing. The ongoing discharge of eight spindle afferents covaried with changes in the center of pressure during postural sway. We conclude that the majority of spindle endings in the small muscles of the foot are silent at rest, which may allow them to encode changes in conformation of the foot when it is loaded during standing. Moreover, these muscle spindle afferents can provide useful proprioceptive information during standing and postural sway. NEW & NOTEWORTHY We have characterized the firing properties of muscle spindles in the intrinsic muscles of the human foot for the first time. The majority of the spindle endings are silent in seated subjects, and most fire tonically during standing, their discharge covarying with center of pressure during postural sway. We conclude that spindle endings in the intrinsic muscles of the foot provide useful proprioceptive information during free standing.
Inhibition of LEF1-Mediated DCLK1 by Niclosamide Attenuates Colorectal Cancer Stemness
Authors: Park So-Yeon , Kim Ji-Young , Choi Jang-Hyun , Kim Jee-Heun , Lee Choong-Jae , Singh Pomila , Sarkar Shubhashish , Baek Jeong-Heum , Nam Jeong-Seok 
Published: November 2018

Abstract

Purpose:
Niclosamide, an FDA-approved anthelmintic drug, has been characterized as a potent Wnt inhibitor that can suppress tumor growth and cancer stem-like cell (CSC) populations. However, the underlying molecular mechanisms remain poorly understood. This study aimed to examine how Wnt inhibition by niclosamide preferentially targets CSCs.

Experimental Design:
The mechanistic role of niclosamide in CSC inhibition was examined in public databases, human colorectal cancer cells, colorectal cancer xenografts, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colorectal cancer model.

Results:
Niclosamide suppresses CSC populations and their self-renewal activities in colorectal cancer cells, and this CSC-targeting effect leads to irreversible disruption of tumor-initiating potential in vivo. Mechanistically, niclosamide downregulates multiple signaling components of the Wnt pathway, specifically lymphoid enhancer-binding factor 1 (LEF1) expression, which is critical for regulating stemness. Subsequently, we identified that the doublecortin-like kinase 1 (DCLK1)-B is a target of LEF1 and upregulates cancer stemness in colorectal cancer cells. We first documented that niclosamide blocks the transcription of DCLK1-B by interrupting the binding of LEF1 to DCLK1-B promoter. DCLK1-B depletion impairs cancer stemness resulting in reduced survival potential and increased apoptosis, thus sensitizing colorectal cancer to chemoradiation.

Conclusions:
Disruption of the LEF1/DCLK1-B axis by niclosamide eradicates cancer stemness and elicits therapeutic effects on colorectal cancer initiation, progression, and resistance. These findings provide a preclinical rationale to broaden the clinical evaluation of niclosamide for the treatment of colorectal cancer.