bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐ and sex‐specific survival of California sea lions (Zalophus californianus) at San Miguel Island, California
Authors: DeLong Robert L. , Melin Sharon R. , Laake Jeffrey L. , Morris Patricia , Orr Anthony J. , Harris Jeffrey D.
Published: August 2017

We conducted a mark‐recapture study of California sea lions (Zalophus californianus) using pups branded on San Miguel Island, California, from 1987 to 2014, and annual resightings from 1990 to 2015. We used the Burnham model (Burnham 1993), an extension of the Cormack‐Jolly‐Seber mark‐recapture model, which includes recoveries of dead animals, to analyze age, sex, and annual patterns in survival. Generally, females had higher survival than males. For female pups, the average annual survival was 0.600 and for male pups it was 0.574. Yearling survival was 0.758 and 0.757 for females and males, respectively. Peak annual survival was at age 5 and was 0.952 for females and 0.931 for males. Pups with larger mass at branding had higher survival as pups and yearlings, but the effect was relative within each cohort because of large between‐cohort variability in survival. Annual variability in sea surface temperature (SST) affected survival. For each 1°C increase in SST, the odds of survival decreased by nearly 50% for pups and yearlings; negative SST anomalies yielded higher survival. Annual variation in male survival was partly explained by leptospirosis outbreaks. Our study provides a unique view of one demographic parameter that contributed to the successful recovery of the California sea lion population.
Intra‐ and inter‐individual variability of Aspergillus fumigatus reactive T‐cell frequencies in healthy volunteers in dependency of mould exposure in residential and working environment
Authors: Wurster Sebastian , Weis Philipp , Page Lukas , Helm Johanna , Lazariotou Maria , Einsele Hermann , Ullmann Andrew J.
Published: August 2017

Invasive aspergillosis remains a deadly disease in immunocompromised patients, whereas the combination of an exaggerated immune response and continuous exposure lead to various hyperinflammatory diseases. This pilot study aimed to gain an overview of the intra‐ and inter‐individual variability in Aspergillus fumigatus reactive T‐helper cells in healthy adults and the correlation with environmental mould exposure. In this flow cytometric study, the frequencies of CD154+ A. fumigatus reactive T cells were evaluated in 70 healthy volunteers. All subjects completed a standardised questionnaire addressing their mould exposure. Subjects with intensive mould exposure in their professional or residential surrounding demonstrated considerably higher mean frequencies of A. fumigatus reactive T‐helper and T‐memory cells. Comparative evaluation of multiple measurements over time demonstrated relatively conserved reactive T‐cell frequencies in the absence of major changes to the exposure profile, whereas those frequently exposed in professional environment or with changes to their risk score demonstrated a marked dependency of antigen reactive T‐cell frequencies on recent mould exposure. This pilot study was the first to provide data on the intra‐individual variability in A. fumigatus reactive T‐cell frequencies and its linkage to mould encounter. Fungus reactive T cells are to be considered a valued tool for the assessment of environmental mould exposure.
Feasibility of monitoring advanced melanoma patients using cell‐free DNA from plasma
Authors: Gangadhar Tara C. , Savitch Samantha L. , Yee Stephanie S. , Xu Wei , Huang Alexander C. , Harmon Shannon , Lieberman David B. , Soucier Devon , Fan Ryan , Black Taylor A. , Morrissette Jennifer J. D. , Salathia Neeraj , Waters Jill , Zhang Shile , Toung Jonathan , van Hummelen Paul , Fan Jian‐Bing , Xu Xiaowei , Amaravadi Ravi K. , Schuchter Lynn M. , Karakousis Giorgos C. , Hwang Wei‐Ting , Carpenter Erica L.
Published: August 2017

To determine the feasibility of liquid biopsy for monitoring of patients with advanced melanoma, cell‐free DNA was extracted from plasma for 25 Stage III/IV patients, most (84.0%) having received previous therapy. DNA concentrations ranged from 0.6 to 390.0 ng/ml (median = 7.8 ng/ml) and were positively correlated with tumor burden as measured by imaging (Spearman rho = 0.5435, p = .0363). Using ultra‐deep sequencing for a 61‐gene panel, one or more mutations were detected in 12 of 25 samples (48.0%), and this proportion did not vary significantly for patients on or off therapy at the time of blood draw (52.9% and 37.5% respectively; p = .673). Sixteen mutations were detected in eight different genes, with the most frequent mutations detected in BRAF, NRAS, and KIT. Allele fractions ranged from 1.1% to 63.2% (median = 29.1%). Among patients with tissue next‐generation sequencing, nine of 11 plasma mutations were also detected in matched tissue, for a concordance of 81.8%.
The C2 protein of tomato leaf curl Taiwan virus is a pathogenicity determinant that interferes with expression of host genes encoding chromomethylases
Authors: Tu Yu‐Ching , Tsai Wen‐Shi , Wei Jyuan‐Yu , Chang Kai‐Ya , Tien Chang‐Ching , Hsiao Hui‐Yu , Fu Shih‐Feng
Published: August 2017

Tomato (Solanum lycopersicum) is one of the most important crops worldwide and is severely affected by geminiviruses. Tomato leaf curl Taiwan virus (ToLCTWV), belonging to the geminiviruses, was isolated in Taiwan and causes tremendous crop loss. The geminivirus‐encoded C2 proteins are crucial for a successful interaction between the virus and host plants. However, the exact functions of the viral C2 protein of ToLCTWV have not been investigated. We analyzed the molecular function(s) of the C2 protein by transient or stable expression in tomato cv. Micro‐Tom and Nicotiana benthamiana. Severe stunting of tomato and N. benthamiana plants infected with ToLCTWV was observed. Expression of ToLCTWV C2‐green fluorescent protein (GFP) fusion protein was predominately located in the nucleus and contributed to activation of a coat protein promoter. Notably, the C2‐GFP fluorescence was distributed in nuclear aggregates. Tomato and N. benthamiana plants inoculated with potato virus X (PVX)‐C2 displayed chlorotic lesions and stunted growth. PVX‐C2 elicited hypersensitive responses accompanied by production of reactive oxygen species in N. benthamiana plants, which suggests that the viral C2 was a potential recognition target to induce host‐defense responses. In tomato and N. benthamiana, ToLCTWV C2 was found to interfere with expression of genes encoding chromomethylases. N. benthamiana plants with suppressed NbCMT3–2 expression were more susceptible to ToLCTWV infection. Transgenic N. benthamiana plants expressing the C2 protein showed decreased expression of the NbCMT3–2 gene and pNbCMT3–2::GUS (β‐glucuronidase) promoter activity. C2 protein is an important pathogenicity determinant of ToLCTWV and interferes with host components involved in DNA methylation.
Angels versus Devils: The Portrayal of Characters in the Gun Policy Debate
Authors: Merry Melissa K.
Published: August 2017

This research examines the role of the devil shift and angel shift in interest group rhetoric using the case of gun policy. The Narrative Policy Framework (NPF) suggests that the devil shift—whereby political actors characterize their opponents as more malicious and powerful than they actually are—is common in intractable policy debates. Through an analysis of e‐mails and press releases by two gun control organizations and two gun rights organizations, I examine how groups portray themselves and their opponents. I identify two dimensions relevant to these portrayals: (1) whether a character in a policy narrative is portrayed as good or evil, and (2) whether a character is portrayed as strong or weak. The findings indicate that while the devil shift is present, the angel shift—that is, the glorification of one's own coalition—is more common in gun policy groups' communications. Two alternative characterizations, which I call the angel in distress and the devil diminished, are also present. The use of these character portrayals varies significantly across political coalitions and as a function of communication purposes. The results suggest a need to reconceptualize character portrayals to better understand how they operate as narrative strategies in the NPF.
Mycorrhizal fungal spore community structure in a manipulated prairie
Authors: Henning Jeremiah A. , Weiher Evan , Lee Tali D. , Freund Deborah , Stefanski Artur , Bentivenga Stephen P.
Published: August 2017

Most plant communities support a diverse assemblage of arbuscular mycorrhizal fungi (AMF). AMF communities have the potential to affect plant community structure and vice versa. We examined AMF sporulation in a 4.5‐ha reconstructed prairie in Eau Claire County, Wisconsin. In fall 2003, the site was planted with varied numbers and combinations of native prairie species from four functional guilds: C3 grasses/sedges, C4 grasses, legume, and nonleguminous forbs. We hypothesized that more diverse plant seeding mixtures would promote AMF diversity. To examine the interaction between plant and fungal communities, plots were divided and subplots treated with the fungicide chlorothalonil to suppress AMF, enriched with ammonium nitrate fertilizer, treated with both fungicide and nitrogen, or remained untreated (control). Soil samples were collected during the summers of 2004, 2006, and 2007 from each subplot. Spores of AMF were extracted, identified to species, and enumerated. Initial plant seeding diversity did not significantly influence spore abundance, fungal diversity, plant productivity, or plant richness 4 years after establishment. Fungal species richness was positively, but weakly, correlated with plant productivity (r2 = 0.11) and plant richness (r2 = 0.09). Fungal community composition changed significantly over time; nitrogen addition, fungicide application, and site characteristics also shaped community composition. After 4 years of treatment, nitrogen and fungicide reduced AMF richness, changed sporulation patterns among AMF taxa, and reduced diversity and productivity in plant communities. Divergence in AMF community is being mirrored by changes in the plant community independent of initial seeding treatments, though causation could not be determined.
Non‐parametric Estimation of the Number of Zeros in Truncated Count Distributions
Authors: Puig Pedro , Kokonendji Célestin C.
Published: August 2017

We present some lower bounds for the probability of zero for the class of count distributions having a log‐convex probability generating function, which includes compound and mixed‐Poisson distributions. These lower bounds allow the construction of new non‐parametric estimators of the number of unobserved zeros, which are useful for capture‐recapture models, or in areas like epidemiology and literary style analysis. Some of these bounds also lead to the well‐known Chao's and Turing's estimators. Several examples of application are analysed and discussed.
Disabilities and sexual expression: A review of the literature
Authors: Campbell Margaret
Published: August 2017

Since the late 1980s and early 1990s, scholars have sought to advance a more nuanced and robust understanding of the sexual lives of disabled people. In doing so, these scholars have identified some of the barriers to sexual expression that disabled people face as well as some of the positive and pleasurable aspects of disabled people's sexual lives. This article reviews research regarding the sexual expression and activity of disabled people as well as some of the challenges to sexual expression that people with disabilities experience. Persons with disabilities—whether they are acquired, congenital, intellectual, physical, and/or sensorial impairments—continue to encounter alienation, stigmatization, and discrimination, particularly in terms of their sexuality. However, I argue that if proper laws, policies, and adequate supports are in place, people with disabilities can further challenge and push past these barriers to engage in a wide array of sexual and erotic acts. Furthermore, although the amount of disability‐sexuality‐related research has increased over past decades, I argue that many intersections of disability and sexuality remain under‐studied and that further research in this field is necessary.
In‐situ analysis of trace elements and Sr–Pb isotopes of K‐feldspars from Tongshankou Cu–Mo deposit, SE Hubei Province, China: Insights into early potassic alteration of the porphyry mineralization system
Authors: Xu Yao‐Ming , Jiang Shao‐Yong
Published: August 2017

In the Tongshankou porphyry deposit (SE Hubei Province, South China), three types of K‐feldspars are recognized: (I) the phenocryst type in the porphyry that crystalized during the magmatic stage, (II) the megacryst type and (III) the vein type in the altered porphyry and orebody that was produced by hydrothermal fluids. A detailed in‐situ analysis of trace elements and Sr–Pb isotopes was carried out on K‐feldspars in an attempt to unravel their formation processes and to trace the element sources during potassic alteration. The Type III K‐feldspars show lower Sr contents and Sr‐isotope ratios but higher Pb contents and Pb‐isotope ratios than the Type I and II K‐feldspars, possibly reflecting a contribution from the country carbonate rocks with less radiogenic Sr but more radiogenic Pb sources, and indicate that the ore‐forming fluids and materials may have been partially derived from external sources such as the host sedimentary rocks during the early potassic alteration stage.
An analysis of movement patterns between zones using taxi GPS data
Authors: Chen Zhanlong , Gong Xi , Xie Zhong
Published: August 2017

The discovery of zones and people's movement patterns supports a better understanding of modern cities and enables a more comprehensive strategy for urban planning. This article proposes a modified method based on previous research to simultaneously discover people's zones and movement patterns, called movement patterns between functional zones (MPFZ). The method attempts to take full advantage of taxi GPS data to identify MPFZs by merging the movement traces satisfying the merging conditions. Considering movement directions, movement numbers and the adjacent constraints that consist of spatial relationship and attribute features, the merging conditions limit the movement traces to be merged. The new MPFZs are discovered by an iteration process and are measured by the following three evaluation indices: v‐value, a‐value and c‐value, which represent coverage, accuracy and their trade‐off. Using a real‐world taxi dataset of Beijing, 24 new MPFZs are discovered, which have higher v‐, a‐ and c‐values than the unmerged MPFZs. The results of the real‐world dataset experiment show that the proposed approach is effective and efficient. The proposed method can also be applied to other types of transportation data and regions by adjusting the dataset utilized and controlling the iteration process.
Survival outcomes following aggressive treatment of oligometastatic breast cancer: a systematic review protocol
Authors: Coombe Robyn , Lisy Karolina , Campbell Jared , Perry Gajen , Prasannan Subhita
Published: August 2017

Review question/objective:

: The objective of this systematic review is to assess the effectiveness of aggressive treatment of oligometastatic breast cancer (OMBC) on survival outcomes by conducting a meta-analysis of current available evidence.

More specifically, the objectives are to identify the effectiveness of intensified multidisciplinary treatment with aggressive locoregional therapies on survival time, five-year survival rates and disease free survival. The population is adult women (18 years and over) with OMBC defined as single or few (five or less) metastases limited to a single organ and the comparative group is conventional palliative treatment aimed at disease control. Secondary objectives to be assessed will be adverse outcomes associated with intensified treatment regimes.
Metformin and Alzheimer's disease, dementia and cognitive impairment: a systematic review protocol
Authors: Campbell Jared M. , Stephenson Matthew D. , de Courten Barbora , Chapman Ian , Bellman Susan M. , Aromataris Edoardo
Published: August 2017

Review question/objective:

The objective of the review is to assess the effect of metformin on the risk, progression and severity of Alzheimer's disease and other forms of dementia, as well as any measures of cognitive performance or impairment.
Regulation of cerebral blood flow and metabolism during exercise
Authors: Smith Kurt J. , Ainslie Philip N.
Published: August 2017

New Findings

What is the topic of this review?

The manuscript collectively combines the experimental observations from >100 publications focusing on the regulation of cerebral blood flow and metabolism during exercise from 1945 to the present day.

What advances does it highlight?

This article highlights the importance of traditional and historical assessments of cerebral blood flow and metabolism during exercise, as well as traditional and new insights into the complex factors involved in the integrative regulation of brain blood flow and metabolism during exercise. The overarching theme is the importance of quantifying cerebral blood flow and metabolism during exercise using techniques that consider multiple volumetric cerebral haemodynamics (i.e. velocity, diameter, shear and flow).

Cerebral function in humans is crucially dependent upon continuous oxygen delivery, metabolic nutrients and active regulation of cerebral blood flow (CBF). As a consequence, cerebrovascular function is precisely titrated by multiple physiological mechanisms, characterized by complex integration, synergism and protective redundancy. At rest, adequate CBF is regulated through reflexive responses in the following order of regulatory importance: fluctuating arterial blood gases (in particularly, partial pressure of carbon dioxide), cerebral metabolism, arterial blood pressure, neurogenic activity and cardiac output. Unfortunately, the magnitude that these integrative and synergistic relationships contribute to governing the CBF during exercise remains unclear. Despite some evidence indicating that CBF regulation during exercise is dependent on the changes of blood pressure, neurogenic activity and cardiac output, their role as a primary governor of the CBF response to exercise remains controversial. In contrast, the balance between the partial pressure of carbon dioxide and cerebral metabolism continues to gain empirical support as the primary contributor to the intensity‐dependent changes in CBF observed during submaximal, moderate and maximal exercise. The goal of this review is to summarize the fundamental physiology and mechanisms involved in regulation of CBF and metabolism during exercise. The clinical implications of a better understanding of CBF during exercise and new research directions are also outlined.
Spontaneous physical activity and mediators of energy homeostasis in the hypothalamus of mice from 4 to 10 months of age
Authors: Benfato Izabelle Dias , Moretto Thaís Ludmilla , de Carvalho Francine Pereira , Barthichoto Marcela , Ferreira Sandra Mara , Costa Júnior José Maria , Lazzarin Mariana Cruz , de Oliveira Flávia , Martinez Carolina , Prado de França Carvalho Carolina , de Oliveira Camila Aparecida Machado
Published: August 2017

New Findings

What is the central question of this study?

Is the initial decline of spontaneous physical activity (SPA) in mice related to impaired insulin and leptin signalling or brain‐derived neurotrophic factor expression in the hypothalamus?

What is the main finding and its importance?

We showed that SPA started to decline at an early stage, concomitantly with an impairment of hypothalamic leptin signalling. Consequently, energy expenditure decreased and glucose tolerance worsened. Our results demonstrate the need to counteract the initial decline in SPA to avoid metabolic impairments and indicate the possible involvement of central leptin in the reduction in SPA with age.

The biological control of physical activity is poorly understood. Age decreases insulin, leptin and brain‐derived neurotrophic factor (BDNF) signalling in the hypothalamus, and all have been shown to modulate spontaneous physical activity (SPA). We investigated the age at which SPA starts to decline and whether this is associated with the emergence of hypothalamic insulin and leptin resistance and reduced BDNF expression. Spontaneous physical activity (and other parameters of locomotion) and energy expenditure were determined monthly in mice from the 4th to the 10th month of age. Metabolic and hypothalamic analyses were performed in 4‐, 6‐ and 10‐month‐old mice. Spontaneous physical activity, distance travelled and speed of locomotion started to decrease in 6‐month‐old mice. The reduction in SPA became more evident from 8 months of age. Energy expenditure decreased from the 8th month. Hypothalamic BDNF protein expression and insulin signalling did not change throughout the time span studied. Leptin signalling decreased at 6 and 10 months compared with 4 months. Also, compared with 4 months, 6‐ and 10‐month‐old mice were glucose intolerant. In conclusion, SPA begins to decline in parallel with reduced hypothalamic leptin signalling. Metabolic impairment also manifests as SPA decreases, highlighting the need to understand the regulation of SPA in order to combat its decline.
A Finite Element Method-Based Potential Theory Approach for Optimal Ice Routing
Authors: Piehl Henry , Milaković Aleksandar-Saša , Ehlers Sören
Published: August 2017

Shipping in ice-covered regions has gained high attention within recent years. Analogous to weather routing, the occurrence of ice in a seaway affects the selection of the optimal route with respect to the travel time or fuel consumption. The shorter, direct path between two points—which may lead through an ice-covered area—may require a reduction of speed and an increase in fuel consumption. A longer, indirect route, could be more efficient by avoiding the ice-covered region. Certain regions may have to be avoided completely, if the ice thickness exceeds the ice-capability of the ship. The objective of this study is to develop a computational method that combines coastline maps, route cost information (e.g., ice thickness), transport task, and ship properties to find the optimal route between port of departure, A, and port of destination, B. The development approach for this tool is to formulate the transport task in the form of a potential problem, solve this equation with a finite element method (FEM), and apply line integration and optimization to determine the best route. The functionality of the method is first evaluated with simple test problems and then applied to realistic transport scenarios.
Biaxial Mechanical Assessment of the Murine Vaginal Wall Using Extension–Inflation Testing
Authors: Robison Kathryn M. , Conway Cassandra K. , Desrosiers Laurephile , Knoepp Leise R. , Miller Kristin S.
Published: August 2017

Progress toward understanding the underlying mechanisms of pelvic organ prolapse (POP) is limited, in part, due to a lack of information on the biomechanical properties and microstructural composition of the vaginal wall. Compromised vaginal wall integrity is thought to contribute to pelvic floor disorders; however, normal structure–function relationships within the vaginal wall are not fully understood. In addition to the information produced from uniaxial testing, biaxial extension–inflation tests performed over a range of physiological values could provide additional insights into vaginal wall mechanical behavior (i.e., axial coupling and anisotropy), while preserving in vivo tissue geometry. Thus, we present experimental methods of assessing murine vaginal wall biaxial mechanical properties using extension–inflation protocols. Geometrically intact vaginal samples taken from 16 female C57BL/6 mice underwent pressure–diameter and force–length preconditioning and testing within a pressure-myograph device. A bilinear curve fit was applied to the local stress–stretch data to quantify the transition stress and stretch as well as the toe- and linear-region moduli. The murine vaginal wall demonstrated a nonlinear response resembling that of other soft tissues, and evaluation of bilinear curve fits suggests that the vagina exhibits pseudoelasticity, axial coupling, and anisotropy. The protocols developed herein permit quantification of biaxial tissue properties. These methods can be utilized in future studies in order to assess evolving structure–function relationships with respect to aging, the onset of prolapse, and response to potential clinical interventions.
Simulation Analysis of Linear Quadratic Regulator Control of Sagittal-Plane Human Walking—Implications for Exoskeletons
Authors: Nataraj Raviraj , van den Bogert Antonie J.
Published: August 2017

The linear quadratic regulator (LQR) is a classical optimal control approach that can regulate gait dynamics about target kinematic trajectories. Exoskeletons to restore gait function have conventionally utilized time-varying proportional-derivative (PD) control of leg joints. But, these PD parameters are not uniquely optimized for whole-body (full-state) performance. The objective of this study was to investigate the effectiveness of LQR full-state feedback compared to PD control to maintain bipedal walking of a sagittal-plane computational model against force disturbances. Several LQR controllers were uniquely solved with feedback gains optimized for different levels of tracking capability versus control effort. The main implications to future exoskeleton control systems include (1) which LQR controllers out-perform PD controllers in walking maintenance and effort, (2) verifying that LQR desirably produces joint torques that oppose rapidly growing joint state errors, and (3) potentially equipping accurate sensing systems for nonjoint states such as hip-position and torso orientation. The LQR controllers capable of longer walk times than respective PD controllers also required less control effort. During sudden leg collapse, LQR desirably behaved like PD by generating feedback torques that opposed the direction of leg-joint errors. Feedback from nonjoint states contributed to over 50% of the LQR joint torques and appear critical for whole-body LQR control. While LQR control poses implementation challenges, such as more sensors for full-state feedback and operation near the desired trajectories, it offers significant performance advantages over PD control.
Finite Element Biomechanics of Optic Nerve Sheath Traction in Adduction
Authors: Shin Andrew , Yoo Lawrence , Park Joseph , Demer Joseph L.
Published: August 2017

Historical emphasis on increased intraocular pressure (IOP) in the pathogenesis of glaucoma has been challenged by the recognition that many patients lack abnormally elevated IOP. We employed finite element analysis (FEA) to infer contribution to optic neuropathy from tractional deformation of the optic nerve head (ONH) and lamina cribrosa (LC) by extraocular muscle (EOM) counterforce exerted when optic nerve (ON) redundancy becomes exhausted in adduction. We characterized assumed isotropic Young's modulus of fresh adult bovine ON, ON sheath, and peripapillary and peripheral sclera by tensile elongation in arbitrary orientations of five specimens of each tissue to failure under physiological temperature and humidity. Physical dimensions of the FEA were scaled to human histological and magnetic resonance imaging (MRI) data and used to predict stress and strain during adduction 6 deg beyond ON straightening at multiple levels of IOP. Young's modulus of ON sheath of 44.6 ± 5.6 MPa (standard error of mean) greatly exceeded that of ON at 5.2 ± 0.4 MPa, peripapillary sclera at 5.5 ± 0.8 MPa, and peripheral sclera at 14.0 ± 2.3 MPa. FEA indicated that adduction induced maximum stress and strain in the temporal ONH. In the temporal LC, the maximum stress was 180 kPa, and the maximum strain was ninefold larger than produced by IOP elevation to 45 mm Hg. The simulation suggests that ON sheath traction by adduction concentrates far greater mechanical stress and strain in the ONH region than does elevated IOP, supporting the novel concept that glaucomatous optic neuropathy may result at least partly from external traction on the ON, rather than exclusively on pressure on the ON exerted from within the eye.
Foot and Ankle Joint Biomechanical Adaptations to an Unpredictable Coronally Uneven Surface
Authors: Segal Ava D. , Yeates Kyle H. , Neptune Richard R. , Klute Glenn K.
Published: August 2017

Coronally uneven terrain, a common yet challenging feature encountered in daily ambulation, exposes individuals to an increased risk of falling. The foot-ankle complex may adapt to improve balance on uneven terrains, a recovery strategy which may be more challenging in patients with foot-ankle pathologies. A multisegment foot model (MSFM) was used to study the biomechanical adaptations of the foot and ankle joints during a step on a visually obscured, coronally uneven surface. Kinematic, kinetic and in-shoe pressure data were collected as ten participants walked on an instrumented walkway with a surface randomly positioned ±15 deg or 0 deg in the coronal plane. Coronally uneven surfaces altered hindfoot–tibia loading, with more conformation to the surface in early than late stance. Distinct loading changes occurred for the forefoot–hindfoot joint in early and late stance, despite smaller surface conformations. Hindfoot–tibia power at opposite heel contact (@OHC) was generated and increased on both uneven surfaces, whereas forefoot–hindfoot power was absorbed and remained consistent across surfaces. Push-off work increased for the hindfoot–tibia joint on the everted surface and for the forefoot–hindfoot joint on the inverted surface. Net work across joints was generated for both uneven surfaces, while absorbed on flat terrain. The partial decoupling and joint-specific biomechanical adaptations on uneven surfaces suggest that multi-articulating interventions such as prosthetic devices and arthroplasty may improve ambulation for mobility-impaired individuals on coronally uneven terrain.
Simplification of a G-Code Feeding Path in Roughing Multi-Axis Electrical Discharging Machining for Shrouded Blisks With a Contour Error Constraint
Authors: Xi Xue-Cheng , Chen Hao , Zhao Wan-Sheng
Published: August 2017

Multi-axis electrical discharging machining (EDM) is the main manufacture method for shrouded blisks, which are key components of aero and rocket engines. Involving both linear and rotational axes, a feeding path for machining a narrow and twisted channel consists of a large number of G-code lines. Accelerations and decelerations at junctions, which connect two neighboring G-code lines, can significantly reduce the machining efficiency. In this paper, a new simplification of feeding paths in roughing EDM for shrouded blisks is proposed in order to reduce the number of junctions on a feeding path. However, deviating from the original feeding path, a simplified feeding path can bring over contour errors which can cause geometrical errors of workpieces. Contour error can thus serve as a criterion for simplifying the original path. Eight vertices of a hexahedron, which contains the electrode, are used to represent all points inside and on an electrode. Forward kinematics of a six-axis EDM machine is used to calculate the contour errors of the eight vertices when the electrode feeds along a simplified path. A simplified feeding path can be found provided that the contour error constraint is respected. Machining tests show that the use of a simplified feeding path in roughing EDM machining can reduce the average total machining time by 26.5% without significant impact on surface roughness and white layer thickness.
Multi-Objective Build Orientation Optimization for Powder Bed Fusion by Laser
Authors: Brika Salah Eddine , Zhao Yaoyao Fiona , Brochu Mathieu , Mezzetta Justin
Published: August 2017

This paper proposes an integrated approach to determine optimal build orientation for powder bed fusion by laser (PBF-L), by simultaneously optimizing mechanical properties, surface roughness, the amount of support structure (SUPP), and build time and cost. Experimental data analysis has been used to establish the objective functions for different mechanical properties and surface roughness. Geometry analysis of the part has been used to estimate the needed SUPP and thus evaluate the build time and cost. Normalized weights are assigned to different objectives depending on their relative importance allowing solving the multi-objective optimization problem using a genetic optimization algorithm. A study case is presented to demonstrate the capabilities of the developed system. The major achievements of this work are the consideration of multiple objectives and the establishment of objective function considering different load direction and heat treatments. A user-friendly graphical user interface was developed allowing to control different optimization process factors and providing different visualization and evaluation tools.
Measurement of the Melt Pool Length During Single Scan Tracks in a Commercial Laser Powder Bed Fusion Process
Authors: Heigel J. C. , Lane B. M.
Published: August 2017

This work presents high-speed thermographic measurements of the melt pool length during single track laser scans on nickel alloy 625 substrates. Scans are made using a commercial laser powder bed fusion (PBF) machine while measurements of the radiation from the surface are made using a high speed (1800 frames per second) infrared camera. The melt pool length measurement is based on the detection of the liquidus–solidus transition that is evident in the temperature profile. Seven different combinations of programmed laser power (49–195 W) and scan speed (200–800 mm/s) are investigated, and numerous replications using a variety of scan lengths (4–12 mm) are performed. Results show that the melt pool length reaches steady-state within 2 mm of the start of each scan. Melt pool length increases with laser power, but its relationship with scan speed is less obvious because there is no significant difference between cases performed at the highest laser power of 195 W. Although keyholing appears to affect the anticipated trends in melt pool length, further research is required.
Bottlenose dolphin (Tursiops truncatus) auditory brainstem responses to frequency-modulated “chirp” stimuli
Authors: Finneran James J. , Mulsow Jason , Jones Ryan , Houser Dorian S. , Burkard Robert F.
Published: August 2017

Previous studies have demonstrated that increasing-frequency chirp stimuli (up-chirps) can enhance human auditory brainstem response (ABR) amplitudes by compensating for temporal dispersion occurring along the cochlear partition. In this study, ABRs were measured in two bottlenose dolphins (Tursiops truncatus) in response to spectrally white clicks, up-chirps, and decreasing-frequency chirps (down-chirps). Chirp durations varied from 125 to 2000 μs. For all stimuli, frequency bandwidth was constant (10–180 kHz) and peak-equivalent sound pressure levels (peSPLs) were 115, 125, and 135 dB re 1 μPa. Up-chirps with durations less than ∼1000 μs generally increased ABR peak amplitudes compared to clicks with the same peSPL or energy flux spectral density level, while down-chirps with durations from above ∼250 to 500 μs decreased ABR amplitudes relative to clicks. The findings generally mirror those from human studies and suggest that the use of chirp stimuli may be an effective way to enhance broadband ABR amplitudes in larger marine mammals.
Androgen Bioassay for the Detection of Nonlabeled Androgenic Compounds in Nutritional Supplements
Authors: Cooper Elliot R. , McGrath Kristine C.Y. , Li XiaoHong , Heather Alison K.
Published: August 2017

Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.
Nonuniform Deformation of the Patellar Tendon During Passive Knee Flexion
Authors: Slane Laura C. , Bogaerts Stijn , Thelen Darryl G. , Scheys Lennart
Published: August 2017

The purpose of this study was to evaluate localized patterns of patellar tendon deformation during passive knee flexion. Ultrasound radiofrequency data were collected from the patellar tendons of 20 healthy young adults during knee flexion over a range of motion of 50°–90° of flexion. A speckle tracking approach was used to compute proximal and distal tendon displacements and elongations. Nonuniform tissue displacements were visible in the proximal tendon (P < .001), with the deep tendon undergoing more distal displacement than the superficial tendon. In the distal tendon, more uniform tendon motion was observed. Spatial variations in percent elongation were also observed, but these varied along the length of the tendon (P < .002), with the proximal tendon remaining fairly isometric while the distal tendon underwent slight elongation. These results suggest that even during passive flexion the tendon undergoes complex patterns of deformation. Proximal tendon nonuniformity may arise from its complex anatomy where the deep tendon inserts onto the patella and the superficial tendon extends to the quadriceps tendon. Such heterogeneity is not captured in whole tendon average assessments, emphasizing the relevance of considering localized tendon mechanics, which may be key to understanding tendon behavior and precursors to injury and disease.
Bone Health of Young Male Gymnasts: A Systematic Review
Authors: Burt Lauren A. , Greene David A. , Naughton Geraldine A.
Published: August 2017

Purpose: To synthesize existing literatures on the impact of gymnastics participation on the skeletal health of young male gymnasts. Methods: Following a systematic search, 12 studies were included in this review. Quality of included studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE modified) criteria. Results: Assessment of skeletal health varied between and within imaging modality protocols. Gymnasts had higher total bone content, greater total and trabecular bone density, larger bone size, a thicker cortex, and higher estimates of bone strength than controls. Recreational studies reported no difference in height or weight between gymnasts and controls; however, elite gymnasts were shorter and lighter than nongymnasts. STROBE scores ranged from 65% to 95%. Conclusion: Gymnastics participation may be beneficial to the bone health of young males as gymnasts had higher bone density and bone mineral content, larger bones, and greater estimates of bone strength than controls.
TRIF-dependent Toll-like receptor signaling suppresses
Scd1
transcription in hepatocytes and prevents diet-induced hepatic steatosis
Authors: Chen Jing , Li Jin , Yiu Jensen H. C. , Lam Jenny K. W. , Wong Chi-Ming , Dorweiler Bernhard , Xu Aimin , Woo Connie W.
Published: August 2017

A TRIF-dependent pathway that restricts viral infection also prevents diet-induced hepatic steatosis.
Breast tumors educate the proteome of stromal tissue in an individualized but coordinated manner
Authors: Wang Xuya , Mooradian Arshag D. , Erdmann-Gilmore Petra , Zhang Qiang , Viner Rosa , Davies Sherri R. , Huang Kuan-lin , Bomgarden Ryan , Van Tine Brian A. , Shao Jieya , Ding Li , Li Shunqiang , Ellis Matthew J. , Rogers John C. , Townsend R. Reid , Fenyö David , Held Jason M.
Published: August 2017

Proteomic analysis of the tumor-associated stroma reveals extensive and coordinated regulation by breast cancers.
Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers
Authors: Venkatesh Mayandi , Barathi Veluchamy Amutha , Goh Eunice Tze Leng , Anggara Raditya , Fazil Mobashar Hussain Urf Turabe , Ng Alice Jie Ying , Harini Sriram , Aung Thet Tun , Fox Stephen John , Liu Shouping , Yang Liang , Barkham Timothy Mark Sebastian , Loh Xian Jun , Verma Navin Kumar , Beuerman Roger W. , Lakshminarayanan Rajamani
Published: August 2017

The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains, whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ε-polylysine (εPL) is noncytotoxic to primary human dermal fibroblasts at concentrations of up to 2,000 μg/ml, suggesting that the presence of an isopeptide backbone has greater cell selectivity than the presence of α-peptide backbones. Both εPL and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt preformed biofilms. εPL displays broad-spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungi. εPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria, and its biocompatibility index is superior to those of cationic antiseptic agents and LPEI. εPL does not interfere with the wound closure of injured rabbit corneas. In a rabbit model of bacterial keratitis, the topical application of εPL (0.3%, wt/vol) decreases the bacterial burden and severity of infections caused by
Pseudomonas aeruginosa
and
Staphylococcus aureus
strains.
In vivo
imaging studies confirm that εPL-treated corneas appeared transparent and nonedematous compared to untreated infected corneas. Taken together, our results highlight the potential of εPL in resolving topical microbial infections.
N-Acylated Derivatives of Sulfamethoxazole Block Chlamydia Fatty Acid Synthesis and Interact with FabF
Authors: Mojica Sergio A. , Salin Olli , Bastidas Robert J. , Sunduru Naresh , Hedenström Mattias , Andersson C. David , Núñez-Otero Carlos , Engström Patrik , Valdivia Raphael H. , Elofsson Mikael , Gylfe Åsa
Published: August 2017

The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that
Chlamydia
is capable of FASII and this pathway is indispensable for
Chlamydia
growth. Previously, a high-content screen with
Chlamydia trachomatis
-infected cells was performed, and acylated sulfonamides were identified to be potent growth inhibitors of the bacteria.
C. trachomatis
strains resistant to acylated sulfonamides were isolated by serial passage of a wild-type strain in the presence of low compound concentrations. Results from whole-genome sequencing of 10 isolates from two independent drug-resistant populations revealed that mutations that accumulated in
fabF
were predominant. Studies of the interaction between the FabF protein and small molecules showed that acylated sulfonamides directly bind to recombinant FabF
in vitro
and treatment of
C. trachomatis
-infected HeLa cells with the compounds leads to a decrease in the synthesis of
Chlamydia
fatty acids. This work demonstrates the importance of FASII for
Chlamydia
development and may lead to the development of new antimicrobials.
Avibactam Restores the Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia to Aztreonam
Authors: Mojica Maria F. , Papp-Wallace Krisztina M. , Taracila Magdalena A. , Barnes Melissa D. , Rutter Joseph D. , Jacobs Michael R. , LiPuma John J. , Walsh Thomas J. , Vila Alejandro J. , Bonomo Robert A.
Published: August 2017

Stenotrophomonas maltophilia
is an emerging opportunistic pathogen, classified by the World Health Organization as one of the leading multidrug-resistant organisms in hospital settings. The need to discover novel compounds and/or combination therapies for
S. maltophilia
is urgent. We demonstrate the
in vitro
efficacy of aztreonam-avibactam (ATM-AVI) against
S. maltophilia
and kinetically characterize the inhibition of the L2 β-lactamase by avibactam. ATM-AVI overcomes aztreonam resistance in selected clinical strains of
S. maltophilia
, addressing an unmet medical need.
In Vitro
Susceptibility to Closthioamide among Clinical and Reference Strains of Neisseria gonorrhoeae
Authors: Miari Victoria F. , Solanki Priya , Hleba Yonek , Stabler Richard A. , Heap John T.
Published: August 2017

Neisseria gonorrhoeae
is one of the leading antimicrobial resistance threats worldwide. This study determined the MICs of closthioamide to be 0.008 to 0.5 mg/liter for clinical
N. gonorrhoeae
strains and related species. Cross-resistance with existing antimicrobial resistance was not detected, indicating that closthioamide could be used to treat drug-resistant
N. gonorrhoeae
.
Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration
Authors: McBride John W. , Dias Nicola , Cameron David , Offord Robin E. , Hartley Oliver , Boyd Peter , Kett Vicky L. , Malcolm R. Karl
Published: August 2017

5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES following single-dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24-mg/ml), intermediate (6.18-mg/ml), and high (32.0-mg/ml; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability, and
in vitro
release testing. Following vaginal gel administration to sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue, and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behavior, with the high-concentration gels exhibiting a greater viscosity and cohesive structure than the intermediate- and low-concentration gels. In
in vitro
release testing, >90% 5P12-RANTES was released from the low- and intermediate-concentration gels after 72 h. For the high-concentration gel, ∼50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilization and/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, vaginal tissue, and serum increased in a dose-dependent manner. The highest concentrations were measured in vaginal fluid (10
5
to 10
7
ng/ml), followed by vaginal tissue (10
4
to 10
6
ng/ml). Both of these concentration ranges are several orders of magnitude above the reported half-maximal inhibitory concentrations. The lowest concentration was measured in serum (<10
2
ng/ml). The 5P12-RANTES pharmacokinetic data are similar to those reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's potency at picomolar concentrations, its strong barrier to resistance, and the full protection that it was observed to provide in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as a microbicide.