bluuebunny/crossref_metadata_2025 huggingface dataset:
Low temperature plasma enhanced deposition of GaP films on Si substrate
Authors: Gudovskikh Alexander S. , Morozov Ivan A. , Uvarov Alexander V. , Kudryashov Dmitriy A. , Nikitina Ekaterina V. , Bukatin Anton S. , Nevedomskiy Vladimir N. , Kleider Jean-Paul
Published: December 2017

Amorphous and microcrystalline GaP films were deposited on Si substrates by time modulated plasma enhanced deposition from trimethylgallium and phosphine using constant hydrogen plasma at a temperature of 250–380 °C. Amorphous GaP films obtained at constant low radio-frequency (RF) power (20 W) mode exhibit the broad feature at 350–360 cm−1 and a shoulder at 370–390 cm−1 in Raman spectra. Amorphous films have smooth surface with root-mean-square (RMS) roughness decreasing from 0.9 to 0.2 nm with increasing deposition temperature from 250 to 380 °C. Small amounts of 3–5 nm GaP nanocrystal inclusions in the amorphous matrix are formed at 380 °C. An increase of RF power to 100 W during Ga and P deposition steps leads to the formation of a GaP crystalline phase as confirmed by transmission electron microscopy. Two peaks in the Raman spectra at 365 and 402 cm−1, which correspond to GaP TO-LO duplet, were observed in this case. However, the microcrystalline GaP layers have rough surface with RMS roughness of 6 nm. A critical role of the hydrogen plasma for GaP growth mechanism is demonstrated. Indeed an effect of the phosphorous accumulation in the deposition chamber during phosphine plasma assisted decomposition step is shown. The hydrogen plasma treatment after P deposition step allows one to avoid an influence of excess phosphorous to the growth process providing a way to obtain ALD like growth of GaP with good thickness uniformity.
Surface-attached hydrogel coatings via C,H-insertion crosslinking for biomedical and bioanalytical applications (Review)
Authors: Prucker Oswald , Brandstetter Thomas , Rühe Jürgen
Published: December 2017

A novel method for the generation of surface-attached hydrogel coatings and their use in biomedical applications is discussed. This short review concentrates on surface architectures that are prepared from prepolymers carrying reactive groups suitable for crosslinking via C,H insertion reactions [C,H insertion crosslinking (CHic)]. Upon photochemical or thermal activation these groups do not only induce the crosslinking of the system, but also connect the forming gel to the surface as long as the surface itself consists of an organic material. C,H groups as the reaction partner are available in abundance at practically all types of organic surfaces such as biomaterials or polymers, rendering the technique almost universally applicable. Surface-attached gels prepared this way show unique swelling properties due to the confinement of the chains, as the obtained essentially two-dimensional gels can only swell in one dimension. This anisotropic swelling does not permit penetration of the layers by macromolecules so that the surfaces become bioinert, i.e., are strongly protein and cell repellent. It is discussed how this property can be used to control the interaction of surfaces with biological species ranging from the level of biomolecules to living cells. A combination of the CHic chemistry and microstructuring techniques opens further avenues for the study of the behavior of cells to the generation of novel bioanalytical devices.
Long-term ambient surface oxidation of titanium oxynitride films prepared by plasma-enhanced atomic layer deposition: An XPS study
Authors: Kot Małgorzata , Łobaza Justyna , Naumann Franziska , Gargouri Hassan , Henkel Karsten , Schmeißer Dieter
Published: December 2017

The surface oxidation of a titanium oxynitride (TiOxNy) film after long-time storage of 25 month in ambient conditions is investigated. The TiOxNy film is prepared by plasma-enhanced atomic layer deposition using tetrakis(dimethylamino)titanium and nitrogen plasma, and the film is characterized by Ar+ ion sputtering of the film surface in combination with x-ray photoelectron spectroscopy (XPS) as well as by angle-resolved XPS. The total thickness of an oxygen-enriched layer at the surface of the TiOxNy films is found to be about 0.7 nm and it consists of a sequence of a 0.4 nm thick TiON/TiO2 enriched layer followed by a 0.3 nm thick TiO2 enriched layer underneath compared to the bulk composition of the film which shows constant values of 29% TiN, 29% TiO2, and 42% TiON. The results suggest that the TiON enrichment takes place initially at the surface followed by a surface and subsurface oxidation.
Attenuation of low-frequency underwater sound using an array of air-filled balloons and comparison to effective medium theory
Authors: Lee Kevin M. , Wilson Preston S. , Wochner Mark S.
Published: December 2017

The ultimate goal of this work is to accurately predict the attenuation through a collection of large (on the order of 10-cm-radius) tethered encapsulated bubbles used in underwater noise abatement systems. Measurements of underwater sound attenuation were performed during a set of lake experiments, where a low-frequency compact electromechanical sound source was surrounded by different arrays of encapsulated bubbles with various individual bubbles sizes and void fractions. The measurements were compared with an existing predictive model [Church, J. Acoust. Soc. Am. 97, 1510–1521 (1995)] of the dispersion relation for linear propagation in liquid containing encapsulated bubbles. Although the model was originally intended to describe ultrasound contrast agents, it is evaluated here for large bubbles, and hence low frequencies, as a design tool for future underwater noise abatement systems, and there is good quantitative agreement between the observations and the model.
The time course of sound category identification: Insights from acoustic features
Authors: Ogg Mattson , Slevc L. Robert , Idsardi William J.
Published: December 2017

Humans have an impressive, automatic capacity for identifying and organizing sounds in their environment. However, little is known about the timescales that sound identification functions on, or the acoustic features that listeners use to identify auditory objects. To better understand the temporal and acoustic dynamics of sound category identification, two go/no-go perceptual gating studies were conducted. Participants heard speech, musical instrument, and human-environmental sounds ranging from 12.5 to 200 ms in duration. Listeners could reliably identify sound categories with just 25 ms of duration. In experiment 1, participants' performance on instrument sounds showed a distinct processing advantage at shorter durations. Experiment 2 revealed that this advantage was largely dependent on regularities in instrument onset characteristics relative to the spectrotemporal complexity of environmental sounds and speech. Models of participant responses indicated that listeners used spectral, temporal, noise, and pitch cues in the task. Aspects of spectral centroid were associated with responses for all categories, while noisiness and spectral flatness were associated with environmental and instrument responses, respectively. Responses for speech and environmental sounds were also associated with spectral features that varied over time. Experiment 2 indicated that variability in fundamental frequency was useful in identifying steady state speech and instrument stimuli.
Metagenome Sequence of a Microbial Community from the Gold Mine Tailings in the Kuzbass Area, Russia
Authors: Mardanov Andrey V. , Beletsky Alexey V. , Ivasenko Denis A. , Karnachuk Olga V. , Ravin Nikolai V.
Published: December 2017

The metagenome of a microbial community of the sediments from a highly acidic iron-rich puddle at the tailings dump of the Komsomolskaya gold mine in the Kuzbass area, Siberia, Russia, was sequenced. Binning of contigs yielded a near-complete genome of the dominant bacterium, representing a novel deep lineage of
Deltaproteobacteria
.
Waste management, informal recycling, environmental pollution and public health
Authors: Yang Hong , Ma Mingguo , Thompson Julian R , Flower Roger J
Published: December 2017

With rapid population growth, especially in low-income and middle-income countries, the generation of waste is increasing at an unprecedented rate. For example, annual global waste arising from waste electrical and electronic equipment alone will have increased from 33.8 to 49.8 million tonnes between 2010 and 2018. Despite incineration and other waste treatment techniques, landfill still dominates waste disposal in low-income and middle-income countries. There is usually insufficient funding for adequate waste management in these countries and uptake of more advanced waste treatment technologies is poor. Without proper management, many landfills represent serious hazards as typified by the landslide in Shenzhen, China on 20 December 2015. In addition to formal waste recycling systems, approximately 15million people around the world are involved in informal waste recycling, mainly for plastics, metals, glass and paper. This review examines emerging public health challenges, in particular within low-income and middle-income countries, associated with the informal sector. While informal recyclers contribute to waste recycling and reuse, the relatively primitive techniques they employ, combined with improper management of secondary pollutants, exacerbate environmental pollution of air, soil and water. Even worse, insufficient occupational health measures expose informal waste workers to a range of pollutants, injuries, respiratory and dermatological problems, infections and other serious health issues that contribute to low life expectancy. Integration of the informal sector with its formal counterparts could improve waste management while addressing these serious health and livelihood issues. Progress in this direction has already been made notably in several Latin American countries where integrating the informal and formal sectors has had a positive influence on both waste management and poverty alleviation.
Subthalamotomy for Parkinson’s disease: clinical outcome and topography of lesions
Authors: Rodriguez-Rojas Rafael , Carballo-Barreda Maylen , Alvarez Lazaro , Guridi Jorge , Pavon Nancy , Garcia-Maeso Ivan , Mací­as Raul , Rodriguez-Oroz Maria C , Obeso Jose Angel
Published: December 2017

Objective

Subthalamotomy is an effective alternative for the treatment of Parkinson’s disease (PD). However, uncertainty about the optimal target location and the possibility of inducing haemichorea-ballism have limited its application. We assessed the correlation between the topography of radiofrequency-based lesions of the subthalamic nucleus (STN) with motor improvement and the emergence of haemichorea-ballism.

Methods

Sixty-four patients with PD treated with subthalamotomy were evaluated preoperatively and postoperatively using the Unified Parkinson’s Disease Rating Scale motor score (UPDRSm), MRI and tractography. Patients were classified according to the degree of clinical motor improvement and dyskinesia scale. Lesions were segmented on MRI and averaged in a standard space. We examined the relationship between the extent of lesion-induced disruption of fibres surrounding the STN and the development of haemichorea-ballism.

Results

Maximum antiparkinsonian effect was obtained with lesions located within the dorsolateral motor region of the STN as compared with those centre-placed in the dorsal border of the STN and the zona incerta (71.3%, 53.5% and 20.8% UPDRSm reduction, respectively). However, lesions that extended dorsally beyond the STN showed lower probability of causing haemichorea-ballism than those placed entirely within the nucleus. Tractography findings indicate that interruption of pallidothalamic fibres probably determines a low probability of haemichorea-ballism postoperatively.

Conclusions

The topography of the lesion is a major factor in the antiparkinsonian effect of subthalamotomy in patients with PD. Lesions involving the motor STN and pallidothalamic fibres induced significant motor improvement and were associated with a low incidence of haemichorea-ballism.
Hypothetical route of the introduction of Schmallenberg virus into Ireland using two complementary analyses
Authors: McGrath Guy , More Simon J , O'Neill Ronan
Published: December 2017

Ireland lost its official freedom from Schmallenberg virus (SBV) in October 2012. The route of introduction is uncertain, with long‐distance displacement of infected Culicoides, biting midges, by suitable wind flows considered to be the most likely source. The authors investigated the potential introduction of SBV into Ireland through a Culicoides incursion event in the summer of 2012. They conducted SBV serology on archived bovine sera to identify the prospective dispersal window, then used atmospheric dispersion modelling during periods around this window to identify environmental conditions the authors considered suitable for atmospheric dispersal of Culicoides from potential infected source locations across Southern England. The authors believe that there was one plausible window over the summer of 2012, on August 10–11, based on suitable meteorological conditions. They conclude that a potential long‐range transportation event of Culicoides appears to have occurred successfully only once during the 2012 vector competent season. If these incursion events remain at a low frequency, meteorological modelling has the potential to contribute cost‐effectively to the alert and response systems for vectorborne diseases in the future.
Zoonotic potential of Salmonella enterica carried by pet tortoises
Authors: Bruce Hayley L , Barrow Paul A , Rycroft Andrew N
Published: December 2017

The prevalence of Salmonella in chelonians is not known in the UK and it is not clear whether such Salmonella strains would be pathogenic for human beings. Some strains, such as members of the Arizonae subgroup, may be unable to cause anything more than very mild disease. To determine the carriage of Salmonella in pet tortoises, cloacal swabs were taken for culture. Salmonella enterica Group D was isolated from 5 of the 89 samples. All five were from the same household of seven tortoises. Salmonella isolates were shown by PCR to carry the invA and spiC genes associated with pathogenicity islands 1 and 2. Each isolate carried both genes indicating they had the genetic basis for disease and enterocyte invasion in human beings. The study indicates a low rate of asymptomatic carriage among the general population of pet tortoises. However, it does suggest that those Salmonella strains colonising the tortoise can carry Salmonella pathogenicity island (SPI)‐1 and SPI‐2 conferring the potential to cause disease in human beings and other animals.
What role does diet play in the decline of puffins?
Authors: Taylor Eleanor
Published: December 2017

Eleanor Taylor explains how bird lovers are helping conservation charity RSPB understand puffin populations.
A protocol for the analysis of aquatic biodiversity by multiple β diversities
Authors: Yokota Masashi , Takeda Jungo , Suzuki Naoki , Sakuramoto Kazumi
Published: December 2017

Species assemblage can be fairly unstable in aquatic ecosystems because of strong environmental constraints. Measuring β diversity is one of the most useful tools for assessing community dynamics and differentiations among communities. Whereas many β diversity measurements have been proposed for these issues, we present here a unifying framework based on the properties of Hill number, q, to unravel the complex changes occurring in dynamic communities. Using ideal numerical examples of an aquatic community, the sensitivity of β diversity with q = 0 ∼ 2 was examined. Whereas β diversity for q = 0 has a higher sensitivity to rare species drift (rapid exchanges or migration of many rare species) than do others, β diversity for q = 2 adequately responds to the variation or changes of dominant species. A scatterplot based on these two β diversity measures is proposed for the detailed examination of aquatic community dynamics. We show that the scatterplot is able to describe the monthly dynamics of dominant and rare species in the phytoplankton assemblage of a freshwater lake in Japan.
Genome size and brain cell density in birds
Authors: Gregory T. Ryan
Published: December 2017

Birds exhibit small, constrained genome sizes relative to many other vertebrates. This has often been attributed to the metabolic constraints of powered flight, which requires small cells for efficient gas exchange. Small cells, in turn, are achieved in part by limiting nucleus size and thus DNA content. However, metabolism is not the only organismal trait that correlates with genome size in birds; relationships have also been reported with body size (positive) and relative brain size (inverse). In this study, a recent data set on cell numbers in the brains of birds was combined with available data on genome sizes to demonstrate a relationship between genome size and density of cells per gram of brain tissue. This suggests that small genomes are relevant not only in the evolution of avian flight but may also be associated with the extraordinary behavioural complexity shown by birds.
A CAPM WITH TRADING CONSTRAINTS AND PRICE BUBBLES
Authors: JARROW ROBERT
Published: December 2017

This paper derives an equilibrium capital asset pricing model (CAPM) in a market with trading constraints and asset price bubbles. The asset price processes are general semimartingales including Markov jump-diffusion processes as special cases, and the trading constraints considered include short sale restrictions, borrowing constraints, and margin requirements, among others. We derive a generalized intertertemporal CAPM and consumption CAPM for these markets. The implications for empirical testing are that additional systematic risk factors will exist in a market with trading constraints and price bubbles as contrasted with an otherwise equivalent unconstrained market with no price bubbles.
A Novel Method for Load Bounds Identification for Uncertain Structures in Frequency Domain
Authors: He Z. C. , Lin X. Y. , Li Eric
Published: December 2017

A novel method for load bounds identification for uncertain structures is proposed in the frequency domain. The uncertain parameters are assumed to locate in their intervals and only their bounds rather than their precise information are needed. To quantitatively describe the effect of the interval uncertainty on the load identification in the frequency ranges, the interval extension is then introduced in the frequency response function (FRF)-based least squares approach. Therefore, the load bounds are determined through the summation of the two separate parts including the midpoint part and the perturbed part of the load. The midpoint part is computed by using the Moore–Penrose pseudo-inversion and the perturbed part is transformed into the first derivatives of the midpoint load with respect to the uncertain parameters by applying the truncated total least squares (TTLS). Two numerical examples are investigated to validate that the proposed method is very effective to predict the load bounds for the uncertain structure in frequency domain.
Static and Free Vibration Analysis of Stiffened Flat Shells by a Cell-Based Smoothed Discrete Shear Gap Method (CS-FEM-DSG3) Using Three-Node Triangular Elements
Authors: Nguyen-Thoi T. , Bui-Xuan T. , Liu G. R. , Vo-Duy T.
Published: December 2017

A cell-based smoothed discrete shear gap method (CS-FEM-DSG3) using three-node triangular element was recently proposed for static, free vibration and buckling analyses of stiffened Mindlin plates. The CS-FEM-DSG3 element is a significant improvement of the original DSG3 element by using smoothing technique to soften the stiffness of the DSG3 element while it has still inherited the locking-free feature of the former. In this paper, the CS-FEM-DSG3 is further extended for the static and free vibration analyses of stiffened flat shells by combining the original plate element CS-FEM-DSG3 with Allman’s plane stress element and a linearly isotropic two-node stiffened beam element. The compatibility of displacement field of stiffeners and shell is applied at the contact positions. Numerical results of the proposed element are compared with those of some existing methods to demonstrate the accuracy and reliability of the proposed method.
IMPACT OF THE USE OF KNOWLEDGE OBTAINED THROUGH INFORMAL EXCHANGES ON THE PERFORMANCE OF INNOVATION PROJECTS: FOR THE ENRICHMENT OF INBOUND OPEN INNOVATION PRACTICES
Authors: DIETSCH DAMIEN , KHEMIRI RIM
Published: December 2017

This study aims to examine the relationship between the acquisition of knowledge through informal channels and performance of innovation projects. We propose that three forms of informal knowledge exchange, namely, knowledge sharing, knowledge presentation and knowledge transfer, positively impact the perceived performance of innovation projects. A survey of 360 individuals involved in innovation projects whose answers were analysed with PLSs reveals that knowledge, obtained through knowledge sharing and knowledge transfer with third parties outside the company by informal route and the simultaneous use of an innovation intermediary as part of these informal exchanges, positively impacts the three elements that have been chosen to measure the operational performance of innovation projects, namely, cost, time and quality. These results provide major contributions to the academic and managerial point of view and open up new vistas for research that derived directly from the demonstration that open innovation not only has to relay on formal agreements, but also to take into account the informal way of knowledge acquisition.
CASE REPORT: UNILATERAL ECTOPIC TESTIS IN THE TUNICA ALBUGINEA CONCURS WITH EPIDIDYMAL HYPERPLASIA IN THE ATROPHIC TESTIS IN A DOG
Authors: Lin Chun-Ming , Eng Hock-Liew , Pang Victor F. , Wang Fun-In
Published: December 2017

A 10-year-old male Fox Terrier presented with two descended testes of different sizes. The left testis was normal, while the right one was atrophic. The tunica albuginea (TA) of the right testis was distributed with brown spots of less than 1[Formula: see text]mm in diameter, and was microscopically determined to be ectopic testis which consists of Leydig cell adenoma, primitive seminiferous tubules (STs), intratubular seminoma, and reduplication of arterioles. At the junction of the TA with the spermatic cord, units of testis primordia were present. The STs of the remaining atrophic (not ectopic) right testis were populated not by germ cells but by ciliated pseudostratified cells mimicking those of the epididymis, as supported by the immunohistochemistry results. During the adaptation process, multiple smaller tubules combined into fewer but larger less convoluted tubules. This is a case of concurrent ectopic testis and arterial malformation in the TA with hypoxia, subsequent testicular atrophy, and epididymal hyperplasia in a dog.
Hamiltonian Nodal Position Finite Element Method for Cable Dynamics
Authors: Ding Huaiping , Zhu Zheng H. , Yin Xiaochun , Zhang Lin , Li Gangqiang , Hu Wei
Published: December 2017

This paper developed a new Hamiltonian nodal position finite element method (FEM) to treat the nonlinear dynamics of cable system in which the large rigid-body motion is coupled with small elastic cable elongation. The FEM is derived from the Hamiltonian theory using canonical coordinates. The resulting Hamiltonian finite element model of cable contains low frequency mode of rigid-body motion and high frequency mode of axial elastic deformation, which is prone to numerical instability due to error accumulation over a very long period. A second-order explicit Symplectic integration scheme is used naturally to enforce the conservation of energy and momentum of the Hamiltonian finite element system. Numerical analyses are conducted and compared with theoretical and experimental results as well as the commercial software LS-DYNA. The comparisons demonstrate that the new Hamiltonian nodal position FEM is numerically efficient, stable and robust for simulation of long-period motion of cable systems.
An Explicit Time Integration Scheme Based on B-Spline Interpolation and Its Application in Wave Propagation Analysis
Authors: Wen W. B. , Duan S. Y. , Tao Y. , Liang Jun , Fang Daining
Published: December 2017

An explicit time integration scheme for hyperbolic equations is proposed using B-spline interpolation and weighted residual method. It has simple formulation and calculation procedure. With one adjustable algorithmic parameter, new scheme has higher accuracy when compared with other excellent explicit schemes. New scheme has controllable and also desirable period elongation which is verified by theoretical analysis and numerical simulations. Especially, a demonstrative dispersion analysis coupled with the corresponding wave propagation demonstrate the desirable numerical dissipation property and the effectiveness of the proposed scheme for wave propagation problems.
Realization of Artificial Nonlinear Spring with Controllable Stiffness
Authors: Kassem Mohammed , Yang Zhichun , Gu Yingsong , Wang Wei , Safwat Ibrahim M.
Published: December 2017

Traditionally, nonlinear stiffness is achieved using mechanical components designed for a specific structure under certain loading conditions. In the present paper, the desired stiffness nonlinearity with various controlled stiffness values is obtained using smart materials. A prototype nonlinear spring is designed by a cantilever beam with bonded macro-fiber composite (MFC). The novel active prototype is modeled, simulated and experimentally validated to realize the artificial nonlinear spring (ANS) approach. To characterize the dynamic behavior of the proposed MFC-beam system, a dynamic linearized model is identified using a fourth order transfer function. Proportional integral (PI) controller is implemented to achieve the required spring stiffness function. According to the applied load estimation technique, three models are used to control the nonlinear stiffness. The results show precise nonlinear responses to measurable static and quasi-static external loads. Unmeasurable loads are real-time estimated and adequately responded. Both softening and hardening springs with a wide range of nonlinear stiffness values are obtained and tuned according to the demands. The proposed approach widens the application range of nonlinear springs and improves their performance.
Biobanking Genetic Material for Agricultural Animal Species
Authors: Blackburn H.D.
Published: December 2017

Biobanking animal germplasm and tissues is a major component of conserving genetic resources. Effectively constructing such gene banks requires an understanding and evaluation of genetic resources, the ability to conserve various tissues through cryopreservation, and a robust information technology infrastructure to allow managers and potential users to fully understand and make use of the collection. Progress has been made internationally in developing national genetic resource collections. As these collections have been developed, it has become apparent that gene banks can serve a multitude of roles, thereby serving short- and long-term needs of research communities and industry. This article documents the development of gene banks and provides examples of how they have been used to date and the extent to which they have captured genetic diversity for future use.
Computational Neuroscience: Mathematical and Statistical Perspectives
Authors: Kass Robert E. , Amari Shun-Ichi , Arai Kensuke , Brown Emery N. , Diekman Casey O. , Diesmann Markus , Doiron Brent , Eden Uri T. , Fairhall Adrienne L. , Fiddyment Grant M. , Fukai Tomoki , Grün Sonja , Harrison Matthew T. , Helias Moritz , Nakahara Hiroyuki , Teramae Jun-nosuke , Thomas Peter J. , Reimers Mark , Rodu Jordan , Rotstein Horacio G. , Shea-Brown Eric , Shimazaki Hideaki , Shinomoto Shigeru , Yu Byron M. , Kramer Mark A.
Published: December 2017

Mathematical and statistical models have played important roles in neuroscience, especially by describing the electrical activity of neurons recorded individually, or collectively across large networks. As the field moves forward rapidly, new challenges are emerging. For maximal effectiveness, those working to advance computational neuroscience will need to appreciate and exploit the complementary strengths of mechanistic theory and the statistical paradigm.
NKG2D-Based CAR T Cells and Radiotherapy Exert Synergistic Efficacy in Glioblastoma
Authors: Weiss Tobias , Weller Michael , Guckenberger Matthias , Sentman Charles L. , Roth Patrick
Published: December 2017

Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T-cell therapy into conventional anticancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFNγ production and cytolytic activity in vitro. Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor rechallenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T-cell treatment resulted in synergistic activity in two independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions. We thus provide preclinical proof-of-concept of NKG2D CAR T-cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.

Significance: These findings provide evidence for synergy of conventional anticancer therapy and CAR T cells and heralds future studies for other treatment combinations. Cancer Res; 78(4); 1031–43. ©2017 AACR.
Peptide Blocking of PD-1/PD-L1 Interaction for Cancer Immunotherapy
Authors: Li Chunlin , Zhang Nengpan , Zhou Jundong , Ding Chen , Jin Yaqing , Cui Xueyuan , Pu Kefeng , Zhu Yimin
Published: December 2017

Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. mAb targeting PD-L1 has been approved to treat urothelial carcinoma, non–small cell lung cancer, or Merkel cell carcinoma by the FDA. However, the high cost of the antibody can limit its application. In our study, targeting PD-L1 peptide (TPP-1), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods. Using a T-cell activation assay and mixed lymphocyte reaction, TPP-1 was verified to interfere with the interaction of PD-1/PD-L1. To examine the inhibitory effect of TPP-1 on tumor growth in vivo, a xenograft mouse model using H460 cells was established. The growth rate of tumor masses in TPP-1 or PD-L1 antibody–treated mice was 56% or 71% lower than that in control peptide–treated mice, respectively, indicating that TPP-1 inhibits, or at least retards, tumor growth. IHC of the tumors showed that IFNγ and granzyme B expression increased in the TPP-1 or PD-L1 antibody–treated groups, indicating that TPP-1 attenuates the inhibitory effect of PD-L1 on T cells and that T cells may get reactivated. On the basis of our data, TPP-1 peptide could work as an alternative to antibodies for tumor immunotherapy. Cancer Immunol Res; 6(2); 178–88. ©2017 AACR.
Evidence of Osteoclastic Activity in the Human Temporal Bone
Authors: Kamakura Takefumi , Nadol Jr. Joseph B.
Published: December 2017

Bone remodeling within the otic capsule has been reported to be inhibited especially at or near the cochlea, except under some pathological conditions such as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur. Microcavitations found in periosteal and endosteal layers of human temporal bone specimens without otosclerosis, Paget's disease, or inflammation as reported in the current study are consistent with osteoclastic bone resorption. Thirty-three temporal bones from 33 patients were prepared for light microscopy and classified into 4 groups: histologically proven dehiscence of the superior semicircular canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older and with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic locations in the temporal bone in all 4 groups, but not in the cochlea or vestibule. Microcavitation within the temporal bone is likely due to osteoclastic activity, and it is seen in both young and old patients, patients with and without otosclerosis, and in cases with SSCD.
Survival in Type 1 and Type 2 Diabetes in a Population Referred for Invasive Evaluation of Coronary Disease
Authors: Mølstad Per , Rødevand Olaf
Published: December 2017

Objectives: To evaluate long-term and time trends of survival in patients with a clinical diagnosis of type 1 and type 2 diabetes compared to patients without diabetes in a population referred for invasive treatment of coronary disease. Methods: Patients examined for heart disease at the Feiring LHL Clinics from March 1999 until December 2014 were followed for survival until 20 September, 2015. This yielded 43,872 patients with a known survival status including 1,326 (3.0%) patients with type 1 diabetes and 4,564 (10.9%) with type 2 diabetes. Results: Cox regression revealed a hazard ratio (HR) in type 1 and type 2 diabetes, respectively, of 1.78 (95% confidence interval [CI] 1.60-1.99) and 1.29 (95% CI 1.21-1.37). Comparing survival in the treatment periods before and after 2007, patients without diabetes and with type 2 diabetes had a reduced HR of 0.78 (95% CI 0.72-0.84) and 0.76 (95% CI 0.63-0.91), respectively, but there was no reduction in type 1 diabetes (HR 1.03; 95% CI 0.74-1.42). Conclusions: Type 1 and type 2 diabetes have excess long-term mortality. In the nondiabetic and type 2 diabetic patients, a reduction in mortality has been noted in recent years, but has not been observed in type 1 diabetic patients.
Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis
Authors: Chang Ke-Vin , Chen Jin-De , Wu Wei-Ting , Huang Kuo-Chin , Hsu Chia-Tzu , Han Der-Sheng
Published: December 2017

Background: Hepatocellular carcinoma (HCC) has multiple prognostic factors, and there is an increase in knowledge about the body composition and physical status of patients with HCC. The present meta-analysis aimed to explore whether loss of skeletal muscle mass is associated with mortality and tumor recurrence in patients with HCC. Method: A systematic search was conducted for published literature using PubMed, Embase, and Scopus. We included cohort or case-control studies investigating patients with HCC. The primary and secondary outcomes were the associations of loss of skeletal muscle mass with overall survival and tumor recurrence, respectively, expressed by a summary hazard ratio (HR) and 95% confidence interval (CI). Result: A total of 13 studies comprising 3,111 patients were included. The summary HRs calculated by either univariate or multivariate analysis both suggested a significant association between sarcopenia and all-cause mortality (crude HR = 2.04, 95% CI: 1.74-2.38; adjusted HR = 1.95, 95% CI: 1.60-2.37). Similarly, loss of skeletal muscle mass was associated with tumor recurrence (crude HR = 1.85, 95% CI: 1.44-2.37; adjusted HR = 1.76, 95% CI: 1.27-2.45). The stratified analysis showed that treatment types and inclusion of body mass index or body weight in the Cox regression model did not modify both clinical outcomes. With an increase in cut-off values of muscle mass on computed tomography images (especially for male patients), there was an insignificant trend of stronger associations between loss of skeletal muscle mass and all-cause mortality. Conclusion: Loss of skeletal muscle mass is associated with increased all-cause mortality and tumor recurrence in patients with HCC. Further prospective studies incorporating measurements of muscle strength and physical function are warranted to see whether inclusion of both parameters better predicts the outcome than use of muscle mass only.
The Depression, Anxiety and Stress Scale (DASS-21) as a Screener for Depression in Substance Use Disorder Inpatients: A Pilot Study
Authors: Beaufort Ilse N. , De Weert-Van Oene Gerdien H. , Buwalda Victor A.J. , de Leeuw J. Rob J. , Goudriaan Anna E.
Published: December 2017

Depression is a common co-morbid disorder in substance use disorder (SUD) patients. Hence, valid instruments are needed to screen for depression in this subpopulation. In this study, the predictive validity of the Depression, Anxiety and Stress Scale (DASS-21) for the presence of a depressive disorder was investigated in SUD inpatients. Furthermore, differences between DASS-21 scores at intake and those recorded one week after inpatient detoxification were assessed in order to determine the measurement point of the assessment of the DASS-21 leading to the best predictive validity. The DASS-21 was administered to 47 patients at intake and shortly after inpatient detoxification. The results of the DASS-21 were compared to the Mini International Neuropsychiatric Interview (MINI), which served as the gold standard. Levels of sensitivity and specificity of 78–89% and 71–76% were found for the DASS-21 assessed after detoxification, satisfactorily predicting depression as diagnosed with the MINI. Total DASS-21 scores as well as the DASS subscale for depression were significantly reduced at the second measurement, compared to the DASS at intake. We conclude that the DASS-21 may be a suitable instrument to screen for depressive disorders in SUD patients when administered (shortly) after detoxification. Future research is needed to support this conclusion.
MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1
Authors: Zhou Bin , Sun Chuandong , Hu Xiao , Zhan Hanxiang , Zou Hao , Feng Yujie , Qiu Fabo , Zhang Shun , Wu Liqun , Zhang Bingyuan
Published: December 2017

Background/Aims: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. Methods: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis. Bioinformatics tools were used to identify the target gene of miR-195. Effects of miR-195 and DCLK1 on proliferation and cell cycle of PC cells were analyzed by MTT, colony formation assays and flow cytometry. Transwell and wound-healing experiments were employed to examine the cellular migration and invasion. A xenograft mouse model was also used to test the effects of miR-195 on tumor growth and metastasis in vivo. Results: The expression level of DCLK1 and miR-195 shows an inverse correlation in PC tissues and cell lines. A higher DCLK1 level is associated with higher TNM (tumor, node, and metastasis) stage, higher rate of lymph node metastasis, and poor survival. Luciferase reporter assay shows that miR-195 directly targets DCLK1. Overexpression of miR-195 inhibits proliferation, migration and invasion of PC cells, whereas downregulation of miR-195 has an opposite role. These actions were similar to the effects of knockdown and overexpression of DCLK1, respectively. Conclusions: These data suggest that miR-195 has tumor suppressor roles in PC by targeting DCLK1. MiR-195-DCLK1 pathway may provide insight into PC progression and represent a novel, promising diagnostic and therapeutic target for PC.
Novel Mitochondria-Targeting Peptide in Heart Failure Treatment
Authors: Daubert Melissa A. , Yow Eric , Dunn Gary , Marchev Sotir , Barnhart Huiman , Douglas Pamela S. , O’Connor Christopher , Goldstein Sidney , Udelson James E. , Sabbah Hani N.
Published: December 2017

Background

Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction.

Methods and Results

In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg
−1
·h
−1
) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (−18 mL;
P
=0.009) and end-systolic volume (−14 mL;
P
=0.005) occurred at end infusion in the highest dose cohort.

Conclusions

This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose–effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02388464.
Ten-Year Mortality in the WISE Study (Women’s Ischemia Syndrome Evaluation)
Authors: Kenkre Tanya S. , Malhotra Pankaj , Johnson B. Delia , Handberg Eileen M. , Thompson Diane V. , Marroquin Oscar C. , Rogers William J. , Pepine Carl J. , Bairey Merz C. Noel , Kelsey Sheryl F.
Published: December 2017

Background—

The WISE study (Women’s Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited.

Methods and Results—

Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2–11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate.

Conclusions—

Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.
Learning Midlevel Auditory Codes from Natural Sound Statistics
Authors: Młynarski Wiktor , McDermott Josh H.
Published: December 2017

Interaction with the world requires an organism to transform sensory signals into representations in which behaviorally meaningful properties of the environment are made explicit. These representations are derived through cascades of neuronal processing stages in which neurons at each stage recode the output of preceding stages. Explanations of sensory coding may thus involve understanding how low-level patterns are combined into more complex structures. To gain insight into such midlevel representations for sound, we designed a hierarchical generative model of natural sounds that learns combinations of spectrotemporal features from natural stimulus statistics. In the first layer, the model forms a sparse convolutional code of spectrograms using a dictionary of learned spectrotemporal kernels. To generalize from specific kernel activation patterns, the second layer encodes patterns of time-varying magnitude of multiple first-layer coefficients. When trained on corpora of speech and environmental sounds, some second-layer units learned to group similar spectrotemporal features. Others instantiate opponency between distinct sets of features. Such groupings might be instantiated by neurons in the auditory cortex, providing a hypothesis for midlevel neuronal computation.
Typifications and taxonomic notes for Veronica subgen. Pseudolysimachium (Plantaginaceae) based on material from the Hungarian Natural History Museum Budapest (BP)
Authors: ALBACH DIRK C. , PIFKÓ DÁNIEL , BARINA ZOLTÁN
Published: December 2017

Veronica subgen. Pseudolysimachium is a group of 30 species ranging across northern Eurasia in various open habitats from dry steppe to swamps. It includes several horticulturally important species that have been crossed in the past. As such, it exemplifies a group with long taxonomic tradition, exemplified by more than 600 valid names, which also indicates its variability. In the process of identifying the evolutionary important units, molecular markers have started to help immensely. However, assigning names to identified significant groups of populations has been hindered by problems in typification. Here, we try to alleviate the problem for the taxa in southeastern Europe, which have been analyzed rigorously using AFLP fingerprints in the past, by lectotypifying 11 names and neotypifying four names, mostly based on specimens found in the Hungarian Natural History Museum Budapest (BP). This allowed revising Veronica barrelieri with its three subspecies and synonyms.