bluuebunny/crossref_metadata_2025 huggingface dataset:
Feature Extraction Acceleration to Stabilize Execution Time for Real-Time Applications in Low-Cost Embedded Systems
Authors: Kim Taek Kyu
Published: July 2019

Extracted features are widely used for image processing. Many research endeavors have been undertaken to extract significant features of fast moving images. Appropriate algorithm processing is necessary to extract features and provide features to the other modules in real time with low-cost embedded systems. The features from accelerated segment test (FAST) algorithm is renowned for feature extraction. FAST is composed of simple arithmetic operators. In this study, FAST is employed to implement the hardware accelerator in a field-programmable gate array for small embedded systems. Meanwhile, the threshold value in FAST affects the number of extracted features and the execution time. The precarious execution time makes it difficult for the system to schedule the timing of system functions and thus degrades the performance. An appropriate method is necessary to stabilize the execution time. A dynamic threshold controller in a FAST hardware accelerator is thus proposed to enable a stable execution time. A proportional integral controller composed of an adder, subtractor, and shifter is applied for low design implementation costs. The proposed approach occupies 2,263 slice flip-flops, 3,498 look-up tables, and 17 block RAMs in a Xilinx Virtex 5 FX field-programmable gate array. It requires 3.87[Formula: see text]ms for continuous 800×480 images from the KITTI benchmark.
Knowledge Management and Institutional Accounting Functional Effectiveness: Evidence from Malaysia
Authors: Ayodele Freida Ozavize , Yao Liu , Haron Hasnah Binti , Dabor Eyasan Leslie
Published: July 2019

Institutional accounting functions are critical actors in the success of every organisation and emphasise distinct effectiveness compared to other practices. Meanwhile existing research has examined general knowledge management (KM) and its association with effectiveness at an overall institutional level. However, studies on the impact of KM capabilities on institutional accounting functional effectiveness (FE) is sparse. This study evaluates the impact of KM on institutional accounting FE based on resource-based theory (RBT) at various levels of analysis. Utilising empirical evidence, accounting knowledge management (AKM)-based effectiveness model was developed. Data were collected through a questionnaire survey of accounting officers in public research institutions in Malaysia. The study data were initially analysed using statistical package for social sciences (SPSS) version 23.0 and hypothesised relationship tested via partial least square structural equation modelling (PLS-SEM). Interestingly, the results provide support for the developed research AKM model underpinned by RBT viewpoint. AKM infrastructure (AKMI) and process capabilities impact institutional accounting FE significantly and AKM process capability partially mediates the influence of AKMI capability. The study offers new insight into the relationship between KM and institutional accounting practices. Thus, they create avenues for future research and directions for KM policy decisions in institutions.
Generalized Vojta–Rémond inequality
Authors: Dill Gabriel A.
Published: July 2019

Following and generalizing unpublished work of Ange, we prove a generalized version of Rémond’s generalized Vojta inequality. This generalization can be applied to arbitrary products of irreducible positive-dimensional projective varieties, defined over the field of algebraic numbers, instead of powers of one fixed such variety. The proof runs closely along the lines of Rémond’s proof.
Thermal-aware Real-time Scheduling Using Timed Continuous Petri Nets
Authors: Desirena-López G. , Ramírez-Treviño A. , Briz J. L. , Vázquez C. R. , Gómez-Gutiérrez D.
Published: July 2019

We present a thermal-aware, hard real-time (HRT) global scheduler for a multiprocessor system designed upon three novel techinques. First, we present a modeling methodology based on Timed Continuous Petri nets (TCPN) that yields a complete state variable model, including job arrivals, CPU usage, power, and thermal behavior. The model is accurate and avoids the calibration stage of
RC
thermal models. Second, based on this model, a linear programming problem (LPP) determines the existence of a feasible HRT thermal-aware schedule. Last, a sliding-mode controller and an online discretization algorithm implement the global HRT scheduler, which is capable of managing thermal constraints, context switching, migrations, and disturbances.
On the Endurance of the d-Choices Garbage Collection Algorithm for Flash-Based SSDs
Authors: Verschoren Robin , Houdt Benny Van
Published: July 2019

Garbage collection (GC) algorithms for flash-based solid-state drives (SSDs) have a profound impact on its performance and many studies have focused on assessing the so-called write amplification of various GC algorithms. In this article, we consider the family of
d
-choices GC algorithms and study (a) the extent in which these algorithms induce unequal wear and (b) the manner in which they affect the lifetime of the drive. For this purpose, we introduce two performance measures: PE fairness and SSD endurance. We study the impact of the
d
-choices GC algorithm on both these measures under different workloads (uniform, synthetic and trace-based) when combined with two different write modes. Numerical results show that the more complex of the two write modes, which requires hot/cold data identification, may not necessarily give rise to a significantly better SSD endurance. Further, the
d
-choices GC algorithm is often shown to strike a good balance between garbage collection and wear leveling for small
d
values (e.g.,
d
= 10), yielding high endurance.
Static Identification of Injection Attacks in Java
Authors: Spoto Fausto , Burato Elisa , Ernst Michael D. , Ferrara Pietro , Lovato Alberto , Macedonio Damiano , Spiridon Ciprian
Published: July 2019

The most dangerous security-related software errors, according to the OWASP Top Ten 2017 list, affect web applications. They are potential injection attacks that exploit user-provided data to execute undesired operations: database access and updates (
SQL injection
); generation of malicious web pages (
cross-site scripting injection
); redirection to user-specified web pages (
redirect injection
); execution of OS commands and arbitrary scripts (
command injection
); loading of user-specified, possibly heavy or dangerous classes at run time (
reflection injection
); access to arbitrary files on the file system (
path-traversal
); and storing user-provided data into heap regions normally assumed to be shielded from the outside world (
trust boundary violation
). All these attacks exploit the same weakness: unconstrained propagation of data from
sources
that the user of a web application controls into
sinks
whose activation might trigger dangerous operations. Although web applications are written in a variety of languages, Java remains a frequent choice, in particular for banking applications, where security has tangible relevance.

This article defines a unified, sound protection mechanism against such attacks, based on the identification of all possible explicit flows of
tainted
data in Java code. Such flows can be arbitrarily complex, passing through dynamically allocated data structures in the heap. The analysis is based on abstract interpretation and is interprocedural, flow-sensitive, and context-sensitive. Its notion of taint applies to reference (non-primitive) types dynamically allocated in the heap and is object-sensitive and field-sensitive. The analysis works by translating the program into Boolean formulas that model all possible data flows. Its implementation, within the Julia analyzer for Java and Android, found injection security vulnerabilities in the Internet banking service and in the customer relationship management of large Italian banks, as well as in a set of open-source third-party applications. It found the command injection, which is at the origin of the 2017 Equifax data breach, one of the worst data breaches ever. For objective, repeatable results, this article also evaluates the implementation on two open-source security benchmarks: the Juliet Suite and the OWASP Benchmark for the automatic comparison of static analyzers for cybersecurity. We compared this technique against more than 10 other static analyzers, both free and commercial. The result of these experiments is that ours is the only analysis for injection that is sound (up to well-stated limitations such as multithreading and native code) and works on industrial code, and it is also much more precise than other tools.
Failure Recovery in Resilient X10
Authors: Grove David , Hamouda Sara S. , Herta Benjamin , Iyengar Arun , Kawachiya Kiyokuni , Milthorpe Josh , Saraswat Vijay , Shinnar Avraham , Takeuchi Mikio , Tardieu Olivier
Published: July 2019

Cloud computing has made the resources needed to execute large-scale in-memory distributed computations widely available. Specialized programming models, e.g., MapReduce, have emerged to offer transparent fault tolerance and fault recovery for specific computational patterns, but they sacrifice generality. In contrast, the Resilient X10 programming language adds
failure containment
and
failure awareness
to a general purpose, distributed programming language. A Resilient X10 application spans over a number of places. Its formal semantics precisely specify how it continues executing after a place failure. Thanks to failure awareness, the X10 programmer can in principle build redundancy into an application to recover from failures. In practice, however, correctness is elusive, as redundancy and recovery are often complex programming tasks.

This article further develops Resilient X10 to shift the focus from failure awareness to failure recovery, from both a theoretical and a practical standpoint. We rigorously define the distinction between recoverable and catastrophic failures. We revisit the
happens-before invariance
principle and its implementation. We shift most of the burden of redundancy and recovery from the programmer to the runtime system and standard library. We make it easy to protect critical data from failure using resilient stores and harness elasticity—dynamic place creation—to persist not just the data but also its spatial distribution.

We demonstrate the flexibility and practical usefulness of Resilient X10 by building several representative high-performance in-memory parallel application kernels and frameworks. These codes are 10× to 25× larger than previous Resilient X10 benchmarks. For each application kernel, the average runtime overhead of resiliency is less than 7%. By comparing application kernels written in the Resilient X10 and Spark programming models, we demonstrate that Resilient X10’s more general programming model can enable significantly better application performance for resilient in-memory distributed computations.
Time-Sync Video Tag Extraction Using Semantic Association Graph
Authors: Yang Wenmain , Wang Kun , Ruan Na , Gao Wenyuan , Jia Weijia , Zhao Wei , Liu Nan , Zhang Yunyong
Published: July 2019

Time-sync comments (TSCs) reveal a new way of extracting the online video tags. However, such TSCs have lots of noises due to users’ diverse comments, introducing great challenges for accurate and fast video tag extractions. In this article, we propose an unsupervised video tag extraction algorithm named Semantic Weight-Inverse Document Frequency (SW-IDF). Specifically, we first generate corresponding semantic association graph (SAG) using semantic similarities and timestamps of the TSCs. Second, we propose two graph cluster algorithms, i.e., dialogue-based algorithm and topic center-based algorithm, to deal with the videos with different density of comments. Third, we design a graph iteration algorithm to assign the weight to each comment based on the degrees of the clustered subgraphs, which can differentiate the meaningful comments from the noises. Finally, we gain the weight of each word by combining Semantic Weight (SW) and Inverse Document Frequency (IDF). In this way, the video tags are extracted automatically in an unsupervised way. Extensive experiments have shown that SW-IDF (dialogue-based algorithm) achieves 0.4210 F1-score and 0.4932 MAP (Mean Average Precision) in high-density comments, 0.4267 F1-score and 0.3623 MAP in low-density comments; while SW-IDF (topic center-based algorithm) achieves 0.4444 F1-score and 0.5122 MAP in high-density comments, 0.4207 F1-score and 0.3522 MAP in low-density comments. It has a better performance than the state-of-the-art unsupervised algorithms in both F1-score and MAP.
PGC-1α regulates mitochondrial properties beyond biogenesis with aging and exercise training
Authors: Halling Jens Frey , Jessen Henrik , Nøhr-Meldgaard Jacob , Buch Bjørg Thiellesen , Christensen Natascha Masselkhi , Gudiksen Anders , Ringholm Stine , Neufer P. Darrell , Prats Clara , Pilegaard Henriette
Published: July 2019

Impaired mitochondrial function has been implicated in the pathogenesis of age-associated metabolic diseases through regulation of cellular redox balance. Exercise training is known to promote mitochondrial biogenesis in part through induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Recently, mitochondrial ADP sensitivity has been linked to reactive oxygen species (ROS) emission with potential impact on age-associated physiological outcomes, but the underlying molecular mechanisms remain unclear. Therefore, the present study investigated the effects of aging and exercise training on mitochondrial properties beyond biogenesis, including respiratory capacity, ADP sensitivity, ROS emission, and mitochondrial network structure, in myofibers from inducible muscle-specific PGC-1α-knockout mice and control mice. Aged mice displayed lower running endurance and mitochondrial respiratory capacity than young mice. This was associated with intermyofibrillar mitochondrial network fragmentation, diminished submaximal ADP-stimulated respiration, increased mitochondrial ROS emission, and oxidative stress. Exercise training reversed the decline in maximal respiratory capacity independent of PGC-1α, whereas exercise training rescued the age-related mitochondrial network fragmentation and the impaired submaximal ADP-stimulated respiration in a PGC-1α-dependent manner. Furthermore, lack of PGC-1α was associated with altered phosphorylation and carbonylation of the inner mitochondrial membrane ADP/ATP exchanger adenine nucleotide translocase 1. In conclusion, the present study provides evidence that PGC-1α regulates submaximal ADP-stimulated respiration, ROS emission, and mitochondrial network structure in mouse skeletal muscle during aging and exercise training.
Fast Determination of the Main Reduced Sulfur Species in Aquatic Systems by a Direct and Second-Derivative Spectrophotometric Method
Authors: Dupraz Sébastien , Ménez Bénédicte , Guyot François
Published: July 2019

The determination of reduced sulfur species in aquatic systems is not an easy and fast task to accomplish regarding the numerous possible interferences and risks of oxidation that occur with the usual methods of quantification. The method presented here is a direct spectrophotometric method that can be used to quantify sulfides, sulfites, and thiosulfates in a simple and rapid way. The principle is based on the comparison of second-derivative absorbance spectra of the same sample at different pH (9.2, 4.7, and 1.0) and selected absorption wavelengths (250 and 278 nm). This method has been successfully tested and has demonstrated liability to (i) avoid the biases due to absorbance overlaps between the different major chemical species and (ii) keep, as a direct method, the advantages over indirect methods on interferences reduction. The limits of detections (LOD) reached for total sulfide, sulfite, and thiosulfate are 1.37, 7.32, and 1.92 µM, respectively. The method displays low accuracy mean and low relative standard deviation (<4%) as well as a good linearity (R2 > 0.999). Accordingly, this method represents a very robust alternative in terms of cost and rapidity for the quantification of reduced sulfur species in different aquatic environments, from freshwaters to saline and polluted systems.
Time‐Dependent Reliability Analysis of RC Deep Beams considering Linear/Nonlinear Creep and Shrinkage Using ANFIS Network and MCS
Authors: Beheshti Aval Seyed Bahram , Ghabdian Mohsen
Published: July 2019

This paper comprehensively studies the effects of linear and nonlinear creep and shrinkage on shear strength and deformation of reinforced concrete (RC) deep beams through a time‐dependent reliability analysis framework. The three‐dimensional finite element‐based program of ABAQUS was used to model RC deep beams. A viscoelastic approach was adopted to model linear creep and shrinkage by a user‐defined material model developed and implemented in user subroutines UMAT and UEXPAN. The software was initially examined using two experimental results for short/long‐term behavior of shallow and deep concrete beams. In the nonlinear range, creep was taken into account by the affinity hypothesis theorem to consider the effect of high‐level sustained loading. Due to the complicated and time‐consuming nature of the finite element method (FEM), adaptive neuro‐fuzzy inference system (ANFIS) and Monte Carlo simulation (MCS) replaced these complex analyses. Finally, based on the numerical results obtained from the analyses of case study samples, it was concluded that, in a serviceability limit state, for RC deep beams, the probability of failure was reduced to less than one‐fifth that for the shallow beams. On the contrary, in a strength limit state, a safety factor of about 1.7∼1.8 could be considered for the effect of sustained high‐level loading on the shear strength of RC deep beams.
Feasibility of Screening Primary Aldosteronism by Aldosterone-to-Direct Renin Concentration Ratio Derived from Chemiluminescent Immunoassay Measurement: Diagnostic Accuracy and Cutoff Value
Authors: Li Tianqi , Ma Yeshuo , Zhang Ying , Liu Yue , Fu Tingting , Zhang Ri , Kang Kai , Yang Yingchao , Wang Lixin , Jiang Yinong , Lu Yan
Published: July 2019

Objectives. Aldosterone-to-plasma renin activity ratio (ARR) derived from traditional radioimmunoassay (RIA) is widely used to detect primary aldosteronism (PA). Recently, aldosterone-to-direct renin concentration ratio (ADRR), which is calculated by direct renin concentration (DRC) measured by chemiluminescent immunoassay (CLIA), is proposed to replace ARR as the screening test method for PA. The purpose of the present study was to estimate the diagnostic accuracy and cutoff value of ADRR as screening test for PA. Methods. 450 hypertensive patients with suspected PA referred to hypertension center of our department were enrolled and underwent screening and confirmatory tests of PA. Plasma renin activity (PRA), DRC, and plasma aldosterone concentration (PAC) were measured by both RIA and CLIA simultaneously during screening and confirmatory test. Results. 386 patients were diagnosed as primary hypertension (PH) and 64 patients as PA. Within-patient correlation between PRA and DRC (r=0.88, P<0.001) and correlation between PAC measured by RIA and CLIA were high (r=0.80, P<0.001). The optimal cutoff value of ADRR was 2.93 (ng/dL)/(mU/L), sensitivity 80.33%, and specificity 92.11%. The optimal cutoff value of ARR was 25.28 (ng/dL)/(ng/mL/h), sensitivity 76.92%, and specificity 93.38%. Conclusion. The optimal cutoff values of ADRR and ARR for screening PA are defined in this patient cohort with high sensitivity and specificity. Our results are of clinical importance for accelerating the extensive use of ADRR as a screening test for PA in daily practice.
A Systems Pharmacology-Based Study of the Molecular Mechanisms of San Cao Decoction for Treating Hypertension
Authors: Ma Chongyang , Zhai Changming , Xu Tian , Lu Fang , Zhang Shuang , Li Changxiang , Wang Qingguo , Cheng Fafeng , Wang Xueqian
Published: July 2019

Traditional Chinese medicine (TCM) has a longstanding history and has gained widespread clinical applications. San Cao Decoction (SCD) is an experience prescription first formulated by Prof. Duzhou Liu. We previously demonstrated its antihypertensive effects; however, to systematically explain the underlying mechanisms of action, we employed a systems pharmacology approach for pharmacokinetic screening and target prediction by constructing protein-protein interaction networks of hypertension-related and putative SCD-related targets, and Database for Annotation, Visualization, and Integrated Discovery enrichment analysis. We identified 123 active compounds in SCD and 116 hypertension-related targets. Furthermore, the enrichment analysis of the drug-target network showed that SCD acts in a multidimensional manner to regulate PI3K-Akt-endothelial nitric oxide synthase signaling to maintain blood pressure. Our results highlighted the molecular mechanisms of antihypertensive actions of medicinal herbs at a systematic level.
Adaptive Guaranteed-Performance Consensus Control for Multi-Agent Systems with an Adjustable Convergence Speed
Authors: Ma Haiying , Jia Xiao , Cai Ning , Xi Jianxiang
Published: July 2019

In this paper, adaptive guaranteed-performance consensus control problems for multiagent systems with an adjustable convergence speed are investigated. A novel adaptive guaranteed-performance consensus protocol is proposed, where the communication weights can be adaptively regulated. By the state space decomposition method and the stability theory, sufficient conditions for guaranteed-performance consensus are obtained and the guaranteed-performance cost is determined. Moreover, the lower bound of the convergence coefficient for multiagent systems is deduced, which is linearly adjustable approximately by changing the adaptive control gain. Finally, simulation examples are introduced to demonstrate theoretical results.
Novel Protein-Repellent and Antibacterial Resins and Cements to Inhibit Lesions and Protect Teeth
Authors: Cao Li , Wu Junling , Zhang Qiang , Baras Bashayer , Bhadila Ghalia , Li Yuncong , Melo Mary Anne S. , Weir Michael D. , Bai Yuxing , Zhang Ning , Xu Hockin H. K.
Published: July 2019

Orthodontic treatment is increasingly popular as people worldwide seek esthetics and better quality of life. In orthodontic treatment, complex appliances and retainers are placed in the patients’ mouths for at least one year, which often lead to biofilm plaque accumulation. This in turn increases the caries-inducing bacteria, decreases the pH of the retained plaque on an enamel surface, and causes white spot lesions (WSLs) in enamel. This article reviews the cutting-edge research on a new class of bioactive and therapeutic dental resins, cements, and adhesives that can inhibit biofilms and protect tooth structures. The novel approaches include the use of protein-repellent and anticaries polymeric dental cements containing 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); multifunctional resins that can inhibit enamel demineralization; protein-repellent and self-etching adhesives to greatly reduce oral biofilm growth; and novel polymethyl methacrylate resins to suppress oral biofilms and acid production. These new materials could reduce biofilm attachment, raise local biofilm pH, and facilitate the remineralization to protect the teeth. This novel class of dental resin with dual benefits of antibacterial and protein-repellent capabilities has the potential for a wide range of dental and biomedical applications to inhibit bacterial infection and protect the tissues.
Game Research on Coal Mine Workers’ Off‐Post Behaviors
Authors: Zeng Jun , Yao Qingguo , Wang Xinhua , Zhang Yansong
Published: July 2019

In order to seek for causes and solutions of off‐post behaviors of coal miners, static and evolutionary games were utilized on the basis of an established strategy simulation model between coal mine enterprise and coal miners. These games were used to determine the revenue matrix of two game parties given off‐post behaviors of coal miners from two levels (coal miners and coal mine enterprise). Thus, equilibrium and dynamic evolutionary analyses of the two parties should be conducted. Results indicated that, in the enterprise’s perspective, inspection cost and punishment intensity are important factors that influence the safety production and economic benefit of coal mine enterprises; in the coal miners’ perspective, wage loss and the constraint degree it generates are essential factors. Furthermore, these factors constitute a key to solving off‐post behaviors of coal miners. Reasonability of the established simulation model was analyzed and verified on the basis of off‐post behaviors of workers from a coal mine that belongs to Yanzhou Coal Mining Co., Ltd. The coal mine enterprise should enhance the inspection of safety production and establish scientific and complete off‐post punishment mechanism. Moreover, the coal mine enterprise should provide proper compensation, treatment, and reward policies of workers to reduce the off‐post behaviors of workers from a coal mine enterprise effectively.
A Proposal for Long-Term Missions of Small Lunar Rovers Using an MLI Curtain System
Authors: Lee Jang-Joon , Kim Kyu-Hong
Published: July 2019

This paper proposes a lunar night survival method for small rovers using an MLI (Multilayer Insulation) curtain system for long-term missions. Until recently, it was difficult to install RHU (Radioisotope Heating Units) or other temperature maintenance devices on small lunar rovers to enable lunar night survival, and so such rovers could only perform short two-week missions. Thermal analysis results show that small rovers could survive during lunar nights by moving into a shelter located inside the MLI curtain of the lander without mounting temperature maintenance devices. In order to enhance the feasibility of the MLI curtain system, we also propose ideas of a double-layer MLI and a rover configuration without solar cells.
Measurement of the Orbital Soft Tissue Volume in Chinese Adults Based on Three-Dimensional CT Reconstruction
Authors: Du Yi , Lu Bing-Yao , Chen Jun , He Jian-Feng
Published: July 2019

Quantitative measurement of the orbital soft tissue volume plays a very important role in the study of orbital diseases. The purpose of this study is to establish a computed tomography- (CT-) based three-dimensional (3D) reconstruction model and measure the orbital soft tissue volume in Chinese adults. We collected data from 103 Chinese adults (52 males and 51 females) who underwent orbital CT. The CT images of these adults were used to reconstruct a 3D model of the orbital bony cavity, orbital fat, extraocular muscle, and intraorbital optic nerve using Mimics software, and their respective volumes were measured. The mean (±SD) orbital bony cavity volume (OV), orbital fat volume (FV), extraocular muscle volume (MV), and intraorbital optic nerve volume (iONV) of the males were 22.2 ± 2.2 cm3, 8.9 ± 1.8 cm3, 1.9 ± 0.34 cm3, and 0.41 ± 0.08 cm3, respectively. The mean OV, FV, MV, and iONV of the females were 20.2 ± 1.5 cm3, 8.1 ± 1.7 cm3, 1.6 ± 0.3 cm3, and 0.36 ± 0.074 cm3, respectively, which were all significantly lower than those in males (all p<0.05). FV (r = 0.370; p<0.001) and MV (r = 0.283; p=0.007) were significantly correlated with body mass index (BMI), while iONV was not correlated with BMI (r = −0.070; p=0.480). This study shows that FV, MV, and iONV were higher in males than in females. With increasing BMI, FV and MV both increased, but iONV did not exhibit this trend.
Immobilizing A Moving Target: CAR T Cells Hit CD22
Authors: Guedan Sonia , Delgado Julio
Published: July 2019

A key mechanism of resistance to chimeric antigen receptor–modified T cells (CAR-T) is loss or downregulation of target antigens. Low antigen expression on cancer cells prevents full CAR-T-cell activation and persistence. Pharmacologic modulation of target antigen expression offers a novel therapeutic strategy to drive more potent and durable responses.

See related article by Ramakrishna et al., p. 5329
Immune Checkpoint Blockade Enhances Shared Neoantigen-Induced T-cell Immunity Directed against Mutated Calreticulin in Myeloproliferative Neoplasms
Authors: Cimen Bozkus Cansu , Roudko Vladimir , Finnigan John P. , Mascarenhas John , Hoffman Ronald , Iancu-Rubin Camelia , Bhardwaj Nina
Published: July 2019

Somatic frameshift mutations in the calreticulin (CALR) gene are key drivers of cellular transformation in myeloproliferative neoplasms (MPN). All patients carrying these mutations (CALR+ MPN) share an identical sequence in the C-terminus of the mutated CALR protein (mut-CALR), with the potential for utility as a shared neoantigen. Here, we demonstrate that although a subset of patients with CALR+ MPN develop specific T-cell responses against the mut-CALR C-terminus, PD-1 or CTLA4 expression abrogates the full complement of responses. Significantly, blockade of PD-1 and CLTA4 ex vivo by mAbs and of PD-1 in vivo by pembrolizumab administration restores mut-CALR–specific T-cell immunity in some patients with CALR+ MPN. Moreover, mut-CALR elicits antigen-specific responses from both CD4+ and CD8+ T cells, confirming its broad applicability as an immunogen. Collectively, these results establish mut-CALR as a shared, MPN-specific neoantigen and inform the design of novel immunotherapies targeting mut-CALR.

Significance:

Current treatment modalities for MPN are not effective in eliminating malignant cells. Here, we show that mutations in the CALR gene, which drive transformation in MPN, elicit T-cell responses that can be further enhanced by checkpoint blockade, suggesting immunotherapies could be employed to eliminate CALR+ malignant cells in MPN.

This article is highlighted in the In This Issue feature, p. 1143
Determinants of Functional Independence or Its Loss following Subthalamic Nucleus Stimulation in Parkinson’s Disease
Authors: Kim Ryul , Yoo Dallah , Jung Yu Jin  , Lee Woong-Woo , Ehm Gwanhee , Yun Ji Young , Kim Hee Jin , Lee Jee-Young , Kim Ji-Young , Kim Han-Joon , Paek Sun Ha , Jeon Beomseok
Published: July 2019

Objective: This study aimed to describe the change in functional status following bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson’s disease (PD) and to identify predictors of postoperative functional dependence. Methods: We included PD patients with bilateral STN-DBS who had complete Schwab & England Activities of Daily Living (S&E ADL) Scale data at baseline and 6 months after surgery from our prospective registry. Functional dependence was defined as an S&E ADL score of less than 80%. All data were collected from the on-medication state and on-stimulation state (after surgery). Logistic regression analyses were performed to determine the factors predictive of functional dependence after surgery. Results: A total of 196 patients were included. At baseline, 41 patients were functionally dependent and the other 155 were functionally independent. Among the patients with preoperative dependence, 32 (78%) became functionally independent after surgery, and this conversion was associated with a lower baseline axial score (p = 0.012). Among the patients with preoperative independence, 21 (14%) developed postoperative dependence, and this conversion was associated with a higher baseline axial score (p = 0.013) and its smaller improvement (p < 0.001). Female sex (odds ratio [OR] 3.214; 95% confidence interval [CI] 1.210–8.542; p = 0.019) and a higher baseline axial score (OR 1.184; 95% CI 1.056–1.327; p = 0.004) significantly predicted the risk of postoperative functional dependence. Conclusions: We found that functional status following bilateral STN-DBS is closely related to preoperative axial symptoms. When loss of independence is a potential target for STN-DBS, clinicians should take into consideration the severity of axial impairment before surgery.
Delayed Cord Clamping versus Early Cord Clamping in Elective Cesarean Section: A Randomized Controlled Trial
Authors: Cavallin Francesco , Galeazzo Beatrice , Loretelli Vittoria , Madella Stefania , Pizzolato Martina , Visentin Silvia , Trevisanuto Daniele
Published: July 2019

Background: Delaying cord clamping is recommended in order to assure placental transfusion. However, the evidence on cord management in elective cesarean section (CS) is limited. Objective: To compare delayed cord clamping (DCC) with early cord clamping (ECC) with regard to postnatal adaptation in neonates born through elective CS. Methods: All neonates born ≥39 weeks’ gestation born through elective CS were assigned to either the DCC or the ECC arm at a 1:1 ratio according to a computer-generated, randomized sequence. The primary outcome was the hematocrit at day 2 of life. Secondary outcomes included: preductal oxygen saturation and heart rate during the first 10 min of life; transcutaneous bilirubin at day 3; and neonatal blood pressures in the first 3 days of life. Additional outcomes included: time to first spontaneous breath; temperature at admission to normal nursery; weight at discharge; and maternal blood losses. Results: Eighty neonates were randomized to the DCC (n = 40) or the ECC (n = 40) arm. The hematocrit at day 2 was significantly higher in the DCC arm than in the ECC arm (mean difference: 6%; 95% CI 3–8; p < 0.0001). The secondary outcome measures were not statistically different between the two arms. No infants needed phototherapy for hyperbilirubinemia during their hospital stay. Conclusions: Delaying cord clamping beyond 60 s increases the hematocrit at day 2 in neonates born through elective CS, without affecting maternal blood losses. Our findings suggest that DCC should be recommended in elective CS, but further studies are warranted to assess long-term outcomes.
Validation of the German Version of the Power of Food Scale in a General Population Sample
Authors: Andreeva Elena , Neumann Maria , Nöhre Mariel , Brähler Elmar , Hilbert Anja , de Zwaan Martina
Published: July 2019

Objective: The Power of Food Scale (PFS) is a self-report instrument for assessing appetitive motivation in the absence of caloric needs. The study aim was to validate the German PFS version in a large population sample. Methods: Complete information on all PFS items was available from 2,421 respondents (age ≥14) of a nationally representative sample of the German population. We examined the psychometric properties of the German PFS version and provided population-based normative data. Results: The 3-factor structure of the original scale was replicated in confirmatory factor analysis. The German PFS version demonstrated good internal consistency (α = 0.92 for the total scale). It was well accepted by the respondents, as indicated by a low proportion of missing item values (≤0.56%). While no significant differences were observed in the PFS mean scores between men and women, the scores increased across BMI categories. PFS was positively correlated with a measure of global eating disorder psychopathology (Eating Disorder Examination-Questionnaire 8) and the ultra-brief Patient Health Questionnaire for depression and anxiety. Conclusions: Our findings suggest that the German PFS version has adequate psychometric properties and good reliability for measuring hedonic hunger in the general population. The provided population-based norms can be used for individual assessment.
The Significance of Vascular Alterations in Acute and Chronic Rejection for Vascularized Composite Allotransplantation
Authors: Kollar Branislav , Kamat Pranitha , Klein Holger J. , Waldner Matthias , Schweizer Riccardo , Plock Jan A.
Published: July 2019

Vascularized composite allotransplantation (VCA) has emerged as a useful reconstructive option for patients suffering from major tissue defects and functional deficits. While the technical feasibility has been optimized and more than 130 VCAs have been performed during the last two decades, hurdles such as acute and chronic allograft rejection, graft deterioration, and eventual functional impairment need to be addressed. Recently, chronic graft rejection and progressive failure have been linked to vascular alterations observed in the allografts. Graft vasculopathy (GV) may play a pivotal role in long-term graft deterioration. The understanding of the underlying pathophysiological processes and their initial triggers is of utmost importance in the prevention, attenuation, and therapy of GV. While there are reports on the etiology and development of GV in solid organ transplantation, there are limited data with respect to chronic rejection and GV in the realm of VCA. Nevertheless, recent reports from long-term VCA recipients suggest that GV could truly jeopardize allografts in the follow-up evaluation. Chronic rejection and GV include different entities and might have different pathways in distinct organs. Herein, we reviewed the current literature on vascular changes during both acute and chronic allograft rejection, with a focus on their clinical and translational significance for VCA.
Validation of Microbiological Testing of Cellular Medicinal Products Containing Antibiotics
Authors: Lotfi Ramin , Rojewski Markus Thomas , Zeplin Philip H. , Funk Wolfgang , Pullig Oliver , Nöth Ulrich , Schrezenmeier Hubert
Published: July 2019

Background: The risk of microbial contamination of cellular products can be reduced when cultured in the presence of antibiotics. This however, may impact the sensitivity of microbiological tests. Given that the addition of antibiotics to cell/tissue products does not guarantee sterility but may just reduce the proliferation rate of microorganisms, microbiological testing of medicinal products remains obligatory. Thus, an appropriate method to test for microbial contamination of antibiotic-containing products has to be validated. Objectives: In the context of microbiological testing of a cellular advance therapy medicinal product, the method was validated and approved by German competent authorities for four different matrices with three matrices containing antibiotics. The paper shall provide help for establishing test methods for other investigational medicinal products which contain antibiotics. Methods: Matrices were spiked individually with Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Streptococcus pyogenes, Escherichia coli, Clostridium sporogenes, Propionibacterium acnes, Candida albicans, and Aspergillus brasiliensis. Samples were pretreated with penicillinase for 1 h before inoculation and incubation in BacT/ALERT iFA Plus and iFN Plus culture bottles using 3D BacT/ALERT automates. Microorganisms within positive BacT/ALERT bottles were specified. The procedure was performed in two different laboratories to prove robustness of test. Results: All nine tested microorganisms were detected within 14 days of incubation in accordance with requirements of the European Pharmacopoiea in terms of sensitivity, specificity and robustness of the test. Penicillin and streptomycin did not have any influence on specifications defined within the investigational medicinal product dossier. Conclusions: Culturing cellular products in the presence of antibiotics can serve as an effective method to reduce contamination risk but only if the chosen antibiotics neither have any influence on specifications of the investigational medicinal product nor interfere with microbiological tests. Consequently, cells and tissues primarily contaminated with microorganisms, like placenta, may be considered as a source of cellular therapeutics when cultured for a sufficient time with antibiotics and tested with a validated method. The choice of microorganisms for the validation of the microbiological test should always consider all conceivable scenarios and should not be reduced to minimal criteria defined in European Pharmacopoiea, wrongfully believing to thus save time and effort.
Unbalanced Y;7 Translocation between Two Low-Similarity Sequences Leading to SRY-Positive 45,X Testicular Disorders of Sex Development
Authors: Uehara Erika , Hattori Atsushi , Shima Hirohito , Ishiguro Akira , Abe Yu , Ogata Tsutomu , Ogawa Eishin , Fukami Maki
Published: July 2019

Unbalanced translocations of Y-chromosomal fragments harboring the sex-determining region Y gene (SRY) to the X chromosome or an autosome result in 46,XX and 45,X testicular disorders of sex development (DSD), respectively. Of these, Y;autosome translocation is an extremely rare condition. Here, we identified a 20-year-old man with a 45,X,t(Y;7)(q11.21;q35) karyotype, who exhibited unilateral cryptorchidism, small testis, intellectual disability, and various congenital anomalies. The fusion junction of the translocation was blunt, and the breakpoint-flanking regions shared only 50% similarity. These results indicate that Y;autosome translocations can occur between 2 low-similarity sequences, probably via nonhomologous end joining. Furthermore, translocations of a Ypterq11.21 fragment to 7q35 likely result in normal or only mildly impaired male-type sexual development, along with various clinical features of 7q deletion syndrome, although their effects on adult testicular function remain to be studied.
Hypercalcemia Is a Risk Factor for the Progression of Aortic Calcification in Kidney Transplant Recipients
Authors: Naganuma Toshihide , Takemoto Yoshiaki , Uchida Junji , Nakatani Tatsuya , Kabata Daijiro , Shintani Ayumi
Published: July 2019

Background/Aims: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. Materials: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. Results: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). Conclusion: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.
Description of two new species of Nannocharax Günther, 1867 (Teleostei: Characiformes: Distichodontidae) from the Cross River, Cameroon
Authors: DUNZ ANDREAS R. , SCHLIEWEN ULRICH K.
Published: July 2019

Two new species of the African characiform genus Nannocharax Günther, 1867 are described from the Cross River in Cameroon. Nannocharax zebra sp. nov. is distinguished from all other described Nannocharax species except N. schoutedeni Poll, 1939, N. latifasciatus Coenen & Teugels, 1989, N. ansorgii Boulenger, 1911 and N. procatopus Boulenger, 1920 by a shorter distance between the posterior border of the anus and the articulation of the first anal-fin ray (2.2–3.7 vs. 4.2–14.2% of SL). It differs from N. schoutedeni by having 39–43 vs. 36 or 37 lateral line scales, from N. latifasciatus by a deeper caudal peduncle (55.9–63.8% vs. 48.1–50.8% of SL), from N. ansorgii by having 12 or 13 rather than 9 anal-fin rays, and from N. procatopus by having a shorter caudal peduncle (11.3–15.2% vs. 18.0% of SL), and by having 39–43 rather than 36 lateral line scales. Nannocharax usongo sp. nov. is distinguished from all other Nannocharax species mainly in the distance from the border of anus to the articulation of first anal-fin ray (0.9–1.8 vs. 2.2–14.2% of SL) and by its body coloration consisting of 7–11 dark blotches along the lateral line often coalesced to one wide black band, and 7–12 small saddle-blotches along the dorsum.
Another case of cryptic diversity in poison frogs (Dendrobatidae: Ameerega)description of a new species from Bolivia
Authors: LÖTTERS STEFAN , SCHMITZ ANDREAS , REICHLE STEFFEN , RÖDDER DENNIS , QUENNET VERENA
Published: July 2019

We describe a new species of poison frog from the Serranías de Santiago and Chochis, isolated Precambrian sandstone massifs in the Chiquitanía region of Bolivia. The new species is morphologically similar to the Brazilian Ameerega braccata and A. flavopicta and best distinguished by larger adult size (27.57 mm versus < 22 mm in A. braccata) and coloration of ventral surfaces in life (light grey to light brown with black marbling versus yellowish white with occasional black marbling in A. flavopicta), respectively. The new species is genetically most closely related to A. flavopicta (uncorrected p-distances of the 16S mitochondrial rRNA gene ca. 2 %) but clearly differs in characteristics of its advertisement call (longer note duration, lower note repetition rate, lower number of pulses per note, and lower fundamental and dominant frequency). The new species can be commonly found in the vicinity of rocks, often near running water, and should be considered 'Least Concern' (LC) under IUCN Red List criteria.
A new genus, Paraxantia gen. nov., with descriptions of four new species (Orthoptera: Tettigoniidae: Phaneropterinae) from China
Authors: LIU CHUN-XIANG , KANG LE
Published: July 2019

Here we report a distinctive new genus Paraxantia gen. nov. (Orthoptera: Tettigoniidae: Phaneropterinae) from southern China. The new genus is distinguished from Xantia and other genera in the subfamily Phaneropterinae by the shape of fastigium verticis, the widened tegmen behind middle, and the complex sclerotized concealed genitalia. Description and important illustrations of four new species P. tibetensis sp. nov., P. hubeiensis sp. nov., P. parasinica sp. nov., and P. bicornis sp. nov. are presented. Xantia sinica Liu is transferred to Paraxantia with redescription and illustration. A key covering type species of Xantia Brunner von Wattenwyl and five species of Paraxantia gen. nov. is provided.
A review of the genus Pholcus (Araneae: Pholcidae) from China
Authors: ZHANG FENG , ZHU MING-SHENG
Published: July 2019

A total of 55 species of the genus Pholcus occurring in China are reviewed here. Among them, 20 species are new to science: Pholcus dali sp. nov., P. fengcheng sp. nov., P. harveyi sp. nov., P. huberi sp. nov., P. kangding sp. nov., P. kunming sp. nov., P. mianshanensis sp. nov., P. paralinzhou sp. nov., P. parayichengicus sp. nov., P. phoenixus sp. nov., P. saaristoi sp. nov., P. shangrila sp. nov., P. songi sp. nov., P. songxian sp. nov., P. sublingulatus sp. nov., P. subwuyiensis sp. nov., P. yangi sp. nov., P. yugong sp. nov., P. zhangae sp. nov., P. zhuolu sp. nov. One new combination is formed: Pholcus elongatus (Yin & Wang, 1981) is transferred from Spermophora. One species, P. opilionoides, has not yet been found in China.