bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of rotational arc station parameter optimized radiation therapy
Authors: Dong P. , Ungun B. , Boyd S. , Xing L.
Published: August 2016

Purpose:

To develop a fast optimization method for station parameter optimized radiation therapy (SPORT) and show that SPORT is capable of matching VMAT in both plan quality and delivery efficiency by using three clinical cases of different disease sites.

Methods:

The angular space from 0° to 360° was divided into 180 station points (SPs). A candidate aperture was assigned to each of the SPs based on the calculation results using a column generation algorithm. The weights of the apertures were then obtained by optimizing the objective function using a state‐of‐the‐art GPU based proximal operator graph solver. To avoid being trapped in a local minimum in beamlet‐based aperture selection using the gradient descent algorithm, a stochastic gradient descent was employed here. Apertures with zero or low weight were thrown out. To find out whether there was room to further improve the plan by adding more apertures or SPs, the authors repeated the above procedure with consideration of the existing dose distribution from the last iteration. At the end of the second iteration, the weights of all the apertures were reoptimized, including those of the first iteration. The above procedure was repeated until the plan could not be improved any further. The optimization technique was assessed by using three clinical cases (prostate, head and neck, and brain) with the results compared to that obtained using conventional VMAT in terms of dosimetric properties, treatment time, and total MU.

Results:

Marked dosimetric quality improvement was demonstrated in the SPORT plans for all three studied cases. For the prostate case, the volume of the 50% prescription dose was decreased by 22% for the rectum and 6% for the bladder. For the head and neck case, SPORT improved the mean dose for the left and right parotids by 15% each. The maximum dose was lowered from 72.7 to 71.7 Gy for the mandible, and from 30.7 to 27.3 Gy for the spinal cord. The mean dose for the pharynx and larynx was reduced by 8% and 6%, respectively. For the brain case, the doses to the eyes, chiasm, and inner ears were all improved. SPORT shortened the treatment time by ∼1 min for the prostate case, ∼0.5 min for brain case, and ∼0.2 min for the head and neck case.

Conclusions:

The dosimetric quality and delivery efficiency presented here indicate that SPORT is an intriguing alternative treatment modality. With the widespread adoption of digital linac, SPORT should lead to improved patient care in the future.
Response to Comment on “Open-ocean fish reveal an omnidirectional solution to camouflage in polarized environments”
Authors: Brady Parrish , Gilerson Alex , Kattawar George , Sullivan Jim , Twardowski Mike , Dierssen Heidi , Cummings Molly
Published: August 2016

Cronin
et al
. take issue with our evidence for polarocryptic carangid fish based on concerns of pseudoreplication, our contrast metric, and habitat. We clarify (i) the importance of camouflage in near-surface open ocean environments and (ii) the use of a Stokes contrast metric and further (iii) conduct individual-based statistics on our data set to confirm the reported polarocrypsis patterns.
Facts versus fallacy
Truth or Truthiness Distinguishing Fact from Fiction by Learning to Think Like a Data Scientist
Howard Wainer
Cambridge University Press, 2016. 228 pp.
Authors: Phillips Christopher J.
Published: August 2016

A statistics-driven treatise teaches readers how to spot lies, half-truths, and outright deception
Benefits of selective feeding
Authors: Lennen Rebecca M.
Published: August 2016

Microbes engineered to digest unusual nutrients outcompete contaminants in chemicals production
Multifunctional T Cell Response to DosR and Rpf Antigens Is Associated with Protection in Long-Term Mycobacterium tuberculosis-Infected Individuals in Colombia
Authors: Arroyo Leonar , Rojas Mauricio , Franken Kees L. M. C. , Ottenhoff Tom H. M. , Barrera Luis F.
Published: August 2016

Multifunctional T cells have been shown to be protective in chronic viral infections. In mycobacterial infections, however, evidence for a protective role of multifunctional T cells remains inconclusive. Short-term cultures of peripheral blood mononuclear cells stimulated with the
Mycobacterium tuberculosis
RD1 antigens 6-kDa early secretory antigenic target (ESAT6) and 10-kDa culture filtrate antigen (CFP10), which are induced in the early infection phase, have been mainly used to assess T cell multifunctionality, although long-term culture assays have been proposed to be more sensitive than short-term assays for assessment of memory T cells, which are essential for long-term immunity. Here we used a long-term culture assay system to study the T cell immune responses to the
M. tuberculosis
latency-associated DosR antigens and reactivation-associated Rpf antigens, compared to ESAT6 and CFP10, in patients with pulmonary tuberculosis (PTB) and household contacts of PTB patients with long-term latent tuberculosis infection (ltLTBI), in a community in which
M. tuberculosis
is endemic. Our results showed that the DosR antigens Rv1737c (
narK2
) and Rv2029c (
pfkB
) and the Rv2389c (
rpfD
) antigen of
M. tuberculosis
induced higher frequencies of CD4
+
or CD8
+
mono- or bifunctional (but not multifunctional) T cells producing interferon gamma (IFN-γ) and/or tumor necrosis alpha (TNF-α) in ltLTBI, compared to PTB. Moreover, the frequencies of CD4
+
and/or CD8
+
T cells with a CD45RO
+
CD27
+
phenotype were higher in ltLTBI than in PTB. Thus, the immune responses to selected DosR and Rpf antigens may be associated with long-term latency, correlating with protection from
M. tuberculosis
reactivation in ltLTBI. Further study of the functional and memory phenotypes may contribute to further discrimination between the different states of
M. tuberculosis
infections.
Evaluation of Semiautomated IS
6110
-Based Restriction Fragment Length Polymorphism Typing for Mycobacterium tuberculosis in a High-Burden Setting
Authors: Said Halima M. , Krishnamani Keshav , Omar Shaheed V. , Dreyer Andries W. , Sansom Bianca , Fallows Dorothy , Ismail Nazir A.
Published: August 2016

The manual IS
6110
-based restriction fragment length polymorphism (RFLP) typing method is highly discriminatory; however, it is laborious and technically demanding, and data exchange remains a challenge. In an effort to improve IS
6110
-based RFLP to make it a faster format, DuPont Molecular Diagnostics recently introduced the IS
6110
-PvuII kit for semiautomated typing of
Mycobacterium tuberculosis
using the RiboPrinter microbial characterization system. This study aimed to evaluate the semiautomated RFLP typing against the standard manual method. A total of 112 isolates collected between 2013 and 2014 were included. All isolates were genotyped using manual and semiautomated RFLP typing methods. Clustering rates and discriminatory indexes were compared between methods. The overall performance of semiautomated RFLP compared to manual typing was excellent, with high discriminatory index (0.990 versus 0.995, respectively) and similar numbers of unique profiles (72 versus 74, respectively), numbers of clustered isolates (33 versus 31, respectively), cluster sizes (2 to 6 and 2 to 5 isolates, respectively), and clustering rates (21.9% and 17.1%, respectively). The semiautomated RFLP system is technically simple and significantly faster than the manual RFLP method (8 h versus 5 days). The analysis is fully automated and generates easily manageable databases of standardized fingerprints that can be easily exchanged between laboratories. Based on its high-throughput processing with minimal human effort, the semiautomated RFLP can be a very useful tool as a first-line method for routine typing of
M. tuberculosis
isolates, especially where Beijing strains are highly prevalent, followed by manual RFLP typing if resolution is not achieved, thereby saving time and labor.
Clinicopathological and prognostic significance of survivin expression in renal cancer patients: a meta-analysis
Authors: Ma Chengquan , Lu Bingxin , Sun Erlin
Published: August 2016

Background

Survivin has been reported to play a role in the diagnosis and prognosis of renal cell carcinoma (RCC); however, published data on this subject are conflicting.

Aim

To conduct a meta-analysis to evaluate the impact of survivin as a prognostic marker and its association with clinicopathological variables in patients with RCC.

Method

Comprehensive searches of electronic databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the Cochrane Library) were updated to June 2016 to retrieve eligible studies. The association strength was measured with relative risks (RRs) and pooled HRs with 95% CIs, which were extracted and pooled to determine the association between survivin expression and patient survival and clinicopathological features.

Results

Ten studies with 1063 cases of RCC were included. Positive survivin expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07 to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The correlation between survivin expression and gender was not significant (pooled RR 0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found between survivin expression and overall survival for patients with RCC (pooled HR 1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17 (univariate model)).

Conclusions

Our results indicate that survivin is of prognostic signiﬁcance in patients with RCC.
Sporadic juvenile lymphosarcoma in a set of triplet calves: haematopoietic chimerism or chance?
Authors: Fry Lindsay Michelle , Snekvik Kevin , McBride Raquel , Parish Steven M
Published: August 2016

A set of four‐month‐old Angus‐Hereford triplet calves, two freemartin heifers and one steer, was presented for generalised lymphadenomegaly and paraparesis. Cytology was consistent with lymphosarcoma and all calves were serologically negative for bovine leukaemia virus. Postmortem examination and histopathology findings confirmed the diagnosis of sporadic juvenile lymphosarcoma. Due to the rarity of sporadic bovine lymphosarcoma, it is unlikely that these three calves simply, spontaneously, developed lymphosarcoma within a month of one another. A shared genetic predisposition to develop lymphosarcoma is possible, but is unlikely given the synchronous development of disease among the triplets. The most parsimonious explanation is that one calf developed lymphosarcoma in utero and transmitted it to its siblings via placental vascular anastomoses, in the same way haematopoietic chimerism develops in freemartin calves. Regardless of pathogenesis, this case demonstrates that spontaneous bovine leukosis, like enzootic bovine leukosis, occasionally affects multiple animals within a single herd at one time.
Is V̇O2 supressed during nonapnoeic facial submersion?
Authors: Anderson Sarah , Chamberlain Maggie R. , Musgrove Samantha , Partusch Antonia , Tice Keagan R.J. , Thorp David B.
Published: August 2016

The mammalian dive response (DR) is described as oxygen-conserving based on measures of bradycardia, peripheral vasoconstriction, and decreased ventilation (V̇E). Using a model of simulated diving, this study examined the effect of nonapnoeic facial submersions (NAFS) on oxygen consumption (V̇O2). 19 participants performed four 2-min NAFS with 8 min of rest between each. Two submersions were performed in 5 °C water, 2 in 25 °C water. Heart rate (HR) was collected using chest strap monitors. A tube connected to the inspired port of a non-rebreathing valve allowed participants to breathe during facial submersion. Expired air was directed to a metabolic cart to determine V̇O2 and V̇E. Baseline (BL) HR, V̇O2, and V̇E values were determined by the average during the 2 min prior to facial submersion; cold shock response (CSR) values were the maximum during the first 30 s of facial submersion; and NAFS values were the minimum during the last 90 s of facial submersion. A 2-way repeated-measures ANOVA indicated that both HR and V̇E were greater during the CSR (92.5 ± 3.6 beats/min, 16.3 ± 0.8 L/min) compared with BL (78.9 ± 3.2 beats/min, 8.7 ± 0.4 L/min), while both were decreased from BL during the NAFS (60.0 ± 4.0 beats/min, 6.0 ± 0.4 L/min) (all, p < 0.05). HRCSR was higher and HRNAFS lower in 5 °C versus 25 °C water (p < 0.05), while V̇E was greater in 5 °C conditions (p < 0.05). V̇O2 exceeded BL during the CSR and decreased below BL during the NAFS (BL: 5.3 ± 0.1, CSR: 9.8 ± 0.4, NAFS: 3.1 ± 0.2 mL·kg−1·min−1, p < 0.05). The data illustrate that NAFS alone contributes to the oxygen conservation associated with the human DR.
Investigation of a new chiral auxiliary derived chemoenzymatically from toluene: experimental and computational study
Authors: Šnajdr Ivan , Froese Jordan , Dudding Travis , Horáková Pavlína , Hudlický Tomáš
Published: August 2016

A tricyclic chiral auxiliary, prepared from the enzymatically derived cis-arene dihydrodiol metabolite of toluene, was investigated as a means of asymmetric induction in several different reactions. The auxiliary was converted to an oxaziridine, and its utility in hydroxylation, providing low levels of enantiomeric excess, was compared with that of Davis’s oxaziridine. Insight into the origin of stereoinduction in this reaction is provided and is based on computational Monte Carlo Multiple Minimum (MCMM) searches using the OPLS3 force field. The use of the auxiliary group in the alkylation of appended esters proved disappointing. Diels-Alder cycloaddition of an acrylate, derived from the auxiliary group, with cyclohexadiene furnished a mixture of diastereomeric adducts in essentially equal amounts. The adducts were separated and the corresponding enantiomeric residues were isolated with good enantiomeric excess. Evidence of reasonable levels of asymmetric induction in the above processes was lacking. Experimental and spectral data are provided for all key compounds.
Precambrian to Early Cretaceous rocks of the Strandja Massif (northwestern Turkey): evolution of a long lasting magmatic arc
Authors: Natal’in Boris A. , Sunal Gürsel , Gün Erkan , Wang Bo , Zhiqing Yang
Published: August 2016

The Strandja Massif, northwestern Turkey, forms a link between the Balkan Zone of Bulgaria, which is correlated with the Variscan orogen in Europe, and the Pontides, where Cimmerian structures are prominent. Five fault-bounded tectonic units form the massif structure. (1) The Kırklareli Unit consists of the Paleozoic basement intruded by the Carboniferous to Triassic Kırklareli metagranites. It is unconformably overlain by Permian and Triassic metasediments. (2) The Vize Unit that is made of Neoproterozoic metasediments, which are intruded by Cambrian metagranites, and overlain by the pre-Ordovician molasse. Unconformably laying the Ordovician quartzites pass upward into quartz schists and then to alternating marble and chert of, possibly, latest Devonian age. Rocks of the Vize Unit are intruded by the late Carboniferous metagranites. The Vize Unit may be correlated with the passive continental margin of the Istanbul Zone. (3) The Mahya accretionary complex and (4) the paired Yavuzdere magmatic arc were formed in the Carboniferous. (5) Nappes consisting of the Jurassic dolomites and marbles thrust to the north in late Jurassic – early Cretaceous time. They occupy the highest structural position on all above-mentioned tectonic units. Tectonic subdivision of the Strandja Massif is supported by new 18 ages of magmatic and detrital zircons. The long duration of subduction-related magmatism in the region and its continuity in the Triassic contradicts with the widely accepted ideas about the dominance of the passive continental margin settings in the tectonic evolution of the Strandja Massif. The massif is interpreted as a fragment of the long-lived, Cambrian to Triassic Silk Road magmatic arc. At least since the late Paleozoic this arc evolved on the northern side of Paleo-Tethys.
Uncertain Distribution-Minimum Spanning Tree Problem
Authors: Zhou Jian , Yi Xiajie , Wang Ke , Liu Jing
Published: August 2016

This paper studies the minimum spanning tree problem on a graph with uncertain edge weights, which are formulated as uncertain variables. The concept of ideal uncertain minimum spanning tree (ideal UMST) is initiated by extending the definition of the uncertain [Formula: see text]-minimum spanning tree to reect the overall properties of the α-minimum spanning tree weights at any confidence level [Formula: see text]. On the basis of this new concept, the definition of uncertain distribution-minimum spanning tree is proposed in three ways. Particularly, by considering the tail value at risk from the perspective of risk management, the notion of uncertain [Formula: see text]-distribution-minimum spanning tree ([Formula: see text]-distribution-UMST) is suggested. It is shown that the [Formula: see text]-distribution-UMST is just the uncertain expected minimum spanning tree when [Formula: see text] = 0. For any [Formula: see text], this problem can be effectively solved via the proposed deterministic graph transformation-based approach with the aid of the [Formula: see text]-distribution-path optimality condition. Furthermore, the proposed definitions and solutions are illustrated by some numerical examples.
A MAGDM Method Based on 2-Tuple Linguistic Heronian Mean and New Operational Laws
Authors: Liu Xi , Tao Zhifu , Chen Huayou , Zhou Ligang
Published: August 2016

In this paper, we investigate the multiple attributes group decision making (MAGDM) problem with 2-tuple linguistic information. According to some closed operational laws of 2-tuple linguistic, some Algebra t-norm and s-norm based Heronian aggregation operators of 2-tuple linguistic information are put forward, the desired properties and the special cases where the parameters take different values are also discussed. Furthermore, a method of MAGDM under 2-tuple linguistic environment is proposed based on the Algebra t-norm and s-norm based 2-tuple linguistic Heronian mean operator or the Algebra t-norm and s-norm based 2-tuple linguistic weighted Heronian mean operator. Finally, a numerical example is presented to demonstrate the proposed method.
Conceptual Difficulties of Standard Quantum Mechanics and the Role of Noise in Overcoming Them
Authors: Ghirardi GianCarlo
Published: August 2016

We briefly review the difficulties of the standard version of quantum mechanics in accounting for all kinds of physical processes (in particular both the micro and the macroscopic ones) and we argue that to overcome such difficulties one has to give up the superposition principle, i.e., to break the linear nature of the theory. We then show that the simple introduction of terms violating the linearity of the deterministic evolution of the standard theory has physically unacceptable consequences. Taking this into account we are led to modify the quantum dynamics by adding to Schrödinger’s equation, besides nonlinear terms, a coupling with an appropriate noise. We show that, with such a move, one can work out a theory which is internally consistent and it allows to account, in a quite simple and physically appealing way, for natural processes including the measurements and the classical behavior of macroscopic bodies. On the basis of our analysis, we are led to conclude that the consideration of the noise represents a crucial element for understanding the laws of nature.
Scheduling Storms and Streams in the Cloud
Authors: Ghaderi Javad , Shakkottai Sanjay , Srikant R.
Published: August 2016

Motivated by emerging big
streaming
data processing paradigms (e.g., Twitter Storm, Streaming MapReduce), we investigate the problem of scheduling graphs over a large cluster of servers. Each graph is a job, where nodes represent compute tasks and edges indicate data flows between these compute tasks. Jobs (graphs) arrive randomly over time and, upon completion, leave the system. When a job arrives, the scheduler needs to partition the graph and distribute it over the servers to satisfy load balancing and cost considerations. Specifically, neighboring compute tasks in the graph that are mapped to different servers incur load on the network; thus a mapping of the jobs among the servers incurs a cost that is proportional to the number of “broken edges.” We propose a low-complexity randomized scheduling algorithm that, without service preemptions, stabilizes the system with graph arrivals/departures; more importantly, it allows a smooth tradeoff between minimizing average partitioning cost and average queue lengths. Interestingly, to avoid service preemptions, our approach does not rely on a Gibbs sampler; instead, we show that the corresponding limiting invariant measure has an interpretation stemming from a loss system.
FE-SViT
Authors: Xi Kai , Hu Jiankun , Kumar B. V. K. Vijaya
Published: August 2016

As a promising bio-cryptographic technique, the fuzzy extractor seamlessly binds biometrics and cryptography for template protection and key generation. However, most existing methods hardly solve the following issues simultaneously: (1) Fingerprint registration, (2) Verification accuracy, (3) Security strength, and (4) Computational efficiency. In this article, we introduce a bio-crypto-oriented fingerprint verification scheme - Selective Vertex-indexed Triangulation (SViT) which maps minutia global topology to local triangulation with minimum information loss. Then, a SViT-based fuzzy extractor framework (FE-SViT) is proposed and high verification accuracy is achieved. The FE-SViT is highly parallelizable and efficient which makes it suitable for embedded devices.
Semantic Feature Mining for Video Event Understanding
Authors: Yang Xiaoshan , Zhang Tianzhu , Xu Changsheng
Published: August 2016

Content-based video understanding is extremely difficult due to the semantic gap between low-level vision signals and the various semantic concepts (object, action, and scene) in videos. Though feature extraction from videos has achieved significant progress, most of the previous methods rely only on low-level features, such as the appearance and motion features. Recently, visual-feature extraction has been improved significantly with machine-learning algorithms, especially deep learning. However, there is still not enough work focusing on extracting semantic features from videos directly. The goal of this article is to adopt unlabeled videos with the help of text descriptions to learn an embedding function, which can be used to extract more effective semantic features from videos when only a few labeled samples are available for video recognition. To achieve this goal, we propose a novel embedding convolutional neural network (ECNN). We evaluate our algorithm by comparing its performance on three challenging benchmarks with several popular state-of-the-art methods. Extensive experimental results show that the proposed ECNN consistently and significantly outperforms the existing methods.
Turning compositionality into composability
Authors: Andersson Björn
Published: August 2016

Compositional theories and technologies facilitate the decomposition of a complex system into components, as well as their integration via interfaces. Component interfaces hide the internal details of the components, thereby reducing integration complexity. A system is said to be composable if the properties established and validated for components in isolation hold once the components are integrated to form the system. This brings us the question: "Is compositionality related to composability?" This paper answers this question in the affirmative; it considers a previously known interface for compositionality and shows that it can be used for composability. It also presents a run-time policing mechanism for this interface.
Cache-aware interfaces for compositional real-time systems
Authors: Phan Linh Thi Xuan , Xu Meng , Lee Insup
Published: August 2016

Interface-based compositional analysis is by now a fairly established area of research in real-time systems. However, current research has not yet fully considered practical aspects, such as the effects of cache interferences on multicore platforms. This position paper discusses the analysis challenges and motivates the need for cache scheduling in this setting, and it highlights several research questions towards cache-aware interfaces for compositional systems on multicore platforms.
Probabilistic component-based analysis for networks
Authors: Santinelli Luca
Published: August 2016

Time-constrained networks have demanded so far for deterministic modeling and analysis in order to guarantee their worst-case behavior. With this work we intend to apply both probabilistic modeling and probabilistic analyses to investigate such networks. The probabilistic framework we propose aims at guaranteeing confidence levels, in the form of probabilities, to the network timing constraints; the deterministic case remain a particular case, the worst-case, within the probabilistic framework. We focus on probabilistic bounds for defining probabilistic interfaces to network components and we study the way that probabilities propagate within networks by accounting for the dependences and the interactions between network components. Finally, we define and apply probabilistic performance metrics for evaluating network behavior with different degree of confidence due to the probabilities.
Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns
Authors: Eftestøl Einar , Egner Ingrid M. , Lunde Ida G. , Ellefsen Stian , Andersen Tom , Sjåland Cecilie , Gundersen Kristian , Bruusgaard Jo C.
Published: August 2016

It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50–60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were increased with high load, suggesting that activation of satellite cells is mechano dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load independent, indicating that the electrical signaling rather than mechanosignaling controls fiber type. RAC-α serine/threonine-protein kinase (Akt) and ribosomal protein S6 kinase β-1 (S6K1) were not significantly differentially activated by load, suggesting that the differences in mechanical factors were not important for activating the Akt/mammalian target of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent, suggesting that mechanosignaling in skeletal muscle is different.
PIP2 in pancreatic β-cells regulates voltage-gated calcium channels by a voltage-independent pathway
Authors: de la Cruz Lizbeth , Puente Erika I. , Reyes-Vaca Arturo , Arenas Isabel , Garduño Julieta , Bravo-Martínez Jorge , Garcia David E.
Published: August 2016

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a membrane phosphoinositide that regulates the activity of many ion channels. Influx of calcium primarily through voltage-gated calcium (CaV) channels promotes insulin secretion in pancreatic β-cells. However, whether CaV channels are regulated by PIP2, as is the case for some non-insulin-secreting cells, is unknown. The purpose of this study was to investigate whether CaV channels are regulated by PIP2 depletion in pancreatic β-cells through activation of a muscarinic pathway induced by oxotremorine methiodide (Oxo-M). CaV channel currents were recorded by the patch-clamp technique. The CaV current amplitude was reduced by activation of the muscarinic receptor 1 (M1R) in the absence of kinetic changes. The Oxo-M-induced inhibition exhibited the hallmarks of voltage-independent regulation and did not involve PKC activation. A small fraction of the Oxo-M-induced CaV inhibition was diminished by a high concentration of Ca2+ chelator, whereas ≥50% of this inhibition was prevented by diC8-PIP2 dialysis. Localization of PIP2 in the plasma membrane was examined by transfecting INS-1 cells with PH-PLCδ1, which revealed a close temporal association between PIP2 hydrolysis and CaV channel inhibition. Furthermore, the depletion of PIP2 by a voltage-sensitive phosphatase reduced CaV currents in a way similar to that observed following M1R activation. These results indicate that activation of the M1R pathway inhibits the CaV channel via PIP2 depletion by a Ca2+-dependent mechanism in pancreatic β- and INS-1 cells and thereby support the hypothesis that membrane phospholipids regulate ion channel activity by interacting with ion channels.
The potassium channels TASK2 and TREK1 regulate functional differentiation of murine skeletal muscle cells
Authors: Afzali Ali M. , Ruck Tobias , Herrmann Alexander M. , Iking Janette , Sommer Claudia , Kleinschnitz Christoph , Preuβe Corinna , Stenzel Werner , Budde Thomas , Wiendl Heinz , Bittner Stefan , Meuth Sven G.
Published: August 2016

Two-pore domain potassium (K2P) channels influence basic cellular parameters such as resting membrane potential, cellular excitability, or intracellular Ca2+-concentration [Ca2+]i. While the physiological importance of K2P channels in different organ systems (e.g., heart, central nervous system, or immune system) has become increasingly clear over the last decade, their expression profile and functional role in skeletal muscle cells (SkMC) remain largely unknown. The mouse SkMC cell line C2C12, wild-type mouse muscle tissue, and primary mouse muscle cells (PMMs) were analyzed using quantitative PCR, Western blotting, and immunohistochemical stainings as well as functional analysis including patch-clamp measurements and Ca2+ imaging. Mouse SkMC express TWIK-related acid-sensitive K+ channel (TASK) 2, TWIK-related K+ channel (TREK) 1, TREK2, and TWIK-related arachidonic acid stimulated K+ channel (TRAAK). Except TASK2 all mentioned channels were upregulated in vitro during differentiation from myoblasts to myotubes. TASK2 and TREK1 were also functionally expressed and upregulated in PMMs isolated from mouse muscle tissue. Inhibition of TASK2 and TREK1 during differentiation revealed a morphological impairment of myoblast fusion accompanied by a downregulation of maturation markers. TASK2 and TREK1 blockade led to a decreased K+ outward current and a decrease of ACh-dependent Ca2+ influx in C2C12 cells as potential underlying mechanisms. K2P-channel expression was also detected in human muscle tissue by immunohistochemistry pointing towards possible relevance for human muscle cell maturation and function. In conclusion, our findings for the first time demonstrate the functional expression of TASK2 and TREK1 in muscle cells with implications for differentiation processes warranting further investigations in physiologic and pathophysiologic scenarios.
Acute kidney injury induces hallmarks of polycystic kidney disease
Authors: Kurbegovic Almira , Trudel Marie
Published: August 2016

Acute kidney injury (AKI) and autosomal dominant polycystic kidney disease (ADPKD) are considered separate entities that both frequently cause renal failure. Since ADPKD appears to depend on a polycystin-1 (Pc1) or Pc2 dosage mechanism, we investigated whether slow progression of cystogenesis in two Pkd1 transgenic mouse models can be accelerated with moderate ischemia-reperfusion injury (IRI). Transient unilateral left ischemic kidneys in both nontransgenic and transgenic mice reproducibly develop tubular dilatations, cysts, and typical PKD cellular defects within 3 mo post-IRI. Similar onset and severity of IRI induced-cystogenesis independently of genotype revealed that IRI is sufficient to promote renal cyst formation; however, this response was not further amplified by the transgene in Pkd1 mouse models. The IRI nontransgenic and transgenic kidneys showed from 16 days post-IRI strikingly increased and sustained Pkd1/Pc1 (>3-fold) and Pc2 (>8-fold) expression that can individually be cystogenic in mice. In parallel, long-term and important stimulation of hypoxia-inducible factor 1α expression was induced as in polycystic kidney disease. While mammalian target of rapamycin signaling is activated, stimulation of the Wnt pathway, with markedly increased active β-catenin and c-Myc expression in IRI renal epithelium, uncovered a similar regulatory cystogenic response shared by IRI and ADPKD. Our study demonstrates that long-term AKI induces cystogenesis and cross talk with ADPKD Pc1/Pc2 pathogenic signaling.
Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
Authors: Corral-Jara Karla F. , Trujillo-Ochoa Jorge L. , Realpe Mauricio , Panduro Arturo , Gómez-Leyva Juan F. , Rosenstein Yvonne , Jose-Abrego Alexis , Roman Sonia , Fierro Nora A.
Published: August 2016

We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein,in vitrostimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor geneHAVCR1/TIM-1was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1.
Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin‐Induced Diabetic Rats Fed with a High‐Fat Diet
Authors: Balbaa Mahmoud , El-Zeftawy Marwa , Ghareeb Doaa , Taha Nabil , Mandour Abdel Wahab
Published: August 2016

The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin‐induced diabetic rats fed with a high‐fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor‐induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I‐OMe‐AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin‐like growth factor‐1 and phosphoinositide‐3 kinase, whereas the expression of ADAM‐17 was downregulated. The expression of ADAM‐17 is corroborated by the analysis of TIMP‐3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor‐α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin‐induced signaling.
Amelioration of Sickle Cell Pain after Parathyroidectomy in Two Patients with Concurrent Hyperparathyroidism: An Interesting Finding
Authors: Muthu John , Ali Mir
Published: August 2016

Patients with sickle cell disease have high morbidity and healthcare utilization due to repeated painful crises. Some coexisting conditions which cause pain similar to sickle cell disease may go undiagnosed in these patients. We report two adults with concurrent hyperparathyroidism who experienced significant improvement in sickle cell pain following parathyroidectomy thereby pointing to hyperparathyroidism as the principal causative factor for their pain. Meticulous evaluation for parathyroid disorders can be rewarding in sickle cell disease.
Expression and Purification of C-Peptide Containing Insulin UsingPichia pastorisExpression System
Authors: Baeshen Mohammed N. , Bouback Thamer A. F. , Alzubaidi Mubarak A. , Bora Roop S. , Alotaibi Mohammed A. T. , Alabbas Omar T. O. , Alshahrani Sultan M. , Aljohani Ahmed A. M. , Munshi Rayan A. A. , Al-Hejin Ahmed , Ahmed Mohamed M. M. , Redwan Elrashdy M. , Ramadan Hassan A. I. , Saini Kulvinder S. , Baeshen Nabih A.
Published: August 2016

Increase in the incidence of Insulin Dependent Diabetes Mellitus (IDDM) among people from developed and developing countries has created a large global market for insulin. Moreover, exploration of new methods for insulin delivery including oral or inhalation route which require very high doses would further increase the demand of cost-effective recombinant insulin. Various bacterial and yeast strains have been optimized to overproduce important biopharmaceuticals. One of the approaches we have taken is the production of recombinant human insulin along with C-peptide in yeastPichia pastoris. We procured a cDNA clone of insulin from Origene Inc., USA. Insulin cDNA was PCR amplified and cloned into yeast vector pPICZ-α. Cloned insulin cDNA was confirmed by restriction analysis and DNA sequencing. pPICZ-α-insulin clone was transformed intoPichia pastoris SuperMan5strain. Several Zeocin resistant clones were obtained and integration of insulin cDNA inPichiagenome was confirmed by PCR using insulin specific primers. Expression of insulin inPichiaclones was confirmed by ELISA, SDS-PAGE, and Western blot analysis. In vivo efficacy studies in streptozotocin induced diabetic mice confirmed the activity of recombinant insulin. In conclusion, a biologically active human proinsulin along with C-peptide was expressed at high level usingPichia pastorisexpression system.
Multivendor Spectral-Domain Optical Coherence Tomography Dataset, Observer Annotation Performance Evaluation, and Standardized Evaluation Framework for Intraretinal Cystoid Fluid Segmentation
Authors: Wu Jing , Philip Ana-Maria , Podkowinski Dominika , Gerendas Bianca S. , Langs Georg , Simader Christian , Waldstein Sebastian M. , Schmidt-Erfurth Ursula M.
Published: August 2016

Development of image analysis and machine learning methods for segmentation of clinically significant pathology in retinal spectral-domain optical coherence tomography (SD-OCT), used in disease detection and prediction, is limited due to the availability of expertly annotated reference data. Retinal segmentation methods use datasets that either are not publicly available, come from only one device, or use different evaluation methodologies making them difficult to compare. Thus we present and evaluate a multiple expert annotated reference dataset for the problem of intraretinal cystoid fluid (IRF) segmentation, a key indicator in exudative macular disease. In addition, a standardized framework for segmentation accuracy evaluation, applicable to other pathological structures, is presented. Integral to this work is the dataset used which must be fit for purpose for IRF segmentation algorithm training and testing. We describe here a multivendor dataset comprised of 30 scans. Each OCT scan for system training has been annotated by multiple graders using a proprietary system. Evaluation of the intergrader annotations shows a good correlation, thus making the reproducibly annotated scans suitable for the training and validation of image processing and machine learning based segmentation methods. The dataset will be made publicly available in the form of a segmentation Grand Challenge.
Health and Social Needs in Three Migrant Worker Communities around La Romana, Dominican Republic, and the Role of Volunteers: A Thematic Analysis and Evaluation
Authors: Miller Aaron S. , Lin Henry C. , Kang Chang-Berm , Loh Lawrence C.
Published: August 2016

Objective.For decades, Haitian migrant workers living in bateyes around La Romana, Dominican Republic, have been the focus of short-term volunteer medical groups from North America. To assist these efforts, this study aimed to characterize various health and social needs that could be addressed by volunteer groups.Design.Needs were assessed using semistructured interviews of community and professional informants, using a questionnaire based on a social determinants of health framework, and responses were qualitatively analysed for common themes.Results.Key themes in community responses included significant access limitations to basic necessities and healthcare, including limited access to regular electricity and potable water, lack of health insurance, high out-of-pocket costs, and discrimination. Healthcare providers identified the expansion of a community health promoter program and mobile medical teams as potential solutions. English and French language training, health promotion, and medical skills development were identified as additional strategies by which teams could support community development.Conclusion.Visiting volunteer groups could work in partnership with community organizations to address these barriers by providing short-term access to services, while developing local capacity in education, healthcare, and health promotion in the long-term. Future work should also carefully evaluate the impacts and contributions of such volunteer efforts.
Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge
Authors: Hung Yu-Chiang , Pan Tai-Long , Hu Wen-Long
Published: August 2016

Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS‐related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF‐α‐induced apoptosis, upregulate caspase‐3, caspase‐8, caspase‐9, endoplasmic reticulum stress, P21, P53, Bax/Bcl‐2, DR5, and AMP‐activated protein kinase, or activate the p38/JNK, mitogen‐activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF‐κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P‐glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Integrated Analysis of the Formation Mechanism of Cracks in a Concrete Dam Using Microseismic Monitoring and Numerical Simulation
Authors: He Gang , Li Biao , Wang Xuben , Xu Nuwen
Published: August 2016

The dam of Guanyinyan hydropower station is composed of a concrete gravity dam in the left bank and a rockfill dam in the right bank. During the operation of the hydropower station, several surface cracks occurred in the concrete gravity dam, which threatened the stability of the dam. To evaluate the evolution trend of the cracks and forecast the potential risk of the dam, the microseismic (MS) monitoring technique and finite-element method were used. First, the concrete three-point bending field test was performed to prove the reliability of the MS technique in monitoring the concrete cracks. The MS monitoring results were consistent with the simulation results. Then, the MS monitoring system was installed in the dam body. By analysing the MS activities before and after the impoundment, the evolution trend of the cracks and potential risk of the dam were evaluated and forecasted. The simulation results were also consistent with the monitoring results. These results can provide significant references for the operation safety of the dam and also present a new thought for the risk evaluation of similar dam engineering.
Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols
Authors: Laganà Antonio Simone , Rossetti Paola , Buscema Massimo , La Vignera Sandro , Condorelli Rosita Angela , Gullo Giuseppe , Granese Roberta , Triolo Onofrio
Published: August 2016

Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS.