bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Analysis of the Exocyst Subunit Sec15 in Candida albicans
Authors: Chavez-Dozal Alba A. , Bernardo Stella M. , Rane Hallie S. , Lee Samuel A. 
Published: October 2015

ABSTRACT

In prior studies of exocyst-mediated late secretion in
Candida albicans
, we have determined that Sec6 contributes to cell wall integrity, secretion, and filamentation. A conditional mutant lacking
SEC6
expression exhibits markedly reduced lateral hyphal branching. In addition, lack of the related t-SNAREs Sso2 and Sec9 also leads to defects in secretion and filamentation. To further understand the role of the exocyst in the fundamental processes of polarized secretion and filamentation in
C. albicans
, we studied the exocyst subunit Sec15. Since
Saccharomyces cerevisiae SEC15
is essential for viability, we generated a
C. albicans
conditional mutant strain in which
SEC15
was placed under the control of a tetracycline-regulated promoter. In the repressed state, cell death occurred after 5 h in the tetR-SEC15 strain. Prior to this time point, the tetR-SEC15 mutant was markedly defective in Sap and lipase secretion and demonstrated increased sensitivity to Zymolyase and chitinase. Notably, tetR-SEC15 mutant hyphae were characterized by a hyperbranching phenotype, in direct contrast to strain tetR-SEC6, which had minimal lateral branching. We further studied the localization of the Spitzenkörper, polarisomes, and exocysts in the tetR-SEC15 and tetR-SEC6 mutants during filamentation. Mlc1-GFP (marking the Spitzenkörper), Spa2-GFP (the polarisome), and Exo70-GFP (exocyst) localizations were normal in the tetR-SEC6 mutant, whereas these structures were mislocalized in the tetR-SEC15 mutant. Following alleviation of gene repression by removing doxycycline, first Spitzenkörper, then polarisome, and finally exocyst localizations were recovered sequentially. These results indicate that the exocyst subunits Sec15 and Sec6 have distinct roles in mediating polarized secretion and filamentation in
C. albicans
.
Measurement in the angiography suite: evaluation of vessel sizing techniques
Authors: Yang Pengfei , Schafer Sebastian , Royalty Kevin , Ahmed Azam , Niemann David , Strother Charles 
Published: October 2015

BackgroundAccurate vessel size measurement is important for neurointervention. Modern angiographic equipment offers various two-dimensional (2D) and 3D measurement methods that have not been systematically evaluated for accuracy and reliability.ObjectiveTo evaluate these methods using anthropomorphic vessel phantoms.Materials and methodsTubing of known sizes (2–5 mm, 1 mm increments) was embedded in 3D-printed skulls to simulate the middle cerebral artery, internal carotid artery, and basilar artery. Each phantom was imaged to gain 3D DSA, 2D DSA, and DynaCT images. Three identical measurement locations were identified on each simulated vessel. Eight measurement methods (four 2D, three 3D, and one DynaCT) were evaluated. Measurements were performed by three independent experienced users on three separate occasions. Intraclass correlation and independent non-parametric analysis were carried out to evaluate the reliability and accuracy of these measurement methods.ResultsBetter reliability was noted for the automatic measurement methods than for the corresponding manual measurement methods. The mean differences with the ground truth for all methods ranged from −0.12 to 0.03 with small SEs (0.02–0.03) and SDs (0.10–0.18). The smallest absolute mean differences were achieved in two automatic measurement methods based on 2D manual calibration and 3D images. In comparison with these two methods, results of measurements based on 2D autocalibration were statistically different.ConclusionsIn our study, automatic analysis using 3D or 2D was the preferred measurement method. Manual calibration on 2D angiograms is necessary to improve the measurement accuracy. It is not known how our results may pertain to other angiographic systems.
Dark matter balls help supernovae to explode
Authors: Froggatt C. D. , Nielsen H. B. 
Published: October 2015

As a solution to the well-known problem that the shock wave potentially responsible for the explosion of a supernova actually tends to stall, we propose a new energy source arising from our model for dark matter. Our earlier model proposed that dark matter should consist of cm-large white dwarf-like objects kept together by a skin separating two different sorts of vacua. These dark matter balls or pearls will collect in the middle of any star throughout its lifetime. At some stage during the development of a supernova, the balls will begin to take in neutrons and then other surrounding material. By passing into a ball nucleons fall through a potential of order 10 MeV, causing a severe production of heat — of order 10 foe for a solar mass of material eaten by the balls. The temperature in the iron core will thereby be raised, splitting up the iron into smaller nuclei. This provides a mechanism for reviving the shock wave when it arrives and making the supernova explosion really occur. The onset of the heating due to the dark matter balls would at first stop the collapse of the supernova progenitor. This opens up the possibility of there being two collapses giving two neutrino outbursts, as apparently seen in the supernova SN1987A — one in Mont Blanc and one 4 h 43 min later in both IMB and Kamiokande.
Dielectric studies of environmentally friendly and flexible lignocelluloses fibrils for miniaturization of patch antenna
Authors: Razaq Aamir , Khan Asim Ali , Asif M. H. , Iqbal Shahid , Ali Jawad , Manzoor Faisal , Awan M. S. 
Published: October 2015

Naturally, existing lignocelluloses fibers showed outstanding potential in paper industry and other conventional applications. On the other hand, lignocellulose fibers are suitable candidate for high-tech applications under the scope of abundance, flexibility, light-weight and environment friendliness. In this study, paper sheets were prepared from lignocelluloses fibers extracted from self-growing plant, typha angustifolia. Lignocelluloses paper sheets were characterized for scanning electron microscopy (SEM), universal testing machine (UTM) and vector network analyzer (VNA). Flexible paper sheets displayed a tensile strength of 9.1 MPa and further used as a substrate in patch antenna to observe dielectric characteristics. The patch antenna is designed at 5.1 GHz which showed return loss less than −10 dB and dielectric constant 3.71. The use of lignocelluloses paper sheet as a substrate in patch antenna will provide the opportunity of miniaturization of size and weight in comparison of a jean substrate based antenna.
Data-Aware Vaccine Allocation Over Large Networks
Authors: Zhang Yao , Prakash B. Aditya 
Published: October 2015

Given a graph, like a social/computer network or the blogosphere, in which an infection (or meme or virus) has been spreading for some time, how to select thekbest nodes for immunization/quarantining immediately? Most previous works for controlling propagation (say via immunization) have concentrated on developing strategies for vaccinationpreemptivelybefore the start of the epidemic. While very useful to provide insights in to which baseline policies can best control an infection, they may not be ideal to makereal-timedecisions as the infection is progressing.In this paper, we study how to immunize healthy nodes, in the presence of already infected nodes. Efficient algorithms for such a problem can help public-health experts make more informed choices, tailoring their decisions to the actual distribution of the epidemic on the ground. First we formulate theData-Aware Vaccinationproblem, and prove it is NP-hard and also that it is hard to approximate. Secondly, we propose three effective polynomial-time heuristics DAVA, DAVA-prune and DAVA-fast, of varying degrees of efficiency and performance. Finally, we also demonstrate the scalability and effectiveness of our algorithms through extensive experiments on multiple real networks including large epidemiology datasets (containing millions of interactions). Our algorithms show substantial gains of up toten timesmore healthy nodes at the end against many other intuitive and nontrivial competitors.
Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma
Authors: Sohn Bo Hwa , Shim Jae-Jun , Kim Sang-Bae , Jang Kyu Yun , Kim Soo Mi , Kim Ji Hoon , Hwang Jun Eul , Jang Hee-Jin , Lee Hyun-Sung , Kim Sang-Cheol , Jeong Woojin , Kim Sung Soo , Park Eun Sung , Heo Jeonghoon , Kim Yoon Jun , Kim Dae-Ghon , Leem Sun-Hee , Kaseb Ahmed , Hassan Manal M. , Cha Minse , Chu In-Sun , Johnson Randy L. , Park Yun-Yong , Lee Ju-Seog 
Published: October 2015

AbstractPurpose: The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC.Experimental Design: We analyzed gene expression data from Mst1/2−/− and Sav1−/− mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses.Results: HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P &lt; 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12–2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P &lt; 0.001).Conclusions: Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. Clin Cancer Res; 22(5); 1256–64. ©2015 AACR.
Bias-Corrected Targeted Next-Generation Sequencing for Rapid, Multiplexed Detection of Actionable Alterations in Cell-Free DNA from Advanced Lung Cancer Patients
Authors: Paweletz Cloud P. , Sacher Adrian G. , Raymond Chris K. , Alden Ryan S. , O'Connell Allison , Mach Stacy L. , Kuang Yanan , Gandhi Leena , Kirschmeier Paul , English Jessie M. , Lim Lee P. , Jänne Pasi A. , Oxnard Geoffrey R. 
Published: October 2015

Abstract
Purpose: Tumor genotyping is a powerful tool for guiding non–small cell lung cancer (NSCLC) care; however, comprehensive tumor genotyping can be logistically cumbersome. To facilitate genotyping, we developed a next-generation sequencing (NGS) assay using a desktop sequencer to detect actionable mutations and rearrangements in cell-free plasma DNA (cfDNA).
Experimental Design: An NGS panel was developed targeting 11 driver oncogenes found in NSCLC. Targeted NGS was performed using a novel methodology that maximizes on-target reads, and minimizes artifact, and was validated on DNA dilutions derived from cell lines. Plasma NGS was then blindly performed on 48 patients with advanced, progressive NSCLC and a known tumor genotype, and explored in two patients with incomplete tumor genotyping.
Results: NGS could identify mutations present in DNA dilutions at ≥0.4% allelic frequency with 100% sensitivity/specificity. Plasma NGS detected a broad range of driver and resistance mutations, including ALK, ROS1, and RET rearrangements, HER2 insertions, and MET amplification, with 100% specificity. Sensitivity was 77% across 62 known driver and resistance mutations from the 48 cases; in 29 cases with common EGFR and KRAS mutations, sensitivity was similar to droplet digital PCR. In two cases with incomplete tumor genotyping, plasma NGS rapidly identified a novel EGFR exon 19 deletion and a missed case of MET amplification.
Conclusions: Blinded to tumor genotype, this plasma NGS approach detected a broad range of targetable genomic alterations in NSCLC with no false positives including complex mutations like rearrangements and unexpected resistance mutations such as EGFR C797S. Through use of widely available vacutainers and a desktop sequencing platform, this assay has the potential to be implemented broadly for patient care and translational research. Clin Cancer Res; 22(4); 915–22. ©2015 AACR.
See related commentary by Tsui and Berger, p. 790
Role of Indoxyl Sulfate as a Predisposing Factor for Atrial Fibrillation in Renal Dysfunction
Authors: Aoki Kohei , Teshima Yasushi , Kondo Hidekazu , Saito Shotaro , Fukui Akira , Fukunaga Naoya , Nawata Tomoko , Shimada Tatsuo , Takahashi Naohiko , Shibata Hirotaka 
Published: October 2015

Background

Renal dysfunction is a major risk factor for atrial fibrillation (
AF
). The uremic toxin indoxyl sulfate may contribute to the progression of cardiac fibrosis and
AF
substrate in renal dysfunction.

Methods and Results

Male Sprague–Dawley rats were assigned randomly to the following groups: 5/6 nephrectomy (5/6Nx) with vehicle, 5/6Nx with
AST
‐120, sham procedure with vehicle, and sham procedure with
AST
‐120. Vehicle and
AST
‐120 were administered for 4 weeks. Serum levels of
IS
were significantly increased in 5/6Nx groups. Expression of malondialdehyde, an indicator of oxidative stress, was upregulated in the left atrium of 5/6Nx groups and was accompanied by an increase in expression of
NADPH
oxidase 2 and 4. Monocyte‐mediated inflammatory signals such as
CD
68, monocyte chemoattractant protein 1, and vascular cell adhesion molecule 1 were also upregulated in 5/6Nx groups. Interstitial fibrosis was promoted heterogeneously, and expression of profibrotic indicators such as transforming growth factor β1, α‐smooth muscle actin, and collagen type 1 was upregulated in left atrium tissue of 5/6Nx groups. In cultured atrial fibroblasts, incubation with
IS
upregulated expression of the markers of oxidative stress, inflammation, and profibrotic factors. These results suggest the direct effects of
IS
on the progression of
AF
substrate.
AF
was consistently and invariably induced by atrial extrastimuli in 5/6Nx groups in electrophysiological experiments.
AST
‐120 treatment significantly alleviated renal dysfunction–induced oxidative stress, inflammation, and atrial fibrosis and, consequently, attenuated
AF
inducibility.

Conclusions

Indoxyl sulfate facilitates atrial fibrosis and
AF
and thus is a novel therapeutic target for prevention of renal dysfunction–induced
AF
.
Survival After Ventricular Fibrillation Cardiac Arrest in the Sao Paulo Metropolitan Subway System: First Successful Targeted Automated External Defibrillator (AED) Program in Latin America
Authors: Gianotto‐Oliveira Renan , Gonzalez Maria Margarita , Vianna Caio Brito , Monteiro Alves Maurício , Timerman Sergio , Kalil Filho Roberto , Kern Karl B. 
Published: October 2015

Background

Targeted automated external defibrillator (
AED
) programs have improved survival rates among patients who have an out‐of‐hospital cardiac arrest (
OHCA
) in
US
airports, as well as European and Japanese railways. The Sao Paulo (Brazil) Metro subway carries 4.5 million people per day. A targeted
AED
program was begun in the Sao Paulo Metro with the objective to improve survival from cardiac arrest.

Methods and Results

A prospective, longitudinal, observational study of all cardiac arrests in the Sao Paulo Metro was performed from September 2006 through November 2012. This study focused on cardiac arrest by ventricular arrhythmias, and the primary endpoint was survival to hospital discharge with minimal neurological impairment. A total of 62 patients had an initial cardiac rhythm of ventricular fibrillation. Because no data on cardiac arrest treatment or outcomes existed before beginning this project, the first 16 months of the implementation was used as the initial experience and compared with the subsequent 5 years of full operation. Return of spontaneous circulation was not different between the initial 16 months and the subsequent 5 years (6 of 8 [75%] vs. 39 of 54 [72%];
P
=0.88). However, survival to discharge was significantly different once the full program was instituted (0 of 8 vs. 23 of 54 [43%];
P
=0.001).

Conclusions

Implementation of a targeted
AED
program in the Sao Paulo Metro subway system saved lives. A short interval between arrest and defibrillation was key for good long‐term, neurologically intact survival. These results support strategic expansion of targeted
AED
programs in other large Latin American cities.
Annual Drought in California: Association with Monthly Precipitation and Climate Phases
Authors: Shukla Shraddhanand , Steinemann Anne , Iacobellis Sam F. , Cayan Daniel R. 
Published: October 2015

AbstractAnnual precipitation in California is more variable than in any other state and is highly influenced by precipitation in winter months. A primary question among stakeholders is whether low precipitation in certain months is a harbinger of annual drought in California. Historical precipitation data from 1895 to 2013 are investigated to identify leading monthly indicators of annual drought in each of the seven climate divisions (CDs) as well as statewide. For this study, drought conditions are defined as monthly/annual (October–September) precipitation below the 20th/30th percentile, and a leading indicator is defined as a monthly drought preceding or during an annual drought that has the strongest association (i.e., joint probability of occurrence) with a statewide annual drought. Monthly precipitation variability and contributions to annual precipitation, along with joint probabilities of drought among the winter months, are first analyzed. Then the probabilities of annual drought and the variability in leading indicators are analyzed according to different climate phases and CDs. This study identified December within a water year as being the leading indicator that is most frequently associated with annual drought statewide (56%) and in most of the CDs (the highest was CD2 at 65%). Associated with its leading-indicator status, December drought was most frequently associated with drought in other winter months (joint probability > 30%). Results from this study can help stakeholders to understand and assess the likelihood of annual drought events given monthly precipitation preceding or early in the water year.
A Novel In Vivo Protocol for Molecular Study of Radiation-Induced Fibrosis in Head and Neck Cancer Patients
Authors: Krisciunas Gintas P. , Platt Michael , Trojanowska Maria , Grillone Gregory A. , Haines Paul C. , Langmore Susan E. 
Published: October 2015

Objectives: Radiation-induced fibrosis is a common complication for patients following head and neck cancer treatment. This study presents a novel minimally invasive protocol for molecular study of fibrosis in the stromal tissues. Methods: Subjects with radiation-induced fibrosis in the head and neck who were at least 6 months post treatment received submental core needle biopsies, followed by molecular processing and quantification of gene expression for 14 select pro-inflammatory and pro-fibrotic genes. Control biopsies from the upper arm were obtained from the same subjects. Patients were followed up at 1 and 2 weeks to monitor for safety and adverse outcomes. Results: Six subjects were enrolled and completed the study. No subjects experienced adverse outcomes or complication. An 18 gauge core biopsy needle with a 10 mm notch inserted for up to 60 seconds was needed. Subcutaneous tissue yielded 3 ng of RNA, amplified to 6 µg of cDNA, allowing for adequately sensitive quantitative polymerase chain reaction (qPCR) analysis of approximately 28 genes. Conclusions: This study demonstrates the safety and utility of a novel technique for the molecular study of fibrosis in head and neck cancer patients. Longitudinal studies of patients undergoing radiation therapy will allow for identification of molecular targets that contribute to the process of fibrosis in the head and neck.
Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample
Authors: Breda Vitor , Rovaris Diego Luiz , Vitola Eduardo Schneider , Mota Nina Roth , Blaya-Rocha Paula , Salgado Carlos Alberto Iglesias , Victor Marcelo Moraes , Picon Felipe Almeida , Karam Rafael Gomes , Silva Katiane Lilian , Rohde Luis Augusto , Bau Claiton Henrique Dotto , Grevet Eugenio Horacio 
Published: October 2015

Objectives: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. Methods: Adult patients with attention-deficit/hyperactivity disorder ( n = 449) and non-attention-deficit/hyperactivity disorder subjects ( n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement ( n = 277) and disagreement ( n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. Results: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta2 < 0.05). Conclusion: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.