bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of DLL3 expression and clinicopathologic features in small cell bladder cancer (SCBC).
Authors: Koshkin Vadim S. , Elson Paul , Magi-Galluzzi Cristina , McKenney Jesse , Smith Karen Streator , Shadrach Bonnie , Emamekhoo Hamid , Isse Kumiko , Saunders Laura , Kavalerchik Edward , Dylla Scott , Bheddah Sheila , Theiss Noah , Watson Sky , Stephenson Andrew J. , Fergany Amr Farouk , Rini Brian I. , Garcia Jorge A. , Grivas Petros
Published: March 2017

382

Background: SCBC is rare with limited data on treatment and outcomes. DLL3, a Notch pathway protein, is expressed in small cell lung cancer (SCLC) and neuroendocrine tumors. Phase I/II trials of the anti-DLL3 antibody-drug conjugate, rovalpituzumab tesirine, are ongoing in SCLC and other solid tumors. DLL3 expression in SCBC and its prognostic implications are unknown. Methods: A retrospective review of clinicopathologic features of 63 patients (pts) with biopsy-confirmed SCBC at Cleveland Clinic (1993-2016) was conducted. Percentage (%) of small cell component (SC%) was defined by independent pathology review in all pts. The % of tumor cells expressing DLL3 (DLL3%) was assessed in 53 pts. Multivariable analyses (MVA) were used to identify predictors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP) (p ≤ .05). Results: Median age was 71 (39-90), 83% were men, 77% current/former smokers, 41 (65%) had cystectomy and 22 (35%) only TURBT. Estimated median OS, PFS and TTP were 22.8, 13.7 and 21.1 months from diagnosis. Median SC% was 100% (5-100%) and 79% of tumors were ≥ 50% SC. DLL3 expression of any level was noted in 68% (36/53) of tumors; 58% of tumors had DLL3 expression in > 10% of cells. SC% correlated with DLL3% (r = 0.33, p = .01). In MVA, increased DLL3% was associated with shorter OS and PFS, while increased SC% was associated with shorter PFS and TTP. Higher pT at cystectomy was associated with shorter OS (Table). Conclusions: Higher DLL3 expression and SC% are associated with worse outcomes in SCBC. Most SCBC tumors express DLL3, a therapeutic target tested in clinical trials. Genomic, epigenetic, transcriptomic and PDL1 evaluation in SCBC are also being pursued to define molecular context. DLL3 expression and other prognostic factors. [Table: see text]
Phase II trial of TI-CE high dose chemotherapy (HDCT) with drug monitoring for individual carboplatin dosing in patients with relapsed advanced germ cell tumors: A multicentric prospective GETUG trial.
Authors: Chevreau Christine , Massard Christophe , Flechon Aude , Delva Remy , Gravis Gwenaelle , Lotz Jean-Pierre , Bay Jacques-Olivier , Gross-Goupil Marine , Fizazi Karim , Mourey Loic , Thomas Fabienne , Filleron Thomas , Olivier Pascale , Culine Stephane , Chatelut Etienne
Published: March 2017

401

Background: HDCT is a valid option of treatment for relapsed advanced GCTs pts. The results of the TICE regimen as salvage therapy in poor risk pts demonstrated a 50% complete response (CR) but with very high variability of measured carboplatin area under the curve (AUC) (between 10.9-36.7 for target AUC = 24 mg.min/mL). We initiated a phase II trial of TICE with therapeutic drug monitoring (TDM) for individual carboplatin dosing in order to target the 3-day AUC to 24 mg/min/mL. Methods: Were included pts with unfavorable relapsed GCTs , secondarily classified according to the International Prognostic Factors Study Group. Pts were treated according the TICE regimen with two cycles combining paclitaxel and ifosfamide followed by three cycles HDCT: carboplatin plus etoposide with stem cell support. Carboplatin dose was adapted on day 3 based on carboplatin clearance (Cl) at day 1, in order to reach the target AUC. The primary endpoint was the CR rate (cCR sCR pCR). A Simon Minimax design was performed using the following hypothesis: p0 = 50%, p1 = 65 α = 5%, β = 10%. Results: Between 03/2009 and 11/2015 101 pts were accrued, 60 pts were treated in first relapse (34 classified as high and very high-risk) and 41 in 2ndor more relapse. 72 pts (71%) received the whole treatment, 12 pts (10%) did not receive any cycle of HDCT. 29pts (26%) stopped treatment earlier, 8 for toxicity. Three pts died on treatment. 35/79 (44.3%) evaluable pts achieved a CR. 19 pts (24%) presented a PRm-. The mean observed carboplatin AUC was 24.5 mg.min/mL (between 18.9 and 28.8) at C1.Following TDM, the modification of the total carboplatin dose during C1 was comprised between -33% and +44%, showing the benefit of TDM in comparison with individual dosing based only on carboplatin Cl predicted according to patient’s renal characteristics. Conclusions: The CR rate observed in this very poor prognosis population was 44.3% and 69.6% CR + PRm-. Carboplatin dose individualization based on TDM allowed to reach more accurately the target AUC compared to previous reports. Clinical trial information: NCT00864318.
Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative magnetic resonance imaging.
Authors: Pedrosa Ivan , Zhang Yue , Udayakumar Durga , Cai Ling , Hu Zeping , Kapur Payal , Diaz de Leon Alberto , Yuan Qing , Yokoo Takeshi , Ye Jin , Mitsche Mathew , Kim Hyeonwoo , McDonald Jeffrey , Xi Yin , Madhuranthakam Ananth J , Lenkinski Robert , Cadeddu Jeffrey A , Brugarolas James , DeBerardinis Ralph
Published: March 2017

460

Background: Dysregulated lipid and glucose metabolism has been implicated in clear cell renal cell carcinoma (ccRCC) progression. Pre-operative tissue-based assessment of tumor metabolic alterations is challenging due to the characteristic heterogeneity of ccRCC. Non-invasive prediction of metabolic alterations in the whole tumor with an imaging method would be appealing for optimal patient management and possibly selection of targeted neoadjuvant therapy. Methods: In this IRB-approved, HIPAA-compliant study, 43 patients (34 M, 9 F) with pathologically confirmed primary ccRCC underwent pre-surgical MRI to quantify whole-tumor intra-tumoral lipid accumulation (% fat fraction, FF) and tumor enhancement (% enhancement) with Dixon-based MRI and dynamic contrast-enhanced MRI, respectively. All patients signed informed consent. Quantitative MRI measures were also obtained from targeted regions of interest within tumors and correlated to lipid accumulation (Oil Red O, ORO) and mass spectrometry-based lipidomics and metabolomics of tissue samples isolated from anatomically co-registered locations in the same tumor using fiducial markers placed at the time of surgery. Linear regression was performed to correlate FF and ORO %. Univariate statistical differences of the metabolites between two groups were analyzed using Student’s t-test. Results: In vivo tumor FF correlated positively with histologic fat content (Spearman correlation coeff. ρ = 0.86, p <0.0001), spectrometric triglycerides (ρ = 0.56, p = 0.0007) and cholesterol (ρ = 0.47, p = 0.006), respectively; and negatively with spectrometric free fatty acids (ρ = -0.44, p = 0.01) and phospholipids (ρ = -0.65, p = 0.001), respectively. ISUP grade 2 and 3 tumors exhibited marked intra-tumoral FF heterogeneity, whereas grade 4 tumors had reduced lipid accumulation compared to grade 3 (p = 0.016). Aqueous metabolites were different in tumors compared to renal parenchyma and 11 metabolites showed significant correlation with tumor vascularity (FDR p <0.05). Conclusions: MRI-derived FF and tumor enhancement correlated with the altered metabolic features of ccRCC and the metabolic heterogeneity within a given tumor.
Health-related quality of life (HRQoL), treatment satisfaction, and work productivity for patients (Pts) with advanced renal cell carcinoma (aRCC) in a chart review across six countries.
Authors: Hawkins Robert , Doan Justin , Deshpande Chinmay , Solem Caitlyn , Yang Shuo , Jiang Shan , Macahilig Cynthia
Published: March 2017

487

Background: The humanistic burden of aRCC is not well understood. We describe HRQoL, functional status, treatment satisfaction, and work productivity reported by pts treated with ≥2 lines of treatment (LOT) for aRCC in 6 countries. Methods: Retrospective, observational medical chart review of adults with stage IIIB/IV aRCC who completed the EuroQoL-5D-3L (EQ-5D), Functional Assessment of Cancer Therapy – General (FACT-G)/FACT-Kidney Symptom Index (FKSI-19), Cancer Therapy Satisfaction Questionnaire (CTSQ), and Work Productivity and Activity Impairment (WPAI) questionnaires. FACT-G scores were examined with regression analysis. Results: All measures were impacted by aRCC (Table). Dimensions affected: EQ-5D, pain/discomfort; FACT-G and FKSI-19, functional/emotional; CTSQ, feelings about side effects; WPAI, activity impairment. EQ-5D, FACT-G, FKSI-19 scores were higher (by minimal important difference) in France and Canada vs. other countries. FACT-G scores differed by region, and were higher in Canada and France vs. the USA. Female sex and 2nd LOT were predictors of lower FACT-G score. Conclusions: This study showed a high humanistic burden on aRCC pts across countries. New treatments with reduced side effects and improved effectiveness can help yield improvements in HRQoL, treatment satisfaction, and work productivity. [Table: see text]
Performance of a validated urine exosome gene expression assay to predict high-grade prostate cancer utilizing the International Society of Urological Pathology (ISUP) 2014 grading system.
Authors: Donovan Michael , Torkler Phillipp , Skog Johan , Noerholm Mikkel , Carroll Peter
Published: March 2017

49

Background: Overdetection and overtreatment of indolent prostate cancer (PCa) remains a significant health issue requiring noninvasive assays to guide the prostate biopsy decision process. We demonstrated that a urine exosome gene expression assay (ExoDx P rostate ( I ntelliScore) (EPI) discriminates GS 7 PCa from GS 6 and benign disease, potentially reducing the number of unnecessary biopsies. The International Society of Urological Pathology (ISUP) proposed a prognostic PCa grading system to accurately reflect the biology of PCa; ISUP separates GS 7 PCa into group 2 (GS 3+4) and group 3 (GS 4+3). We sought to evaluate the performance of the EPI test according to the newly proposed ISUP system. Methods: The 519 patient validation cohort was re-annotated using ISUP and assessed benign (B) +/- ISUP 1 and B+ISUP 1+2 (GS 3+3, GS 3+4) from ISUP 3-5 (GS >= 4+3). We used validated / adjusted cut-points to assess performance with the AUC, sensitivity, specificity and NPV. In addition, we investigated the association of the EPI score with the benign biopsies (BB) and ISUP groups in the combined training and test cohort (n=774). Results: Applying the adjusted cut point (EPI 20) on the 519 ISUP cohort discriminated benign biopsies (BB) + ISUP 1 from >/=ISUP 2, 37% of biopsies avoided, NPV of 90%, equivalent to Gleason grading. Utilizing either the validated (15.6) or adjusted cut points on BB+ISUP 1+ 2 vs. >/=ISUP 3 (dominant pattern 4), 26% vs 37% biopsies avoided, with an improved NPV 98%. In the combined training / test cohort, higher EPI scores were significantly associated with ISUP categories. In this analysis EPI in BB vs. all ISUP groups (p<0.0001); BB+ISUP 1 vs. >/= ISUP2 (p<0.0001) and BB+ISUP 1+2 vs. >/=ISUP3 (p<0.0001); supporting accurate discrimination in high grade PCa. Conclusions: The EPI test is a noninvasive, first-catch non-DRE gene expression assay that accurately discriminates low-grade from high-grade PCa in both ISUP as well as Gleason score based grading systems. The test has the potential to reduce the number of unnecessary biopsies and performs equally well in contemporary approaches to PCa stratification.
Pembrolizumab (pembro) plus low-dose ipilimumab (ipi) for patients (pts) with advanced renal cell carcinoma (RCC): Phase 1 KEYNOTE-029 study.
Authors: Choueiri Toni K. , Hodi F. Stephen , Thompson John A. , McDermott David F. , Hwu Wen-Jen , Lawrence Donald P. , Dawson Nancy Ann , Wong Deborah Jean Lee , Bhatia Shailender , James Marihella , Shu Xinxin , Homet Moreno Blanca , Ibrahim Nageatte , Perini Rodolfo F. , Ribas Antoni , Atkins Michael B.
Published: March 2017

510

Background: The CTLA-4 antibody ipi and the PD-1 antibody pembro have demonstrated efficacy in pts with advanced malignancies. While these immune checkpoint inhibitors have shown robust activity as monotherapy, combination therapy may further improve outcomes. KEYNOTE-029 (NCT02089685) is a phase 1/2 study designed to assess the safety and efficacy of pembro + ipi or pegylated interferon alfa-2b (IFN-α) in pts with advanced melanoma or RCC. Here we report data from the phase 1 portion of the study in pts with RCC treated with pembro + ipi. Methods: Pts ≥18 years with advanced/unresectable or metastatic clear cell RCC who received ≥1 prior therapy for metastatic disease, had ≥1 measurable lesion per RECIST v1.1, and ECOG PS 0-1 were enrolled. Pts received pembro 2 mg/kg Q3W + low-dose ipi (1 mg/kg Q3W for 4 doses) until disease progression, unacceptable toxicity, investigator/patient decision, or 2 years of pembro treatment. AEs were monitored throughout treatment and for 30 days thereafter and graded per NCI CTCAE v4.0. Primary end point was safety; primary efficacy end point was ORR assessed per RECIST v1.1 by independent central imaging vendor review. Results: As of the March 17, 2016, data cutoff, 10 pts with RCC received pembro + low-dose ipi. 60% were male, 70% were white, median age was 61 years (range, 48-70 years), 40% received 2 prior lines of therapy, and 40% received prior immunotherapy. With a median follow-up of 17.4 months (0.9-23.5 months), 70% of pts experienced treatment-related AEs (TRAEs) of any grade, most commonly fatigue (30%); and 50% experienced grade 3/4 TRAEs, most commonly increased lipase (20%). 50% of pts discontinued pembro because of TRAEs, most commonly increased lipase (40%). There were no treatment-related deaths. ORR was 20% (2 partial responses); median duration of response was not reached (14.1+-17.1 months+). An additional 3 pts had stable disease; disease control rate was 50%. Conclusions: The combination of pembro + low-dose ipi for 4 doses, followed by pembro monotherapy, demonstrates a manageable toxicity profile and preliminary antitumor activity in pts with advanced RCC. Clinical trial information: NCT02089685.
Outcomes based on age in the phase 3 METEOR trial of cabozantinib (cabo) versus everolimus (eve) in patients with advanced renal cell carcinoma (RCC).
Authors: Donskov Frede , Motzer Robert J. , Voog Eric , Hovey Elizabeth J. , Grüllich Carsten , Nott Louise M. , Cuff Katharine , Gil Thierry , Jensen Niels Viggo , Chevreau Christine , Negrier Sylvie , Depenbusch Reinhard , Bergmann Lothar , Cornelio Izzy , Champsaur Anne , Escudier Bernard , Pal Sumanta K. , Powles Thomas , Choueiri Toni K.
Published: March 2017

517

Background: In the METEOR study (NCT01865747), cabo demonstrated improved progression-free survival (median 7.4 vs. 3.8 mo; HR 0.58, 95% CI 0.45–0.74; p<0.0001), OS (median 21.4 vs. 16.5 mo; HR 0.66, 95% CI 0.53-0.83, p=0.0003), and objective response rate (17% vs. 3%; p<0.0001) compared with eve in patients (pts) with advanced RCC who had received prior VEGFR TKI therapy (Choueiri NEJM 2015, Lancet Oncol 2016). Here we evaluate the impact of changes in target lesion size from baseline on OS. Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed per independent radiology review by CT/MRI scans at baseline, every 8 weeks for the first 12 months, and every 12 weeks thereafter. Three subgroups were defined by best change in target lesion size from baseline: decrease ≥30%, decrease <30%, and any increase. Results: The rate of target lesion regression was higher in the cabo arm (75%) compared with the eve arm (48%). A higher fraction of pts had a decrease ≥30% in target lesion size in the cabo arm, while a higher fraction of pts had an increase in target lesion size in the eve arm (Table). Medians for OS with cabo were not estimable (NE) (95% CI, NE‒NE), 20.8 mo (95% CI, 18.1‒NE), and 11.1 mo (95% CI, 7.6‒15.2) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Medians for OS with eve were NE (95% CI, 19.3‒NE), 18.0 mo (95% CI, 15.9‒20.4), and 14.0 mo (95% CI, 10.5‒16.3) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Median duration of follow-up for OS was 18.7 mo (IQR 16.1–21.1) for cabo and 18.8 mo (16.0–21.2) for eve. A higher proportion of pts received subsequent anticancer therapy in the any increase subgroup compared with the other subgroups. Conclusions: Cabo demonstrated a higher rate of tumor target lesion regression than eve, and greater target lesion regression was associated with improved OS in pts with advanced RCC. Clinical trial information: NCT01865747.
Evaluation of sexual function on a randomized trial of a prostate rectal spacer.
Authors: Hamstra Daniel A. , Shah Dhiren , Kurtzman Steven , Sylvester John , Zimberg Shawn H. , Hudes Richard S. , Karsh Lawrence Ivan , Logsdon Mark D. , Beyer David , Kos Michael , Hsi R. Alex , Forsythe Kevin , Soffen Edward M , Francke Patrick M , Zhang Hong , DeWeese Theodore L. , Ellis Rodney J. , Bogart Jeffrey , Mantz Constantine , Mariados Neil
Published: March 2017

69

Background: The SpaceOAR phase 3 trial showed that a hydrogel spacer between the prostate and rectum decreased rectal dose and toxicity while improving bowel quality of life (QOL) after image guided prostate IMRT to 79.2 Gy. Here we evaluated dose to penile bulb as well as sexual function on this trial Methods: Sexual QOL was measured with the Expanded Prostate Cancer Index Composite (EPIC) by mean summary scores and the proportion of patients with a minimally important decline (MID) (11 points). Stratification was based on severe erectile dysfunction (ED)(EPIC < = 60) vs not. The single question on “Erections sufficient for intercourse over the preceding 4 weeks” was also evaluated. Results: Median Follow-up was 37 months with 63% of men evaluable at 3 years. With spacer the dose to the penile bulb was reduced for mean (21 vs 11 Gy), Dmax (46 vs 36 Gy), and V10-V30 (all p < 0.05). Baseline sexual function was 53 (±24) with 54% having severe ED with no difference between arms (p > 0.1). At 3 years average EPIC score was 39.7 (± 23) and 82% had severe ED with no differences between arms (p > 0.1). At enrollment 42% had EPIC > 60 with average summary of 77 (±8.3) which at 3 years was 53 (±24.8). In this sub-group at 3 years a higher EPIC was observed on the Spacer arm (57.7 (±24.1) vs. 44.6 (± 24.4)) which met the threshold for an MID without statistical significance (p = 0.07). Based on MID and twice that there was a trend favoring Spacer with 53% vs 75% for 11-point decline (p = 0.064) and 41% vs 60% for 22 point decline (p = 0.11). A small number of these men were potent at baseline and evaluable both at baseline and 3 years (n = 49). Of these 37.5% in the Control arm had erections sufficient for intercourse at 3 years as compared to 66.7% (p = 0.07) in the Spacer arm. Power analysis revealed 35% power to detect a change of 11 points between arms and 27% power to detect a difference of 22 points. Conclusions: The use of a hydrogel spacer decreased dose to the penile bulb with a suggestion of a clinically significant improvement in patient reported sexual function and potency. These did not achieve statistical significance potentially due to the high prevalence of ED at baseline and, therefore, the small evaluable sample size. Analysis of penile bulb dose and QOL is ongoing. Clinical trial information: NCT01538628.
A radical shift in perspective: mitochondria as regulators of reactive oxygen species
Authors: Munro Daniel , Treberg Jason R.
Published: March 2017

Mitochondria are widely recognized as a source of reactive oxygen species (ROS) in animal cells, where it is assumed that over-production of ROS leads to an overwhelmed antioxidant system and oxidative stress. In this Commentary, we describe a more nuanced model of mitochondrial ROS metabolism, where integration of ROS production with consumption by the mitochondrial antioxidant pathways may lead to the regulation of ROS levels. Superoxide and hydrogen peroxide (H2O2) are the main ROS formed by mitochondria. However, superoxide, a free radical, is converted to the non-radical, membrane-permeant H2O2; consequently, ROS may readily cross cellular compartments. By combining measurements of production and consumption of H2O2, it can be shown that isolated mitochondria can intrinsically approach a steady-state concentration of H2O2 in the medium. The central hypothesis here is that mitochondria regulate the concentration of H2O2 to a value set by the balance between production and consumption. In this context, the consumers of ROS are not simply a passive safeguard against oxidative stress; instead, they control the established steady-state concentration of H2O2. By considering the response of rat skeletal muscle mitochondria to high levels of ADP, we demonstrate that H2O2 production by mitochondria is far more sensitive to changes in mitochondrial energetics than is H2O2 consumption; this concept is further extended to evaluate how the muscle mitochondrial H2O2 balance should respond to changes in aerobic work load. We conclude by considering how differences in the ROS consumption pathways may lead to important distinctions amongst tissues, along with briefly examining implications for differing levels of activity, temperature change and metabolic depression.
The independence of eye movements in a stomatopod crustacean is task dependent
Authors: Daly Ilse M. , How Martin J. , Partridge Julian C. , Roberts Nicholas W.
Published: March 2017

Stomatopods have an extraordinary visual system, incorporating independent movement of their eyes in all three degrees of rotational freedom. In this work, we demonstrate that in the peacock mantis shrimp, Odontodactylus scyllarus, the level of ocular independence is task dependent. During gaze stabilization in the context of optokinesis, there is weak but significant correlation between the left and right eyes in the yaw degree of rotational freedom, but not in pitch and torsion. When one eye is completely occluded, the uncovered eye does not drive the covered eye during gaze stabilization. However, occluding one eye does significantly affect the uncovered eye, lowering its gaze stabilization performance. There is a lateral asymmetry, with the magnitude of the effect depending on the eye (left or right) combined with the direction of motion of the visual field. In contrast, during a startle saccade, the uncovered eye does drive a covered eye. Such disparate levels of independence between the two eyes suggest that responses to individual visual tasks are likely to follow different neural pathways.
3′ Uridylation controls mature microRNA turnover during CD4 T-cell activation
Authors: Gutiérrez-Vázquez Cristina , Enright Anton J. , Rodríguez-Galán Ana , Pérez-García Arantxa , Collier Paul , Jones Matthew R. , Benes Vladimir , Mizgerd Joseph P. , Mittelbrunn María , Ramiro Almudena R. , Sánchez-Madrid Francisco
Published: March 2017

Activation of T lymphocytes requires a tight regulation of microRNA (miRNA) expression. Terminal uridyltransferases (TUTases) catalyze 3′ nontemplated nucleotide addition (3′NTA) to miRNAs, which may influence miRNA stability and function. Here, we investigated 3′NTA to mature miRNA in CD4 T lymphocytes by deep sequencing. Upon T-cell activation, miRNA sequences bearing terminal uridines are specifically decreased, concomitantly with down-regulation of TUT4 and TUT7 enzymes. Analyzing TUT4-deficient T lymphocytes, we proved that this terminal uridyltransferase is essential for the maintenance of miRNA uridylation in the steady state of T lymphocytes. Analysis of synthetic uridylated miRNAs shows that 3′ addition of uridine promotes degradation of these uridylated miRNAs after T-cell activation. Our data underline post-transcriptional uridylation as a mechanism to fine-tune miRNA levels during T-cell activation.
B-cell tolerance and autoimmunity
Authors: Tsubata Takeshi
Published: March 2017

Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1. Self-reactive B cells generated by somatic mutations during GC reaction are also eliminated. Fas is not directly involved in this process but prevents persistence of GC reaction that allows generation of less stringently regulated B cells, including self-reactive B cells. Defects in self-tolerance preferentially cause lupus-like disease with production of anti-nuclear antibodies, probably due to the presence of a large potential B-cell repertoire reactive to nucleic acids and the presence of nucleic acid-induced activation mechanisms in various immune cells, including B cells and dendritic cells. A feed-forward loop composed of anti-nuclear antibodies produced by B cells and type 1 interferons secreted from nucleic acid-activated dendritic cells plays a crucial role in the development of systemic lupus erythematosus.
Contents
Authors: AMS Editorial
Published: March 2017

Research papers

Technical paper

Technical notes

Rewievers in year 2016
An Integer solution in Intuitionistic Transportation Problem with Application in Agriculture
Authors: Lone M. A , Mir S. A , Wani M.S
Published: March 2017

In this paper, we investigate a Transportation problem which is a special kind of linear programming in which profits; supply and demands are considered as Intuitionistic triangular fuzzy numbers. The crisp values of these Intuitionistic triangular fuzzy numbers are obtained by defuzzifying them and the problem is formulated into linear programming problem. The solution of the formulated problem is obtained through LINGO software. If the obtained solution is non-integer then Branch and Bound method can be used to obtain an integer solution.
Workload Consolidation using Task Scheduling Strategy Based on Genetic Algorithm in Cloud Computing
Authors: Vihol Ronak , Patel Hiren , Patel Nimisha
Published: March 2017

Offering “Computing as a utility” on pay per use plan, Cloud computing has emerged as a technology of ease and flexibility for thousands of users over last few years. Distribution of dynamic workload among available servers and efficient utilization of existing resources in datacenter is one of the major concerns in Cloud computing. The load balancing issue needs to take into consideration the utilization of servers, i.e. the resultant utilization should not exceed the preset upper limits to avoid service level agreement (SLA) violation and should not fall beneath stipulated lower limits to avoid keeping some servers in active use. Scheduling of workload is regarded as an optimization problem that considers many varying criterion such as dynamic environment, priority of incoming applications, their deadlines etc. to improve resource utilization and overall performance of Cloud computing. In this work, a Genetic Algorithm (GA) based novel load balancing mechanism is proposed. Though not done in this work, in future, we aim to compare performance of proposed algorithms with existing mechanisms such as first come first serve (FCFS), Round Robin (RR) and other search algorithms through simulations.
Virtual Reality Treatments for Specific Phobias: A Review
Authors: Roy Sumit , Kavitha R
Published: March 2017

Virtual reality is becoming one of the seamless technology which can be used to treat several psychological problems such as anxiety disorders. With the advancement of technology virtual reality is becoming available to ordinary practitioners to carry out non-clinical therapies. An effective virtual reality system provides the user with total immersion and becomes a part of the virtual world. This study provides an insight as how virtual reality could provide means to overpower anxiety disorders through a controlled environment which is being projected to participants suffering from specific phobias.
Z-Dijkstra’s Algorithm to solve Shortest Path Problem in a Z-Graph
Authors: Biswas Siddhartha
Published: March 2017

In this paper the author introduces the notion of Z-weighted graph or Z-graph in Graph Theory, considers the Shortest Path Problem (SPP) in a Z-graph. The classical Dijkstra’s algorithm to find the shortest path in graphs is not applicable to Z-graphs. Consequently the author proposes a new algorithm called by Z-Dijkstra's Algorithm with the philosophy of the classical Dijkstra's Algorithm to solve the SPP in a Z-graph.
Predictive Analytics – The Cognitive Analysis
Authors: Narayana T , Shaik Sohail , Kaur S
Published: March 2017

Predictive analytics plays an important role in the decision-making process and intuitive business decisions, by overthrowing the traditional instinct process. Predictive analytics utilizes data-mining techniques in order to predict the future outcomes with a high level of certainty. This advanced branch of data engineering is composed of various analytical and statistical methods which are used to develop models that predict the future occurrences. This paper examines the concepts of predictive analytics and various mining methods to achieve the prior. In conclusion, paper discusses process and issues involved in the knowledge discovery process.
Churn Analysis in Telecommunication Using Logistic Regression
Authors: Sebastian Helen , Wagh Rupali
Published: March 2017

Since the beginning of data mining the discovery of knowledge from the Databases has been carried out to solve various problems and has helped the business come up with practical solutions. Large companies are behind improving revenue due to the increase loss in customers.

The process where one customer leaves one company and joins another is called as churn. This paper will be discussing how to predict the customers that might churn, R package is being used to do the prediction. R package helps represent large dataset churn in the form of graphs which will help to depict the outcome in the form of various data visualizations. Churn is a very important area in which the telecom domain can make or lose their customers and hence the business/industry spends a lot of time doing predictions, which in turn helps to make the necessary business conclusions. Churn can be avoided by studying the past history of the customers. Logistic Regression is been used to make necessary analysis. To proceed with logistic regression we must first eliminate the outliers that are present, this has be achieved by cleaning the data (for redundancy, false data etc) and the resultant has been populated into a prediction excel using which the analysis has been performed.
Ambulance Tracking System Using Restful Api
Authors: Vikas C. S. , Immanuel Ashok
Published: March 2017

Saving peoples live is the most important in today’s world. The best way to save lives is to have an ambulance system which is effective and can be reachable to the user/client, this paper gives the solution which focus to make the ambulance available to a nearby user/client/patient in the least possible time which will help save many lives. After extensive study and analysis new technology evolved. Navigator.geolocation method based on RestFUL Web Services is used this will help the ambulance location to be updated in the database so that it can be seen by the user who is using this application and makes it easy for him to book the ambulance. The client’s location will be pin pointed on the google map and even the ambulance which is nearby the user will be pin pointed on the map, once the patient is on board the ambulance location is taken and then the list of hospitals are pointed out on the map which helps the ambulance driver to choose the nearby hospital to take the patient on time.
A Comparative Review on Different Methods of Face Recognition
Authors: Dawa Tenzin , Vijayalakshmi N
Published: March 2017

Face Recognition is a biometric system which can be used to identify or verify a person from digital image by using the facial features that are unique to each other. There are many techniques which can be used in a face recognition system. In this paper we review some of the algorithms and compare them to see which technique is better compared to one another. Techniques that are compared in this technique are Non-negative matrix factorization (NMF) with Support Vector Machine (SVM), Partial Least Squares (PLS) with Hidden Markov Model (HMM) and Local Ternary Pattern (LTP) with Booth’s Algorithm.
Hubungan antara Gangguan Tidur dengan Gangguan Mental Emosional Anak Usia 4-6 Tahun di Semarang
Authors: Lukmasari Adriana , Hartanto Fitri , Bahtera Tjipta , Muryawan Muhammad Heru
Published: March 2017

Latar belakang. Tidur adalah salah satu kebutuhan dasar untuk mendukung tumbuh kembang anak. Diagnosis dini gangguan tidur masih asing bagi orang tua karena pengetahuan tentang kualitas tidur yang kurang. Gangguan tidur dikaitkan dengan regulasi emosional otak.Tujuan. Menentukan hubungan antara gangguan tidur dan mental emosional pada anak usia 4-6 tahun di Semarang.Metode. Penelitian cross sectional pada anak usia 4-6 tahun sekolah taman kanak-kanak di Kota Semarang dari bulan April-Mei 2016 berdasarkan kriteria inklusi. Cluster sampling dilakukan dalam seleksi mata pelajaran. Gangguan skala tidur untuk anak sleep disturbances scale for children (SDSC) digunakan sebagai alat skrining, sementara perkembangan emosi dan tingkah laku anak digunakan SDQ. Data dianalisis dengan menggunakan SPSS 22, chi-square, dan Fisher exact dengan signifikansi p<0,05.Hasil. Didapat 208 subyek dengan prevalensi gangguan tidur 73,6%. Terdapat hubungan yang signifikan dari gangguan tidur dengan jumlah SDQ skor (RP 2,3, IK95%: 1,1-4,7; p=0,02), skor emosional (RP 2,7, IK95%: 1,3-5,5; p=0,003) dan melakukan skor (RP 1,8, IK95%: 1,1-2,8; p=0,005). Tidak terdapat hubungan yang signifikan dari gangguan tidur pada hiperaktif, masalah dengan teman sebaya, dan perilaku prososial. Kategori pendapatan orang tua, tingkat pendidikan ibu, dan jenis kelamin tidak terbukti sebagai faktor perancu.Kesimpulan. Terdapat hubungan antara gangguan tidur dan masalah mental emosional dalam 4-6 tahun anak.
Left ventricular remodeling leads to heart failure in mice with cardiac‐specific overexpression of VEGF‐B167: echocardiography and magnetic resonance imaging study
Authors: Lottonen‐Raikaslehto Line , Rissanen Riina , Gurzeler Erika , Merentie Mari , Huusko Jenni , Schneider Jurgen E. , Liimatainen Timo , Ylä‐Herttuala Seppo
Published: March 2017

Cardiac‐specific overexpression of vascular endothelial growth factor (VEGF)‐B167 is known to induce left ventricular hypertrophy due to altered lipid metabolism, in which ceramides accumulate to the heart and cause mitochondrial damage. The aim of this study was to evaluate and compare different imaging methods to find the most sensitive way to diagnose at early stage the progressive left ventricular remodeling leading to heart failure. Echocardiography and cardiovascular magnetic resonance imaging were compared for imaging the hearts of transgenic mice with cardiac‐specific overexpression of VEGF‐B167 and wild‐type mice from 5 to 14 months of age at several time points. Disease progression was verified by molecular biology methods and histology. We showed that left ventricular remodeling is already ongoing at the age of 5 months in transgenic mice leading to heart failure by the age of 14 months. Measurements from echocardiography and cardiovascular magnetic resonance imaging revealed similar changes in cardiac structure and function in the transgenic mice. Changes in histology, gene expressions, and electrocardiography supported the progression of left ventricular hypertrophy. Longitudinal relaxation time in rotating frame (T1ρ) in cardiovascular magnetic resonance imaging could be suitable for detecting severe fibrosis in the heart. We conclude that cardiac‐specific overexpression of VEGF‐B167 leads to left ventricular remodeling at early age and is a suitable model to study heart failure development with different imaging methods.
δ-Fibonacci and δ-lucas numbers, δ-fibonacci and δ-lucas polynomials
Authors: Wituła Roman , Hetmaniok Edyta , Słota Damian , Pleszczyński Mariusz
Published: March 2017

In this paper, with reference to the previous work [WITUŁA, R.—SŁOTA, D.: δ-Fibonacci numbers, Appl. Anal. Discrete Math. 3 (2009), 310–329] concerning the, so called, δ-Fibonacci numbers, the concepts of δ-Lucas numbers, δ-Fibonacci and δ-Lucas polynomials are introduced. There are discussed the basic properties of such objects, as well as their applications, especially for description of certain polynomials and identities of algebraic and trigonometric type. Many from among these identities describe the binomial transformations of the respective integer sequences and polynomials. Similarly as for δ-Fibonacci numbers, also for δ-Lucas numbers some attractive identities–bridges are obtained, connecting these numbers in practice with every sequence of integer numbers.
Closed hereditary coreflective subcategories in epireflective subcategories of Top
Authors: Pitrová Veronika
Published: March 2017

The aim of this paper is to investigate closed hereditary coreflective subcategories in epireflective subcategories A of Top, mainly in the case that ZD ⊆ A ⊆ Tych. Particularly the closed hereditary coreflective hull of the one-point compactification of the discrete space on the set of all non-negative integers in such epireflective subcategories is studied. It is proved that under some set-theoretic assumptions it is the whole category A.
The Religion of Absolute Pragmatism: Josiah Royce and Community’s Loyalty
Authors: Stünkel Knut Martin
Published: March 2017

The article examines Josiah Royce’s contribution to the debate on a modern concept of religion. It emerges in the discussion with William James’ thinking. Taking his point of departure from a pragmatic interpretation of the notion of the absolute, Royce describes the loyalty of communities as a manifestation of unity, promoting and defining individual creativity and variability. Manifesting man’s need for salvation ‘religion’ formally represents directedness towards an absolute aim that is expressed in a creative community of interpreters.
Visuelle Mehrsprachigkeit in der Metropole Ruhr – eine Projektpräsentation: Aufbau und Funktionen der Bilddatenbank „Metropolenzeichen“
Authors: Mühlan-Meyer Tirza , Lützenkirchen Frank
Published: March 2017

The article presents findings from the interdisciplinary research-project “Signs of the Metropolises: Visual multilingualism in the Ruhr-Area/Germany” (funded by MERCUR), which investigates the occurrence, regional distribution, function, production and perception of visual multilingualism in representative neighbourhoods of the cities Duisburg, Essen, Bochum and Dortmund. The focus of this paper will be on the structure and features of an online data base – the main corpus of the project – and its application opportunities for the sociolinguistic and linguistic landscape research. The image database encompasses about 25,595 geo-coded digital photographs. The photographs are linked to a map of the Ruhr Area to show the distribution and density of visual multilingualism. The image database also provides metadata for the following categories according to Scollon and Scollon (2003) and Backhaus (2007): choice of language/variety, type of discourse (e.g. commercial, regulatory, transgressive, commemorative), type of name (e.g. institution, shop, gastronomy, toponym), information management (e.g. complete, partial, extended), appearance, typography (e.g. Antiqua, Grotesque, Fraktur type, handwritten), and size. This tagging system allows complex search strategies to analyse sociolinguistic and geographical aspects of visual multilingualism.
Die kommunikative Konstruktion von Kultur: Chinesische und deutsche Anredepraktiken im Gebrauch
Authors: Günthner Susanne
Published: March 2017

As a result of the structuralistically-based distinction betweenlangueandparole, with its bias towardslangueand its emphasis on the detection of universals, the questions of language in authentic contexts, linguistic diversity, the social construction of reality and cultural conventions have been neglected and have even been treated as „irrelevant for linguistic research“ (Ehlich 2006) in „mainstream linguistics“. However, promising new lines of research on language, communication and culture are emerging, which „constitute language’s latest pendulum swing back into the world of culture“ (Enfield 2013). This article contributes to recent developments within Anthropological Linguistics and, thus, to the study of language as a cultural resource and communicating as a cultural practice. On the basis of a contrastive analysis of Chinese and German SMS-communication, this paper aims at investigating practices of addressing related and non-related co-participants by means of kinship terms. The analysis reveals how communicative practices are related to cultural conventions. I will argue that intersubjective communication not only represents the natural habitat for the construction and modification of cultural formations, but it also constitutes the empirically observable site of everyday constructions of culturality.
Nonlocal Symmetries and Consistent Riccati Expansions of the (2+1)-Dimensional Dispersive Long Wave Equation
Authors: Feng Lian-Li , Tian Shou-Fu , Zhang Tian-Tian
Published: March 2017

In this article, the (2+1)-dimensional dispersive long wave equation (DLWE) is investigated, which is derived in the context of a water wave propagating in narrow infinitely long channels of finite constant depth. By using of the truncated Painlevé expansion, we construct its nonlocal symmetry and Bäcklund transformation. After implanting the equation into an enlarged one, then the residual symmetry is localised. Meanwhile, the symmetry group transformation can be computed from the prolonged system. Furthermore, the equation is verified to be consistent Riccati expansion (CRE) solvable. Outing from the CRE, the soliton-cnoidal wave interaction solution in terms of Jacobi elliptic functions and the third type of incomplete elliptic integral are studied, respectively.
TARPUKARIO LIETUVOS MOKESČIAI ŠIUOLAIKINĖS LIETUVOS MOKESČIŲ TEISĖS POŽIŪRIU
Authors: Burneikaitė Indra
Published: March 2017

Straipsnyje analizuojama mokesčių samprata, požymiai, rūšys, funkcijos bei privačių įmonių pelno apmokestinimo našta tarpukario Lietuvoje šiuolaikinės Lietuvos mokesčių teisės požiūriu.
PACIENTŲ SVEIKATAI PADARYTOS ŽALOS ATLYGINIMO BE KALTĖS MODELIS
Authors: Morkūnaitė Monika
Published: March 2017

Straipsnyje, atsižvelgus į pastaraisiais metais Lietuvoje vykstančias diskusijas, teikiamus teisės aktų projektus dėl žalos, pacientų patirtos teikiant sveikatos priežiūros paslaugas, atlyginimo teisinio reguliavimo keitimo, yra pristatomas Lietuvoje siūlomas įgyvendinti žalos atlyginimo be kaltės modelis bei pagrindiniai jo taikymo aspektai. Visa tai papildoma konstruktyvia šio modelio realaus įgyvendinimo ir veikimo kritika bei yra vertinama, ar iš tiesų siūlomas įgyvendinti žalos atlyginimo be kaltės modelis yra ta teisinio reguliavimo balansavimo priemonė, kuria yra suderinami tiek pacientų, tiek sveikatos priežiūros įstaigų, tiek visos visuomenės interesai ir jis turėtų būti įgyvendinamas Lietuvoje.
TEISINIAI POŽIŪRIAI APIBRĖŽIANT PRIVATUMO IR VIEŠOJO INTERESO PUSIAUSVYRĄ
Authors: Lytvynenko Anatoliy
Published: March 2017

The article encompasses a narrow topic in media law, namely the problem of utilization of personal data by media personnell, informational agencies as well as broadcasting enterprises. Since conventional personal data maintenance procedures expounded in appropriate data protection acts are almost explicitly exempt for journalistic, artistic or literary purposes, the issue of preserving a proper equipoise between the right to one’s privacy and the freedom of speech remains a crucial topic for analysis and theory assemblage.
Effectiveness of youth policy model in belarus at the contemporary stage of development
Authors: Sechko Natalia , Romanova Svetlana
Published: March 2017

Since 1991 Belarus has been implementing a youth policy. Scientific problem was formulated as follows: How effective is the model of youth policy in Belarus? The present paper aimed at investigating the extent how young people are informed about the directions of youth policy; how do they evaluate its implementation; what kind of support do they need; what should be changed in the youth policy in order to increase its effectiveness. Research methodology: neoinstitutional ana-ysis of the youth policy model on the basis of legislation and government programs. Empirical research is based on an online survey of 387 respondents. It was revealed that young people are least informed about the mechanisms of support in the labor market and about the support of young families. The key moment in the development of the state youth policy in Belarus is that support should be provided to all youth, and not to certain categories of it.
Motivating employees of the public organization: case study of the higher education institution
Authors: Stachowska Sylwia , Czaplicka-Kozłowska Iwona Zofia
Published: March 2017

One of the most significant managerial functions is motivating which leads to the implementation of the particular organizational objectives, to shaping of engagement and loyalty of its members and, consequently, to the raising effectiveness of their actions. The properly constructed solutions in the area of employee motivating process may result in the several benefits for the organization, which is true also for the public institutions including the academic ones. The aim of the herein study was the identification of the factors which have an impact on the motivation of employees of the higher education institution. The research was conducted with the questionnaire survey among the non-academic employees of the University of Warmia and Mazury in Olsztyn, Poland. The conducted survey concludes that the motivation of employees is affected by various factors, mostly concerning the remuneration for work and also with the self-development possibilitities, interpersonal relations, and effective communication. It is vital and worth to use the knowledge about them for improving the quality and efficiency of the organization.
‘It wasn’t because a woman couldn’t do a man’s job’
Authors: Pawelczyk Joanna
Published: March 2017

Women currently serve in 95 percent of all US Army occupations and make up 16.3 percent of the active Army forces. Numerous measures have been taken in the form of regulations and policies to advance the presence and position of women in the military (e.g., the recent lifting of the ban on women serving in combat roles). It is claimed, however, that the broader ideology of masculinity prevalent in the institution is much more effective in constraining women’s participation than either specific institutional or interpersonal limitations. This paper, drawing on membership categorization analysis and conversation analysis, exposes some of the gendered propositions and gender ideologies produced by war veterans in the context of interviews. To this end, selected interviews with American female and male war veterans taken from the Veterans History Project (run by the Library of Congress) are qualitatively scrutinized. The analysis demonstrates how gender is occasioned and accounted for when describing military experiences and dayto-day operation of the army. It furthermore reveals the categorization work performed by the veterans that allows us to access various commonsense assumptions concerning the positions of women and men in the contemporary US Army. All in all, the paper points to the continuous relevance of gender in the military.