bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Machine Group Scheduling with Position Dependent Processing Times and Ready Times
Authors: Zhang Xingong , Xie Qiulian
Published: July 2015

We investigate a single machine group scheduling problem with position dependent processing times and ready times. The actual processing time of a job is a function of positive group-dependent job-independent positional factors. The actual setup time of the group is a linear function of the total completion time of the former group. Each job has a release time. The decision should be taken regarding possible sequences of jobs in each group and group sequence to minimize the makespan. We show that jobs in each group are scheduled in nondecreasing order of its release time and the groups are arranged in nondecreasing order of some certain conditions. We also present a polynomial time solution procedure for the special case of the proposed problem.
Application of Biomaterials and Inkjet Printing to Develop Bacterial Culture System
Authors: Srimongkon Tithimanan , Mandai Shusaku , Enomae Toshiharu
Published: July 2015

We created an automated bioassay system based on inkjet printing. Compared to conventional manual bacterial culture systems our printing approach improves the quality as well as the processing speed. A hydrophobic/hydrophilic pattern as a container supporting a culture medium was built on filter paper using a toluene solution of polystyrene for hydrophobization, followed by toluene printing to create several hydrophilic areas. As culture media we used a novel poly(vinyl alcohol) based hydrogel and a standard calcium alginate hydrogel. The poly(vinyl alcohol) hydrogel was formed by physical crosslinking poly(vinyl alcohol) with adipic acid dihydrazide solutions. The conditions of poly(vinyl alcohol) gelation were optimized for inkjet printability and the optimum mixture ratio was determined. The calcium alginate hydrogel was formed by chemical reaction between sodium alginate and CaCl2solutions. Together with nutrients both hydrogel solutions were successfully printed on paper by means of the modified inkjet printer. The amount of each solution was demanded simply by outputting CMYK values. In the last step bacterial cells were printed on both hydrogel media. For both media we achieved a stable bacteria growth which was confirmed by microscopical imaging of the developed bacterial colonies.
Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis
Authors: Garg Lohit , Gupta Sagar , Swami Abhishek , Zhang Ping
Published: July 2015

Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.
Comparative Analysis of Amino Acids, Nucleosides, and Nucleobases inThais clavigerafrom Different Distribution Regions by Using Hydrophilic Interaction Ultra-Performance Liquid Chromatography Coupled with Triple Quadrupole Tandem Mass Spectrometry
Authors: Ge Yahui , Tang Yuping , Guo Sheng , Liu Xin , Zhu Zhenhua , Liu Pei , Duan Jin-ao
Published: July 2015

Thais clavigera, as function food, is distributed widely along the coasts of China. To compare and tap its potentially nutritional and functional values, hydrophilic interaction ultra-performance liquid chromatography coupled with triplequadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) was used for simultaneous identification and quantification of amino acids, nucleosides, and nucleobases in the extracts ofT. clavigerafrom 19 sea areas in China, and a PCA was further performed for comparing their content variation in different distribution regions. The total contents of amino acids varied from 116.74 mg/g to 298.58 mg/g being higher than contents of nucleosides and nucleobases that varied from 2.65 mg/g and 20.49 mg/g. Among the habitats, Hainan province had content advantages on others. By PCA, samples collected from different regions were classified into three groups. For specific constituents, lysine accounted for large part of essential amino acids; glycine and taurine also play important roles in the delicate taste and health care function of it. Inosine takes up most of total contents of nucleosides and nucleobases. These results provided good data for establishing quality standard ofT. clavigerarelated products and their further development and utilization.
Automatic Fusion of Hyperspectral Images and Laser Scans Using Feature Points
Authors: Zhang Xiao , Zhang Aiwu , Meng Xiangang
Published: July 2015

Automatic fusion of different kinds of image datasets is so intractable with diverse imaging principle. This paper presents a novel method for automatic fusion of two different images: 2D hyperspectral images acquired with a hyperspectral camera and 3D laser scans obtained with a laser scanner, without any other sensor. Only a few corresponding feature points are used, which are automatically extracted from a scene viewed by the two sensors. Extraction method of feature points relies on SURF algorithm and camera model, which can convert a 3D laser scan into a 2D laser image with the intensity of the pixels defined by the attributes in the laser scan. Moreover, Collinearity Equation and Direct Linear Transformation are used to create the initial corresponding relationship of the two images. Adjustment is also used to create corrected values to eliminate errors. The experimental result shows that this method is successfully validated with images collected by a hyperspectral camera and a laser scanner.
Disseminated Herpes Simplex Virus with Fulminant Hepatitis
Authors: Rimawi Bassam H. , Meserve Joseph , Rimawi Ramzy H. , Min Zaw , Gnann John W.
Published: July 2015

Disseminated herpes simplex virus (HSV) is a rare cause of acute fulminant liver failure. We hereby present a case series of three patients with acute disseminated HSV with necrotizing hepatitis successfully treated with a week course of acyclovir. Early empiric administration of acyclovir therapy while awaiting confirmatory tests is critical in this potentially lethal disease.
Radical Cystectomy with Ileal Conduit Urinary Diversion in a Patient with a Left Ventricular Assist Device
Authors: Pariser Joseph J. , Weiner Adam B. , Steinberg Gary D.
Published: July 2015

Left ventricular assist device (LVAD) is an option for the surgical management of severe heart failure, and radical cystectomy remains the standard of care for muscle-invasive bladder cancer. Given a complicated population in terms of comorbidities and management for patients with an LVAD, there is little experience with major urologic procedures, which require balancing the benefits of surgery with considerable perioperative risks. We report our experience performing the first radical cystectomy with ileal conduit in a patient with an LVAD and muscle-invasive bladder cancer.
Predicting Metabolic Syndrome Using the Random Forest Method
Authors: Worachartcheewan Apilak , Shoombuatong Watshara , Pidetcha Phannee , Nopnithipat Wuttichai , Prachayasittikul Virapong , Nantasenamat Chanin
Published: July 2015

Aims. This study proposes a computational method for determining the prevalence of metabolic syndrome (MS) and to predict its occurrence using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. The Random Forest (RF) method is also applied to identify significant health parameters. Materials and Methods. We used data from 5,646 adults aged between 18–78 years residing in Bangkok who had received an annual health check‐up in 2008. MS was identified using the NCEP ATP III criteria. The RF method was applied to predict the occurrence of MS and to identify important health parameters surrounding this disorder. Results. The overall prevalence of MS was 23.70% (34.32% for males and 17.74% for females). RF accuracy for predicting MS in an adult Thai population was 98.11%. Further, based on RF, triglyceride levels were the most important health parameter associated with MS. Conclusion. RF was shown to predict MS in an adult Thai population with an accuracy >98% and triglyceride levels were identified as the most informative variable associated with MS. Therefore, using RF to predict MS may be potentially beneficial in identifying MS status for preventing the development of diabetes mellitus and cardiovascular diseases.
Association Analysis of Genetic Variants with Type 2 Diabetes in a Mongolian Population in China
Authors: Bai Haihua , Liu Haiping , Suyalatu Suyalatu , Guo Xiaosen , Chu Shandan , Chen Ying , Lan Tianming , Borjigin Burenbatu , Orlov Yuriy L. , Posukh Olga L. , Yang Xiuqin , Guilan Guilan , Osipova Ludmila P. , Wu Qizhu , Narisu Narisu
Published: July 2015

The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations.
A Novel Numerical Method of Two-Dimensional Fredholm Integral Equations of the Second Kind
Authors: Ma Yanying , Huang Jin , Li Hu
Published: July 2015

A novel numerical method is developed for solving two-dimensional linear Fredholm integral equations of the second kind by integral mean value theorem. In the proposed algorithm, each element of the generated discrete matrix is not required to calculate integrals, and the approximate integral operator is convergent according to collectively compact theory. Convergence and error analyses of the approximate solution are provided. In addition, an algorithm is given. The reliability and efficiency of the proposed method will be illustrated by comparison with some numerical results.
Online Scheduling with Delivery Time on a Bounded Parallel Batch Machine with Limited Restart
Authors: Liu Hailing , Wan Long , Yan Zhigang , Yuan Jinjiang
Published: July 2015

We consider the online (over time) scheduling of equal length jobs on a bounded parallel batch machine with batch capacitybto minimize the time by which all jobs have been delivered with limited restart. Here, “restart” means that a running batch may be interrupted, losing all the work done on it, and jobs in the interrupted batch are then released and become independently unscheduled jobs, called restarted jobs. “Limited restart” means that a running batch which contains some restarted jobs cannot be restarted again. Whenb=2, we propose a best possible online algorithmH(b=2)with a competitive ratio of1+α, whereαis the positive solution of2α(1+α)=1. Whenb≥3, we present a best possible online algorithmH(b≥3)with a competitive ratio of1+β, whereβis the positive solution ofβ(1+β)2=1.
Onset of Intense Surface Enhanced Raman Scattering and Aggregation in the Au@Ag System
Authors: Bhatia Priya , Consiglio Joseph , Diniz John , Lu Jia E. , Hoff Christopher , Ritz-Schubert Shelby , Terrill Roger H.
Published: July 2015

Gold core/silver shell (Au@Ag) nanoparticles of ~37 ± 5 nm diameter generate intense SERS (λEX=785 nm) responses in solution when they interact with the SERS labels rhodamine 6G (R6G), 4-mercaptopyridine (MPY), and 4-mercaptobenzoic acid (MBA). Herein the relationship between SERS intensity, aggregation, and adsorption phenomenon isobserved by titrating Au@Ag with the above labels. As the labels adsorb to the Au@Ag, they drive aggregation as evidenced by the creation of NIR extinction peaks, and the magnitude of this NIR extinction (measured at 830 nm) correlates very closely to magnitude of the intense SERS signals. The label MBA is an exception since it does not trigger aggregation nor does it result in intense SERS; rather intense SERS is recovered only after MBA coated Au@Ag is aggregated with KCl. An “inner filter” model is introduced and applied to compensate for solution extinction when the exciting laser radiation is significantly attenuated. This model permits a summary of the SERS responses in the form of plots of SERS intensity versus the aggregate absorption at 830 nm, which shows the excellent correlation between intense SERS and LSPR bands extinction.
Increased Standardised Incidence Ratio of Malignant Pleural Mesothelioma in Taiwanese Asbestos Workers: A 29-Year Retrospective Cohort Study
Authors: Lin Cheng-Kuan , Chang Yu-Ying , Wang Jung-Der , Lee Lukas Jyuhn-Hsiarn
Published: July 2015

Objective. This paper aimed to determine the standardised incidence ratio (SIR) of malignant pleural mesothelioma (MPM) in workers exposed to asbestos in Taiwan.Methods. All workers employed in asbestos-related factories and registered by the Bureau of Labour Insurance between 1 March, 1950, and 31 December, 1989, were included in the study and were followed from 1 January, 1980, through 31 December, 2009. Incident cases of all cancers, including MPM (ICD-9 code: 163), were obtained from the Taiwan Cancer Registry. SIRs were calculated based on comparison with the incidence rate of the general population of Taiwan and adjusted for age, calendar period, sex, and duration of employment.Results. The highest SIR of MPM was found for male workers first employed before 1979, with a time since first employment more than 30 years (SIR 4.52, 95% CI: 2.25–8.09). After consideration of duration of employment, the SIR for male MPM was 5.78 (95% CI: 1.19–16.89) for the workers employed for more than 20 years in asbestos-related factories.Conclusions. This study corroborates the association between occupational asbestos exposure and MPM. The highest risk of MPM was found among male asbestos workers employed before 1979 and working for more than 20 years in asbestos-related factories.
Modification ofS. cerevisiaeGrowth Dynamics Using Low Frequency Electromagnetic Fields in the 1-2 kHz Range
Authors: Barabáš Ján , Radil Roman , Malíková Ivona
Published: July 2015

This paper details our further experiments pertaining to the influence of low frequency electromagnetic fields (LF EMF) on the growth dynamics of two wild-typeSaccharomyces cerevisiaestrands. We opted to explore frequencies beyond the usual 50–60 Hz range, motivated by the ion parametric resonance theory and several studies which discovered and recorded endogenous biosignals in variousSaccharomyces cerevisiaestrands in the 0.4–2.0 kHz frequency range, most probably stemming from microtubules. Both yeast strands used in our experiments have been subjected to continuous 66-hour session of LF EMF exposure (frequencies 1.2, 1.4, 1.6, 1.8, and 2.0 kHz; average magnetic flux density 2.43 mT) under identical ambient conditions. Experiment results indicate a frequency-dependent proliferative response of both yeast strands.
Single-Machine Scheduling with Workload-Dependent Maintenance Duration to Minimize Maximum Lateness
Authors: Wang Ting , Xu Dehua
Published: July 2015

A single-machine scheduling problem with a mandatory maintenance whose duration is workload-dependent is considered. The start time of the maintenance is restricted to a time window. The objective is to determine the start time of the maintenance and schedule all the jobs to the machine such that the maximum lateness is minimized. An approximation algorithm based on the classical Earliest Due Date first rule is proposed. It is showed that the proposed algorithm is optimal for some special cases and that it has a tight bound for the scheduling problem under consideration.
Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Villegas-Rivera Geannyne , Román-Pintos Luis Miguel , Cardona-Muñoz Ernesto Germán , Arias-Carvajal Oscar , Rodríguez-Carrizalez Adolfo Daniel , Troyo-Sanromán Rogelio , Pacheco-Moisés Fermín Paul , Moreno-Ulloa Aldo , Miranda-Díaz Alejandra Guillermina
Published: July 2015

Objective. To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN).Methods. We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis.Results. LPO levels were reduced in both statin arms after 16 weeks of treatment (p<0.05versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores.Discussion. EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered withNCT02129231.
Challenges and Strategies of Laboratory Diagnosis for Newly Emerging Influenza Viruses in Taiwan: A Decade after SARS
Authors: Lin Jih-Hui , Wu Ho-Sheng
Published: July 2015

Since the first case of severe acute respiratory syndrome (SARS) in Taiwan was identified in March 2003, viral respiratory infections, in particular the influenza virus, have become a national public health concern. Taiwan would face a serious threat of public health problems if another SARS epidemic overlapped with a flu outbreak. After SARS, the Taiwan Centers for Disease Control accelerated and strengthened domestic research on influenza and expanded the exchange of information with international counterparts. The capacity of influenza A to cross species barriers presents a potential threat to human health. Given the mutations of avian flu viruses such as H7N9, H6N1, and H10N8, all countries, including Taiwan, must equip themselves to face a possible epidemic or pandemic. Such preparedness requires global collaboration.
Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples
Authors: Palmer Raymond F. , Heilbrun Lynne , Camann David , Yau Alice , Schultz Stephen , Elisco Viola , Tapia Beatriz , Garza Noe , Miller Claudia
Published: July 2015

Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.
Absence of themecA Gene in Methicillin ResistantStaphylococcus aureusIsolated from Different Clinical Specimens in Shendi City, Sudan
Authors: Elhassan Mogahid M. , Ozbak Hani A. , Hemeg Hassan A. , Elmekki Miskelyemen A. , Ahmed Leila M.
Published: July 2015

Absolute dependence onmecA gene as the defining standard in determining the resistance ofS. aureusto methicillin became the subject of distrust by many researchers. The present study aimed to determine the frequency ofmecA gene in methicillin resistantS. aureus(MRSA) isolates using polymerase chain reaction and to correlate its presence to conventional method. In this regard, two hundredS. aureusisolates were collected from patients with different diseases attending different hospitals in Shandi City, Sudan. Phenotypic Kirby-Bauer method confirmed the existence of methicillin resistantS. aureusin 61.5% of the subjected isolates with MICs ranging from 4 μg/mL to 256 μg/mL when usingE-test. However, when amplifying a 310 bp fragment of themecA gene by PCR, twelve out of the 123 MRSA isolates (9.8%) weremecA negative, whereas all the 77 methicillin sensitiveS. aureus(MSSA) weremecA negative. In conclusion, this study drew attention to the credibility of themecA gene and its usefulness in the detection of all MRSA strains without referring to the traditional methods. Hence, it is highly recommended to consider alternative mechanisms forβ-lactam resistance that may compete withmecA gene in the emergence of MRSA phenomenon in the community.
Light of Planck-2015 on Noncanonical Inflation
Authors: Saaidi Kh. , Mohammadi A. , Golanbari T.
Published: July 2015

Slow-roll inflationary scenario is considered in noncanonical scalar field model supposing a power-law function for kinetic term and using two formalisms. In the first approach, the potential is picked out as a power-law function, that is, the most common approach in studying inflation. Hamilton-Jacobi approach is selected as the second formalism, so that the Hubble parameter is introduced as a function of scalar field instead of the potential. Employing the last observational data, the free parameters of the model are constrained, and the predicted form of the potential and attractor behavior of the model are studied in detail.
Design of a Minimized Complementary Illusion Cloak with Arbitrary Position
Authors: Shi Yan , Zhang Lin , Tang Wei , Li Long , Liang Chang-Hong
Published: July 2015

This paper has developed a complementary illusion cloak to hide the objects with arbitrary shapes and sizes. In the proposed cloak, a complementary cloak is first introduced by using the trapezoid coordinate transformation. Then an illusion device in terms of another trapezoid coordinate transformation is designed to cloak the object. With two coordinate transformations, the complementary illusion cloak device can be arbitrarily placed to hide the target object, and the sizes of the antiobject used to cloak the object are obviously compressed. Numerical results including target objects with different shapes are given to verify correctness and effectiveness of the proposed cloak.
The Beneficial Effect ofEquisetum giganteumL. againstCandidaBiofilm Formation: New Approaches to Denture Stomatitis
Authors: Alavarce Rafaela A. S. , Saldanha Luiz L. , Almeida Nara Ligia M. , Porto Vinicius C. , Dokkedal Anne L. , Lara Vanessa S.
Published: July 2015

Equisetum giganteumL. (E. giganteum), Equisetaceae, commonly called “giant horsetail,” is an endemic plant of Central and South America and is used in traditional medicine as diuretic and hemostatic in urinary disorders and in inflammatory conditions among other applications. The chemical composition of the extract EtOH 70% ofE. giganteumhas shown a clear presence of phenolic compounds derived from caffeic and ferulic acids and flavonoid heterosides derived from quercitin and kaempferol, in addition to styrylpyrones.E. giganteum, mainly at the highest concentrations, showed antimicrobial activity against the relevant microorganisms tested:Escherichia coli,Staphylococcus aureus, andCandida albicans. It also demonstrated antiadherent activity onC. albicansbiofilms in an experimental model that is similar to dentures. Moreover, all concentrations tested showed anti-inflammatory activity. The extract did not show cytotoxicity in contact with human cells. These properties might qualifyE. giganteumextract to be a promising alternative for the topic treatment and prevention of oral candidiasis and denture stomatitis.
Dipeptidyl Peptidase-4 Inhibition May Stimulate Progression of Carcinoid Tumor
Authors: Pech Vladimir , Abusaada Khalid , Alemany Carlos
Published: July 2015

Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as saxagliptin, have gained a rapid growth in use in the treatment of type 2 diabetes mellitus in the past decade. Although they are considered to have a good safety profile, controversy exists regarding their potential to stimulate neoplasm growth. We report here a patient with metastatic carcinoid tumor. His disease was stable for several years with plasma serotonin level (which was used to monitor disease progression) in 700–800 ng/mL range. After initiation of treatment with saxagliptin, however, his serotonin level almost doubled (1358 ng/mL), concerning progression of the disease. After discontinuation of saxagliptin, serotonin level returned to baseline quickly, while other laboratory markers, such as complete blood count (CBC), comprehensive metabolic profile (CMP) with liver function tests (LFTs), and lactate dehydrogenase (LD), remained unchanged before, during, and after the treatment with saxagliptin. This temporal correlation suggests a possible interaction between the activity of carcinoid tumors and the use of DPP-4 inhibitors. Although we were not able to find any literature providing a direct evidence that saxagliptin alters progression of the carcinoid tumors, we recommend alternative management for the treatment of diabetes in patients with carcinoid or other neuroendocrine tumors.
Parallel-Machine Scheduling with Time-Dependent and Machine Availability Constraints
Authors: Miao Cuixia , Zou Juan
Published: July 2015

We consider the parallel-machine scheduling problem in which the machines have availability constraints and the processing time of each job is simple linear increasing function of its starting times. For the makespan minimization problem, which is NP-hard in the strong sense, we discuss the Longest Deteriorating Rate algorithm and List Scheduling algorithm; we also provide a lower bound of any optimal schedule. For the total completion time minimization problem, we analyze the strong NP-hardness, and we present a dynamic programming algorithm and a fully polynomial time approximation scheme for the two-machine problem. Furthermore, we extended the dynamic programming algorithm to the total weighted completion time minimization problem.
miR-634 Activates the Mitochondrial Apoptosis Pathway and Enhances Chemotherapy-Induced Cytotoxicity
Authors: Fujiwara Naoto , Inoue Jun , Kawano Tatsuyuki , Tanimoto Kousuke , Kozaki Ken-ichi , Inazawa Johji
Published: July 2015

Some tumor-suppressing miRNAs target multiple oncogenes concurrently and therefore may be useful as cancer therapeutic agents. Further, such miRNAs may be useful to address chemotherapeutic resistance in cancer, which remains a primary clinical challenge in need of solutions. Thus, cytoprotective processes upregulated in cancer cells that are resistant to chemotherapy are a logical target for investigation. Here, we report that overexpression of miR-634 activates the mitochondrial apoptotic pathway by direct concurrent targeting of genes associated with mitochondrial homeostasis, antiapoptosis, antioxidant ability, and autophagy. In particular, we show how enforced expression of miR-634 enhanced chemotherapy-induced cytotoxicity in a model of esophageal squamous cell carcinoma, where resistance to chemotherapy remains clinically problematic. Our findings illustrate how reversing miR-634–mediated cytoprotective processes may offer a broadly useful approach to improving cancer therapy. Cancer Res; 75(18); 3890–901. ©2015 AACR.
Impact of Smoking and Excess Body Weight on Overall and Site-Specific Cancer Mortality Risk
Authors: Meyer Julia , Rohrmann Sabine , Bopp Matthias , Faeh David
Published: July 2015

Background: Smoking and excess body weight are major preventable risk factors for premature death. This study aimed at analyzing their single and combined association with site-specific cancer mortality.

Methods: Our study population comprised 35,784 men and women of ages 14 to 99 years, who participated in population-based health surveys conducted 1977–1993 in Switzerland and were followed up for mortality until 2008. Multivariable Cox proportional hazards models were calculated for different cancer sites, and population attributable fractions were derived.

Results: The hazard ratio of dying from cancer (all sites) was 2.32 (95% confidence interval, 2.04–2.63) for heavy smokers (vs. never smokers) and 1.15 (1.01–1.32) for obese [body mass index (BMI) ≥ 30 kg/m2] vs. normal weight individuals. Heavy smoking (≥20 cigarettes/day) was associated with increased mortality due to cancer of the lung, upper aero-digestive tract, pancreas, bladder, liver, and the total of remaining sites. Obesity was associated with higher risk of dying from cancer of the liver and the female genital tract (essentially corpus or cervix uteri and ovary). More than 20% of all cancer deaths in our population were attributable to ever smoking and overweight (BMI ≥ 25 kg/m2).

Conclusions: Smoking was a much stronger risk factor for cancer than excess body weight. For lung, liver, and pancreatic cancer, the combination of excess body weight and smoking lead to cumulated higher risks.

Impact: Our findings support recommendations for obese persons to quit smoking despite potential postcessation weight gain. Cancer Epidemiol Biomarkers Prev; 24(10); 1516–22. ©2015 AACR.
Intrathecal Administration of Tumor-Infiltrating Lymphocytes Is Well Tolerated in a Patient with Leptomeningeal Disease from Metastatic Melanoma: A Case Report
Authors: Glitza Isabella C. , Haymaker Cara , Bernatchez Chantale , Vence Luis , Rohlfs Michelle , Richard Jessie , Lacey Carol , Mansaray Rahmatu , Fulbright Orenthial J. , Ramachandran Renjith , Toth Christopher , Wardell Seth , Patel Sapna P. , Woodman Scott E. , Hwu Wen-Jen , Radvanyi Laszlo G. , Davies Michael A. , Papadopoulos Nicholas E. , Hwu Patrick
Published: July 2015

Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes and few treatment options. We present a case of intrathecal (i.t.) administration of autologous tumor-infiltrating lymphocytes (TIL) in a patient with LMD from metastatic melanoma. The patient developed LMD after previous treatments with surgery, high-dose bolus interleukin-2 (HD IL2), and systemic TIL infusion and experienced radiographic progression after intrathecal IL2 (i.t. IL2) therapy. The patient received weekly treatment with increasing numbers of i.t. TIL followed by twice-weekly i.t. IL2. The patient received three i.t. TIL infusions and did not experience any toxicities beyond those expected with i.t. IL2 therapy. Analysis of cerebrospinal fluid demonstrated increased inflammatory cytokines following the i.t. treatments. Subsequent imaging demonstrated disease stabilization, and neurological deficits also remained stable. The patient expired 5 months after the initiation of i.t. TIL therapy with disease progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph nodes, but without LMD progression. These results demonstrate the safety of i.t. administration of TIL in melanoma patients with LMD and support the feasibility of conducting a prospective clinical trial to determine this therapy's clinical benefit among these patients. Cancer Immunol Res; 3(11); 1201–6. ©2015 AACR.
Analysis of Stereotactic Accuracy in Patients Undergoing Deep Brain Stimulation Using Nexframe and the Leksell Frame
Authors: Bot Maarten , van den Munckhof Pepijn , Bakay Roy , Sierens Diane , Stebbins Glenn , Verhagen Metman Leo
Published: July 2015

Objective: To determine and compare the accuracy of Nexframe and the Leksell stereotactic frame in deep brain stimulation (DBS) procedures. Background: The ‘frameless' Nexframe uses bone fiducials rather than a head-mounted frame, which offers potential benefits for both the patient and the surgical team. Accuracy of lead implantation and factors affecting this accuracy are of crucial importance but have not been extensively studied for the frameless system. Design/Methods: The location of 194 (Leksell frame, n = 116; Nexframe, n = 78) DBS leads was determined on postoperative MRI. Obtained stereotactic coordinates were compared with expected intraoperative target coordinates. Resulting absolute errors in the X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) were then used to calculate the vector error (VE). The vector error describes the total error in 3-D space and represents our main outcome measure. Results: The vector error (mean ± SD) was 2.8 ± 1.3 for Nexframe and 2.5 ± 1.2 for the Leksell frame (p = 0.43). For Nexframe, absolute X, Y, and Z errors were 1.4 ± 1.3, 1.7 ± 1.2, and 1.0 ± 0.9 mm. For the Leksell frame, the absolute X, Y, and Z errors were 1.4 ± 1.0, 1.2 ± 1.0, and 1.3 ± 0.9 mm. On the anterior-posterior plane (Y coordinate), the Leksell frame was more accurate than Nexframe (p = 0.04). In contrast, Nexframe was more accurate on the dorsal-ventral plane (Z coordinate) (p = 0.04). There was no difference in accuracy between the two methods on the medial-lateral plane (X coordinate). Conclusion: This comparison of Nexframe and the Leksell frame shows that both techniques have equivalent overall 3-D accuracy.
Effect of the Total Extract of Averrhoacarambola (Oxalidaceae) Root on the Expression Levels of TLR4 and NF-κB in Streptozotocin-Induced Diabetic Mice
Authors: Xu Xiaohui , Liang Tao , Lin Xing , Wen Qingwei , Liang Xingmei , Li Weisi , Qin Feizhang , Zheng Ni , Ming Jianjun , Huang Renbin
Published: July 2015

Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-κB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. Results: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.
MiR-499-5p Contributes to Hepatic Insulin Resistance by Suppressing PTEN
Authors: Wang Lei , Zhang Ning , Pan Hua-ping , Wang Zun , Cao Zhen-yu
Published: July 2015

Background: Type 2 diabetes afflicts 95% of diabetes patients. Recent data suggest that miRNAs play a key role in insulin production, secretion and function. This study aims to explore the specific role of miR-499-5p in hepatic insulin resistance. Methods: The miRNA expression levels in the livers of db/db mice were analyzed using miRNA chips and were verified by real-time PCR. miR-499-5p mimics and an inhibitor were transfected into NCTC1469 cells. Then, the PI3K/AKT signaling pathway and glycogen level were determined. The target genes of miR-499-5p were predicted by bioinformatics and then confirmed by dual luciferase reporter assay and Western blot. To establish an insulin resistance (IR) animal model, C57BL/6 mice were fed a high-fat diet (HFD). The level of miR-499-5p in the livers of HFD-fed mice was upregulated through tail vein injection of adenovirus vectors (ad) containing miR-499-5p mimics. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to determine glucose tolerance and insulin tolerance, respectively. Results: MicroRNA chips and qPCR showed that miR-499-5p was significantly decreased in the livers of db/db mice. Downregulation of miR-499-5p impaired the insulin signaling pathway and glycogen synthesis, whereas upregulation of miR-499-5p promoted the insulin signaling pathway and glycogen synthesis in NCTC1469 cells. The dual luciferase reporter assay and Western blot demonstrated that PTEN was the target gene of miR-499-5p. Compared with the control group, miR-499-5p was increased 2.1-fold in the livers of HFD-fed mice. By tail vein injection of adenovirus vector containing miR-499-5p mimics, GTT and ITT were improved in HFD-fed mice. Conclusion: Downregulation of the miR-499-5p level impaired the PI3K/AKT/GSK signaling pathway and glycogen synthesis by targeting PTEN.
Lipopolysaccharide Induces Autophagic Cell Death through the PERK-Dependent Branch of the Unfolded Protein Response in Human Alveolar Epithelial A549 Cells
Authors: Li Shaoying , Guo Liang , Qian Pin , Zhao Yunfeng , Liu Ao , Ji Fuyun , Chen Liutong , Wu Xueling , Qian Guisheng
Published: July 2015

Background: Alveolar epithelial cell death plays a critical role in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. Increased autophagy has a dual effect on cell survival. However, it is not known whether autophagy promotes death or survival in human alveolar epithelial cells exposed to LPS. Methods: Genetic and pharmacological approaches were used to evaluate the effect of autophagy on A549 cell viability upon LPS exposure. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways were examined with immunoblotting studies to further explore underlying mechanisms. Results: Treatment with LPS (50 µg/ml) led to autophagy activation and decreased cell viability in A549 cells. Blocking autophagy via short interfering RNA or inhibitor significantly decreased, whereas rapamycin increased, the LPS-induced effect on viability. ER stress was activated in LPS-stimulated A549 cells, and ER stress inhibitor reduced LPS-induced autophagy. LPS activated only the PERK pathway and had rarely effect on the ATF6 and IRE1 branches of the UPR in A549 cells. Moreover, the knockdown of PERK and ATF4 attenuated LPS-induced autophagy and promoted cell survival. Conclusion: In human alveolar epithelial A549 cells, LPS induces autophagic cell death that depends on the activation of the PERK branch of the UPR upon ER stress.
Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells
Authors: Tsang Siu Wai , Zhang Hong-Jie , Chen Ye-Gao , Auyeung Kathy Ka-Wai , Bian Zhao-Xiang
Published: July 2015

Background: Eruberin A (2, 3-dehydroflavonoid), a flavanol glycoside isolated from Pronephrium penangianum, has been used as a blood-nourishing folk medicine for centuries; however, it indeed possesses a variety of other health-promoting benefits including anti-fibrotic bioactivity. Activation of pancreatic stellate cells (PSCs) is the key initiating step in pancreatic fibrosis, which is a characteristic feature associated with chronic pancreatitis and pancreatic adenocarcinoma. Methods: The anti-fibrotic effect of eruberin A and the underlying mechanisms of its anti-fibrotic action in LTC-14 cells, which retained essential characteristics and morphological features of primary PSCs, were examined by means of real-time polymerase chain reactions, Western blotting and immunostaining. Results: The application of eruberin A (20 µg/ml) effectively inhibited the expression levels of fibrotic mediators namely alpha-smooth muscle actin, fibronectin and type I-collagen, so as the sonic hedgehog signaling pathway components post transforming growth factor-beta (5 ng/ml) stimulation. Eruberin A treatment also led to a notable decrease in the activation of nuclear factor-kappaB (NF-κB) and the phosphorylation of phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT). Conclusion: Our results demonstrated that eruberin A significantly suppressed the expression levels of fibrotic mediators in PSCs, and we suggest that its anti-fibrotic mechanism was associated with an attenuation of the PI3K/AKT/NF-κB signaling pathway.
Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer
Authors: Wang Zhongli , Liu Chao
Published: July 2015

Background/Aims: Effective treatment of gastric cancer (GC) requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs) in GC appears to be a critical question. Methods: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV) that carries diphtheria toxin fragment A (DTA) under the control of Lgr5 promoter (AAV-pLgr5-DTA) to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. Results: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. Conclusion: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.
Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation
Authors: Xue Huaming , Tu Yihui , Ma Tong , Liu Xiaodong , Wen Tao , Cai Minwei , Xia Zhidao , Mei Jiong
Published: July 2015

Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). Interleukin-1 beta (IL-1β) is widely used as a chondrocyte apoptosis-inducing agent, while lactoferrin (LF) is an anabolic reagent which has the potential to inhibit chondrocyte apoptosis. We assessed the effects of LF on cartilage degeneration in IL-1β-induced chondrocytes and in a rat model of OA, and explored the potential molecular mechanisms involved. Methods: Human articular chondrocytes (HACs) were treated with IL-1β alone or in combination with LF. MTT and flow cytometric assays were used to detect changes after treatment with LF. Western blotting was used to examine the relevant molecules regulating apoptosis. Results: We found that IL-1β reduced the viability of HACs, whereas 200 μg/mL of LF significantly counteracted the inhibitory effect of IL-1β. LF significantly inhibited IL-1β-induced HAC apoptosis. The protein expression of the apoptotic markers Caspase-3 and PARP was also significantly reduced in the LF treatment group when analyzed by western blotting. Furthermore, we found that LF triggered CREB1 phosphorylation in IL-1β-induced HAC apoptosis through AKT1 signaling. In addition, LF promoted the repair of articular cartilage damage in a rat OA model with elevated p-CREB levels. Conclusions: These studies suggest that LF has an anti-apoptotic effect on IL-1β-induced chondrocytes, and thus may be a promising novel therapeutic agent for OA.
Sealant versus Fluoride in Primary Molars of Kindergarten Children Regularly Receiving Fluoride Varnish: One-Year Randomized Clinical Trial Follow-Up
Authors: Honkala Sisko , ElSalhy Mohamed , Shyama Maddi , Al-Mutawa Sabiha A. , Boodai Hanan , Honkala Eino
Published: July 2015

Objectives: The objectives of this study were to measure the caries preventive effect of sealants applied to occlusal surfaces of primary molars compared to fluoride varnish applications, and to assess the retention rate of sealants after 1 year. Methods: 147 first-grade pupils from two kindergarten schools in Kuwait, whose parents gave their written consent, were included. The children were examined by one dentist using the International Caries Detection and Assessment System. After the examination, sealants and fluoride varnish were applied on the selected occlusal surfaces of primary molars by another dentist. The jaw quadrant for intervention was selected randomly; molars on the contralateral side of the mouth received the contralateral intervention. Examinations and intervention were provided on the school premises in the mobile dental unit with a portable spotlight. Moisture was controlled by cotton rolls, suction and air drying. The follow-up examinations were conducted after 1 year. All children received fluoride varnish before and 6 months after the intervention. Results: From 267 matched pairs of occlusal surfaces of primary molars, varnished surfaces were significantly more likely to develop new caries lesions than the sealed ones (odds ratio = 2.92; 95% confidence interval = 1.82-4.71) during the 1-year follow-up. The majority (73.0%) of the sealants were completely retained and 15.1% partially. Conclusions: Sealing fissures seems to be better in preventing occlusal caries lesions in primary molars than applying only fluoride varnish. After 1 year, the majority of sealants were retained sound.