bluuebunny/crossref_metadata_2025 huggingface dataset:
Epithelial oestrogen receptor α is dispensable for the development of oestrogen‐induced cervical neoplastic diseases
Authors: Son Jieun , Park Yuri , Chung Sang‐Hyuk
Published: March 2018

Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E2) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E2 mainly functions through oestrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα‐coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted Esr1 in the cervical epithelium but not in the stroma. We found that E2 induced cervical epithelial cell proliferation in epithelial ERα‐deficient mice. We also found that E2 promoted the development of CIN and CxCa in epithelial ERα‐deficient K14E7 mice and that all neoplastic epithelial cells were negative for ERα. In addition, proliferation indices were similar between ERα– and ERα+ CxCa. These results indicate that epithelial ERα is not necessary for E2‐induced CIN and CxCa. Taking these findings together, we conclude that stromal ERα rather than epithelial ERα mediates oncogenic E2 signalling in CxCa. Our results support stromal ERα signalling as a therapeutic target for the disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization
Authors: Gucciardo Erika , Loukovaara Sirpa , Korhonen Ani , Repo Pauliina , Martins Beatriz , Vihinen Helena , Jokitalo Eija , Lehti Kaisa
Published: March 2018

Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady‐state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three‐dimensional whole‐mount immunofluorescence and electron microscopy, heterogeneity in patient‐derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic‐like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo‐cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic‐like capillaries in vivo and developed Prox1+ capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium‐activating concentrations. These results indicate that the ischaemia‐induced and inflammation‐induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients
Authors: MacLean Jessica , MacDonald Tamara , Digout Carol , Smith Nadine , Rigby Krista , Kulkarni Ketan
Published: March 2018

Background

Central venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE).

Procedure

Case records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval. Data regarding demographics, clinical diagnosis, CVC dysfunction, characteristics of CVCs, and VTE were pooled from multiple data sources.

Results

Seven hundred and forty‐one patients required ≥1 CVC. 26.3% of patients required tPA for ≥1 episodes of CVC dysfunction. Requirement of one or more doses of tPA for episodes of CVC dysfunction increased the odds of VTE by two times (95% confidence interval, 1.1–3.6). Patients that required ≥1 doses of tPA required significantly more CVCs (2.05 ± 1.29 per individual patient, 55% of the patients needed >1 CVCs) as compared to the remainder (1.52 ± 0.95 per individual patient, 32% needed >1 CVCs) (P = 0.0001). Multivariate analysis revealed age > 10 years, diagnosis of sarcoma, and tunneled line were independently associated with tPA requirement.

Conclusion

We determined independent risk factors associated with requirement of tPA for CVC dysfunction. Requirement of tPA for CVC dysfunction was associated with significantly increased risk of VTE and requirement of more CVCs. These observations can assist in identification of patients at increased risk of CVC dysfunction and inform approaches to reduce CVC loss and VTE.
Enhanced dielectric thermal stability and permittivity of flexible composite films based on BaTiO3 nanoparticles highly filled PVDF/PAN blend nanofibrous membranes
Authors: Wang Bin , Ma Yue , Na Bing , Lv Ruihua , Liu Hesheng , Li Weiping , Zhou Haiying
Published: March 2018

Polymer film capacitors with high stability and reliability at elevated temperatures are promising for next‐generation power electronic systems and hybrid electric vehicles. In this work, sandwich‐structured composite films with good dielectric thermal stability were fabricated based on hybrid membranes of poly(vinylidene fluoride)/polyacrylonitrile blend nanofibrous skeleton highly filled with BaTiO3 nanoparticles. Composite films with 64.7 vol% BaTiO3 nanoparticles in the core layer exhibited high permittivity (38.1) and low loss (0.046) at 1 kHz and room temperature, and the dielectric permittivity and loss were only slightly increased to 41.5 and 0.08, respectively, at 120°C. Good dispersion and high loading of BaTiO3 nanoparticles in the composites films contributed to enhanced dielectric thermal stability and permittivity. Moreover, the composite films showed good flexibility, which could be ascribed to its sandwich‐structure. Our work paves a generic way to fabricate flexible composite films with excellent dielectric thermal stability via high loadings of ceramic nanoparticles. POLYM. COMPOS., 39:E1841–E1848, 2018. © 2018 Society of Plastics Engineers
Evaluation of the US Food and Drug Administration sentinel analysis tools in confirming previously observed drug‐outcome associations: The case of clindamycin and Clostridium difficile infection
Authors: Carnahan Ryan M. , Kuntz Jennifer L. , Wang Shirley V. , Fuller Candace , Gagne Joshua J. , Leonard Charles E. , Hennessy Sean , Meyer Tamra , Archdeacon Patrick , Chen Chih‐Ying , Panozzo Catherine A. , Toh Sengwee , Katcoff Hannah , Woodworth Tiffany , Iyer Aarthi , Axtman Sophia , Chrischilles Elizabeth A.
Published: March 2018

Purpose

The Food and Drug Administration's Sentinel System developed parameterized, reusable analytic programs for evaluation of medical product safety. Research on outpatient antibiotic exposures, and Clostridium difficile infection (CDI) with non‐user reference groups led us to expect a higher rate of CDI among outpatient clindamycin users vs penicillin users. We evaluated the ability of the Cohort Identification and Descriptive Analysis and Propensity Score Matching tools to identify a higher rate of CDI among clindamycin users.

Methods

We matched new users of outpatient dispensings of oral clindamycin or penicillin from 13 Data Partners 1:1 on propensity score and followed them for up to 60 days for development of CDI. We used Cox proportional hazards regression stratified by Data Partner and matched pair to compare CDI incidence.

Results

Propensity score models at 3 Data Partners had convergence warnings and a limited range of predicted values. We excluded these Data Partners despite adequate covariate balance after matching. From the 10 Data Partners where these models converged without warnings, we identified 807 919 new clindamycin users and 8 815 441 new penicillin users eligible for the analysis. The stratified analysis of 807 769 matched pairs included 840 events among clindamycin users and 290 among penicillin users (hazard ratio 2.90, 95% confidence interval 2.53, 3.31).

Conclusions

This evaluation produced an expected result and identified several potential enhancements to the Propensity Score Matching tool. This study has important limitations. CDI risk may have been related to factors other than the inherent properties of the drugs, such as duration of use or subsequent exposures.
Development of algorithms for identifying fatal cardiovascular disease in Medicare claims
Authors: Xie Fenglong , Colantonio Lisandro D. , Curtis Jeffrey R. , Kilgore Meredith L. , Levitan Emily B. , Monda Keri L. , Safford Monika M. , Taylor Ben , Woodward Mark , Muntner Paul
Published: March 2018

Background

Cause of death is often not available in administrative claims data.

Objective

To develop claims‐based algorithms to identify deaths due to fatal cardiovascular disease (CVD; ie, fatal coronary heart disease [CHD] or stroke), CHD, and stroke.

Methods

Reasons for Geographic and Racial Differences in Stroke (REGARDS) study data were linked with Medicare claims to develop the algorithms. Events adjudicated by REGARDS study investigators were used as the gold standard. Stepwise selection was used to choose predictors from Medicare data for inclusion in the algorithms. C‐index, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess algorithm performance. Net reclassification index (NRI) was used to compare the algorithms with an approach of classifying all deaths within 28 days following hospitalization for myocardial infarction and stroke to be fatal CVD.

Results

Data from 2,685 REGARDS participants with linkage to Medicare, who died between 2003 and 2013, were analyzed. The C‐index for discriminating fatal CVD from other causes of death was 0.87. Using a cut‐point that provided the closest observed‐to‐predicted number of fatal CVD events, the sensitivity was 0.64, specificity 0.90, PPV 0.65, and NPV 0.90. The algorithms resulted in positive NRIs compared with using deaths within 28 days following hospitalization for myocardial infarction and stroke. Claims‐based algorithms for discriminating fatal CHD and fatal stroke performed similarly to fatal CVD.

Conclusion

The claims‐based algorithms developed to discriminate fatal CVD events from other causes of death performed better than the method of using hospital discharge diagnosis codes.
Folding of granulin domains
Authors: Dastpeyman Mohadeseh , Smout Michael J. , Wilson David , Loukas Alex , Daly Norelle L.
Published: March 2018

Granulins are a family of protein growth factors that are involved in a range of biological functions, including wound repair, inflammation, and tumor growth. They are often expressed as part of large precursor proteins containing multiple granulin domains. Individual granulin domains are characterized by a conserved arrangement of 12 cysteine residues that form six disulfide bonds. Despite the conservation of the cysteine residues, there is significant sequence variation between granulins from different species. The initial structure determined for this family indicated the presence of a well‐defined structure with a laddered arrangement of the six disulfide bonds and a β‐hairpin stack. However, subsequent studies have shown the structure‐function relationships of granulins are quite complex. Recent studies have indicated some granulins might have potential as wound healing agents, and studies aimed at understanding the structure‐function relationships of this family are likely to enhance this potential in drug design. This review provides an overview of the structure‐based studies of granulins, including the folding of truncated peptides derived from granulins from different species.
Low‐cost bifunctional initiators for bidirectional living cationic polymerization of olefins. III. centrally functionalized polyisobutylenes
Authors: Nugay Turgut , Deodhar Tejal , Nugay Nihan , Kennedy Joseph Paul
Published: March 2018

Allyl‐telechelic polyisobutylene (A‐PIB‐A) produced by the bis‐benzocyclobutane dichloride (bBCB‐diCl) initiator contains the bis‐benzocyclobutane (bBCB) fragment at the center of the macromolecule (A‐PIB‐bBCB‐PIB‐A). Thermolysis of A‐PIB‐bBCB‐PIB‐A quantitatively converts the central bBCB fragment to a substituted conjugated tetraene (A‐PIB‐tetraene‐PIB‐A). The structure of A‐PIB‐tetraene‐PIB‐A was anticipated from small molecule models and identified/quantitated by 1H NMR spectroscopy. This is the first time a reactive functional group was introduced at the statistical center of a (telechelic) PIB. Subsequently, the A‐PIB‐tetraene‐PIB‐A was peroxidized to an epoxy derivative. Reaction of the A‐PIB‐tetraene‐PIB‐A with HSCH2CH2OH produced HOCH2‐telechelic PIB containing a central CH2OH function, and hydrosilation with HSi(Me2)‐O‐Si(Me2)H produced SiH‐telechelic PIB with a central SiH function. Reactions with maleic anhydride, tetracyanoethylene, butyl lithium, and potassium permanganate have also been examined. In sum, A‐PIB‐bBCB‐PIB‐A and A‐PIB‐tetraene‐PIB‐A are useful intermediates for the synthesis of novel PIB‐based materials for various end uses under investigation. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1140–1145
Study on the Curing System of Polytriazole Adhesive for Composite Solid Propellant
Authors: Liu Fang‐Bo , Zhang Xi‐Long , Jiang Wei‐Sheng , Yu Fang‐Yuan , Deng Jian‐Ru
Published: March 2018

Polyether/polyester with terminal alkynyl groups, bis‐alkynyl chain extender (BEBA), tri‐alkynyl crosslinking agent (TMPTPE) and bis‐azide curing agent (BPDBA) were synthesized to prepare a series of polytriazole elastomers. The effects of factors including curing parameters (Rt), hard segment content (H%), and crosslinking agent content (C%) on the mechanical properties of cured films were investigated. And the crosslinking network of polytriazole elastomer was evaluated by swelling experiment. The compatibility and mechanical properties of polytriazole adhesive with plasticizer were also studied. The results showed that the tensile strength of the polytriazole adhesive and the elongation at break were changed from 0.71 MPa to 5.72 MPa, 300 % to 720 %, respectively. The polytriazole cross‐linked network structure was able to be well controlled by the loading of crosslinking agent. Moreover, the strong polar plasticizer was compatible with polytriazole adhesive and formed a high plasticizer elastomer.
Cervical flexor muscle training reduces pain, anxiety, and depression levels in patients with chronic neck pain by a clinically important amount: A prospective cohort study
Authors: Nazari Goris , Bobos Pavlos , Billis Evdokia , MacDermid Joy C.
Published: March 2018

Background and Purpose

Neck pain is the fourth leading cause of disability in the United States and exerts an important socio‐economic burden around the world. The aims of this study were to determine the effectiveness of deep and superficial flexor muscle training in addition to home‐based exercises in reducing chronic neck pain and anxiety/depression levels.

Methods

This was a prospective cohort study. Patients between 18 and 65 years old with chronic neck pain were eligible to participate if they had disability levels at least 5 out of 50 on the Neck Disability Index. Patients were divided into three groups: Group A received deep neck flexor and home‐based exercises; Group B received superficial muscle and home‐based exercises; and Group C received home‐based exercises only. The Numeric Pain Rating Scale (NPRS), Neck Disability Index, and Hospital Anxiety and Depression Scale were administered at baseline and 7 weeks later.

Results

The highest improvements in pain intensity levels were observed in Group A with 4.75 (1.74) NPRS points, and the lowest were in Group C with 1.00 (1.10). The highest reductions in anxiety and depression levels were noted in Group A (2.80) and Group B (1.65), respectively. The highest improvements in pain intensity levels were observed among Groups A versus C with 2.80 (0.52) NPRS. The highest reductions in anxiety and depression levels were noted among Groups A versus C with 1.75 (1.10) points and Groups B versus C with 1.60 (0.90) points, respectively.

Conclusions

Deep and superficial flexor muscle training along with home‐based exercises is likely to reduce chronic neck pain and anxiety/depression levels by a clinically relevant amount. Future larger scaled randomized controlled trials are warranted to further support these findings.
MAGI2 is an independent predictor of biochemical recurrence in prostate cancer
Authors: David Stephanie N. , Arnold Egloff Shanna A. , Goyal Rajen , Clark Peter E. , Phillips Sharon , Gellert Lan L. , Hameed Omar , Giannico Giovanna A.
Published: March 2018

Background

Membrane‐associated guanylate kinase, WW and PDZ domain‐containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer.

Methods

Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology.

Results

MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, −0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880‐0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%).

Conclusions

These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post‐operative surveillance intervals.
Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid‐ to long‐term continence
Authors: Furrer Marc A. , Vilaseca Antoni , Corradi Renato B. , Boxler Silvan , Thalmann George N. , Nguyen Daniel P.
Published: March 2018

Background

A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long‐term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy.

Methods

From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow‐up. One‐fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery.

Results

For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47‐0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point.

Conclusions

Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid‐term to long‐term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low‐ to intermediate‐risk prostate cancer.
Temporal efficacy of neonicotinoid seed treatments against Frankliniella fusca on cotton
Authors: D'Ambrosio Damon A , Huseth Anders S , Kennedy George G
Published: March 2018

BACKGROUND

Reports of neonicotinoid seed treatment (NST) failure against Frankliniella fusca in the mid‐south and southeastern USA led to the discovery of widespread resistance in these insect populations. Previous studies of NSTs in other crops have shown the concentration of the insecticide to change over time, which could reduce its efficacy. To understand this temporal effect in cotton with F. fusca, our study examined how plant age alters the effects of NSTs (imidacloprid, imidacloprid + thiodicarb and thiamethoxam) by examining larval establishment at multiple seedling ages during the period of cotton seedling susceptibility to this insect. Additionally, we used F. fusca populations with differing neonicotinoid sensitivity levels to understand how resistance impacts this changing efficacy.

RESULTS

Greenhouse studies showed that larval numbers were significantly greater on older NST‐grown cotton seedlings. The population with elevated neonicotinoid resistance had a more rapid increase in larval number on thiamethoxam‐treated plants over time.

CONCLUSION

NSTs reduce the number of F. fusca larvae on younger seedlings, but this effect declines as seedlings age. The duration of efficacy is shorter against neonicotinoid‐resistant populations. Neonicotinoid resistance in cotton‐infesting F. fusca populations may be accelerated by this time‐dependent decrease in efficacy, which likely encourages low‐dose exposure to these insecticides. © 2018 Society of Chemical Industry
Cascading effects of combining synthetic herbivore‐induced plant volatiles with companion plants to manipulate natural enemies in an agro‐ecosystem
Authors: Salamanca Jordano , Souza Brígida , Rodriguez‐Saona Cesar
Published: March 2018

BACKGROUND

Whether tactics to manipulate natural enemies in agro‐ecosystems enhance their ecosystem function and services remains debatable. We conducted field experiments in 2015–2016 to test the hypothesis that attraction of natural enemies to herbivore‐induced plant volatiles (HIPVs), alone or in combination with companion plants, increases crop productivity. Our treatments consisted of bean plants alone or baited with methyl salicylate (MeSA; an HIPV), or combined with coriander (a companion plant), or with both MeSA and coriander. Numbers of arthropods were visually sampled in each treatment. Sentinel aphids were used to measure ecosystem function (i.e. predation). Plant damage and biomass, and the number and weight of pods and seeds, were measured as a proxy for ecosystem services.

RESULTS

MeSA and coriander, when alone or combined, increased the abundance of insect predators from six families, reduced herbivore (e.g. spider mite and thrips) populations, and increased aphid predation. MeSA and coriander also reduced damage by spider mites. MeSA with or without coriander did not, however, increase crop biomass or any yield parameters.

CONCLUSIONS

MeSA alone or combined with coriander attracted different predator communities, altered pest communities, and reduced damage; however, these results did not cascade down to improve crop productivity. © 2018 Society of Chemical Industry
How are the expression patterns of gut antimicrobial peptides modulated by human gastrointestinal diseases? A bridge between infectious, inflammatory, and malignant diseases
Authors: Dias Bastos Paulo André , Lara Santos Lúcio , Pinheiro Vitorino Rui Miguel
Published: March 2018

The human gut barrier is the tissue exposed to the highest load of microorganisms, harbouring 100 trillion bacteria. In addition, the gut's renewal rate outruns that of any other human tissue. Antimicrobial peptides (AMPs) are highly optimized defense molecules in the intestinal barrier optimized to maintain gastrointestinal homeostasis. Alterations in AMPs activity can lead to or result from human gastrointestinal diseases. In this review, unique, conserved, or otherwise regular alterations in the expression patterns of human AMPs across gastrointestinal inflammatory and infectious diseases were analyzed for pattern elucidation. Human gastrointestinal diseases are associated with alterations in gut AMPs' expression patterns in a peptide‐specific, disease‐specific, and pathogen‐specific way, modulating human gastrointestinal functioning. Across diseases, there is a (i) marked reduction in otherwise constitutively expressed AMPs, leading to increased disease susceptibility, and a (ii) significant increase in the expression of inducible AMPs, leading to tissue damage and disease severity. Infections and inflammatory conditions are associated with altered gene expression in the gut, whose patterns may favour cellular metaplasia, mucosal dysfunction, and disease states. Altered expression of AMPs can thus thrive disease severity and evolution since its early stages. Nevertheless, the modulation of AMP expression patterns unveils promising therapeutic targets.
Myricetin suppresses breast cancer metastasis through down‐regulating the activity of matrix metalloproteinase (MMP)‐2/9
Authors: Ci Yingqian , Zhang Yubo , Liu Yanjie , Lu Shuai , Cao Jianhua , Li Huajun , Zhang Jing , Huang Zongyu , Zhu Xudong , Gao Jin , Han Mei
Published: March 2018

Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA‐Mb‐231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP‐2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real‐time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound‐healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP‐2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration‐dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA‐Mb‐231Br cells through suppressing the protein expression of MMP‐2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.
Robust parameter design optimization for type‐Iright censored data
Authors: Khamkanya Anintaya , Cho Byung Rae , Isik Tugce
Published: March 2018

Robust parameter design (RPD) aims to build product quality in the early design phase of product development by optimizing operating conditions of process parameters. A vast majority of the current RPD studies are based on an uncensored random sample from a process distribution. In reality, censoring schemes are widely implemented in lifetime testing, survival analysis, and reliability studies in which the value of a measurement is only partially known. However, there has been little work on the development of RPD when censored data are under study. To fill in the research gaps given practical needs, this paper proposes response surface–based RPD models that focus on survival times and hazard rate. Primary tools used in this paper include the Kaplan‐Meier estimator, Greenwood's formula, the Cox proportional hazards regression method, and a nonlinear programming method. The experimental modeling and optimization procedures are demonstrated through a numerical example. Various response surface–based RPD optimization models are proposed, and their RPD solutions are compared.
Fine speciation of active sites in zeolites by a CO probe: Dynamics and IR frequencies
Authors: Rejmak Paweł , Datka Jerzy , Broclawik Ewa
Published: March 2018

The influence of system dynamics onto infrared spectra calculated and measured for probe molecules weakly interacting with active sites is discussed. OH stretching frequencies for Brønsted sites in Y zeolite and their shift on CO adsorption (measured by IR spectroscopy at ca. 170 K) are simulated from AIMD trajectory, based on BO DFT calculations. We present here very good agreement between experimental and computed OH frequency red‐shift on CO adsorption in dealuminated zeolite Y. It is shown that extracting nonharmonic OH frequencies from ab initio molecular dynamics trajectory provides better estimate of experimental IR results than standard vibrational analyses due to realistic computational model and better correspondence with experimental conditions.
Influence of the protein and DFT method on the broken‐symmetry and spin states in nitrogenase
Authors: Cao Lili , Ryde Ulf
Published: March 2018

The enzyme nitrogenase contains a complicated MoFe7CS9 cofactor with 35 possible broken‐symmetry (BS) states. We have studied how the energies of these states depend on the geometry, the surrounding protein, the DFT functional and the basis set, studying the resting state, a one‐electron reduced state and a protonated state. We find that the effect of the basis set is small, up to 11 kJ/mol. Likewise, the effect of the surrounding protein is restricted, up to 10 and 7 kJ/mol for the electrostatic and van der Waals energy terms. Single‐point energies calculated on a single geometry give a good correlation (R2 = 0.92‐0.98) to energies calculated after geometry optimization, but some BS states may be disfavored by up to 37 kJ/mol. A change from the pure TPSS functional to the hybrid B3LYP functional may change the relative energies by up to 58 kJ/mol and the correlation between the two results is only 0.57‐0.72. Both functionals agree that BS7 is the most stable BS state and that the ground spin state is the quartet for the resting state and the quintet for the reduced state. With the TPSS functional, the BS6 state is the second most stable state, always at least 21 kJ/mol less stable than the BS7 state. However, with the B3LYP functional, BS10 is the second most stable state and for the protonated state it comes close in energy. Based on these results, we suggest a procedure how to consider the 35 BS states in future investigations of the nitrogenase reaction mechanism.
The negative differential resistance mechanism of a molecular device based on double‐cage fluorinated fullerene C20F18(NH)2C20F18: A theoretical study
Authors: Bian Jiang‐yu , Zhang Yang , Chang Ying‐fei
Published: March 2018

The electronic transport properties of the molecular device based on double‐cage fluorinated fullerene C20F18(NH)2C20F18 were studied theoretically. The results show that the device exhibits two negative differential resistance (NDR) peaks in its I‐V curve. The NDR peak under low bias voltage originates from the bias‐induced alignment of the molecular orbitals, and the conduction channel being suppressed at a certain bias voltage is the main reason for the NDR peak under a relatively high bias voltage.
Vegetation community response to hydrologic and geomorphic changes following dam removal
Authors: Lisius G. L. , Snyder N. P. , Collins M. J.
Published: March 2018

Dam removal can restore fish passage, natural flow regimes, sediment transport in streams, dispersal of organic matter, and drift of aquatic insects. However, dam removal also impacts the riparian vegetation, with both immediate and delayed responses. In this study, we measure vegetation change at the Merrimack Village Dam site on the Souhegan River in Merrimack, NH, USA. The August 2008 removal caused a ~3‐m drop in water level and rapid erosion of impounded sediment, with ~50% removed in the first 3 months. Terrace, floodplain, and wetland communities were surveyed in summer 2007, 2009, 2014, and 2015. Temporal change was quantified using Analysis of Similarity on the Bray–Curtis dissimilarity matrix. Only herbaceous vegetation closest to the river channel and in the off‐channel wetland changed significantly. The herbaceous plots directly adjacent to the impoundment eroded to bare sand in 2009, but by 2014, the original riparian fringe community had re‐established in the newly developed floodplain. Between 2007 and 2014, the off‐channel wetland area changed from aquatic species to a stable terrestrial community that persisted without significant change in 2015. The vegetation response was greatest in areas with the largest geomorphic and hydrologic change. These included the channel margin where erosion and bank slumping created an unstable scarp. The mid‐channel island and off‐channel wetland were strongly affected by the lowered water table. However, large unvegetated areas never persisted nor did the areal coverage of invasive species expand, which are two frequent concerns of dam removal stakeholders.
Building cancer prognosis systems with survival function clusters
Authors: Muñoz Johanna , Murua Alejandro
Published: March 2018

In oncology, risk groups are usually constructed by dividing the population in blocks of patients with similar health conditions and demographics levels. Even for a handful of factors, the number of risk groups may be large, which complicates the analyses. There is a need to cluster together homogeneous blocks of patients into larger entities with similar survival characteristics. We develop and compare several techniques to detect these patient meta‐blocks. Our prognosis systems are based on the integrated absolute distance between the survival functions associated with patient blocks. We propose the use of vectorization of survival curves and of principled ensemble algorithms for clustering. We test these methods on different complexity scenarios. The best performing methods are then used to create prognosis systems for the NCIC lung cancer database, a longitudinal study of the U.S. lung cancer patients who were followed from 1988 to 2009.
Distribution‐preserving k‐anonymity
Authors: Wei Dennis , Natesan Ramamurthy Karthikeyan , Varshney Kush R.
Published: March 2018

Preserving the privacy of individuals by protecting their sensitive attributes is an important consideration during microdata release. However, it is equally important to preserve the quality or utility of the data for at least some targeted workloads. We propose a novel framework for privacy preservation based on the k‐anonymity model that is ideally suited for workloads that require preserving the probability distribution of the quasi‐identifier variables in the data. Our framework combines the principles of distribution‐preserving quantization and k‐member clustering, and we specialize it to 2 variants that respectively use intra‐cluster and Gaussian dithering of cluster centers to achieve distribution preservation. We perform theoretical analysis of the proposed schemes in terms of distribution preservation, and describe their utility in workloads such as covariate shift and transfer learning where such a property is necessary. Using extensive experiments on real‐world Medical Expenditure Panel Survey data, we demonstrate the merits of our algorithms over standard k‐anonymization for a hallmark health care application where an insurance company wishes to understand the risk in entering a new market. Furthermore, by empirically quantifying the reidentification risk, we also show that the proposed approaches indeed maintain k‐anonymity.
Global climate change in U.S. high school curricula: Portrayals of the causes, consequences, and potential responses
Authors: Meehan Casey R. , Levy Brett L. M. , Collet‐Gildard Lauren
Published: March 2018

Broad misconceptions about global climate change (GCC) could hinder efforts to address this large‐scale problem, and curricular materials can play a substantial role in what students learn about GCC. This study examines how U.S. high school textbooks and supplemental curricular materials published between 2007 and 2012 portray the causes, consequences, and potential responses to GCC. Our data included text segments related to these topics in five science textbooks, four social studies textbooks, and eight sets of GCC supplemental materials. To analyze these text segments, we conducted several rounds of coding, first categorizing curricula by their acceptance of the human causes of GCC and then coding relevant text segments on several dimensions related to the consequences of and potential responses to GCC. Findings indicate that (1) about half the curricula portray human activity as a major cause of current climate change, (2) most curricula include information about climatic changes but few details about potentially proximal, near‐term impacts of GCC, and (3) most curricula offer a narrow set of strategies for responding to GCC. These findings suggest that educators should critically examine curricular materials they use to teach about GCC and that scholars should continually examine how GCC is portrayed to youth.
Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease
Authors: Ringden Olle , Baygan Arjang , Remberger Mats , Gustafsson Britt , Winiarski Jacek , Khoein Bita , Moll Guido , Klingspor Lena , Westgren Magnus , Sadeghi Behnam
Published: March 2018

Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One-year survival in the two groups was 47% (95% confidence interval [CI] 23–68) and 76% (95% CI 51–89), respectively (p = .016). For the SR patients, 1-year survival was 73% (95% CI 37–90) in SR group 2 (n = 11), which was better than 31% (95% CI 11–54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5–42) in BM-MSC treated (n = 15; p = .0015), and 3% (95% CI 0–14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT-02172937.)
Comparative sustainable development in sub‐Saharan Africa
Authors: Asongu Simplice A.
Published: March 2018

Motivated by sustainable development challenges in sub‐Saharan Africa, this study assesses the comparative persistence of environmental unsustainability in a sample of 44 countries in the subregion for the period 2000–2012. The empirical evidence is based on Generalized Method of Moments. Of the six hypotheses tested, it is not feasible to assess the hypothesis on resource‐wealth because of issues in the degrees of freedom. For the remaining hypotheses, the following findings are established. (i) Hypothesis 1 postulating that middle‐income countries have a lower level of persistence in carbon dioxide (CO2) emissions is valid for CO2 per‐capita emissions, CO2 emissions from electricity and heat production and CO2 emissions from liquid fuel consumption. (ii) Hypothesis 2 that countries on the edge of French civil law is valid for CO2 emissions from liquid fuel consumption and CO2 intensity, but not for CO2 per‐capita emissions. (iii) Hypothesis 3 on the postulation that politically unstable countries reflect more persistence is valid for CO2 per‐capita emissions. (iv) Hypothesis 5 on the propensity for landlocked countries to be associated with more persistence in CO2 emissions is valid for CO2 per‐capita emissions but not for CO2 emissions from liquid fuel consumption. (v) Hypothesis 6 maintaining that Christianity‐dominated countries are more environmentally friendly with regard to CO2 emissions is valid for CO2 per‐capita emissions but not for CO2 emissions from liquid fuel consumption and CO2 intensity. Implications for policy and theory are discussed.
Dell's SupportAssist customer adoption model: enhancing the next generation of data‐intensive support services
Authors: Ghaffarzadegan Navid , Rad Armin A. , Xu Ran , Middlebrooks Sam E. , Mostafavi Sarah , Shepherd Michael , Chambers Landon , Boyum Todd
Published: March 2018

We developed a decision support system to model, analyze, and improve market adoption of Dell's SupportAssist program. SupportAssist is a proactive and preventive support service capability that can monitor system operations data from all connected Dell devices around the world and predict impending failures in those devices. Performance of such data‐intensive services is highly interconnected with market adoption: service performance depends on the richness of the customer database, which is influenced by customer adoption that in turn depends on customer satisfaction and service performance—a reinforcing feedback loop. We developed the SupportAssist adoption model (SAAM). SAAM utilizes various data sources and modeling techniques, particularly system dynamics, to analyze market response under different strategies. Dell anticipates improving market adoption of SupportAssist and revenue from support services, as results of using this analytical tool.

Copyright © 2018 The Authors System Dynamics Review published by John Wiley & Sons Ltd on behalf of System Dynamics Society
Likelihood‐based analysis of outcome‐dependent sampling designs with longitudinal data
Authors: Zelnick Leila R. , Schildcrout Jonathan S. , Heagerty Patrick J.
Published: March 2018

The use of outcome‐dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters. The motivating scenario is when outcome data exist for all cohort members but key exposure variables will be gathered only on a subset. Inference with outcome‐dependent sampling designs that also incorporates incomplete information from those individuals who did not have their exposure ascertained has been investigated for univariate but not longitudinal outcomes. Therefore, with a continuous longitudinal outcome, we explore the relative contributions of various sources of information toward the estimation of key regression parameters using a likelihood framework. We evaluate the efficiency gains that alternative estimators might offer over random sampling, and we offer insight into their relative merits in select practical scenarios. Finally, we illustrate the potential impact of design and analysis choices using data from the Cystic Fibrosis Foundation Patient Registry.
Five recommendations for software evolvability
Authors: Rajlich Václav
Published: March 2018

Evolvability of software lies in intersection of 3 factors: evolving system properties, human factors present in the developer team, and evolution demands. The paper presents 5 recommendations that enhance software evolvability: defined processes of software change, distinction between evolving and stabilized part of the code, analyzable code segments, significant concept encapsulation, and avoidance of wrapping.
Effects of endogenous and exogenous D1/D5 dopamine receptor activation on LTP in ventral and dorsal CA1 hippocampal synapses
Authors: Papaleonidopoulos Vassilios , Kouvaros Stylianos , Papatheodoropoulos Costas
Published: March 2018

Hippocampus is importantly involved in dopamine‐dependent behaviors and dopamine is a significant modulator of synaptic plasticity in the hippocampus. Moreover, the dopaminergic innervation appears to be disproportionally segregated along the hippocampal longitudinal (dorsoventral) axis with unknown consequences for synaptic plasticity. In this study we examined the actions of endogenously released dopamine and the effects of exogenous D1/D5 dopamine receptor agonists on theta‐burst stimulation‐induced long‐term potentiation (LTP) of field excitatory synaptic potential (fEPSP) at Schaffer collateral‐CA1 synapses in slices from dorsal (DH) and ventral hippocampus (VH). Furthermore, we quantified D1 receptor mRNA and protein expression levels in DH and VH. We found that blockade of D1/D5 receptors by SCH 23390 (20 μM) significantly reduced the magnitude of LTP in both DH and VH similarly suggesting that dopamine endogenously released during TBS, presumably mimicking low activity of DA neurons, exerts a homogeneous modulation of LTP along the hippocampal long axis. Moderate to high concentrations of the selective partial D1/D5 receptor agonist SKF 38393 (50‐150 μM) did not significantly change LTP in either hippocampal segment. However, the full D1 receptor selective agonist SKF 82958 (10 μM) significantly enhanced LTP in VH but not DH. Furthermore, the expression of D1 receptor mRNA and protein was considerably higher in VH compared with DH. These results suggest that the dynamic range of D1/D5 receptor‐mediated dopamine effects on LTP may be higher in VH than DH and that VH may be specialized to acquire information about behaviorally relevant strong stimuli signaled by the dopamine system.