bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheology as a Tool to Predict the Release of Alpha-Lipoic Acid from Emulsions Used for the Prevention of Skin Aging
Authors: Isaac Vera Lucia Borges , Chiari-Andréo Bruna Galdorfini , Marto Joana Marques , Moraes Jemima Daniela Dias , Leone Beatriz Alves , Corrêa Marcos Antonio , Ribeiro Helena Margarida
Published: December 2015

The availability of an active substance through the skin depends basically on two consecutive steps: the release of this substance from the vehicle and its subsequent permeation through the skin. Hence, studies on the specific properties of vehicles, such as their rheological behavior, are of great interest in the field of dermatological products. Recent studies have shown the influence of the rheological features of a vehicle on the release of drugs and active compounds from the formulation. In this context, the aim of this study was to evaluate the influence of the rheological features of two different emulsion formulations on the release of alpha-lipoic acid. Alpha-lipoic acid (ALA) was chosen for this study because of its antioxidant characteristics, which could be useful for the prevention of skin diseases and aging. The rheological and mechanical behavior and thein vitrorelease profile were assayed. The results showed that rheological features, such as viscosity, thixotropy, and compliance, strongly influenced the release of ALA from the emulsion and that the presence of a hydrophilic polymer in one of the emulsions was an important factor affecting the rheology and, therefore, the release of ALA.
Spindle Cell Carcinoma of the Larynx: A Confusing Diagnosis for the Pathologist and Clinician
Authors: Bostanci Asli , Ozbilim Gulay , Turhan Murat
Published: December 2015

Laryngeal spindle cell carcinoma (SpCC) is an uncommon subtype of squamous cell carcinoma which represents 0.5% of all laryngeal squamous cell carcinomas. It is a biphasic tumor consisting of the combination of a malignant mesenchymal spindle cell component and a squamous cell component that includes dysplasia, carcinoma in situ, or invasive carcinoma. Although it has aggressive biological features, the probability of making a diagnosis in the early stages is high as it often leads to obstructive symptoms in the early period. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a 60-year-old laryngeal SpCC case that was effectively treated with wide local excision followed by adjuvant radiotherapy was presented with the literature.
Evaluation of Subcision for the Correction of the Prominent Nasolabial Folds
Authors: Robati R. M. , Abdollahimajd F. , Robati A. M.
Published: December 2015

Background.A prominent nasolabial fold (NLF) is a cosmetic problem. Currently, numerous therapeutic modalities are available for pronounced NLFs with variable efficacy.Objective.To determine the efficacy and safety of subcision using a hypodermic needle for the correction of the prominent NLFs and its effect on skin elasticity.Methods.Sixteen patients with prominent NLFs underwent subcision. The investigators’ assessment of improvement and the patients’ satisfaction were both recorded 1 and 6 months after the procedure. Also, we evaluate the skin elasticity of NLFs before and after the treatment using a sensitive biometrologic device with the measurement of cutaneous resonance running time (CRRT).Results.Thirteen (81.25%) patients showed a moderate improvement at 1st month and 13 (81.25%) patients had at least a mild improvement at 6th month. There was no persistent side effect lasting more than a few days. Mean CRRT at 1 and 6 months after the treatment was significantly higher compared to the baseline.Conclusion.Subcision may be considered effective for the correction of pronounced NLFs. However, further controlled studies with larger sample size are necessary to assess the efficacy of this technique in particular with use of more objective assessment of skin biometric characteristics. This trial is registered withIRCT201108097270N1(registered on January 27, 2012).
Rotation Estimation for Wide-Angle Inverse Synthetic Aperture Radar Imaging
Authors: Zhou Wei , Yeh Chun-mao , Jin Rui-jin , Yang Jian , Song Jian-she
Published: December 2015

To present focused ISAR imaging results in the homogenous range and cross-range domain, an integrated scheme is proposed to estimate both the targets equivalent rotational velocity (RV) and rotational center (RC). The RV estimation is improved by radial projection combined with keystone processing, and then the RC is estimated through image entropy minimization. Finally, delicate imaging results may be obtained for wide-angle scenarios. Experiment results are provided to demonstrate the effectiveness of the proposed method.
The Evolving Scale and Profile of Cancer Worldwide: Much Ado About Everything
Authors: Bray Freddie
Published: December 2015

Today, cancer is responsible for one in three premature deaths from noncommunicable diseases worldwide, and the number of annual cancer diagnoses will rise to well over 20 million by the year 2030. That cancer is of profound importance to future global health reflects both recent gains in human development as well as mortality transitions that are centuries old. Still, cancer is complex, and the extensive geographical and temporal heterogeneity alerts us to the need for targeted, local approaches to cancer control. The study of trends in specific cancer types remains essential in monitoring and evaluating such strategies and as a descriptive tool for hypothesizing possible contributory factors. Of greatest necessity is an expansion of the availability of high-quality data. To improve the limited cancer incidence data available in low- and middle-income countries (LMIC), the Global Initiative for Cancer Registry Development (http://gicr.iarc.fr) is an international partnership supporting countries to redraw the surveillance map. Cancer Epidemiol Biomarkers Prev; 25(1); 3–5. ©2015 AACR.

See related article by Torre et al., p. 16
CCR 20th Anniversary Commentary: Autologous T Cells—The Ultimate Personalized Drug for the Immunotherapy of Human Cancer
Authors: Rosenberg Steven A.
Published: December 2015

The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. Clin Cancer Res; 21(24); 5409–11. ©2015 AACR.

See related article by Rosenberg et al., Clin Cancer Res 2011;17(13) July 1, 2011;4550–7
A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib
Authors: Lee Ji Yun , Sun Jong-Mu , Lim Sung Hee , Kim Hae Su , Yoo Kwai Han , Jung Ki Sun , Song Haa-Na , Ku Bo Mi , Koh Jiae , Bae Yeon-Hee , Lee Se-Hoon , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju
Published: December 2015

Purpose: In this phase Ib/II study, we aimed to assess the safety and efficacy of afatinib plus nimotuzumab (N) in advanced non–small cell lung cancer (NSCLC) patients with acquired resistance to gefitinib or erlotinib.

Experimental Design: In phase Ib stage, patients received afatinib (40 mg or 30 mg once daily) plus nimotuzumab (100 mg or 200 mg once weekly) for 28-day cycles to determine the recommended phase II dose (RPIID). The safety and efficacy of RPIID dose was evaluated in phase II stage.

Results: In total, 50 patients were enrolled (13 to phase Ib and 37 to phase II). In the first dose-finding cohort (afatinib 40 mg plus nimotuzumab 100 mg), one patient experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and in the subsequent cohort (afatinib 40 mg plus nimotuzumab 200 mg), two DLTs (grade 3 diarrhea and grade 3 neutropenia) occurred in 2 of 6 patients. Accordingly, RPIID was determined as afatinib 40 mg plus nimotuzumab 100 mg. In 44 patients treated with RPIID, 7 (16%) patients had grade 3 toxicities; skin rash (7%), diarrhea (5%), acne (2%), and fatigue (2%). The overall response rate was 23% and the median duration of response was 4.3 months (range, 0.7–16.2 months). The median progression-free survival and overall survival were 4.0 months [95% confidence interval (CI), 2.3–5.7 months] and 11.7 months (95% CI, 9.4–14.0 months), respectively.

Conclusions: Combination treatment of afatinib and nimotuzumab demonstrated an acceptable safety profile and encouraging antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib. Larger phase III trial is warranted to confirm its efficacy and safety. Clin Cancer Res; 22(9); 2139–45. ©2015 AACR.
Expression and Function of Phosphodiesterase Type 5 in Human Breast Cancer Cell Lines and Tissues: Implications for Targeted Therapy
Authors: Catalano Stefania , Campana Antonella , Giordano Cinzia , Győrffy Balázs , Tarallo Roberta , Rinaldi Antonio , Bruno Giuseppina , Ferraro Aurora , Romeo Francesco , Lanzino Marilena , Naro Fabio , Bonofiglio Daniela , Andò Sebastiano , Barone Ines
Published: December 2015

Purpose: By catalyzing cGMP hydrolysis, phosphodiesterase (PDE) 5 is a critical regulator of its concentration and effects in different (patho)physiologic processes, including cancers. As PDE5 is a known druggable target, we investigated the clinical significance of its expression in breast cancer and the underlying mechanisms by which it may contribute to tumor progression.

Experimental Design: PDE5 expression was evaluated in seven breast cancer cell lines by RT-PCR and immunoblotting. To examine the impact of PDE5 on cancer phenotype, MCF-7 cells expressing lower levels of the enzyme were engineered to stably overexpress PDE5. Proliferation was evaluated by MTT assays, motility and invasion by wound-healing/transmigration/invasion assays, transcriptome-profiling by RNA-sequencing, and Rho GTPase signaling activation by GST-pulldown assays and immunoblotting. Clinical relevance was investigated by IHC on tissues and retrospective studies from METABRIC cohort.

Results: PDE5 is differentially expressed in each molecular subtype of both breast cancer cell lines and tissues, with higher levels representing a startling feature of HER2-positive and triple-negative breast cancers. A positive correlation was established between elevated PDE5 levels and cancers of high histologic grade. Higher PDE5 expression correlated with shorter patient survival in retrospective analyses. On molecular level, stable PDE5 overexpression in Luminal-A–like MCF-7 cells resulted in enhanced motility and invasion through Rho GTPase signaling activation. Treatment of PDE5-stable clones with selective ROCK or PDE5 inhibitors completely restored the less motile and weak invasive behavior of control vector cells.

Conclusions: PDE5 expression enhances breast cancer cell invasive potential, highlighting this enzyme as a novel prognostic candidate and an attractive target for future therapy in breast cancers. Clin Cancer Res; 22(9); 2271–82. ©2015 AACR.
A Novel Crizotinib-Resistant Solvent-Front Mutation Responsive to Cabozantinib Therapy in a Patient with ROS1-Rearranged Lung Cancer
Authors: Drilon Alexander , Somwar Romel , Wagner Jacob P. , Vellore Nadeem A. , Eide Christopher A. , Zabriskie Matthew S. , Arcila Maria E. , Hechtman Jaclyn F. , Wang Lu , Smith Roger S. , Kris Mark G. , Riely Gregory J. , Druker Brian J. , O'Hare Thomas , Ladanyi Marc , Davare Monika A.
Published: December 2015

Purpose: Rearranged ROS1 is a crizotinib-sensitive oncogenic driver in lung cancer. The development of acquired resistance, however, poses a serious clinical challenge. Consequently, experimental and clinical validation of resistance mechanisms and potential second-line therapies is essential.

Experimental Design: We report the discovery of a novel, solvent-front ROS1D2033N mutation in a patient with CD74-ROS1–rearranged lung adenocarcinoma and acquired resistance to crizotinib. Crizotinib resistance of CD74-ROS1D2033N was functionally evaluated using cell-based assays and structural modeling.

Results: In biochemical and cell-based assays, the CD74-ROS1D2033N mutant demonstrated significantly decreased sensitivity to crizotinib. Molecular dynamics simulation revealed compromised crizotinib binding due to drastic changes in the electrostatic interaction between the D2033 residue and crizotinib and reorientation of neighboring residues. In contrast, cabozantinib binding was unaffected by the D2033N substitution, and inhibitory potency against the mutant was retained. Notably, cabozantinib treatment resulted in a rapid clinical and near-complete radiographic response in this patient.

Conclusions: These results provide the first example of successful therapeutic intervention with targeted therapy to overcome crizotinib resistance in a ROS1-rearranged cancer. Clin Cancer Res; 22(10); 2351–8. ©2015 AACR.
DNA Alkylating Agent Protects Against Spontaneous Hepatocellular Carcinoma Regardless of O6-Methylguanine-DNA Methyltransferase Status
Authors: Herzig Maryanne C.S. , Zavadil Jessica A. , Street Karah , Hildreth Kim , Drinkwater Norman R. , Reddick Traci , Herbert Damon C. , Hanes Martha A. , McMahan C. Alex , Reddick Robert L. , Walter Christi A.
Published: December 2015

Hepatocellular carcinoma is increasingly important in the United States as the incidence rate rose over the last 30 years. C3HeB/FeJ mice serve as a unique model to study hepatocellular carcinoma tumorigenesis because they mimic human hepatocellular carcinoma with delayed onset, male gender bias, approximately 50% incidence, and susceptibility to tumorigenesis is mediated through multiple genetic loci. Because a human O6-methylguanine-DNA methyltransferase (hMGMT) transgene reduces spontaneous tumorigenesis in this model, we hypothesized that hMGMT would also protect from methylation-induced hepatocarcinogenesis. To test this hypothesis, wild-type and hMGMT transgenic C3HeB/FeJ male mice were treated with two monofunctional alkylating agents: diethylnitrosamine (DEN; 0.025 μmol/g body weight) on day 12 of life with evaluation for glucose-6-phosphatase-deficient (G6PD) foci at 16, 24, and 32 weeks or N-methyl-N-nitrosurea (MNU; 25 mg MNU/kg body weight) once monthly for 7 months starting at 3 months of age with evaluation for liver tumors at 12 to 15 months of age. No difference in abundance or size of G6PD foci was measured with DEN treatment. In contrast, it was unexpectedly found that MNU reduces liver tumor prevalence in wild-type and hMGMT transgenic mice despite increased tumor prevalence in other tissues. hMGMT and MNU protections were additive, suggesting that MNU protects through a different mechanism, perhaps through the cytotoxic N7-alkylguanine and N3-alkyladenine lesions which have low mutagenic potential compared with O6-alkylguanine lesions. Together, these results suggest that targeting the repair of cytotoxic lesions may be a good preventative for patients at high risk of developing hepatocellular carcinoma. Cancer Prev Res; 9(3); 245–52. ©2015 AACR.
Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation
Authors: Lim Jong-Hyung , Mitroulis Ioannis , Ferreira Anaisa , Chen Lan-Sun , Gercken Bettina , Steffen Anja , Kemter Elisabeth , Ameln Anne Klotzsche-von , Waskow Claudia , Hosur Kavita , Chatzigeorgiou Antonios , Ludwig Barbara , Wolf Eckhard , Hajishengallis George , Chavakis Triantafyllos , Kourtzelis Ioannis , Kotlabova Klara
Published: December 2015

Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood–islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Supportive management strategies for disseminated intravascular coagulation
Authors: Hunt Beverley J. , Kinasewitz Gary T. , Wada Hideo , Cate Hugo ten , Thachil Jecko , Levi Marcel , Vicente Vicente , D’Angelo Armando , Nisio Marcello Di , Squizzato Alessandro
Published: December 2015

The cornerstone of the management of disseminated intravascular coagulation (DIC) is the treatment of the underlying condition triggering the coagulopathy. However, a number of uncertainties remain over the optimal supportive treatment. The aim of this study was to provide evidence and expert-based recommendations on the optimal supportive haemostatic and antithrombotic treatment strategies for patients with DIC. A working group defined five relevant clinical scenarios. Published studies were systematically searched in the MEDLINE and EMBASE databases (up to May 2014). Seven internationally recognised experts were asked to independently provide clinical advice. A two-phase blinded data collection technique was used to reach consensus. Only three randomised controlled trials (RCTs) on the supportive management of DIC were identified. The RCTs (overall less than 100 patients) investigated the use of fresh frozen plasma and platelet transfusion and found no differences in survival between the intervention and control groups. The experts’ approach was heterogeneous, although there was consensus that supportive management should vary according to the underlying cause, clinical manifestations and severity of blood test abnormalities. Platelet transfusion should be given to maintain platelet count > 50×109/l in case of bleeding while a lower threshold of 20 to 30×109/l may be used in DIC without bleeding. Thromboprophylaxis with low-molecular-weight heparin is advised until bleeding ensues or platelet count drops below 30×109/l. In conclusion, in the absence of solid evidence from RCTs, an individualised supportive management of DIC is advisable based on the type of underlying disease, presence of bleeding or thrombotic complications and laboratory tests results.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Left Atrial Appendage Remodeling After Lariat Left Atrial Appendage Ligation
Authors: Kreidieh Bahij , Rojas Francia , Schurmann Paul , Dave Amish S. , Kashani Amir , Rodríguez-Mañero Moisés , Valderrábano Miguel
Published: December 2015

Background—

Left atrial appendage (LAA) ligation with the Lariat device is being used for stroke prevention in atrial fibrillation. Residual leaks into the LAA are commonly reported after the procedure. Little is known about the anatomic LAA remodeling after Lariat ligation.

Methods and Results—

In an exploratory study, we evaluated LAA 3-dimensional geometry via computed tomographic scan in 31 consecutive patients before Lariat closure and after a minimum of 30 days post procedure. Thirteen patients were classified as unfavorable cases based on anatomic criteria. Our population had an average age of 70±12 years, a mean CHADS2 (congestive heart failure, hypertension, age>75, diabetes mellitus, history of stroke) score of 3.2±1.2, a mean CHADS2VASC (CHADS2 in addition to female sex, ages 65–75, as well as double impact of age >75, vascular disease) of 4.2±1.5, and a mean HASBLED (hypertension, abnormal renal/liver function, stroke, bleeding predisposition/history, labile international normalized ratio, elderly, drugs/alcohol) bleeding score of 4.0±1.1. Successful suture deployment was achieved in all cases, but 3 patients had intraprocedural residual flow into the LAA (leak). On follow-up, 10 patients (32%) had recanalized residual LAA cavities, which were morphologically similar to the original LAA, albeit significantly smaller in volume (22.5±13.3% of the original volume). Recanalization was not associated with age, sex, comorbid conditions, stroke or bleeding risk scores, follow-up interval, baseline LAA volume, or morphology. Unfavorable cases had anatomic outcomes comparable with those of the anatomically favorable population. No patients have exhibited thromboembolism after 842±338 days post ligation.

Conclusions—

Incomplete LAA ligation after Lariat is common. However, the remodeled LAA cavity is dramatically reduced. Diminished cavity size and tightening of the LAA orifice may play a role in the reduction of thrombus formation.
Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation
Authors: Piccini Jonathan P. , Hellkamp Anne S. , Washam Jeffrey B. , Becker Richard C. , Breithardt Günter , Berkowitz Scott D. , Halperin Jonathan L. , Hankey Graeme J. , Hacke Werner , Mahaffey Kenneth W. , Nessel Christopher C. , Singer Daniel E. , Fox Keith A.A. , Patel Manesh R.
Published: December 2015

Background—

Patients with atrial fibrillation (AF) often take multiple medications.

Methods and Results—

We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on ≥10. Although polypharmacy was not associated with higher risk of stroke or non–central nervous system embolism (adjusted hazard ratio, 1.02 for ≥10 versus 0–4 medications; 95% confidence interval, 0.76–1.38), it was associated with higher risks of the combined end point of stroke, non–central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for ≥10 versus 0–4 medications; 95% confidence interval, 1.18–1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for ≥10 versus 0–4 medications; 95% confidence interval, 1.31–1.65). There was no significant difference in primary efficacy (adjusted interaction
P
=0.99) or safety outcomes (adjusted interaction
P
=0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52–0.95; interaction
P
=0.0074). There was no evidence of differential outcomes in those treated with ≥1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors.

Conclusions—

In a population of patients with atrial fibrillation, two thirds were on ≥5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00403767.
Genetic Variation in Renal Expression of
Folate Receptor 1
(
Folr1
) Gene Predisposes Spontaneously Hypertensive Rats to Metabolic Syndrome
Authors: Pravenec Michal , Kožich Viktor , Krijt Jakub , Sokolová Jitka , Zídek Václav , Landa Vladimír , Mlejnek Petr , Šilhavý Jan , Šimáková Miroslava , Škop Vojtěch , Trnovská Jaroslava , Kazdová Ludmila , Kajiya Takashi , Wang Jiaming , Kurtz Theodore W.
Published: December 2015

Metabolism of homocysteine and other sulfur amino acids is closely associated with metabolism of folates. In this study, we analyzed the possible role of folates and sulfur amino acids in the development of features of the metabolic syndrome in the BXH/HXB recombinant inbred strains derived from the spontaneously hypertensive rat (SHR) and Brown Norway progenitors. We mapped a quantitative trait locus for cysteine concentrations to a region of chromosome 1 that contains a
cis
-acting expression quantitative trait locus regulating mRNA levels of
folate receptor 1
(
Folr1
) in the kidney. Sequence analysis revealed a deletion variant in the
Folr1
promoter region of the SHR. Transfection studies demonstrated that the SHR-promoter region of
Folr1
is less effective in driving luciferase reporter gene expression than the Brown Norway promoter region of
Folr1
. Results in the SHR.BN-chr.1 congenic strain confirmed that the SHR variant in
Folr1
cosegregates with markedly reduced renal expression of
Folr1
and renal folate reabsorption, decreased serum levels of folate, increased serum levels of cysteine and homocysteine, increased adiposity, ectopic fat accumulation in liver and muscle, reduced muscle insulin sensitivity, and increased blood pressure. Transgenic rescue experiments performed by expressing a
Folr1
transgene in the SHR ameliorated most of the metabolic disturbances. These findings are consistent with the hypothesis that inherited variation in the expression of
Folr1
in the kidney influences the development of the metabolic syndrome and constitutes a previously unrecognized genetic mechanism that may contribute to increased risk for diabetes mellitus and cardiovascular disease.
Elevated Transglutaminase Activity Triggers Angiotensin Receptor Activating Autoantibody Production and Pathophysiology of Preeclampsia
Authors: Liu Chen , Luo Renna , Elliott Serra E. , Wang Wei , Parchim Nicholas F. , Iriyama Takayuki , Daugherty Patrick S. , Blackwell Sean C. , Sibai Baha M. , Kellems Rodney E. , Xia Yang
Published: December 2015

Background

Preeclampsia (
PE
) is a life‐threatening hypertensive disorder of pregnancy associated with autoantibodies, termed
AT
1
‐
AA
, that activate the
AT
1
angiotensin receptor. Although the pathogenic nature of these autoantibodies has been extensively studied, little is known about the molecular cause of their generation.

Methods and Results

Here we show that tissue transglutaminase (
TG
2), an enzyme that conducts posttranslational modification of target proteins, directly modified the 7‐amino acid (7‐aa) epitope peptide that localizes to the second extracellular loop of the
AT
1
receptor. These findings led us to further discover that plasma transglutaminase activity was induced and contributed to the production of
AT
1
‐
AA
and disease development in an experimental model of
PE
induced by injection of
LIGHT
, a tumor necrosis factor superfamily member. Key features of
PE
were regenerated by adoptive transfer of purified IgG from
LIGHT
‐injected pregnant mice and blocked by the 7‐amino acid epitope peptide. Translating our mouse research to humans, we found that plasma transglutaminase activity was significantly elevated in
PE
patients and was positively correlated with
AT
1
‐
AA
levels and
PE
features.

Conclusions

Overall, we provide compelling mouse and human evidence that elevated transglutaminase underlies
AT
1
‐
AA
production in
PE
and highlight novel pathogenic biomarkers and innovative therapeutic possibilities for the disease.
Enhanced Neural Processing of Goal-directed Actions After Active Training in 4-Month-Old Infants
Authors: Bakker Marta , Sommerville Jessica A. , Gredebäck Gustaf
Published: December 2015

The current study explores the neural correlates of action perception and its relation to infants' active experience performing goal-directed actions. Study 1 provided active training with sticky mittens that enables grasping and object manipulation in prereaching 4-month-olds. After training, EEG was recorded while infants observed images of hands grasping toward (congruent) or away from (incongruent) objects. We demonstrate that brief active training facilitates social perception as indexed by larger amplitude of the P400 ERP component to congruent compared with incongruent trials. Study 2 presented 4-month-old infants with passive training in which they observed an experimenter perform goal-directed reaching actions, followed by an identical ERP session to that used in Study 1. The second study did not demonstrate any differentiation between congruent and incongruent trials. These results suggest that (1) active experience alters the brains' response to goal-directed actions performed by others and (2) visual exposure alone is not sufficient in developing the neural networks subserving goal processing during action observation in infancy.
Atmospheric Controls on Seasonal and Interannual Variations in the Precipitation Isotope in the East Asian Monsoon Region
Authors: Cai Zhongyin , Tian Lide
Published: December 2015

Understanding variations in isotopic composition of precipitation from monsoon regions is crucial for its utilization in paleoclimate studies. This study explores the relationship between precipitation δ18O data for the East Asian monsoon (EAM) region archived in Global Network for Isotopes in Precipitation (GNIP) and the cloud data archived in ISCCP and their linkage with large-scale atmospheric circulation patterns. Results show that precipitation δ18O are significantly and positively correlated with cloud-top pressure (CTP) on both local and regional scales. Mechanically speaking, the stronger the monsoon convection precipitation, the higher the cloud and the lower the condensation temperature and thus the lower the precipitation δ18O. This result implies that the sharp drop in precipitation δ18O in the early summer in monsoonal Asia is related to the atmospheric circulation pattern rather than the different moisture sources, as was previously assumed. This result helps explain the processes leading to the observed “amount effect.” A comparison of atmospheric circulation patterns with precipitation δ18O on an interannual scale shows that the positive CTP anomalies in the central Indo-Pacific within the weak Walker circulation (El Niño) can be associated with positive δ18O anomalies, while negative CTP anomalies in the central Indo-Pacific within the strong Walker circulation (La Niña) can be linked to negative δ18O anomalies. This result further confirms the aforementioned conclusion. This is important for understanding paleoclimatic change in monsoonal Asia, as interannual variations in stable isotopes in that region have received less attention in the past.
On the Movements of the North Atlantic Subpolar Front in the Preinstrumental Past*
Authors: Marchal Olivier , Waelbroeck Claire , Colin de Verdière Alain
Published: December 2015

Three sediment records of sea surface temperature (SST) are analyzed that originate from distant locations in the North Atlantic, have centennial-to-multicentennial resolution, are based on the same reconstruction method and chronological assumptions, and span the past 15 000 yr. Using recursive least squares techniques, an estimate of the time-dependent North Atlantic SST field over the last 15 kyr is sought that is consistent with both the SST records and a surface ocean circulation model, given estimates of their respective error (co)variances. Under the authors’ assumptions about data and model errors, it is found that the 10°C mixed layer isotherm, which approximately traces the modern Subpolar Front, would have moved by ~15° of latitude southward (northward) in the eastern North Atlantic at the onset (termination) of the Younger Dryas cold interval (YD), a result significant at the level of two standard deviations in the isotherm position. In contrast, meridional movements of the isotherm in the Newfoundland basin are estimated to be small and not significant. Thus, the isotherm would have pivoted twice around a region southeast of the Grand Banks, with a southwest–northeast orientation during the warm intervals of the Bølling–Allerød and the Holocene and a more zonal orientation and southerly position during the cold interval of the YD. This study provides an assessment of the significance of similar previous inferences and illustrates the potential of recursive least squares in paleoceanography.
The effectiveness of m-TMI-grafted-PP as a coupling agent for wood polymer composites
Authors: Chauhan Shakti , Aggarwal Pankaj , Karmarkar Ajay
Published: December 2015

The effectiveness of m-isopropenyl-α,α-dimethylbenzyl isocyanate-grafted-polypropylene ( m-TMI-g-PP) as a coupling agent was evaluated for wood flour filled polypropylene composites. The performance was compared with the conventionally used maleic anhydride grafted polypropylene (MAPP) coupling agent in terms of mechanical properties. Rubberwood flour filled polypropylene composites were prepared at varying proportion (1 wt% to 9 wt% of wood fibers) of m-TMI-g-PP and MAPP coupling agents. Composites with m-TMI-g-PP coupling agent exhibited consistently superior strength properties as compared to MAPP at all concentrations of coupling agents inferring that m-TMI-g-PP is a better coupling agent. About 6–9 wt% coupling agent with respect to wood fiber was found to be the optimal level of coupling agent. The effect of filler content and fiber dimension on the properties of composites with m-TMI-g-PP coupling agent was also studied. Tensile strength, flexural strength and tensile modulus increased with increasing filler content in the composites with the coupling agent. At 50% filler loading, composites with coupling agent exhibited about 50%, 78% and 270% improvement in tensile strength, flexural strength and tensile modulus, respectively, over virgin polypropylene. Fiber aspect ratio was found to have a significant effect on the tensile strength of the composites.
The Emotional Dynamics of Consent
Authors: Stannard John E
Published: December 2015

Consent is one of the most powerful concepts known to the law; in particular, it can provide a defence in the criminal context by converting unlawful conduct to that which is not only lawful but even to be encouraged. Despite this, the task of formulating a general theory of consent in criminal law has not been an easy one, not least because of the different situations in which it operates. Given that consent fundamentally involves the subjective attitude of the person concerned to the conduct in question, this paper sets out to explore the dynamics of consent by considering a number of factors, including the way in which it operates as a defence to different crimes, the problems to which consent gives rise in the criminal context and the emotional factors which can influence someone to grant it. It is argued that the development of the law both from a theoretical and a practical perspective requires a more informed and nuanced concept of consent in terms of the emotional dynamics involved.
Informativeness, Timing and Tempo in Lexical Self-Repair
Authors: Plug Leendert
Published: December 2015

This paper presents a study of the temporal organization of lexical repair in spontaneous Dutch speech. It assesses the extent to which offset-to-repair duration and repair tempo can be predicted on the basis of offset timing, reparandum tempo and measures of the informativeness of the crucial lexical items in the repair. Specifically, we address the expectations that repairs that are initiated relatively early are produced relatively fast throughout, and that relatively highly informative repairs are produced relatively slowly. For informativeness, we implement measures based on repair semantics, lexical frequency counts and cloze probabilities. Our results highlight differences between factual and linguistic error repairs, which have not been consistently distinguished in previous studies, and provide some evidence to support the notion that repairs that are initiated relatively early are produced relatively fast. They confirm that lexical frequency counts are rough measures of contextual predictability at best, and reveal very few significant effects of our informativeness measures on the temporal organization of lexical self-repair. Moreover, although we can confirm that most repairs have a repair portion that is fast relative to its reparandum, this cannot be attributed to the relative informativeness of the two portions. Our findings inform the current debate on the division of labour between inner and overt speech monitoring, and suggest that, although the influence of informativeness on speech production is extensive, it is not ubiquitous.
(Re)locating sacredness in Shanghai
Authors: Hingley Liz , Vermander Benoît , Zhang Liang
Published: December 2015

Shanghai is a metropolis that sees itself as the cradle of Chinese ‘modernity’, the birthplace of the revolutionary movement, and a hub of cultural and religious diversity – a multilayered identity enshrined in a number of ‘sacred spaces’. This article focuses on the way sacredness continues to be engineered in today’s Shanghai, mapping the religious landscape through the exploration of four dimensions – namely, ‘landmarks’, ‘compounds’, ‘privacy’, and ‘waterways’. The article assesses the role played by churches, temples, and mosques, by home and working spaces, by waterways and virtual networks, in the shaping of an urban sacred space satisfying a variety of needs and traditions while being symbolically organized into a consistent territory. In the context of a religiously vibrant global city, locating ‘sacredness’ means understanding it as a process of ceaseless dislocation and relocation.
‘You can vote with your feet if you want’. Users’ responses to religious services in the context of food charity in a Finnish city
Authors: Salonen Anna Sofia
Published: December 2015

Drawing on an ethnographic study of the food charity venues in a Finnish city, the article explores how food assistance recipients respond to the religious services they are presented with when seeking material assistance from a religious organization. The study shows that the religious services integrated into the food delivery system are rarely directly criticized, but rather responded to favourably. Any criticism of them is expressed through tacit resistance. The reciprocal relationship between receiving food and participating in religious practice remains mostly implicit, the food recipients’ responses to the religious services being framed by the notion of choice, which undermines the possibility of open criticism of the integration of religious services into the food delivery programmes.
Comparative analysis on yarn mechanism and yarn properties of different jet vortex spinning systems
Authors: Han Chenchen , Xue Wenliang , Cheng Longdi
Published: December 2015

Changing the process of jet vortex spun yarn will result in the change of its structure, and further changing its properties. In this article a comparative study is carried out about three aspects, namely the internal structure of the nozzle, the internal flow field distribution of the nozzle, and the yarn properties of MVS861 and MVS870. The correlation between the yarn formation process and yarn properties will be discussed theoretically, which will be validated by designed experiments. There is significant meaning for researching the correlation between yarn formation process and yarn structure because, on the one hand, it can optimize the process of yarn formation and improve the structure of key components used to form yarn, and on the other hand, it can guide theoretically the design of the yarn structure.
Application of amber filler for production of novel polyamide composite fiber
Authors: Gaidukovs Sergejs , Lyashenko Inga , Rombovska Julija , Gaidukova Gerda
Published: December 2015

The present investigation is connected to the field of medical textiles, which includes the development and application of composite fibers. The aim of the paper is the processing and investigation of polyamide 6 (PA6)–amber composite fibers. The use of amber filler for the preparation of a new type of polymer composite fiber is described in detail for the first time. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and granulometry testing were used to test the structure and the size of the prepared amber particles. The obtained amber particles were characterized by an average size of up to 3 µm and a regular shape. Fourier transform infrared (FTIR) spectroscopy investigations showed that amber in the dispersed state does not change its chemical structure and contains one of the active compounds—succinic acid. The effect of the amber filler inclusion on the melt-spinning routes of fully drawn yarns (FDY) and pre-oriented yarns (POY) was determined. Amber composite fibers general use is medical fabric (compression socks and tights); it is biocompatible with skin cells.
Response of air drag force of the polyethylene terephthalate (PET) yarn treated via dielectric barrier discharge (DBD) plasma to its varying surface characteristics
Authors: Liu Shuai , Feng Zhihua , Liu Deqi , Zhang Xiaofei , Zhang Liang
Published: December 2015

In this paper, non-thermal plasma induced by dielectric barrier discharge (DBD) air discharging was used to treat the moving polyethylene terephthalate (PET) yarn samples and the motionless samples, respectively. The air drag force of the resultant samples was tested, and their surface characteristics were analyzed by X-ray photoelectron spectroscopy (XPS) for chemical composition and by scanning electron microscopy (SEM) for microscopic morphology. The results of the drag force of the samples indicated that, compared with the pristine yarn, the drag force of the samples treated via the two types of plasma treatment clearly varied under different processing conditions. The maximal drag force was 28.26cN for the moving sample treated at 34 V control voltage for 30 s in the discharge zone (zone A) and 27.81cN for the motionless sample treated at 36 V control voltage for 60 s in the long-lived plasma species treating zone (zone B), which increased by 18.9% and 17.0% over that of untreated sample (23.77cN), respectively. The fluctuation of the drag force probably depends on the change of the chemical composition and microstructure of the polyethylene terephthalate yarn surface, which implies that the feasibility of weaving efficiency improvement for an air-jet loom could be realized via controlling and optimizing the dielectric barrier discharge operating conditions.
Illness invalidation from spouse and family is associated with depression in diabetic patients with first superficial diabetic foot ulcers
Authors: Sehlo Mohammad G , Alzahrani Owiss H , Alzahrani Hasan A
Published: December 2015

Objectives

(1) To assess the prevalence of depressive disorders in a sample of diabetic patients with their first superficial diabetic foot ulcer. (2) To evaluate the association between illness invalidation from spouse, family, and depressive disorders in those patients.

Methods

Depressive disorders and severity were diagnosed by the Structured Clinical Interview for DSM-IV Axis Ι disorders, clinical version, and the spouse and family scales of the Illness Invalidation Inventory, respectively (3*I). Physical functioning was also assessed using the Physical Component of The Short Form 36 item health-related quality of life questionnaire.

Results

The prevalence of depressive disorders was 27.50% (22/80). There was a significant decrease in physical health component summary mean score and a significant increase in ulcer size, Center for Epidemiologic Studies–Depression Scale, spouse discounting, spouse lack of understanding, and family discounting mean scores in the depressed group compared to the non-depressed group. Higher levels of spouse discounting, spouse understanding, and family discounting were significant predictors of diagnosis of depressive disorders and were strongly associated with increased severity of depressive symptoms in diabetic patients with first superficial diabetic foot ulcers. Poor physical functioning was associated with increased depressive symptom severity.

Conclusion

This study demonstrated that illness invalidation from spouse and family is associated with diagnosis of depressive disorders and increased severity of depressive symptoms in diabetic patients with first superficial diabetic foot ulcers.
Novel optimal control of semi-active suspension considering a hysteresis model for MR damper
Authors: Moradi Nerbin Mohammad , Mojed Gharamaleki Reza , Mirzaei Mehdi
Published: December 2015

In this paper, a new form of the Bouc–Wen model is identified. This model, which includes hysteresis loop, is suitable to use in controller design. The modified Bouc–Wen model is employed as an experimental model to identify the new model. Evaluation of the proposed model illustrated that this model has good accuracy in small velocity area. A novel approach of model predictive control is employed to derive the control input or magneto-rheological damper current, with respect to constraints. This controller gives analytical control law by means of the Karush–Kuhn–Tucker (KKT) optimization method in order to solve the constrained optimization problem. One of the main advantages of this controller is its analytical form, which allows easy implementation of the controller, and this special form leads to rapid calculation of the control input. Simulations show that the proposed control strategy establishes an appropriate trade-off between suspension criteria, including ride comfort and road holding.
‘Still out on the street waging this fight’: Women irregular workers and industrial action in Korea
Authors: Young Kim , Broadbent Kaye
Published: December 2015

This article reviews the 510-day strike by women irregular workers in the South Korean retail industry, and analyses factors which made a group of women irregular workers, whose employment conditions render them the most marginal employees, to sustain a lengthy struggle despite financial and family pressures. This article argues there are three factors behind the struggle: first their desire to address the employment discrimination and inhumane treatment they faced at work; second their belief that the struggle was larger than just their immediate demands; and third the solidarity and support they received from both the union and full-time colleagues and from the broader community.