bluuebunny/crossref_metadata_2025 huggingface dataset:
Shapes and Origins of Cracks and Correlations with Lamellae Assembly in Poly(L‐lactic acid)
Authors: Woo Eamor M. , Lugito Graecia , Nurkhamidah Siti
Published: November 2016

Just like ring bands in spherulites are not all of a simple type, cracks in crystallized spherulites of polymers can display a wide variety of patterns. Poly(L‐lactic acid) (PLLA) upon crystallization and cooling was found to exhibit as many as four crack types of different directions and patterns, which cannot be feasibly explained simply by the directional difference in coefficients of thermal expansion. Depending on crystallization temperature (Tc), PLLA crystallizes into ringless or ring‐banded spherulites; whereas, the crack patterns are dramatically different in these two types of spherulites. In ring‐banded spherulites of PLLA crystallized at intermediate Tc, two uniquely different crack types are present: (1) twin‐circumferential cracks coinciding with the dark‐bright and bright‐dark boundary, and (2) radial short‐segmental voids coinciding on the bright bands in spherulites. By contrast, only circumferential cracks are present in PLLA ringless spherulites, where crack patterns are influenced by Tc's. Although all cracks in PLLA spherulite are triggered by cooling from Tc, evidence indicates that the crack patterns and ring‐band types (or ringless) are highly correlated and likely both are associated with the lamellar orientation, patterns, and coarseness in spherulites.
Nanoporous Crystalline Polymer Materials for Environmental Applications
Authors: Daniel Christophe , Guerra Gaetano
Published: November 2016

Nanoporous crystalline phases can be obtained with syndiotactic polystyrene (s‐PS) and poly(2,6‐dimethyl‐1,4‐phenylene)oxide (PPO) materials characterized by a large variety of morphologies such as film, powder, or aerogel. These nanoporous crystalline materials are characterized by a high sorption capacity of volatile organic compounds (VOC) also when present in traces in air and water and thus are potentially interesting for environmental applications such as air/water purification. Different aspects relative to the structure and the sorption properties of these innovative polymeric materials are presented in this report.
Adhesion of Human Mesenchymal Stem Cells and Differentiation of SH‐SY5Y Cells on Amyloid Fibrils
Authors: Jacob Reeba S. , Sen Shamik , Maji Samir K.
Published: November 2016

Amyloids are protein/peptide aggregates traditionally associated with many human disorders. However recent evidences suggest that amyloids are also capable of performing various native biological functions in host organisms. Many lower organisms including bacteria and algae use the highly ordered and adhesive property of amyloids for adhesion to host/substrates and/or for colonization, thus suggesting amyloids could serve as extracellular matrices (ECMs). Recently, we had reported that mammalian cells can adhere on amyloids using membrane‐fibril interactions and integrin‐based focal adhesion. In the current study, we demonstrate the nanotopography of amyloid fibrils for adhesion of human mesenchymal stem cells (hMSCs). Further, we also investigate the amyloid surface for differentiation of neuroblastoma cells SH‐SY5Y. Our present study delineates the role of amyloid self‐assembly in cell adhesion and differentiation.
Global transcriptome responses including small RNAs during mixed‐species interactions with methicillin‐resistant Staphylococcus aureus and Pseudomonas aeruginosa
Authors: Miller Christine L. , Van Laar Tricia A. , Chen Tsute , Karna S. L. Rajasekhar , Chen Ping , You Tao , Leung Kai P.
Published: November 2016

Pseudomonas aeruginosa and Staphylococcus aureus mixed‐species biofilm infections are more resilient to biocide attacks compared to their single‐species counterparts. Therefore, this study used an in vitro model recapitulating bacterial burdens seen in in vivo infections to investigate the interactions of P. aeruginosa and S. aureus in biofilms. RNA sequencing (RNA‐seq) was utilized to identify the entire genomic response, both open reading frames (ORFs) and small RNAs (sRNAs), of each species. Using competitive indexes, transposon mutants validated uncharacterized PA1595 of P. aeruginosa and Panton–Valentine leukocidin ORFs of S. aureus are required for competitive success. Assessing spent media on biofilm development determined that the effects of these ORFs are not solely mediated by mechanisms of secretion. Unlike PA1595, leukocidin (lukS‐PV) mutants of S. aureus lack a competitive advantage through contact‐mediated mechanisms demonstrated by cross‐hatch assays. RNA‐seq results suggested that during planktonic mixed‐species growth there is a robust genomic response or active combat from both pathogens until a state of equilibrium is reached during the maturation of a biofilm. In mixed‐species biofilms, P. aeruginosa differentially expressed only 0.3% of its genome, with most ORFs necessary for growth and biofilm development, whereas S. aureus modulated approximately 5% of its genome, with ORFs suggestive of a phenotype of increased virulence and metabolic quiescence. Specific expression of characterized sRNAs aligned with the genomic response to presumably coordinate the adaptive changes necessary for this homeostatic mixed‐species biofilm and sRNAs may provide viable foci for the design of future therapeutics.
Polymetallic nodules, sediments, and deep waters in the equatorial North Pacific exhibit highly diverse and distinct bacterial, archaeal, and microeukaryotic communities
Authors: Shulse Christine N. , Maillot Brianne , Smith Craig R. , Church Matthew J.
Published: November 2016

Concentrated seabed deposits of polymetallic nodules, which are rich in economically valuable metals (e.g., copper, nickel, cobalt, manganese), occur over vast areas of the abyssal Pacific Ocean floor. Little is currently known about the diversity of microorganisms inhabiting abyssal habitats. In this study, sediment, nodule, and water column samples were collected from the Clarion‐Clipperton Zone of the Eastern North Pacific. The diversities of prokaryote and microeukaryote communities associated with these habitats were examined. Microbial community composition and diversity varied with habitat type, water column depth, and sediment horizon. Thaumarchaeota were relatively enriched in the sediments and nodules compared to the water column, whereas Gammaproteobacteria were the most abundant sequences associated with nodules. Among the Eukaryota, rRNA genes belonging to the Cryptomonadales were relatively most abundant among organisms associated with nodules, whereas rRNA gene sequences deriving from members of the Alveolata were relatively enriched in sediments and the water column. Nine operational taxonomic unit (OTU)s were identified that occur in all nodules in this dataset, as well as all nodules found in a study 3000–9000 km from our site. Microbial communities in the sediments had the highest diversity, followed by nodules, and then by the water column with <1/3 the number of OTUs as in the sediments.
Role and regulation of Glycogen synthase kinase‐3 beta in bovine spermatozoa
Authors: Belenky Michael , Breitbart Haim
Published: November 2016

The serine/threonine kinase Glycogen synthase kinase 3 (GSK‐3) is a master switch that regulates a multitude of cellular pathways, including the acrosome reaction in sperm. In epididymal sperm cells, for example, GSK‐3 activity correlates with inhibition of motility—yet no direct pathways connecting GSK‐3 activation with loss of motility have been described. Indeed, the details of how GSK‐3 is regulated during sperm capacitation and the acrosome reaction remains obscure. To this end, we addressed the involvement of the GSK‐3 beta isoform in several known pathways that contribute to motility and the acrosome reaction. We established that Protein kinase A (PKA) is the main regulator of GSK‐3β in sperm, as pre‐treatment of cells with a GSK‐3 inhibitor prior to addition of H89, an inhibitor of PKA, attenuated the motility loss induced by blocking PKA activity. Both induced and spontaneous acrosome reactions also occurred less frequently in sperm treated with GSK‐3 inhibitors. Finally, we observed a slow decline in phosphorylation of GSK‐3β on Ser 9, which represents an inhibited state, during sperm capacitation; this phenotype is reversed during the induced acrosome reaction, in parallel to activation of Protein phosphatase 1. These results suggest that maintenance of sperm motility and acrosome reaction timing are mediated by PKA through the regulation of GSK‐3 beta activity. Mol. Reprod. Dev. 84: 8–18, 2017. © 2016 Wiley Periodicals, Inc.
Overweight or about right? A norm comparison explanation of perceived weight status
Authors: Robinson E. , Kersbergen I.
Published: November 2016

Objectives

Body‐weight norms may explain why personal evaluations of weight status are often inaccurate. Here, we tested a ‘norm comparison’ explanation of weight status perceptions, whereby personal evaluations of weight status are biased by perceived body‐weight norms.

Methods

Study 1 examined whether perceptions of how one's own body weight compares to an average person predict personal evaluations of weight status. Study 2 examined whether manipulating perceptions of how one's own body weight compares to an average person influences whether or not a person identifies their own weight status as being overweight.

Results

In Study 1, if participants rated their body weight as being similar to the body weight of an average person, they were less likely to identify their weight status as being overweight. In Study 2, participants that were led to believe that their body weight was heavier than the average person were more likely to perceive their own weight status as being overweight.

Conclusions

Personal perceptions of weight status are likely to be shaped by a ‘norm comparison’ process. As overweight becomes more normal, underestimation of weight status amongst individuals with overweight and obesity will be more common.
The influence of business associations on legislation: The case of Kenya
Authors: Irwin David , Githinji Mary
Published: November 2016

Interest groups seek to influence public policy. Business associations specifically seek to influence policy related to the environment in which their members operate, with the intention of making it easier for the members, and the wider private sector, to “do business.” Scholars question whether interest groups are influential and, if so, the degree to which their activity influences public policy. Even if they do influence public policy at the margins, it is questionable how effective they are in influencing legislation. As a result, there is little exploration of the factors that may determine whether business membership organizations (BMOs) are likely to be successful. This paper explores the efforts of two BMOs in Kenya to influence legislation: In one case, the BMO persuaded the government to introduce legislation to regulate an activity that had previously not been subject to legislation; in the other, a BMO sought to persuade the government to amend its own proposals to replace existing legislation with new legislation. In both cases, we find evidence that the BMO was successful, though one BMO was significantly more successful than the other. We review the factors perceived by the BMOs to have led to their success. Neither was in a position to rely on economic or other power to strong‐arm the government. Both followed a predominantly insider strategy though with occasional media back‐up. Both were successful on the more “technical” issues. Key factors include the use of a champion, engaging across government, supplying information, and providing evidence and good argumentation.
Differences in VigiBase® reporting of aminoglycoside and capreomycin‐suspected ototoxicity during tuberculosis treatment
Authors: Sagwa Evans L. , Souverein Patrick C. , Ribeiro Inês , Leufkens Hubert G. M. , Mantel‐Teeuwisse Aukje K.
Published: November 2016

Purpose

To evaluate the association between the use of streptomycin, amikacin, kanamycin and capreomycin in tuberculosis (TB) treatment and the pharmacovigilance reporting of ototoxicity (deafness or hearing loss, tinnitus and vertigo). Second, to analyze patient demographic and geographic factors that influence the reporting of ototoxicity in TB treatment.

Methods

A case/non‐case disproportionality analysis of the VigiBase® individual case safety reports (ICSRs) of patients treated for TB using multidrug regimens that contain either of streptomycin, amikacin, kanamycin or capreomycin. Cases were reports of ototoxicity; non‐cases were other adverse drug reactions (ADRs). The unit of analysis was the drug–ADR pair. We calculated reporting odds ratios (RORs) and their 95% confidence intervals (CI). The referent drug was streptomycin.

Results

By June 2014, there were 3361 drug–ADR pairs in VigiBase® (1693 ICSRs) where the parenteral administration of the four drugs for TB treatment was suspected of causing the reported ADRs. Deafness, tinnitus and vertigo were reported in 576 drug–ADR pairs (cases), the rest being other ADRs (non‐cases). Reporting of deafness was most disproportionately associated with amikacin use (ROR 9.3; 95%CI 3.8–23.0), followed by kanamycin use (ROR 4.3; 95%CI 1.3–14.2). Reporting of vertigo was inversely associated with capreomycin use (ROR 0.1; 95%CI 0.01–0.4). Geographic region affected the reporting of ototoxicity while age and sex did not.

Conclusion

Spontaneous reporting of deafness cases within VigiBase® was most disproportionately associated with amikacin use, followed by kanamycin. There were regional variations in the global reporting of ototoxicity. These findings should be verified through a follow up study. Copyright © 2016 John Wiley & Sons, Ltd.
Why hot melts do not stick to cold surfaces
Authors: Treffer Daniel Franz , Khinast Johannes Gregor
Published: November 2016

Many industrial polymer processing operations (e.g., extrusion, injection molding, etc.) include solid‐to‐liquid or liquid‐to‐solid phase changes at non‐isothermal interfaces. Stickiness (tack) can occur depending on the process conditions. However, prediction of tack formation is not trivial. This work presents a hypothesis for tack formation between molten polymers and solids under non‐isothermal conditions. Our hypothesis states that strong adhesion requires wetting (and thus surface creation) at the interface upon contact and, consequently, contact temperatures above the polymer's solidification point. Lower contact temperatures result in a solid–solid interface with negligible adhesion. It was suggested that the contact temperature determines the existence or non‐existence of surface sticking. The hypothesis was supported by non‐isothermal tack experiments, which showed that the change from stickiness to non‐stickiness was surprisingly pronounced with changing surface temperature of the solid material. From a practical perspective, the work may be useful both for professionals (e.g., designing new processing equipment and performing process troubleshooting) and home users (e.g., working with hot melt glue or 3d printers). POLYM. ENG. SCI., 57:1083–1089, 2017. © 2016 Society of Plastics Engineers
Cost‐Effectiveness Analysis of Second‐Line Chemotherapy Agents for Advanced Gastric Cancer
Authors: Lam Simon W. , Wai Maya , Lau Jessica E. , McNamara Michael , Earl Marc , Udeh Belinda
Published: November 2016

Study Objective

Gastric cancer is the fifth most common malignancy and second leading cause of cancer‐related mortality. Chemotherapy options for patients who fail first‐line treatment are limited. Thus the objective of this study was to assess the cost‐effectiveness of second‐line treatment options for patients with advanced or metastatic gastric cancer.

Design

Cost‐effectiveness analysis using a Markov model to compare the cost‐effectiveness of six possible second‐line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care.

Measurements and Main Results

The model was performed from a third‐party payer's perspective to compare lifetime costs and health benefits associated with studied second‐line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness‐to‐pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1‐way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified WTP threshold, our base case analysis demonstrated that irinotecan alone is the most cost‐effective regimen, and both paclitaxel alone and the combination of paclitaxel and ramucirumab were not cost‐effective (ICER more than $50,000). Both 1‐way sensitivity analyses and PSA demonstrated the model's robustness. PSA illustrated that paclitaxel plus ramucirumab was extremely unlikely to be cost‐effective at a WTP threshold less than $400,000/QALY gained.

Conclusion

Irinotecan alone appears to be the most cost‐effective second‐line regimen for patients with gastric cancer. Paclitaxel may be cost‐effective if the WTP threshold was set at $160,000/QALY gained.
Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple Myeloma: An Evolving Therapeutic Strategy
Authors: Chung Clement
Published: November 2016

Multiple myeloma (referred to henceforth as myeloma) is a B‐cell malignancy characterized by unregulated growth of plasma cells in the bone marrow. The treatment paradigm for myeloma underwent significant evolution in the last decade, with an improved understanding of the pathogenesis of the disease as well as the development of therapeutic agents that target not only the tumor cells but also their microenvironment. Despite these therapeutic advances, the prognosis of patients with relapsed or refractory myeloma remains poor. Accordingly, a need exists for new therapeutic avenues that can overcome resistance to current therapies and improve survival outcomes. In addition, myeloma is associated with progressive immune dysregulation, with defects in T‐cell immunity, natural killer cell function, and the antigen‐presenting capacity of dendritic cells, resulting in a tumor microenvironment that promotes disease tolerance and progression. Together, the immunosuppressive microenvironment and oncogenic mutations activate signaling networks that promote myeloma cell survival. Immunotherapy incorporates novel treatment options (e.g., monoclonal antibodies, antibody‐drug conjugates, chimeric antigen receptor T‐cell therapy, immune checkpoint inhibitors, bispecific antibodies, and tumor vaccines) either alone or in combination with existing lines of therapies (e.g., immunomodulatory agents, proteasome inhibitors, and histone deacetylase inhibitors) to enhance the host anti myeloma immunity within the bone marrow microenvironment and improve clinical response. Following the U.S. Food and Drug Administration approval of daratumumab and elotuzumab in 2015, more immunotherapeutic agents are expected to be become available as valuable treatment options in the near future. This review provides a basic understanding of the role of immunotherapy in modulating the bone marrow tumor microenvironment and its role in the treatment of myeloma. Clinical efficacy and safety of recently approved therapeutic monoclonal antibodies (daratumumab, elotuzumab) are discussed, along with the therapeutic potential of emerging immunotherapies (antibody‐drug conjugates, chimeric antigen receptor T‐cell therapy, tumor vaccines, and immune checkpoint inhibitors).
Preparation of polypropylene microspheres for selective laser sintering via thermal‐induced phase separation: Roles of liquid–liquid phase separation and crystallization
Authors: Wang Shao‐Jie , Liu Jian‐Ye , Chu Li‐Qiu , Zou Hao , Zhang Shi‐Jun , Wu Chang‐Jiang
Published: November 2016

Although selective laser sintering (SLS) has been widely applied in many fields, more research work is needed to develop proper polymer microspheres for SLS. Thermal‐induced phase separation (TIPS) is a facile way but rarely reported to prepare the polymer microspheres. The roles of liquid–liquid phase separation (LLPS) and crystallization in the TIPS process are not clear. In this study, proper polypropylene (PP) microspheres for SLS are successfully prepared via TIPS with xylene. The diameters and morphologies of these PP microspheres can be regulated easily by changing the PP concentration and the quench temperature. The large undercooling drives the solution into the metastable LLPS region and produces PP microspheres with smooth surfaces. The PP crystallization occurs both on the LLPS interface and inside the polymer‐rich phase when the solution is quenched to a temperature near the binodal line, and the tiny bent lamellae are formed on the microsphere surface. At higher temperature only PP crystallization occurs, which results in the formation of PP particles consisting of packed lamellae. The PP microspheres prepared here are suitable for SLS and promote the development of SLS potentially. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 320–329
Interaction network of the ribosome assembly machinery from a eukaryotic thermophile
Authors: Baßler Jochen , Ahmed Yasar Luqman , Kallas Martina , Kornprobst Markus , Calviño Fabiola R. , Gnädig Marén , Thoms Matthias , Stier Gunter , Ismail Sherif , Kharde Satyavati , Castillo Nestor , Griesel Sabine , Bastuck Sonja , Bradatsch Bettina , Thomson Emma , Flemming Dirk , Sinning Irmgard , Hurt Ed
Published: November 2016

Ribosome biogenesis in eukaryotic cells is a highly dynamic and complex process innately linked to cell proliferation. The assembly of ribosomes is driven by a myriad of biogenesis factors that shape pre‐ribosomal particles by processing and folding the ribosomal RNA and incorporating ribosomal proteins. Biochemical approaches allowed the isolation and characterization of pre‐ribosomal particles from Saccharomyces cerevisiae, which lead to a spatiotemporal map of biogenesis intermediates along the path from the nucleolus to the cytoplasm. Here, we cloned almost the entire set (∼180) of ribosome biogenesis factors from the thermophilic fungus Chaetomium thermophilum in order to perform an in‐depth analysis of their protein–protein interaction network as well as exploring the suitability of these thermostable proteins for structural studies. First, we performed a systematic screen, testing about 80 factors for crystallization and structure determination. Next, we performed a yeast 2‐hybrid analysis and tested about 32,000 binary combinations, which identified more than 1000 protein–protein contacts between the thermophilic ribosome assembly factors. To exemplary verify several of these interactions, we performed biochemical reconstitution with the focus on the interaction network between 90S pre‐ribosome factors forming the ctUTP‐A and ctUTP‐B modules, and the Brix‐domain containing assembly factors of the pre‐60S subunit. Our work provides a rich resource for biochemical reconstitution and structural analyses of the conserved ribosome assembly machinery from a eukaryotic thermophile.
Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population‐Based Study
Authors: Wang Rong , Zeidan Amer M. , Yu James B. , Soulos Pamela R. , Davidoff Amy J. , Gore Steven D. , Huntington Scott F. , Gross Cary P. , Ma Xiaomei
Published: November 2016

BACKGROUND

To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients.

METHODS

We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999–2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results—Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery.

RESULTS

Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow‐up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16–9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07–2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity‐modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09–2.54).

CONCLUSIONS

Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow‐up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437–445, 2017. © 2016 Wiley Periodicals, Inc.
Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
Authors: Hall RG , Pasipanodya JG , Meek C , Leff RD , Swancutt M , Gumbo T
Published: November 2016

Trimethoprim‐sulfamethoxazole (TMP‐SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global “pandemic” it is vital that we evaluate the effect of obesity on trimethoprim‐sulfamethoxazole concentrations. We conducted a prospective clinical experiment based on optimized design strategies and artificial intelligence algorithms and found that weight and body mass index (BMI) had a profound effect on drug clearance and volume of distribution, and followed nonlinear fractal geometry‐based relationships. The findings were confirmed by demonstrating decreased TMP‐SMX peak and area under the concentration‐time curves in overweight patients based on standard regression statistics. The nonlinear relationships can now be used to identify new TMP‐SMX doses in overweight and obese patients for each of the infections caused by the >60 pathogens for which the drug is indicated.
Neutral beam etching for device isolation in AlGaN/GaN HEMTs
Authors: Hemmi Fuyumi , Thomas Cedric , Lai Yi‐Chun , Higo Akio , Guo Alex , Warnock Shireen , del Alamo Jesús A. , Samukawa Seiji , Otsuji Taiichi , Suemitsu Tetsuya
Published: November 2016

In this article, we report a suppression of leakage current and an improvement of isolation breakdown voltage on GaN‐based high electron mobility transistors (HEMTs) by means of neutral beam (NB) etching. The plasma damage during dry etching process is one of the key reasons for an isolation leakage current, gate leakage current, and current collapse in GaN HEMTs. Since NB etching is virtually free from electrical charges and has few UV photons, it is possible to reduce plasma damage on an etched surface and improve device characteristics. In this work, we introduced NB etching to the device isolation process of GaN HEMTs and characterized isolation leakage currents at DC and step‐stress bias conditions. We also measured the breakdown voltages on two‐terminal test element arrays. We compared the characteristics with samples etched by conventional plasma‐like beam (PB) etching. Our results suggest that NB etching reduces the leakage current through the etched surface of the mesa isolation, which results in superior breakdown voltages.
Increase in the emission wavelength (over 1800 nm) of InAs quantum dots grown on InP substrates using a dot‐in‐well structure
Authors: Akahane Kouichi , Matumoto Atsushi , Umezawa Toshimasa , Yamamoto Naokatsu , Hashimoto Keita , Takai Hiroshi
Published: November 2016

A dot‐in‐well structure for quantum dot (QD) growth on InP (001) vicinal substrates was introduced to increase the emission wavelength. The emission wavelength of the QDs changed from 1600 nm in conventional structures to 1850 nm in the proposed dot‐in‐well structure, when measured at room temperature. The emission intensity of this dot‐in‐well structure was the same as that of the conventional structure, implying that the dot‐in‐well structure did not degrade crystal quality.
The role of spin–orbit coupling in the electronic structure of iron‐based superconductors
Authors: Borisenko Sergey , Evtushinsky Daniil , Liu Zhonghao , Morozov Igor , Kappenberger Rhea , Wurmehl Sabine , Büchner Bernd , Yaresko Alexander , Kim Timur , Hoesch Moritz , Wolf Thomas , Zhigadlo Nikolai
Published: November 2016

Spin–orbit coupling (SOC) is a fundamental interaction in solids that can induce a broad spectrum of unusual physical properties from topologically non‐trivial insulating states to unconventional pairing in superconductors. In iron‐based superconductors (IBS) its role has so far been considered insignificant with the models based on spin‐ or orbital fluctuations pairing being the most advanced in the field. In this review we discuss the recent direct observation of SOC by angle‐resolved photoemission spectroscopy (ARPES).

Electron‐like Fermi surface of LiFeAs split by SOC.
A method to realize traceability in development processes
Authors: Dreves Rainer , Hällmayer Frank , Haunert Lutz , Sechser Bernhard , Rieß Armin
Published: November 2016

The SoQrates Working Group “Traces” develops methods for documenting a continuous flow of information and takes into account the transparency of the activities of the different disciplines. Particularly, the level of detail, accuracy, and completeness of the interfaces are considered. These methods consider also the required traceability demanded by different standards. By using the developed methods, a platform development with reusable components is possible. In combination with an efficient variant management, existing components can be combined to new customer products in a very short time (design to market). The closed traceability approach increases quality and safety veritably without additional resources. This paper describes the current results of the SoQrates Working Group “Traces” as a method description with best practice examples of the participating companies and research institutions.
Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis
Authors: Hasebe Takashi , Fujimoto Kenta , Kajita Mitsuko , Fu Liezhen , Shi Yun-Bo , Ishizuya-Oka Atsuko
Published: November 2016

In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development.
NNLO QCD corrections for Drell-Yan p ZT and $$ {\phi}_{{}^{\eta}}^{\ast } $$ observables at the LHC
Authors: Gehrmann-De Ridder A. , Gehrmann T. , Glover E.W.N. , Huss A. , Morgan T.A.
Published: November 2016

Abstract

Drell-Yan lepton pairs with finite transverse momentum are produced when the vector boson recoils against (multiple) parton emission(s), and is determined by QCD dynamics. At small transverse momentum, the fixed order predictions break down due to the emergence of large logarithmic contributions. This region can be studied via thepTZdistribution constructed from the energies of the leptons, or through the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distribution that relies on the directions of the leptons. For sufficiently small transverse momentum, the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗observable can be measured experimentally with better resolution. We study the smallpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distributions up to next-to-next-to-leading order (NNLO) in perturbative QCD. We compute the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distributions for the fully inclusive production of lepton pairs via Z/γ∗to NNLO and normalise them to the NNLO cross sections for inclusive Z/γ∗production. We compare our predictions with the$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗distribution measured by the ATLAS collaboration during LHC operation at 8 TeV. We find that at moderate to large values of$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗, the NNLO effects are positive and lead to a substantial improvement in the theory-data comparison compared to next-to-leading order (NLO). At small values ofpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗, the known large logarithmic enhancements emerge through and we identify the region where resummation is needed. We find an approximate relationship between the values ofpTZand$$ {\phi}_{{}^{\eta}}^{\ast } $$ϕη∗where the large logarithms emerge and find perturbative consistency between the two observables.
Identification of Recurrence—Predictive Indicators in Stage I Colorectal Cancer
Authors: Lee Jun Ho , Lee Jong Lyul , Park In Ja , Lim Seok‐Byung , Yu Chang Sik , Kim Jin Cheon
Published: November 2016

Background

Patients with stage I colorectal cancer (CRC) rarely experience recurrences; therefore, few risk factors for recurrence are known. This study was designed to evaluate oncologic outcomes of patients with stage I CRC and to identify risk factors for recurrence after curative surgery.

Methods

A retrospective cohort of 860 patients from a single institution who underwent curative surgery for stage I CRC between July 1995 and June 2010 was enrolled. Patients who were diagnosed with hereditary, synchronous, or metachronous cancer and those who received preoperative chemoradiotherapy were excluded. Patients from whom fewer than 12 lymph nodes were retrieved were also excluded.

Results

The 860 patients included 402 (46.7%) with colon tumors and 458 (53.3%) with rectal tumors. Thirty‐five patients (4.1%) experienced recurrences; local and systemic recurrence rates were 1.1 and 3.0%, respectively. The 5‐year overall survival and recurrence‐free survival (RFS) rates were 93.5 ± 0.8% and 95.7 ± 0.8%, respectively. Multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) concentration ≥6 ng/mL (hazard ratio [HR] 3.354, 95% confidence interval [CI] 1.373–8.195, p = 0.008) and lymphovascular invasion (LVI) (HR 2.676, 95% CI 1.097–6.531, p = 0.031) were independent risk factors for RFS.

Conclusions

The overall recurrence rate among patients with stage I CRC after curative surgery was 4.1%. Elevated serum CEA and LVI were significantly associated with recurrence. Large‐scale, multicenter studies are needed to confirm the prognostic value of these risk factors.
Development and Validation of a Scoring System to Predict Surgical Site Infection After Ventral Hernia Repair: A Michigan Surgical Quality Collaborative Study
Authors: Karamanos Efstathios , Kandagatla Pridvi , Watson Jenna , Schmoekel Nathan , Siddiqui Aamir
Published: November 2016

Introduction

Surgical site infections (SSIs) are a rare but significant complication following an elective ventral hernia repair. This study aims to develop a risk assessment tool in order to predict the risk of developing SSIs postoperatively.

Methods

All patients undergoing an elective ventral hernia repair were identified using the Michigan Surgical Quality Collaborative (MSQC) database. Patients’ demographics, comorbidities and technical aspects of the operations were extracted. Logistic regressions were used to create a predictive scoring system for SSIs.

Results

A total of 4983 were included. SSIs occurred in 3.4% of the patient population. A stepwise forward logistic regression identified the need to use drains, BMI, wound classification at the end of the surgery, presence of severe adhesions, a history of CAD, the need for intensive care after surgery, the use of pressors, EtOH abuse and history of PVD as being independently associated with the development of postoperative surgical site infections.

Conclusion

In patients undergoing an elective hernia repair, the incidence of SSI is low. Several preoperative and perioperative factors can contribute to the development of SSIs.
Metabolism of sn‐1(3)‐Monoacylglycerol and sn‐2‐Monoacylglycerol in Caecal Enterocytes and Hepatocytes of Brown Trout (Salmo trutta)
Authors: Li Keshuai , Olsen Rolf Erik
Published: November 2016

sn‐2‐Monoacylglycerol (2‐MAG) and sn‐1(3)‐monoacylglycerol [1(3)‐MAG] are important but yet little studied intermediates in lipid metabolism. The current study compared the metabolic fate of 2‐MAG and 1(3)‐MAG in isolated caecal enterocytes and hepatocytes of brown trout (Salmo trutta). 1(3)‐Oleoyl [9,10‐3H(N)]‐glycerol and 2‐Oleoyl [9,10‐3H(N)]‐glycerol were prepared by pancreatic lipase digestion of triolein [9,10‐3H(N)]. The 1(3)‐MAG and 2‐MAG were efficiently absorbed by enterocytes and hepatocytes at similar rates. The 2‐MAG was quickly resynthesized into TAG through the monoacylglycerol acyltransferase (EC: 2.3.1.22, MGAT) pathway in both tissues, whereas 1(3)‐MAG was processed into TAG and phospholipids at a much slower rate, suggesting 2‐MAG was the preferred substrates for MGAT. Further analysis showed that 1(3)‐MAG was synthesized into 1,3‐DAG, but there were no accumulation of 1,3‐DAG in either enterocytes or hepatocytes, which contrasts that of mammalian studies. Some of the 1(3)‐MAG may be acylated to 1,2(2,3)‐DAG and then utilized for TAG synthesis. Alternatively, 1(3)‐MAG can be hydrolyzed to free fatty acid and glycerol, and re‐synthesized into TAG through the glycerol‐3‐phosphate (Gro‐3‐P) pathway. The overall data suggested that the limiting step of the intracellular 1(3)‐MAG metabolism is the conversion of 1(3)‐MAG itself.
Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data
Authors: Barlev Arie , Lin Vincent W. , Katz Aaron , Hu Kuolung , Cong Ze , Barber Beth
Published: November 2016

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.
Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets
Authors: Shojaee Saeed , Nokhodchi Ali , Maniruzzaman Mohammed
Published: November 2016

Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected.
One Size May Not Fit All: How Obesity Among Mexican-Origin Youth Varies by Generation, Gender, and Age
Authors: Frisco Michelle L. , Quiros Susana , Van Hook Jennifer
Published: November 2016

Immigrants’ health (dis)advantages are increasingly recognized as not being uniform, leading to calls for studies investigating whether immigrant health outcomes are dependent on factors that exacerbate health risks. We answer this call, considering an outcome with competing evidence about immigrants’ vulnerability versus risk: childhood obesity. More specifically, we investigate obesity among three generations of Mexican-origin youth relative to one another and to U.S.-born whites. We posit that risk is dependent on the intersection of generational status, gender, and age, which all influence exposure to U.S. society and weight concerns. Analyses of National Health and Nutrition Examination Studies (NHANES) data suggest that accounting for ethnicity and generation alone misses considerable gender and age heterogeneity in childhood obesity among Mexican-origin and white youth. For example, second-generation boys are vulnerable to obesity, but the odds of obesity for first-generation girls are low and on par with those of white girls. Findings also indicate that age moderates ethnic/generational differences in obesity among boys but not among girls. Overall, ethnic/generational patterns of childhood obesity do not conform to a “one size fits all” theory of immigrant health (dis)advantage, leading us to join calls for more research considering how immigrants’ characteristics and contexts differentially shape vulnerability to disease and death.
Young Children’s Developmental Ecologies and Kindergarten Readiness
Authors: Mollborn Stefanie
Published: November 2016

Children enter the crucial transition to school with sociodemographic disparities firmly established. Domain-specific research (e.g., on poverty and family structure) has shed light on these disparities, but we need broader operationalizations of children’s environments to explain them. Building on existing theory, this study articulates the concept of developmental ecology—those interrelated features of a child’s proximal environment that shape development and health. Developmental ecology links structural and demographic factors with interactional, psychological, and genetic factors. Using the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B), this study conducts latent class analyses to identify how 41 factors from three domains—namely, household resources, health risks, and ecological changes—cluster within children as four overarching developmental ecologies. Because it documents how numerous factors co-occur within children, this method allows an approximation of their lived environments. Findings illuminate powerful relationships between race/ethnicity, parental age, socioeconomic background, and nativity and a child’s developmental ecology, as well as associations between developmental ecology and kindergarten cognition, behavior, and health. Developmental ecology represents a major pathway through which demographic characteristics shape school readiness. Because specific factors have different implications depending on the ecologies in which they are embedded, findings support the usefulness of a broad ecological approach.