bluuebunny/crossref_metadata_2025 huggingface dataset:
TNF‐α promoter polymorphisms and risk of recurrence in patients with squamous cell carcinomas of the nonoropharynx
Authors: Zhang Caiyun , Sturgis Erich M. , Zheng Hongliang , Zafereo Mark E. , Wei Qingyi , Li Guojun
Published: February 2014

Functional polymorphisms of tumor necrosis factor‐alpha (TNF‐α) may play a critical role in the regulation of immune and inflammatory responses and could affect transcriptional levels of the TNF‐α gene and thus contribute to carcinogenesis and outcomes of cancer patients. In a cohort study, we explored the associations between TNF‐α polymorphisms and risk of recurrence of squamous cell carcinoma of the nonoropharynx (SCCNOP). We used log‐rank test and multivariable Cox models to evaluate the associations between TNF‐α polymorphisms and risk of recurrence. In overall comparisons, patients with the TNF‐α ‐857 CC, TNF‐α ‐863 CC and TNF‐α ‐1031 TT genotypes had significantly worse disease‐free survival (log‐rank, p = 0.014, log‐rank, p = .020, and log‐rank, p = .002, respectively) and higher risk of disease recurrence than patients with the corresponding variant genotypes, respectively (hazard ratio [HR], 1.4, 95% CI, 1.1–1.9, HR, 1.4, 95% CI, 1.0–1.8 and HR, 1.6, 95% CI, 1.2–2.2, respectively). However, no significant association was detected for the TNF‐α ‐308 polymorphism. Moreover, in further stratified analyses based on smoking status and treatment, we found that the associations of the TNF‐α ‐857, TNF‐α ‐863 and TNF‐α ‐1031 polymorphisms with risk of recurrence were more pronounced in smokers and patients treated with chemoradiation. Our findings support a significant role of the TNF‐α ‐857, TNF‐α ‐863 and TNF‐α ‐1031 polymorphisms in recurrence of SCCNOP, especially in smokers and patients treated with chemoradiation. Future prospective studies with larger sample size are needed to confirm these findings.
Transcriptomic analysis of a transgenic zebrafish hepatocellular carcinoma model reveals a prominent role of immune responses in tumour progression and regression
Authors: Li Zhen , Luo Huaien , Li Caixia , Huo Xiaojing , Yan Chuan , Huang Xiaoqian , Al‐Haddawi Muthafar , Mathavan Sinnakaruppan , Gong Zhiyuan
Published: February 2014

Using our previously established xmrk transgenic zebrafish, hepatocellular carcinoma (HCC) was generated by induced expression of xmrk, which encoded a hyperactive epidermal growth factor receptor (EGFR) homolog, and regressed by suppression of xmrk expression. To investigate molecular changes in liver tumour progression and regression, RNA‐Seq was performed for induced HCC and early and late stages of liver tissues during tumour regression. We found that Xmrk‐induced zebrafish HCC shared strong molecular characteristics with a human HCC subtype (S2), which shows activated Myc signalling, upregulated phosphor‐S6 and epithelial cell adhesion molecule. In the HCC stage, there were enhanced proteasome, antigen processing and presentation, aminosugars metabolisms, p53 and cell cycle pathways. During tumour regression, the transcriptomic profile showed a reversed trend of molecular changes compared with human HCC progression. Interestingly, distinct immune responses in tumour progression and regression were observed, including increased major histocompatibility complex class I (MHCI) at the HCC stage, enriched immune cell trafficking signals and inflammation in early regression and enhanced MHCII in late regression. Both neutrophils and macrophages were enriched during tumour progression and regression; however, the distribution of neutrophils and macrophages in HCC was relatively uniform, whereas both types of immune cells were regionally clustered during tumour regression, especially with dominant blood vessel association of macrophage in late regression, suggesting differential functions of these immune cells in tumour progression and regression. As tumour regression in our model resembles the targeted inhibition of EGFR in cancer therapy, our observations may provide molecular insights into the targeted inhibition and highlight the importance of immune response in tumour regression.
Inherited variation in the PARP1 gene and survival from melanoma
Authors: Davies John R. , Jewell Rosalyn , Affleck Paul , Anic Gabriella M. , Randerson‐Moor Juliette , Ozola Aija , Egan Kathleen M. , Elliott Faye , García‐Casado Zaida , Hansson Johan , Harland Mark , Höiom Veronica , Jian Guan , Jönsson Göran , Kumar Rajiv , Nagore Eduardo , Wendt Judith , Olsson Håkan , Park Jong Y. , Patel Poulam , Pjanova Dace , Puig Susana , Schadendorf Dirk , Sivaramakrishna Rachakonda P. , Snowden Helen , Stratigos Alexander J. , Bafaloukos Dimitrios , Ogbah Zighereda , Sucker Antje , Van den Oord Joost J. , Van Doorn Remco , Walker Christy , Okamoto Ichiro , Wolter Pascal , Barrett Jennifer H. , Timothy Bishop D. , Newton‐Bishop Julia
Published: February 2014

We report the association of an inherited variant located upstream of the poly(adenosine diphosphate‐ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single‐strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma‐specific survival (MSS). Results were combined using random effects meta‐analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin‐fixed paraffin‐embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04–1.28, p = 0.005, eleven cohorts) and MSS (HR = 1.20 per allele, 95% CI 1.01–1.39, p = 0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS.
Behavior and reproduction of the rotifer Brachionus plicatilis species complex under different light wavelengths and intensities
Authors: Kim Hee‐Jin , Sawada Chihona , Hagiwara Atsushi
Published: February 2014

We investigated the influence of light on phototactic behavior and reproduction in two species of rotifer from the Brachionus plicatilis species complex (B. plicatilis sensu stricto (s. s.) and Brachionus manjavacas). This was done to understand how light effects these species so that we might use this knowledge to establish a more efficient aquaculture protocol. We used four different light wavelengths (white, with peaks at 460 and 570 nm; blue at 470 nm; green at 525 nm; and red at 660 nm) and four intensities (i.e., 0.5–30.0 W/m2). Using micro‐spectrophotometry we determined that eyespots of these two Brachionus species absorbed blue and green light 5.5 times more than red light. B. plicatilis s. s. showed positive phototaxis under white, blue, and green light at lower light intensities, but no phototaxis under red light at all intensities (0.5, 6.2, 15.0, and 30.0 W/m2). Similar patterns of phototaxis were observed in B. manjavacas and did not differ among mictic, amictic females, and male rotifers. Population growth rate of B. plicatilis s. s. under dark condition was 1.1–1.2 times higher than that under white light condition. No significant differences were observed in population growth rate at 3.8 and 6.2 W/m2 at all light wavelengths. On the other hand, population growth rates at 0.5 and 1.6 W/m2 were the lowest under blue light. According to these results, both wavelength and intensity of light affect the population growth of rotifers, which in turn may be influenced by the rotifers' wavelength‐dependent phototaxis.
Molecular biomarkers of phospholipidosis in rat blood and heart after amiodarone treatment
Authors: Bocchini Nicola , Giantin Mery , Crivellente Federica , Ferraresso Serena , Faustinelli Ivo , Dacasto Mauro , Cristofori Patrizia
Published: February 2014

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and concurrent development of concentric lamellar bodies. It is induced in humans and in animals by drugs with a cationic amphiphilic structure. The purpose of the present study was to identify a set of molecular biomarkers of PLD in rat blood and heart, hypothetically applicable in preclinical screens within the drug development process. A toxicological study was set up in rats orally treated up to 11 days with 300 mg kg–1 per day–1 amiodarone (AMD). Light and transmission electron microscopy investigations were performed to confirm the presence of lamellar bodies indicative of phospholipid accumulation. The effects of AMD upon the transcriptome of these tissues were estimated using DNA microarray technology. Microarray data analysis showed that a total of 545 and 8218 genes were modulated by AMD treatment in heart and blood, respectively. Some genes implicated in the phospholipid accumulation in cells, such as phospholipase A2, showed similar alterations of gene expression. After transcriptome criteria of analysis and target selection, including also the involvement in the onset of PLD, 7 genes (Pla2g2a, Pla2g7, Gal, Il1b, Cebpb, Fcgr2b, Acer 2) were selected as candidate biomarkers of PLD in heart and blood tissues, and their potential usefulness as a sensitive screening test was screened and confirmed by quantitative Real‐Time PCR analysis. Collectively, these data underscore the importance of transcriptional profiling in drug discovery and development, and suggest blood as a surrogate tissue for possible phospholipid accumulation in cardiomyocytes. Copyright © 2014 John Wiley & Sons, Ltd.
How Cost Ratios Can Destroy Value
Authors: Lee Reginald Tomas
Published: February 2014

Every day, in practically every organization, managers and executives use cost ratios in a way that can lead to poor or uninformed business decisions. Efficiency will not reduce costs, and looking at efficiency the wrong way will not highlight opportunities. Only by making the right assumptions, using the right math, and applying the right ratio in the proper context will you be able to eliminate the noise created by cost ratios.
Using LinkedIn to Boost Top Financial Careers
Authors: Crant John
Published: February 2014

How important is it for financial executives already near the top of their careers to use an online networking tool like LinkedIn? Author John Crant, a career coach and former vice president of a national recruiting firm, says that the old career rules have changed—and senior executives have to change with them. He reveals some key strategies in using your LinkedIn account and profile.
Can Management Accountants Influence Productivity? The Case of Production Efficiency Variances
Authors: Mertins Lasse , White Lourdes F.
Published: February 2014

Here's a thought: Why not use production efficiency variances to influence productivity right on the production floor? This article describes an experiment designed to compare three ways in which companies can present production efficiency variances, using percentages, dollars, and “smiley” faces.
Are 90% of Organizations Still Failing to Execute on Strategy?
Authors: Desroches Denis , Hatch Toby , Lawson Raef
Published: February 2014

For 30 years now, it's often been said that less than 10% of organizations can fully implement their strategies. Even assuming this used to be valid, is it still? This article reports results from a recent online survey about what actually contributes to successfully executing strategy.
Potent Antiproliferative Effects of 25‐Hydroxy‐16‐ene‐23‐yne‐vitamin D3 That Resists the Catalytic Activity of Both CYP27B1 and CYP24A1
Authors: Rhieu Steve Y. , Annalora Andrew J. , LaPorta Erika , Welsh JoEllen , Itoh Toshimasa , Yamamoto Keiko , Sakaki Toshiyuki , Chen Tai C. , Uskokovic Milan R. , Reddy G. Satyanarayana
Published: February 2014

The potency of 25‐hydroxyvitamin D3 (25(OH)D3) is increased by several fold through its metabolism into 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) by cytochrome P450 27B1 (CYP27B1). Thus, the pivotal role of 1α‐hydroxylation in the activation of vitamin D compounds is well known. Here, we examined the metabolism of 25‐hydroxy‐16‐ene‐23‐yne‐vitamin D3 (25(OH)‐16‐ene‐23‐yne‐D3), a synthetic analog of 25(OH)D3 in a cell‐free system and demonstrated that 25(OH)‐16‐ene‐23‐yne‐D3 is neither activated by CYP27B1 nor inactivated by cytochrome P450 24A1 (CYP24A1). These findings were also confirmed in immortalized normal human prostate epithelial cells (PZ‐HPV‐7) which are known to express both CYP27B1 and CYP24A1, indicating that the structural modifications featured in 25(OH)‐16‐ene‐23‐yne‐D3 enable the analog to resist the actions of both CYP27B1 and CYP24A1. To provide intelligible structure‐function information, we also performed molecular docking analysis between the analog and CYP27B1. Furthermore, 25(OH)‐16‐ene‐23‐yne‐D3 was found to suppress the growth of PZ‐HPV‐7 cells with a potency equivalent to 1α,25(OH)2D3. The antiproliferative activity of 25(OH)‐16‐ene‐23‐yne‐D3 was found to be vitamin D receptor (VDR)‐dependent as it failed to inhibit the growth of mammary tumor cells derived from VDR‐knockout mice. Furthermore, stable introduction of VDR into VDR‐knockout cells restored the growth inhibition by 25(OH)‐16‐ene‐23‐yne‐D3. Thus, we identified 25‐hydroxy‐16‐ene‐23‐yne‐vitamin D3 as a novel non‐1α‐hydroxylated vitamin D analog which is equipotent to 1α,25(OH)2D3 in its antiproliferative activity. We now propose that the low potency of the intrinsic VDR‐mediated activities of 25(OH)D3 can be augmented to the level of 1α,25(OH)2D3 without its activation through 1α‐hydroxylation by CYP27B1, but by simply preventing its inactivation by CYP24A1. J. Cell. Biochem. 115: 1392–1402, 2014. © 2014 Wiley Periodicals, Inc.
RhoA‐Mediated Inhibition of Vascular Endothelial Cell Mobility: Positive Feedback Through Reduced Cytosolic p21 and p27
Authors: Hsu Yung‐Ho , Chang Chih‐Cheng , Yang Nian‐Jie , Lee Yi‐Hsuan , Juan Shu‐Hui
Published: February 2014

We previously identified that activation of the aryl hydrocarbon receptor (AhR) by 3‐methylcholanthrene (3MC) exerts antiproliferative and antimigratory effects on human umbilical vein endothelial cells (HUVECs) through the upregulation of p21/p27 transcription and RhoA activation. In this study, we investigated the mechanisms of 3MC‐mediated downregulation of cytosolic p21/ p27, and the effects of 3MC on RhoA activation and cell migration, in mouse cerebral vascular endothelial cells (MCVECs). Our results indicated that 3MC reduced the phosphorylation of p21/p27 through AhR/RhoA/PTEN‐mediated PI3K/Akt inactivation, which reduced cytosolic p21/p27 retention, causing RhoA activation through positive feedback. Downregulation of p21/p27 by siRNA, and cytosolic p21/p27 by the nuclear export blocker leptomycin B, further reduced cell migration in the 3MC‐treated cells. Reduced cytosolic p21/p27 expression led to reduced interaction between RhoA and the RhoA inhibitor p190RhoGAP, causing RhoA activation. Treatment with YS‐49 activated PI3K/Akt, a downstream target of RhoA, to reduce RhoA/PTEN activation in the 3MC‐treated cells, whereas treatment with wortmannin, a PI3K inhibitor, activated RhoA/PTEN. Gain‐ and loss‐of‐function analyses revealed that constitutively active (CA) Akt1, but not CA Akt2, inactivated RhoA and stimulated migratory activity. Considering the essential role of RhoA activation in cell migration, we evaluated the potential use of simvastatin, a RhoA inhibitor, as a therapeutic intervention in vivo using matrigel plug formation assays. Our results provide a molecular basis for the therapeutic application of simvastatin to reduce RhoA/PTEN activation, restore cytosolic levels of phosphorylated p21/p27, and induce angiogenic processes. J. Cell. Physiol. 229: 1455–1465, 2014. © 2014 Wiley Periodicals, Inc.
Roles of universal three‐dimensional image analysis devices that assist surgical operations
Authors: Sakamoto Tsuyoshi
Published: February 2014

The circumstances surrounding medical image analysis have undergone rapid evolution. In such a situation, it can be said that “imaging” obtained through medical imaging modality and the “analysis” that we employ have become amalgamated. Recently, we feel the distance between “imaging” and “analysis” has become closer regarding the imaging analysis of any organ system, as if both terms mentioned above have become integrated. The history of medical image analysis started with the appearance of the computer. The invention of multi‐planar reconstruction (MPR) used in the helical scan had a significant impact and became the basis for recent image analysis. Subsequently, curbed MPR (CPR) and other methods were developed, and the 3D diagnostic imaging and image analysis of the human body have started on a full scale. Volume rendering: the development of a new rendering algorithm and the significant improvement of memory and CPUs contributed to the development of “volume rendering,” which allows 3D views with retained internal information. A new value was created by this development; computed tomography (CT) images that used to be for “diagnosis” before that time have become “applicable to treatment.” In the past, before the development of volume rendering, a clinician had to mentally reconstruct an image reconfigured for diagnosis into a 3D image, but these developments have allowed the depiction of a 3D image on a monitor. Current technology: Currently, in Japan, the estimation of the liver volume and the perfusion area of the portal vein and hepatic vein are vigorously being adopted during preoperative planning for hepatectomy. Such a circumstance seems to be brought by the substantial improvement of said basic techniques and by upgrading the user interface, allowing doctors easy manipulation by themselves. The following describes the specific techniques. Future of post‐processing technology: It is expected, in terms of the role of image analysis, for better or worse, that computer‐aided diagnosis (CAD) will develop to a highly advanced level in every diagnostic field. Further, it is also expected in the treatment field that a technique coordinating various devices will be strongly required as a surgery navigator. Actually, surgery using an image navigator is being widely studied, and coordination with hardware, including robots, will also be developed.
Endoscopic removal technique of migrated pancreatic plastic stents
Authors: Matsumoto Kazuyuki , Katanuma Akio , Maguchi Hiroyuki
Published: February 2014

Endoscopic pancreatic stenting (EPS) is used for various pancreatic conditions. With the increasing use of pancreatic stents, many complications have been observed. Especially, proximal stent migration presents a more serious condition because of the possibility of pancreatic duct (PD) damage. However, the removal of proximally migrated stents is technically challenging because of the small PD diameter, the bended PD course, the presence of PD strictures, and the lack of suitable devices for stent removal. Thus, few cases of surgical intervention have been encountered. In this study, we review the endoscopic treatment of proximally migrated pancreatic plastic stents. We classify migrated stent conditions into four types according to stent and PD conditions. In Type A, the main pancreatic duct (MPD) has no stricture. In Type B, the stent is positioned across the stricture on the MPD. In Type C, the stent is positioned further away from the stricture on the MPD. The tip of the proximal stent is located in the MPD in types A thru C. In Type D, the tip of the proximal stent is located in a branch duct. We introduced the strategy of endoscopic removal technique of each type of migrated plastic stents.
A New Pathway for Phthalazine Derivatives via Metal‐Free Cyclization of ortho‐Alkynylphenyl Ketones and Hydrazine
Authors: Dong Chune , Liao Zongquan , Xu Xiaoyan , Zhou Haibing
Published: February 2014

A one‐step synthetic protocol for phthalazine derivatives has been developed. In the presence of Et3N, a series of phthalazine derivatives were conveniently prepared in high yield by the reaction of ortho‐alkynylphenyl ketones and hydrazine under mild reaction conditions. The structure was unambiguously confirmed by X‐ray crystallographic analysis of product 2i.
Synthesis of Polysubstituted α‐Pyrones Using Zinc‐Catalyzed Addition–Cyclization Reactions
Authors: Liu Wei‐Bing , Chen Cui , Zhang Qing , Zhu Zhi‐Bo
Published: February 2014

Various polysubstituted α‐pyrone derivatives have been directly synthesized via a hydroalkylation of Michael additional reaction following a cyclized process catalyzed by the Lewis acid of Zn(OAc)2. This protocol provides a new convenient and step‐economical route to construct heterocycles. Fourteen examples are obtained from easily available materials with moderate to good yields.
Stereoselective Epoxidation of Cyclic Dienes and Trienes by Dioxiranes
Authors: D'Accolti Lucia , Annese Cosimo , Aresta Antonella , Fusco Caterina
Published: February 2014

Epoxides are essential building blocks in organic chemistry. The epoxidation of unsubstituted cyclic dienes 2, 3, 4 and triene 5 using dimethyldioxirane (1a) and its trifluoro analog 1b methyl(trifluoromethyl)dioxirane has been investigated. The excellent yields obtained (90–98%) are accompanied by outstandingly high diastereoselectivities (90–98%). Interpretation of results based upon the early idea that polar groups can direct the dioxirane attack by dipole–dipole interaction provides a likely rationale, along with a more generalized mechanistic view.
Improved obstetric safety through programmatic collaboration
Authors: Goffman Dena , Brodman Michael , Friedman Arnold J. , Minkoff Howard , Merkatz Irwin R.
Published: February 2014

Healthcare safety and quality are critically important issues in obstetrics, and society, healthcare providers, patients and insurers share a common goal of working toward safer practice, and are continuously seeking strategies to facilitate improvements. To this end, 4 New York City voluntary hospitals with large maternity services initiated a unique collaborative quality improvement program. It was facilitated by their common risk management advisors, FOJP Service Corporation, and their professional liability insurer, Hospitals Insurance Company. Under the guidance of 4 obstetrics and gynecology departmental chairmen, consensus best practices for obstetrics were developed which included: implementation of evidence based protocols with audit and feedback; standardized educational interventions; mandatory electronic fetal monitoring training; and enhanced in‐house physician coverage. Each institution developed unique safety related expertise (development of electronic documentation, team training, and simulation education), and experiences were shared across the collaborative. The collaborative group developed robust systems for audit of outcomes and documentation quality, as well as enforcement mechanisms. Ongoing feedback to providers served as a key component of the intervention. The liability carrier provided financial support for these patient safety innovations. As a result of the interventions, the overall AOI for our institutions decreased 42% from baseline (January–June 2008) to the most recently reviewed time period (July–December 2011) (10.7% vs 6.2%, p < 0.001). The Weighted Adverse Outcome Score (WAOS) also decreased during the same time period (3.9 vs 2.3, p = 0.001.) Given the improved outcomes noted, our unique program and the process by which it was developed are described in the hopes that others will recognize collaborative partnering with or without insurers as an opportunity to improve obstetric patient safety.
Grant award program partnerships with your professional liability insurance carrier: An innovative approach to loss prevention and improved patient safety
Authors: Cox Phillip M. , Rebstock Jan , Jenkins Randall C. , Dewar Marvin A. , Gruber Laura
Published: February 2014

The financial success of a malpractice insurance program is directly influenced by how effectively the covered providers respond to risk. This article describes a University Self‐Insurance Program partnership to provide small grants to providers who have the expertise and passion for a specific risk reduction activity that is cost effective and measurable and has a high probability of improving patient care and reducing claims or lawsuits. Implementation of this small grant concept can be tailored to become operational in virtually any setting from an independent medical practice to a multistate healthcare system.
Followership in Leadership Studies: A Case of Leader–Follower Trade Approach
Authors: Malakyan Petros G.
Published: February 2014

The current article acknowledges the absence of followership from the leadership literature for many years. Major theories of leadership are reviewed to assert that (1) modern leadership studies have been developed strictly from the leader's perspective with little or no attention on followership, (2) leadership studies have primarily been based on the static understanding of leadership (leaders always remain leaders),1 and (3) there seems to be a need for a new paradigm for leader–follower relationships, which may result in organic relationships between leaders and followers through exchange of leadership and followership functions and roles. Thus, it is argued that the mutuality of relationships and influence between the follower and the leader exists. To address the need for a new paradigm for leadership, the leader–follower trade (LFT) approach is introduced, which may result in the nonstatic and organic approach to leadership–followership as two valuable human behavioral functions. In this case, leadership and followership functions and roles may be traded or exchanged by the positional leaders and followers in different situations or organizational settings toward mutual respect, empowerment, and effectiveness.
Fine morphology of the jaw apparatus of Puncturella noachina (Fissurellidae, Vetigastropoda)
Authors: Vortsepneva Elena , Ivanov Dmitry , Purschke Günter , Tzetlin Alexander
Published: February 2014

Jaws of various kinds occur in virtually all groups of Mollusca, except for Polyplacophora and Bivalvia. Molluscan jaws are formed by the buccal epithelium and either constitute a single plate, a paired formation or a serial structure. Buccal ectodermal structures in gastropods are rather different. They can be nonrenewable or having final growth, like the hooks in Clione (Gastropoda, Gymnosomata). In this case, they are formed by a single cell. Conversely, they can be renewable during the entire life span and in this case they are formed by a set of cells, like the formation of the radula. The fine structure of the jaws was studied in the gastropod Puncturella noachina. The jaw is situated in the buccal cavity and consists of paired elongated cuticular plates. On the anterior edge of each cuticular plate there are numerous longitudinally oriented rodlets disposed over the entire jaw surface and immersed into a cuticular matrix. The jaw can be divided into four zones situated successively toward the anterior edge: 1) the posterior area: the zone of formation of the thick cuticle covering the entire jaw and forming the electron‐dense outer layer of the jaw plate; 2) the zone of rodlet formation; 3) the zone of rodlet arrangement; and 4) the anterior zone: the free scraping edge of the plate, or the erosion zone. In the general pattern of jaw formation, Puncturella noachina resembles Testudinalia tessulata (Patellogastropoda) studied previously. The basis of the jaw is a cuticular plate formed by the activity of the strongly developed microvillar apparatus of the gnathoepithelium. However, the mechanism of renewal of the jaw anterior part in P. noachina is much more complex as its scraping edge consists not just of a thick cuticular matrix rather than of a system of denticles being the projecting endings of rodlets. J. Morphol. 275:775–787, 2014. © 2014 Wiley Periodicals, Inc.
Femtosecond laser‐induced cell‐cell surgical attachment
Authors: Katchinskiy Nir , Godbout Roseline , Goez Helly R. , Elezzabi Abdulhakem Y.
Published: February 2014

Background and Objective

Laser‐induced cell‐cell surgical attachment using femtosecond laser pulses is reported.

Study Design/Materials and Methods

We have demonstrated the ability to attach single cells using sub‐10 femtosecond laser pulses, with 800 nm central wavelength delivered from a Ti:Sapphire laser. To check that the cells did not go through a cell‐fusion process, a fluorescent dye Calcein AM was used to verify that the fluorescent dye did not migrate from a dyed cell to a non‐dyed cell. The mechanical integrity of the attached joint was assessed using an optical tweezer.

Results

Attachment of cells was performed without the induction of cell‐cell fusion, with attachment efficiency of 95%, and while preserving the cells' viability. Cell‐cell attachment was achieved by delivery of one to two trains of femtosecond laser pulses lasting 15 ms each.

Conclusions

Laser‐induced ionization process led to an ultrafast reversible destabilization of the phospholipid layer of the cellular membrane. The inner cell membrane remained intact during the attachment procedure, and isolation of the cells' cytoplasm from the surrounding medium was obtained. A strong physical attachment between the cells was obtained due to the bonding of the membranes' ionized phospholipid molecules and the formation of a joint cellular membrane at the connection point. The cellular attachment technique, femtosecond laser‐induced cell‐cell surgical attachment, can potentially provide a platform for the creation of engineered tissue and cell cultures. Lasers Surg. Med. 46:335–341, 2014. © 2014 Wiley Periodicals, Inc.
Dexamethasone‐Loaded Reconstitutable Charged Polymeric (PLGA)n‐b‐bPEI Micelles for Enhanced Nuclear Delivery of Gene Therapeutics
Authors: Mishra Deepa , Kang Han Chang , Cho Hana , Bae You Han
Published: February 2014

This study investigates the potential of dexamethasone (Dex) to enhance the nuclear accumulation and subsequent gene expression of plasmid DNA (pDNA) delivered using a charged polymeric micelle‐based gene delivery system. (PLGA)n‐b‐bPEI25kDa block copolymers are synthesized and used to prepare Dex‐loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI1.8kDa is coated on the complexes using a Layer‐by‐Layer (LbL) technique to construct DexCM/pDNA/bPEI1.8kDa complexes (i.e., LbL‐DexCM polyplexes) that are 100–180 nm in diameter and have a zeta potential of 30–40 mV. In MCF7 cells, LbL‐DexCM polyplexes cause 3–13‐fold higher transfection efficiencies compared to LbL‐CM polyplexes and show negligible cytotoxicity. LbL‐DexCM3 polyplexes induce much higher nuclear delivery of pDNA compared to LbL‐CM3 polyplexes. These results suggest that Dex‐loaded polyplexes could be used in gene and drug delivery applications to increase nuclear accumulation of therapeutic payloads, further leading to a decrease in the dose of the drug and gene necessary to achieve equivalent therapeutic effects.
Enzymatically Cross‐Linked Gelatin/Chitosan Hydrogels: Tuning Gel Properties and Cellular Response
Authors: da Silva Marcelo A. , Bode Franziska , Drake Alex F. , Goldoni Silvia , Stevens Molly M. , Dreiss Cécile A.
Published: February 2014

This work investigates the effect of combining physical and chemical gelation processes in a biopolymer blend: chitosan and tilapia fish gelatin. Chemical (C) gels are obtained by cross‐linking with the microbial enzyme transglutaminase at 37 °C. Hybrid physical‐co‐chemical (PC) gels are cross‐linked at 21 °C, below gelatin gelation temperature. These protocols provide two microenvironments for the gelation process: in C gels, both gelatin and chitosan are present as single strands; in PC gels, cross‐linking proceeds within a transient physical gel of gelatin, filled by chitosan strands. The chitosan/gelatin chemical networks generated in PC gels show a consistently higher shear modulus than pure C gels; they are also less turbid than their C gels counterparts, suggesting a more homogeneous network. Finally, chitosan enhances the gels' shear modulus in all gels. Proliferation assays show that MC3T3 cells proliferate in these mixed, hybrid gels and better so on PC gels than in C mixed gels.
Light‐Induced Catalyst and Solvent‐Free High Pressure Synthesis of High Density Polyethylene at Ambient Temperature
Authors: Ceppatelli Matteo , Bini Roberto
Published: February 2014

The combined effect of high pressure and electronic photo‐excitation has been proven to be very efficient in activating extremely selective polymerisations of small unsaturated hydrocarbons in diamond anvil cells (DAC). Here we report an ambient temperature, large volume synthesis of high density polyethylene based only on high pressure (0.4–0.5 GPa) and photo‐excitation (~350 nm), without any solvent, catalyst or radical initiator. The reaction conditions are accessible to the current industrial technology and the laboratory scale pilot reactor can be scaled up to much larger dimensions for practical applications. FTIR and Raman spectroscopy, and X‐ray diffraction, indicate that the synthesised material is of comparable quality with respect to the outstanding crystalline material obtained in the DAC. The polydispersity index is comparable to that of IV generation Ziegler‐Natta catalysts. Moreover the crystalline quality of the synthesised material can be further enhanced by a thermal annealing at 373 K and ambient pressure.

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On the spatial distribution of rainfall nowcasting errors due to orographic forcing
Authors: Foresti Loris , Seed Alan
Published: February 2014

The goal of this research is to study the effect of orography on the spatial distribution of rainfall nowcasting errors. Twenty months of forecasts of hourly rainfall accumulations from the short‐term ensemble prediction system (STEPS) for the weather radar composite over eastern Victoria, Australia, were verified against radar observations. The verification was stratified according to six different flow regimes derived by applying a k‐means clustering algorithm on the archive of motion fields. STEPS biases were found to have a strong flow‐regime dependence, which appears as an underestimation of rainfall on the windward side of terrain features followed by an overestimation on the leeward side. In the regions characterized by strong orographic forcing, the relative contribution of the bias to the root mean square error (RMSE) of the nowcast is locally important. The results also highlighted areas where the errors in the radar rainfall estimates contributed a significant fraction of the observed forecast error. These promising results open ways to integrate flow‐dependent and spatially inhomogeneous growth and decay mechanisms in the stochastic simulation of radar rainfall fields performed by STEPS.
Health‐related quality‐of‐life and treatment targets in myasthenia gravis
Authors: Utsugisawa Kimiaki , Suzuki Shigeaki , Nagane Yuriko , Masuda Masayuki , Murai Hiroyuki , Imai Tomihiro , Tsuda Emiko , Konno Shingo , Nakane Shunya , Suzuki Yasushi , Fujihara Kazuo , Suzuki Norihiro
Published: February 2014

Introduction: The aim of this study was to determine factors affecting health‐related quality of life (HRQOL) and to propose appropriate treatment targets for patients with myasthenia gravis (MG). Methods: We evaluated 640 consecutive patients with MG seen at 11 neurological centers. Two‐year follow‐up data were obtained for 282 patients. Correlations between detailed clinical factors and the Japanese version of the 15‐item MG‐specific QOL scale score were analyzed. Results: In a cross‐sectional analysis of 640 MG patients, multivariate regression revealed that disease severity, as evaluated by the MG Composite (P < 0.0001), total dose of oral prednisolone during the last year (P = 0.002), and Cushingoid appearance index (P = 0.0004), showed significant negative effects on HRQOL, but the quantitative MG score and current prednisolone dose did not. Conclusions: Achieving minimal manifestations (MM) status or better with prednisolone ≤5 mg/day was found to exert a major positive impact on HRQOL in both the cross‐sectional and 2‐year follow‐up patient samples and can be recommended as a treatment target. Muscle Nerve 50: 493–500, 2014
Operations sequencing for a multi‐stage production inventory system
Authors: Shi Jim (Junmin) , Yue Xiaohang , Zhao Yao
Published: February 2014

This article studies operations sequencing for a multi‐stage production inventory system with lead times under predictable (deterministic) yield losses and random demand. We consider various cases with either full or partial release of work‐in‐process inventories, for either pre‐operation or post‐operation cost structures, and under either the total discounted or average cost criteria. We derive necessary and sufficient criteria for the optimal sequence of operations in all cases. While the criteria differ in their specific forms, they all lead to the same principal: those operations with (1) lower yields, (2) lower processing costs, (3) longer lead times, and (4) lower inventory holding costs should be placed higher upstream in the system.Copyright © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 144–154, 2014
Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet‐induced obesity
Authors: Walewski José L. , Ge Fengxia , Lobdell Harrison , Levin Nancy , Schwartz Gary J. , Vasselli Joseph R. , Pomp Afons , Dakin Gregory , Berk Paul D.
Published: February 2014

Objective

Microarray studies identified Ch12:orf39 (Spexin) as the most down‐regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.

Methods

Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet‐induced obesity (DIO). Its effects on adipocyte [3H]‐oleate uptake were determined.

Results

In humans, Spexin gene expression was down‐regulated 14.9‐fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects.

Conclusions

Spexin gene expression is markedly down‐regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.
Fracture toughness of walnut particles (Juglans regia L.) and coconut fiber‐reinforced hybrid biocomposite
Authors: Kumar Rao Dinesh , Chandra Gope Prakash
Published: February 2014

The rectangular specimens with an edge crack were subjected to symmetric three‐point bending and asymmetric four‐point bending to determine the mode I and mode II fracture toughness of the walnut particle and coconut fiber‐reinforced biocomposite. Epoxy resin was used as matrix material and 10 wt% of coconut fiber and 20 wt% of walnut shell particle were used as reinforcing materials. The mode I and mode II fracture toughness and mechanical tests were conducted on a servo hydraulic universal testing machine and the results were analyzed and discussed. POLYM. COMPOS., 36:167–173, 2015. © 2014 Society of Plastics Engineers
Preparation and Characterization of hybrid graphene oxide composite and its application in paracetamol microbiosensor
Authors: Khan Anish , Khan Aftab A.P. , Asiri Abdullah M. , Alamry Khalid A.
Published: February 2014

Graphene oxides decorated with Sn(II) (Sn‐GO) were prepared via a redox reaction between graphene oxide (GO) and SnCl2. GO was reacted Sn2+ leading to a homogeneous distribution of Sn on GO. An electrochemical sensor based on the electrocatalytic activity of functionalized graphene oxide for sensitive detection of paracetamol is presented. The electrochemical behaviors of paracetamol on grapheme modified carbon fiber electrodes were investigated by DC potential amperometry. The results showed that the Sn‐GO‐modified electrode exhibited excellent electrocatalytic activity to paracetamol. A redox process of paracetamol at the modified electrode was obtained. Such electrocatalytic behavior of graphene oxide is attributed to its unique physical and chemical properties, e.g., subtle electronic characteristics, attractive π–π interaction, and strong adsorptive capability. This electrochemical sensor shows an excellent performance for detecting paracetamol with a detection limit of 8 µM, a response time of 27 s, and a satisfied recovery. The sensor shows great promise for simple, sensitive, and quantitative detection and screening of paracetamol. We have investigated the composite properties of the self‐assembled electrodes for biological compounds analysis and showed that the Sn‐GO composite biosensor can achieve great sensitivity without significant bio material. The sensor shows great promise for simple, sensitive, and quantitative detection and screening of paracetamol. POLYM. COMPOS., 36:221–228, 2015. © 2014 Society of Plastics Engineers
Theoretical mechanistic studies on the degradation of alizarin yellow R initiated by hydroxyl radical
Authors: Jiao Xiaowei , Yu Hang , Kong Qingwei , Luo Yi , Chen Qiang , Qu Jingping
Published: February 2014

The degradation of azo dyes has attracted many research efforts not only due to the resulting environmental problems but also because the azo compounds with various substituents may show different degradation mechanism. It has been computationally found here, for the first time, that the HO• initiated cleavages of C–N and N–N bonds of alizarin yellow R with carboxyl group are kinetically competitive. In view of the formation of HO• adducts, the C–N and N–N bond cleavages of the hydrazone tautomer of alizarin yellow R are also kinetically competitive, but the former is more thermodynamically favorable. This result is different from that previously reported for the hydrozone tautomers of Acid Orange 7 and Acid Orange 8 containing hydroxyl and azo groups in neighboring positions, which are favorable to follow C–N bond cleavage mechanism both kinetically and thermodynamically. The decarboxylation occurs via an attack of HO• to the benzene ring carbon connecting to the carboxyl group rather than a direct attack of HO• to the carboxyl carbon atom. The anion form has higher reactivity than the neutral form in all of the reactions investigated. In addition, a water molecule as a proton relay reagent could significantly reduce the energy barrier for the N–N bond cleavage of alizarin yellow R. Copyright © 2014 John Wiley & Sons, Ltd.
Challenges in the theoretical description of nanoparticle reactivity: Nano zero‐valent iron
Authors: Karlický František , Otyepka Michal
Published: February 2014

The reactivity of iron atoms, clusters, and nanoparticles (nZVI) is of increasing interest owing to their important practical applications, ranging from the steel industry to water remediation technologies. Here, we provide an overview of computational methods and models that can be applied to study nanoscale zero‐valent iron (nZVI) reactions and discuss their benefits and limitations. We also report current progress in calculations through recent examples treating the reactivity of nZVI particles. Finally, we consider the potential use of highly accurate methods with favorable scaling (such as quantum Monte Carlo or random phase approximation), which are currently considered too computationally expensive but are expected to become more amenable in the future as computer power increases. © 2014 The Authors International Journal of Quantum Chemistry Published by Wiley Periodicals, Inc.
Targeted learning in real‐world comparative effectiveness research with time‐varying interventions
Authors: Neugebauer Romain , Schmittdiel Julie A. , van der Laan Mark J.
Published: February 2014

In comparative effectiveness research (CER), often the aim is to contrast survival outcomes between exposure groups defined by time‐varying interventions. With observational data, standard regression analyses (e.g., Cox modeling) cannot account for time‐dependent confounders on causal pathways between exposures and outcome nor for time‐dependent selection bias that may arise from informative right censoring. Inverse probability weighting (IPW) estimation to fit marginal structural models (MSMs) has commonly been applied to properly adjust for these expected sources of bias in real‐world observational studies. We describe the application and performance of an alternate estimation approach in such a study. The approach is based on the recently proposed targeted learning methodology and consists in targeted minimum loss‐based estimation (TMLE) with super learning (SL) within a nonparametric MSM. The evaluation is based on the analysis of electronic health record data with both IPW estimation and TMLE to contrast cumulative risks under four more or less aggressive strategies for treatment intensification in adults with type 2 diabetes already on 2+ oral agents or basal insulin. Results from randomized experiments provide a surrogate gold standard to validate confounding and selection bias adjustment. Bootstrapping is used to validate analytic estimation of standard errors. This application does the following: (1) establishes the feasibility of TMLE in real‐world CER based on large healthcare databases; (2) provides evidence of proper confounding and selection bias adjustment with TMLE and SL; and (3) motivates their application for improving estimation efficiency. Claims are reinforced with a simulation study that also illustrates the double‐robustness property of TMLE. Copyright © 2014 John Wiley & Sons, Ltd.