bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagal nerve stimulation without dissecting the carotid sheath during intraoperative neuromonitoring of the recurrent laryngeal nerve in thyroid surgery
Authors: Wu Che‐Wei , Dionigi Gianlorenzo , Chen Hui‐Chun , Chen Hsiu‐Ya , Lee Ka‐Wo , Lu I‐Cheng , Chang Pi‐Ying , Hsiao Pi‐Jung , Ho Kuen‐Yao , Chiang Feng‐Yu
Published: September 2012

Background

Vagal nerve stimulation (VNS) has been recommended as a routine procedure during intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN). However, many surgeons have been discouraged from performing VNS because of the need for opening the carotid sheath. The purpose of this study was to investigate the feasibility and reliability of VNS without carotid sheath dissection.

Methods

Two hundred twenty patients with 376 nerves at risk were enrolled in this study. VNS without nerve exposure during IONM was applied by simply pressing a ball‐tip stimulator on the space between the carotid artery and jugular vein.

Results

VNS without nerve exposure was feasible in all cases and did not result in any morbidity. All VNS signals were successfully obtained within 30 minutes of the start of the operation and all showed a clear and reliable laryngeal electromyography (EMG) response that was similar to that from the conventional method in which nerve exposure for VNS is applied.

Conclusions

VNS without dissecting the carotid sheath is feasible and reliable, rendering it a simple, safe, and surgeon‐friendly procedure during IONM. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1443–1447, 2013
Deletion of the RNA‐editing enzyme ADAR1 causes regression of established chronic myelogenous leukemia in mice
Authors: Steinman Richard A. , Yang Qiong , Gasparetto Maura , Robinson Lisa J. , Liu Xiaoping , Lenzner Diana E. , Hou Jingzhou , Smith Clayton , Wang Qingde
Published: September 2012

Patients with chronic myelogenous leukemia (CML) respond well to tyrosine kinase inhibitors (TKIs) of the Bcr‐Abl oncoprotein. However, intolerance and resistance to these agents remains a challenge, and TKIs are unable to eradicate rare leukemia‐initiating cells. Leukemia treatment would benefit from a better understanding of molecular signals that are necessary for the survival of leukemia‐initiating cells but dispensable for normal hematopoietic stem cells. Leukemia‐initiating cells in CML can arise from myeloid progenitor cells, a population that we have reported in normal hematopoiesis to depend on the RNA‐editing enzyme adenosine deaminase acting on RNA‐1 (ADAR1). We now report that Bcr‐Abl transformed leukemic cells were ADAR1‐dependent in a conditional ADAR1 knockout mouse model. ADAR1 deletion reversed leukocytosis and splenomegaly, and preferentially depleted primitive Lin‐Sca+Kit+ (LSK) leukemic cells but not LSK cells lacking the leukemic oncoprotein. ADAR1 deletion ultimately normalized the peripheral white blood count, eliminating leukemic cells as assessed by PCR. These results uncover a novel requirement for ADAR1 in myeloid leukemic cells and indicate that ADAR1 may comprise a new molecular target for CML‐directed therapeutics.
18β‐glycyrrhetinic acid inhibits hepatocellular carcinoma development by reversing hepatic stellate cell‐mediated immunosuppression in mice
Authors: Kuang Penghao , Zhao Wenxiu , Su Weixue , Zhang Zhengqi , Zhang Lei , Liu Jianming , Ren Guangli , Yin Zhenyu , Wang Xiaomin
Published: September 2012

Hepatic stellate cells (HSCs) have immunosuppressive capabilities and contribute to the occurrence and development of hepatocellular carcinoma (HCC). Thus, activated HSCs may be a suitable target for HCC therapy. Our study used mixed leukocyte reactions (MLR) in vitro to demonstrate that 18β‐glycyrrhetinic acid (GA) could reverse HSC‐mediated immunosuppression by reducing T‐cell apoptosis and regulatory T (Treg) cells expression, thereby enhancing the ability of T cells to attack tumor cells and attenuating HCC cell invasiveness. Moreover, we established a HCC orthotopic implantation model in immunocompetent C57BL/6 mice, which suggested that GA played a protective role in HCC development by reducing immunosuppression mediated by HSCs in the tumor microenvironment.
Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women
Authors: Moseley Kendall F , Weaver Connie M , Appel Lawrence , Sebastian Anthony , Sellmeyer Deborah E
Published: September 2012

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (−11.3 mmol/d on 60 mmol/d; −29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (−46 ± 15.9 mg/d) and 90 mmol/d (−59 ± 31.6 mg/d) compared with placebo (p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus −80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance (p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (−34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; −71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed. © 2013 American Society for Bone and Mineral Research.
Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia
Authors: Barros Nilana MT , Hoac Betty , Neves Raquel L , Addison William N , Assis Diego M , Murshed Monzur , Carmona Adriana K , McKee Marc D
Published: September 2012

X-linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization-inhibiting, acidic serine- and aspartate-rich motif (ASARM)-containing peptides, which are proteolytically derived from the mineral-binding matrix proteins of the SIBLING family (small, integrin-binding ligand N-linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full-length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ∼35 kDa OPN fragment that was not present in wild-type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild-type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full-length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization-inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.
The US postmarketing surveillance study of adult osteosarcoma and teriparatide: Study design and findings from the first 7 years
Authors: Andrews Elizabeth B , Gilsenan Alicia W , Midkiff Kirk , Sherrill Beth , Wu Yun , Mann Beth H , Masica Daniel
Published: September 2012

The Osteosarcoma Surveillance Study, an ongoing 15-year surveillance study initiated in 2003, is a postmarketing commitment to the United States (US) Food and Drug Administration to evaluate a potential association between teriparatide, rhPTH(1–34), a recombinant human parathyroid hormone analog (self-injectable medication to treat osteoporosis), and development of osteosarcoma in response to a finding from preclinical (animal) studies. Incident cases of primary osteosarcoma diagnosed in adults (aged ≥40 years) on or after January 1, 2003, are identified through population-based state, regional, and comprehensive cancer center registries in the US. Information on possible prior treatment with teriparatide, on demographics, and on risk factors is ascertained by patient or proxy telephone interview after patient consent. Between June 2004 and September 30, 2011, 1448 cases (diagnosed 2003 to 2009) were identified by participating cancer registries (estimated to be 62% of all adult cases in the US for that time period); 549 patients or proxies were interviewed. Interviewed patients were similar to noninterviewed patients with regard to mean age, sex, race, and geographical distribution and tumor type and site of tumor. Mean age of those interviewed was 61 years, 46% were female, 86% were white, and 77% were alive when the case was reported to the study investigators. Data collected in the study provide descriptive information on a large number of adults with osteosarcoma, an uncommon malignant bone tumor. After 7 years of the study, there were no osteosarcoma patients who had a prior history of teriparatide treatment. Thus, approximately halfway through this 15-year study, the study has not detected a pattern indicative of a causal association between teriparatide treatment and osteosarcoma in humans. © 2012 American Society for Bone and Mineral Research.
miR‐200c enhances radiosensitivity of human breast cancer cells
Authors: Lin Jing , Liu Cong , Gao Fu , Mitchel R.E.J. , Zhao Luqian , Yang Yanyong , Lei Jixiao , Cai Jianming
Published: September 2012

Due to the intrinsic resistance of many tumors to radiotherapy, current methods to improve the survival of cancer patients largely depend on increasing tumor radiosensitivity. It is well‐known that miR‐200c inhibits epithelial–mesenchymal transition (EMT), and enhances cancer cell chemosensitivity. We sought to clarify the effects of miR‐200c on the radiosensitization of human breast cancer cells. In this study, we found that low levels of miR‐200c expression correlated with radiotolerance in breast cancer cells. miR‐200c overexpression could increase radiosensitivity in breast cancer cells by inhibiting cell proliferation, and by increasing apoptosis and DNA double‐strand breaks. Additionally, we found that miR‐200c directly targeted TANK‐binding kinase 1 (TBK1). However, overexpression of TBK1 partially rescued miR‐200c mediated apoptosis induced by ionizing radiation. In summary, miR‐200c can be a potential target for enhancing the effect of radiation treatment on breast cancer cells. J. Cell. Biochem. 114: 606–615, 2013. © 2012 Wiley Periodicals, Inc.
Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: Protective role of antioxidant vitamins (C & E)
Authors: Rajesh Parsanathan , Sathish Sampath , Srinivasan Chinnapaiyan , Selvaraj Jayaraman , Balasubramanian Karundevi
Published: September 2012

Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H2O2 and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP‐induced changes. It is concluded that DEHP‐induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. J. Cell. Biochem. 114: 558–569, 2013. © 2012 Wiley Periodicals, Inc.
A novel tumor metastasis suppressor gene LASS2/TMSG1 interacts with vacuolar ATPase through its homeodomain
Authors: Yu Wenjuan , Wang Leiming , Wang Yuewei , Xu Xiaoyan , Zou Pengcheng , Gong Miaozi , Zheng Jie , You Jiangfeng , Wang Hua , Mei Fang , Pei Fei
Published: September 2012

LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non‐metastatic and metastatic cancer cell variants of human prostate carcinoma PC‐3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V‐ATPase, ATP6V0C) and regulate V‐ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V‐ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC‐3M‐1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V‐ATPase expression among different transfected cells and the control. However, V‐ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH‐dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno‐electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC‐3M‐1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V‐ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V‐ATPase. Their interaction could play important roles in the apoptosis of tumor cells. J. Cell. Biochem. 114: 570–583, 2013. © 2012 Wiley Periodicals, Inc.
Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus
Authors: Akash Muhammad Sajid Hamid , Rehman Kanwal , Chen Shuqing
Published: September 2012

Type 2 diabetes mellitus (T2DM) is characterized by progressive β‐cell dysfunctioning and insulin resistance. This article reviews recent literature with special focus on inflammatory mechanisms that provoke the pathogenesis of T2DM. We have focused on the recent advances in progression of T2DM including various inflammatory mechanisms that might induce inflammation, insulin resistance, decrease insulin secretion from pancreatic islets and dysfunctioning of β‐cells. Here we have also summarized the role of various pro‐inflammatory mediators involved in inflammatory mechanisms, which may further alter the normal structure of β‐cells by inducing pancreatic islet's apoptosis. In conclusion, it is suggested that the role of inflammation in pathogenesis of T2DM is crucial and cannot be neglected. Moreover, the insight of inflammatory responses in T2DM may provide a new gateway for the better treatment of diabetes mellitus. J. Cell. Biochem. 114: 525–531, 2013. © 2012 Wiley Periodicals, Inc.
Signet ring cell mixed histology may show more aggressive behavior than other histologies in early gastric cancer
Authors: Huh Cheal Wung , Jung Da Hyun , Kim Jie‐Hyun , Lee Yong Chan , Kim Hyunki , Kim Hoguen , Yoon Sun Och , Youn Young Hoon , Park Hyojin , Lee Sang In , Choi Seung Ho , Cheong Jae‐Ho , Noh Sung Hoon
Published: September 2012

Background

Signet ring cell carcinoma (SRC) of the stomach is known to have different microscopic and biologic characteristics compared to non‐SRC. The pathologic report has documented partly SRC component with main histologies. However, the clinical significance of SRC mixture has not been reported. Aim was to investigate clinicopathologic features of mixed‐SRC histology in early gastric cancer (EGC).

Methods

Two thousand two hundred eight patients were diagnosed with EGC and underwent surgery. The patients were divided into three groups such as adenocarcinoma with partly SRC (mixed‐SRC group), only adenocarcinoma (adenocarcinoma group), and SRC (SRC group). Clinicopathologic characteristics were compared.

Results

The SRC group was more associated with younger age, female, mid‐body, mucosa‐confined, depressed type, lower lymph node metastasis (LNM), lower lymphovascular invasion, and better survival rate than adenocarcinoma group. The mixed‐SRC group was more associated with younger age, female, upper‐body, and depressed type than adenocarcinoma group, similar to SRC group. However, the mixed‐SRC group showed more submucosal invasion, larger size, and higher LNM than other groups. The mixed‐SRC component was one of the independent risk factors of LNM.

Conclusions

Mixed‐SRC histology in EGC showed more aggressive behavior than other histologies. Clinical considerations of mixed‐SRC histology may be helpful to decide on a specific cancer treatment. J. Surg. Oncol. 2013;107:124–129. © 2012 Wiley Periodicals, Inc.
Rheological and thermal behaviors of commercial poly(aryletherketone)s
Authors: White Kevin L. , Jin Lin , Ferrer Nangelie , Wong Minhao , Bremner Tim , Sue Hung‐Jue
Published: September 2012

The mechanical properties and thermal stability of several grades of poly(aryletherketone)s (PAEKs) were investigated using thermal, rheological, and dynamic mechanical characterization. Detailed rheological characterization revealed that several grades of poly(etheretherketone) (PEEK) exhibit relaxation behavior characteristic of a long‐chain branched structure. The potentially branched PEEKs showed greater mechanical damping behavior than the linear‐chain PEEKs. The molecular weight dependence on zero‐shear viscosity for several linear‐chain polymers indicates that the PEEKs behave as rigid chains in the melt. Differences in chain structure do not significantly influence dynamic mechanical behavior in the solid state but affect stability at elevated temperatures. The potentially branched PEEKs are most susceptible to oxidation in air, but exhibit much greater stability in nitrogen. Poly(etherketone) is highly susceptible to degradation in both air and nitrogen environments. Implications of this study for development of high‐performance PAEKs are discussed. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers
Anti‐Microbial Activity and Composition of Manuka and Portobello Honey
Authors: Schneider Monika , Coyle Shirley , Warnock Mary , Gow Iain , Fyfe Lorna
Published: September 2012

Recently renewed interest in the therapeutic properties of honey has led to the search for new antimicrobial honeys. This study was undertaken to assess the antimicrobial activity and composition of a locally produced Portobello honey (PBH) on three bacteria known to infect wounds. Manuka honey (MH) was used for comparative purposes. Broth culture and agar disc diffusion assays were used to investigate the antimicrobial properties of honey. The honeys were tested at four concentrations: 75%, 50%, 10% and 1% (v/v) and compared with an untreated control. The composition of honey was determined by measuring: polyphenol content by Folin Ciocalteau method, antioxidant capacity by ferric ion reducing power assay, hydrogen peroxide (H2O2) by catalase test, pH and sugar content by pH strips and refractometer, respectively. Both honeys at 75% and 50% inhibited the majority of the three bacteria tested. 10% PBH exhibited antimicrobial activity to the lesser extent than 10% MH. The difference was very significant (p ≤ 0.001). Both honeys were acidic with pH 4, and both produced H2O2. The sugar content of PBH was higher than MH, but the difference was not significant. The MH had significantly higher levels of the polyphenols and antioxidant activity than PBH. Copyright © 2012 John Wiley & Sons, Ltd.
Hybrid‐type observer design based on a sufficient condition for observability in switched nonlinear systems
Authors: Shim Hyungbo , Tanwani Aneel
Published: September 2012

This paper presents a sufficient condition for observability of continuous‐time switched nonlinear systems that also involve state jumps. Without the assumption of observability of individual modes, the sufficient condition is based on gathering partial information from each mode so that the state is completely recovered after several switchings. Based on the sufficient condition, a hybrid‐type observer is designed, which comprises a copy of the actual plant and an error correction scheme at discrete time instants. In order to execute the proposed design, the observable component of the state at each mode needs to be estimated without transients or ‘peaking’ (caused by high‐gain observers), and this motivates us to introduce a back‐and‐forth estimation technique. Under the assumption of persistent switching, analysis shows that the estimate thus generated converges asymptotically to the actual state of the system. Simulation results validate the utility of the proposed algorithm. Copyright © 2012 John Wiley & Sons, Ltd.
Polymer Grafting to Single‐Walled Carbon Nanotubes: Effect of Chain Length on Solubility, Graft Density and Mechanical Properties of Macroscopic Structures
Authors: Chadwick Ryan C. , Khan Umar , Coleman Jonathan N. , Adronov Alex
Published: September 2012

Single‐walled carbon nanotubes are grafted with polystyrene chains employing a graft‐to protocol. Thermogravimetric analysis allows calculation of the grafted chain density and average interchain separation on the nanotube surface as a function of molecular weight. The separation scales with molecular weight as a power law with an exponent of ca. 0.588, showing the grafted chains to be in a swollen random walk conformation. This implies that chain packing is controlled by coil size in solution. In addition, the dispersed concentration of functionalized nanotubes scales with the size of the steric potential barrier that prevents aggregation of polymer functionalized nanotubes. It is also shown that the molecular weight of the grafted chains significantly affects the mechanical properties of nanotube films.
Reflection and intention: Interpersonal boundaries in teaching and learning
Authors: Schwartz Harriet L.
Published: September 2012

Setting, adjusting, and maintaining boundaries with students is a deeply reflective process that challenges us to consider and reconsider our assumptions and understandings of ourselves, our students, and our position as educators.
Wind integration: experience, issues, and challenges
Authors: Holttinen Hannele
Published: September 2012

The challenge of wind integration is to make best use of the variable and uncertain power source while maintaining the continuous balance between consumption and generation and high level of reliability in the power system. There is already experience of operating power systems with large amounts of wind power and integration studies give estimates on wind power impacts. Power systems are equipped to handle variability and uncertainty that comes from the electricity consumption, the load. Short‐term wind forecasting is required to manage large amounts of wind power. The main impacts of wind integration are investments in grid infrastructure and efficiency losses in power plants when following the increased variations and uncertainty in the power system. Wind power will lower emissions while replacing energy produced by fossil fuels and can also replace some power plant capacity. However, wind's lower capacity value compared to conventional power plants is one integration impact of wind power, meaning higher total installed capacity in power systems with high wind penetration. Managing options for wind integration impacts includes proper wind power plant grid‐connection rules, increasing transmission capacity and increasing flexibility that is available from generation plants and demand side. Further development of models and tools is required to study how entire power systems can be operated during the hours and days of very high penetration levels covering 60–80% of load.

This article is categorized under:

Wind Power > Systems and Infrastructure

Wind Power > Climate and Environment

Fossil Fuels > Systems and Infrastructure
Screening for congenital disorders of glycosylation in the first weeks of life
Authors: Thiel Christian , Meßner‐Schmitt Dorothea , Hoffmann Georg F. , Körner Christian
Published: September 2012

Inherited monogenetic human disorders due to deficiencies in the complex metabolic pathways for N‐ and O‐glycosylation of glycoconjugates are termed ‘congenital disorders of glycosylation’ (CDG). Since the number of these defects with mostly severe multisystemic phenotypes has been rapidly expanding in recent years, the interest of paediatricians has also increased resulting in a rising amount of patient samples with the suspicion of CDG. In general, primary diagnostics for CDG start with investigations on the glycosylation state of serum transferrin, the ‘gold standard’ in the field for many years. However, the use of transferrin shows an analytical problem in the time span from birth up to the 3rd month of life. In this developmental period oligosaccharide moieties N‐linked to proteins are often incomplete, resembling a CDG pattern and leading to false‐positive results. It is therefore necessary to establish a reliable and fast diagnostic procedure for this span of life. Here we show that the glycosylation state of serum α‐1‐antitrypsin is already fully existent shortly after birth allowing an alternative diagnostic approach for the investigation of CDG in the first weeks of life. The method can easily be established in every laboratory especially with previous experience in transferrin analysis.
The relationship between bone marrow edema and bone changes in the mandibular condyle: A longitudinal study with MR imaging
Authors: Higuchi Keisuke , Chiba Masatoshi , Kondo Takemitsu , Echigo Seishi
Published: September 2012

Purpose: Decreased signal intensity on T1‐ or proton‐density weighted magnetic resonance imaging (MRI) and increased signal intensity on T2‐weighted MRI in the bone marrow space are thought to reflect bone marrow edema (BME). The purpose of this study was to determine whether condyle BME is associated with condyle bone changes.

Methods: The subjects were 57 patients [65 temporomandibular joints (TMJs)] with TMJ disorders showing condyle BME on initial MRI. Condyle bone changes were compared between TMJs that showed a persistent BME pattern (group P, 43 TMJs in 40 patients) and those that showed normal bone marrow signals, indicating disappearance of BME (group D, 21 TMJs in 22 patients) on follow‐up MRI.

Results: (1) In TMJs with a condyle with a normal shape on initial MRI, condyle bone changes were present in 53.9% of TMJs in group P in follow‐up MRI, whereas the normally shaped condyle remained in all TMJs in group D. (2) In TMJs with condyle erosion on initial MRI, condyle erosion was also present in 35.7% of TMJs in group P in follow‐up MRI, but had disappeared in all TMJs in group D. (3) In TMJs with condyle osteophytes on initial MRI, erosion was present in 22.2% of TMJs in group P, whereas osteophytes remained in all TMJs in group D.

Conclusions: The longitudinal study showed that condyle BME is associated with condyle bone changes and may cause condyle erosion.
Open and closed domains in the mouse genome are configured as 10‐nm chromatin fibres
Authors: Fussner Eden , Strauss Mike , Djuric Ugljesa , Li Ren , Ahmed Kashif , Hart Michael , Ellis James , Bazett‐Jones David P
Published: September 2012

The mammalian genome is compacted to fit within the confines of the cell nucleus. DNA is wrapped around nucleosomes, forming the classic ‘beads‐on‐a‐string’ 10‐nm chromatin fibre. Ten‐nanometre chromatin fibres are thought to condense into 30‐nm fibres. This structural reorganization is widely assumed to correspond to transitions between active and repressed chromatin, thereby representing a chief regulatory event. Here, by combining electron spectroscopic imaging with tomography, three‐dimensional images are generated, revealing that both open and closed chromatin domains in mouse somatic cells comprise 10‐nm fibres. These findings indicate that the 30‐nm chromatin model does not reflect the true regulatory structure in vivo.
Ground state properties of graphene in Hartree-Fock theory
Authors: Hainzl Christian , Lewin Mathieu , Sparber Christof
Published: September 2012

We study the Hartree-Fock approximation of graphene in infinite volume, with instantaneous Coulomb interactions. First we construct its translation-invariant ground state and we recover the well-known fact that, due to the exchange term, the effective Fermi velocity is logarithmically divergent at zero momentum. In a second step we prove the existence of a ground state in the presence of local defects and we discuss some properties of the linear response to an external electric field. All our results are non-perturbative.
Electromagnetic fluctuation-induced interactions in randomly charged slabs
Authors: Rezvani Vahid , Sarabadani Jalal , Naji Ali , Podgornik Rudolf
Published: September 2012

Randomly charged net-neutral dielectric slabs are shown to interact across a featureless dielectric continuum with long-range electrostatic forces that scale with the statistical variance of their quenched random charge distribution and inversely with the distance between their bounding surfaces. By accounting for the whole spectrum of electromagnetic field fluctuations, we show that this long-range disorder-generated interaction extends well into the retarded regime where higher order (non-zero) Matsubara frequencies contribute significantly. This occurs even for highly clean samples with only a trace amount of charge disorder and shows that disorder effects can be important down to the nanoscale. As a result, the previously predicted non-monotonic behavior for the total force between dissimilar slabs as a function of their separation distance is substantially modified by higher order contributions, and in almost all cases of interest, we find that the equilibrium inter-surface separation is shifted to substantially larger values compared to predictions based solely on the zero-frequency component. This suggests that the ensuing non-monotonic interaction is more easily amenable to experimental detection. The presence of charge disorder in the intervening dielectric medium between the two slabs is shown to lead to an additional force that can be repulsive or attractive depending on the system parameters and can, for instance, wash out the non-monotonic behavior of the total force when the intervening slab contains a sufficiently large amount of disorder charges.
Optical parameters of ZnTe determined using continuous-wave terahertz radiation
Authors: Constable E. , Lewis R. A.
Published: September 2012

The optical parameters of three ZnTe crystal wafers of different thicknesses were determined using transmittance measurements of continuous-wave terahertz radiation from a two-color photomixing source. The parameters are extracted by fitting the transmittance data with theoretical curves generated using a Drude-Lorentz dielectric model of the crystal and a bootstrap statistical analysis of the fits. It was found at room temperature that the low and high frequency dielectric constants are ϵ(0)=9.8±0.2 and ϵ(∞)=7.3±0.6, respectively. The transverse optical phonon frequency was found to be νTO=6.0±1.3 THz. Sample specific properties such as the plasma, collision, and phonon damping frequencies were determined and used for an approximate calculation of carrier concentration. The results are compared with a comprehensive review of earlier values from the literature. Our results are consistent with previous work, falling within the spread of accepted values, and demonstrate that this method is particularly suited for determining the low and high frequency dielectric constants of semiconductor samples.
Unidirectional acoustic transmission based on source pattern reconstruction
Authors: Li Y. , Tu J. , Liang B. , Guo X. S. , Zhang D. , Cheng J. C.
Published: September 2012

It is demonstrated both theoretically and experimentally that unidirectional acoustic transmission can be achieved through a simple structure consisting of only a uniform stiff plate and periodic rectangular gratings. Essentially distinct from the previous related works based on the utilizing of nonlinear effect or the partial band of the sonic crystal, it is attributed to one-side pattern reconstruction of acoustic plane waves induced by the periodic gratings, which can be physically modeled by forced vibration of the plate under periodic loads. The current structure takes the advantages of high transmission efficiency, small size, and broad bandwidth, which should open more possibilities for the miniaturization and integration of the one-way acoustic devices as well as further improvement of their performance.
Unexpected crossover dynamics of single polymer in a corrugated tube
Authors: De Virgiliis Andres , Kuban Lukasz , Paturej Jaroslaw , Mukherji Debashish
Published: September 2012

We present molecular dynamics study of a generic (coarse-grained) model for single-polymer diffusion confined in a corrugated cylinder. For a narrow tube, i.e., diameter of the cylinder δ < 2.3, the axial diffusion coefficient D|| scales as D|| ∝ N−3/2, with chain length N, up to N ≈ 100 and then crosses over to Rouse scaling for the larger N values. The N−3/2 scaling is due to the large fluctuation of the polymer chain along its fully stretched equilibrium conformation. The stronger scaling, namely N−3/2, is not observed for an atomistically smooth tube and/or for a cylinder with larger diameter.
Closely related bird species demonstrate flexibility between beak morphology and underlying developmental programs
Authors: Mallarino Ricardo , Campàs Otger , Fritz Joerg A. , Burns Kevin J. , Weeks Olivia G. , Brenner Michael P. , Abzhanov Arhat
Published: September 2012

The astonishing variation in the shape and size of bird beaks reflects a wide range of dietary specializations that played an important role in avian diversification. Among Darwin’s finches, ground finches (
Geospiza
spp.) have beaks that represent scaling variations of the same shape, which are generated by alterations in the signaling pathways that regulate growth of the two skeletal components of the beak: the prenasal cartilage (pnc) and the premaxillary bone (pmx). Whether this developmental mechanism is responsible for variation within groups of other closely related bird species, however, has remained unknown. Here, we report that the Caribbean bullfinches (
Loxigilla
spp.), which are closely related to Darwin’s finches, have independently evolved beaks of a novel shape, different from
Geospiza
, but also varying from each other only in scaling. However, despite sharing the same beak shape, the signaling pathways and tissues patterning
Loxigilla
beaks differ among the three species. In
Loxigilla noctis
, as in
Geospiza
, the pnc develops first, shaped by
Bmp4
and
CaM
signaling, followed by the development of the pmx, regulated by
TGFβIIr
,
β-catenin
, and
Dkk3
signaling. In contrast, beak morphogenesis in
Loxigilla violacea
and
Loxigilla portoricensis
is generated almost exclusively by the pmx through a mechanism in which
Ihh
and
Bmp4
synergize to promote expansion of bone tissue. Together, our results demonstrate high flexibility in the relationship between morphology and underlying developmental causes, where different developmental programs can generate identical shapes, and similar developmental programs can pattern different shapes.
Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors
Authors: McTigue Michele , Murray Brion William , Chen Jeffrey H. , Deng Ya-Li , Solowiej James , Kania Robert S.
Published: September 2012

Analyses of compounds in clinical development have shown that ligand efficient-molecules with privileged physical properties and low dose are less likely to fail in the various stages of clinical testing, have fewer postapproval withdrawals, and are less likely to receive black box safety warnings. However, detailed side-by-side examination of molecular interactions and properties within single drug classes are lacking. As a class, VEGF receptor tyrosine kinase inhibitors (VEGFR TKIs) have changed the landscape of how cancer is treated, particularly in clear cell renal cell carcinoma, which is molecularly linked to the VEGF signaling axis. Despite the clear role of the molecular target, member molecules of this validated drug class exhibit distinct clinical efficacy and safety profiles in comparable renal cell carcinoma clinical studies. The first head-to-head randomized phase III comparative study between active VEGFR TKIs has confirmed significant differences in clinical performance [Rini BI, et al. (2011)
Lancet
378:193–1939]. To elucidate how fundamental drug potency–efficiency is achieved and impacts differentiation within the VEGFR TKI class, we determined potencies, time dependence, selectivities, and X-ray structures of the drug–kinase complexes using a VEGFR2 TK construct inclusive of the important juxtamembrane domain. Collectively, the studies elucidate unique drug–kinase interactions that are dependent on distinct juxtamembrane domain conformations, resulting in significant potency and ligand efficiency differences. The identified structural trends are consistent with in vitro measurements, which translate well to clinical performance, underscoring a principle that may be broadly applicable to prospective drug design for optimal in vivo performance.
The widely used small subunit 18S rDNA molecule greatly underestimates true diversity in biodiversity surveys of the meiofauna
Authors: Tang Cuong Q. , Leasi Francesca , Obertegger Ulrike , Kieneke Alexander , Barraclough Timothy G. , Fontaneto Diego
Published: September 2012

Molecular tools have revolutionized the exploration of biodiversity, especially in organisms for which traditional taxonomy is difficult, such as for microscopic animals (meiofauna). Environmental (eDNA) metabarcode surveys of DNA extracted from sediment samples are increasingly popular for surveying biodiversity. Most eDNA surveys use the nuclear gene-encoding small-subunit rDNA gene (18S) as a marker; however, different markers and metrics used for delimiting species have not yet been evaluated against each other or against morphologically defined species (morphospecies). We assessed more than 12,000 meiofaunal sequences of 18S and of the main alternatively used marker [Cytochrome
c
oxidase subunit I (COI) mtDNA] belonging to 55 datasets covering three taxonomic ranks. Our results show that 18S reduced diversity estimates by a factor of 0.4 relative to morphospecies, whereas COI increased diversity estimates by a factor of 7.6. Moreover, estimates of species richness using COI were robust among three of four commonly used delimitation metrics, whereas estimates using 18S varied widely with the different metrics. We show that meiofaunal diversity has been greatly underestimated by 18S eDNA surveys and that the use of COI provides a better estimate of diversity. The suitability of COI is supported by cross-mating experiments in the literature and evolutionary analyses of discreteness in patterns of genetic variation. Furthermore its splitting of morphospecies is expected from documented levels of cryptic taxa in exemplar meiofauna. We recommend against using 18S as a marker for biodiversity surveys and suggest that use of COI for eDNA surveys could provide more accurate estimates of species richness in the future.
Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers
Authors: Rahimov Fedik , King Oliver D. , Leung Doris G. , Bibat Genila M. , Emerson Charles P. , Kunkel Louis M. , Wagner Kathryn R.
Published: September 2012

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal
P
value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a “molecular signature” in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids.
Spatiotemporal Distributions of Threadfin Shad in Tropical Reservoirs
Authors: Neal J. Wesley , Prchalová Marie
Published: September 2012

Effective predator management requires accurate knowledge of prey availability and dynamics, yet prey species are rarely studied as intensely as their predatory counterparts. Almost nothing is known about the biology or behavior of threadfin shad Dorosoma petenense in tropical environments, despite that this species is the primary prey in many systems. The goals of this study were to examine spatial and temporal patterns in threadfin shad abundance in tropical reservoirs and to refine protocols for sampling this species. A custom, 3 × 3-m frame trawl was used to sample four reservoirs in Puerto Rico every 3 months for 1 year. Samples were stratified by longitudinal section (upper and lower lake) and by depth strata (0–3, 3–6, 6–9 m). Threadfin shad densities varied markedly among seasons, reservoirs, longitudinal sections, and depth (overall model: F  36, 188 = 32.0, P < 0.001, coefficient of variation [CV] = 22.1%, r  2 = 0.86). Density estimates from samples were highest in spring and winter when there was substantially more larval production, and density fluctuated as much as 42-fold among seasons within reservoirs. Differences in mean density were as much as 23 times greater in productive reservoirs than in the least productive reservoir during the same season. Longitudinal variability was substantial between upper and lower reservoir sections (mean percent difference = 70%), but patterns were not consistent among reservoirs or seasons. Threadfin shad showed clear preference for shallow depth strata where 75.4% of fish were collected in the 0–3-m stratum, and only 2.4% collected in the 6–9-m stratum. Oxygen profiles suggested that threadfin shad selected shallow depths even when dissolved oxygen levels were suitable in deeper depth strata. Understanding spatiotemporal patterns in threadfin shad distributions will improve sampling programs in terms of timing and frequency of sampling, longitudinal and vertical sampling design, and sample size requirements.

Received March 19, 2012; accepted June 2, 2012
Pain is Not Associated with Worse Office-Based Buprenorphine Treatment Outcomes
Authors: Fox Aaron D. , Sohler Nancy L. , Starrels Joanna L. , Ning Yuming , Giovanniello Angela , Cunningham Chinazo O.
Published: September 2012

Physical pain is common among individuals seeking treatment for opioid dependence. Pain may negatively impact addiction treatment. The authors prospectively studied opioid-dependent individuals initiating office-based buprenorphine treatment, comparing buprenorphine treatment outcomes (treatment retention and opioid use) among participants with and without pain (baseline pain or persistent pain). Among 82 participants, 60% reported baseline pain and 38% reported persistent pain. Overall, treatment retention was 56% and opioid use decreased from 89% to 26% over 6 months. In multivariable analyses, the authors found no association between pain and buprenorphine treatment outcomes. Opioid-dependent individuals with and without pain can achieve similar success with buprenorphine treatment.
Results of a Statewide Survey of Adolescent Substance Use Screening Rates and Practices in Primary Care
Authors: Harris Sion Kim , Herr-Zaya Kathleen , Weinstein Zohar , Whelton Kathleen , Perfas Fernando , Castro-Donlan Carolyn , Straus John , Schoneman Karen , Botticelli Michael , Levy Sharon
Published: September 2012

Professional guidelines recommend annual screening, brief intervention, and referral to treatment (SBIRT) as part of health maintenance for all adolescents, but reported screening rates have been low and no report has documented the techniques being used. The objective of this study was to describe the results of a statewide questionnaire regarding adolescent substance use screening rates and techniques used by primary care physicians practicing in Massachusetts. A questionnaire was mailed to every licensed physician registered as practicing pediatrics ( N = 2176), family medicine ( N = 1335), or both ( N = 8) in the Massachusetts Board of Medicine database. After eliminating physicians who did not provide care for adolescents, the survey response rate was 28% and the final analyzable sample consisted of 743 surveys. Less than half of respondents reported using a validated adolescent screening tool. The majority of respondents used ineffective screening practices for adolescent substance use. Further physician training is recommended to encourage the use of developmentally appropriate screening tools and interventions for adolescents.