bluuebunny/crossref_metadata_2025 huggingface dataset:
E-governance Readiness: Challenges for India
Authors: Sebastian M.P. , Supriya K.K.
Published: September 2013

Governments and public sector organizations around the globe are relying on information and communication technologies (ICTs) to reform the functioning of the system and provide better service delivery mechanisms for their citizens. E-governance is the effective use of ICTs, particularly the Web-based Internet applications, for better governance and service delivery. Indian government, like its global counterparts, is using ICT and E-governance as part of its broader governance modernization programmes. This article presents an overview of the E-governance scenario in India. It evaluates the readiness, capability and willingness of the government to provide E-services in terms of the factors like telecommunication infrastructure, human capital and web presence. Based on the assessment, the factors which hinder the E-initiatives development and the barriers for the effective implementation are identified. These barriers are then classified into the three dimensions which determine the E-governance readiness.  A strategy for improving the E-governance readiness in India is also proposed.
Mapping Sponsorship-linked Marketing in Indian Premier League
Authors: Gupta Anil , Naik Anish Yousaf , Arora Neelika
Published: September 2013

Sponsorships have not been subjected to extensive research in an emerging economy like India, till date, which is considered virgin in terms of sponsorship research. Having this in mind, the article focuses on mapping sponsorship scenario in Indian Premier League (IPL) and aims at meeting three main objectives: (a) Mapping sponsorship scenario in Indian Premier League (IPL), (b) to categorize sponsors in Indian Premier League into various categories and highlight the importance of Industry-IPL fit and (c) to discuss the impact of micro-level factors on sponsorship-linked marketing. For the purpose, official websites of IPL and all teams were scanned (from 19 March to 3 April 2012) resulting into the identification of 119 sponsors with varying level of prominence, relatedness and sponsors’ hierarchy. Researchers advised brand managers that they should first weigh their brand’s prominence and relatedness coupled with taking into account their target customers rather than taking impulse decisions to compete with their competitors’ sponsorship activities. The study contributes to the knowledge of the academicians who will be able to understand the potential of future researches that could be done. On the other hand, the study also provides an advantage to marketing executives/sport managers about how they can effectively and efficiently manage their individual brands in a cluttered media environment.
Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice
Authors: Cheung Alice M. S. , Nguyen Long V. , Carles Annaick , Beer Philip , Miller Paul H. , Knapp David J. H. F. , Dhillon Kiran , Hirst Martin , Eaves Connie J.
Published: September 2013

Key Points

The use of barcoding to track lineages in 196 human CD34+ CB clones in serially sampled primary and secondary transplanted NSG mice is described. Detection of early transient clones with later, more stable clones and definitive evidence of sustained self-renewal of multipotency is presented.
Clinical and biological implications of driver mutations in myelodysplastic syndromes
Authors: Papaemmanuil Elli , Gerstung Moritz , Malcovati Luca , Tauro Sudhir , Gundem Gunes , Van Loo Peter , Yoon Chris J. , Ellis Peter , Wedge David C. , Pellagatti Andrea , Shlien Adam , Groves Michael John , Forbes Simon A. , Raine Keiran , Hinton Jon , Mudie Laura J. , McLaren Stuart , Hardy Claire , Latimer Calli , Della Porta Matteo G. , O’Meara Sarah , Ambaglio Ilaria , Galli Anna , Butler Adam P. , Walldin Gunilla , Teague Jon W. , Quek Lynn , Sternberg Alex , Gambacorti-Passerini Carlo , Cross Nicholas C. P. , Green Anthony R. , Boultwood Jacqueline , Vyas Paresh , Hellstrom-Lindberg Eva , Bowen David , Cazzola Mario , Stratton Michael R. , Campbell Peter J.
Published: September 2013

Key Points

MDS is characterized by mutations in >40 genes, a complex structure of gene-gene interactions and extensive subclonal diversification. The total number of oncogenic mutations and early detection of subclonal mutations are significant prognostic variables in MDS.
Experience-dependent persistent expression of zif268during rest is preserved in the aged dentate gyrus
Authors: Gheidi Ali , Azzopardi Erin , Adams Allison A , Marrone Diano F
Published: September 2013

Background

Aging is typically accompanied by memory decline and changes in hippocampal function. Among these changes is a decline in the activity of the dentate gyrus (DG) during behavior. Lasting memory, however, is thought to also require recapitulation of recent memory traces during subsequent rest – a phenomenon, termed memory trace reactivation, which is compromised in hippocampal CA1 with progressive age. This process has yet to be assessed in the aged DG, despite its prominent role in age-related memory impairment. Using zif268 transcription to measure granule cell recruitment, DG activity in adult and aged animals was assessed both during spatial exploration and as animals remained at rest in the home cage in order to detect potential memory-related replay.

Results

Consistent with the observation of memory trace reactivation in DG, the probability that an individual granule cell transcribes zif268 during rest in the animal’s home cage is increased by recent experience in a novel environment. Surprisingly, a comparable increase was observed in the probability of granule cells in the aged DG expressing zif268 during rest. Moreover, no significant age-related difference was observed in the number of granule cells expressing zif268 during rest. Thus, the number and pattern of granule cell expression of zif268 during rest is preserved in aged animals, despite a significant decline in exploration-related zif268 expression.

Conclusions

These data lead to the hypothesis that the input the aged DG receives from backprojections from CA3 (the region widely hypothesized to mediate reactivation) remains functionally intact despite loss of innervation from the perforant path.
Perception of soft mechanical stress in Arabidopsis leaves activates disease resistance
Authors: Benikhlef Lehcen , L’Haridon Floriane , Abou-Mansour Eliane , Serrano Mario , Binda Matteo , Costa Alex , Lehmann Silke , Métraux Jean-Pierre
Published: September 2013

Background

In a previous study we have shown that wounding of Arabidopsis thaliana leaves induces a strong and transient immunity to Botrytis cinerea, the causal agent of grey mould. Reactive oxygen species (ROS) are formed within minutes after wounding and are required for wound–induced resistance to B. cinerea.

Results

In this study, we have further explored ROS and resistance to B. cinerea in leaves of A. thaliana exposed to a soft form of mechanical stimulation without overt tissue damage. After gentle mechanical sweeping of leaf surfaces, a strong resistance to B. cinerea was observed. This was preceded by a rapid change in calcium concentration and a release of ROS, accompanied by changes in cuticle permeability, induction of the expression of genes typically associated with mechanical stress and release of biologically active diffusates from the surface. This reaction to soft mechanical stress (SMS) was fully independent of jasmonate (JA signaling). In addition, leaves exposed soft mechanical stress released a biologically active product capable of inducing resistance to B. cinerea in wild type control leaves.

Conclusion

Arabidopsis can detect and convert gentle forms of mechanical stimulation into a strong activation of defense against the virulent fungus B. cinerea.
Increased urinary IgM excretion in patients with chest pain due to coronary artery disease
Authors: Tofik Rafid , Ekelund Ulf , Torffvit Ole , Swärd Per , Rippe Bengt , Bakoush Omran
Published: September 2013

Background

Micro-albuminuria is a recognized predictor of cardiovascular morbidity and mortality in patients with coronary artery disease. We have previously reported, in diabetic and non-diabetic patients, that an increased urinary excretion of IgM is associated with higher cardiovascular mortality. The purpose of this study was to investigate the pattern of urinary IgM excretion in patients with acute coronary syndrome (ACS) and its correlation to cardiovascular outcome.

Methods

Urine albumin, and IgM to creatinine concentration ratios were determined in 178 consecutive patients presenting with chest pain to the Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty eight (23 female) patients had ACS, 55 (19 female) patients had stable angina (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS).

Results

Urine albumin and IgM excretions were significantly higher in patients with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS-chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1 female) patients died of cardiovascular cause. A high degree of albuminuria and IgM-uria significantly predicted cardiovascular mortality and morbidity (HR = 2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (≥3 mg/mmol) with high IgM-uria (≥0.005 mg/mmol) had a 3-fold higher risk for cardiovascular new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p = 0.001).

Conclusion

In patients with chest pain, an increased urine IgM excretion, is associated with coronary artery disease and long-term cardiovascular complications. Measuring urine IgM concentration could have a clinical value in risk stratification of patients with ACS.
MR-guided focused ultrasound for the novel and innovative management of osteoarthritic knee pain
Authors: Izumi Masashi , Ikeuchi Masahiko , Kawasaki Motohiro , Ushida Takahiro , Morio Kazuo , Namba Hirofumi , Graven-Nielsen Thomas , Ogawa Yasuhiro , Tani Toshikazu
Published: September 2013

Background

Severe knee pain associated with osteoarthritis (OA) is one of the most common and troublesome symptoms in the elderly. Recently, local bone denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a promising tool for pain palliation of bone metastases. The purpose of this study was to develop a novel treatment for knee OA using MRgFUS, and to validate its safety and efficacy.

Methods

Eight patients with medial knee pain and eligible for total knee arthroplasty were included. MR-guided focused sonication treatments were applied to bone surface just below the rim osteophyte of medial tibia plateau with real-time monitoring of the temperature in the target sites. The pain intensity during walking was assessed on a 100 mm visual analog scale (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also evaluated over several test sites adjacent to the sonication area and control sites one month after treatment.

Results

Six patients (75%) showed immediate pain alleviation after treatment, and four of them demonstrated long-lasting effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in medial knee were significantly increased after treatment (Median; pre- 358 kpa vs post- 534 kpa, p?<?0.0001). There were no adverse side effects or complications during and after treatment.

Conclusions

These initial results illustrate the safety and efficacy of the newly developing MRgFUS treatment. Significant increase of PPTs on treated area showed successful denervation effect on the nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for noninvasive pain management of knee OA.

Trial registration

Trial Registration:UMIN000010193
Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single institution experience
Authors: Sai Ke , Mou Yong-gao , Zeng Jing , Lv Yan-chun , Xi Shao-yan , Guan Su , Zhang Xiang-heng , Wang Jian , Ke Chao , Guo Jian-gui , Chen Yin-sheng , Chen Zhong-ping
Published: September 2013

Background

Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients.

Methods

Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed.

Results

Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients.

Conclusions

For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients.
Short-term psychotherapeutic treatment in adolescents engaging in non-suicidal self-injury: a randomized controlled trial
Authors: Fischer Gloria , Brunner Romuald , Parzer Peter , Resch Franz , Kaess Michael
Published: September 2013

Background

Worldwide, prevalence rates of adolescent non-suicidal self-injury (NSSI) range between 13 and 45%. In Germany, lifetime prevalence of NSSI is around 25% in non-clinical samples, and the one-year prevalence for repetitive NSSI is 4%. NSSI is present in the context of several axis I and II disorders (for example, affective disorders or borderline personality disorder); however, preliminary evidence suggests that it would be justified to consider NSSI as its own diagnostic category. Despite the large impact of this behavior, there is still a lack of evidence-based, specific, and effective manualized treatment approaches for adolescents with NSSI.

Methods/Design

The study is designed as a randomized controlled trial (RCT) to test the effectiveness of a new cognitive-behavioral treatment manual for self-harming adolescents - the ‘Cutting-Down-Programme’ (CDP). A total of 80 adolescents aged between 12 and 17 years from a region in Southern Germany who have engaged in repetitive NSSI (≥5 incidents) in the last 6 months will be randomized into a treatment group (CDP) or a control group that will receive treatment as usual (TAU). The adolescents will be assessed by means of structured interviews and questionnaires at three time points (before treatment, directly after treatment and six months after treatment). Primary outcome criterion is a significant reduction (or remission) in the frequency of NSSI. Secondary outcome criteria are depressivity as well as general well-being and self-worth. Additionally, comorbid psychiatric disorders and childhood adversity will be evaluated as predictors of therapeutic outcome.

Discussion

Recently, a pilot study in the United Kingdom showed significant reductions in self-harming behavior, depressive symptoms and trait anxiety. This is the first RCT to test the effectiveness of a short-term psychotherapeutic intervention in outpatients engaging in NSSI.

Trial registration

The study is registered in the German Clinical Trials Register DRKS00003605.
Familial summer-type hypersensitivity pneumonitis in Japan: two case reports and review of the literature
Authors: Nakajima Akira , Saraya Takeshi , Mori Takeshi , Ikeda Reiko , Sugita Takashi , Watanabe Takayasu , Fujiwara Masachika , Takizawa Hajime , Goto Hajime
Published: September 2013

Background

Hypersensitivity pneumonitis is defined as an allergic lung disease that occurs in response to inhalation of fungal antigens, bacterial antigens, chemicals, dusts, or animal proteins. The incidence of summer-type hypersensitivity pneumonitis is higher in the summer season, especially in Japan, due to the influence of the hot and humid environment and the common style of wood house or old concrete condominiums.

Case presentation

The present report describes a case of a middle-aged married couple who lived in the same house and who simultaneously suffered from summer-type hypersensitivity pneumonitis. This report analyzes these two cases in terms of environmental research and its microbiological, radiological, and pathological aspects. This case report is followed by a review of family occurrences of summer-type hypersensitivity pneumonitis from 22 studies with a total of 49 patients (including the two present cases) in Japan.

Conclusion

Summer-type hypersensitivity pneumonitis may be unrecognized and misdiagnosed as pneumonia or other respiratory diseases. A greater understanding of the clinical, pathologic, and environmental features of summer-type hypersensitivity pneumonitis might help improve diagnosis and delivery of appropriate management for this condition.
IDOMAL: the malaria ontology revisited
Authors: Topalis Pantelis , Mitraka Elvira , Dritsou Vicky , Dialynas Emmanuel , Louis Christos
Published: September 2013

Background

With about half a billion cases, of which nearly one million fatal ones, malaria constitutes one of the major infectious diseases worldwide. A recently revived effort to eliminate the disease also focuses on IT resources for its efficient control, which prominently includes the control of the mosquito vectors that transmit the Plasmodium pathogens. As part of this effort, IDOMAL has been developed and it is continually being updated.

Findings

In addition to the improvement of IDOMAL’s structure and the correction of some inaccuracies, there were some major subdomain additions such as a section on natural products and remedies, and the import, from other, higher order ontologies, of several terms, which were merged with IDOMAL terms. Effort was put on rendering IDOMAL fully compatible as an extension of IDO, the Infectious Disease Ontology. The reason for the difficulties in fully reaching that target were the inherent differences between vector-borne diseases and “classical” infectious diseases, which make it necessary to specifically adjust the ontology’s architecture in order to comprise vectors and their populations.

Conclusions

In addition to a higher coverage of domain-specific terms and optimizing its usage by databases and decision-support systems, the new version of IDOMAL described here allows for more cross-talk between it and other ontologies, and in particular IDO. The malaria ontology is available for downloading at the OBO Foundry (http://www.obofoundry.org/cgi-bin/detail.cgi?id=malaria_ontology) and the NCBO BioPortal (http://bioportal.bioontology.org/ontologies/1311).
In vitro parameter optimization for spatial control of focused ultrasound ablation when using low boiling point phase-change nanoemulsions
Authors: Puett Connor , Phillips Linsey C , Sheeran Paul S , Dayton Paul A
Published: September 2013

Background

Phase-shift nanoemulsions (PSNEs) provide cavitation sites when the perfluorocarbon (PFC) nanodroplets (ND) are vaporized to microbubbles by acoustic energy. Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites. However, spatial control over the ablation region can be problematic when cavitation is used to enhance heating. This study explored relationships between vaporization, ablation, and the PSNE concentration in vitro to optimize the acoustic intensity and insonation time required for spatially controlled ablation enhancement using a PSNE that included a volatile PFC component.

Methods

HIFU (continuous wave at 1 MHz; insonation times of 5, 10, 15, and 20 s; cool-down times of 2, 4, and 6 s; peak negative pressures of 2, 3, and 4 MPa) was applied to albumin-acrylamide gels containing PFC agents (1:1 mix of volatile decafluorobutane and more stable dodecafluoropentane at 105 to 108 PFC ND per milliliter) or agent-free controls. Vaporization fields (microbubble clouds) were imaged by conventional ultrasound, and ablation lesions were measured directly by calipers. Controlled ablation was defined as the production of ‘cigar’-shaped lesions corresponding with the acoustic focal zone. This control was considered to be lost when ablation occurred in prefocal vaporization fields having a predominantly ‘tadpole’ or oblong shape.

Results

Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity. Working with the maximum concentration-intensity combinations resulting in controlled ablation demonstrated a dose-responsive relationship between insonation time and volumes of both the vaporization fields (approximately 20 to 240 mm3) and the ablation lesions (1 to 135 mm3) within them.

Conclusions

HIFU ablation was enhanced by this PSNE and could be achieved using intensities ≤650 W/cm2. Although the ablation lesions were located within much larger microbubble clouds, optimum insonation times and intensities could be selected to achieve an ablation lesion of desired size and location for a given PSNE concentration. This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.
Overexpression of a modified 6-phosphofructo-1-kinase results in an increased itaconic acid productivity in Aspergillus niger
Authors: van der Straat Laura , Tamayo-Ramos Juan A , Schonewille Tom , de Graaff Leo H
Published: September 2013

A modified 6-phosphofructo-1-kinase was expressed in a citrate producing Aspergillus niger strain in combination with cis-aconitate decarboxylase from Aspergillus terreus to study the effect on the production of itaconic acid. The modified pfkA gene was also expressed in combination with the itaconic acid biosynthetic cluster from A. terreus, which consists of cis- aconitate decarboxylase cadA, a putative mitochondrial transporter mttA and a putative plasmamembrane transporter mfsA. The combined expression of pfkA and cadA resulted in increased citrate levels, but did not show increased itaconic acid levels. The combined expression of pfkA with the itaconic acid biosynthetic cluster resulted in significantly increased itaconic acid production at earlier time points. Also the itaconic acid productivity increased significantly. The maximum itaconic acid productivity that was reached under these conditions was 0.15 g/L/h, which is only a factor 17 lower than the 2.5 g/L/h that according to the US Department of Energy should be achieved to have an economically feasible production process.
Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape
Authors: Day Kenneth , Waite Lindsay L , Thalacker-Mercer Anna , West Andrew , Bamman Marcas M , Brooks James D , Myers Richard M , Absher Devin
Published: September 2013

Background

DNA methylation is an epigenetic modification that changes with age in human tissues, although the mechanisms and specificity of this process are still poorly understood. We compared CpG methylation changes with age across 283 human blood, brain, kidney, and skeletal muscle samples using methylation arrays to identify tissue-specific age effects.

Results

We found age-associated CpGs (ageCGs) that are both tissue-specific and common across tissues. Tissue-specific ageCGs are frequently located outside CpG islands with decreased methylation, and common ageCGs show the opposite trend. AgeCGs are significantly associated with poorly expressed genes, but those with decreasing methylation are linked with higher tissue-specific expression levels compared with increasing methylation. Therefore, tissue-specific gene expression may protect against common age-dependent methylation. Distinguished from other tissues, skeletal muscle ageCGs are more associated with expression, enriched near genes related to myofiber contraction, and closer to muscle-specific CTCF binding sites. Kidney-specific ageCGs are more increasingly methylated compared to other tissues as measured by affiliation with kidney-specific expressed genes. Underlying chromatin features also mark common and tissue-specific age effects reflective of poised and active chromatin states, respectively. In contrast with decreasingly methylated ageCGs, increasingly methylated ageCGs are also generally further from CTCF binding sites and enriched within lamina associated domains.

Conclusions

Our data identified common and tissue-specific DNA methylation changes with age that are reflective of CpG landscape and suggests both common and unique alterations within human tissues. Our findings also indicate that a simple epigenetic drift model is insufficient to explain all age-related changes in DNA methylation.
Mechanical properties of shale-gas reservoir rocks — Part 2: Ductile creep, brittle strength, and their relation to the elastic modulus
Authors: Sone Hiroki , Zoback Mark D.
Published: September 2013

We studied the elastic moduli, ductile creep behavior, and brittle strength of shale-gas reservoir rocks from Barnett, Haynesville, Eagle Ford, and Fort St. John shale in a series of triaxial laboratory experiments. We found a strong correlation between the shale compositions, in particular, the volume of clay plus kerogen and intact rock strength, frictional strength, and viscoplastic creep. Viscoplastic creep strain was approximately linear with the applied differential stress. The reduction in sample volume during creep suggested that the creep was accommodated by slight pore compaction. In a manner similar to instantaneous strain, there was more viscoplastic creep in samples deformed perpendicular to the bedding than parallel to the bedding. The tendency to creep also correlated well with the static Young’s modulus. We explained this apparent correlation between creep behavior and elastic modulus by appealing to the stress partitioning that occurs between the soft components of the shales (clay and kerogen) and the stiff components (quartz, feldspar, pyrite, and carbonates). Through a simple 1D analysis, we found that a unique relation between the creep compliance and elastic modulus, independent of composition and orientation, can be established by considering the individual creep behavior of the soft and stiff components that arises from the stress partitioning within the rock. This appears to provide a mechanical explanation for why long-term ductile deformational properties can appear to correlate with short-term elastic properties in shale-gas reservoir rocks.
Mct8-Deficient Mice Have Increased Energy Expenditure and Reduced Fat Mass That Is Abrogated by Normalization of Serum T3 Levels
Authors: Di Cosmo Caterina , Liao Xiao-Hui , Ye Honggang , Ferrara Alfonso Massimiliano , Weiss Roy E. , Refetoff Samuel , Dumitrescu Alexandra M.
Published: September 2013

Children with monocarboxylate transporter 8 (MCT8) deficiency lose weight, even when adequately nourished. Changes in serum markers of thyroid hormone (TH) action compatible with thyrotoxicosis suggested that this might be due to T3 excess in peripheral tissues. Mct8-deficient mice (Mct8KO) replicate the human thyroid phenotype and are thus suitable for metabolic studies so far unavailable in humans. In the current work, compared with wild-type (Wt) mice, Mct8KO mice were leaner due to reduced fat mass. They tended to use more carbohydrates and fewer lipids during the dark phase. Mct8KO mice had increased total energy expenditure (TEE) and food and water intake, with normal total activity, indicating hypermetabolism. To determine whether this is due to the high serum T3, we studied mice deficient in both Mct8 and deiodinase 1 (Mct8D1KO) with serum T3 similar to Wt mice and Wt mice given L-T3 to raise their serum T3 to the level of Mct8KO mice. Contrary to Mct8KO, Mct8D1KO mice had similar fat mass, TEE, and food intake as their D1KO littermates, whereas T3-treated Wt mice showed increased food intake and TEE, similar to Mct8KO mice. In skeletal muscle, Mct8KO mice had increased T3 content and TH action and increased glucose metabolism, which improved in Mct8D1KO mice. These studies indicate that the high serum T3 in MCT8 deficiency increases the TEE and fails to maintain weight despite adequate calorie intake. This is mediated by tissues that are not predominantly MCT8 dependent for TH transport, including skeletal muscle. Normalizing serum T3 level by deleting deiodinase 1 corrects body composition and the metabolic alterations caused by the MCT8 deficiency.
Pancreatic Duct Ligation After Almost Complete β-Cell Loss: Exocrine Regeneration but No Evidence of β-Cell Regeneration
Authors: Cavelti-Weder Claudia , Shtessel Maria , Reuss Joshua E. , Jermendy Agnes , Yamada Takatsugu , Caballero Francisco , Bonner-Weir Susan , Weir Gordon C.
Published: September 2013

There has been great interest in the extent of β-cell regeneration after pancreatic duct ligation (PDL) and whether α- to β-cell conversion might account for β-cell regeneration after near-complete β-cell loss. To assess these questions, we established a PDL-model in adult male rats after almost complete beta-cell depletion achieved by giving a single high dose of streptozocin (STZ) in the fasted state. Because of the resultant severe diabetes, rats were given islet cell transplants to allow long-term follow-up. Although animals were followed up to 10 months, there was no meaningful β-cell regeneration, be it through replication, neogenesis, or α- to β-cell conversion. In contrast, the acinar cell compartment underwent massive changes with first severe acinar degeneration upon PDL injury followed by the appearance of pancreatic adipocytes, and finally near-complete reappearance of acini. We conclude that β-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats.
Localization of CaSR Antagonists in CaSR-expressing Medullary Thyroid Cancer
Authors: Ding Haiming , Yusof Adlina Mohd , Kothandaraman Shankaran , Saji Motoyasu , Wang Chaojie , Kumar Krishan , Milum Keisha , Carleton Michelle , Pan Xueliang , Ringel Matthew D. , Tweedle Michael F. , Phay John E.
Published: September 2013

Objective:

Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo.

Design:

We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was further radiolabeled with 125I and evaluated in nude mice with and without heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do not express CaSR, respectively.

Results:

Two newly synthesized compounds, 9 and 11, exhibited better antagonistic activity than Calhex 231. The half-life of 125I-compound 9 in nude mice without xenografts was 9.9 hours. A biodistribution study in nude mice bearing both tumors demonstrated that the uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24 hours: 0.39 ± 0.24 vs 0.18 ± 0.12 percentage of injected dose per gram of tissue (%ID/g) (P = .002), with a ratio of 2.25 ± 0.62. Tumor-to-background ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to-blood values increased from 2.02 ± 0.52 at 1 hour to 3.29 ± 0.98 at 24 hour (P = .015) for TT tumors, and 1.7 ± 0.56 at 1 hour to 1.48 ± 0.33 at 24 hour (P = .36) for MZ-CRC-1 tumors.

Conclusions:

Our new CaSR antagonists specifically inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors in vivo, and therefore have the potential to serve as scaffolds for further development as imaging pharmaceuticals.
Vitamin D3 Effects on Lipids Differ in Statin and Non-Statin-Treated Humans: Superiority of Free 25-OH D Levels in Detecting Relationships
Authors: Kane Lynn , Moore Kelly , Lütjohann Dieter , Bikle Daniel , Schwartz Janice B.
Published: September 2013

Context:

Inverse associations between 25-OH vitamin D levels and cardiovascular morbidity and mortality have been reported.

Objectives:

Our goals were to 1) investigate effects of correcting inadequate D status on lipids, 2) determine whether free 25-OH D is better correlated with lipids than total 25-OH D.

Design:

A randomized, double-blind placebo-controlled trial was performed.

Setting:

Participants resided in the general community.

Participants:

Adults with inadequate D status were randomized to D3: 14 men, 12 women, age 60 ± 8 years (mean ± SD) or placebo: 12 men, 11 women: 59 ±12 years.

Intervention:

Responses to 12-week oral vitamin D3 titrated (1000–3000 IU/d) to achieve 25-OH D levels ≥25 ng/mL were compared to placebo.

Main Outcome Measures:

Measurements were 25-OH D (tandem mass spectometry), free 25-OH D (direct immunoassay), lipids (directly measured triglyceride, cholesterol, and subfractions; plant sterols and cholesterol synthesis precursors), and safety labs before and after 6 and 12 weeks D3 or placebo. Data were analyzed by repeated measures ANOVA and linear regression.

Results:

Vitamin D3 was titrated to 1000 IU/d in 15/26 (58%), to 2000 IU/d in 10, and 3000 IU/d in one patient. D3 had no effect on cholesterol or cholesterol subfractions except for trends for decreases in atorvastatin-treated patients (cholesterol, P = .08; low-density lipoprotein [LDL] cholesterol, P = .05). Decreased campesterol concentrations (P = .05) were seen with D3 but not placebo in statin-treated patients. Relationships between total 25-OH D and lipids were not detected, but inverse linear relationships were detected between free 25-OH D and triglycerides (P = .03 for all participants [n = 49], P = .03 in all statin-treated [n = 19], and P = .0009 in atorvastatin-treated [n = 11]), and between free 25-OH D and LDL cholesterol (P = .08 overall, P = .02 in all statin-treated, and P = .03 for atorvastatin-treated), and total cholesterol (P = .09 overall; P = .04 for all statin-treated, and P = .05 for atorvastatin-treated).

Conclusions:

Vitamin D lipid-lowering effects appear limited to statin-treated patients and are likely due to decreased cholesterol absorption. Relationships between lipids and D metabolites were only detected when free 25-OH D was measured, suggesting the superiority of determining free 25-OH D levels compared to total 25-OH vitamin D levels when analyzing biologic responses.
Sinonasal Paraganglioma With Long-Delayed Recurrence and Metastases: Genetic and Imaging Findings
Authors: Michel Justin , Taïeb David , Jolibert Marianne , Torrents Julia , Wassef Michel , Morange Isabelle , Essamet Wassim , Barlier Anne , Dessi Patrick , Fakhry Nicolas
Published: September 2013

Context:

Sinonasal paragangliomas have rarely been reported in the literature. They are often aggressive.

Patient:

We report an original case of sinonasal paragangliomas with a tumor recurrence diagnosed 13 years after resection of the primary tumor. Somatostatin receptor scintigraphy and [18F]-fluorodeoxyglucose positron emission tomography/computed tomography were the most sensitive functional imaging techniques, and they ruled out distant metastases. Interestingly, [18F]-fluorodihydroxyphenylalanine positron emission tomography/computed tomography was negative, a feature that may be considered a sign of functional dedifferentiation. Screening for germline mutations of the SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 was negative.

Conclusion:

The diagnosis of malignancy remains challenging at initial diagnosis, and patients should be followed during their entire lifetime.
Coordinated ventilation and spiracle activity produce unidirectional airflow in the hissing cockroach,Gromphadorhina portentosa
Authors: Heinrich Erica C. , McHenry Matthew J. , Bradley Timothy J.
Published: September 2013

Insects exchange respiratory gases via an extensive network of tracheal vessels that open to the surface of the body through spiracular valves. Although gas exchange is known to increase with the opening of these spiracles, it is not clear how this event relates to gas flow through the tracheal system. We examined the relationship between respiratory airflow and spiracle activity in a ventilating insect, the hissing cockroach Gromphadorhina portentosa, to better understand the complexity of insect respiratory function. Using simultaneous video recordings of multiple spiracular valves, we found that abdominal spiracles open and close in unison during periods of ventilation. Additionally, independent recordings of CO2 release from the abdominal and thoracic regions, and observations of hyperoxic tracer gas movement, indicate that air is drawn into the thoracic spiracles and expelled from the abdominal spiracles. Our video recordings suggest that this unidirectional flow is driven by abdominal contractions that occur when the abdominal spiracles open. The spiracles then close as the abdomen relaxes and fills with air from the thorax. Therefore, the respiratory system of the hissing cockroach functions as a unidirectional pump through the coordinated action of the spiracles and abdominal musculature. This mechanism may be employed by a broad diversity of large insects that utilize active ventilation.
Spectral tuning of Amazon parrot feather coloration by psittacofulvin pigments and spongy structures
Authors: Tinbergen Jan , Wilts Bodo D. , Stavenga Doekele G.
Published: September 2013

The feathers of Amazon parrots are brightly coloured. They contain a unique class of pigments, the psittacofulvins, deposited in both barbs and barbules, causing yellow or red coloured feathers. In specific feather areas spongy nanostructured barb cells exist, reflecting either in the blue or blue-green wavelength range. The blue-green spongy structures are partly enveloped by a blue-absorbing, yellow-colouring pigment acting as a spectral filter, thus yielding a green coloured barb. Applying reflection and transmission spectroscopy, we characterized the Amazons' pigments and spongy structures, and investigated how they contribute to the feather coloration. The reflectance spectra of Amazon feathers are presumably tuned to the sensitivity spectra of the visual photoreceptors.
Exclusive localization of carbonic anhydrase in bacteriocytes of the deep-sea clamCalyptogena okutaniiwith thioautotrophic symbiotic bacteria
Authors: Hongo Yuki , Nakamura Yoshimitsu , Shimamura Shigeru , Takaki Yoshihiro , Uematsu Katsuyuki , Toyofuku Takashi , Hirayama Hisako , Takai Ken , Nakazawa Masatoshi , Maruyama Tadashi , Yoshida Takao
Published: September 2013

Deep-sea Calyptogena clams harbor thioautotrophic intracellular symbiotic bacteria in their gill epithelial cells. The symbiont fixes CO2 to synthesize organic compounds. Carbonic anhydrase (CA) of the host catalyzes the reaction CO2 + H2O ↔ HCO3- + H+, and is assumed to facilitate inorganic carbon (Ci) uptake and transport to the symbiont. However, the localization of CA in gill tissue remains unknown. We therefore analyzed mRNA sequences, proteins and CA activity in Calyptogena okutanii using expression sequence tag, SDS-PAGE with LC-MS/MS. It was shown that acetazolamide-sensitive soluble CA was abundantly expressed in the gill tissue of C. okutanii, and the enzyme was purified by affinity chromatography. Mouse monoclonal antibodies against the CA of C. okutanii were used in Western blot analysis and immunofluorescence staining of the gill tissues of C. okutanii, showing that CA was exclusively localized in the symbiont-harboring cells (bacteriocytes) in gill epithelial cells. Western blot analysis and measurement of activity showed that CA was abundantly (26-72% of total soluble protein) detected in the gill tissues of not only Calyptogena clams but also deep-sea Bathymodiolus mussels that harbor thioautotrophic or methanotrophic symbiotic bacteria, but was not detected in a nonsymbiotic mussel, Mytilus sp. The present study showed that CA is abundant in the gill tissues of deep-sea symbiotic bivalves and specifically localizes in the cytoplasm of bacteriocytes of C. okutanii. These indicate that the Ci supply process to symbionts in the vacuole (symbiosome) in bacteriocytes is essential for symbiosis.
Effects of running on human Achilles tendon length-tension properties in the free and gastrocnemius components
Authors: Lichtwark Glen A. , Cresswell Andrew G. , Newsham-West Richard J.
Published: September 2013

The elastic properties of the human Achilles tendon are important for locomotion, however in vitro tests suggest that repeated cyclic contractions lead to tendon fatigue; an increase in length in response to stress applied. In vivo experiments have not, however, demonstrated mechanical fatigue in the Achilles tendon, possibly due to the limitations of using two-dimensional ultrasound imaging to assess tendon strain. This study used freehand three-dimensional ultrasound (3DUS) to determine whether the free Achilles tendon (calcaneus to soleus) or the gastrocnemius tendon (calcaneus to gastrocnemius) demonstrated tendon fatigue after running exercise. Participants (n = 9) underwent 3DUS scans of the Achilles tendon during isometric contractions at four ankle torque levels (passive, 14, 42 and 70 N.m) before and after a 5 km run at a self selected pace (10-14km.h-1). Running had a significant main effect on the length of the free Achilles tendon (p < 0.01) with a small increase in length across the torque range. However the mean lengthening effect was small (<1%) and was not accompanied by a change in free tendon stiffness. There was no significant change in the length of the gastrocnemius tendon or the free tendon cross sectional area. While the free tendon was shown to lengthen, the lack of change in stiffness suggests the tendon exhibited mechanical creep rather than fatigue. These effects were much smaller than that predicted from in vitro experiments, possibly due to the different loading profile encountered and the ability of the tendon to repair in vivo.
Sources of Information for Innovative Activity of Enterprises. Types, Importance, Measurement
Authors: Krawczyk Marzena
Published: September 2013

Innovation determines expansion or just existence of enterprises. It’s an important element of competitive advantage and it is a characteristic that encourages customers to buy novelties. Unfortunately, with innovation activity closely related is uncertainty risk, that means insecurity that costly process of creating innovation solutions will succeed. By dint of necessity of high costs of innovation activity, only small percent of enterprises have their own research and development buck-up. More and more popular become external sources of information for innovative activity, such as: customers, research and development networks, conferences, scientist publications and journals. The paper presents sources of information used by polish enterprises in innovation activity, classify them and show its essence and importance. Main attention is put on sources, which according to modern theories of innovation and practice of innovative firms, are the most important, that means internal R&D activity and customers. An additional value of the paper is a discussion on the ways and the sense of measure the influence of chosen sources of information on the process of creation innovations in companies.
Property Rights of Scientific Knowledge in Terms of Creating Innovation
Authors: Pohulak-Żołędowska Elżbieta
Published: September 2013

Scientific knowledge has nowadays became one of the most important factors which foster innovation-based development of economies. The key role here play universities and higher education institutions which – under market pressure – also change their attitude to the knowledge creation. Originally focused on their educational duties, nowadays universities have became the real research leaders – ready to answer the market needs. The growing importance of new knowledge application to the industry, the tightening university-industry links, the impact of industry funding on knowledge production within universities or even the emergence of industrial knowledge, show how important private funding becomes at present. On the other hand the dominant portion of universities research activity is covered by public funds which, from another point of view, is important for the future prospects of modern economies. The aim of the article is to show the dependence of private and public funding of academic innovations. Methods used are: critical analysis of the literature, analysis of the statistical data.
Scale and Scope of Cooperation Between Food Retailers and their Economic Condition
Authors: Cyrek Piotr
Published: September 2013

Dynamic changes of economic structures resulting partially from globalization processes and international integration, strengthened by technological development induce economic entities to search for strategic as well as operational solutions that enable to gain and maintain competitive advantage. The statements seem to be especially important for retail trade entities that, apart from domestic competition, are forced to compete with retailers with foreign capital, that possess not only rich financial resources but also a lot of advantages in technical, organizational or managerial fields. Theoretical indication to improve such situation is to cooperate. In the paper there was taken an attempt to define scale and scope of cooperation between retailers functioning in podkarpackie voivodeship. There was verified a thesis about existence of relationship between cooperation activity and economic condition of the entities under research. Expectations of entrepreneurs who consider engagement in relations with their competitors were presented. Destimulants and stimulants of development of cooperation in trade were analysed as well. Conclusions in the paper were based on data extracted from the own research realized in the form of questionnaire survey in a group of 292 retailers functioning in podkarpackie voivodeship.
SolverStudio: A New Tool for Better Optimisation and Simulation Modelling in Excel
Authors: Mason Andrew J
Published: September 2013

Excel's built-in Solver optimiser provides millions of spreadsheet users with easy access to optimisation, and is often used in teaching introductory optimisation courses. However, more sophisticated users often prefer to use modelling languages such as AMPL, GAMS, or PuLP, and so these are often taught in more advanced courses. Unfortunately, the command line and text file interfaces these systems employ present unnecessary barriers to their use. We have developed a new free Excel add-in, SolverStudio, that combines the power of modelling languages—including AMPL, GAMS, PuLP, GMPL, and Gurobi's Python environment—with the familiarity and ease of use of Excel. SolverStudio also brings cloud-based optimisation to Excel by providing easy access to the NEOS online solvers, and simulation capabilities via the Python-based SimPy software. We believe that SolverStudio will support and encourage the greater use in classrooms of Excel-based optimisation and simulation.