bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Thorough QT Study of Teduglutide in Healthy Subjects
Authors: Hartmann Manfred , Timmer Wolfgang , Schultz Armin , Nave Rüdiger , Luehmann Reinhold , Krause Stephan , Lahu Gezim , Scholpp Joachim 
Published: April 2012

AbstractTeduglutide, an analog of the endogenous hormone glucagon‐like peptide‐2, is currently being developed for the treatment of short bowel syndrome. This study investigated the potential effects of teduglutide on cardiac conduction and repolarization. Seventy‐two healthy volunteers underwent 4 treatment periods in randomized order with a single subcutaneous injection of placebo, 5 and 20 mg teduglutide, and a single oral 400‐mg dose of moxifloxacin. The primary variable to investigate the effect on cardiac repolarization was the difference between QTcF after administration versus predose. The observed upper bounds of the 95% one‐sided confidence intervals were 3.0 ms (5 mg) and 4.5 ms (20 mg). Arithmetic mean curves of QTcF intervals over time of both doses of teduglutide and of placebo were almost superposable. Assay sensitivity for the positive control moxifloxacin was shown. In conclusion, teduglutide at intended therapeutic and supratherapeutic doses had no effect on cardiac repolarization. No safety concerns were identified. Treatment with teduglutide was well tolerated.
Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency
Authors: Kawai Tomoki , Nishikomori Ryuta , Izawa Kazushi , Murata Yuuki , Tanaka Naoko , Sakai Hidemasa , Saito Megumu , Yasumi Takahiro , Takaoka Yuki , Nakahata Tatsutoshi , Mizukami Tomoyuki , Nunoi Hiroyuki , Kiyohara Yuki , Yoden Atsushi , Murata Takuji , Sasaki Shinya , Ito Etsuro , Akutagawa Hiroshi , Kawai Toshinao , Imai Chihaya , Okada Satoshi , Kobayashi Masao , Heike Toshio 
Published: April 2012

Abstract
Somatic mosaicism has been described in several primary immunodeficiency diseases and causes modified phenotypes in affected patients. X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the NF-κB essential modulator (NEMO) gene and manifests clinically in various ways. We have previously reported a case of XL-EDA-ID with somatic mosaicism caused by a duplication mutation of the NEMO gene, but the frequency of somatic mosaicism of NEMO and its clinical impact on XL-EDA-ID is not fully understood. In this study, somatic mosaicism of NEMO was evaluated in XL-EDA-ID patients in Japan. Cells expressing wild-type NEMO, most of which were derived from the T-cell lineage, were detected in 9 of 10 XL-EDA-ID patients. These data indicate that the frequency of somatic mosaicism of NEMO is high in XL-ED-ID patients and that the presence of somatic mosaicism of NEMO could have an impact on the diagnosis and treatment of XL-ED-ID patients.
Effective enhancement of Pseudomonas stutzeri D-phenylglycine aminotransferase functional expression in Pichia pastoris by co-expressing Escherichia coli GroEL-GroES
Authors: Jariyachawalid Kanidtha , Laowanapiban Poramaet , Meevootisom Vithaya , Wiyakrutta Suthep 
Published: April 2012

Abstract

Background
D-phenylglycine aminotransferase (D-PhgAT) of Pseudomonas stutzeri ST-201 catalyzes the reversible stereo-inverting transamination potentially useful in the application for synthesis of D-phenylglycine and D-4-hydroxyphenylglycine using L-glutamate as a low cost amino donor substrate in one single step. The enzyme is a relatively hydrophobic homodimeric intracellular protein difficult to express in the soluble functionally active form. Over-expression of the dpgA gene in E. coli resulted in the majority of the D-PhgAT aggregated into insoluble inclusion bodies that failed to be re-natured. Expression in Pichia pastoris was explored as an alternative route for high level production of the D-PhgAT.

Results
Intracellular expression of the codon-optimized synthetic dpgA gene under the P

AOX1
promoter in P. pastoris resulted in inactive D-PhgAT associated with insoluble cellular fraction and very low level of D-PhgAT activity in the soluble fraction. Manipulation of culture conditions such as addition of sorbitol to induce intracellular accumulation of osmolytes, addition of benzyl alcohol to induce chaperone expression, or lowering incubation temperature to slow down protein expression and folding rates all failed to increase the active D-PhgAT yield. Co-expression of E. coli chaperonins GroEL-GroES with the D-PhgAT dramatically improved the soluble active enzyme production. Increasing gene dosage of both the dpgA and those of the chaperones further increased functional D-PhgAT yield up to 14400-fold higher than when the dpgA was expressed alone. Optimization of cultivation condition further increased D-PhgAT activity yield from the best co-expressing strain by 1.2-fold.

Conclusions
This is the first report on the use of bacterial chaperones co-expressions to enhance functional intracellular expression of bacterial enzyme in P. pastoris. Only two bacterial chaperone genes groEL and groES were sufficient for dramatic enhancement of functionally active D-PhgAT expression in this yeast. With the optimized gene dosage and chaperone combinations, P. pastoris can be attractive for intracellular expression of bacterial proteins since it can grow to a very high cell density which is translated into the higher volumetric product yield than the E. coli or other bacterial systems.
Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery
Authors: Prassas Ioannis , Chrystoja Caitlin C , Makawita Shalini , Diamandis Eleftherios P 
Published: April 2012

Abstract

Background
There is an important need for the identification of novel serological biomarkers for the early detection of cancer. Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics.

Methods
Previous studies have focused on either gene or protein expression databases for the identification of candidates. We developed a strategy that mines six publicly available gene and protein databases for tissue-specific proteins, selects proteins likely to enter the circulation, and integrates proteomic datasets enriched for the cancer secretome to prioritize candidates for further verification and validation studies.

Results
Using colon, lung, pancreatic and prostate cancer as case examples, we identified 48 candidate tissue-specific biomarkers, of which 14 have been previously studied as biomarkers of cancer or benign disease. Twenty-six candidate biomarkers for these four cancer types are proposed.

Conclusions
We present a novel strategy using bioinformatics to identify tissue-specific proteins that are potential cancer serum biomarkers. Investigation of the 26 candidates in disease states of the organs is warranted.
A highly efficient β-glucosidase from the buffalo rumen fungus Neocallimastix patriciarum W5
Authors: Chen Hsin-Liang , Chen Yo-Chia , Lu Mei-Yeh Jade , Chang Jui-Jen , Wang Hiaow-Ting Christine , Ke Huei-Mien , Wang Tzi-Yuan , Ruan Sz-Kai , Wang Tao-Yuan , Hung Kuo-Yen , Cho Hsing-Yi , Lin Wan-Ting , Shih Ming-Che , Li Wen-Hsiung 
Published: April 2012

Abstract

Background
Cellulose, which is the most abundant renewable biomass on earth, is a potential bio-resource of alternative energy. The hydrolysis of plant polysaccharides is catalyzed by microbial cellulases, including endo-β-1,4-glucanases, cellobiohydrolases, cellodextrinases, and β-glucosidases. Converting cellobiose by β-glucosidases is the key factor for reducing cellobiose inhibition and enhancing the efficiency of cellulolytic enzymes for cellulosic ethanol production.

Results
In this study, a cDNA encoding β-glucosidase was isolated from the buffalo rumen fungus Neocallimastix patriciarum W5 and is named NpaBGS. It has a length of 2,331 bp with an open reading frame coding for a protein of 776 amino acid residues, corresponding to a theoretical molecular mass of 85.1 kDa and isoelectric point of 4.4. Two GH3 catalytic domains were found at the N and C terminals of NpaBGS by sequence analysis. The cDNA was expressed in Pichia pastoris and after protein purification, the enzyme displayed a specific activity of 34.5 U/mg against cellobiose as the substrate. Enzymatic assays showed that NpaBGS was active on short cello-oligosaccharides from various substrates. A weak activity in carboxymethyl cellulose (CMC) digestion indicated that the enzyme might also have the function of an endoglucanase. The optimal activity was detected at 40°C and pH 5 ~ 6, showing that the enzyme prefers a weak acid condition. Moreover, its activity could be enhanced at 50°C by adding Mg2+ or Mn2+ ions. Interestingly, in simultaneous saccharification and fermentation (SSF) experiments using Saccharomyces cerevisiae BY4741 or Kluyveromyces marxianus KY3 as the fermentation yeast, NpaBGS showed advantages in cell growth, glucose production, and ethanol production over the commercial enzyme Novo 188. Moreover, we showed that the KY3 strain engineered with the NpaNGS gene can utilize 2 % dry napiergrass as the sole carbon source to produce 3.32 mg/ml ethanol when Celluclast 1.5 L was added to the SSF system.

Conclusion
Our characterizations of the novel β-glucosidase NpaBGS revealed that it has a preference of weak acidity for optimal yeast fermentation and an optimal temperature of ~40°C. Since NpaBGS performs better than Novo 188 under the living conditions of fermentation yeasts, it has the potential to be a suitable enzyme for SSF.
Sex and age-level differences of walking time in preschool children on an obstacle frame
Authors: Kasuga Kosho , Demura Shin-ichi , Aoki Hiroki , Shin Sohee , Sugiura Hiroki , Uchida Yu 
Published: April 2012

Abstract

Background
Stepping over an obstacle is a kind of compound movement that makes walking more difficult, especially for preschool children. This study examines sex and age-level differences in walking time in preschool children on an obstacle frame.

Methods
The participants included 324 healthy preschool children: four-year-old boys (51) and girls (51), five-year-old boys (50) and girls (60), and six-year-old boys (62) and girls (50). A 5 cm- or 10 cm-high obstacle (depth 11.5 cm, width 23.5 cm) was set at the halfway point of a 200 cm × 10 cm walking course.

Results
The participants walked to the end of the course and back as fast as possible under three conditions: no obstacle, low obstacle and high obstacle. Walking time showed age-level differences in all conditions, but there were no differences in sex. Age levels were divided into two groups, with one group within the first six months of their birthday, and the second group within the last six months of that year. Walking time for children in the first half of their fourth year was longer than that of the five- and six-year-old children. In addition, for children in the last half of their fourth year, walking time was longer than both sexes in the last half of their fifth and sixth years. The children in the latter half of their fifth year had a longer walking time in the high obstacle condition than those in the last half of their sixth year. In the four-year-old participants, walking time was shorter with no obstacles than with a high obstacle frame.

Conclusions
In the above data, obstacle course walking time does not show a gender difference, except that the four-year-old participants needed longer than the five- and six-year-old children. Setting the obstacle 10 cm high also produced a different walking time in the five- and six-year-old participants. The high obstacle step test (10 cm) best evaluated the dynamic balance of preschool children.
Naïve adult stem cells from patients with Hutchinson-Gilford progeria syndrome express low levels of progerin in vivo
Authors: Wenzel Vera , Roedl Daniela , Gabriel Diana , Gordon Leslie B. , Herlyn Meenhard , Schneider Reinhard , Ring Johannes , Djabali Karima 
Published: April 2012

Summary
Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by segmental accelerated aging and early death from coronary artery disease or stroke. Nearly 90% of HGPS sufferers carry a G608G mutation within exon 11 of LMNA, producing a truncated form of prelamin A, referred to as “progerin”. Here, we report the isolation of naïve multipotent skin-derived precursor (SKP) cells from dermal fibroblast cultures from HGPS donors. These cells form spheres and express the neural crest marker, nestin, in addition to the multipotent markers, OCT4, Sox2, Nanog and TG30; these cells can self-renew and differentiate into smooth muscle cells (SMCs) and fibroblasts. The SMCs derived from the HGPS-SKPs accumulate nuclear progerin with increasing passages. A subset of the HGPS-naïve SKPs express progerin in vitro and in situ in HGPS skin sections. This is the first in vivo evidence that progerin is produced in adult stem cells, and implies that this protein could induce stem cells exhaustion as a mechanism contributing to aging. Our study provides a basis on which to explore therapeutic applications for HGPS stem cells and opens avenues for investigating the pathogenesis of other genetic diseases.
Longitudinal Assessment of Intellectual Abilities of Children With Williams Syndrome: Multilevel Modeling of Performance on the Kaufman Brief Intelligence Test—Second Edition
Authors: Mervis Carolyn B. , Kistler Doris J. , John Angela E. , Morris Colleen A. 
Published: April 2012

AbstractMultilevel modeling was used to address the longitudinal stability of standard scores (SSs) measuring intellectual ability for children with Williams syndrome (WS). Participants were 40 children with genetically confirmed WS who completed the Kaufman Brief Intelligence Test—Second Edition (KBIT-2; A. S. Kaufman & N. L. Kaufman, 2004) 4–7 times over a mean of 5.06 years. Mean age at first assessment was 7.44 years (range  =  4.00–13.97 years). On average, KBIT-2 Composite IQ, Verbal SS, and Nonverbal SS were stable from 4 to 17 years, although there were significant individual differences in intercept (Composite IQ, Verbal SS, Nonverbal SS) and slope (Composite IQ, Nonverbal SS). Maternal education was significantly related to Verbal SS intercept. No significant sex differences were found. Implications for studies of genotype/phenotype correlations in WS are discussed.
Arkanum der Macht
Authors: Jedlitschka Karsten 
Published: April 2012

Vorspann
Geheimdienste verwahren ihre Dokumente an besonders sicheren Orten. Die Staatssicherheit der DDR schuf sich dafür die „Geheime Ablage“, die mit etwa 13.000 Aktenbänden ein eigenes Archiv im Zentralarchiv war. Wie brisant waren die Dokumente wirklich, die dort abgelegt wurden und größter Geheimhaltung unter-lagen? Karsten Jedlitschka, als Mitarbeiter der Stasi Unterlagen Behörde ein Insider, weiß wovon er spricht: Die „Geheime Ablage“ enthält heute frei zugängliche Akten über besonders wichtige Operative Vorgänge, vor allem aber Unterlagen über mora¬lisches oder strafrechtlich relevantes Fehlverhalten von Stasi Mitarbeitern und SED Genossen.
Corrosion Rates of Zircaloy-4 by Hydrogen Measurement under High pH, Low Oxygen and Low Temperature Conditions
Authors: SAKURAGI Tomofumi , MIYAKAWA Hideaki , NISHIMURA Tsutomu , TATEISHI Tsuyoshi 
Published: April 2012

ABSTRACTCorrosion tests of Zircaloy-4 were performed in a dilute NaOH solution (pH =12.5) at 303 K for 90 days using the gas flow system (oxygen; < 1 ppb) and a batch method (oxygen; < 0.1 ppm). The corrosion rate was determined by measuring gaseous hydrogen and the hydrogen absorbed into Zircaloy-4 assuming the following reaction:where x represents the Zircaloy-4 hydrogen absorption ratio. The initial hydrogen content in the Zircaloy-4 specimen was controlled to be below 10 ppm. The corrosion rate decreased with time (90-day values: 2.46×10-3 and 2.37×10-3 μm/y for the gas flow method and 6.72×10-2 μm/y for the batch test). The Zircaloy-4 hydrogen absorption ratio during corrosion was over 90%. The large amount of hydrogen absorbed in Zircaloy-4 will play an important role in the long-term safety for the disposal of irradiated Zircaloy materials.
Implementing Rapid HIV Testing With or Without Risk-Reduction Counseling in Drug Treatment Centers: Results of a Randomized Trial
Authors: Metsch Lisa R. , Feaster Daniel J. , Gooden Lauren , Matheson Tim , Mandler Raul N. , Haynes Louise , Tross Susan , Kyle Tiffany , Gallup Dianne , Kosinski Andrzej S. , Douaihy Antoine , Schackman Bruce R. , Das Moupali , Lindblad Robert , Erickson Sarah , Korthuis P. Todd , Martino Steve , Sorensen James L. , Szapocznik José , Walensky Rochelle , Branson Bernard , Colfax Grant N. 
Published: April 2012

Objectives. We examined the effectiveness of risk reduction counseling and the role of on-site HIV testing in drug treatment. Methods. Between January and May 2009, we randomized 1281 HIV-negative (or status unknown) adults who reported no past-year HIV testing to (1) referral for off-site HIV testing, (2) HIV risk-reduction counseling with on-site rapid HIV testing, or (3) verbal information about testing only with on-site rapid HIV testing. Results. We defined 2 primary self-reported outcomes a priori: receipt of HIV test results and unprotected anal or vaginal intercourse episodes at 6-month follow-up. The combined on-site rapid testing participants received more HIV test results than off-site testing referral participants (P < .001; Mantel-Haenszel risk ratio = 4.52; 97.5% confidence interval [CI] = 3.57, 5.72). At 6 months, there were no significant differences in unprotected intercourse episodes between the combined on-site testing arms and the referral arm (P = .39; incidence rate ratio [IRR] = 1.04; 97.5% CI = 0.95, 1.14) or the 2 on-site testing arms (P = .81; IRR = 1.03; 97.5% CI = 0.84, 1.26). Conclusions. This study demonstrated on-site rapid HIV testing’s value in drug treatment centers and found no additional benefit from HIV sexual risk-reduction counseling.
Supporting the Integration of HIV Testing Into Primary Care Settings
Authors: Myers Janet J. , Bradley-Springer Lucy , Kang Dufour Mi-Suk , Koester Kimberly A. , Beane Stephanie , Warren Nancy , Beal Jeffrey , Frank Linda Rose 
Published: April 2012

Objectives. We examined the efforts of the US network of AIDS Education and Training Centers (AETCs) to increase HIV testing capacity across a variety of clinical settings. Methods. We used quantitative process data from 8 regional AETCs for July 1, 2008, to June 30, 2009, and qualitative program descriptions to demonstrate how AETC education helped providers integrate HIV testing into routine clinical care with the goals of early diagnosis and treatment. Results. Compared with other AETC training, HIV testing training was longer and used a broader variety of strategies to educate more providers per training. During education, providers were able to understand their primary care responsibility to address public health concerns through HIV testing. Conclusions. AETC efforts illustrate how integration of the principles of primary care and public health can be promoted through professional training.
Treatment of dematiaceous fungal keratitis in a dog
Authors: Pucket Jonathan D. , Allbaugh Rachel A. , Rankin Amy J. 
Published: April 2012

Abstract
Case Description—A 9-year-old castrated male Bichon Frise was evaluated because of a 3-week history of a nonhealing corneal ulcer and corneal pigmentation of the left eye.
Clinical Findings—Ophthalmic examination of the left eye revealed conjunctival hyperemia, corneal neovascularization, corneal edema, corneal ulceration, and central corneal pigmentation. Intraocular structures of the left eye could not be visually examined because of the diffuse nature of the corneal lesions. The right eye had anterior cortical incipient cataracts, nuclear sclerosis, and an inactive chorioretinal scar.
Treatment and Outcome—Superficial lamellar keratectomy of the left eye was performed for both therapeutic and diagnostic purposes. Histologic evaluation of corneal biopsy specimens revealed dematiaceous fungal keratitis of the left eye, and topical administration of voriconazole was used to successfully resolve the keratitis. Seven months after diagnosis of dematiaceous fungal keratitis, the dog had no clinical signs or history of recurrence of the keratitis.
Clinical Relevance—Dematiaceous fungal keratitis should be considered as a possible cause of nonhealing corneal ulceration with heavy pigment deposition in dogs. Results suggested that lamellar keratectomy along with topical administration of voriconazole can be used successfully to treat dematiaceous fungal keratitis in dogs.
Methodology for conformance testing of spatial data infrastructure components including an example of its implementation in Slovakia
Authors: Kliment T. , Tuchyňa M. , Kliment M. 
Published: April 2012

Methodology for conformance testing of spatial data infrastructure components including an example of its implementation in SlovakiaBefore any spatial data infrastructure (SDI) is implemented as fully operational, many relevant testing procedures should take place. Such procedures should evaluate the compliancy level of particular SDI components against the relevant standards and implementing rules. Hence, they should ensure a high interoperability level. Many testing activities have already been performed within the implementation of the European SDI (INSPIRE - Infrastructure for Spatial Information in the European Community). Nevertheless, a common and versatile testing methodology, which is possible to use at any level of SDI realization is still lacking. This paper proposes a conformance testing methodology for selected SDI components applicable via network services for the discovery, view and downloading of data. An example of such an implementation has taken place within an environmental SDI developed by the Slovak Environmental Agency. A testing report template summarizing the results of the tests is proposed to be considered as a common template on a national level to be used within the implementation of a National Infrastructure for Spatial Information in the Slovak Republic.
Experimental verification of the resistance of glass beams
Authors: Slivanský M. 
Published: April 2012

Experimental verification of the resistance of glass beamsExperimental research at the Department of Steel and Timber Structures at SUT in Bratislava focused on the verification of the behavior of modern glass structures. Four types of glass beams were tested - laminated beams made of annealed (ANG) and fully tempered glass (FTG) in interactions with or without steel elements (as reinforcement). The results of the experimental research were also compared with theoretical models using FEM calculations.