bluuebunny/crossref_metadata_2025_split huggingface dataset:
A metabolic biosignature of early response to anti-tuberculosis treatment
Authors: Mahapatra Sebabrata , Hess Ann M , Johnson John L , Eisenach Kathleen D , DeGroote Mary A , Gitta Phineas , Joloba Moses L , Kaplan Gilla , Walzl Gerhard , Boom W Henry , Belisle John T 
Published: February 2014

Abstract

Background
The successful treatment of tuberculosis (TB) requires long-term multidrug chemotherapy. Clinical trials to evaluate new drugs and regimens for TB treatment are protracted due to the slow clearance of Mycobacterium tuberculosis (Mtb) infection and the lack of early biomarkers to predict treatment outcome. Advancements in the field of metabolomics make it possible to identify metabolic profiles that correlate with disease states or successful chemotherapy. However, proof-of-concept of this approach has not been provided for a TB-early treatment response biosignature (TB-ETRB).

Methods
Urine samples collected at baseline and during treatment from 48 Ugandan and 39 South African HIV-seronegative adults with pulmonary TB were divided into discovery and qualification sets, normalized to creatinine concentration, and analyzed by liquid chromatography-mass spectrometry to identify small molecule molecular features (MFs) in individual patient samples. A biosignature that distinguished baseline and 1 month treatment samples was selected by pairwise t-test using data from two discovery sample sets. Hierarchical clustering and repeated measures analysis were applied to additional sample data to down select molecular features that behaved consistently between the two clinical sites and these were evaluated by logistic regression analysis.

Results
Analysis of discovery samples identified 45 MFs that significantly changed in abundance at one month of treatment. Down selection using an extended set of discovery samples and qualification samples confirmed 23 MFs that consistently changed in abundance between baseline and 1, 2 and 6 months of therapy, with 12 MFs achieving statistical significance (p < 0.05). Six MFs classified the baseline and 1 month samples with an error rate of 11.8%.

Conclusions
These results define a urine based TB-early treatment response biosignature (TB-ETRB) applicable to different parts of Africa, and provide proof-of-concept for further evaluation of this technology in monitoring clinical responses to TB therapy.
Efficient extraction of proteins from formalin-fixed paraffin-embedded tissues requires higher concentration of tris(hydroxymethyl)aminomethane
Authors: Kawashima Yusuke , Kodera Yoshio , Singh Anil , Matsumoto Masaomi , Matsumoto Hiroyuki 
Published: February 2014

Abstract

Background
Numerous formaldehyde-fixed and paraffin-embedded clinical tissues have been created in the past decades and stored in pathological depositories at hospitals as well as in clinical laboratories worldwide. In addition to the archived tissues, formaldehyde-fixation is also mandatory for preparing proteomics samples from diseased patients or animal models in order to inactivate contagious agents. Protein extraction from formaldehyde-fixed tissues is hampered by the Schiff base formation between the amino groups of proteins and formaldehyde. Although achievement of the highest extraction efficiency of proteins from the formaldehyde-fixed tissues is essential for obtaining maximum proteomics information, no attention has been paid to the concentration dependence of tris(hydroxymethyl)aminomethane on the extraction efficacy. We suspected that the concentration of tris(hydroxymethyl)aminomethane affects the protein extraction efficiency because of its property as a primary amine that reverses the Schiff base formation between the primary amines of proteins and formaldehyde. Thus we pursued optimization of the component and protocol of protein extraction buffer to achieve better extraction efficiency of proteins from formaldehyde-fixed and paraffin-embedded tissues.

Results
In order to simulate protein extraction from diseased tissues we made formaldehyde-fixed and paraffin-embedded samples from mouse liver slices and investigated the protein extraction efficiency and speed by changing the concentration of the protein extraction buffer component tris(hydroxymethyl)aminomethane under various extraction conditions. We find, as expected, that tris(hydroxymethyl)aminomethane significantly affects the performance of protein extraction from the formaldehyde-fixed and paraffin-embedded samples both in the extraction yield and in the extraction speed.

Conclusions
We recommend the concentration of tris(hydroxymethyl)aminomethane in protein extraction buffer to be higher than 300 mM when extraction is conducted for 90 min at 90°C to achieve the most efficient protein extraction in a shorter time. The information will be essential for performing the most efficient protein extraction from formaldehyde-fixed and paraffin-embedded tissue samples for proteomics analysis.
Achieving low-complexity maximum-likelihood detection for the 3D MIMO code
Authors: Liu Ming , Crussière Matthieu , Hélard Maryline , Hélard Jean-François 
Published: February 2014

Abstract
The 3D Multiple-input multiple-output (MIMO) code is a robust and efficient space-time block code (STBC) for the distributed MIMO broadcasting but suffers from high maximum-likelihood (ML) decoding complexity. In this paper, we first analyze some properties of the 3D MIMO code to show that the 3D MIMO code is fast decodable. It is proven that the ML decoding performance can be achieved with a complexity of O(M
4.5) instead of O(M
8) in quasi-static channel with M-ary square QAM modulations. Consequently, we propose a simplified ML decoder exploiting the unique properties of the 3D MIMO code. Simulation results show that the proposed simplified ML decoder can achieve much lower processing time latency compared to the classical sphere decoder with Schnorr-Euchner enumeration.
Fetal demise and associated factors following umbilical cord prolapse in Mulago hospital, Uganda: a retrospective study
Authors: Wasswa Esau Wangi , Nakubulwa Sarah , Mutyaba Twaha 
Published: February 2014

Abstract

Background
Umbilical cord prolapse is an obstetric complication associated with high perinatal morbidity and mortality. A few interventions may improve fetal outcome. In developed countries these have advanced to giving intrauterine fetal resuscitation. Conditions in low resource settings do not allow for some of these advanced techniques. Putting the mother in knee chest position and immediate delivery may be the only options possible.
We set out to determine the incidence of fetal demise and associated factors following umbilical cord prolapsed (UCP) in Mulago Hospital, Uganda.

Methods
In a retrospective study conducted in Mulago hospital, Uganda, file records of mothers who delivered between 1st January 2000 to 31st December 2009 and had pregnancies complicated by umbilical cord prolapse with live fetus were selected. We collected information on referral status, cord position, cervical dilatation, fetal heart state at the time of diagnosis of UCP, diagnosis to delivery interval, use of knee chest position, mode of delivery, birth weight and fetal outcome.
We computed incidence of fetal demise following UCP and determined factors associated with fetal demise in pregnancies complicated by UCP.

Results
Of 438 cases with prolapsed cord, 101(23%) lost their babies within 24 hours after birth or were delivered dead. This gave annual cumulative incidence of fetal death following UCP of 23/1000 live UCP cases delivered /year.
The major factors associated with fetal outcome in pregnancies complicated by UCP included; diagnosis to delivery interval <30 min, RR 0.79 (CI 0.74-0.85), mode of delivery, RR 1.14 (CI 1.02-1.28), knee chest position, RR 0.81 (CI 0.70-0.95).

Conclusions
The annual cumulative incidence of fetal death in our study was 23/1000 live UCP cases delivery per year for the period of 10 years studied. Cesarean section reduced perinatal mortality by a factor of 2. Diagnosis to delivery interval <30 minutes and putting mother in knee chest position were protective against fetal death.
Uptake and sorption of aluminium and fluoride by four green algal species
Authors: Pitre Danaé , Boullemant Amiel , Fortin Claude 
Published: February 2014

Abstract

Background
We examined the uptake and sorption of aluminium (Al) and fluoride (F) by green algae under conditions similar to those found in the effluents of the aluminium industry. We took into account the speciation of Al in the medium since Al can form stable complexes with F and these complexes may play a role in the uptake and sorption of Al. We compared the capacity of four species of green algae (i.e. Chlamydomonas reinhardtii, Pseudokirchneriella subcapitata, Chlorella vulgaris, and Scenedesmus obliquus) to accumulate and adsorb Al and F. The selected algae were exposed during 4 days, covering all growth phases of algae, to a synthetic medium containing Al and F at pH 7.0. During this period, dissolved Al as well as cellular growth were followed closely. At the end of the exposure period, the solutions were filtered in order to harvest the algal cells. The cells were then rinsed with enough ethylene diaminetetraacetic acid to remove loosely bound ions from the algal surface, determined from the filtrates. Finally, the filters were digested in order to quantify cellular uptake.

Results
Little difference in Al removal was observed between species. Aluminium sorption (15%) and uptake (26%) were highest in P. subcapitata, followed by C. reinhardtii (7% and 17% respectively), S. obliquus (13% and 5%), and C. vulgaris (7% and 2%). However, none of these species showed significant uptake or sorption of F. We also studied the influence of pH on the uptake and sorption of Al and F by P. subcapitata. We measured a combined uptake and sorption of Al of 50% at pH 7.5, of 41% at pH 7.0, and of 4% at pH 5.5. Thus, accumulation was reduced with acidification of the medium as expected by the increased competition with protons and possibly by a reduced bioavailability of the Al-F complexes which dominated the solution at low pH.

Conclusion
Out of the four tested species, P. subcapitata showed the highest sorption of aluminium and fluoride under our test conditions. These results provide key information on the development of an environmental biotechnology which can be applied to industrial effluents.
Half-life measurements of chemical inducers for recombinant gene expression
Authors: Politi Nicolo’ , Pasotti Lorenzo , Zucca Susanna , Casanova Michela , Micoli Giuseppina , Cusella De Angelis Maria Gabriella , Magni Paolo 
Published: February 2014

Abstract

Background
Inducible promoters are widely spread genetic tools for triggering, tuning and optimizing the expression of recombinant genes in engineered biological systems. Most of them are controlled by the addition of a specific exogenous chemical inducer that indirectly regulates the promoter transcription rate in a concentration-dependent fashion. In order to have a robust and predictable degree of control on promoter activity, the degradation rate of such chemicals should be considered in many applications like recombinant protein production.

Results
In this work, we use whole-cell biosensors to assess the half-life of three commonly used chemical inducers for recombinant Escherichia coli: Isopropyl β-D-1-thiogalactopyranoside (IPTG), anhydrotetracycline (ATc) and N-(3-oxohexanoyl)-L-homoserine lactone (HSL). A factorial study was conducted to investigate the conditions that significantly contribute to the decay rate of these inducers. Temperature has been found to be the major factor affecting ATc, while medium and pH have been found to highly affect HSL. Finally, no significant degradation was observed for IPTG among the tested conditions.

Conclusions
We have quantified the decay rate of IPTG, ATc and HSL in many conditions, some of which were not previously tested in the literature, and the main effects affecting their degradation were identified via a statistics-based framework. Whole-cell biosensors were successfully used to conduct this study, yielding reproducible measurements via simple multiwell-compatible assays. The knowledge of inducer degradation rate in several contexts has to be considered in the rational design of synthetic biological systems for improving the predictability of induction effects, especially for prolonged experiments.
The use of 2D fingerprint methods to support the assessment of structural similarity in orphan drug legislation
Authors: Franco Pedro , Porta Nuria , Holliday John D , Willett Peter 
Published: February 2014

Abstract

Background
In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of 2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought.

Results
143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset.

Conclusions
Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities.
Development of STS and CAPS markers for variety identification and genetic diversity analysis of tea germplasm in Taiwan
Authors: Hu Chih-Yi , Tsai You-Zen , Lin Shun-Fu 
Published: February 2014

Abstract

Background
Tea (Camellia sinensis) is an important economic crop in Taiwan. Particularly, two major commercial types of tea (Paochong tea and Oolong tea) which are produced in Taiwan are famous around the world, and they must be manufactured with specific cultivars. Nevertheless, many elite cultivars have been illegally introduced to foreign countries. Because of the lower cost, large amount of “Taiwan-type tea” are produced and imported to Taiwan, causing a dramatic damage in the tea industry. It is very urgent to develop the stable, fast and reliable DNA markers for fingerprinting tea cultivars in Taiwan and protecting intellectual property rights for breeders. Furthermore, genetic diversity and phylogenetic relationship evaluations of tea germplasm in Taiwan are imperative for parental selection in the cross-breeding program and avoidance of genetic vulnerability.

Results
Two STS and 37 CAPS markers derived from cytoplasmic genome and ESTs of tea have been developed in this study providing a useful tool for distinguishing all investigated germplasm. For identifying 12 prevailing tea cultivars in Taiwan, five core markers, including each one of mitochondria and chloroplast, and three nuclear markers, were developed. Based on principal coordinate analysis and cluster analysis, 55 tea germplasm in Taiwan were divided into three groups: sinensis type (C. sinensis var. sinensis), assamica type (C. sinensis var. assamica) and Taiwan wild species (C. formosensis). The result of genetic diversity analysis revealed that both sinensis (0.44) and assamica (0.41) types had higher genetic diversity than wild species (0.25). The close genetic distance between the first (Chin-Shin-Oolong) and the third (Shy-Jih-Chuen) prevailing cultivars was found, and many recently released varieties are the descents of Chin-Shin-Oolong. This implies the potential risk of genetic vulnerability for tea cultivation in Taiwan.

Conclusions
We have successfully developed a tool for tea germplasm discrimination and genetic diversity analysis, as well as a set of core markers for effective identification of prevailing cultivars in Taiwan. According to the results of phylogenetic analysis on prevailing tea cultivars, it is necessary to broaden genetic diversity from wild species or plant introduction in future breeding programs.
Development of an Immunoassay for the Kidney-Specific Protein myo-Inositol Oxygenase, a Potential Biomarker of Acute Kidney Injury
Authors: Gaut Joseph P , Crimmins Dan L , Ohlendorf Matt F , Lockwood Christina M , Griest Terry A , Brada Nancy A , Hoshi Masato , Sato Bryan , Hotchkiss Richard S , Jain Sanjay , Ladenson Jack H 
Published: February 2014

Abstract

BACKGROUND
Acute kidney injury (AKI) affects 45% of critically ill patients, resulting in increased morbidity and mortality. The diagnostic standard, plasma creatinine, is nonspecific and may not increase until days after injury. There is significant need for a renal-specific AKI biomarker detectable early enough that there would be a potential window for therapeutic intervention. In this study, we sought to identify a renal-specific biomarker of AKI.

METHODS
We analyzed gene expression data from normal mouse tissues to identify kidney-specific genes, one of which was Miox. We generated monoclonal antibodies to recombinant myo-inositol oxygenase (MIOX) and developed an immunoassay to quantify MIOX in plasma. The immunoassay was tested in animals and retrospectively in patients with and without AKI.

RESULTS
Kidney tissue specificity of MIOX was supported by Western blot. Immunohistochemistry localized MIOX to the proximal renal tubule. Serum MIOX, undetectable at baseline, increased 24 h following AKI in mice. Plasma MIOX was increased in critically ill patients with AKI [mean (SD) 12.4 (4.3) ng/mL, n = 42] compared with patients without AKI [0.5 (0.3) ng/mL, n = 17] and was highest in patients with oliguric AKI [20.2 (7.5) ng/mL, n = 23]. Plasma MIOX increased 54.3 (3.8) h before the increase in creatinine.

CONCLUSIONS
MIOX is a renal-specific, proximal tubule protein that is increased in serum of animals and plasma of critically ill patients with AKI. MIOX preceded the increases in creatinine concentration by approximately 2 days in human patients. Large-scale studies are warranted to further investigate MIOX as an AKI biomarker.
Effect of supplemental vitamin D and calcium on serum sclerostin levels
Authors: Dawson-Hughes Bess , Harris Susan S , Ceglia Lisa , Palermo Nancy J 
Published: February 2014

ObjectiveSerum sclerostin levels have been reported to be inversely associated with serum 25OHD levels, but the effect of vitamin D and calcium supplementation on serum sclerostin levels is unknown. This study was carried out to determine whether vitamin D and calcium supplementation altered serum sclerostin levels in healthy older adults.DesignWe measured serum sclerostin levels at baseline and after 2 years in 279 men and women who participated in a placebo-controlled vitamin D (700 IU/day) and calcium (500 mg/day) intervention trial carried out in men and women aged ≥65 years.MethodSerum sclerostin levels were measured using the MesoScale Discovery chemiluminescence assay.ResultsIn the men, sclerostin levels increased over 2 years by 4.11±1.81 ng/l (13.1%) in the vitamin D plus calcium-supplemented group and decreased by 3.16±1.78 ng/l (10.9%) in the placebo group (P=0.005 for difference in change). Adjustments for the season of measurement, baseline physical activity levels, baseline serum sclerostin levels, and total body bone mineral content did not substantially alter the changes. In the women, there was no significant group difference in change in serum sclerostin levels either before or after the above-mentioned adjustments. In both the sexes, vitamin D and calcium supplementation significantly increased serum ionized calcium levels and decreased parathyroid hormone levels.ConclusionMen and women appear to have different serum sclerostin responses to vitamin D and calcium supplementation. The reason for this difference remains to be determined.
Stability characteristic of hypersonic flow over a blunt wedge under freestream pulse wave
Authors: Tang Xiaojun , Lv Hongqing , Meng Xiangnan , Wang Zhenqing , Lv Qin 
Published: February 2014

AbstractTo investigate the stability characteristic of hypersonic flow under the action of a freestream pulse wave, a high-order finite difference method was employed to do direction numerical simulation (DNS) of hypersonic unsteady flow over an 8° half-wedge-angle blunt wedge with freestream slow acoustic wave. The evolution of disturbance wave modes in the boundary layer under a pulse wave and a continuous wave are compared, and the wall temperature effect on the hypersonic boundary layer stability for a pulse wave disturbance is discussed. Results show that, both for a pulse wave and a continuous wave in freestream, the disturbance waves inside the nose boundary layer are mainly a fundamental mode; the Fourier amplitude of pressure disturbance mode in the boundary layer for a pulse wave is far less than that for a continuous wave, and the band frequency of the former is wider than that of the latter. All disturbance modes decay rapidly along the streamwise in the nose boundary layer. In the non-nose boundary layer, the dominant mode is transferred from fundamental mode into second harmonic. The transformation of dominant mode for a pulse wave appears much earlier than that for a continuous wave. Different frequency disturbance modes present different changes along streamline in the boundary layer, and the frequency band narrows around the second harmonic mode along the streamwise. Keen competition and the transformation of energy exist among different modes in the boundary layer. Wall temperature modifies the stability characteristic of the hypersonic boundary layer, which presents little effect on the development of fundamental modes and cooling wall could accelerates the growth of the high frequency mode as well as the dominant mode transformation.
Cosmological sigma model with non-minimal coupling to the target space
Authors: Shchigolev Victor 
Published: February 2014

AbstractA homogeneous and isotropic Universe in the framework of a nonlinear sigma model with non-minimal coupling to the target space is considered. Preliminary investigation of a two-component model of this sort is conducted. Some solutions for this model are given. Perspectives and directions of development of such a sort of models are discussed.