bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altering the selection capabilities of common cloning vectors via restriction enzyme mediated gene disruption
Authors: Manna Sam , Harman Ashley , Accari Jessica , Barth Christian 
Published: March 2013

Abstract

Background
The cloning of gene sequences forms the basis for many molecular biological studies. One important step in the cloning process is the isolation of bacterial transformants carrying vector DNA. This involves a vector-encoded selectable marker gene, which in most cases, confers resistance to an antibiotic. However, there are a number of circumstances in which a different selectable marker is required or may be preferable. Such situations can include restrictions to host strain choice, two phase cloning experiments and mutagenesis experiments, issues that result in additional unnecessary cloning steps, in which the DNA needs to be subcloned into a vector with a suitable selectable marker.

Results
We have used restriction enzyme mediated gene disruption to modify the selectable marker gene of a given vector by cloning a different selectable marker gene into the original marker present in that vector. Cloning a new selectable marker into a pre-existing marker was found to change the selection phenotype conferred by that vector, which we were able to demonstrate using multiple commonly used vectors and multiple resistance markers. This methodology was also successfully applied not only to cloning vectors, but also to expression vectors while keeping the expression characteristics of the vector unaltered.

Conclusions
Changing the selectable marker of a given vector has a number of advantages and applications. This rapid and efficient method could be used for co-expression of recombinant proteins, optimisation of two phase cloning procedures, as well as multiple genetic manipulations within the same host strain without the need to remove a pre-existing selectable marker in a previously genetically modified strain.
Enhancing sorafenib-mediated sensitization to gemcitabine in experimental pancreatic cancer through EMAP II
Authors: Awasthi Niranjan , Zhang Changhua , Hinz Stefan , Schwarz Margaret A , Schwarz Roderich E 
Published: March 2013

Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies and tends to be relatively resistant to conventional therapies. Activated Ras oncogene mutations are found in up to 90% of PDAC, leading to activation of the Ras/Raf/MEK/ERK signaling pathway. Sorafenib is a multikinase inhibitor of the Ras/Raf/MEK/ERK pathway and of tumor angiogenesis. Endothelial monocyte activating polypeptide II (EMAP) enhances gemcitabine effects in PDAC. Antitumor activity of sorafenib was evaluated in combination with gemcitabine (Gem) and the antiangiogenic agent EMAP in experimental PDAC.

Methods
Cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. Animal survival studies were performed in murine PDAC xenografts.

Results
Sorafenib decreased phospho-MEK, phospho-ERK1/2, phospho-p70S6K and phospho-4EBP-1 expression in PDAC cells. Sorafenib inhibited in vitro proliferation of all four PDAC cell lines tested. Additive effects on cell proliferation inhibition were observed in the gemcitabine-sorafenib combination in PDAC cells, and in combinations of sorafenib or EMAP with gemcitabine in endothelial (HUVEC) and fibroblast (WI-38) cells. Sorafenib, alone or in combination with gemcitabine and EMAP, induced apoptosis in HUVECs and WI-38 cells as observed via increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. Compared to controls (median survival: 22 days), animal survival increased after Gem therapy (29 days) but not in sorafenib (23 days) or EMAP therapy alone (25 days). Further increases in survival occurred in combination therapy groups Gem+sorafenib (30 days, p=0.004), Gem+EMAP (33 days, p=0.002), and Gem+sorafenib+EMAP (36 days, p=0.004), but not after the sorafenib+EMAP combination (24 days).

Conclusions
These findings demonstrate that the addition of a polymechanistic antiangiogenic agent such as EMAP can enhance the combination treatment effects of sorafenib and cytotoxic PDAC therapy.
Cell division promotes efficient retrotransposition in a stable L1 reporter cell line
Authors: Xie Yi , Mates Lajos , Ivics Zoltán , Izsvák Zsuzsanna , Martin Sandra L , An Wenfeng 
Published: March 2013

Abstract

Background
Long interspersed element type one (L1) actively modifies the human genome by inserting new copies of itself. This process, termed retrotransposition, requires the formation of an L1 ribonucleoprotein (RNP) complex, which must enter the nucleus before retrotransposition can proceed. Thus, the nuclear import of L1 RNP presents an opportunity for cells to regulate L1 retrotransposition post-translationally. The effect of cell division on L1 retrotransposition has been investigated by two previous studies, which observed varied degrees of inhibition in retrotransposition when primary cell strains or cancer cell lines were experimentally arrested in different stages of the cell cycle. However, seemingly divergent conclusions were reached. The role of cell division on retrotransposition remains highly debated.

Findings
To monitor both L1 expression and retrotransposition quantitatively, we developed a stable dual-luciferase L1 reporter cell line, in which a bi-directional tetracycline-inducible promoter drives the expression of both a firefly luciferase-tagged L1 element and a Renilla luciferase, the latter indicative of the level of promoter induction. We observed an additional 10-fold reduction in retrotransposition in cell-cycle arrested cells even after retrotransposition had been normalized to Renilla luciferase or L1 ORF1 protein levels. In synchronized cells, cells undergoing two mitoses showed 2.6-fold higher retrotransposition than those undergoing one mitosis although L1 expression was induced for the same amount of time.

Conclusions
Our data provide additional support for an important role of cell division in retrotransposition and argue that restricting the accessibility of L1 RNP to nuclear DNA could be a post-translational regulatory mechanism for retrotransposition.
Enhancing Wi-Fi fingerprinting for indoor positioning using human-centric collaborative feedback
Authors: Luo Yan , Hoeber Orland , Chen Yuanzhu 
Published: March 2013

Abstract
Position information is an important aspect of a mobile device’s context. While GPS is widely used to provide location information, it does not work well indoors. Wi-Fi network infrastructure is found in many public facilities and can be used for indoor positioning. In addition, the ubiquity of Wi-Fi-capable devices makes this approach especially cost-effective.
In recent years, “folksonomy”-like systems such as Wikipedia or Delicious Social Bookmarking have achieved huge successes. User collaboration is the defining characteristic of such systems. For indoor positioning mechanisms, it is also possible to incorporate collaboration in order to improve system performance, especially for fingerprinting-based approaches.
In this article, a robust and efficient model is devised for integrating human-centric collaborative feedback within a baseline Wi-Fi fingerprinting-based indoor positioning system. Experiments show that the baseline system performance (i.e., positioning error and precision) is improved by collecting both positive and negative feedback from users. Moreover, the feedback model is robust with respect to malicious feedback, quickly self-correcting based on subsequent helpful feedback from users.
Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses' Health Study II
Authors: Fortner Renée T , Eliassen A Heather , Spiegelman Donna , Willett Walter C , Barbieri Robert L , Hankinson Susan E 
Published: March 2013

Abstract
Introduction
Prior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women.

Methods
We evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses.

Results
In analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9), Ptrend = 0.02). Luteal estrone, free estradiol and progesterone were not associated with risk. Androgens were suggestively or significantly associated with risk when the sample was restricted to invasive tumors (for example, testosterone: OR: 1.4 (1.0 to 2.0), Ptrend = 0.23) and ER+/PR+ disease (testosterone: OR: 1.7 (1.1 to 2.6) Ptrend = 0.10; dehydroepiandrosterone sulfate (DHEAS) OR: 1.3 (0.8 to 2.0) Ptrend = 0.05). SHBG was not associated with breast cancer risk. The results varied by menopausal status at diagnosis, with follicular estradiol suggestively positively associated with breast cancers in women premenopausal at diagnosis (OR: 1.1 (0.9 to 1.3) and significantly inversely associated with postmenopausal disease (OR: 0.6 (0.4 to 0.9); Pheterogeneity < 0.01).

Conclusions
Androgens were associated with modestly increased risk of breast cancer in this population, with stronger associations for invasive and ER+/PR+ disease. Luteal phase estradiol levels were suggestively associated with ER+/PR+ tumors but no other strong associations were observed with estrogens. Associations with follicular phase estrogens may vary by menopausal status at diagnosis, but case numbers were limited. Additional studies to confirm the role of premenopausal hormones in the etiology of both premenopausal and postmenopausal breast cancer are needed.
Cethromycin: A New Ketolide Antibiotic
Authors: Mansour Hanine , Chahine Elias B , Karaoui Lamis R , El-Lababidi Rania M 
Published: March 2013

OBJECTIVE To review the pharmacology, chemistry, microbiology, in vitro susceptibility, mechanism of resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, drug interactions, dosage, and administration of cethromycin, a new ketolide antibiotic. DATA SOURCES Literature was obtained through searching PubMed (1950-October 2012), International Pharmaceutical Abstracts (1970-October 2012), and a bibliographic review of published articles. Search terms included cethromycin, ABT-773, ketolide antibiotic, and community-acquired pneumonia. STUDY SELECTION AND DATA EXTRACTION All available in vitro and preclinical studies, as well as Phase 1, 2, and 3 clinical studies published in English were evaluated to summarize the pharmacology, chemistry, microbiology, efficacy, and safety of cethromycin in the treatment of respiratory tract infections. DATA SYNTHESIS Cethromycin, a new ketolide, has a similar mechanism of action to telithromycin with an apparently better safety profile. Cethromycin displays in vitro activity against selected gram-positive, gram-negative, and atypical bacteria. The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older. Based on clinical studies, the recommended dose is 300 mg orally once a day without regard to meals. Cethromycin has an orphan drug designation for tularemia, plague, and anthrax prophylaxis. The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009; a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin. Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-related. CONCLUSIONS Cethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia. It was denied approval by the FDA in 2009 pending more evidence to show its efficacy, with more recent studies showing its noninferiority to antibiotics for the same indication.
Parental Expectations Regarding Postschool Social Attainments of Adolescents with Autism Spectrum Disorders in Singapore
Authors: Poon Kenneth K. 
Published: March 2013

Abstract
This study sought to understand the parental expectations of social attainments in the postschool years. The parents of 20 adolescents with autism spectrum disorders (ASD) attending special schools were interviewed. Most expected their children would be working in sheltered workshops or unemployed. All parents indicated that their children would live with them until they were unable to provide appropriate care, and nearly half expressed wishes for relatives to care for them thereafter. None expected any independent access to the community. Analysis of the interviews suggested that the adolescents' learning and behavior, parental concerns, availability of formal resources, and societal factors influenced parents' expectations. Implications for working with Asian populations and for service delivery in Singapore are discussed.
Perpetual American options in a diffusion model with piecewise-linear coefficients
Authors: Gapeev Pavel V. , Rodosthenous Neofytos 
Published: March 2013

Abstract
We derive closed form solutions to the discounted optimal stopping problems related to the pricing of the perpetual American standard put and call options in an extension of the Black–Merton–Scholes model with piecewise-constant dividend and volatility rates. The method of proof is based on the reduction of the initial optimal stopping problems to the associated free-boundary problems and the subsequent martingale verification using a local time-space formula. We present explicit algorithms to determine the constant hitting thresholds for the underlying asset price process, which provide the optimal exercise boundaries for the options.
Coupled microstructural-compositional evolution informed by a thermodynamic database using the hybrid Potts-phase field model
Authors: Cox Jordan J. , Homer Eric R. , Tikare Veena 
Published: March 2013

ABSTRACTA recently introduced hybrid Potts-phase field method has demonstrated the ability to evolve microstructures in conjunction with compositional fields tied to different phases. In this approach, Monte Carlo Potts methods are used to evolve the microstructure while phase field methods are used to evolve the composition, and the two fields are coupled through free energy functionals. Recent developments of the model allow different multi-component alloy systems to be simulated by using thermodynamic databases and kinetic quantities to dictate the behavior. An example of the method using the aluminum-silicon binary system is demonstrated.
ON ENABLING NANOCRYSTALLINE DIAMOND FOR DEVICE USE: NOVEL ION BEAM METHODOLOGY AND THE REALIZATION OF SHALLOW N-TYPE DIAMOND
Authors: Khan A.H. , Sumant A.V. 
Published: March 2013

AbstractDespite the many superior attributes of diamond, electronic device performance to date has fallen well behind theoretical expectation. The potential realization of highly efficient electronic polycrystalline diamond devices has been more than limited by certain technological challenges such as maintaining efficient/shallow n-type doping without higher density of defects or incorporation of sp2 bonded carbon as a result of doping(during ion implantation process). Specific n-type diamond reports demonstrating phosphorus doping (with activation energy reported in the range of 485 meV to 600 meV in (100) oriented systems have been particularly problematic as a lower solubility is found as compared to (111) oriented synthesis efforts, in addition to the reported self-compensating nature. Amongst the previous reports of Phosphorus-doped diamond nearly all experimental reports to date show visual crystallographic dislocation/pitting on the (100) facet with even moderate doping where dislocations have been observed to be incorporated into the bulk volume during growth. These dislocations, which are known carrier scattering sites, subsequently lower mobility rendering poor conductance and high resistivity. Due to this well-known sensitivity of phosphorus incorporation to the crystal quality, typically lower in polycrystalline than homoepitaxial films, polycrystalline-based experimental reports have been largely absent. With respect to Phosphorus in-situ doping based efforts, rendered films demonstrate both the visually identifiable pitting and electronically identifiable poor conduction characteristic, and with respect to ion beam doping efforts, complete graphitic flaking at even moderate doses (i.e. greater than 3x1017cm−3). Motivated by these shortcomings and the success of recent experimentation, we present the methodology and data from our recent successful fabrication of polycrystalline diamond P+-i-N junction (diode) with high crystal quality, high power handling capability, high current density, low threshold voltage, and ohmic contact, under room temperature operation, previously undemonstrated across all diamond material types. The superior electrical performance of the device was obtained by novel ion beam methodology designed to resolve previously unaddressed issues relating to n-type doping of diamond materials. A high current density of approximately 104 A/cm2 is attained at 20V forward bias.
Fabrication of Large-Area Organic Photovoltaics Using a Draw-Bar Coating Technique
Authors: Mulligan Cara J. , Nicolaidis Nicolas C. , Vaughan Ben , Zhou Xiaojing , Belcher Warwick J. , Dastoor Paul C. 
Published: March 2013

ABSTRACTOrganic photovoltaic (OPV) devices were fabricated using a novel draw bar premetered coating technique, whereby a meniscus of fluid is dragged across a substrate to leave a trailing wet film. The results showed that coating thickness could be controlled by varying the coating speed, rod diameter, gap height, amount of solution injected, rod diameter, rod composition material and number of layers. Devices on PET with active areas of 10 cm2 and active layer thicknesses ranging from 35 to 475 nm were produced using the technique. Active layers of 160 nm were the optimum of thicknesses trialled, achieving typical best efficiencies around 0.4 %. Devices with films thinner than 90 nm did not function due to short-circuiting. The draw-bar coating method has the advantage of allowing controlled deposition of a wide range of film thicknesses with no solution wastage.
Development of a Coupled Dual Continuum and Discrete Fracture Model for the Simulation of Unconventional Reservoirs
Authors: Moinfar Ali , Varavei Abdoljalil , Sepehrnoori Kamy , Johns Russell T. 
Published: March 2013

Abstract
Accurate modeling of hydrocarbon production is a necessary, yet challenging step for economic exploitation of unconventional resources. One of the main challenges is to model flow to a horizontal well from a complex network of hydraulic and natural fractures. Many unconventional reservoirs comprise well-developed natural fracture networks with multiple orientations and complex hydraulic fracture patterns based on microseismic data. Conventional dual porosity and dual permeability models are not adequate for modeling these complex networks of natural and hydraulic fractures. Also, it is neither practical nor advantageous to model a large number of pre-existing fractures with a discrete fracture model. Therefore, an appropriate approach to model production from low-permeability reservoirs is to perform discrete fracture modeling for hydraulic fractures and employ a dual continuum approach for numerous natural fractures.
We have developed a coupled dual continuum and discrete fracture method to simulate production from unconventional oil and gas reservoirs. Large-scale hydraulic fractures (macro-fractures) are modeled explicitly using a discrete fracture model, called EDFM, and numerous small-scale natural fractures (micro-fractures) are modeled using a dual continuum approach. The hybrid model includes three domains: matrix, discrete-fracture, and continuum-fracture domains. A systematic approach is devised to calculate transport parameters between all three domains. Moreover, EDFM allows for not only transverse and longitudinal hydraulic fractures but also macro-fractures of any orientation. Thus, the coupled model provides an effective and reliable environment to improve stimulation designs and completion strategies.
We present several examples in this study to show the applicability, robustness, and performance of the hybrid method for the simulation of unconventional oil and gas reservoirs. We examine multi-stage hydraulic fractures with multiple configurations in the presence of numerous pre-existing fractures. Simulations show a noticeable contribution from natural fracture networks on total production. Furthermore, for the tight oil reservoir examined in this study, the stimulation scheme with longer hydraulic fractures improves cumulative oil production compared to the scheme with larger number of shorter hydraulic fractures. We also examine production from a tight gas reservoir wherein hydraulic fractures partially penetrate the formation height. Simulations indicate that inefficient fracture treatment can result in significant loss of production.