bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technology Disruption in the Simulation Industry
Authors: Smith Roger 
Published: June 2009

The military simulation industry has been transformed by technological advances multiple times in its history. In some cases those changes have come from within the industry, and in others they have been introduced from outside of the mainstream and have disrupted the established status quo. These external disruptions have traditionally made significant contributions to the state of the art in the field. However, in doing so they have negated millions of dollars in government funding that could have been more valuably applied had the sponsors understood the disruptive forces that were at work. These events have also overturned a number of leading companies in the field and replaced them with upstarts whose technology contained the seeds for future advances. In this paper, we explore the impact that computer game technologies are having on the simulation industry. These technologies initially provided low-end capabilities for a small niche of the industry. However, over time they have improved to the point that they are more powerful than many of the established tools in the field. This disruption is following the well-established innovation model that was put forward by Harvard professor Clayton Christensen. Game technologies entered the industry as a “toy” application, but they now offer the foundation upon which the next generation of successful systems will be built. PC game technologies are just one of the waves of disruption that are entering and will permanently change the simulation industry. Future disruptions will arise from game consoles, web-based 3-D environments, and wireless technologies. These disruptions will spur the growth of new types of companies and threaten the positions of established companies in the industry. There are technological and economical forces at work in the gaming and military simulation markets that will create a wave of change throughout the industry. This wave will spread cheaper, more powerful, and more accessible simulations and simulators across the modern military.
2-phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells
Authors: Steele Andrew J. , Prentice Archibald G. , Hoffbrand A. Victor , Yogashangary Birunthini C. , Hart Stephen M. , Lowdell Mark W. , Samuel Edward R. , North Janet M. , Nacheva Elisabeth P. , Chanalaris Anastasios , Kottaridis Panagiotis , Cwynarski Kate , Wickremasinghe R. Gitendra 
Published: June 2009

Abstract
We studied the actions of 2-phenylacetylenesulfonamide (PAS) on B-chronic lymphocytic leukemia (CLL) cells. PAS (5-20 μM) initiated apoptosis within 24 hours, with maximal death at 48 hours asassessed by morphology, cleavage of poly(ADP-ribose) polymerase (PARP), caspase 3 activation, and annexin V staining. PAS treatment induced Bax proapoptotic conformational change, Bax movement from the cytosol to the mitochondria, and cytochrome c release, indicating that PAS induced apoptosis via the mitochondrial pathway. PAS induced approximately 3-fold up-regulation of proapoptotic Noxa protein and mRNA levels. In addition, Noxa was found unexpectedly to be bound to Bcl-2 in PAS-treated cells. PAS treatment of CLL cells failed to up-regulate p53, suggesting that PAS induced apoptosis independently of p53. Furthermore, PAS induced apoptosis in CLL isolates with p53 gene deletion in more than 97% of cells. Normal B lymphocytes were as sensitive to PAS-induced Noxa up-regulation and apoptosis as were CLL cells. However, both T lymphocytes and bone marrow hematopoietic progenitor cells were relatively resistant to PAS. Our data suggest that PAS may represent a novel class of drug that induces apoptosis in CLL cells independently of p53 status by a mechanism involving Noxa up-regulation.
TIPT2 and geminin interact with basal transcription factors to synergize in transcriptional regulation
Authors: Pitulescu Mara E , Teichmann Martin , Luo Lingfei , Kessel Michael 
Published: June 2009

AbstractBackgroundThe re-replication inhibitor Geminin binds to several transcription factors including homeodomain proteins, and to members of the polycomb and the SWI/SNF complexes.ResultsHere we describe the TATA-binding protein-like factor-interacting protein (TIPT) isoform 2, as a strong binding partner of Geminin. TIPT2 is widely expressed in mouse embryonic and adult tissues, residing both in cyto- and nucleoplasma, and enriched in the nucleolus. Like Geminin, also TIPT2 interacts with several polycomb factors, with the general transcription factor TBP (TATA box binding protein), and with the related protein TBPL1 (TRF2). TIPT2 synergizes with geminin and TBP in the activation of TATA box-containing promoters, and with TBPL1 and geminin in the activation of the TATA-less NF1 promoter. Geminin and TIPT2 were detected in the chromatin near TBP/TBPL1 binding sites.ConclusionTogether, our study introduces a novel transcriptional regulator and its function in cooperation with chromatin associated factors and the basal transcription machinery.
"PolyMin": software for identification of the minimum number of polymorphisms required for haplotype and genotype differentiation
Authors: Frei Ursula K , Wollenweber Bernd , Lübberstedt Thomas 
Published: June 2009

Abstract

Background
Analysis of allelic variation for relevant genes and monitoring chromosome segment transmission during selection are important approaches in plant breeding and ecology. To minimize the number of required molecular markers for this purpose is crucial due to cost and time constraints. To date, software for identification of the minimum number of required markers has been optimized for human genetics and is only partly matching the needs of plant scientists and breeders. In addition, different software packages with insufficient interoperability need to be combined to extract this information from available allele sequence data, resulting in an error-prone multi-step process of data handling.

Results

PolyMin, a computer program combining the detection of a minimum set of single nucleotide polymorphisms (SNPs) and/or insertions/deletions (INDELs) necessary for allele differentiation with the subsequent genotype differentiation in plant populations has been developed. Its efficiency in finding minimum sets of polymorphisms is comparable to other available program packages.

Conclusion
A computer program detecting the minimum number of SNPs for haplotype discrimination and subsequent genotype differentiation has been developed, and its performance compared to other relevant software. The main advantages of PolyMin, especially for plant scientists, is the integration of procedures from sequence analysis to polymorphism selection within a single program, including both haplotype and genotype differentiation.
High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery
Authors: Cervantes Serena , Prudhomme Jacques , Carter David , Gopi Krishna G , Li Qian , Chang Young-Tae , Le Roch Karine G 
Published: June 2009

Abstract

Background
Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS) to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes.

Results
After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells.

Conclusion
This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.
A mitotic recombination map proximal to the APC locus on chromosome 5q and assessment of influences on colorectal cancer risk
Authors: Howarth Kimberley , Ranta Susanna , Winter Eitan , Teixeira Ana , Schaschl Helmut , Harvey John J , Rowan Andrew , Jones Angela , Spain Sarah , Clark Susan , Guenther Thomas , Stewart Aengus , Silver Andrew , Tomlinson Ian 
Published: June 2009

Abstract

Background
Mitotic recombination is important for inactivating tumour suppressor genes by copy-neutral loss of heterozygosity (LOH). Although meiotic recombination maps are plentiful, little is known about mitotic recombination. The APC gene (chr5q21) is mutated in most colorectal tumours and its usual mode of LOH is mitotic recombination.

Methods
We mapped mitotic recombination boundaries ("breakpoints") between the centromere (~50 Mb) and APC (~112 Mb) in early colorectal tumours.

Results
Breakpoints were non-random, with the highest frequency between 65 Mb and 75 Mb, close to a low copy number repeat region (68–71 Mb). There were, surprisingly, few breakpoints close to APC, contrary to expectations were there constraints on tumorigenesis caused by uncovering recessive lethal alleles or if mitotic recombination were mechanistically favoured by a longer residual chromosome arm. The locations of mitotic and meiotic recombination breakpoints were correlated, suggesting that the two types of recombination are influenced by similar processes, whether mutational or selective in origin. Breakpoints were also associated with higher local G+C content. The recombination and gain/deletion breakpoint maps on 5q were not, however, associated, perhaps owing to selective constraints on APC dosage in early colorectal tumours. Since polymorphisms within the region of frequent mitotic recombination on 5q might influence the frequency of LOH, we tested the 68–71 Mb low copy number repeat and nearby tagSNPs, but no associations with colorectal cancer risk were found.

Conclusion
LOH on 5q is non-random, but local factors do not greatly influence the rate of LOH at APC or explain inter differential susceptibility to colorectal tumours.
Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats
Authors: Trias Elman L , Hassantoufighi Arash , Prince Gregory A , Eichelberger Maryna C 
Published: June 2009

AbstractBackgroundIncreased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (Sigmodon hispidus) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.MethodsLung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.ResultsAdult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (Penh) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute toPenhwere different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase inPenhin infant animals.ConclusionWhile respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.
Comparison and prediction of pullout strength of conical and cylindrical pedicle screws within synthetic bone
Authors: Tsai Wen-Chi , Chen Po-Quang , Lu Tung-Wu , Wu Shing-Sheng , Shih Kao-Shang , Lin Shang-Chih 
Published: June 2009

Abstract

Background
This study was designed to derive the theoretical formulae to predict the pullout strength of pedicle screws with an inconstant outer and/or inner diameter distribution (conical screws). For the transpedicular fixation, one of the failure modes is the screw loosening from the vertebral bone. Hence, various kinds of pedicle screws have been evaluated to measure the pullout strength using synthetic and cadaveric bone as specimens. In the literature, the Chapman's formula has been widely proposed to predict the pullout strength of screws with constant outer and inner diameters (cylindrical screws).

Methods
This study formulated the pullout strength of the conical and cylindrical screws as the functions of material, screw, and surgery factors. The predicted pullout strength of each screw was compared to the experimentally measured data. Synthetic bones were used to standardize the material properties of the specimen and provide observation of the loosening mechanism of the bone/screw construct.

Results
The predicted data from the new formulae were better correlated with the mean pullout strength of both the cylindrical and conical screws within an average error of 5.0% and R
2 = 0.93. On the other hand, the average error and R
2 value of the literature formula were as high as -32.3% and -0.26, respectively.

Conclusion
The pullout strength of the pedicle screws was the functions of bone strength, screw design, and pilot hole. The close correlation between the measured and predicted pullout strength validated the value of the new formulae, so as avoid repeating experimental tests.
Dermoscopy as a technique for the early identification of foot melanoma
Authors: Bristow Ivan R , Bowling Jonathan 
Published: June 2009

AbstractMalignant melanoma is the most common primary malignant tumour arising on the foot. Where improvements in the prognosis have been observed for patients with melanoma elsewhere on the skin, pedal lesions are still frequently delayed in presentation through neglect or misdiagnosis. Detection of foot melanoma relies on the health care practitioner's skills and observations in recognising early changes. Recent publications have documented the use a dermoscopy as a tool to improve recognition of such suspicious lesions. This paper reviews current literature with a special emphasis of its potential applications on plantar and nail unit melanoma. Data from these studies suggest that the technique is a useful and significant adjunct to clinical examination, which ultimately may lead to earlier recognition of this aggressive tumour.
A geometric analysis of hallux valgus: correlation with clinical assessment of severity
Authors: Piqué‐Vidal Carlos , Vila Joan 
Published: June 2009

AbstractBackgroundApplication of plane geometry to the study of bunion deformity may represent an interesting and novel approach in the research field of hallux valgus. For the purpose of contributing to development of a different perspective in the assessment of hallux valgus, this study was conducted with three objectives: a) to determine the position on the intersection point of the perpendicular bisectors of the longitudinal axes of the first metatarsal and proximal phalanx (IP), b) to correlate the location of this point with hallux valgus deformity according to angular measurements and according to visual assessment of the severity carried out by three independent observers, and c) to assess whether this IP correlated with the radius of the first metatarsophalangeal arc circumference.MethodsMeasurements evaluated were intermetatarsal angle (IMA), hallux valgus angle (HVA), and proximal phalangeal articular angle (PPAA). The Autocad® program computed the location of the IP inside or outside of the foot. Three independent observers rated the severity of hallux valgus in photographs using a 100‐mm visual analogue scale (VAS).ResultsMeasurements of all angles except PPAA showed significantly lower values when the IP was located out of the foot more distantly and vice versa, significantly higher values for severe deformities in which the IP was found inside the foot (p < 0.001). The IP correlated significantly with VAS scores and with the length of the radius of the circle that included the first metatarsophalangeal arc circumference (p < 0.001)ConclusionThe IP is a useful indicator of hallux valgus deformity because correlated significantly with IMA and HVA measurements, VAS scores obtained by visual inspection of the degree of deformity, and location of the center of the first metatarsophalangeal arc circumference.
The p.A2215D Thyroglobulin Gene Mutation Leads to Deficient Synthesis and Secretion of the Mutated Protein and Congenital Hypothyroidism with Wide Phenotype Variation
Authors: Pardo Viviane , Vono-Toniolo Jussara , Rubio Ileana G. S. , Knobel Meyer , Possato Roberta F. , Targovnik Hector M. , Kopp Peter , Medeiros-Neto Geraldo 
Published: June 2009

Context: Thyroglobulin (TG) is a large glycoprotein and functions as a matrix for thyroid hormone synthesis. TG gene mutations give rise to goitrous congenital hypothyroidism (CH) with considerable phenotype variation.Objectives: The aim of the study was to report the genetic screening of 15 patients with CH due to TG gene mutations and to perform functional analysis of the p.A2215D mutation.Design: Clinical evaluation and DNA sequencing of the TG gene were performed in all patients. TG expression was analyzed in the goitrous tissue of one patient. Human cells were transfected with expression vectors containing mutated and wild-type human TG cDNA.Results: All patients had an absent rise of serum TG after stimulation with recombinant human TSH. Sequence analysis revealed three previously described mutations (p.A2215D, p.R277X, and g.IVS30+1G&gt;T), and two novel mutations (p.Q2142X and g.IVS46-1G&gt;A). Two known (g.IVS30+1G/p.A2215D and p.A2215D/p.R277X) and one novel (p.R277X/g.IVS46-1G&gt;A) compound heterozygous constellations were also identified. Functional analysis indicated deficiency in TG synthesis, reduction of TG secretion, and retention of the mutant TG within the cell, leading to an endoplasmic reticulum storage disease, whereas small amounts of mutant TG were still secreted within the cell system.Conclusion: All studied patients were either homozygous or heterozygous for TG gene mutations. Two novel mutations have been detected, and we show that TG mutation p.A2215D promotes the retention of TG within the endoplasmic reticulum and reduces TG synthesis and secretion, causing mild hypothyroidism. In the presence of sufficient iodine supply, some patients with TG mutations are able to compensate the impaired hormonogenesis and generate thyroid hormone.
Predictors of Pregnancy in Women with Polycystic Ovary Syndrome
Authors: Rausch Mary E. , Legro Richard S. , Barnhart Huiman X. , Schlaff William D. , Carr Bruce R. , Diamond Michael P. , Carson Sandra A. , Steinkampf Michael P. , McGovern Peter G. , Cataldo Nicholas A. , Gosman Gabriella G. , Nestler John E. , Giudice Linda C. , Leppert Phyllis C. , Myers Evan R. , Coutifaris Christos ,   for the Reproductive Medicine Network
Published: June 2009

Context: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. The selection of first-line therapies for ovulation induction is empiric.
Objective: The aim of the study was to develop a clinically useful predictive model of live birth with varying ovulation induction methods.
Design, Setting, and Participants: We built four prognostic models from a large multicenter randomized controlled infertility trial of 626 women with PCOS performed at academic health centers in the United States to predict success of ovulation, conception, pregnancy, and live birth, evaluating the influence of patients’ baseline characteristics.
Interventions: Ovulation was induced with clomiphene, metformin, or the combination of both for up to six cycles or conception.
Main Outcome Measure: The primary outcome of the trial was the rate of live births.
Results: Baseline free androgen index, baseline proinsulin level, interaction of treatment arm with body mass index, and duration of attempting conception were significant predictors in all four models. History of a prior loss predicted ovulation and conception, but not pregnancy or live birth. A modified Ferriman Gallwey hirsutism score of less than 8 was predictive of conception, pregnancy, and live birth (although it did not predict ovulation success). Age was a divergent predictor based on outcome; age greater than 34 predicted ovulation, whereas age less than 35 was a predictive factor for a successful pregnancy and live birth. Smoking history had no predictive value.
Conclusions: A live birth prediction chart developed from basic clinical parameters (body mass index, age, hirsutism score, and duration of attempting conception) may help physicians counsel and select infertility treatments for women with PCOS.
The probability of a live birth after ovulation induction in PCOS women can be estimated based on their age, body mass index, hirsutism, and duration of attempted conception.
Laus deorum e strutture inniche nei Panegirici latini di etá imperiale
Authors: La Bua Giuseppe 
Published: June 2009

Abstract
Latin prose Panegyrics are a fourth-century product of Gallic rhetorical schools; they celebrate the emperor's virtues by widely employing structures and topoi commonly associated with epideictic theory and practice. This paper explores the presence of hymnic features within the corpus of the Latin Panegyrics. The following passages are investigated: 1) the celebration of Diocletian and Maximian as Iovius and Herculius in Panegyrics 10(2).1–6 and 11(3).3; 2) the praise of the Tiber and the hymn to the supreme God in the Panegyric dedicated to Constantine 12(9).18; 26; 3) the hymn to Greece in the Panegyric to Julian 3(11).8. The analysis shows how the panegyrists re-worked the laudatory material by adapting the style and topoi of hymns to gods to praise of the emperor.