bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling time-dependent transcription effects of HER2 oncogene and discovery of a role for E2F2 in breast cancer cell-matrix adhesion
Authors: Bollig-Fischer Aliccia , Marchetti Luca , Mitrea Cristina , Wu Jiusheng , Kruger Adéle , Manca Vincenzo , Drăghici Sorin 
Published: July 2014

Abstract
Motivation: Oncogenes are known drivers of cancer phenotypes and targets of molecular therapies; however, the complex and diverse signaling mechanisms regulated by oncogenes and potential routes to targeted therapy resistance remain to be fully understood. To this end, we present an approach to infer regulatory mechanisms downstream of the HER2 driver oncogene in SUM-225 metastatic breast cancer cells from dynamic gene expression patterns using a succession of analytical techniques, including a novel MP grammars method to mathematically model putative regulatory interactions among sets of clustered genes.
Results: Our method highlighted regulatory interactions previously identified in the cell line and a novel finding that the HER2 oncogene, as opposed to the proto-oncogene, upregulates expression of the E2F2 transcription factor. By targeted gene knockdown we show the significance of this, demonstrating that cancer cell-matrix adhesion and outgrowth were markedly inhibited when E2F2 levels were reduced. Thus, validating in this context that upregulation of E2F2 represents a key intermediate event in a HER2 oncogene-directed gene expression-based signaling circuit. This work demonstrates how predictive modeling of longitudinal gene expression data combined with multiple systems-level analyses can be used to accurately predict downstream signaling pathways. Here, our integrated method was applied to reveal insights as to how the HER2 oncogene drives a specific cancer cell phenotype, but it is adaptable to investigate other oncogenes and model systems.
Availability and implementation: Accessibility of various tools is listed in methods; the Log-Gain Stoichiometric Stepwise algorithm is accessible at http://www.cbmc.it/software/Software.php .
Contact: bollig@karmanos.org
Supplementary information: Supplementary data are available at Bioinformatics online.
Margherita Datini
Authors: James Carolyn 
Published: July 2014

The 252 extant letters of Margherita Datini (b. 1360–d. 1423) to her husband, the merchant Francesco di Marco Datini (b. c. 1335–d. 1410), represent the largest collection of early Italian vernacular correspondence by a lay woman to have come to light. They are all the more unusual because Francesco’s letters to Margherita also survive, enabling us to follow a marital conversation that continued for almost three decades. The couple’s exchanges reveal a very different portrait of marriage than was envisaged by prescriptive texts of the period. Or rather, the letters provide evidence that Margherita and Francesco had a conventional enough view of how their relationship should be conducted, but the challenges of everyday life in an urban environment riven by factionalism and competitiveness forced them often to ignore the gender stereotypes of their day. Fourteenth-century advice manuals, such as Paola da Certaldo’s Libro di buoni costumi, described female virtue in narrow terms and demarcated the roles of husband and wife strictly, recommending that women be confined to the household and restrained from participating in men’s affairs. Margherita, however, collaborated in the supervision of Francesco’s building projects, even occasionally pursued the merchant’s debtors, and offered her husband shrewd advice, revealing the extent to which she was fully conversant with contemporary politics. She was cognizant of the need to participate in the social networking that was a fundamental feature of Florentine society and cultivated the magnate connections of her own aristocratic family to secure useful allies for the more humbly-born Francesco. Margherita’s inability to bear children was a source of bitter disappointment to the couple, but it indubitably facilitated her ability to take on a greater role in her husband’s affairs than was usual. The Datini couple’s letters also reveal many details about their households in Florence and Prato. The routines and experiences of the servants, neighbors, friends, and relatives with whom Margherita associated are documented in colloquial and evocative prose, providing a rare view of women’s social interactions and emotions in a period blighted by recurring outbreaks of plague, an unstable political climate, and difficult economic conditions.
Charlemagne
Authors: France John 
Published: July 2014

Historians have always been fascinated by the life of Charlemagne and, in particular, deeply concerned to explain the enormous expansion of his dominions. In 768 he became joint ruler of the Frankish lands, but the death of his brother Carloman in 771 left him as sole ruler of the whole realm of his father Pepin III (b. 741–d. 768). By 774 he had made inroads into Saxony, conquered the old kingdom of the Lombards, and dominated the Italian Peninsula. Campaigns in Spain later led to the establishment of a frontier zone against the Islamic power there, while a long and bitter conflict enabled him to annex the lands of the hostile Saxons and to enforce their conversion to Christianity. He even launched campaigns deep into Central Europe, destroying the Avar power in what we now call Hungary though without being able to conquer the area. However, the sources for his reign, and most especially for its military aspects, are very limited and often difficult to use (see Source Studies). These difficulties are enormously increased by the general tenor of writing on Charlemagne and certain specific controversies that bear upon his reign. Almost all studies of Charlemagne are admiring: the only real exception is that of The Carolingian Empire: The Age of Charlemagne (Fichtenau 1957, cited under the Reign of Charlemagne). Indeed, the legend of Charlemagne, born from such admiration, enormously complicates our perception, and it remains powerful to this day. In addition, a whole new way of looking at the transition from the ancient to the medieval world has been inspired by The World of Late Antiquity: From Marcus Aurelius to Muhammad (Brown 1971, cited under the Context of Charlemagne’s Reign), which posited a gradual and perhaps essentially peaceful transition from Roman to medieval. This matters for military history because an optimistic view of the survival of Roman institutions affects what one may think of the ability of Charlemagne to raise and sustain armies, and it also suggests a continuity of discipline of the standing armies of Rome. In short, how the history of early medieval Europe is understood profoundly influences the understanding of Charlemagne’s inheritance from the past and, most particularly, his military institutions and resources.
Hebrew
Authors: Sadan Tsvi , Schwarzwald Ora 
Published: July 2014

Hebrew belongs to the family of Semitic languages, which is part of the larger family of Afroasiatic languages. It spans more than three millennia, paralleling the history of the Jewish people—first in the Land of Israel, then in the Diaspora, and again in the Land of Israel and the State of Israel. It is customary to divide the language into the following four historical periods: Biblical Hebrew, Rabbinic Hebrew (also known as Mishnaic Hebrew), Medieval Hebrew, and Modern Hebrew (alternatively referred to as Contemporary Hebrew, Israeli Hebrew, or even simply Israeli). Two further divisions should also be noted: Hebrew of the Second Temple period, and oral traditions of Hebrew. Biblical Hebrew in its narrow sense (c. 1000–530 bce) is attested mainly in the pre-exilic books of the Hebrew Bible. Hebrew in the Second Temple period (530 bce–70 ce) is a transient stage between Biblical Hebrew and Rabbinic Hebrew; the post-exilic books of the Hebrew Bible and the Dead Sea Scrolls are its main corpora. Rabbinic Hebrew (70–c. 500 ce) is further divided, according to whether it was still spoken or not, into Tannaitic Hebrew or Rabbinic Hebrew I (70–c. 200 ce), which is the language of the Mishna, and Amoraic Hebrew or Rabbinic Hebrew II (c. 200–500 ce), which is the language of the Hebrew part of the Palestinian and Babylonian Talmuds. Medieval Hebrew (c. 500–c. 1850) includes various works of poetry and prose produced in major Jewish communities. Oral traditions of Hebrew refer to recitations of the Hebrew Bible and the Mishna in traditional Jewish communities after Biblical Hebrew and Rabbinic Hebrew ceased to be spoken; these traditions are still preserved among certain circles. Modern Hebrew in its narrow sense (c. 1850 to the present) is a planned and unplanned amalgam of the earlier phases of Hebrew (as well as Jewish Aramaic), with a heavy grammatical and lexical influence from Yiddish, Russian, etc. It now fulfills all the social functions of a modern society, both in speech and in writing as well as online. It is also an important lingua franca of Hebrew linguistics (and many other areas of Jewish studies). In each of these divisions of Hebrew, as well as in the first group of sections (dealing with the language in general), selected important works in the following areas are mentioned, where relevant: encyclopedia, introductory works, dictionaries, bibliographies, journals, collected works, history, writing system, language “revival,” grammar in general, (articulatory) phonetics, phonology, morphology, syntax, semantics, pragmatics, discourse analysis, (meta-)lexicography, onomastics, sociolinguistics, psycholinguistics, and the spoken language.
Bacillus subtilis attachment to Aspergillus niger hyphae results in mutually altered metabolism
Authors: Benoit Isabelle , van den Esker Marielle H. , Patyshakuliyeva Aleksandrina , Mattern Derek J. , Blei Felix , Zhou Miaomiao , Dijksterhuis Jan , Brakhage Axel A. , Kuipers Oscar P. , de Vries Ronald P. , Kovács Ákos T. 
Published: July 2014

SummaryInteraction between microbes affects the growth, metabolism and differentiation of members of the microbial community. While direct and indirect competition, like antagonism and nutrient consumption have a negative effect on the interacting members of the population, microbes have also evolved in nature not only to fight, but in some cases to adapt to or support each other, while increasing the fitness of the community. The presence of bacteria and fungi in soil results in various interactions including mutualism. Bacilli attach to the plant root and form complex communities in the rhizosphere. Bacillus subtilis, when grown in the presence of Aspergillus niger, interacts similarly with the fungus, by attaching and growing on the hyphae. Based on data obtained in a dual transcriptome experiment, we suggest that both fungi and bacteria alter their metabolism during this interaction. Interestingly, the transcription of genes related to the antifungal and putative antibacterial defence mechanism of B. subtilis and A. niger, respectively, are decreased upon attachment of bacteria to the mycelia. Analysis of the culture supernatant suggests that surfactin production by B. subtilis was reduced when the bacterium was co‐cultivated with the fungus. Our experiments provide new insights into the interaction between a bacterium and a fungus.
A follow‐up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months
Authors: Ijäs H , Vääräsmäki M , Saarela T , Keravuo R , Raudaskoski T 
Published: July 2014

ObjectiveTo compare the growth and development of children born to mothers with gestational diabetes mellitus (GDM) requiring pharmacological treatment, and randomised to treatment with metformin or insulin.DesignFollow‐up of a randomised controlled trial (RCT) comparing metformin and insulin treatment of GDM.SettingData were gathered during routine visits to child welfare clinics at the ages of 6, 12, and 18 months, including weight and height measurements, and assessment of motor, social, and linguistic development.SampleThe children of mothers with GDM randomised to metformin (n = 47) or insulin (n = 50) treatment during pregnancy.MethodsData were collected from the structured questionnaire filled in at the child welfare clinics.Main outcome measuresThe growth and development of the children until the age of 18 months.ResultsChildren exposed to metformin were significantly heavier (10.47 versus 9.85 kg, 95% CI 0.04–1.20) at the age of 12 months and taller and heavier (83.9 vs 82.2 cm, 95% CI 0.23–3.03, 12.05 vs 11.32 kg, 95% CI 0.04–1.43) at the age of 18 months. The mean ponderal index (PI) did not differ significantly. The motor, social, or linguistic development evaluated at the age of 18 months did not differ between the groups.ConclusionsChildren prenatally exposed to metformin were heavier at the 12 months measurements and taller and heavier at the 18 months measurements than those exposed to insulin, but their body composition defined by PI did not differ. Over the short term, metformin does not seem to be harmful with regards to early motor, linguistic, or social development.
Effect of Massachusetts Health Reform on Chronic Disease Outcomes
Authors: Stryjewski Tomasz P. , Zhang Fang , Eliott Dean , Wharam J. Frank 
Published: July 2014

ObjectiveTo determine whether Massachusetts Health Reform improved health outcomes in uninsured patients with hyperlipidemia, diabetes, or hypertension.Data SourcePartners HealthCare Research Patient Data Registry (RPDR).Study DesignWe examined 1,463 patients with hyperlipidemia, diabetes, or hypertension who were uninsured in the 3 years before the 2006 Massachusetts Health Reform implementation. We assessed mean quarterly total cholesterol, glycosylated hemoglobin, and systolic blood pressure in the respective cohorts for five follow‐up years compared with 3,448 propensity score‐matched controls who remained insured for the full 8‐year study period. We used person‐level interrupted time series analysis to estimate changes in outcomes adjusting for sex, age, race, estimated household income, and comorbidity. We also analyzed the subgroups of uninsured patients with poorly controlled disease at baseline, no evidence of established primary care in the baseline period, and those who received insurance in the first follow‐up year.Principal FindingsIn 5 years after Massachusetts Health Reform, patients who were uninsured at baseline did not experience detectable trend changes in total cholesterol (−0.39 mg/dl per quarter, 95 percent confidence interval [−1.11 to 0.33]), glycosylated hemoglobin (−0.02 percent per quarter [−0.06 to 0.03]), or systolic blood pressure (−0.06 mmHg per quarter [−0.29 to 0.18]). Analyses of uninsured patients with poorly controlled disease, no evidence of established primary care in the baseline period, and those who received insurance in the first follow‐up year yielded similar findings.ConclusionsMassachusetts Health Reform was not associated with improvements in hyperlipidemia, diabetes, or hypertension control after 5 years. Interventions beyond insurance coverage might be needed to improve the health of chronically ill uninsured persons.
Underrepresentation of Heroin Involvement in Unintentional Drug Overdose Deaths in Allegheny County, PA
Authors: Mertz Kristen J. , Janssen Jennifer K. , Williams Karl E. 
Published: July 2014

AbstractDrugs contributing to overdose deaths are listed on death certificates, but their validity is rarely studied. To assess the accuracy of “morphine” and “codeine” listings on death certificates for unintentional overdose deaths in Allegheny County, PA, investigative and laboratory reports were reviewed. Deaths were reclassified as heroin‐related if documentation showed 6‐monoacetylmorphine in blood or urine, “stamp bags” or drug paraphernalia at scene, history of heroin use, or track marks. Deaths were considered morphine‐related if notes indicated morphine use, prescription, or morphine at scene, or codeine‐related if the codeine blood level exceeded morphine. Of 112 deaths with morphine but not heroin listed on the death certificate, 74 met heroin criteria and 21 morphine criteria. Of 20 deaths with both morphine and heroin listed, only one met morphine criteria. Of 34 deaths with codeine listed, only five were attributed to codeine. Consideration of patient history, death scene evidence, and expanded toxicology testing may improve the accuracy of death certificate drug listings.
Color Me Noisy: Example‐based Rendering of Hand‐colored Animations with Temporal Noise Control
Authors: Fišer J. , Lukáč M. , Jamriška O. , Čadík M. , Gingold Y. , Asente P. , Sýkora D. 
Published: July 2014

AbstractWe present an example‐based approach to rendering hand‐colored animations which delivers visual richness comparable to real artwork while enabling control over the amount of perceived temporal noise. This is important both for artistic purposes and viewing comfort, but is tedious or even intractable to achieve manually. We analyse typical features of real hand‐colored animations and propose an algorithm that tries to mimic them using only static examples of drawing media. We apply the algorithm to various animations using different drawing media and compare the quality of synthetic results with real artwork. To verify our method perceptually, we conducted experiments confirming that our method delivers distinguishable noise levels and reduces eye strain. Finally, we demonstrate the capabilities of our method to mask imperfections such as shower‐door artifacts.
Hero Wavelength Spectral Sampling
Authors: Wilkie A. , Nawaz S. , Droske M. , Weidlich A. , Hanika J. 
Published: July 2014

AbstractWe present a spectral rendering technique that offers a compelling set of advantages over existing approaches. The key idea is to propagate energy along paths for a small, constant number of changing wavelengths. The first of these, the hero wavelength, is randomly sampled for each path, and all directional sampling is solely based on it. The additional wavelengths are placed at equal distances from the hero wavelength, so that all path wavelengths together always evenly cover the visible range.A related technique, spectral multiple importance sampling, was already introduced a few years ago. We propose a simplified and optimised version of this approach which is easier to implement, has good performance characteristics, and is actually more powerful than the original method. Our proposed method is also superior to techniques which use a static spectral representation, as it does not suffer from any inherent representation bias. We demonstrate the performance of our method in several application areas that are of critical importance for production work, such as fidelity of colour reproduction, sub‐surface scattering, dispersion and volumetric effects. We also discuss how to couple our proposed approach with several technologies that are important in current production systems, such as photon maps, bidirectional path tracing, environment maps, and participating media.
Utility of a new reusable clip device for endoscopic treatment
Authors: Shinozaki Satoshi , Sunada Keijiro , Otake Toshiya , Lefor Alan T. , Yamamoto Hironori 
Published: July 2014

Background and AimExisting reusable endoscopic clip devices have some problems regarding opening the device and precise control of clip application. The aim of the present study was to evaluate reusable clip devices for endoscopic treatment.MethodsAbility to close a large defect and grip force were evaluated using ex‐vivo porcine colon. We assessed clip loading and opening in a non‐clinical setting and describe the resulting learning curve. To evaluate clinical utility, data for clip application in 72 post‐endoscopic mucosal resection (EMR) defects in 40 patients were retrospectively analyzed.ResultsThere was no difference in the ability to close a 20‐mm full‐thickness defect and the grip force comparing the new clip device (ZEOCLIP®) and a previously used reusable clip device (EZClip®). Although the time to load the ZEOCLIP was almost same as the EZClip, the time to open the ZEOCLIP was significantly shorter than the EZClip (P < 0.001). Opening width of the ZEOCLIP was significantly wider than the EZClip (P < 0.05). We successfully accomplished closure of post‐EMR defects by clip application in 72 lesions using ZEOCLIP. Reopening/repositioning and restoring it to the working channel were more frequently carried out in a non‐easy location than in an easy location (11/35 [31%] vs 4/37 [11%], P = 0.030; and 21/35 [60%] vs 1/37 [3%], P < 0.001, respectively).ConclusionsZEOCLIP is more quickly and easily opened to its maximum width compared with EZClip, and is feasible for clip application after EMR.
Evidence for perceptual neglect of environmental features in hippocampal‐lesioned pigeons during homing
Authors: Gagliardo Anna , Pollonara Enrica , Coppola Vincent J. , Santos Carlos D. , Wikelski Martin , Bingman Verner P. 
Published: July 2014

AbstractThe importance of the vertebrate hippocampus in spatial cognition is often related to its broad role in memory. However, in birds, the hippocampus appears to be more specifically involved in spatial processes. The maturing of GPS‐tracking technology has enabled a revolution in navigation research, including the expanded possibility of studying brain mechanisms that guide navigation in the field. By GPS‐tracking homing pigeons released from distant, unfamiliar sites prior to and after hippocampal lesion, we observed, as has been reported previously, impaired navigational performance post‐lesion over the familiar/memorized space near the home loft, where topographic features constitute an important source of navigational information. The GPS‐tracking revealed that many of the lost pigeons, when lesioned, approached the home area, but nevertheless failed to locate their loft. Unexpectedly, when they were hippocampal‐lesioned, the pigeons showed a notable change in their behaviour when navigating over the unfamiliar space distant from home; they actually flew straighter homeward‐directed paths than they did pre‐lesion. The data are consistent with the hypothesis that, following hippocampal lesion, homing pigeons respond less to unfamiliar visual, topographic features encountered during homing, and, as such, offer the first evidence for an unforeseen, perceptual neglect of environmental features following hippocampal damage.
Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae
Authors: Yamada Takaaki , Hasegawa Seiji , Inoue Yu , Date Yasushi , Arima Masaru , Yagami Akiko , Iwata Yohei , Takahashi Masayuki , Yamamoto Naoki , Mizutani Hiroshi , Nakata Satoru , Matsunaga Kayoko , Akamatsu Hirohiko 
Published: July 2014

AbstractIt has been reported that the abnormal regulation of melanocyte stem cells (McSCs) causes hair greying; however, little is known about the role of McSCs in skin hyperpigmentation such as solar lentigines (SLs). To investigate the involvement of McSCs in SLs, the canonical Wnt signalling pathway that triggers the differentiation of McSCs was analysed in UVB‐induced delayed hyperpigmented maculae in mice and human SL lesions. After inducing hyperpigmented maculae on dorsal skin of F1 mice of HR‐1× HR/De, which was formed long after repeated UVB irradiation, the epidermal Wnt1 expression and the number of nuclear β‐catenin‐positive McSCs were increased as compared to non‐irradiated control mice. Furthermore, the expression of dopachrome tautomerase (Dct), a downstream target of β‐catenin, was significantly upregulated in McSCs of UVB‐irradiated mice. The Wnt1 expression and the number of nuclear β‐catenin‐positive McSCs were also higher in human SL lesions than in normal skin. Recombinant Wnt1 protein induced melanocyte‐related genes including Dct in early‐passage normal human melanocytes (NHEMs), an in vitro McSC model. These results demonstrate that the canonical Wnt signalling pathway is activated in SL lesions and strongly suggest that the accelerated differentiation of McSCs is involved in SL pathogenesis.