bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers
Authors: Šuštić Tonći , van Wageningen Sake , Bosdriesz Evert , Reid Robert J. D. , Dittmar John , Lieftink Cor , Beijersbergen Roderick L. , Wessels Lodewyk F. A. , Rothstein Rodney , Bernards René 
Published: November 2018

AbstractBackgroundMutations inKRASare frequent in human cancer, yet effective targeted therapeutics for these cancers are still lacking. Attempts to drug the MEK kinases downstream of KRAS have had limited success in clinical trials. Understanding the specific genomic vulnerabilities ofKRAS-driven cancers may uncover novel patient-tailored treatment options.MethodsWe first searched for synthetic lethal (SL) genetic interactions with mutantRASin yeast with the ultimate aim to identify novel cancer-specific targets for therapy. Our method used selective ploidy ablation, which enables replication of cancer-specific gene expression changes in the yeast gene disruption library. Second, we used a genome-wide CRISPR/Cas9-based genetic screen inKRASmutant human colon cancer cells to understand the mechanistic connection between the synthetic lethal interaction discovered in yeast and downstream RAS signaling in human cells.ResultsWe identify loss of the endoplasmic reticulum (ER) stress sensorIRE1as synthetic lethal with activatedRASmutants in yeast. InKRASmutant colorectal cancer cell lines, genetic ablation of the human ortholog ofIRE1,ERN1, does not affect growth but sensitizes to MEK inhibition. However, an ERN1 kinase inhibitor failed to show synergy with MEK inhibition, suggesting that a non-kinase function of ERN1 confers MEK inhibitor resistance. To investigate how ERN1 modulates MEK inhibitor responses, we performed genetic screens inERN1knockoutKRASmutant colon cancer cells to identify genes whose inactivation confers resistance to MEK inhibition. This genetic screen identified multiple negative regulators of JUN N-terminal kinase (JNK) /JUN signaling. Consistently, compounds targeting JNK/MAPK8 or TAK1/MAP3K7, which relay signals from ERN1 to JUN, display synergy with MEK inhibition.ConclusionsWe identify the ERN1-JNK-JUN pathway as a novel regulator of MEK inhibitor response inKRASmutant colon cancer. The notion that multiple signaling pathways can activate JUN may explain whyKRASmutant tumor cells are traditionally seen as highly refractory to MEK inhibitor therapy. Our findings emphasize the need for the development of new therapeutics targeting JUN activating kinases, TAK1 and JNK, to sensitizeKRASmutant cancer cells to MEK inhibitors.
Cause of Death in Follicular Lymphoma in the First Decade of the Rituximab Era: A Pooled Analysis of French and US Cohorts
Authors: Sarkozy Clémentine , Maurer Matthew J. , Link Brian K. , Ghesquieres Hervé , Nicolas Emmanuelle , Thompson Carrie A. , Traverse-Glehen Alexandra , Feldman Andrew L. , Allmer Cristine , Slager Susan L. , Ansell Stephen M. , Habermann Thomas M. , Bachy Emmanuel , Cerhan James R. , Salles Gilles 
Published: November 2018

Purpose Although the life expectancy of patients with follicular lymphoma (FL) has increased, little is known of their causes of death (CODs) in the rituximab era. Patients and Methods We pooled two cohorts of newly diagnosed patients with FL grade 1-3A. Patients were enrolled between 2001 and 2013 in two French referral institutions (N = 734; median follow-up 89 months) and 2002 and 2012 in the University of Iowa and Mayo Clinic Specialized Program of Research Excellence (SPORE; N = 920; median follow-up 84 months). COD was classified as being a result of lymphoma, other malignancy, treatment related, or all other causes. Results Ten-year overall survival was comparable in the French (80%) and US (77%) cohorts. We were able to classify COD in 248 (88%) of 283 decedents. In the overall cohort, lymphoma was the most common COD, with a cumulative incidence of 10.3% at 10 years, followed by treatment-related mortality (3.0%), other malignancy (2.9%), other causes (2.2%), and unknown (3.0%). The 10-year cumulative incidence of death as a result of lymphoma or treatment was higher than death as a result of all other causes for each age group (including patients ≥ 70 years of age at diagnosis [25.4% v 16.6%]) Follicular Lymphoma International Prognostic Index score 3 to 5 (27.4% v 5.2%), but not Follicular Lymphoma International Prognostic Index score 0 to 1 (4.0% v 3.7%); for patients who failed to achieve event-free survival within 24 months from diagnosis (36.1% v 7.0%), but not for patients who achieved event-free survival within 24 months of diagnosis (6.7% v 5.7%); and for patients with a history of transformed FL (45.9% v 4.7%), but not among patients without (8.1% v 6.2%). Overall, 77 of 140 deaths as a result of lymphoma occurred in patients whose FL transformed after diagnosis. Conclusion Despite the improvement in overall survival in patients with FL in the rituximab era, their leading COD remains lymphoma, especially after disease transformation. Treatment-related mortality also represents a concern, which supports the need for less-toxic therapies.
МОДЕЛЬ СИСТЕМЫ УПРАВЛЕНИЯ РАБОТОЙ С ОДАРЕННЫМИ ДЕТЬМИ В РЕГИОНЕ
Authors: Parfenova Galina Leonidovna , Kolesova Svetlana Vladislavovna 
Published: November 2018

Предмет работы: моделирование и управление пролонгированным сопровождением и развитием детской одаренности в образовательном процессе.Цель работы: обоснование и создание модели системы управления работой с одаренными детьми в регионе, которая позволит ее реальным и потенциальным участникам осуществлять продуктивное взаимодействие, комплексное психолого-педагогическое, научное сопровождение одаренных детей в образовательном пространстве, создавать условия для успешной самореализации одаренных личностей различного возраста.Методологическая основа работы: системный, культурологический, субъектный и личностно-ориентированный подходы.Метод работы: моделирование – построение структурно-функциональной и описательной моделей.Результаты: обоснована актуальность разработки и внедрения в национальное образовательное пространство модели системы управления работой с одаренными детьми в регионе; показана структура, направления и содержание деятельности университетского Центра развития одаренности, его взаимодействие с другими структурными подразделениями университета, координация работы Центра с образовательными, культурными, спортивными учреждениями и учреждениями дополнительного образования в регионе.Область применения результатов: обучение, воспитание, развитие, профессиональная ориентация одаренных детей, психолого-педагогическое сопровождение одаренных детей в образовании.Выводы: представленная система управления работой с одаренными детьми направлена не только на развитие одаренности ребенка, но и на становление его личности, сохранение и укрепление его здоровья, а также повышение психологической и педагогической культуры окружающих взрослых. Модель может быть адаптирована к особенностям конкретного региона России.
ПРЕДСТАВЛЕНИЯ ОБ ИДЕАЛЬНОЙ ЖЕНЩИНЕ У МУЖЧИН С РАЗНОЙ САМООЦЕНКОЙ
Authors: Zarubko Elena Yurievna 
Published: November 2018

Цель статьи – изучить особенности представлений об идеальной женщине у мужчин с разной самооценкой.Метод и методология исследования. В исследовании участвовали 102 респондента мужского пола. Выборку составили три возрастные группы: 18–24 года, 26–32 года, 33–40 лет. В каждой возрастной группе 34 респондента. Самооценка измерялась методикой изучения самооценки Т. Дембо–С. Рубинштейн в модификации П.В. Яньшина, в результате респонденты были разделены на четыре группы по уровню самооценки: завышенная (n=30 человек), высокая (n=30), средняя (n=30), низкая(n=12). Представления об идеальной женщине измерялись семантическим дифференциалом. Данные обрабатывались методами факторного и кластерного анализа.Результаты. Выявлено значительное сходство в представлениях мужчин с разной самооценкой о том, какой должна быть идеальная женщина (заботливая, понимающая, честная, преданная, стройная и фигуристая). В целом мужчины видят в качестве идеала женщину, соответствующую традиционному женскому образу. Традиционный образ женщины имеет позитивную коннотацию и противопоставляется современному образу. Важную роль в образе идеальной женщины играет внешняя привлекательность. Выявлены особенности представлений об идеальной женщине, специфичные для мужчин с разной самооценкой. У мужчин с низкой самооценкой в образе идеальной женщины преобладают традиционно женские характеристики (понимающая, не вульгарная, чистоплотная, хозяйственная), у мужчин с завышенной самооценкой в образе идеальной женщины преобладают характеристики «эмансипированной» женщины (целеустремленная, самостоятельная, с характером).Область применения результатов. Результаты могут использоваться в консультативной практике для оптимизации отношений в паре, например, для работы с ожиданиями к партнёру; для помощи в решении личностных проблем, связанных с гендерной идентичностью.
ЛИЧНОСТНЫЕ И НЕИЗМЕНЯЕМЫЕ КАТЕГОРИИ ИДЕНТИЧНОСТИ ВОСПИТАТЕЛЕЙ В ЗАВИСИМОСТИ ОТ ОБРАЗОВАНИЯ И КОНФЕССИИ
Authors: Kolinichenko Irina Aleksandrobna , Voronkina Lubov Borisovna 
Published: November 2018

Цель. В статье анализируются результаты исследования различий между личностными и неизменяемыми категориями идентичности у воспитателей дошкольных учреждений в двух независимых группах, отличающихся по степени получения образования (незаконченное высшее и законченное высшее) и конфессиональной принадлежности (христианство и мусульманство).Методы исследования. Исследование различий между категориями идентичности испытуемых проводилось при помощи включенного наблюдения и методики М. Куна-Маркпатленда (в модификации). Статистический анализ различий – с помощью непараметрического U-критерия Манна-Уитни пакета Statistica for Windows 8.Результаты. Выявлены межгрупповые различия при оценке характеристик идентичности в зависимости от образования и конфессии. На высоком уровне значимости категория личностной идентичности выше у воспитателей, получивших высшее образование 5–7 лет назад, чем у испытуемых, получающих его в период исследования. Межгрупповые различия при оценке идентичности в зависимости от принадлежности к конфессии, желательность неизменяемых категорий статистически более выражены в группе воспитателей, обозначивших себя как христиан в отличие от воспитателей, приписывающих себе мусульманскую конфессию.Область применения результатов. Результаты исследования могут быть применены в сфере психологического сопровождения развития личности воспитателей дошкольных учреждений и прогнозирования профессионального развития больших социальных групп воспитателей.
La sutura de los mundos. Políticas del lenguaje en Rubén Darío
Authors: Link Daniel 
Published: November 2018

La obra de Rubén Darío es un hito que vuelve a encontrar toda su fuerza en la discusión de los paradigmas hegemónicos en el campo de los estudios comparados, la Weltliteratur, el hispanismo y los estudios transatlánticos, no como caso para ser analizado sino como lugar de enunciación teórica que, como no podía ser de otra manera, anticipa algunos desarrollos de la teoría poscolonial y los estudios subalternos.
Darío (como Caupolicán) no sólo soporta un mundo sobre sus espaldas, sino que interrumpe toda ilusión de homogeneidad y toda arrogancia en relación con algún centro. Nos dice que la lengua y el poema están en un lugar imposible y encuentra en esa imposibilidad un principio teórico, una ontología del presente y de nosotros mismos.
El efecto del exilio en las obras de Juan José Saer y Daniel Moyano. Propuesta metodológica para analizar procesos redaccionales y de archivo
Authors: Viña Diego , Bernabei Verónica 
Published: November 2018

Este trabajo se centra en las obras y los archivos de Juan José Saer y Daniel Moyano, a partir de algunos interrogantes y de una propuesta metodológica en torno a los procesos escriturales y de archivación que tienen como cuestión de fondo el efecto del exilio en la obra de un autor. A la hora de analizar dichos procesos utilizando como punto de partida un archivo de obra, encontramos que una disposición en el espacio de los datos permite comprender hiatos o blancos que se destacan en una cronología establecida a partir de la lectura. Estas reflexiones se sostienen, por tanto, en una indagación sobre la temporalidad de la escritura y su materialización a partir de un dimensionamiento espacial de los documentos. Nos preguntamos cómo es posible ver la escritura; esto es, cómo se pueden representar y explicar, en el espacio, las vicisitudes literarias, editoriales y vivenciales que conforman el recorrido de un escritor. Y a partir de esto, cómo es posible ver la evolución de un archivo a medida que los investigadores intervienen los documentos.
Para responder a los interrogantes proponemos articular documentos pre–redaccionales y redaccionales inventariados y organizados que conforman nuestro objeto «literario» con otros documentos, fechas y datos contextuales en torno a los autores. Lo hacemos partiendo de un modelo gráfico que elaboramos para dilucidar los procesos redaccionales en la obra de Saer, en principio, y que luego extendimos a la escritura y el archivo de Moyano. Las dos cronologías permiten ver la incidencia que puede tener la constitución de un fondo documental para ampliar o desocultar distintas facetas o períodos de producción.
Im Auftrag des Rechts. Christliche und jüdische Regensburger Anwälte beim Innsbrucker Prozess (1516-1519)
Authors: Nickel Veronika 
Published: November 2018

Abstract
The expulsion of the Jewish Community from Regensburg (Ratisbon) in 1519 was one of the last and well-known expulsions of Jews from an Imperial City on the brink of the modern era. Little attention has been paid to a lawsuit between the Regensburg City Council and the Jewish Community which was initiated three years before 1519. Both the City Council and the Jewish Community sent specially authorised delegates as attorneys to attend the trial held in front of the Regiment in Innsbruck/Austria. Hans Hirsdorfer, Hansgraf of Regensburg, was usually dispatched to Innsbruck as the Christian representative while Isaak Walch made the journey in order to represent the Jewish Community. Their powers of attorney, along with other sources such as account books, give us deep insights into their scope of action regarding personal as well as juridical matters.
A report of chronic intestinal pseudo-obstruction related to systemic lupus erythematosus
Authors: Wang Ruiqiang , Zheng Bowen , Wang Biyue , Ma Pupu , Chen Fengmei , Tang Lin 
Published: November 2018

Abstract
Chronic intestinal pseudo-obstruction (CIPO) is a functional gastrointestinal disorder with symptoms of ileus. CIPO can either be idiopathic or secondary to other diseases such as systemic lupus erythematosus (SLE). SLE is involved in many parts of the gastrointestinal system with variable clinical presentations. Reports about reduplicated CIPO as a complication of SLE is infrequent. A 49-year-old female suffering from clinical symptoms of ileus has been hospitalized 3 times over 1 year. Her examination results showed no observation of mechanical obstruction. In August 2017, she came to the nephrology department due to edema in both lower limbs along with symptoms of ileus. After thorough examination, she was diagnosed with secondary CIPO related to SLE. Results of renal biopsy confirmed to be lupus nephritis (Class III-(A) + V). The symptoms of ileus are gradually improved after treatment of full-dose intravenous corticosteroid for 5 days.
Using superoscillations for superresolved imaging and subwavelength focusing
Authors: Gbur Greg 
Published: November 2018

Abstract
It is now well-appreciated that a bandlimited wave can possess oscillations much more rapidly than those predicted by the bandlimit itself, in a phenomenon known as superoscillation. Such superoscillations are required to be of dramatically smaller amplitude than the signal they are embedded in, and this has initially led researchers to consider them of limited use in applications. However, this view has changed in recent years and superoscillations have been employed in a number of systems to beat the limits of conventional diffraction theory. In this review, we discuss the current state of research on superoscillations in terms of superresolved imaging and subwavelength focusing, including the use of special non-diffracting and Airy beams to carry transverse superoscillating patterns. In addition, we discuss recent analogous works on using superoscillations to break the temporal resolution limit, and also consider the recently introduced inverse of superoscillations, known as suboscillations.
An inverse approach to the characterisation of material parameters of piezoelectric discs with triple-ring-electrodes
Authors: Feldmann Nadine , Jurgelucks Benjamin , Claes Leander , Schulze Veronika , Henning Bernd , Walther Andrea 
Published: November 2018

Abstract
For its usage in simulation-based design processes a precise knowledge of the employed material properties is inevitable. In the case of piezoelectric ceramics, the provided material parameters often suffer from large uncertainties and even inconsistencies since the standardised measurement procedure needs several specimens to determine a single set of material parameters. In contrast, the presented measurement set-up allows to calculate material parameters using one unique disc-shaped specimen with an optimised electrode topology. Using an inverse problem approach, fitting material parameters can be found using an optimisation procedure.
Feasibility of Improving the Mechanical Properties of Concrete Pavement Using Basalt Fibers
Authors: Sarkar Alireza , Hajihosseini Majid 
Published: November 2018

Abstract
Many research studies have so far been done to improve the mechanical properties of concrete pavement by using basalt fiber; these studies have indicated the positive effects of this fiber on concrete pavements. Accordingly, the idea of applying this fiber, which is proportional to the concrete mix design and is commonly used in this geographical area, was introduced. Therefore, based on the type and amount of basalt fiber content recommended in the technical literature, the effect of using this fiber in two conventional mix designs was evaluated. In order to determine the effect of the fiber on mechanical properties affecting pavement design, the influence of the alkaline environment of cement on the fiber was initially examined. Then, concrete samples containing this fiber are subjected to tensile, compression, and bending tests. The results showed that in the mix design commonly used in this area, the use of basalt fiber in accordance with the recommended amounts indicated in most studies may lead to a minor improvement in the toughness index and indirect tensile strength of concrete samples and to negative effects on four-point bending and compressive strength.
Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity
Authors: Huijbers Willem , Schultz Aaron P. , Papp Kathryn V. , LaPoint Molly R. , Hanseeuw Bernard , Chhatwal Jasmeer P. , Hedden Trey , Johnson Keith A. , Sperling Reisa A. 
Published: November 2018

Animal studies demonstrate that hyperactive neurons facilitate early accumulation and spread of tau and amyloid-β proteins in the pathological cascade of Alzheimer's disease (AD). Human neuroimaging studies have linked hippocampal hyperactivity to amyloid-β accumulation, apolipoprotein ε4 (APOE4) and clinical progression from prodromal AD to clinical dementia. The relationship between hippocampal hyperactivity and early AD molecular pathology (amyloid-β and tau accumulation) before clinical symptoms remains to be elucidated. Here, we studied 120 clinically normal older humans (80 females/40 males) enrolled in the Harvard Aging Brain Study. We measured functional magnetic resonance imaging (fMRI) activity during successful memory encoding and amyloid-β accumulation with PiB-positron emission tomography imaging. Additionally, we measured tau accumulation using AV1451 PET imaging in a subset of 87 participants. In this subset, we found that inferior temporal tau accumulation was associated with increased fMRI activity in the hippocampus, but showed no clear association with amyloid. Together, the findings support a hypothetical model of the evolution of preclinical AD that place hippocampal hyperactivity concurrent with spread of tau pathology to neocortical regions before clinical impairment.SIGNIFICANCE STATEMENTThe circumstances under which the hippocampus becomes hyperactive in preclinical stages of Alzheimer's disease (AD) have thus far remained elusive. Recent advances in positron emission tomography (PET) tracers now enablein vivocharacterization of amyloid-β and tau accumulation. Here, we combine amyloid and tau PET with functional magnetic resonance imaging (fMRI) to examine the association between Alzheimer's disease pathology and memory-related brain activity in clinically normal older adults. We found an association between increased hippocampal activity and tau accumulation in the inferior temporal cortex. These data suggest that the pathogenesis of hippocampal hyperactivity occurs concurrent with the spread of tau pathology from the entorhinal cortex to the neocortex, before the clinical manifestations of Alzheimer's disease.
LHX3 deficiency presenting in the United States with severe developmental delay in a child of Syrian refugee parents
Authors: Ahern Susan , Daniels Mark , Bhangoo Amrit 
Published: November 2018

Summary
In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) transcription factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype.

Learning points:

Describe an unusual presentation of undertreated pituitary hormone deficiencies in early life

Combined pituitary hormone deficiency due to a novel mutation in pituitary transcription factor, LHX3

Describe the clinical phenotype of combined pituitary hormone deficiency due to LHX3 mutations