bluuebunny/crossref_metadata_2025 huggingface dataset:
السياسات الاقتصادية وقدرتها في إصلاح مناخ الاستثمار في العراق بعد عام 2003
Authors: عبد الوهاب إكرام عبد العزيز
Published: February 2020

يعد مناخ الاستثمار المحرك الرئيس للتنمية الاقتصادية، وإذا ما تم تهيئة مناخ استثماري ملائم وجاذب يأخذ بنظر الاعتبار القضايا الاقتصادية والإدارية والسياسية والبيئية، فإن ذلك من شأنه أن يسهم في تطوير الصناعة ونقل التكنولوجيا وتنويع الإنتاج الزراعي وزيادة انتاجيته وتعزيز الاقتصاد الأخضر، ودعم النمو المستدام والشامل. وبالتالي فإن تحليل مناخ الاستثمار في بلد ما يمكن أن يوفر أسباب وجذور تعقد المشاكل في الاقتصاد، ففي الاقتصاد العراقي، تبين أن المشكلة لا تنتهي جذورها في الاقتصاد، وإنما كانت جذور المشكلة أعمق من ذلك وهي متأصلة في إدارة الاقتصاد، وبالتالي، فقد اتضح أن بيئة الاستثمار في العراق تعاني من إدارة غير رشيدة انعكست بشكل اختلالات معقدة في الاقتصاد العراقي مما شكل بيئة طاردة للاستثمار. ومن خلال ما تقدم، فإن البحث يفترض وجود معوقات إدارية وامنية ومالية ونقدية فضلا عن تفشي الفساد بأشكاله مارست تاثيراً معرقلاً لاتساع نطاق عمل الاستثمار  وتنوع مساراته بحكم تأثيرها على بيئة الاستثمار. وقد توصل البحث إلى اثبات هذه الفرضية، إضافة إلى ان تحسين مناخ الاستثمار  متوقف على تغيير المنهجية الكلية للسياسات الإدارية والاقتصادية , مالية ونقدية وغيرها  وكيفية التنسيق مع بعضها البعض بشكل فعال. كما إن البحث توصل إلى أن السبب الرئيس لسوء إدارة الاقتصاد هو الغياب شبه الكلي لركائز الحكم الرشيد؛ وذلك بسبب العوامل السلبية الضاغطة عليه. وبالتالي أدى هذا إلى عدم وجود سياسة واضحة تعتمدها الحكومة لتحسن مناخ الاستثمار, فخطط التنمية الوطنية لم يصادق عليها البرلمان كما ان الكثير من الاستراتيجيات التي وافقت عليها الحكومة كان ينقصها الآليات المناسبة لتنفيذها لذلك فإن أهم توصية جاء بها البحث هو أن غرس وتثبيت ركيزة المسائلة بقواعدها وأركانها وضوابطها في البيئة المؤسسية، قبل البدء بأي إصلاح؛ وذلك من أجل تصحيح مسار إدارة الاقتصاد الكلي.
The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene
Authors: Cristina Fugazza  , Gloria Barbarani  , Sudharshan Elangovan  , Maria Giuseppina Marini  , Serena Giolitto  , Isaura Font-Monclus  , Maria Franca Marongiu  , Laura Manunza  , John Strouboulis  , Claudio Cantù  , Fabio Gasparri  , Silvia M.L. Barabino  , Yukio Nakamura  , Sergio Ottolenghi  , Paolo Moi  , Antonella Ellena Ronchi
Published: February 2020

The human fetal γ-globin gene is repressed in the adult stage through complex regulatory mechanisms involving transcription factors and epigenetic modifiers. Reversing γ-globin repression, or maintaining its expression by manipulating regulatory mechanisms, has become a major clinical goal in the treatment of β-hemoglobinopathies. Here, we identify the orphan nuclear receptor Coup-TFII (NR2F2/ARP-1) as an embryonic/fetal stage activator of γ-globin expression. We show that Coup-TFII is expressed in early erythropoiesis of yolk sac origin, together with embryonic/fetal globins. When overexpressed in adult cells (including peripheral blood cells from human healthy donors and β039 thalassemic patients) Coup-TFII activates the embryonic/fetal globins genes, overcoming the repression imposed by the adult erythroid environment. Conversely, the knock-out of Coup-TFII increases the β/γ+β globin ratio. Molecular analysis indicates that Coup-TFII binds in vivo to the β-locus and contributes to its conformation. Overall, our data identify Coup-TFII as a specific activator of the γ-globin gene.
NCOA4-mediated ferritinophagy in macrophages is crucial to sustain erythropoiesis in mice
Authors: Antonella Nai  , Maria Rosa Lidonnici  , Giorgia Federico  , Mariateresa Pettinato  , Violante Olivari  , Federica Carrillo  , Simonetta Geninatti Crich  , Giuliana Ferrari  , Clara Camaschella  , Laura Silvestri  , Francesca Carlomagno
Published: February 2020

The Nuclear Receptor Coactivator 4 (NCOA4) promotes ferritin degradation and Ncoa4-ko mice in C57BL/6 background show microcytosis and mild anemia, aggravated by iron deficiency. To understand tissue specific contribution of NCOA4-mediated ferritinophagy we explored the effect of Ncoa4 genetic ablation in the iron-rich strain Sv129/J. Increased body iron content protects mice from anemia and, in basal conditions, Sv129/J Ncoa4-ko mice show only microcytosis; nevertheless, when fed a low-iron diet they develop a more severe anemia compared to wild-type animals. Reciprocal bone marrow (BM) transplantation from wild-type donors into Ncoa4-ko and from Ncoa4-ko into wild-type mice revealed that microcytosis and susceptibility to iron deficiency anemia depend on BM-derived cells. Erythropoiesis reconstitution with RBC count and hemoglobin normalization occurred at the same rate in transplanted animals independently of the genotype. Importantly, NCOA4 loss did not affect terminal erythropoiesis in iron deficiency, both in total and specific BM Ncoa4-ko animals compared to controls. On the contrary, upon a low iron diet, spleen from wild-type animals with Ncoa4-ko BM displayed marked iron retention compared to (wild-type BM) controls, indicating defective macrophage iron release in the former. Thus, EPO administration failed to mobilize iron from stores in Ncoa4-ko animals. Furthermore, Ncoa4 inactivation in thalassemic mice did not worsen the hematological phenotype. Overall our data reveal a major role for NCOA4-mediated ferritinophagy in macrophages to favor iron release for erythropoiesis, especially in iron deficiency.
Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies
Authors: Roberto Mina  , Francesca Bonello  , Maria Teresa Petrucci  , Anna Marina Liberati  , Concetta Conticello  , Stelvio Ballanti  , Pellegrino Musto  , Attilio Olivieri  , Giulia Benevolo  , Andrea Capra  , Milena Gilestro  , Piero Galieni  , Michele Cavo  , Agostina Siniscalchi  , Antonio Palumbo  , Vittorio Montefusco  , Gianluca Gaidano  , Paola Omedé  , Mario Boccadoro  , Sara Bringhen
Published: February 2020

Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p.
Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients.
ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).
Depiction of Adolescents Smoking Behaviour in Urban and Suburban
Authors: Toghur Arifani Lubis  , R. Kintoko Rochadi
Published: February 2020

Smoking is a fatal issue that has not yet been resolved and spread even among adolescents particularly in Indonesia. This study aim to depict the adolescents smoking behavior in SMPN three Medan or urban areas and MTS Amin Darussalam Deli Serdang or suburban areas. This cross sectional study conducted on October. Data were collected using questionnaires toward students from both school. Results shows majority respondent in urban have good knowledge, negative attitude toward cigarette and non-smokers but interested in smoking, majority of former smokers in urban firstly tried smoking during sixth grade elementary because of peer influence, smoking occasionally, ever smoked one to five cigarettes per day, quit smoking because of self-awareness and still have interest in smoking. Furthermore, majority respondent in suburban have bad bad knowledge, negative attitude toward cigarette, smoker, firstly tried smoking during sixth grade elementry because of peer influence, smoking occasionally, ever smoked one to five cigarettes per day and have no intention to quit smoking, majority of former smokers quit smoking because of caught by parent or teacher and still have interest in smoking.  In conclusion, there is difference of smoking behavior between urban and suburban, the depiction of smoking behavior in suburban is worse than in urban because it has higher number of smokers, poorly dominant of knowledge and have no intention to quit smoking.
Promotion of vaginal birth in Bangladesh
Authors: Siddiqua SF
Published: February 2020

Abstract not available

Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 3-6
Serum Ferritin Status of Patients with Type 2 DM Attending OPD of BIRDEM General Hospital
Authors: Begum Khadiza , Islam Fahmida , Aktar Farjana , Aziz Murshida , Tahiya Tohfa E Ayub
Published: February 2020

Background: In recent times much is talked about of serum ferritin, an acute phase reactant a marker of iron stores in the body and its association with diabetes mellitus. Studies implicate that increased body iron stores and subclinical hemochromatosis has been associated with the development of glucose intolerance, type 2 diabetes and its micro as well as macrovascular complications.

Material & Methods: This study was carried out to examine and to observe for any relationship between serum ferritin with Type 2 diabetes mellitus. Our study populations were included 163. Among them 81 type 2 diabetes patients as a case (M=49,F=32, mean 44.68 age in years)and 82 normal healthy individual as a control ( M=35, F=47 , mean 34.71 in years).

Results: Majority were healthy outpatients who had come for regular checkup and were matched with controls. Serum ferritin and FBS were estimated and other investigations. Results showed that although Serum ferritin was in the normal range value it was increased in type 2 diabetes patients than in controls and was statistically significant, we did get a positive correlation with duration of diabetes. It can be concluded that there were positive associations between serum ferritin and FBG, age, sex among study groups.

Conclusion: In conclusion our study shows that there is significant correlation between increased serum ferritin in diabetes compared to individuals with normal blood sugars in this part and hyper ferritinemia may be one of the causes for development of insulin resistance before overt diabetes.

Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 7-10
Fertility Control Behavior among the Clay Modeler Women in Rural Area
Authors: Rahman Md Mahfuzur , Rahman Md Atiqur , Jnui Rizona , Kawser Abu , Shahin Khalid Omar , Aasha Sumaiya Salam , Ferdous Jannatul
Published: February 2020

Background: Fertility control behavior of women in different cultural practices greatly influences the demographic pattern of a country. The high fertility rate is associated with maternal and infant mortality rate. The aim of this study was to find out the fertility control behavior of the clay modeler women in rural area.

Material and Methods: This descriptive type cross sectional study was carried out among 1360 respondents by purposive sampling technique from19th to 21st January, 2019 in different villages of Dhamrai Upazila, Dhaka. Data were collected by duly pretested a semi-structured questionnaire through face to face interview. Data were analyzed manually and by using computer.

Results: Then study revealed that majority of the respondents 79% were Muslims by religion and about 76% respondents were found within the age 25-44 years with mean age 34.8±8.6 years. About 32% & 35% respondents were found primary & secondary level of education respectively. Moreover, 16% respondents monthly income were less than TK 2000 and 37% respondents had 2-3 number of children. About 79% respondents were using the fertility control measures only. Among the users 67% respondents were using Oral pills, 10% & 8% were using IUCD and Injections respectively. Adherence factors for contraceptive use were husband's support 85%; support of family members 90% and availability of contraceptive materials were found 97%. On the other hand, non-adherence factors for contraceptive use were religious barrier 91%; fear of complications 97% and insultations 85%. In this study, Overall perceptions on fertility control measures and time interval for birth spacing found positive.

Conclusion: Intensified efforts should be made towards creating public awareness and strengthening perception regarding fertility control behavior to overcome those non-adherence factors for contraceptive uses.

Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 29-34
Socio-demographic and Clinical Characteristics of Patient with Thyroid Cancer
Authors: Hossain AKM Farhad , Siddiqui Md Mahmudur Rahman , Khatun Sayada Fatema
Published: February 2020

Background: Thyroid cancer is the most common malignant disease in endocrine system. It is an emerging public health issue associated with burden on the family, community and the nation. The aim of this study is to determine the socio-demographic and clinical characteristics of patient with thyroid cancer attending in tertiary hospital.

Methods: This cross sectional study was conducted among 246 thyroid cancer patients in two tertiary hospitals of Dhaka city from 01 July 2018 to 30 June 2019. The subjects were selected purposively following specific selection criteria and maintaining ethical issues. Data were collected by face to face interview using a semi-structured questionnaire and checklist. Data were analyzed by the statistical package for the social science (SPSS) version 23.

Results: This study revealed that majority (74.4%) of respondents was female, married (72%), housewife (61.4%), rural respondent (41.1%) and had primary education (69%). Mean (± SD) age of the respondent was 37.85(±12.20) years (Range 14-70 years) and mean (± SD) monthly family income was Tk. 17681(±10602). Out of 246 cases, 204 (82.9%) was papillary and 42 (17.1%) was follicular carcinoma. Various clinical presentations included visible neck swelling in 225 (91.5%), swollen lymph node in 103 (41.9%), pain 90 (36.6%), Difficulties in swallowing 87 (35.4%), Hoarseness of voice in 141 (57.3%), cough along with swelling 47(19.1%), Difficulties in breathing due to swelling in 13(5.3%) of the patients.

Conclusion: Incidence of thyroid cancer has increased worldwide specially in female patients in 3rd and 4th decades of life. As thyroid cancer is a growing public health problem in Bangladesh, proper screening and early diagnostic facilities at all level should be available to measure its actual burden in the country.

Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 54-58
Extensive Genital Warts in Man Hampering Conjugal Life: A Case Report
Authors: Rahman ATM Mostafizur , Chowdhury Tanvir Ahmed , Nafisa Ali , Rahman Mahbubur
Published: February 2020

Genital warts, commonly known as condyloma acuminata, caused by the proliferation of squamous epithelial cells in the presence of sexually transmission of human papilloma Virus (HPV) infection. In human, HPV infection results in simple condyloma acuminatum, giant condyloma or Buschke-LÖwenstein tumour, and seldom penile carcinoma. There are several modalities of treatment options available for genital warts- medical and surgical, alone or in combination. Sometimes extensive genital warts represent a district entity resulting from HPV infection and require surgical management. We present the case of a 42-year-old male; rickshaw puller had multiple professional female sexual partners, who presented with extensive genital warts in penoscrotal region. Lesions were treated due to failure of medical management, by wide electrosurgical excision and rotation scrotal skin flaps

Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 82-85
Прогрев стержневых стальных конструкций с частичной и полной огнезащитой наружной поверхности при огневом воздействии
Authors: Botyan Sergey , Zhamoydik Sergey , Kudryashov Vadim , Olesiyuk Nikolay
Published: February 2020

Цель. На основе экспериментальных исследований и теоретических данных определить теплофизические характеристики вспучивающегося огнезащитного состава и оценить прогрев стержневых стальных конструкций с частичной (трехсторонней) и полной огнезащитой наружной поверхности в условиях воздействия высоких температур в сопоставлении с результатами огневых испытаний.

Методы. Экспериментальные исследования, моделирование в системе конечно-элементного анализа.

Результаты. На основе серии экспериментальных и теоретических исследований в системе конечно-элементного анализа ANSYS решена теплотехническая задача огнестойкости стержневых стальных конструкций с частичной и полной огнезащитой наружной поверхности. Экспериментальные исследования использованы для оценки эффективных значений теплофизических характеристик вспучивающегося состава (Sika Unitherm ASR) путем решения обратной задачи теплопроводности для расчетной конечно-элементной модели с использованием методов параметрической оптимизации. Полученные теплофизические характеристики позволили оценить прогрев стержневых стальных конструкций с частичной и полной огнезащитой наружной поверхности в условиях воздействия высоких температур и сопоставить с результатами огневых испытаний.

Область применения исследований. Полученные результаты могут быть использованы для решения задач огнестойкости стержневых стальных конструкций с частичной и полной огнезащитой наружной поверхности при проектировании и строительстве зданий и сооружений.
Тензометрические исследования напряженного состояния цистерн пожарных автомобилей при различных режимах движения
Authors: Kovtun Vadim , Korotkevich Sergey , Pasovets Vladimir
Published: February 2020

Цель. Экспериментальное подтверждение эффективности применения разработанных методик и рекомендаций, обеспечивающих повышение эксплуатационного ресурса, увеличение запаса прочности и межремонтного периода модернизированных цистерн пожарных автомобилей, эксплуатируемых в аварийно-спасательных подразделениях на территории Республики Беларусь.

Методы. Компьютерное моделирование, методы тензометрии.

Результаты. Экспериментальным путем исследовано напряженное состояние серийно изготавливаемой и модернизированной цистерны пожарного автомобиля при различных эксплуатационных режимах движения. Подтверждены результаты теоретических расчетов, полученные методом компьютерного моделирования. В статье представлено описание эксперимента, обработка и анализ полученных результатов.

Область применения исследований. Результаты исследований применены при проектировании и разработке конструкций оболочечного типа.
К вопросу расчета ранга организации по гражданской обороне с использованием упрощенного метода анализа иерархий
Authors: Bulva Aleksandr , Karpilenya Nikolay
Published: February 2020

Цель. Выработать предложения по расчету ранга организаций по гражданской обороне с использованием упрощенного метода анализа иерархий.

Методы. Исследование выполнено с помощью метода анализа иерархий, предложенного Н.В. Сербиновской и Б.Ю. Сербиновским.

Результаты. Усовершенствована и приведена к практическому виду методика расчета ранга организаций по гражданской обороне. Доработан порядок расчета и приведен пример применения методики.

Область применения исследований. Результаты исследований могут использоваться при обосновании мероприятий гражданской обороны, а также при разработке соответствующих планирующих документов.
Психологические аспекты профессионально важных качеств пожарных-спасателей
Authors: Germatskaya Ekaterina
Published: February 2020

Цель. Описание условий работы пожарных-спасателей, их профессионально важных качеств и умений, психологических аспектов их формирования. Определение навыков и умений, которые необходимы пожарным-спасателям для успешного выполнения профессиональных задач.
Методы. Теоретический анализ исследований по изучению профессиональных качеств пожарных-спасателей, их навыков и умений.
Результаты. Описаны условия трудовой деятельности спасателей. Предпринята попытка рассмотреть понятия «профессионально важные навыки пожарных-спасателей» и «профессионально важные умения пожарных-спасателей», определить, в чем их принципиальная разница. Выявлено, что отсутствие или недостаточное развитие профессионально важных качеств снижает эффективность профессиональной деятельности спасателей. Описаны и структурированы по отдельным группам профессионально важные качества специалистов экстремального профиля, определена их роль при ликвидации последствий чрезвычайных ситуаций.
Область применения исследований. Представленные результаты могут быть использованы для дальнейшего изучения условий и факторов формирования навыков и умений пожарных-спасателей для разработки программы развития профессиональных умений специалистов экстремального профиля.
Dynamics of carbonate sediment production by Halimeda: implications for reef carbonate budgets
Authors: Castro-Sanguino C , Bozec YM , Mumby PJ
Published: February 2020

Reef carbonate production and sediment generation are key processes for coral reef development and shoreline protection. The calcified green alga Halimeda is a major contributor of calcareous sediments, but rates of production and herbivory upon Halimeda are driven by biotic and environmental factors. Consequently, estimating rates of calcium carbonate (CaCO3) production and transformation into sediment requires the integration of Halimeda gains and losses across habitats and seasons, which is rarely considered in carbonate budgets. Using seasonal rates of recruitment, growth, senescence and herbivory derived from observations and manipulative experiments, we developed an individual-based model to quantify the annual cycle of Halimeda carbonate and sediment production at Heron Island, Great Barrier Reef. Halimeda population dynamics were simulated both within and outside branching Acropora canopies, which provide refuge from herbivory. Shelter from herbivory allowed larger Halimeda thalli to grow, leading to higher rates of carbonate accumulation (3.9 and 0.9 kg CaCO3 m-2 yr-1 within and outside Acropora canopies, respectively) and sediment production (2.5 versus 1.0 kg CaCO3 m-2 yr-1, respectively). Overall, 37% of the annual carbonate production was transformed into sediments through senescence (84%) and fish herbivory (16%), with important variations among seasons and habitats. Our model underlines that algal rates of carbonate production are likely to be underestimated if herbivory is not integrated into the carbonate budget, and reveals an important indirect pathway by which structurally complex coral habitats contribute to reef carbonate budgets, suggesting that coral losses due to climate change may lead to further declines in reef sediment production.
Seasonally specific responses to wind patterns and ocean productivity facilitate the longest animal migration on Earth
Authors: Hromádková T , Pavel V , Flousek J , Briedis M
Published: February 2020

Migratory strategies of animals are broadly defined by species’ eco-evolutionary dynamics, while behavioural plasticity according to the immediate environmental conditions en route is crucial for energy efficiency and survival. The Arctic tern Sterna paradisaea is known for its remarkable migration capacity, as it performs the longest migration known by any animal. Yet, little is known about the ecology of this record-breaking journey. Here, we tested how individual migration strategies of Arctic terns are adapted to wind conditions and fuelling opportunities along the way. To this end, we deployed geolocators on adult birds at their breeding sites in Svalbard, Norway. Our results confirm fundamental predictions of optimal migration theory: Arctic terns tailor their migration routes to profit from (1) tailwind support during the movement phase and (2) food-rich ocean areas during the stopover phase. We also found evidence for seasonally distinct migration strategies: terns prioritize fuelling in areas of high ocean productivity during the southbound autumn migration and rapid movement relying on strong tailwind support during the northbound spring migration. Travel speed in spring was 1.5 times higher compared to autumn, corresponding to an increase in experienced wind support. Furthermore, with their pole-to-pole migration, Arctic terns experience approximately 80% of all annual daylight on Earth (the most by any animal), easing their strictly diurnal foraging behaviour. However, our results indicate that during migration daylight duration is not a limiting factor. These findings provide strong evidence for the importance of interaction between migrants and the environment in facilitating the longest animal migration on Earth.
Effects of Electrical Stimulation at Different Locations in the Central Nucleus of Amygdala on Gastric Motility and Spike Activity
Authors: HE F. , AI H.-B.
Published: February 2020

The aim of the study was to determine the effects of electrical stimulation of different locations in the central nucleus of amygdala (CNA) on gastric motility and spike activity in dorsal vagal complex. Gastric motility index (GMI) and firing rate (FR) of dorsal vagal complex neurons were measured in adult Wistar rats respectively. Neuronal spikes in dorsal vagal complex (DVC) were recorded extracellularly with single-barrel glass microelectrodes. Each type of responses elicited by electrical stimulation in medial (CEM) and lateral (CEL) subdivisions of CNA were recorded, respectively. GMI was significantly increased after stimulation of CEM (p<0.01), and significantly decreased in response to CEL stimulation (p<0.01). After stimulation of CEM, FR in medial nucleus of the solitary tract (mNST) decreased by 31.6 % (p<0.01) and that in dorsal motor nucleus of the vagus (DMNV) increased by 27.1 % (p<0.01). On the contrary, FR in mNST increased (p<0.01) and that in DMNV decreased in response to CEL stimulation (p<0.05). In conclusions, our findings indicated that different loci of CNA may mediate differential effects on gastric activity via changes in the firing of brainstem neurons controlling gut activity.
Combined Incubation of Cadmium, Docosahexaenoic and Eicosapentaenoic Acid Affecting the Oxidative Stress and Antioxidant Response in Human Hepatocytes In Vitro
Authors: LINHARTOVA P. , GAZO I. , SAMPELS S.
Published: February 2020

Human hepatocellular cells Hep G2 were used to investigate the effects of the intake of contaminated fish on oxidative stress. Uptake of heavy metal contaminated fish was mimicked by incubating the cells with a combination of cadmium chloride (Cd2+) as possible contaminant and a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as important fatty acids (FA) specific for fish. The main aim of this study was to determine the effects of these co-incubations (FA, Cd2+) on lipid and protein oxidation. In addition we also evaluated the antioxidant response of the cells using two different methods (SOD and TAC). Pre-incubation with the chosen FA significantly reduced the oxidative stress caused by incubation with Cd2+. We measured an increased level of carbonyl proteins (CP) in the cells pre-incubated with bovine serum albumin (BSA) and post-incubated with Cd2+.
Novel Porcine Model of Acute Severe Cardiogenic Shock Developed by Upper-Body Hypoxia
Authors: OSTADAL P. , MLCEK M. , STRUNINA S. , HRACHOVINA M. , KRUGER A. , VONDRAKOVA D. , JANOTKA M. , HALA P. , KITTNAR O. , NEUZIL P.
Published: February 2020

Despite the urgent need for experimental research in the field of acute heart failure and, particularly cardiogenic shock, currently there are only limited options in large animal models enabling research using devices applied to human subjects. The majority of available models are either associated with an unacceptably high rate of acute mortality or are incapable of developing sufficient severity of acute heart failure. The objective of our research was to develop a novel large animal model of acute severe cardiogenic shock. Advanced left ventricular dysfunction was induced by global myocardial hypoxia by perfusing the upper body (including coronary arteries) with deoxygenated venous blood. The model was tested in 12 pigs: cardiogenic shock with signs of tissue hypoxia developed in all animals with no acute mortality. Cardiac output decreased from a mean (± SD) of 6.61±1.14 l/min to 2.75±0.63 l/min, stroke volume from 79.7±9.8 ml to 25.3±7.8 ml and left ventricular ejection fraction from 61.2±4.3 % to 17.7±4.8 % (P≤0.001 for all comparisons). In conclusion, the porcine model of acute cardiogenic shock developed in the present study may provide a basis for studying severe left ventricular dysfunction, low cardiac output and hypotension in large animals. The global myocardial hypoxia responsible for the decrease in cardiac contractility was not associated with acute death in this model.
Two layer graphene heterostructures for waves slowing down: operator approach to waveguide problem
Authors: Yakovleva Marina A. , Batrakov Konstantin G.
Published: February 2020

Slowing down the phase velocity of light in media has various applications. The generation of electromagnetic radiation using coherent Cherenkov mechanism is among them. Meanwhile, there is a need for compact terahertz radiation sources. Due to outstanding graphene properties, heterostructures consisting of alternating graphene/dielectric layers can operate as a medium for the generation of terahertz radiation. In the present paper, the slowing down and propagation coefficients for the modes supported in a two-layer graphene structure are studied. The study is conducted by means of the operator approach to wave propagation in stratified structures. The operator approach allows one to use coordinates-free notations and to consider consequently arbitrarily complex heterostructures (including anisotropic layers, for instance). The influence of interlayer distance and the value of graphene chemical potential on waves slowdown is determined. The obtained results open up prospects for creating a new type of terahertz radiation sources.
Le(s) Visage(s) de Garbo: Negotiating Discourses of Authorship and Stardom in Jacques Feyder's The Kiss (1929)
Authors: Nevin Barry
Published: February 2020

This article examines The Kiss, émigré director Jacques Feyder's first Hollywood film, with two goals in mind. First, it considers the production and reception of the film, drawing on contemporary periodicals to illustrate Feyder's contribution to the film; second, drawing on Gilles Deleuze's conceptualisation of mirror images in cinema, it argues that The Kiss constitutes an important turning-point within Feyder's output as well as a key illustration of his authorial signature, looking towards the complex portrayals of women which feature in his most famous French films of the 1930s. Key to this analysis is how Feyder mobilizes mirrors to confront spectators with their own collusion in the construction of Greta Garbo's star persona in her films and portraits, and to open broader debates regarding the intersection between authorship and star personae.
Sustainability Performance Indicators and Non-Financial Information Reporting. Evidence from the Italian Case
Authors: Raucci Domenico , Tarquinio Lara
Published: February 2020

Non-financial reporting is a growing topic, and the adoption of the EU Directive 2014/95/EU on non-financial information (NFI) is increasing the use of this reporting. One of the most distinctive elements of guidelines and standards that are widely used to draw-up reports on NFI is sustainability performance indicators (SPIs). SPIs can provide a significant value-added to non-financial corporate communication, and they are useful tools to support internal decision-making processes. The purpose of this study is to examine the effects produced on SPIs disclosure by the entry into force of the Italian Decree implementing the Directive on NFI. Content analysis method is used to analyze indicators disclosed by Italian companies before and after the adoption of the Decree. Findings show that each category of SPIs was largely used by the companies of our 2012 sample, but a reduction of the quantity of indicators disclosed was documented in 2017. Therefore, after the introduction of mandatory disclosure of NFI, companies seem to focus only on indicators considered more “relevant” according to the Directive. This research represents one of the preliminary analysis on the adoption of the Directive in Italy and on its first effects on NFI reporting practices.
The Efficiency of Live-Capture Traps for the Study of Red Fox (Vulpes vulpes) Cubs: A Three-Year Study in Poland
Authors: Mierzejewska Ewa J. , Dwużnik Dorota , Tołkacz Katarzyna , Bajer Anna , Panek Marek , Grzybek Maciej
Published: February 2020

Safe and efficient techniques for the live capture of carnivores are limited. In this study, we identified some of the factors that could affect the success of capturing red fox cubs with live capture traps (also known as cage traps). During a three-year period, we analysed 32 captures of 25 fox cubs (1.3 captures/fox). We assessed the impact of the following factors: sex of animals, month of trapping, weather conditions recorded for each trap-night, the willingness of cubs to explore and enter cage traps, the researchers’ activity around den complexes before trapping and distances to the nearest village or farm. The overall trap rate (32 captures, including recaptured cubs) and the trap rate for individual cubs (25 captures) was 11.2 cubs/100 trap-nights and 8.7/100 trap-nights, respectively. Animals other than foxes were captured only three times, thus the selectivity of the cage-trapping method was high (32/35 = 91.4%). The probability of capturing one cub per night was 70.2% (32 cubs/47 nights). Cubs inhabiting dens in the vicinity of human settlements were less likely to explore and enter traps. Vixens were more likely to relocate their litters if the activity of the staff setting the traps was intense at the trapping site. The success of trapping was higher during poor weather as, for example, during rain or thunderstorms. None of the trapped animals suffered any injuries. Whereas cage trapping can be an effective and safe capture method for juvenile foxes, capture efficiency is affected by the experience of the trappers and a range of other factors including weather and distance to human settlements.
Diverse Perspectives. A Review of Women Architects: Mode(s) of (R)existing. Reflections Based on a Cycle of Talks
Authors: Barros dos Reis Patricia Orfila
Published: February 2020

The book Women Architects: Mode(s) of (R)existing. Reflections Based on a Cycle of Talks (2018, edited by Patrícia Santos Pedrosa, Joana Pestana Lages, and Lia Gil Antunes, Lisbon, Women in Architecture Association, 100p), published as a bilingual collection (Portuguese and English), is structured around thirteen narratives by women architects, from a cycle of talks which took place from September 2017 to March 2018 in Lisbon. The book presents a concise record of the event’s purpose, which was to initiate a debate that takes into account both the gender perspective and women architects’ invisibility, as well as their multiple implications in the creation of Portuguese architecture, cities and territories within a traditionally male profession.
Association of Multiple Sclerosis Phenotypes with Single Nucleotide Polymorphisms of IL7R, LAG3, and CD40 Genes in a Jordanian Population: A Genotype-Phenotype Study
Authors: AL-Eitan Laith , Al Qudah Malak , Al Qawasmeh Majdi
Published: February 2020

It is thought that genetic variations play a vital role in the Multiple Sclerosis (MS) etiology. However, the role of genetic factors that influence the clinical features of MS remains unclear. We investigated the correlation between 21 single nucleotide polymorphisms within three genes (IL7R, LAG3, and CD40) and MS clinical characteristics in the Jordanian population. Blood samples and clinical phenotypic data were collected from 218 Arab Jordanian MS patients, vitamin D was measured, genomic DNA was extracted, and genotyping of the candidate genes’ polymorphisms were analyzed using the Sequenom MassARRAY® system. The association of these single nucleotide polymorphisms (SNPs) with MS was performed using a Chi-square, Fisher exact test, and one-way ANOVA. We found a significant association between vitamin D deficiency and three SNPs of the IL7R gene, namely rs987107 (P-value = 0.047), rs3194051 (P-value = 0.03), and rs1494571 (P-value = 0.036), in addition to two SNPs of CD40, namely rs1883832 and rs6074022 (P-value = 0.049 for both). rs3194051 of the IL7R gene (P-value = 0.003) and rs1922452 of the LAG3 gene (P-value = 0.028) were strongly associated with comorbidity. The number of relapses before drug onset was found to be correlated with IL7R SNPs rs969128 (P-value = 0.04) and rs1494555 (P-value = 0.027), whereas the expanded disability status scale (EDSS) was associated with rs1494555 polymorphism of IL7R gene (P-value = 0.026). Current findings indicate important correlations between certain SNPs and the risk of various phenotypes of multiple sclerosis in the Jordanian community. Therefore, this will not only contribute to the understanding of MS, but will also assist with the development of personalized treatment procedures.
NAD- and NADPH-Contributing Enzymes as Therapeutic Targets in Cancer: An Overview
Authors: Pramono Alvinsyah Adhityo , Rather Gulam M. , Herman Herry , Lestari Keri , Bertino Joseph R.
Published: February 2020

Actively proliferating cancer cells require sufficient amount of NADH and NADPH for biogenesis and to protect cells from the detrimental effect of reactive oxygen species. As both normal and cancer cells share the same NAD biosynthetic and metabolic pathways, selectively lowering levels of NAD(H) and NADPH would be a promising strategy for cancer treatment. Targeting nicotinamide phosphoribosyltransferase (NAMPT), a rate limiting enzyme of the NAD salvage pathway, affects the NAD and NADPH pool. Similarly, lowering NADPH by mutant isocitrate dehydrogenase 1/2 (IDH1/2) which produces D-2-hydroxyglutarate (D-2HG), an oncometabolite that downregulates nicotinate phosphoribosyltransferase (NAPRT) via hypermethylation on the promoter region, results in epigenetic regulation. NADPH is used to generate D-2HG, and is also needed to protect dihydrofolate reductase, the target for methotrexate, from degradation. NAD and NADPH pools in various cancer types are regulated by several metabolic enzymes, including methylenetetrahydrofolate dehydrogenase, serine hydroxymethyltransferase, and aldehyde dehydrogenase. Thus, targeting NAD and NADPH synthesis under special circumstances is a novel approach to treat some cancers. This article provides the rationale for targeting the key enzymes that maintain the NAD/NADPH pool, and reviews preclinical studies of targeting these enzymes in cancers.
Mutant p53-Associated Molecular Mechanisms of ROS Regulation in Cancer Cells
Authors: Cordani Marco , Butera Giovanna , Pacchiana Raffaella , Masetto Francesca , Mullappilly Nidula , Riganti Chiara , Donadelli Massimo
Published: February 2020

The TP53 tumor suppressor gene is the most frequently altered gene in tumors and an increasing number of studies highlight that mutant p53 proteins can acquire oncogenic properties, referred to as gain-of-function (GOF). Reactive oxygen species (ROS) play critical roles as intracellular messengers, regulating numerous signaling pathways linked to metabolism and cell growth. Tumor cells frequently display higher ROS levels compared to healthy cells as a result of their increased metabolism as well as serving as an oncogenic agent because of its damaging and mutational properties. Several studies reported that in contrast with the wild type protein, mutant p53 isoforms fail to exert antioxidant activities and rather increase intracellular ROS, driving a pro-tumorigenic survival. These pro-oxidant oncogenic abilities of GOF mutant p53 include signaling and metabolic rewiring, as well as the modulation of critical ROS-related transcription factors and antioxidant systems, which lead ROS unbalance linked to tumor progression. The studies summarized here highlight that GOF mutant p53 isoforms might constitute major targets for selective therapeutic intervention against several types of tumors and that ROS enhancement driven by mutant p53 might represent an “Achilles heel” of cancer cells, suggesting pro-oxidant drugs as a therapeutic approach for cancer patients bearing the mutant TP53 gene.
Enhanced CXCR4 Expression Associates with Increased Gene Body 5-Hydroxymethylcytosine Modification but not Decreased Promoter Methylation in Colorectal Cancer
Authors: Stuckel Alexei J. , Zhang Wei , Zhang Xu , Zeng Shuai , Dougherty Urszula , Mustafi Reba , Zhang Qiong , Perreand Elsa , Khare Tripti , Joshi Trupti , West-Szymanski Diana C. , Bissonnette Marc , Khare Sharad
Published: February 2020

In colorectal cancer (CRC), upregulation of the C-X-C motif chemokine receptor 4 (CXCR4) is correlated with metastasis and poor prognosis, highlighting the need to further elucidate CXCR4’s regulation in CRC. For the first time, DNA methylation and 5-hydroxymethylcytosine aberrations were investigated to better understand the epigenetic regulation of CXCR4 in CRC. CXCR4 expression levels were measured using qPCR and immunoblotting in normal colon tissues, primary colon cancer tissues and CRC cell lines. Publicly available RNA-seq and methylation data from The Cancer Genome Atlas (TCGA) were extracted from tumors from CRC patients. The DNA methylation status spanning CXCR4 gene was evaluated using combined bisulfite restriction analysis (COBRA). The methylation status in the CXCR4 gene body was analyzed using previously performed nano-hmC-seal data from colon cancers and adjacent normal colonic mucosa. CXCR4 expression levels were significantly increased in tumor stromal cells and in tumor colonocytes, compared to matched cell types from adjacent normal-appearing mucosa. CXCR4 promoter methylation was detected in a minority of colorectal tumors in the TCGA. The CpG island of the CXCR4 promoter showed increased methylation in three of four CRC cell lines. CXCR4 protein expression differences were also notable between microsatellite stable (MSS) and microsatellite instable (MSI) tumor cell lines. While differential methylation was not detected in CXCR4, enrichment of 5-hydroxymethylcytosine (5hmC) in CXCR4 gene bodies in CRC was observed compared to adjacent mucosa.
MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma
Authors: Forschner Andrea , Hilke Franz-Joachim , Bonzheim Irina , Gschwind Axel , Demidov German , Amaral Teresa , Ossowski Stephan , Riess Olaf , Schroeder Christopher , Martus Peter , Klumpp Bernhard , Gonzalez-Menendez Irene , Garbe Claus , Niessner Heike , Sinnberg Tobias
Published: February 2020

Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients’ responses to ICI and survival. Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.
Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers
Authors: Jaud Manon , Philippe Céline , Di Bella Doriana , Tang Weiwei , Pyronnet Stéphane , Laurell Henrik , Mazzolini Laurent , Rouault-Pierre Kevin , Touriol Christian
Published: February 2020

During carcinogenesis, almost all the biological processes are modified in one way or another. Among these biological processes affected, anomalies in protein synthesis are common in cancers. Indeed, cancer cells are subjected to a wide range of stresses, which include physical injuries, hypoxia, nutrient starvation, as well as mitotic, oxidative or genotoxic stresses. All of these stresses will cause the accumulation of unfolded proteins in the Endoplasmic Reticulum (ER), which is a major organelle that is involved in protein synthesis, preservation of cellular homeostasis, and adaptation to unfavourable environment. The accumulation of unfolded proteins in the endoplasmic reticulum causes stress triggering an unfolded protein response in order to promote cell survival or to induce apoptosis in case of chronic stress. Transcription and also translational reprogramming are tightly controlled during the unfolded protein response to ensure selective gene expression. The majority of stresses, including ER stress, induce firstly a decrease in global protein synthesis accompanied by the induction of alternative mechanisms for initiating the translation of mRNA, later followed by a translational recovery. After a presentation of ER stress and the UPR response, we will briefly present the different modes of translation initiation, then address the specific translational regulatory mechanisms acting during reticulum stress in cancers and highlight the importance of translational control by ER stress in tumours.
Calcium- and Voltage-Dependent Dual Gating ANO1 is an Intrinsic Determinant of Repolarization in Rod Bipolar Cells of the Mouse Retina
Authors: Paik Sun-Sook , Park Yong Soo , Kim In-Beom
Published: February 2020

TMEM16A/anoctamin1 (ANO1), a calcium (Ca2+)-activated chloride (Cl−) channel, has many functions in various excitable cells and modulates excitability in both Ca2+- and voltage-gating modes. However, its gating characteristics and role in primary neural cells remain unclear. Here, we characterized its Ca2+- and voltage-dependent components in rod bipolar cells using dissociated and slice preparations of the mouse retina. The I-V curves of Ca2+-dependent ANO1 tail current and voltage-gated Ca2+ channel (VGCC) are similar; as ANO1 is blocked by VGCC inhibitors, ANO1 may be gated by Ca2+ influx through VGCC. The voltage-dependent component of ANO1 has outward rectifying and sustained characteristics and is clearly isolated by the inhibitory effect of Cl− reduction and T16Ainh-A01, a selective ANO1 inhibitor, in high EGTA, a Ca2+ chelator. The voltage-dependent component disappears due to VGCC inhibition, suggesting that Ca2+ is the essential trigger for ANO1. In perforated current-clamping method, the application of T16Ainh-A01 and reduction of Cl− extended excitation periods in rod bipolar cells, revealing that ANO1 induces repolarization during excitation. Overall, ANO1 opens by VGCC activation during physiological excitation of the rod bipolar cell and has a voltage-dependent component. These two gating-modes concurrently provide the intrinsic characteristics of the membrane potential in rod bipolar cells.