bluuebunny/crossref_metadata_2025 huggingface dataset:
Zakres swobody artystycznej we Francji – wybrane aspekty
Authors: Pawluczuk-Bućko Paulina
Published: February 2020

W opracowaniu podjęto próbę analizy normatywnego kształtu granic wolności twórczości artystycznej we Francji. Z uwagi na to, że Francja odpokoleń uchodzi za kolebkę kultury i sztuki, ukazano zakres ingerencji prawa karnego w powszechnie uznaną wolność twórczości artystycznej – właśnie na przykładzie tego państwa. W artykule zwrócono również uwagę, iż kult wolności i kreatywności opanował rynek sztuki, przyczyniając się dopowstania sporów interpretacyjnych w orzecznictwie i doktrynie. Ilość procesów przeciwko artystom stanowi dowód na to, że jednak pewien zakres cenzury we Francji wciąż istnieje. Liczne skandale, procesy ożywiają debatę wokół wolności twórczości artystycznej. Autorka omówiła charakterystykęwybranych przestępstw popełnionych z przekroczeniem wolności artystycznej, wskazując na zasady odpowiedzialności karnej. W opracowaniu omówiono zakres swobody artystycznej we Francji w aspekcie ochrony praw autorskich i pokrewnych, swobody wypowiedzi, a także w zakresie swobody artystycznego wyrazu w kinematografii i teatrze.
Zasady procesowe w procesie karnym Szwajcarii – część 1
Authors: Trefilov Aleksandr
Published: February 2020

Podstawę procesu karnego stanowią zasady procesowe, które determinują jego przeznaczenie, narzędzia oraz procedurę stosowania prawa. Zasady procesowe obowiązują na wszystkich etapach postępowania – od śledztwa do wykonania wyroku i mają bezpośredni związek z efektywnością procesu. W artykule autor analizuje zasady procesowe zawarte w Kodeksie postępowania karnego Szwajcarii z 2007 r. Szczególną uwagę zwraca na zasady legalizmu, poszanowania godności człowieka, sprawiedliwości, praworządności, niezależności organów procesowych oraz zakończenia postępowania w rozsądnym terminie.
Ciężar dowodu i in dubio pro reo w prawie Unii Europejskiej
Authors: Gontarski Waldemar
Published: February 2020

Zgodnie zart. 6 ust. 2 dyrektywy 2016/343, państwa członkowskie zapewniają, aby wszelkie wątpliwości co do winy rozstrzygano na korzyść podejrzanego lub oskarżonego, także w sytuacji, gdy sąd dokonuje oceny, czy uniewinnić daną osobę. Przeto już na etapie postępowania przygotowawczego,przynajmniej od dnia 1 kwietnia 2018 r. (termin transpozycji dyrektywy) wszelkie wątpliwości co do ustaleń faktycznych i dowodów oraz wykładnii stosowania przepisów prawa rozstrzygać należy na korzyść podejrzanego. Na gruncie dyrektywy jest to zasada absolutna, czyli odpadają wszelkie wyjątki.
Management of an odontoid synchondrosis fracture causing chronic translational anterior atlanto-axial subluxation in a child with autism: case report
Authors: Fuell William , Bradley Lucas , Richter Gresham T. , Kazemi Noojan , Albert Gregory , McCarthy Richard , Ocal Eylem
Published: February 2020

The authors report an unusual case of an odontoid synchondrosis fracture causing chronic translational anterior atlanto-axial subluxation and present a discussion of the unique management of this case. Traumatic translational anterior atlanto-axial subluxation is a rare manifestation within pediatrics. Patients with preexisting abnormalities in ligamentous or bony structures may present with unusual symptomatology, which could result in delay of treatment. A 6-year-old male patient with autism who presented with acute respiratory arrest was noted to have an odontoid synchondrosis fracture and severe anterior translational atlanto-axial subluxation. Initial attempts at reduction with halo traction were tried for first-line treatment. However, because of concern regarding possible inadvertent worsening of the impingement, the presence of comorbid macrocephaly, and possible instability with only C1–2 fusion, a posterior C1 laminectomy was performed. Further release of the C1–2 complex and odontoid peg from extensive fibrous tissue allowed for complete reduction. Acute injuries of the C1–2 complex may not present as expected, and the presence of pain is not a reliable symptom. Halo traction is an appropriate initial treatment, but some patients may require surgical realignment and stabilization.
Model Pembelajaran Cooperative Learning Tipe Reciprokal Teaching Dalam Meningkatkan Hasil Belajar
Authors: Arifin Nur Rizqi , Yasri Budi
Published: February 2020

Rendahnya hasil belajar merupakan salah satu masalah dalam penelitian ini, karena hasil belajar merupakan tolok ukur keberhasilan proses pembelajaran. Rendahnya hasil belajar dilatarbelakangi oleh berbagai faktor diantaranya penggunaan model pembelajaran oleh pendidik. Metode penelitian yang digunakan adalah metode eksperimen. Teknik analisis data yang digunakan adalah uji homogenitas, N-Gain, dan Uji-t. Penelitian ini menghasilkan simpulan sebagai berikut: 1) Terdapat perbedaan hasil belajar peserta didik yang menggunakan model pembelajaran kooperatif tipe (Reciprokal Teaching) pada pengukuran awal (Pretest) dan pengukuran akhir (Postest) dengan rata-rata nilai pretest sebesar 49,33 dan rata-rata nilai posttest sebesar sebesar 83,33. Dengan nilai N.Gain hasil belajar peserta didik dari pretest ke posttest diperoleh angka sebesar 0,66. 2) Terdapat perbedaan hasil belajar peserta didik yang menggunakan model pembelajaran kooperatif tipe reciprokal teaching dengan yang menggunakan metode konvensional pada pengukuran akhir (posttest) dengan rata-rata nilai hasil belajar peserta didik yang menggunakan model pembelajaran kooperatif learning tipe reciprokal teaching pada pengukuran akhir (Posttest) sebesar 83,33. Sedangkan rata-rata nilai hasil belajar peserta didik yang menggunakan metode pembelajaran konvensional pada pengukuran akhir (Posttest) sebesar 62,33 dan hasil uji t menghasilkan  sebesar 9,09 dengan  1,67 dapat disimpulkan bahwa  >  atau 9,09 > 1,67 (Ha diterima). Kata kunci: Model pembelajaran, Kooperatif Learning tipe Reciprokal Teaching, Hasil Belajar
Improving the competitiveness of mechanical engineering
Authors: Kushnarev L. I , Aleshin V. F
Published: February 2020

The low level of competitiveness of Russian machinery and equipment is due, first of all, to an insufficient level of workmanship and reliability indicators. In terms of technical characteristics, the level of resource saving, the implementation of modern technological methods and methods for the manufacturing of products, works and services, many models of modern machinery are not inferior, and often surpass foreign analogues. But the low level of reliability indicators and, above all, the reliability of machines in the end significantly reduce the efficiency of its use in real production and economic conditions of consumers of equipment. The work is aimed at searching and substantiating directions for improving the quality of manufacturing and reliability indicators of domestic machinery and equipment based on the creation of proprietary production and technological systems and complexes and the introduction of a proprietary method of technical service. Improving the quality of Russian equipment on an innovative organizational and technological basis will ensure the necessary technological breakthrough in mechanical engineering with the minimum needs of production and technical resources in a short time. Studies indicate the need to reorganize engineering enterprises into large firms, branded production and technological systems and complexes that can provide a sharp and significant increase in the quality of equipment to the level of the best world analogues. The organization of large engineering companies allows solving the quality problems of machinery and equipment at all the main stages of their life cycle: design, construction, production, operation and disposal. At the same time, the efficiency of resolving emerging issues is significantly increased, since all structural divisions of the company are managed from a single center, whose strategic goal is to comprehensively improve the quality of engineering products. A quick and significant increase in the competitiveness of domestic machinery and equipment based on an increase in their manufacturing quality and reliability indicators is possible only with the introduction of their proprietary technical service. The company service system will allow establishing and excluding the causes of operational failures of machinery.
Kehidupan Sosial Masyarakat Arab Masa Awal Kehadiran Pendidikan Islam
Authors: Satir Muhammad
Published: February 2020

The social condition of the Arabs before Islam was known as the 'period of ignorance' or the age of ignorance, caused by social, political, morality and social relations in real conditions of error. To understand the jahiliyyah habits of the Arabs, the all-wise God sent an Apostle, Muhammad SAW. polite, humble, generous, brave, honest and trustworthy, they believe in "al-amiin". Arab education at the beginning of Islamic education was not well organized. However, education developed and they had at that time divided into three fields of knowledge. First, the knowledge of the nasab (history), history, and the influence of religion. Second, Ru'ya (dream) knowledge. Third, knowledge about reflection, the knowledge which according to Imam Gazali is a despicable science. While the science of poetry is the knowledge that is only controlled by people who are approved, and it is a sign of anxiety from the Arab community at that time.
Pengaruh Lingkungan Terhadap Perilaku Agresif Verbal Siswa Dalam Berkomunikasi
Authors: Agung Prasetya  , Fauzi Taty , Ramadhani Erfan
Published: February 2020

Verbal aggressive behavior is a negative behavior that is often found in everyday life. Researchers found verbal forms of student behavior when communicating with friends such as taunting friends by mentioning the name of a parent, hurting a friend by calling him an illegitimate child, and speaking harshly to the teacher. This study aims to determine whether there is an influence of the school environment on students' verbal aggressive behavior in communication. The population of this research is VIII grade students. The research sample of 160 people were selected using the Stratified Random Sampling technique. Data analysis using correlational product moment with the results of r_count of 0.328 and r_tabel value of 0.148 or in other words r_count> r_tabel = 0.328> 0.148. This shows the influence of the school environment on students' verbal aggressive behavior in communication.
Minat Membaca dan Implementasinya dalam Bimbingan dan Konseling
Authors: Marimbun Marimbun
Published: February 2020

Reading interst is a strong desire that  accompanied  a sense of pleasure of enjoyment of reading with self­­-will. Reading is a demand for individuals because reading is an effective activity to gain insight and knowledge. Surah Al-Alaq which is the first letter to come down is a reading order. Furthermore, the mandate of regulations and legislation also invites reading culture and encourages people to enjoy reading. The problematics of some of the research results indicate that Indonesian interest in reading is still relatively low. Therefore how important are efforts to foster interest in reading. Improving  interest in reading must be done through families, education units and the community. One of the factors influencing reading interest is the teacher. Counseling teacher/ Counselor is a teacher assigned to carry out guidance and counseling activities in schools responsible for providing various service activities in developing various student potentials and encouraging national education goals. Guidance counseling at schools is expected to be more intensive in order to improve students interest in reading through various types of counseling services. As for some services that can be applied in improving interest in reading such as orientation services, information, group guidance and individual counseling.
The Suppression Effect of Kebar Extract on Endometriosis Lesion MDA and TNF -a Independent to VEGF A Study in Endometriosis Mice Mode
Authors: Trisetiyono Yuli , Pramono Noor , Hidayat Syarief T. , Widjiati Widjiati
Published: February 2020

Background: The pathogenesis of endometriosis remains unclear, and involves multifactorial etiologies. The increase in oxidative stress is known to be associated with this disease. Oxidative stress increases angiogenesis and supports the proliferation of endometriosis tissue in the peritoneal cavity. Kebar grass, a medicinal plant, is expected to increase antioxidant defense resulting in decreased oxidative stress, inflammation, angiogenesis, and reduced endometrial tissue implants.

 

Objective: To investigate the effects of Kebar grass extract administration to MDA serum levels, TNF-a and VEGF expression, and the extension of the endometriotic lesions in mice model.

 

Methods: This study was experimentally designed. It was conducted in the Department of Obstetrics Gynecology, Faculty of Medicine Diponegoro, University and Faculty of Veterinary Medicine, Airlangga University. Twenty-one mice were divided into three groups: the first group is control of 7 untreated endometriosis mice model, the second group consisted of 7 mice injected with leuprolide acetate 1mg/kgBB single dose, and the last group consisted of 7 mice fed with Kebar grass extract 3mg/day for 14 days. MDA serum level was measured by spectrophotometry, TNF-a  and VEGF expression by IHC using Rammele Scale Index (ImmunoReactive Score), whereas the extension of the endometriotic lesions was measured using computerize tracing.

 

Results: Both Kebar grass extract and leuprolide acetate administration significantly decrease MDA serum levels in endometriosis mice model, compare with the control group, (0.09Â±0.02 nmol, 0.11Â±0.07 nmol, and 0.30Â±0.06 nmol, respectively; p=0.001). TNF-Î± expression of the group treated with Kebar grass extract was lower than leuprolide acetate and control group (2.43Â±1.521 %, 4.86Â±0.458 %, and 7.26Â±2.898 %, respectively; p=0.002). However, there was no significant difference in VEGF expression among study groups (4.34Â±2.40 %, 5.11Â±1.95 %, and 7.40Â±3.49 % respectively; p=0.116). Finally, the extension of the endometriotic lesions of the mouse models administered with Kebar grass extract and leuprolide acetate was smaller than the control group (0 mm2, 4.54Â±7.75 mm2, and 34.80Â±13.09 mm2 respectively; p=0.005).

 

Conclusion: Kebar grass extract has the effect of decreasing MDA serum levels and reducing TNF-Î± expression, resulted in smaller endometriotic lesions in mice, even though it does not affect VEGF expression.

 

Keywords: malondialdehyde, tumour necrosis factor alpha, vascular endothelial growth factor, endometriotic lesion, kebar grass extract, endometriosis mouse
Adaptation and identity shifts after migration and return migration: Turkish qualified returnees from Germany and the US
Authors: Yilmaz Sener Meltem
Published: February 2020

This study looks at the adaptation experiences of Turkish qualified migrants who returned to Turkey after living in Germany and the US, discussing their identity shifts both during the period spent in the host country and after the return. I look at their i- pre-migration familiarity with the language and culture of the host country, ii- social groups in the host country, iii- association memberships in the host country, iv- frequency of their visits to Turkey, v- the extent to which they followed the developments in Turkey, vi- reasons behind the decision to return, vii- re-adaptation to the home country culture after return, and viii- relationships with other returnees and host country nationals after return. By focusing on these aspects of their experiences, I aim to demonstrate the kinds of orientations they have had to the host and home country cultures, and the identity shifts they had both after migration and return. I also discuss whether there are any differences between the returnees from Germany and the US in terms of these dimensions.
Mosquitofish avoid thermal stress by moving from open water to the shade of the mangrove Rhizophora mangle
Authors: Hendy IW , Burt O , Clough S , Young L , Cragg SM
Published: February 2020

Mangrove trees provide environmental buffering for animals by reducing daytime water thermal maxima. Shade from Rhizophora mangle trees reduces thermal stress for the mosquitofish Gambusia affinis. Data were collected from mangrove forests in Quintana Roo, Mexico, at 2 sites: (1) Soliman Bay, a mangrove forest decoupled from direct ocean water, and (2) La Lunita with semi-direct access to ocean water. During cooler morning hours at Soliman Bay, large numbers of mosquitofish foraged in open channels. At the same time, few mosquitofish utilised shaded areas within the R. mangle prop roots. When channels exceeded water temperatures above 38°C, mosquitofish migrated into the shaded areas provided by R. mangle trees. Channel water reached a daytime maximum temperature of 46°C, while daytime-shaded R. mangle areas remained 6.2°C cooler. Temperature rise and abundance shifts were not found in La Lunita, which has water temperatures of 27 to 28°C throughout the day. Size distributions between both localities showed mosquitofish caught in Soliman Bay to be >10% smaller than the mosquitofish from La Lunita, which had a greater abundance of mature adults. In Soliman Bay, mosquitofish were small, and the thermal stresses may impose serious developmental impacts that would be reduced by occupying water shaded by R. mangle. Refuge from R. mangle provides environmental buffering for fish, and future increasing water temperatures may reveal a greater use of this little-known mechanism. This study provides an example of a mechanism whereby mangroves support intertidal biodiversity through environmental buffering.
Olfactory Bulbectomy in Methamphetamine-Treated Rat Mothers Induces Impairment in Somatic and Functional Development of Their Offspring
Authors: ŠLAMBEROVÁ R. , RUDÁ-KUČEROVÁ J. , BABINSKÁ Z. , ŠEVČÍKOVÁ M.
Published: February 2020

Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.
Dom narodnoga zdravlja u Osijeku
Authors: Živaković-Kerže Zlata
Published: February 2020

Velikim zalaganjem Andrije Štampara 1920-ih i 1930-ih došlo je do reorganizacije i unaprjeđivanja zdravstvene službe. Pri tome je golemo značenje imala njegova zamisao o potrebi osnivanja i otvaranja domova zdravlja diljem Kraljevine Srba, Hrvata i Slovenaca, tj. potonje Kraljevine Jugoslavije. Otvaranjem Doma narodnoga zdravlja u Osijeku s brojnim službama, napose dispanzerskom i protuepidemijskom, osigurana je u gradu na Dravi bolja zdravstvena zaštita stanovništva. Rad Doma narodnoga zdravlja odvijao se potpuno u skladu s tadašnjim programom socijalne medicine koju je zastupao Štampar, koji je do 1930. u nekoliko navrata boravio u Osijeku. U sastavu novootvorenoga Doma narodnoga zdravlja djelovale su gradska i školska poliklinika, sanitarna inspekcija, anti-TBC i kožno‑venerični dispanzer, antitrahomska i antirabična stanica, dječji dispanzer, zubni odjel i Higijenski zavod, dok su pokusne životinje, potrebne za rad zavodskoga bakteriološkog laboratorija, držane – do izgradnje posebne dvorišne zgrade (1958/59) – u dvorišnoj zgradi koja se nalazila uz zgradu u kojoj je danas Odjel neurologije, dakle u sklopu osječke Opće bolnice.
What Do Coordinators Do? Mental Health Policy Implementation as Translation
Authors: Darcis Coralie , Thunus Sophie
Published: February 2020

Coordination is described as a widespread function emerging in relation to policy plans inducing collaboration between different sectors, organizations and professions. This paper suggests seeing the implementation phase as a translation process, one where the content of policy plans is reinvented primarily through discussion rather than linearly transferred from the political to the professional arena. It focuses on the function of coordinator with a view to examining how this function is performed and questions its influence on the local translation of both policy plans. The data collection was part of two research projects focusing on the reform of Belgian mental healthcare and the creation of care pathways for forensic patients, combining document analysis, interviews (n = 82) and observations (n = 58). The results highlight the inherent ambiguity of the coordinators’ working environment, the socially-disputed nature of their function and define the coordinators as connection-makers who exert power over processes rather than people or structures. It demonstrates that coordinators influence the policy process by inducing discussions at meetings and the documents subsequently produced. In conclusion, this paper defines coordinators as process managers whose work largely consists of translating policy plans through event connectivity and contextualizing practices. Given the importance of translation in policy implementation, this paper calls for a reconsideration of policy evaluation as well as of the coordinators’ recruitment and training procedures.
Neural Network Model Analysis for Investigation of NO Origin in a High Mountain Site
Authors: Aruffo Eleonora , Di Carlo Piero , Cristofanelli Paolo , Bonasoni Paolo
Published: February 2020

Measurements of nitrogen oxide (NO), ozone (O3), and meteorological parameters have been carried out between September and November 2013 in a high mountain site in Central Italy at the background station of Mt. Portella (2401 m a.s.l.). Three NO plumes, with concentrations up to about 10 ppb, characterized the time series. To investigate their origin, single hidden layer feedforward neural networks (FFNs) have been developed setting the NO as the output neuron. Five different simulations have been carried out maintaining the same FFNs architecture and varying the input nodes. To find the best simulations, the number of the neurons in the hidden layer varied between 1 and 40 and 30 trials models have been evaluated for each network. Using the correlation coefficient (R), the normalized mean square error (NMSE), the fractional bias (FB), the factor of 2 (FA2) and the t-student test, the FFNs results suggest that two of the three NO plumes are significantly better modeled when considering the dynamical variables (with the highest R of 0.7996) as FFNs input compare to the simulations that include as input only the photochemical indexes (with the lowest R of 0.3344). In the Mt. Portella station, transport plays a crucial role for the local NO level, as demonstrated by the back-trajectories; in fact, considering also the photochemical processes, the FFNs results suggest that transport, more than local sources or the photochemistry, can explain the observed NO plumes, as confirmed by all the statistical parameters.
The Influence of the Atlantic Multidecadal Oscillation on the Choco Low-Level Jet and Precipitation in Colombia
Authors: Loaiza Cerón Wilmar , Andreoli Rita Valeria , Kayano Mary Toshie , Ferreira de Souza Rodrigo Augusto , Jones Charles , Carvalho Leila M. V.
Published: February 2020

This study examines the influence of the Atlantic Multidecadal Oscillation (AMO) on the Choco Low-level Jet (CJ) variations during the 1983–2016 period. Considering the September–November (SON) 925 hPa zonal wind index in the CJ core, a significant breakpoint occurs in 1997 with larger values after 1997. The changes in the CJ and Caribbean Low-Level Jet (CLLJ), and their related ocean-atmospheric patterns and impacts on precipitation over Colombia were analyzed considering separately the 1983–1996 and 1998–2016 periods, which overlap the cold and warm AMO phases, respectively. During the 1998–2016 period, the negative sea surface temperature (SST) anomalies in the tropical Pacific Ocean and the positive ones in the Caribbean Sea and Tropical North Atlantic (TNA) strengthen the CJ and weaken the CLLJ, and moisture is transported into Central and Western Colombia increasing the rainfall there. Our results indicate that part of the CJ strengthening after 1997 was due to a higher percentage of intense CJ events coinciding with La Niña events during the warm AMO and cold Pacific Decadal Oscillation (PDO) background. However, the AMO-related SST and sea level pressure (SLP) variations in the TNA seem to be more crucial in modulating the CJ and CLLJ intensities, such that CJ is weakened (intensified) and CLLJ is intensified (weakened) before (after) 1997. As far as we know, the relations of the CJ and CLLJ intensities to the AMO phases were not examined before and might be useful for modeling studies.
Design and Characterization of an “All-in-One” Lentiviral Vector System Combining Constitutive Anti-GD2 CAR Expression and Inducible Cytokines
Authors: Zimmermann Katharina , Kuehle Johannes , Dragon Anna Christina , Galla Melanie , Kloth Christina , Rudek Loreen Sophie , Sandalcioglu I. Erol , Neyazi Belal , Moritz Thomas , Meyer Johann , Rossig Claudia , Altvater Bianca , Eiz-Vesper Britta , Morgan Michael Alexander , Abken Hinrich , Schambach Axel
Published: February 2020

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.
Clinical Relevance of Immune Checkpoints on Circulating Tumor Cells in Breast Cancer
Authors: Papadaki Maria A. , Koutsopoulos Anastasios V. , Tsoulfas Panormitis G. , Lagoudaki Eleni , Aggouraki Despoina , Monastirioti Alexia , Koutoulaki Chara , Apostolopoulou Christina A. , Merodoulaki Aikaterini C. , Papadaki Chara , Mavroudis Dimitrios , Agelaki Sofia
Published: February 2020

The role of CD47 and PD-L1 expression on circulating tumor cells (CTCs) remains unclear, and it is currently unknown whether their distribution varies between the blood and tumor tissue in breast cancer (BC). In this study, CD47 and PD-L1 expression was investigated a) on peripheral blood mononuclear cell (PBMC) cytospins from early (n = 100) and metastatic (n = 98) BC patients, by triple immunofluorescence for CD47/PD-L1/Cytokeratins, and b) on matched primary and/or metastatic tumor tissue from CTC-positive patients using immunohistochemistry. CD47+and/orPD-L1+ CTCs were detected in 11%, 16.9%, and 29.6% of early, recurrent, and de novo metastatic patients (p = 0.016). In metastatic disease, CD47highand/orPD-L1high CTCs were associated with disease progression (p = 0.005) and shorter progression-free survival (PFS) (p = 0.010), and independently predicted for an increased risk of relapse (HR: 2.719; p = 0.008) and death (HR: 2.398; p = 0.034). PD-L1 expression rates differed between CTCs and tissue tumor cells and between peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) (positive concordance of 3.8% and 4%, respectively). CD47 expression also differed between CTCs and tumor cells (positive concordance of 11.5%). In conclusion, CTCs expressing CD47 and PD-L1 have independent poor prognostic implications in metastatic BC, indicating a potential role of innate and adaptive immune evasion mechanisms in their metastatic potential. The clinical value of the parallel assessment of the peripheral and local immune response merits further evaluation in BC.
Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis
Authors: Darvekar Sagar , Juzenas Petras , Oksvold Morten , Kleinauskas Andrius , Holien Toril , Christensen Eidi , Stokke Trond , Sioud Mouldy , Peng Qian
Published: February 2020

Extracorporeal photopheresis (ECP), a modality that exposes isolated leukocytes to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light, is used to treat conditions such as cutaneous T-cell lymphoma and graft-versus-host disease. However, the current procedure of ECP has limited selectivity and efficiency; and produces only partial response in the majority of treated patients. Additionally, the treatment is expensive and time-consuming, so the improvement for this modality is needed. In this study, we used the concept of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor of an endogenously synthesized photosensitizer protoporphyrin IX (PpIX) in combination with blue light to explore the possibility of targeting activated human blood T cells ex vivo. With various T-cell activation protocols, a high ALA-induced PpIX production took place in activated CD3+, CD4+CD25+, and CD8+ T cell populations with their subsequent killing after blue light exposure. By contrast, resting T cells were much less damaged by the treatment. The selective and effective killing effect on the activated cells was also seen after co-cultivating activated and resting T cells. Under our clinically relevant experimental conditions, ALA-PDT killed activated T cells more selectively and efficiently than 8-MOP/UV-A. Monocyte-derived dendritic cells (DCs) were not affected by the treatment. Incubation of ALA-PDT damaged T cells with autologous DCs induced a downregulation of the co-stimulatory molecules CD80/CD86 and also upregulation of interleukin 10 (IL-10) and indoleamine 2,3-dioxygenase expression, two immunosuppressive factors that may account for the generation of tolerogenic DCs. Overall, the data support the potential use of ALA-PDT strategy for improving ECP by selective and effective killing of activated T cells and induction of immune tolerance.
Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy
Authors: Ortega-García María Belén , Mesa Alberto , Moya Elisa L.J. , Rueda Beatriz , Lopez-Ordoño Gabriel , García Javier Ángel , Conde Verónica , Redondo-Cerezo Eduardo , Lopez-Hidalgo Javier Luis , Jiménez Gema , Peran Macarena , Martínez-González Luis J. , del Val Coral , Zwir Igor , Marchal Juan Antonio , García María Ángel
Published: February 2020

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients’ data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.
NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models
Authors: McDonald J. Tyson , Stainforth Robert , Miller Jack , Cahill Thomas , Silveira Willian A. da , Rathi Komal S. , Hardiman Gary , Taylor Deanne , Costes Sylvain V. , Chauhan Vinita , Meller Robert , Beheshti Afshin
Published: February 2020

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. Methods: We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 to 1.0 Gy for ground studies, as well as samples flown in low Earth orbit (LEO) with total doses of 1.0 mGy to 30 mGy, were utilized. Results: From this analysis, we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. Conclusions: We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.
Approaches for Selective Oxidation of Methane to Methanol
Authors: Sharma Richa , Poelman Hilde , Marin Guy B. , Galvita Vladimir V.
Published: February 2020

Methane activation chemistry, despite being widely reported in literature, remains to date a subject of debate. The challenges in this reaction are not limited to methane activation but extend to stabilization of the intermediate species. The low C-H dissociation energy of intermediates vs. reactants leads to CO2 formation. For selective oxidation, nature presents methane monooxygenase as a benchmark. This enzyme selectively consumes methane by breaking it down into methanol. To assemble an active site similar to monooxygenase, the literature reports Cu-ZSM-5, Fe-ZSM-5, and Cu-MOR, using zeolites and systems like CeO2/Cu2O/Cu. However, the trade-off between methane activation and methanol selectivity remains a challenge. Density functional theory (DFT) calculations and spectroscopic studies indicate catalyst reducibility, oxygen mobility, and water as co-feed as primary factors that can assist in enabling higher selectivity. The use of chemical looping can further improve selectivity. However, in all systems, improvements in productivity per cycle are required in order to meet the economical/industrial standards.
Application of Various Metal-Organic Frameworks (MOFs) as Catalysts for Air and Water Pollution Environmental Remediation
Authors: Jang Sanha , Song Sehwan , Lim Ji Hwan , Kim Han Seong , Phan Bach Thang , Ha Ki-Tae , Park Sungkyun , Park Kang Hyun
Published: February 2020

The use of metal-organic frameworks (MOFs) to solve problems, like environmental pollution, disease, and toxicity, has received more attention and led to the rapid development of nanotechnology. In this review, we discuss the basis of the metal-organic framework as well as its application by suggesting an alternative of the present problem as catalysts. In the case of filtration, we have developed a method for preparing the membrane by electrospinning while using an eco-friendly polymer. The MOFs were usable in the environmental part of catalytic activity and may provide a great material as a catalyst to other areas in the near future.
Effect of Ethanol on the Morphology and Textual Properties of ZSM-5 Zeolite
Authors: Liu Xiuru , Sun Yiqing
Published: February 2020

The morphology of ZSM-5 zeolite impacts the adsorption, separation and diffusion of molecules. The morphology and textural properties of ZSM-5 zeolites were adjusted by regulating the content of ethanol in the synthesis gel. When the ratio of ethanol/SiO2 was lower than 2, the obtained crystals were isolated particles. With higher ethanol concentration, the chainlike zeolite was generated due to the condensation of terminal Si-OH groups. The crystals stacked more and more compactly with the increase in ethanol concentration, resulting in decreased specific surface area, total volume and mesoporous volume. The crystal size increased gradually with the increase in the ethanol concentration. Moreover, some other small molecular alcohols could also induce the formation of chainlike morphology of ZSM-5.
Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL/STAT5 Pathway
Authors: Sarno Federica , Pepe Giacomo , Termolino Pasquale , Carafa Vincenzo , Massaro Crescenzo , Merciai Fabrizio , Campiglia Pietro , Nebbioso Angela , Altucci Lucia
Published: February 2020

Some species of clover are reported to have beneficial effects in human diseases. However, little is known about the activity of the forage plant Trifolium repens, or white clover, which has been recently found to exert a hepatoprotective action. Scientific interest is increasingly focused on identifying new drugs, especially natural products and their derivatives, to treat human diseases including cancer. We analyzed the anticancer effects of T. repens in several cancer cell lines. The phytochemical components of T. repens were first extracted in a methanol solution and then separated into four fractions by ultra-high-performance liquid chromatography. The effects of the total extract and each fraction on cancer cell proliferation were analyzed by MTT assay and Western blotting. T. repens and, more robustly, its isoflavonoid-rich fraction showed high cytotoxic effects in chronic myelogenous leukemia (CML) K562 cells, with IC50 values of 1.67 and 0.092 mg/mL, respectively. The block of cell growth was associated with a total inhibition of BCR-ABL/STAT5 and activation of the p38 signaling pathways. In contrast, these strongly cytotoxic effects did not occur in normal cells. Our findings suggest that the development of novel compounds derived from phytochemical molecules contained in Trifolium might lead to the identification of new therapeutic agents active against CML.
Silencing of PARP2 Blocks Autophagic Degradation
Authors: Jankó Laura , Sári Zsanett , Kovács Tünde , Kis Gréta , Szántó Magdolna , Antal Miklós , Juhász Gábor , Bai Péter
Published: February 2020

Poly(ADP-Ribose) polymerases (PARPs) are enzymes that metabolize NAD+. PARP1 and PARP10 were previously implicated in the regulation of autophagy. Here we showed that cytosolic electron-dense particles appear in the cytoplasm of C2C12 myoblasts in which PARP2 is silenced by shRNA. The cytosolic electron-dense bodies resemble autophagic vesicles and, in line with that, we observed an increased number of LC3-positive and Lysotracker-stained vesicles. Silencing of PARP2 did not influence the maximal number of LC3-positive vesicles seen upon chloroquine treatment or serum starvation, suggesting that the absence of PARP2 inhibits autophagic breakdown. Silencing of PARP2 inhibited the activity of AMP-activated kinase (AMPK) and the mammalian target of rapamycin complex 2 (mTORC2). Treatment of PARP2-silenced C2C12 cells with AICAR, an AMPK activator, nicotinamide-riboside (an NAD+ precursor), or EX-527 (a SIRT1 inhibitor) decreased the number of LC3-positive vesicles cells to similar levels as in control (scPARP2) cells, suggesting that these pathways inhibit autophagic flux upon PARP2 silencing. We observed a similar increase in the number of LC3 vesicles in primary PARP2 knockout murine embryonic fibroblasts. We provided evidence that the enzymatic activity of PARP2 is important in regulating autophagy. Finally, we showed that the silencing of PARP2 induces myoblast differentiation. Taken together, PARP2 is a positive regulator of autophagic breakdown in mammalian transformed cells and its absence blocks the progression of autophagy.
Characterization of Tanzanian Avocado Using Morphological Traits
Authors: Juma Ibrahim , Nyomora Agnes , Hovmalm Helena Persson , Fatih Moneim , Geleta Mulatu , Carlsson Anders S. , Ortiz Rodomiro Octavio
Published: February 2020

Two-hundred and twenty-six old avocado trees (Persea americana Mill) derived from seeds were selected from eight districts of the Mbeya, Njombe and Songwe regions in Tanzania. The tree, leaf, fruit and seed characteristics were studied using the descriptors for avocado (Persea spp.) from the International Plant Genetic Resources Institute. Cross tabulation and Chi-square tests were conducted in order to assess the distribution of traits between districts and altitude ranges. Principle coordinate analysis (PCoA) and hierarchical cluster analysis (HCA) were used to assess variation of traits within and among districts. Various morphological features were observed among the samples which point to the existence of the Mexican, Guatemalan and West Indian avocado races in Tanzania. The biplot from PCoA revealed extensive variation between the sampled trees at the district level but no clear groupings of the samples based on geographic location. Likewise, dendrograms ensuing from the neighbor–joining and Wards methods displayed that the avocado samples from the same district and even region differed considerably. This morphological trait variation suggests high diversity that may help in planning germplasm management and conservation, as well as breeding strategies in the future.
Venomous Snake Abundance Within Snake Species’ Assemblages Worldwide
Authors: Luiselli Luca , Sale Leonardo , Akani Godfrey C. , Amori Giovanni
Published: February 2020

Venomous snakes are among the main sources of mortality for humans in rural regions, especially in tropical countries. In this study, a meta-analysis of quantitative community ecology studies on snake assemblages throughout the world was conducted in order to evaluate variation in the frequency of occurrence of venomous species and venomous individuals by habitat and continent. A bibliographic search was done by consulting “Google Scholar” and “ISI Web of Knowledge”. In total, 24,200 results were obtained from our bibliographic search, out of which 60 independent studies reporting raw and analyzable quantitative data from 81 distinct snake communities were retained and used for analyses. A snow-ball procedure was also used to uncover additional studies to include in the analyses. We gathered data on a total of 30,537 snake individuals, with an average of almost 30% of venomous individuals. The mean number of sympatric species was 19, whereas the mean number of sympatric venomous species was almost 5. Venomous snake species accounted for 24.4% of the total species in each community—almost the same as the overall percentage of venomous snake species known worldwide (about 24%). The frequency of occurrence of venomous individuals did not differ significantly between tropical and temperate snake communities, and the same was true for the frequency of venomous species within each community. Thus, the greater number of snakebites in tropical countries is not due to there being more venomous snake species or individuals. The total number of species and the number of venomous species observed in each community were positively correlated, and there was a significant difference among continents in terms of the mean number of species in each community. Within communities, there were inter-continental and inter-habitat differences in both the percentage of venomous species and in the percentage of venomous individuals. The Generalized Linear Model (GLM) revealed that the frequency of venomous species at a local scale depended only on the total number of species inhabiting a given site, whereas the frequency of venomous individuals within communities depended on both the total number of species and a habitat–continent interaction. Our meta-analysis could enable the appropriate authorities/agencies to take the relative abundance of venomous species/individuals within snake assemblages into consideration for a better positioning of the first aid centers in locations where snake antivenoms should be available.