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1
Mihu, Riko. "Hunting and Trapping Technique Among Idu Mishmi Community of Arunachal Pradesh." Dera Natung Government College Research Journal 5, no. 1 (2020): 17–24. http://dx.doi.org/10.56405/dngcrj.2020.05.01.03.
Повний текст джерелаАнотація:
The tribal people obtain their numerous requirements from the area they inhabit with the help simplest tools and without any technical aid. They face multiple challenges with the modern way of life but yet these people are the most caring and loving people. Idu Mishmi is one of the scheduled tribes in Arunachal Pradesh. It has a population that spread over Dibang Valley, Lower Dibang Valley, Lohit, and some parts of the East Siang district of Arunachal Pradesh. Idu Mishmi community of the state is also one of the tribes involved in hunting and trapping activities for live subsistence and leisure purposes too. From this piece of study, the author tries to understand the hunting and trapping technique used by the Idu tribe. This hunting and trapping are obsolete nowadays. Nevertheless, Hunting and trapping shall remain strongly linked to local culture and tradition as long as tribal lives exist.
2
Alexandro, Rinto, Pernandes Pernandes, Eli Karliani, Fendy Hariatama, and Tonich Uda. "The Implementation of Nucu Ngoruh in The Traditional Marriage of The Dayak Siang Tribe." Jurnal Ilmiah Pendidikan Pancasila dan Kewarganegaraan 7, no. 2 (July 15, 2022): 387. http://dx.doi.org/10.17977/um019v7i2p387-394.
Повний текст джерелаАнотація:
This study aimed to analyze the implementation, support, and inhibiting factors of nucu ngoruh in Dayak Siang traditional weddings. A qualitative method with observation, interviews, and documentation was utilized to get the research finding. The implementation of nucu ngoruh in traditional Dayak Siang marriages in Saripoi Village consisted of two versions. The first version of the wedding procession was making pondong, making lawang sakepeng, making hompong, and the marriage contract process. The second version of the marriage procession was pantan pulut, pali manasai, ngiap or kandan ngiap, second hompong and third hompong, which includes hompong balanga, lawang sakepeng, Manasai dance, hompong human/female, and the bride and groom sat side by side on the Mura gong. The supporting factor for nucu ngoruh was that indigenous peoples highly respected the provisions of social and divine values, so indigenous people adjusted to the provisions for the preparation of traditional goods, and the procession of traditional marriages might also be under customary rules. Finally, there were four inhibiting factors for nucu ngoruh. First, the groom was not ready either physically or mentally. The second was the lack of financial support provided. The third was the absence of people who mastered the art of sculpture was make statues to complete the implementation of the traditional Dayak Siang wedding. Fifth, there was no written text or manual procedure for implementing the traditional Dayak Siang wedding procession.
3
Koyu, Geri. "British Frontier Policy and Creation of Native Agents (Kotokis, Jamadars and Gams) in Siang Valley." Dera Natung Government College Research Journal 7, no. 1 (December 2022): 46–60. http://dx.doi.org/10.56405/dngcrj.2022.07.01.05.
Повний текст джерелаАнотація:
In the nineteenth and twentieth century, the Siang Valley of Arunachal Pradesh witnessed the British policy of creating native agents such as Kotokis, Jamadars and Gams to facilitate colonial political control in the valley. The injection of such native agents interfered with the indigenous political setting of the valley. The present paper tries to discern the factors behind the policy of creating native agents, its process and the effects it had on the tribal society of Siang Valley.
4
Boyle, Jason B., Deanna M. Kennedy, Chaoyi Wang, and Charles Shea. "Optimizing the Control of High Index of Difficulty Movements: The Role of the Tracking Template." Journal of Motor Learning and Development 4, no. 1 (June 2016): 80–99. http://dx.doi.org/10.1123/jmld.2015-0016.
Повний текст джерелаАнотація:
An experiment by Boyle, Kennedy, and Shea (2012) demonstrated that practice tracking a template created from a sine wave results in enhanced performance and transfer on a reciprocal aiming task with an index of difficulty (ID) of 6. An experiment was conducted to determine whether tracking a template constructed from recorded participants' performance with ID = 6 would provide the same benefit. Participants were assigned to one of four groups (Fitts–master, Fitts–yoked, sine–master, and sine–yoked). After acquisition, visual templates were constructed for the Fitts–yoked and sine–yoked conditions. The templates were generated from the unique displacement data of the Fitts– and sine–master participants. These made up the training template for the Fitts– and sine–yoked participants. After acquisition, all participants were asked to perform test trials under their respective acquisition conditions (Test 1) and test trials under ID = 6 reciprocal aiming conditions (Test 2). Results indicated faster movement times in the sine-wave training groups on Test 2 than in both Fitts groups. These results indicate that the presentation of a tracking template can result in lower dwell times in the Fitts–yoked pairing on Test 2. However, the findings indicate the need to use templates that guide the movement in a way that promotes an equal acceleration–deceleration profile paired with smooth target reversal.
5
Wang, Qi Rui, and Wei Fan. "Ramie Fiber Modification Trials under Different Conditions." Applied Mechanics and Materials 268-270 (December 2012): 245–49. http://dx.doi.org/10.4028/www.scientific.net/amm.268-270.245.
Повний текст джерелаАнотація:
The test studied three ways of modification effect for ramie fiber, included PVC coated, MMA graft and silane coupling. Also the diverse factors for modification were explored under the situations of hydrophilicity, biodegradability and parasitotropism. The results showed that: All modified ways for KH-570 silane coupling, PVC coated, and MMA graft could reduce bibulous rate of ramie fiber effectively, which PVC coated was best (10.42 %), while bibulous rate of MMA graft was 10.56 %. Both of all were lower than the bibulous rate of unmodified (4-5 %). Then soaked in conditions of distilled water, anaerobic sludge and anaerobic sludge, the mass loss unmodified were largest, loss of minimum were MMA grafting, MMA grafting and KH-570 coupling, with the mass loss rate were 11.67 %,21.23 % and 22.73%,respectively. With the situation of high salt concentration, the modified fiber degraded significantly that all of the degradation rate were lower than 8%. The biological properties of ramie fiber were effectively enhanced by modification way of MMA grafted, in aspects of hydrophilicity, biodegradability. Under the condition of MMA grafting, microbial growth and purifying effect, the service life of the fiber was prolonged efficacious.
6
Abdulhameed, Jamal Ismael, Ahmed H. Ali, and Ismail Hakkı Kara. "Developing Crumbed Rubber Tires / Epoxy Composite, by Surface Treatment with Different Silane Coupling Agents." Materials Science Forum 1077 (December 15, 2022): 39–45. http://dx.doi.org/10.4028/p-h41ugr.
Повний текст джерелаАнотація:
Converting used tries to useful materials and avoiding harmful effects of accumulation used tires, is a great economic and environmental issue. Using of crumbing rubber of used tires CRT as filler materials shows declining in mechanical properties of CRT/polymer composites as weak bonding between CRT and polymeric matrices. This work include, CRT surface treating by three kinds of silane coupling agent, Trimethoxysilyl propyl methacrylate, 3-chloropropyl triethoxy silane and Silicic acid, before using as filler materials in epoxy matrix. 10 wt. % of non-treated and treated CRT/epoxy composite specimens have been prepared and tested to evaluate effect of CRT surface treatment into composite mechanical properties. The results show that modulus of elasticity, tensile strength, and fracture toughness of treated CRT/epoxy composite could improve by 56%, 30%, 36% respectively comparing with that of non-treated CRT/epoxy, after treating by 3-chloropropyl triethoxy silane coupling agent, whereas surface treating by other types of silane coupling agents could produce less mechnical improvement but still better that of non-treated.
7
Wei, Zhonghua. "The complete mitochondrial genomes of five Agrilinae (Coleoptera, Buprestidae) species and phylogenetic implications." ZooKeys 1092 (April 6, 2022): 195–212. http://dx.doi.org/10.3897/zookeys.1092.80993.
Повний текст джерелаАнотація:
Five complete mitochondrial genomes of five species from the subfamily Agrilinae were sequenced and annotated, including Coraebus diminutus Gebhardt, 1928 (15,499 bp), Coraebus cloueti Théry, 1893 (15,514 bp), Meliboeus sinae Obenberger, 1935 (16,108 bp), Agrilus sichuanus Jendek, 2011 (16,521 bp), and Sambus femoralis Kerremans, 1892 (15,367 bp). These mitogenomes ranged from 15,367 to 16,521 bp in length and encoded 37 typical mitochondrial genes: 13 protein-coding genes (13 PCGs), 2 ribosomal RNA genes (2 rRNAs), 22 transfer RNA genes (22 tRNAs), and a control region (CR). Most of PCGs had typical ATN start codons and terminated with TAR or an incomplete stop codon T–. Among these five mitogenomes, Leu2, Ile, Phe, Ser2, Gly, Met, and Val were the seven most frequently encoded amino acids. Interestingly, in A. sichuanus, a 774 bp insertion was present at trnW and trnC junction, which is unusual in Buprestidae. Additionally, phylogenetic analyses were performed based on three kinds of nucleotide matrixes (13 PCGs, 2 rRNAs, and 13 PCGs + 2 rRNAs) using Bayesian inference and maximum-likelihood methods. The results showed that the clade of Buprestidae was well separated from outgroups and all Agrilinae species formed to a single highly supported clade. The tribe Coraebini was polyphyletic, as the genus Meliboeus (Coraebini) clustered with the genus Trachys (Tracheini). The rRNA genes had important impact for the tree topology of Agrilinae. Compared to the tribes Tracheini and Agrilini, the tribe Coraebini is a younger group.
8
Rosner, Burton S., Joel B. Talcott, Caroline Witton, James D. Hogg, Alexandra J. Richardson, Peter C. Hansen, and John F. Stein. "The Perception of "Sine-Wave Speech" by Adults With Developmental Dyslexia." Journal of Speech, Language, and Hearing Research 46, no. 1 (February 2003): 68–79. http://dx.doi.org/10.1044/1092-4388(2003/006).
Повний текст джерелаАнотація:
Numerous studies have shown that, as a group, children or adults with developmental dyslexia perceive isolated syllables or words abnormally. Continuous speech containing reduced acoustic information also might prove perceptually difficult to such listeners. They might, however, exploit the intact syntactic and semantic features present in whole utterances, thereby compensating fully for impaired speech perception. "Sine-wave speech" sentences afford a test of these competing possibilities. The sentences contain only 4 frequency-modulated sine waves, lacking many acoustic cues present in natural speech. Adults with and without dyslexia were asked to orally reproduce 9 sine-wave utterances, each occurring in 4 immediately successive trials. Participants with dyslexia reported fewer words than did control listeners. Practice, phonological contrasts, and word position affected both groups similarly. Comprehension of sine-wave sentences seems impaired in many, but not all, adults with dyslexia. A reduced auditory memory capacity may contribute to this deficit.
9
Cadamuro, Daniela, and Yoh Tanimoto. "Wedge-local observables for factorizing S-matrix with gap in the coupling constant." Reviews in Mathematical Physics 30, no. 04 (April 19, 2018): 1850010. http://dx.doi.org/10.1142/s0129055x18500101.
Повний текст джерелаАнотація:
In the bootstrap approach to integrable quantum field theories in the [Formula: see text]-dimensional Minkowski space, one conjectures the two-particle S-matrix and tries to study local observables. We find a family of two-particle S-matrices parametrized by two positive numbers, which are separated from the free field or any other known S-matrix. We propose candidates for observables in wedge-shaped regions and prove their commutativity in the weak sense. The sine-Gordon model is conjectured to be equivalent to the Thirring model, and its breather–breather S-matrix components (where the first breather corresponds to the scalar field of the sine-Gordon model) are closed under fusion. Yet, the residues of the poles in this breather–breather S-matrix have wrong signs and cannot be considered as a separate model. Our S-matrices differ from the breather–breather S-matrix in the sine-Gordon model by CDD factors which adjust the signs, so that this sector alone satisfies reasonable assumptions.
10
Chandra Deo, Md Ramjan, Chandra Deo, L. Wangchu, P. Sarma, Amit Kumar Singh, and Shivani Dobhal. "Ethnobotany of indigenous (Traditional) vegetables in Adi tribe of East Siang region of Arunachal Pradesh, India." Environment Conservation Journal 22, no. 3 (December 19, 2021): 299–307. http://dx.doi.org/10.36953/ecj.2021.22335.
Повний текст джерелаАнотація:
Arunachal Pradesh is known as land of rising Sun which is the biggest in terms of area-wise amongst the state of north east India.The region has 26 major tribe; each tribe has its own enormous indigenous knowledge on the uses of wild plants. Among the tribe, Adi community is one of the major tribe inhabited in the region which has its own habitual way of using horticultural (vegetables) resources for sustaining livelihood. Most of the plants are also ethnically important without wich diverse rituals and festivals (Solung) of adi community remain unfinished. The current servey was under taken interviewed through planned questionaire. In our investigation among 25 wild species, 5 species belong to the Solanaceae family which was found to be most widely used family followed by Apiaceae, Rutaceae, Urticaceae and Araceae. Investigation on the basis of plant parts used reveals that the edible parts of the plants such as 6 species found to be widely used though leaves followed by 3 species fruits and 3 species whole plants besides these other plant parts like young tender leaves, tender stalks, petioles, rhizome also has been observed. This study is aim to initiated the basic information of these valuable herbs vegetable species for popularizing in future. These can compete with the best vegetables if appropriate study is initiated for production and ethanomedicine improvement.
11
Harris, Keith. "Towards a post-anthropocentric aesthetics: Kerry Tribe’s Exquisite Corpse." Journal of Urban Cultural Studies 9, no. 1 (June 1, 2022): 111–29. http://dx.doi.org/10.1386/jucs_00051_1.
Повний текст джерелаАнотація:
Kerry Tribe’s recent film on the Los Angeles River, Exquisite Corpse (2016), blurs the lines between genres. With aspects of documentary and experimental filmmaking, it captures interactions among human and non-human life, ecological systems and machines along the river. This article develops a post-anthropocentric aesthetics from the film by drawing on Sianne Ngai’s book, Our Aesthetic Categories (2012), and Rosi Braidotti’s (2013) work on post-anthropocentrism. Bringing these resources together leads to three productive transformations of Ngai’s categories: the commodity aesthetic of cuteness becomes the differential aesthetic of interaction; the performative aesthetic of zaniness becomes the functional aesthetic of activity; and the discursive aesthetic of information becomes the peri-discursive aesthetic of sensation. The article concludes by arguing that these three aesthetic categories are well suited for describing how the contemporary built environment and the complexity of life within it might be perceived and assessed and, following Jacques Rancière, affirms these categories’ role in building a politics that is attuned to such complexities.
12
Dehnavi, Saeed Daneshvar, Mahdi Shahparasti, Mohsen Simab, and Seyed Mohammad Bagher Mortazavi. "Employing Interface Compensators to Enhance the Power Quality In Hybrid AC/DC Microgrids." Ciência e Natura 37 (December 19, 2015): 357. http://dx.doi.org/10.5902/2179460x20796.
Повний текст джерелаАнотація:
After the introduction of distributed generators, regarding the challenges these networks face, employing AC/DC Hybrid microgrids would be an undeniable issue due to its many advantages and it will certainly find a significant position. Thus, discussing the power quality in this type of microgrids and clean power for feeding the load via this microgrid is a drastic challenge. This paper proposing a hybrid microgrid with 2 interface converters, one placed in series and the other placed in parallel, tries to accomplish these control objectives in an AC microgrid in order to improve power quality: input sine current with Cosϕ=1 and output sine voltage with normal value when source voltage is abnormal and non-sinusoidal, besides, non-linear loads’ presence. Simulation results verify the favorable performance of converters and effective functionality of control systems.
13
Avenarius, Martin. "'Neque id sine magna Servii laude…', Historisierung der Rechtswissenschaft und Genese von System und Methode bei Donellus." Tijdschrift voor Rechtsgeschiedenis / Revue d'Histoire du Droit / The Legal History Review 74, no. 1-2 (2006): 61–93. http://dx.doi.org/10.1163/157181906776931199.
Повний текст джерелаАнотація:
AbstractIn recent literature, the French humanist Hugo Donellus (1527–1591) is generally acknowledged as the creator of a civil law system. His system is generally understood as devised to present and explain Roman law. But in fact, Donellus does not organize the legal rules with the help of systematic elements from outside the law. He tries to reach back to the roots of classical Roman law, i.e. the ars iuris of Servius Sulpicius Rufus. Based on structural elements of the ars iuris that are preserved by the sources, Donellus tries to reorganize the law. He anticipates a methodological strategy that would prove to be successful in the 19th century: to understand law as the result of a long-term development. On the basis of this perspective he tries to reach back to the historical origins of law in order to make further dogmatical development possible. Thus, Donellus appears as a predecessor of the historical school of law.
14
Krämer, Sibylle. "Die Rettung des Ontologischen durch das Ontische?" Zeitschrift für Medien- und Kulturforschung 8, no. 2 (2017): 125–42. http://dx.doi.org/10.28937/1000107977.
Повний текст джерелаАнотація:
"Das Konzept der ›operativen Ontologien‹ ist nicht einfach zu verstehen. Dieser Artikel versucht Potenzial und Schranken dieser Idee auszuloten. Der methodische Ansatz der operativen Ontologie zielt darauf, dass das ›Ontische‹ im Sinne des phänomenal je Gegebenen das ›Ontologische‹ im Sinne der Erklärbarkeit und Verstehbarkeit von Welt bedingt und aus sich hervortreibt: Das Ontische gebiert das Ontologische. Was das bedeutet, wird einerseits anhand von Bernhard Siegerts Begriff ›Kulturtechnik‹ sowie andererseits anhand von Lorenz Engells Begriff der ›Ontographie‹ rekonstruiert sowie kritisch kommentiert. The concept of ‘operative ontologies’ is not easy to understand. The article tries to explore the potential and limitations of this idea. The methodological approach of operative ontology aims at the fact that the ‘ontic’ (in the sense of the phenomenally given) deter- mines and produces the ‘ontological’ (in the sense of the comprehensibility of the world): The ontic gives birth to the ontological. The meaning of this statement is reconstructed with reference to Bernhard Siegert’s concept of ‘cultural technique’ as well as Lorenz Engell’s notion of ‘ontography’ and is further- more critically commented upon. "
15
Kobza, Piotr. "Accession of Iceland to the European Union: A Failure Beyond Repair?" European Foreign Affairs Review 22, Issue 2 (April 1, 2017): 129–45. http://dx.doi.org/10.54648/eerr2017008.
Повний текст джерелаАнотація:
The EU membership negotiations of Iceland (2009–2013), suspended sine die by Reykjavik after the parliamentary elections to the Althingi in the spring of 2013, were commonly assessed as unsuccessful mainly due to specificities of Iceland as a Nordic country, wary of the European integration and whose economic interests were hardly in line with relevant EU legislation. The present article tries to balance the picture insofar as it concentrates on the conduct of the accession process of Iceland to the EU seen from the ‘Brussels’ side, and tries to answer if the process was conducted by the EU with enough leadership and energy. It also gives some recommendations as to a possibility to relaunch the process.
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Ranganathan, Parvathi, Xueyan Yu, Caroline Na, Ramasamy Santhanam, Sharon Shacham, Michael Kauffman, Alison Walker, et al. "Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia." Blood 120, no. 9 (August 30, 2012): 1765–73. http://dx.doi.org/10.1182/blood-2012-04-423160.
Повний текст джерелаАнотація:
AbstractChromosome maintenance protein 1 (CRM1) is a nuclear export receptor involved in the active transport of tumor suppressors (eg, p53 and nucleophosmin) whose function is altered in cancer because of increased expression and overactive transport. Blocking CRM1-mediated nuclear export of such proteins is a novel therapeutic strategy to restore tumor suppressor function. Orally bioavailable selective inhibitors of nuclear export (SINE) that irreversibly bind to CRM1 and block the function of this protein have been recently developed. Here we investigated the antileukemic activity of KPT-SINE (KPT-185 and KPT-276) in vitro and in vivo in acute myeloid leukemia (AML). KPT-185 displayed potent antiproliferative properties at submicromolar concentrations (IC50 values; 100-500nM), induced apoptosis (average 5-fold increase), cell-cycle arrest, and myeloid differentiation in AML cell lines and patient blasts. A strong down-regulation of the oncogene FLT3 after KPT treatment in both FLT3-ITD and wild-type cell lines was observed. Finally, using the FLT3-ITD–positive MV4-11 xenograft murine model, we show that treatment of mice with oral KPT-276 (analog of KPT-185 for in vivo studies) significantly prolongs survival of leukemic mice (P < .01). In summary, KPT-SINE are highly potent in vitro and in vivo in AML. The preclinical results reported here support clinical trials of KPT-SINE in AML.
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Louw, Stefan, Astrid M. L. Kappers, and Jan J. Koenderink. "Haptic Detection of Sine-Wave Gratings." Perception 34, no. 7 (July 2005): 869–85. http://dx.doi.org/10.1068/p5425.
Повний текст джерелаАнотація:
We studied human haptic perception of sine-wave gratings. In the first experiment we measured the dependence of amplitude detection thresholds on the number of cycles and on the wavelength of the gratings. In haptic perception of sine-wave gratings, the results are in agreement with neural summation. The rate at which detection thresholds decrease with increasing number of cycles is much higher than can be accounted for by probability summation alone. Further, neural summation mechanisms describe the detection thresholds accurately over the whole spatial range probed in the experiment, that is wavelengths from 14 mm up to 225 mm. Earlier, we found a power-law dependence of thresholds on the spatial width of Gaussian profiles (Louw et al, 2000 Experimental Brain Research132 369–374). The current results extend these findings; the power-law dependence holds not only for Gaussian profiles, but also for a broad range of sine-wave gratings with the number of cycles varying between 1 and 8. Haptic perception involves tactual scanning combined with an active, dynamic exploration of the environment. We measured characteristics of the velocity and force with which stimuli were scanned while performing a psychophysical task. One particularly surprising finding was that, without being instructed, participants maintained an almost constant scanning velocity during each 45-min session. A constant velocity in successive trials of the experiment might facilitate or even be necessary for discrimination. Further, a large systematic dependence of velocity on scanning length was found. An eightfold increase in scanning length resulted in about a fourfold increase in scanning velocity. A second experiment was conducted to study the influence of scanning velocity on psychophysical detection thresholds. This was done by systematically imposing specific scanning velocities to the participants while the thresholds were measured. The main result of the second experiment was that psychophysical detection thresholds are constant over a relatively broad range of scanning velocities.
18
Kumar, Naresh, Sanjeev Kumar, Bikram Singh, B. P. Mishra, Barun Singh, and Vikas Singh. "Traditional practices of utilization and conservation of non-wood forest products by Adi tribes of Arunachal Pradesh." Journal of Applied and Natural Science 7, no. 1 (June 1, 2015): 111–18. http://dx.doi.org/10.31018/jans.v7i1.573.
Повний текст джерелаАнотація:
The survey was carried out during 2009-11 to collect the information of Non-Wood Forest Products (NWFPs) utilized by the Adi tribes of East Siang District of Arunachal Pradesh. It was observeds that Adi tribes used to collect different NWFPs such as wild fruits (Artocarpus heterophyllum Lam., Castanopsis indica (Roxb. ex Lindl.) A. DC., Canarium strictum Roxb. etc.), vegetables (Bauhinia variegata L., Clerodendrum colebrookianum Walp., Diplazium esculentum (Retz.) Sw., Moringa oleifera Lam. etc.), spices (Cinnamomum tamala Nees & Eber.,Cinnamomum zeylanicum Blume. and Piper longum L.), fibres (Calamus flagellum Griff. ex Mart., Dendrocalamus hemiltonii Nees et Arn. ex Munro, Pandanus nepaulensis H. St. John and Sterculia villosa Roxb.), floss (Bombax ceiba L.,), broom grass (Thysanolaena maxima (Roxb.) Ktze.), thatching material (Livistona jenkinsiana Griff.), various bamboo and cane species, and other miscellaneous products from the forests and community lands. NWFPs played a significant role in supporting the livelihood of Adi tribes as it has been observed that 32.50 %, 56.67 % and 10.83 % people were earning < Rs. 3000, Rs. 3000 - 6000 and > Rs. 6000, respectively from the sale of different NWFPs. Majority of respondents (80.83 %) were having the opinion that the availability of different NWFPs has declined considerably and maximum (85 %) respondents advocated that the availability of these products would further decrease in future also. Further, Adi tribal community is playing an important role in conservation of different NWFPs yielding species by domesticating them in their home gardens.
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Fischer, Melissa A., Sharon Y. Friedlander, Maria P. Arrate, Hua Chang, Agnieszka E. Gorska, Londa D. Fuller, Haley E. Ramsey, et al. "Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies." Blood Advances 4, no. 3 (February 11, 2020): 586–98. http://dx.doi.org/10.1182/bloodadvances.2019000359.
Повний текст джерелаАнотація:
Abstract The selective inhibitor of nuclear export (SINE) compounds selinexor (KPT-330) and eltanexor (KPT-8602) are from a novel class of small molecules that target exportin-1 (XPO1 [CRM1]), an essential nucleo-cytoplasmic transport protein responsible for the nuclear export of major tumor suppressor proteins and growth regulators such as p53, p21, and p27. XPO1 also affects the translation of messenger RNAs for critical oncogenes, including MYC, BCL2, MCL1, and BCL6, by blocking the export of the translation initiation factor eIF4E. Early trials with venetoclax (ABT-199), a potent, selective inhibitor of BCL2, have revealed responses across a variety of hematologic malignancies. However, many tumors are not responsive to venetoclax. We used models of acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) to determine in vitro and in vivo responses to treatment with venetoclax and SINE compounds combined. Cotreatment with venetoclax and SINE compounds demonstrated loss of viability in multiple cell lines. Further in vitro analyses showed that this enhanced cell death was the result of an increase in apoptosis that led to a loss of clonogenicity in methylcellulose assays, coinciding with activation of p53 and loss of MCL1. Treatment with SINE compounds and venetoclax combined led to a reduction in tumor growth in both AML and DLBCL xenografts. Immunohistochemical analysis of tissue sections revealed that the reduction in tumor cells was partly the result of an induction of apoptosis. The enhanced effects of this combination were validated in primary AML and DLBCL patient cells. Our studies reveal synergy with SINE compounds and venetoclax in aggressive hematologic malignancies and provide a rationale for pursuing this approach in a clinical trial.
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Garang, Kuir ë. "Birth of a State: Rethinking South Sudanese Collective Identity through Identity Anchors." Modern Africa: Politics, History and Society 9, no. 2 (January 24, 2022): 5–37. http://dx.doi.org/10.26806/modafr.v9i2.330.
Повний текст джерелаАнотація:
Following the independence of South Sudan in 2011, the coherence of South Sudanese “national” identity has come into question. Before the Southern secession, Northerners were united by a common language and religion, but Southerners did not have this uniting reality. For this reason, scholars now wonder whether there is a collective South Sudanese identity because the sine qua non of unity among South Sudanese tribes was a collective opposition to Northern Sudan. However, the present article defends a collective South Sudanese identity based on how “nation-building” has been undertaken historically. It also argues that tribal diversity in itself does not negate the presence of a South Sudanese collective “national” identity because internal tribal divisions are a global phenomenon and “tribal” and “national” identities are activated contextually.
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Danggen, Orik. "Ethnomedicinal Plant Knowledge among the Adi Tribe of Yingkiong and Mariyang Valley, Upper Siang District, Arunachal Pradesh, India." International Journal of Pure & Applied Bioscience 6, no. 1 (February 28, 2018): 1504–11. http://dx.doi.org/10.18782/2320-7051.5432.
Повний текст джерела
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Winiharti, Menik. "English Participial Clauses Aand The Strategies Applied In Their Indonesian Translations." Lingua Cultura 1, no. 1 (May 31, 2007): 1. http://dx.doi.org/10.21512/lc.v1i1.256.
Повний текст джерелаАнотація:
This study analyses the English participial clauses and how they are translated into Indonesian as appearing in Sidney Sheldon’s novel Morning, Noon and Night (1995) which is translated by Hendarto Setiadi as Pagi, Siang dan Malam (1996). This study tries to find out the distribution of the types and the syntactic functions of the participial clauses appearing in the novel and answer the question of what the strategies applied in the translations are. To reach these objectives, this study employs an exploratory-interpretive design since the data are collected nonexperimentally, the type of data collected is qualitative, and the type of analysis is interpretive.
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Barnett, Michael L. "Suitability of gingival indices for use in therapeutic trials. Is bleeding a sine qua non?" Journal of Clinical Periodontology 23, no. 6 (June 1996): 582–86. http://dx.doi.org/10.1111/j.1600-051x.1996.tb01828.x.
Повний текст джерела
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O'NEILL, C. J. A., R. J. DOBBS, S. M. DOBBS, and P. W. NICHOLSON. "Measurement of Compliance with Medication: The sine qua non of Clinical Trials in Old Age?" Age and Ageing 20, no. 2 (1991): 77–79. http://dx.doi.org/10.1093/ageing/20.2.77.
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Dames, Kevin D., Jeremy D. Smith, and Gary D. Heise. "Averaging Trials Versus Averaging Trial Peaks: Impact on Study Outcomes." Journal of Applied Biomechanics 33, no. 3 (June 2017): 233–36. http://dx.doi.org/10.1123/jab.2016-0164.
Повний текст джерелаАнотація:
Gait data are commonly presented as an average of many trials or as an average across participants. Discrete data points (eg, maxima or minima) are identified and used as dependent variables in subsequent statistical analyses. However, the approach used for obtaining average data from multiple trials is inconsistent and unclear in the biomechanics literature. This study compared the statistical outcomes of averaging peaks from multiple trials versus identifying a single peak from an average profile. A series of paired-samples t tests were used to determine whether there were differences in average dependent variables from these 2 methods. Identifying a peak value from the average profile resulted in significantly smaller magnitudes of dependent variables than when peaks from multiple trials were averaged. Disagreement between the 2 methods was due to temporal differences in trial peak locations. Sine curves generated in MATLAB confirmed this misrepresentation of trial peaks in the average profile when a phase shift was introduced. Based on these results, averaging individual trial peaks represents the actual data better than choosing a peak from an average trial profile.
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London, Cheryl, Luis feo Bernabe, Sandra Barnard, William Kisseberth, Antonella Borgatti, Michael Henson, Heather Wilson, et al. "Evaluation Of The Novel, Orally Bioavailable Selective Inhibitor Of Nuclear Export (SINE) Verdinexor (KPT-335) In Spontaneous Canine Cancer: Results Of Phase I and Phase II Clinical Trials." Blood 122, no. 21 (November 15, 2013): 5149. http://dx.doi.org/10.1182/blood.v122.21.5149.5149.
Повний текст джерелаАнотація:
Abstract SINE (Selective Inhibitors of Nuclear Export) block the activity of XPO1/CRM1, 1 of 7 nuclear export proteins in cells, forcing the nuclear retention of key tumor suppressor proteins (TSP), leading to selective apoptosis of tumor cells. The purpose of these studies was to evaluate the in vitro activity of SINE against canine tumor cell lines and investigate the biological activity of Verdinexor (KPT-335) in dogs with spontaneous cancers as proof of principle for human clinical studies with SINE. Several different canine tumor cell lines including those derived from Non-Hodgkin Lymphoma (NHL) exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of Verdinexor was performed in dogs with cancer with an emphasis on NHL given in vitro activity demonstrated against the tumor cell lines. The maximum tolerated dose (MTD) was 1.75 mg/kg twice per week although biological activity was observed at 1 mg/kg. Clinical benefit including Partial Response (PR) and Stable Disease (SD) for at least 4 weeks was observed in 9/14 dogs with NHL with a median time to progression of 66 days (range 35-256). A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg Verdinexor on a Monday/Wednesday/Friday (MWF) regimen; clinical benefit (PR + SD) was observed in 4/6 dogs with a median time to progression of 83 days (range 35-250+). Toxicities were primarily gastrointestinal in nature consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care and dose modulation. A validated health related Quality of Life (QOL) form used to assess dogs during treatment demonstrated that the overall quality of life did not decrease in dogs in this study supporting the notion that clinical toxicities associated with Verdinexor are generally well tolerated. Based on these findings, a Phase IIb study was performed in 58 dogs with either newly diagnosed or relapsed NHL. Drug was administered initially at 1.5 mg/kg MWF, but this dosing regimen was changed to 1.25 mg/kg M/Th due to the high rate of anorexia and weight loss on the MWF regimen; dose escalation was permitted to 1.5 mg/kg on the M/Th regimen. The objective response rate was 34% (1 CR, 19 PR) with an additional 33 dogs experiencing SD for a minimum of 4 weeks, resulting in a of 91% disease control rate. While the median time to progression was approximately 5 weeks, 19 dogs (32%) remained on study drug for >8 weeks; several dogs continue to receive Verdinexor. Laboratory abnormalities were minimal and clinical toxicities were mild on the M/Th regimen. Together, these data provide robust evidence that the novel orally bioavailable XPO1 inhibitor Verdinexor exhibits single agent biological activity in a spontaneous large animal model of human NHL. Furthermore, Verdinexor was well tolerated even in the absence of supportive care, suggesting that SINE compounds could exhibit good long-term tolerability in people. Disclosures: London: Zoetis: Honoraria, Research Funding; Karyopharm: Consultancy, Research Funding; Abbott: Honoraria. Modiano:Karyopharm: Research Funding. Saint-Martin:Karyopharm: Employment. McCauley:Karyopharm : Employment, Equity Ownership, Patents & Royalties. Shacham:Karyopharm : Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics Inc.: Employment.
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Prosperi, Martina R. "Syaman Rapongan’s ‘The mythology of Badai Bay’: A symbolic father’s legacy." East Asian Journal of Popular Culture 7, no. 2 (October 1, 2021): 189–205. http://dx.doi.org/10.1386/eapc_00048_1.
Повний текст джерелаАнотація:
Syaman Rapongan (1957–present) is a Tao Indigenous author from the Orchid Island (Taiwan) and Badaiwan de shenhua, a collection of his tribe’s myths, was his first publication. In its introduction, he explains how these myths’ intrinsic value system allows him to face the difficulties of our modernized and globalized society, where individuals often lose their sense of belonging and life’s meaning. The Lacanian psychoanalyst Massimo Recalcati traces this lack of meaning back to a loss of the ‘symbolic father’, who once provided the individual with both the interdicting function of a symbolic law and the recognition – thus, the word – to participate and speak in society. After a few years in Taiwan, where he studied and worked until the 1980s, Syaman Rapongan returned to Orchid Island and rediscovered this sense of belonging by re-appropriating Tao legends, rituals, productive skills, thus receiving his own father and the other tribe members’ recognition. The father figure as the storyteller par excellence passing on that symbolic word is the giver of Badaiwan de shenhua. Moreover, father-like characters and father-related emblematic images (e.g. the house), significantly recur both in these myths and in several subsequent stories. Taking advantage of Recalcati’s reflection, this article integrates an ecocritical approach to Syaman Rapongan’s literature by interpreting its recovery of the Indigenous paradigm as a recovery of the symbolic father. Through the analysis of examples from Badaiwan de shenhua and other stories, it demonstrates how the cosmopolitan value of his narrative does not reside so much in the revival of an ante-litteram ‘ecological’ lifestyle, but in its sine qua non, or the recovery of the ‘symbolic father’.
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Crochiere, Marsha, Boris Klebanov, Erkan Baloglu, Ori Kalid, Trinayan Kashyap, William Senapedis, Diego del Alamo, et al. "In Vitro and in Vivo Quantification of Exportin-1 (XPO1) Occupancy By the Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor in Multiple Myeloma, Acute Myeloid Leukemia, and Healthy PBMCs." Blood 124, no. 21 (December 6, 2014): 5196. http://dx.doi.org/10.1182/blood.v124.21.5196.5196.
Повний текст джерелаАнотація:
Abstract Introduction: SINE are a family of small molecules that selectively inhibit nuclear export by forming a slowly reversible covalent bond with Cysteine 528 (Cys528) in the cargo binding pocket of Exportin 1 (XPO1/CRM1). SINE binding to XPO1 leads to forced nuclear retention and activation of major tumor suppressor proteins (TSPs) such as p53, FOXO, pRB and IkB, resulting in selective death of cancer cells. Selinexor is an orally bioavailable SINE compound currently in human phase I and II clinical trials for advanced hematological and solid cancers. Oral selinexor demonstrates maximal pharmacokinetic exposure at 1-2 hours in humans with associated increases in pharmacodynamic markers of XPO1 inhibition in 2-4 hours that last for up to 48 hours. The goal of this study was to develop a binding assay that would enable quantification of XPO1 occupancy in PBMCs from patients following oral administration of selinexor. Methods: To measure the binding of SINE to XPO1, biotinylated leptomycin B (LMB) was utilized. Biotinylated LMB binds covalently and irreversibly to Cys528 in the cargo-binding site of free XPO1 with activity confirmed to be similar to that of unmodified LMB in cytotoxicity assays. To measure SINE binding to XPO1 in vitro, cancer cell lines and PBMCs from normal human donors were treated with SINE compounds prior to treatment with biotinylated LMB. Any XPO1 that did not bind SINE instead binds to biotinylated LMB and can be quantified. In in vivo studies, mice were treated with selinexor, followed by collection of PBMCs for treatment with biotinylated LMB. After incubation with biotinylated LMB, cells were harvested, lysed, and protein lysates were subjected to pull-down experiments with streptavidin-conjugated beads followed by immunoanalysis of XPO1. Results: To evaluate selinexor-XPO1 binding kinetics in vitro, MM.1S, AML2, AML3, and HEL cells were treated with 0 - 10 µM of SINE compounds and unbound XPO1 was pulled down from cell lysates treated with biotinylated LMB. Immunoanalysis showed that 50% XPO1 occupancy with selinexor was achieved at 0.07 µM in MM.1S, 0.1 µM in AML2, 0.03 µM in AML3, and 0.12 µM in HEL cells. Selinexor-XPO1 occupancy experiments using human PBMCs isolated from donor whole blood showed 50% XPO1 occupancy at 0.05 µM. In mice, 50% XPO1 occupancy in PMBCs was achieved after 4 hours treatment with 1.2 mg/kg (3.6 mg/m2) selinexor, while 90% XPO1 occupancy was achieved at 8.1 mg/kg (24.3 mg/m2). Mice treated with a single dose of selinexor from 1.5 to 10 mg/kg for 4-96 hours revealed sustained, dose dependent XPO1 occupancy in PBMCs for up to 72 hours. Conclusions: We have developed a sensitive and robust assay to measure selinexor binding to XPO1 that can be used to evaluate drug exposure following treatment with oral selinexor in preclinical and clinical studies. Studies are ongoing to determine whether there is a correlation between XPO1 occupancy (pharmacodynamics measurement) with disease response in patients with solid and hematological malignancies. Disclosures Crochiere: Karyopharm: Employment. Klebanov:Karyopharm Therpeutics: Employment. Baloglu:Karyopharm: Employment. Kalid:Karyopharm Therapeutics: Employment. Kashyap:Karyopharm Therapeutics: Employment. Senapedis:Karyopharm: Employment. del Alamo:Karyopharm: Employment. Rashal:Karyopharm Therapeutics: Employment. Tamir:Karyopharm: Employment. McCauley:Karyopharm Therapeutics: Employment, Equity Ownership. Carlson:Karyopharm Therapeutics: Employment. Savona:Karyopharm: Consultancy, Equity Ownership; Gilead: Consultancy; Incyte: Consultancy; Celgene: Consultancy. Kauffman:Karyopharm Therapeutics, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Shacham:Karyopharm Therapeutics, Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Landesman:Karyopharm Therapeutics: Employment.
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Carey, James R., Connie L. Bogard, Bradley A. King, and Vera J. Suman. "Finger-Movement Tracking Scores in Healthy Subjects." Perceptual and Motor Skills 79, no. 1 (August 1994): 563–76. http://dx.doi.org/10.2466/pms.1994.79.1.563.
Повний текст джерелаАнотація:
The purpose of this study was to examine the effects of age, sex, and hand preference on precise control of voluntary movement at the index finger metacarpophalangeal joint in able-bodied volunteers. An electrogoniometer was attached to this joint and connected to a computer. The computer screen displayed a sine wave target that each subject attempted to track with careful extension and flexion finger movements. Accuracy index scores were calculated for the extension phases, flexion phases, and the total sine wave. Each subject performed three tracking trials and the average for each of the above scores was computed. The results showed that younger subjects tracked significantly more accurately than older subjects and men tracked significantly more accurately than women. Also, the subjects tracking with the nonpreferred hand (15 right, 105 left) tracked significantly more accurately than those subjects tracking with the preferred hand (112 right, 8 left) in the flexion phases of the test. The data from these able-bodied subjects provide a base for comparison of patients' data, which may be helpful in the early recognition and monitoring of problems with precision in movement control.
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Moore, Kelli. "Affective Architectures: Photographic Evidence and the Evolution of Courtroom Visuality." Journal of Visual Culture 17, no. 2 (August 2018): 207–22. http://dx.doi.org/10.1177/1470412918783841.
Повний текст джерелаАнотація:
This article examines the courtroom situation, focusing on courtroom spectatorship, architecture, and visuality in US trials. Visual evidence is situated within the architectural apparatus of the courtroom to examine how affect unfolds between a testifying witness and courtroom audience members. The movement of photographic evidence during judicial proceedings is linked to the disruption of temporal and spatial equilibrium. The idea is introduced that a feeling of vertigo is produced in the testifying witness and audience participants. Following Sianne Ngai’s conception of the ‘minor affects’, it is proposed that disconcertion and confusion are characteristics of witness testimony and thus important political affects to note in analyses of the relationship between vision and the discovery of justice in legal spectatorship.
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Teixeira, Marcus Zulian. "Scientific evidence of the homeopathic epistemological model." International Journal of High Dilution Research - ISSN 1982-6206 10, no. 34 (December 23, 2021): 46–64. http://dx.doi.org/10.51910/ijhdr.v10i34.421.
Повний текст джерелаАнотація:
Homeopathy is based on principles and a system of knowledge different from the ones supporting the conventional biomedical model: this epistemological conflict is the underlying reason explaining why it is so difficult to accept by present-day scientific reason. To legitimize homeopathy according to the standards of the latter, research must confirm the validity of its basic assumptions: principle of therapeutic similitude, trials of medicines on healthy individuals, individualized prescriptions and use of high dilutions. Correspondingly, basic research must supply experimental data and models to substantiate these principles of homeopathy, whilst clinical trials aim at confirming the efficacy and effectiveness of homeopathy in the treatment of disease. This article discusses the epistemological model of homeopathy relating its basic assumptions with data resulting from different fields of modern experimental research and supporting its therapeutic use on the outcomes of available clinical trials. In this regard, the principle of individualization of treatment is the sine qua non condition to make therapeutic similitude operative and consequently for homeopathic treatment to exhibit clinical efficacy and effectiveness.
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Daelemans, Dirk, Eline Boons, Els Vanstreels, Maarten Jacquemyn, Tatiane C. Nogueira, Jasper E. Neggers, Thomas Vercruysse, et al. "Selective Inhibitors of Nuclear Export (SINE) Compounds Suppress Both HIV Replication and AIDS Related Lymphoma." Blood 126, no. 23 (December 3, 2015): 2751. http://dx.doi.org/10.1182/blood.v126.23.2751.2751.
Повний текст джерелаАнотація:
Abstract Infection with human immunodeficiency virus (HIV) compromises the immune system leaving infected individuals vulnerable to other pathologies including cancer. HIV-infected patients have an increased risk of cancer development as compared to the general population. Primary effusion lymphoma (PEL), a high-grade non-Hodgkin lymphoma with very poor prognosis, typically affects individuals infected with HIV in advanced stages of acquired immune deficiency syndrome (AIDS). While the use of anti-HIV drugs is associated with better prognosis, treating cancer in HIV-infected patients is often challenging due to potential drug interactions between anti-cancer agents and antiretroviral drugs. We demonstrate that inhibition of the exportin-1 (CRM1/XPO1) mediated nuclear protein transport by SINE compounds results in effective suppression of HIV replication, which was quantified by measuring virus-associated core antigen (p24) by ELISA. In addition by using MTT, assays, Annexin staining, FACS and immunoblot analysis we demonstrated that XPO1 inhibition induced cell cycle arrest and apoptosis in PEL cell lines (BC-1, BCBL-1, and JSC-1) at similar doses. SINE blocked the nuclear export of the late viral partially and unspliced RNA species encoding for the viral structural proteins. In BC-1 PEL cells inhibition of XPO1 resulted in the nuclear accumulation of p53 tumor suppressor protein as well as inhibition of NF-κB activity. In vivo, oral administration twice a week for 4 weeks, 20 mg/kg of the clinical SINE compound selinexor (currently in phase I/II clinical trials) led to a significant suppression of the BC-1 PEL growth in vivo. These findings provide a strong basis for inhibiting XPO1 as a novel strategy for the combined treatment of HIV and PEL or other AIDS-related cancers. Disclosures Tamir: Karyopharm: Employment. Kauffman:Karyopharm: Employment, Equity Ownership. Shacham:Karyopharm: Employment, Equity Ownership. Landesman:Karyopharm: Employment.
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Pastuszko, Marian. "Obrzędy i ceremonie sprawowania Eucharystii (kanony 923-930)." Prawo Kanoniczne 36, no. 1-2 (June 5, 1993): 69–130. http://dx.doi.org/10.21697/pk.1993.36.1-2.05.
Повний текст джерелаАнотація:
Praesens articulus proemio, parte principali, conclusione et argumento lingua latina exarato, constat. In proemio duae notiones, nempe ritus et caeremoniarum praesentantur. In principali parte articuli canones 923—930 Codicis Juris Canonici Papae Joannis Pauli II exponuntur. — Can. 923 permittit christifidelibus Cacrificium Eucharisticum participare et sacram Communionem suscipere quolibet ritu catholico, firmo praescripto can. 844. — Ad normam can. 924 Eucharisticum Sacrificium celebrari debet ex pane mere triticeo, recenter confecto ( = materia ex qua Sacramenti Eucharistiae) et vino naturali, de genimine vitis, non corrupto ( = item materia ex qua Sacramenti Eucharistiae). — Vino in ritu praeparationis donorum admiscendum est paulum aquae. — Secundum can. 925 sacra Communio distribui potest uno e tribus modis: 1. sub sola specie panis, 2. sub specie panis et vini, 3. sub sola specie vini. Hic tertius modus adhibetur solummodo in casu necessitatis ex parte fidelis sacram Communionem suscipientis. — Can. 926 obligat sacerdotes Ecclesiae romano — catholicae ad adhibendum panem azymum in celebratione Eucharistiae, iuxta traditionem antiquam. Etiam urgente extrema necessitate, unam tantum materiam (seu aut panem aut vinum) sine altera aut etiam utramque (seu et panem et vinum) extra Eucharisticam celebrationem consecrare severrimet prohibet can. 927. — In Ecclesia romano — catholica usque ad Concilium Vaticanum II (1963— 1965) Eucharisticum Sacrificium lingua latina celebrabatur. Ab illo tempore sine populo adhuc lingua latina celebrari, sed cum populo ordinarie peragitur lingua sacerdotis Missam celebrantis et populi participantis, dummodo textus liturgici legitime approbati sint a Sede Apostolica (can. 928). — Sacerdotes et diaconi tam in Missae Sacrificio celebrando quam in sacra Communione administranda sacras vestes a rubricis praescriptas deferre debent (can. 929). — Sacerdotes infirmi aut aetate provecti si stare nequeant, Sacrificium Eucharisticum celebrare possunt sedentes, servatis tamen omnibus praescriptis liturgicis, et non coram populo, nisi de licentia ordinarii. — Sacerdotes caeci autem vel alia infirmitate laborantes, licite Sacrificium Eucharisticum celebrant, adhibendo quemlibet textum Missae (utique ex probatis), adstante si casus ferat, alio sacerdote aut diacono vel instructo laico (can. 930 § 1 et § 2). Sub fine articuli quaedam inconvenientia indicatur, quae consistit in hoc, quod titulus articuli III De Ritibus et caeremoniis Eucharisticae celebrationis loquitur, sed canones 924—930 vocem „caeremoniae” non habent, et solummodo de ritibus, non autem de caeremoniis tractant. — Tandem non sine aliqua melancholia confitetur auctor: feci, quod potui, faciant meliora potentes.
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Mili, Rajiv, Prasanna Samal, and Mihin Dollo. "Extraction of non-timber forest products from shifting agriculture fallow land by Adi tribe in Siang districts of Arunachal Pradesh, North East India." Journal of Non-Timber Forest Products 17, no. 1 (March 1, 2010): 7–18. http://dx.doi.org/10.54207/bsmps2000-2010-adu6d3.
Повний текст джерелаАнотація:
This paper attempts to document NTFPs diversity in the shifting agriculture fallow land of Adi tribe in Siang districts in Arunachal Pradesh. A total of 62 species belonging to 57 genera and 38 families were recorded, which have significant role in livelihood sustenance of Adi community. Among all the NTFP species, angiosperms contributed highest number of 56 species followed by 4 species of pteridophytes and 2 species of fungi. Based upon the different broad uses, these NTFPs species have been grouped into 10 categories. Of which, highest of 24 species is use as vegetable followed by medicine 23 spp., handicraft 13 spp., animal feeds 7 spp., ritual 6 spp., etc. Depending upon the extraction and utilization of plant and plant parts by the Adis, it was observed that leaf is the most dominant plant part used as NTFPs, which only contributed 35 numbers of species followed by stem 20 species. During survey, it has been recorded that a total of 18 species are marketed and as many as 8 spp. are sold at the rate of twenty rupee only per kg. Further, it is advocated that by value addition and creating market linkages, the income from NTFPs could be enhanced, which will help in developing alternative livelihood for shifting cultivators. Therefore, the need of hours is to recognize the importance of NTFPs to mitigate the environmental degradation through sustainable harvesting by maintaining the forest intact.
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Naing, Aung, Siqing Fu, Apostolia Maria Tsimberidou, Shubham Pant, Sarina Anne Piha-Paul, Filip Janku, David S. Hong, et al. "Phase IB study to evaluate the safety of selinexor in combination with multiple standard chemotherapy agents in patients with advanced malignancies." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS2603. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps2603.
Повний текст джерелаАнотація:
TPS2603 Background: Selinexor is a first-in-class, slowly reversible, Selective Inhibitor of Nuclear Export (SINE) compound that specifically blocks XPO1. Inhibition of XPO1 results in nuclear localization, accumulation, and reactivation of tumor suppressor proteins, therefore selectively inducing apoptosis in cancer cells, while largely sparing normal cells. This unique property of XPO1 inhibition has been deployed as a novel therapeutic strategy with success in several solid tumors and hematologic malignancy clinical trials. Preclinical studies have shown that SINE compounds behave synergistically to enhance cancer cell death with combined with different therapeutic agents. This Phase I trial is based on such preclinical evidence. The primary objective of the study is to establish the safety and tolerability of selinexor when given in combination with thirteen standard chemotherapy regimens. The secondary objectives are to determine disease control and progression-free survival of patients receiving selinexor administered with standard chemotherapy treatments in specific tumor subsets. Methods: Adult patients ≥ 18 years of age are eligible if they have histologically confirmed neoplasms (excluding hematological malignancies and brain tumors) that are refractory to established therapy known to provide clinical benefit for their condition. Patients are required to have either measurable disease (RECIST 1.1) or evaluable disease, and an ECOG performance status of 0-1. Enrollment is ongoing for dose escalation with the plan for dose expansion as follows: Clinical trial information: NCT02419495. [Table: see text]
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Nuñez Erices, Gonzalo. "Boundaries and Things. A Metaphysical Study of the Brentano-Chisholm Theory." KRITERION – Journal of Philosophy 33, no. 2 (July 1, 2019): 15–48. http://dx.doi.org/10.1515/krt-2019-330203.
Повний текст джерелаАнотація:
Abstract The fact that boundaries are ontologically dependent entities is agreed by Franz Brentano and Roderick Chisholm. This article studies both authors as a single metaphysical account about boundaries. The Brentano-Chisholm theory understands that boundaries and the objects to which they belong hold a mutual relationship of ontological dependence: the existence of a boundary depends upon a continuum of higher spatial dimensionality, but also is a conditio sine qua non for the existence of a continuum. Although the view that ordinary material objects and their boundaries (or surfaces) ontologically depend on each other is correct, it does not grasp their asymmetric relationship: while the existence of a surface rigidly depends upon the existence of the very object it belongs to, the existence of a physical object generically depends upon having some surface. In modal terms, both are two kinds of de re ontological dependence that this article tries to distinguish.
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Grzywacz, Anna. "Realizacja konstytucyjnej zasady nullum crimen sine lege certa w świetle art. 115 ust. 3 u stawy o prawie autorskim i prawach pokrewnych." Studenckie Prace Prawnicze, Administratywistyczne i Ekonomiczne 25 (September 24, 2018): 125–39. http://dx.doi.org/10.19195/1733-5779.25.8.
Повний текст джерелаАнотація:
Realization of a nullum crimen sine lege certa principle in light of Article 115 Paragraph 3 of a Polish Copyright ActThe aim of the article is to analyze the content of Article 115 Paragraph 3 of the Polish Copyright Act and to examine the constitutionality of the provision based on the nullum crimen sine lege certa principle expressed in Article 42 of the Constitution. The basis for the allegation of the unconstitutionality of the provision is the Article’s use of the phrase: “Who […] otherwise violates”, which is, in the opinion of the doctrine, imprecise and contrary to the principle of legal certainty in matters of criminal law. Basing on the quoted regulations and the practice the author tries to answer a question whether the content of Article 115 Paragraph 3 of the Polish Copyright Act is constitutional and subjects the issue of using such clauses to the polemics. The article presents arguments for the rightness of such regulation as well as opposing views and the final conclusion based on the judgment of February 17, 2015, in which the Constitutional Tribunal adjudicated on the conformity of the regulation with the Constitution. Despite the approving position of the Constitutional Tribunal the issue of the constitutionality of the provision is still controversial and causes problems in the classification of acts as prohibited under the Copyright Act. Nevertheless, the use of complementary clauses in particular containing the phrase: “Who […] otherwise violates” seems to be unavoidable due to the dynamic development of technology and law. The principle of legal certainty can be implemented using a pro-constitutional interpretation in order to maximize the alignment of legal norms with the objectives and values expressed in the Constitution. This paper will also examine the secondary issue of criminal law protection of intellectual property rights with an emphasis on copyright law.
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Shacham, Sharon, Sandra Barnard, William Kisseberth, Daisuke Ito, Kiersten Jensen, Antonella Borgotti, Michael Henson, et al. "Results of a Phase I Dose Escalation Study of the Novel, Oral CRM1 Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Dogs with Spontaneous Non-Hodgkin's Lymphomas (NHL)." Blood 120, no. 21 (November 16, 2012): 161. http://dx.doi.org/10.1182/blood.v120.21.161.161.
Повний текст джерелаАнотація:
Abstract Abstract 161 Introduction. Nuclear-cytoplasmic transport is highly regulated by karyopherin proteins – importins and exportins – through the nuclear pore complex. Of the seven known exportins, most tumor suppressor proteins (TSP) and IkB, the inhibitor of NF-kB, are transported out of the nucleus exclusively by exportin 1 (XPO1), more commonly called CRM1. SINE compounds bind irreversibly CRM1/XPO1, forcing the nuclear retention and activation of TSP and IkB, leading to selective tumor cell death. In vitro, SINEs demonstrate potent cytotoxic activity against tumor cells at nanomolar concentrations with minimal effects on normal cells in vitro. KPT-335 and related SINEs show oral bioavailability, good tolerability, and potent activity in multiple mouse xenograft models. Hematologic cancers are particularly vulnerable to SINE induced apoptosis, and effects on normal tissues are minimal at antitumor doses. Methods. Cytotoxicity was assessed in vitro with MTT and apoptosis assays. In order to evaluate the therapeutic potential of SINE in a spontaneous, large animal malignancy with many similarities to human disease including NF-kB activation, dogs with relapsed or newly diagnosed NHL were treated with KPT-335 in this dose escalation study. The primary objective was to evaluate the adverse events (AEs) and to establish the maximum tolerated dose (MTD) of KPT-335 orally in capsules. The secondary objectives were to determine the optimal dosing regimen, correlate pharmacodynamic markers and drug levels, and provide evidence of biological activity. We report the interim results defining the MTD and AEs of KPT-335 in dogs with NHL. All dogs had progressive disease (PD) on entry into the trial. Dogs with newly diagnosed or relapsed NHL, metastatic osteosarcoma (OSA), melanoma (MEL) and mast cell tumor (MCT) were eligible with preference given to NHL. The initial KPT-335 dose was 1 mg/kg (equivalent to 20mg/m2) orally with food on a Monday/Thursday schedule. At least 3 dogs were included in each cohort, and dose was escalated by 0.25mg/kg increments. CBC, serum chemistries, clotting times, drug peak plasma level and response to therapy were assessed at each weekly visit. Tumor samples will be obtained before and after treatment in an expansion cohort once the optimal dosing regimen has been determined. Results. Three structurally related SINE compounds including KPT-335 showed potent cytotoxicity of primary and immortalized canine B cell lymphomas in vitro (EC50<100 nM). The Phase 1 dose escalation study with KPT-335 oral included doses of 1mg/kg twice weekly and continued up to 2mg/kg (Table 1). Doses up to 1.75mg/kg were very well tolerated for over 3 months. At 1.75mg/kg, mild to moderate anorexia, weight loss and alkaline phosphatase elevation (possibly related to prednisone use) were observed. DLTs occurred at 2mg/kg including anorexia and vomiting without diarrhea. Laboratory parameters showed minimal or no changes at doses below the DLT. Discussion. Oral KPT-335 shows single agent disease stabilization and tumor reduction in dogs with NHL, the majority of who have diffuse large B cell lymphoma (DLBCL) relapsed after chemotherapy (typically CHOP). The activation of TSP and the neutralization of NF-kB activity by nuclear localization of IkB may contribute to the antitumor activity of SINE in canine NHL. AEs associated with drug administration include primarily anorexia, with vomiting at the DLT dose; diarrhea and significant laboratory changes were not observed. These observations are consistent with the effects of SINEs in other animal species. Conclusion. The novel SINE KPT-335 exhibits single agent biological activity with good tolerability in a relevant spontaneous large animal model of newly diagnosed and chemotherapy refractory cancer. The MTD and no adverse effect level of KPT-335 given by mouth twice weekly to dogs with NHL are ∼1.75 and 1.25 mg/kg, respectively, with anorexia, weight loss and vomiting as DLTs. Additional cohorts at doses of ≥1.25mg/kg given with increased frequency are being enrolled. These data are directly relevant to the development of oral KPT-330, a related SINE, currently in Phase 1 human clinical trials. Disclosures: Shacham: Karyopharm Therapeutics: Employment. Barnard:Karyopharm: Research Funding. Kisseberth:Karyopharm: Research Funding. Ito:Karyopharm: Research Funding. Jensen:Karyopharm: Research Funding. Borgotti:Karyopharm: Research Funding. Henson:Karyopharm: Research Funding. Wilson:Karyopharm: Research Funding. McCauley:Karyopharm Therapeutics Inc: Employment. Modiano:Karyopharm: Research Funding. Kauffman:Karyopharm Therapeutics Inc: Employment. London:Karyopharm: Research Funding.
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Faix, Martin, and Ondrej Svacek. "DEALING WITH THE PAST: PROSECUTION AND PUNISHMENT OF COMMUNIST CRIMES IN CENTRAL AND EASTERN EUROPEAN COUNTRIES / LIDAR COM O PASSADO: PROCESSOS PENAIS E PUNIÇÃO DE CRIMES COMUNISTAS NA EUROPA CENTRAL E ORIENTAL." Espaço Jurídico Journal of Law [EJJL] 16 (February 19, 2016): 31–50. http://dx.doi.org/10.18593/ejjl.v16i3.9787.
Повний текст джерелаАнотація:
This article addresses issues arising in the context of transition to democracy in Central and Eastern Europe, namely in Germany (former East Germany), Czech Republic, Slovakia and Hungary. The contribution reflects various means of transitional justice which were applied in these countries: access to the archives of secret police, lustration and prosecution of the crimes of the past (successor trials). Central issue of this article is the criminal prosecution of communist crimes. Here authors focus their attention on two interrelated aspects: choice of applicable law and statutory limitations, which both are linked to the principle of legality. Practice and methods in prosecution of the communist crimes adopted across the analyzed countries reveal considerable heterogeneity and from comparative perspective pose a unique legal laboratory. Despite differences in applicable law, including treatment and interpretation of statutory limitations, and differences in overall outcomes of prosecution and punishment of the communist crimes, all countries were conformed to requirements of the principle of legality. The article thus confirms that states, when dealing with their past, enjoy a wide margin of appreciation.Keywords: Communist crimes. Central and Eastern Europe. Transitional justice. Successor trials. Nullum crimen sine lege.
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Hing, Zachary A., Ho Yee Joyce Fung, Parvathi Ranganathan, Shaneice Mitchell, Dalia El-Gamal, Jennifer A. Woyach, Katie Williams, et al. "Next Generation XPO1 Inhibitor Shows Improved Efficacy and In Vivo Tolerability in Hematologic Malignancies." Blood 126, no. 23 (December 3, 2015): 317. http://dx.doi.org/10.1182/blood.v126.23.317.317.
Повний текст джерелаАнотація:
Abstract Restoring nuclear localization of tumor suppressors by blocking exportin 1 (XPO1) holds promise as a new therapeutic paradigm in many cancers, including chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Oral selective inhibitor of nuclear export (SINE) compounds that covalently modify XPO1 were recently discovered and are exciting new compounds to implement this strategy. Selinexor, the clinical lead SINE, has made progress in Phase I/II clinical trials and is generally well tolerated, but limited to twice weekly dosing, with supportive care. The discovery of novel SINE compounds with improved tolerability is therefore of considerable clinical interest and represents a significant contribution beyond the targeted therapies currently available for hematologic malignancies and a variety of other cancers where upregulation of XPO1 is observed. Presented herein is the discovery of KPT-8602, the next generation SINE compound that shows lower brain penetration, improved tolerability allowing continuous dosing, and improved efficacy beyond any current XPO1 inhibitor. Results: Our crystallography data revealed that KPT-8602 binds covalently to XPO1 through a Michael acceptor that is activated by an electron withdrawing pyrimidyl moiety, allowing a 2-fold increased reversible interaction with XPO1 compared to earlier SINE compounds. The crystal structure of the KPT-8602-XPO1 complex showed interactions between XPO1 and the activating pyrimidyl group. In vitro pull-downs using immobilized GST-nuclear export sequences and purified recombinant XPO1 demonstrated greater reversible binding of KPT-8602 compared to KPT-330 (selinexor). In vivo toxicology studies demonstrated that KPT-8602 possesses lower brain penetration compared to KPT-330 allowing for continuous dosing and improved tolerability. Our results also showed that KPT-8602 induced a comparable level of cytotoxicity as well as inhibition of cell proliferation compared to KPT-330 in primary CLL tumors and in a representative panel of DLBCL cell lines. Furthermore, KPT-8602 inhibited proliferation and induced apoptosis in AML cell lines and primary AML blasts while inducing nuclear accumulation of p53 and NPM1. We hypothesized that these improved pharmacological parameters would allow daily KPT-8602 to abrogate disease progression in CLL and AML animal models. The Eµ-TCL1-C57BL/6 transplant model of CLL was used to evaluate the therapeutic benefit of continuous dosing of KPT-8602. Eµ-TCL1-engrafted mice were treated with KPT-8602 given daily or 2x/week. The KPT-8602 daily cohort had significantly improved survival with a median overall survival of 70 vs 50 days (vs vehicle 33 days), compared to those treated only 2x/week with KPT-8602 (p=0.001). Mice treated with KPT-330 2x/week showed a similar survival to mice treated with KPT-8602 2x/week. Mice given daily KPT-8602 had significantly smaller spleens and reduced circulating leukemic cells compared to all the other groups (p<0.001 for all comparisons). We recently showed the combination of KPT-330 and ibrutinib (bruton tyrosine kinase inhibitor) increases survival compared to ibrutinib alone in Eµ-TCL1-engrafted mice. We therefore tested the effect of KPT-330+ibrutinib or KPT-8602+ibrutinib in a cohort of Eµ-TCL1-engrafted mice compared to any agent alone. Notably, the combination of KPT-8602 to ibrutinib was able to further improve the survival induced by KPT-330+ibrutinib (p=0.008). We next assessed the activity of KPT-8602 in a human leukemia xenograft model of AML where NOD/SCID γ mice were inoculated with MV4-11 cells obtained from spleens of primary MV4-11 xenografts. Recipient mice given KPT-8602 5x/week showed strikingly better outcomes with a median survival of 58 vs 35 days compared to KPT-8602 2x/week (p<0.0001) and KPT-330 2x/week (p<0.0001). Conclusion: Consistent with the in vitro finding of a two-fold enhanced reversibility of XPO1-KPT-8602 binding and lower brain penetration, our data indicate that KPT-8602 allows a prolonged frequent dosing schedule, which leads to an excellent therapeutic benefit and less toxicity in animal models of CLL and AML. These data suggest that KPT-8602 represents a new treatment paradigm and warrants further evaluation in clinical trials of patients with hematologic malignancies, particularly in combination with ibrutinib or other second generation Btk inhibitors. Disclosures Baloglu: Karyopharm Therapeutics Inc.: Employment, Equity Ownership. Shacham:Karyopharm: Employment, Equity Ownership. Kauffman:Karyopharm: Employment, Equity Ownership. Byrd:Acerta Pharma BV: Research Funding. Chook:Karyopharm Therapeutics Inc.: Consultancy.
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Hösle, Vittorio. "On Some Specific Traits of Russian Culture." Zeitschrift für Medien- und Kulturforschung 8, no. 1 (2017): 61–78. http://dx.doi.org/10.28937/1000107622.
Повний текст джерелаАнотація:
"The essay discusses the question in which sense there are continuities between the pre-Soviet, the Soviet, and the post-Soviet phase of Russian culture. It discovers in the rejection of the bourgeois value system an important constant factor. Even if originally rooted in the specific orthodox Christian sensibility, it helped prepare the Soviet revolution and survived even after 1991. From the Song of Igor’s Campaign to Tolstoy’s dramas, Eisenstein’s films and his film theory, and Maxim Kantor’s iconic interpretations of the late Soviet Union and its aftermath the essay tries to unveil crucial features of Russian culture. Der Aufsatz diskutiert die Frage, in welchem Sinne es Kontinuitäten zwischen der vor-sowjetischen, der sowjetischen und der post-sowjetischen Phase der russischen Kultur gibt, und entdeckt in der Ablehnung des bürgerlichen Wertesystems einen wichtigen konstanten Faktor. Auch wenn sie ursprünglich in der spezifischen orthodoxen christlichen Sensibilität verwurzelt war, half sie, die sowjetische Revolution vorzubereiten, und überlebte auch noch nach 1991. Von dem Igorlied bis hin zu Tolstois Dramen, Eisensteins Filmen und Filmtheorie sowie Maxim Kantors ikonischen Interpretationen der späten Sowjetunion und ihren Nachwirkungen enthüllt der Aufsatz entscheidende Merkmale der russischen Kultur. "
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Anderson, Keilin, and Adaena Sinclair-Blakemore. "Ne bis in idem, nulla poena sine lege and Domestic Prosecutions of International Crimes in the Aftermath of a Trial at the International Criminal Court." International Criminal Law Review 21, no. 1 (March 8, 2021): 35–66. http://dx.doi.org/10.1163/15718123-21010001.
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Abstract The outcome of an icc trial – be it a conviction or acquittal – receives significant attention. However, what happens to a defendant in the aftermath of the proceeding garners little discussion. This article seeks to fill this gap in the literature by analysing how the ne bis in idem and nulla poena sine lege principles, enshrined in Articles 20(2) and 23 of the Rome Statute, protect defendants from subsequent prosecutions and punishments by states and regional courts following their trials at the icc. We argue that these provisions do not provide adequate protection. Further, we argue that given the icc’s limited power to enforce compliance with these provisions as well as the primary role that states enjoy in the enforcement of international criminal law, the most appropriate way to address this issue is through the inclusion of robust protections in domestic legislation and the constituent instruments of regional courts.
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Ziade, Nelly, Michel Bou Absi, and Xenofon Baraliakos. "Peripheral spondyloarthritis and psoriatic arthritissine psoriase: are we dealing with semantics or clinically meaningful differences?" RMD Open 8, no. 2 (November 2022): e002592. http://dx.doi.org/10.1136/rmdopen-2022-002592.
Повний текст джерелаАнотація:
Diagnosing peripheral spondyloarthritis (pSpA) remains a significant challenge due to the lack of specific disease biomarkers and the overlap with other SpA subtypes, mainly psoriatic arthritis (PsA), which represents a diagnostic challenge particularly in the absence of skin psoriasis (PsAsine psoriase). This narrative review aimed to compare the epidemiology, genetic susceptibility, pathophysiology, classification criteria, disease phenotype and burden, and therapeutic guidelines between patients diagnosed with pSpA and those with PsAsine psoriase,to determine if the two entities should be considered jointly or distinctly. Globally, pSpA appears to be more inclusive compared with PsAsine psoriase. Areas of similarities include age of onset, number of joints involved and prevalence of axial involvement. However, patients with pSpA have a male gender predominance, a higher prevalence of HLA-B27, enthesitis and involvement of large joints of the lower limbs, whereas patients with PsAsine psoriasehave a higher prevalence HLA-Cw6, dactylitis and involvement of hand distal interphalangeal joints. Therefore, the difference between pSpA and PsAsine psoriasegoes beyond semantics. The few dissimilarities should drive scientific efforts to reach a better characterisation of pSpA as an individual disease. Accordingly, randomised clinical trials should target patients with well-defined pSpA to identify effective therapies in this population.
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Zhang, Hao P., Miriam LeGare, and Sang K. Lee. "Effects of Three Stimulus Parameters on Eye Position in Cerebral Palsied Adults." Perceptual and Motor Skills 87, no. 1 (August 1998): 355–73. http://dx.doi.org/10.2466/pms.1998.87.1.355.
Повний текст джерелаАнотація:
Bilateral eye position was measured in 6 cerebral palsied adults to assess the effects of stimulus dimension (horizontal, vertical), amplitude (±4°, ±6°, ± 8°), and frequency (0.3, 0.5, 0.7 Hz) on saccadic and pursuit movements. The head-free, corneal reflection method was used for 54 10-sec. trials of square, triangle, and sine wave stimuli. Shared variance between each eye's position and the stimulus was tested by Wilcoxon T (dimension) and Friedman analysis of variance (amplitude, frequency) showing that the effects of saccadic and pursuit dimension and amplitude were individualized with regard to subject and right and left eye positions. The bilateral eye position of 5 of 6 subjects was affected by saccadic frequency; pursuit frequency affected bilateral eye position of 4 of 6 subjects. The lowest shared variance (critical difference in ranks) was at 0.7 Hz. The results are discussed with regard to subjects' disability, stimulus velocity, and frequency of directional reversal. Reversal may be the most critical stimulus property.
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Jardin, Fabrice, Anais Pujals, Laura Pelletier, Elodie Bohers, Vincent Camus, Sylvain Mareschal, Sydney Dubois, et al. "Recurrent Mutations of the Exportin 1 Gene (XPO1) in Primary Mediastinal B-Cell Lymphoma: A Lysa Study." Blood 126, no. 23 (December 3, 2015): 129. http://dx.doi.org/10.1182/blood.v126.23.129.129.
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Abstract Background and aim of the study Primary mediastinal B-cell lymphoma (PMBL) is an entity of aggressive B-cell lymphoma that is clinically and biologically distinct from the other molecular subtypes of diffuse large B-cell lymphoma (DLBCL). We recently detected by Whole exome sequencing a recurrent point mutation in the XPO1 (exportin 1) gene (also referred to as chromosome region maintenance 1; CRM1), which resulted in the Glu571Lys (p.E571K) missense substitution in 2 refractory/relapsed PMBL (Dubois et al., ICML 2015; Mareschal et al. AACR 2015). XPO1 is a member of the Karyopherin-b superfamily of nuclear transport proteins. XPO1 mediates the nuclear export of numerous RNAs and cellular regulatory proteins, including tumor suppressor proteins. This mutation is in the hydrophobic groove of XPO1 that binds to the leucine-rich nuclear export signal (NES) of cargo proteins. In this study, we investigated the prevalence, specificity, and biological / clinical relevance of XPO1 mutations in PMBL. Patients and methods High-throughput targeted or Sanger sequencing of 117 PMBL patients and 3 PMBL cell lines were performed. PMBL cases were defined either molecularly by gene expression profile (mPMBL cohort) or by standard histological method (hPMBL cohort) and enrolled in various LYSA (LYmphoma Study Association) clinical trials. To assess the frequency and specificity of XPO1 mutations, cases of classical Hodgkin lymphoma (cHL) and primary mediastinal grey zone lymphoma (MGZL) were analysed. Cell experiments were performed to assess the impact of the E571 mutation on the activity of selective inhibitor of nuclear export (SINE) molecules. Results XPO1 mutations were present in 28/117 (24%) PMBL cases but were rare in cHL cases (1/19, 5%) and absent from MGZL cases (0/20). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in PMBL cases defined by gene expression profiling (n = 32), as compared to hPMBL cases (n = 85, 13%). No difference in age, International Prognostic Index (IPI) or bulky mass was observed between the PMBL patients harboring mutant and wild-type XPO1 in the overall cohort whereas a female predominance was noticed in the mPMBL cohort. Based on a median follow-up duration of 42 months, XPO1 mutant patients exhibited significantly decreased PFS (3y PFS = 74% [CI95% 55-100]) compared to wild-type patients (3y PFS = 94% [CI95% 83-100], p=0.049) in the mPMBL cohort. In 4/4 tested cases, the E571K variant was also detected in cell-free circulating plasmatic DNA, suggesting that the mutation can be used as a biomarker at the time of diagnosis and during follow-up. Importantly, the E571K variant was detected as a heterozygous mutation in MedB-1, a PMBL-derived cell line, whereas the two other PMBL cell lines tested, Karpas1106 and U-2940, did not display any variants in XPO1 exon 15. KPT-185, the SINE compound that blocks XPO1-dependent nuclear export, induced a dose-dependent decrease in cell proliferation and increased cell death in the PMBL cell lines harbouring wild type or mutated alleles. To test directly if XPO1 mutation from E571 to E571K alters XPO1 inhibition by SINE compounds, the mutated protein was tested in vitro. The E571XPO1 mutated allele was transiently transfected into osteosarcoma U2OS cells which stably express the fluorescently labelled XPO1 cargo REV. Cells were treated with the clinical SINE compound selinexor, which is currently in phase I/II clinical trials and nuclear localization of REV-GFP was analysed in red transfected cells. The results showed that the nuclear export of the mutated XPO1 protein was inhibited by selinexor similarly to the wild-type XPO1 protein (Figure 1). Conclusion Although the oncogenic properties of XPO1 mutations remain to be determined, their recurrent selection in PMBL strongly supports their involvement in the pathogenesis of this curable aggressive B-cell lymphoma. XPO1 mutations were primarily observed in young female patients who displayed a typical PMBL molecular signature. The E571K XPO1 mutation represents a novel hallmark of PMBL but does not seem to interfere with SINE activity. Rev-GFP (green fluorescent) expressing U2OS cells were transfected with wild type XPO1-RFP (red fluorescent protein), XPO1-C528S-RFP, XPO1-E571K-mCherry, and XPO1-E571G-mCherry. The cells were then treated with 1µM KPT-330 for 8 hours. Figure 1. Rev-GFP expressing U2OS cells transfected with XPO1 variants. Figure 1. Rev-GFP expressing U2OS cells transfected with XPO1 variants. Disclosures Landesman: Karyopharm Therapeutics: Employment. Senapedis:Karyopharm Therapeutics, Inc.: Employment, Patents & Royalties. Argueta:Karyopharm Therapeutics: Employment. Milpied:Celgene: Honoraria, Research Funding.
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Mourinha, Marisa. "O português lá fora: algumas reflexões sobre a circulação da literatura de língua portuguesa." Cadernos de Literatura Comparada, no. 43 (2020): 269–85. http://dx.doi.org/10.21747/21832242/litcomp43a16.
Повний текст джерелаАнотація:
The dissemination of a literary work depends on several factors, but its availability to the public is a sine qua non and, for that reason, translation plays a capital role in this process. However, literary works from periph-eral systems will thus have particular difficulty in finding its way to their potential readers. We know that a translation into a central language may be a way for a work from a peripheral system to reach others of a similar dimension or condition (Sapiro 2008), but central systems do tend to leave little space for translated literature (Even-Zohar 1990). One should not be surprised, then, to learn that for Casanova “Translation is the major prize and weapon in international literary competition” (Casanova 2004: 133). How, in that case, can Portuguese language literature aspire to a place which could grant it more visibility? What are the main actors involved in the process? This paper tries to assess what circuits do these cultural products have access to, and how the selection of works and authors to be translated mirrors, if at all, a cultural project and/or policy.
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Tandyanto, Yulius. "Membaca 'Kebenaran' Nietzsche." MELINTAS 31, no. 2 (November 23, 2015): 130. http://dx.doi.org/10.26593/mel.v31i2.1622.130-153.
Повний текст джерелаАнотація:
<p>Nietzsche’s early work that gives wide exploration of the idea of truth is his unpublished essay entitled <em>Wahrheit und Lüge in Ausermoralischen Sinne </em>(1872). His controversial statement in this essay was “Truths are illusions”, opening many interpretations among scholars in understanding his position on truth. Sarah Kofman argues that it is useless to speak about truth in Nietzsche’s philosophy, for values are neither true nor false. Referring values to truth means forgetting to place oneself “beyond good and evil.” Unlike Kofman, Maudemarie Clark separates sharply Nietzsche’s critique of metaphysics and his denial of truth. Clark argues that Nietzsche rejects metaphysics and eventually overcomes it in his own work, but also that he ultimately affirms the existence of truths and therefore does not undermine his own theory when he claims truth for his own position. Clark’s strategy in defending her theses tries to explain that there is a turning (<em>Kehre</em>) in Nietzsche’s position. This article wants to offer an interpretation that Nietzsche does not make a new theory of truth in <em>WL</em>, but rather examines and constates truths that hold true. With his subtile and metaphoric style, Nietzsche might want to vivify the symbolic and figurative elements in language before the truth or reality that already escapes languages.</p>
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Rosebeck, Shaun, Mattina Alonge, Jagoda Jasielec, Anoop Mayampurath, Samuel L. Volchenboum, Sharon Shacham, Michael Kauffman, and Andrzej Jakubowiak. "Gene Expression and Transcription Factor (TF) Activation Profiling Identifies Suppression of Multiple Myeloma (MM) Cell Survival and Chemoresistance Pathways By Inhibition of XPO1/CRM1-Dependent Nuclear Export with Selinexor." Blood 124, no. 21 (December 6, 2014): 3444. http://dx.doi.org/10.1182/blood.v124.21.3444.3444.
Повний текст джерелаАнотація:
Abstract INTRODUCTION Despite improved response rates following the use of novel therapeutics, including proteasome inhibitors (PI) and immunomodulatory drugs, the majority of MM patients develop chemoresistance and relapse. Thus, it is essential to identify novel drugs that overcome resistance and promote remission. Our previous work detailed the synergistic activity of combined treatment with selective inhibitor of nuclear export (SINE) selinexor and PI carfilzomib (CFZ) in MM (Rosebeck et al, Blood 2013:122(21):279). In this study, we sought to characterize the underlying mechanism of selinexor, a novel drug being tested in multiple phase I/II clinical trials of advanced-stage cancers. METHODS Plasma cells (PC) were purified from MM patient bone marrow (BM) aspirates using EasySep (STEMCELL Tech). RPMI 8226, 8226/Dox40, and MM1S cells were cultured in RPMI1640/10% FBS. RNA was isolated with RNeasy minicolumns (Qiagen) from control or MM1S cells treated for 6 hrs with selinexor. Gene expression profiling was done on Illumina HumanHT12 microarray and InfernoRDN. Differentially expressed genes were input into Ingenuity Pathway Analysis software (Qiagen). Fisher’s exact test was used to calculate p-values for significant pathway enrichment. TF profiling plate array was from Signosis. RESULTS Selinexor treatment inhibited key MM pathway regulators including transforming growth factor beta 1 (TGFB1; p=1.65E-14), which is involved in paracrine BM signaling and bone formation, and the epidermal growth factor (EGF) receptor HER2 (p=4.84E-08), which deregulates EGF signaling and promotes survival. SINE also affected integrin-associated signaling (p=2.42E-03), which controls MM/BM stromal cell adhesion and contributes to chemoresistance. We profiled SINE-dependent changes in TF activation and found increased DNA binding of cAMP response element-binding protein (CREB), which represses IL-6 production, an essential MM cell survival cytokine, and retinoid X receptor (RXR), which is associated with MM cell death. We also found impaired DNA binding of heat shock factors (HSF), which sensitizes MM cells to PI, Kruppel-like factor 4 (KLF4) and multidrug resistance (MDR) promoter-enhancing factors 1 and 2 (MEF-1/2), which are associated with chemoresistance in MM, nuclear respiratory factor 1 (NRF-1), which mediates a recovery pathway to compensate for reduced proteasome function, and paxillin 2 (Pax2), a transcriptional repressor of p53 and enhancer of Wilms tumor protein (WT1). In addition, TF associated with poor prognosis MM, including the pre-B cell homeobox (PBX) oncogene, soluble mucin 1 (SMUC), and WT1, were inhibited. Next, we tested the ability of selinexor to overcome drug resistance in MM cells. 8226/Dox40 are insensitive to the effects of CFZ via upregulation of p-glycoprotein, however selinexor effectively killed these cells. Importantly, we demonstrate efficacy of SINE on PC from patients refractory to and/or relapsing (R/R) on PI-containing regimens. Additionally, we will present preliminary responses from CFZ-refractory patients enrolled in our newly-opened multi-site phase I clinical trial conducted in the MM Research Consortium combining selinexor and CFZ with dexamethasone in R/R MM (NCT02199665). CONCLUSIONS Our results suggest selinexor-dependent inhibition of pathways that promote intrinsic MM cell survival and contribute to chemoresistance in the BM milieu, which may be mediated by suppression of essential growth factors and genes involved in MM cell/BM stroma adhesion. We also found inhibition of TF that may influence MDR/PI resistance either directly (KLF4, MEF-1/2) or indirectly (HSF, NRF-1). Finally, we demonstrate the ability of SINE to overcome MDR in MM cells and PC from patients with R/R disease. Our studies provide evidence of the pleiotropic effects of SINE and underscore the potential of selinexor to be an effective therapeutic for advanced-stage cancers, including MM. Disclosures Shacham: Karyopharm Therapeutics Inc.: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Kauffman:Karyopharm Therapeutics: Employment. Jakubowiak:Bristol Myers-Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SkylineDx: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Gao, Qiang, Yuxin Zhang, Zhe Wang, Enzeng Dong, Xiaolin Song, and Yu Song. "Channel Projection-Based CCA Target Identification Method for an SSVEP-Based BCI System of Quadrotor Helicopter Control." Computational Intelligence and Neuroscience 2019 (December 16, 2019): 1–13. http://dx.doi.org/10.1155/2019/2361282.
Повний текст джерелаАнотація:
The brain-computer interface (BCI) plays an important role in assisting patients with amyotrophic lateral sclerosis (ALS) to enable them to participate in communication and entertainment. In this study, a novel channel projection-based canonical correlation analysis (CP-CCA) target identification method for steady-state visual evoked potential- (SSVEP-) based BCI system was proposed. The single-channel electroencephalography (EEG) signals of multiple trials were recorded when the subject is under the same stimulus frequency. The CCAs between single-channel EEG signals of multiple trials and sine-cosine reference signals were obtained. Then, the optimal reference signal of each channel was utilized to estimate the test EEG signal. To validate the proposed method, we acquired the training dataset with two testing conditions including the optimal time window length and the number of the trial of training data. The offline experiments conducted a comparison of the proposed method with the traditional canonical correlation analysis (CCA) and power spectrum density analysis (PSDA) method using a 5-class SSVEP dataset that was recorded from 10 subjects. Based on the training dataset, the online 3D-helicopter control experiment was carried out. The offline experimental results showed that the proposed method outperformed the CCA and the PSDA methods in terms of classification accuracy and information transfer rate (ITR). Furthermore, the online experiments of 3-DOF helicopter control achieved an average accuracy of 87.94 ± 5.93% with an ITR of 21.07 ± 4.42 bit/min.
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Yin, Huilan, Jing Zhang, Yanming Qi, and Dongping Li. "Design and Implementation of University Students Scientific Research Ability Evaluation System Based on Neural Network." Scientific Programming 2022 (February 18, 2022): 1–10. http://dx.doi.org/10.1155/2022/4744774.
Повний текст джерелаАнотація:
At present, many colleges attach more and more importance to the cultivation of scientific research ability of college students. However, there is no unified standard to effectively measure the cultivation effect. The current performance inference method cannot comprehensively evaluate the scientific research ability of college students. Few scholars have directly analyzed the college students’ scientific research ability from the internal and external influencing factors. Therefore, this paper tries to design and implement a neural network analysis system for scientific research ability evaluation of college students. After surveying the status quo of scientific research ability evaluation of college students in northern China’s Hebei Province, a hierarchical evaluation index system was constructed for college students’ scientific research ability, referring to the existing evaluation index systems, and the weights were designed for the evaluation indices. Next, the backpropagation (BP) neural network was optimized by chaotic sine-cosine grasshopper optimization algorithm (CSCGOA) and used to establish a neural network analysis system for scientific research ability evaluation of college students. The proposed system was proved effective through experiments. The relevant results effectively enhance the scientific level and accuracy of the evaluation of college students’ scientific research ability, improve the cultivation of college students, and provide a scientific basis for colleges to understand the scientific research ability of their students.