Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological inhibition of S6K1 facilitates platelet activation by enhancing Akt phosphorylation

Abstract Platelet activation and thrombus formation is a delicate process involving a series of crosstalk between different pathways. P70 ribosomal S6 kinase1 (S6K1) is a member of serine/threonine kinases and can be phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1). S6K1 is widely reported to play important roles in cancers and metabolic diseases, but the role of S6K1 and the importance of phosphorylation on Thr229 in platelet activation have not been defined. PF-4708671 is a recently synthesized highly specific inhibitor of S6K1. In this study, we tested PF-4708671 to assess the role of S6K1 in platelet. PF-4708671 facilitated mouse and human platelet aggregation and ATP secretion induced by collagen, thrombin, and adenosine diphosphate through enhanced Akt and Gsk3β phosphorylation. PF-4708671 also accelerated integrin αIIbβ3-mediated clot retraction and spreading. Intravenously given PF-4708671 shortened the occlusion time in arterial thrombosis model. Further results demonstrated that S6K1 was phosphorylated by PDK1 on Thr229 in the resting platelets and dephosphorylated in response to agonist stimulation. PDK1-deficient mice showed higher aggregation when PI3K–Akt–Gsk3β signaling was blocked by the Gsk3β-inhibitor SB216763. Thus, S6K1 Thr229 phosphorylation might function as a regulator that prevents platelets from activation. S6K1 inhibition may yield potential pro-thrombotic effects and should be used cautiously when considered as a therapy.
Broadcasts for a billion: the growth of commercial television in China.

At present, Chinese television reaches 35% of the population (80-90% in urban areas) and is used by the government as a source of education and information. In recognition of the potential market represented by 1.1 billions consumers, Western advertisers have commissioned elaborate market research studies. Drama, sports, news, and movies are consistently identified as the favorite type of programming among Chinese television viewers. About 75% of Beijing adults watch television daily, making the medium both an important target for advertising campaigns and a way for Westerners to influence Chinese business and government leaders. Western advertisers have tended to concentrate their investments in the more urban, affluent regions where products have the greatest likelihood of being sold. There has been a recent trend, however, toward industrial commercials, with British and French companies buying television time to promote their image as partners in China's modernization. Key to the future of commercial advertising on Chinese Television. In many provinces, local television stations have developed a unique character and portray different sociocultural values than the national channel. Outside advertisers have sometimes experienced problems with local networks that substitute local advertising without informing the network. To correct this situation, the government is enacting pro-sponsor regulations that forbid the preemption of the national channel and its advertisements. At the same time, efforts are being made to improve relationships with local television stations by either paying them a fee or airing local commercials on the national network.
Exploration of heuristic scheduling algorithms for 3D multicore processors

In this paper, we explore heuristic scheduling algorithms for future multicore processors. It is expected that hundreds or even thousands of cores will be integrated on a single chip, known as a Chip Multiprocessor (CMP). To reduce on-chip communication delay and improve efficiency, three-dimensional (3D) integration with Through Silicon Vias (TSVs) is introduced to replace the traditional two-dimensional (2D) implementation. Multiple functional layers can be stacked in 3D CMPs. However, operating system process scheduling has not been well addressed for such systems. We define a model for 3D CMPs, and propose a heuristic scheduling algorithm which aims to reduce cache access latencies and the delay of inter process communication. We explore different scheduling methods and discuss the advantages and disadvantages of our algorithm. Experimental results show that under three different workloads, the execution times of our scheduling method in two configurations are reduced by 14.5% and 5.86% respectively, compared with the other scheduling methods. Two scheduling methods from different heuristics for 8-thread tasks are also compared. This research provides a guideline for designing scheduling algorithms for future 3D CMPs.
Tumoral and tissue‐specific expression of the major human β‐tubulin isotypes

The β‐tubulins are microtubule components encoded by a multigene family, which produces slightly different proteins with complex expression patterns. Several widely used anticancer drugs base their activity on β‐tubulin binding, microtubule dynamics alteration, and cell division blockage. The expression of these drug targets in tumoral and normal cells could be of crucial importance for therapy outcome, unfortunately, the complex β‐tubulin expression patterns have been poorly characterized in human. In this study, we developed a quantitative RT‐PCR technique that accurately determines the mRNA expression of the eight human β‐tubulin isotypes, encoding class I, IIa, IIb, III, IVa, IVb, V, and VI and applied it to 21 nontumoral tissues and 79 tumor samples belonging to seven cancer types. In the nontumoral tissues, we found that, overall, TUBB (I), TUBB2C (IVb), and TUBB6 (V) were ubiquitous, TUBB1(VI) was hematopoietic cell‐specific, and TUBB2A (IIa), TUBB2B (IIb), TUBB3 (III), and TUBB4 (IVa) had high expression in brain; however, the contribution of the different isotypes to the total β‐tubulin content varied for each tissue and had a complex pattern. In tumoral tissues, most isotypes exhibited an altered expression in specific tumor types or related to tumoral characteristics. In general, TUBB3 showed a great increase in expression while TUBB6 expression was largely decreased in most tumors. Thus, normal tissues showed a complex β‐tubulin isotype distribution, which could contribute to the toxicity profile of the microtubule‐binding drugs. In addition, the specific isotypes significantly altered in tumors might represent markers for drug response. © 2010 Wiley‐Liss, Inc.
Dynamiques de réseau et image de marque dans les quartiers créatifs spontanés. Le cas du quartier des Olivettes à Nantes

Depuis le debut des annees 2000, la planification de quartiers creatifs par les pouvoirs publics dans le cadre de strategies de marketing territorial s'est multipliee. En parallele, des quartiers creatifs resultant d'une agglomeration spontanee de travailleurs creatifs (artistes, designers, architectes…) emergent. L'objectif de cet article est de mettre en lumiere les realites en termes de reseau et d'image de ces quartiers situes en-dehors des perimetres « creatifs » officiels. Pour cela, le cas d'un quartier creatif spontane a Nantes (les Olivettes) va etre analyse sur la base d'enquetes qualitatives et mis en perspective avec le Quartier de la Creation officiel de la ville. Organises sous la forme d'un club selectif ancre dans le quartier, les travailleurs creatifs des Olivettes developpent des reseaux collaboratifs dynamises par la proximite de valeurs qui les lie. Ils font egalement emerger une image de marque en valorisant leur appartenance au « vrai » quartier creatif de la ville et en cherchant a renforcer l'agglomeration spatiale d'activites des secteurs culturels et creatifs.
Analysis of causes of delay in Indian construction projects and mitigation measures

Purpose Construction projects in India continue to suffer excessive delays. This paper aims to investigate the delay causes in India by project sector (transport, power, buildings and water) and carry out a comparative study of delay causes in design build (DB) projects with that of design bid build (DBB) projects along with mitigation measures. Design/methodology/approach A questionnaire survey was conducted among major clients, contractors and consultants in India. Importance Index was used for ranking of the delay causes. Projects were categorized based on the type, and causes of delay in each project type were identified. Projects were also categorized based on type of contract, and delay causes in DB and DBB projects were compared. Statistical analysis of responses by Cronbach’s alpha, one-way analysis of variance, Kruskal–Wallis tests was carried out with Statistical Package for Social Sciences. Semi-structured in-depth interviews were conducted with senior industry professionals to develop exhaustive mitigation measures. Findings The research findings indicate finance-related causes as the most critical causes of delay in Indian projects. Delay in settlement of claims, contractor’s financial difficulties, delay in payment for extra work/variations by owner, late payment from contractor to subcontractor or suppliers, variation orders/changes of scope by owner during construction and changes in design by owner were the highly ranked delay causes. The research found no significant difference in the delay causes in DB and DBB projects. Originality/value This is the first study wherein delay causes for various project types within a single country are identified. In addition, the study has identified and compared the delay causes in DB projects and DBB projects. Mitigation measures developed in this study will help professionals and project managers not just in India but other developing countries as well to alleviate delay causes and in improvement of project timelines.
The Evolution of Private Labels in Food Proposals: The Case of the Top Four Italian Retailers and the Purchase Propensity of Consumers

The presence of products marked with the brand of the retailer is not a novelty in the mass distribution circuit. In the last decades, private labels (PLs) increased in a relevant way, upgrading the competition with the proposals coming from branded products. Since the beginning of the last century, this comparison attracted the attention of many scholars. Different factors were analyzed as, for example, the brand value, the trust in the distribution company or other elements that underlined the acceptance of PLs products. Actually, thanks to a new and consolidated trend in the market, it is possible to register an evolution of PLs, with a relevant specialization. The aim of the present work is to analyze, in the Italian context, this evolution, observing the food proposals of the main PLs. In addition, this differentiation is compared with the purchase propensity of consumers. The final purpose is to discover the effective match between market demand and the value propositions of qualified Italian retailers. The study is organized with a theoretical background to define in a structured way the topic. After, there are the evidences of the research, carried out on a double way. First there is the panel of the PLs proposals at the beginning of 2018, referred to the first four groups in the Italian market. Therefore, considering the categories represented by these products, a survey has been conducted to discover the acceptance of the consumers. Final results show how this panorama is become complex and when differentiation is able to fit the desires of customers. This study provides relevant implications from the marketing point of view. It is a valid contribution for practitioners and scholars, giving a further vision in the evolution of PLs foodstuffs.
Modular Session Types for Objects

Session types allow communication protocols to be specified type-theoretically so that protocol implementations can be verified by static type checking. We extend previous work on session types for distributed object-oriented languages in three ways. (1) We attach a session type to a class definition, to specify the possible sequences of method calls. (2) We allow a session type (protocol) implementation to be modularized, i.e. partitioned into separately-callable methods. (3) We treat session-typed communication channels as objects, integrating their session types with the session types of classes. The result is an elegant unification of communication channels and their session types, distributed object-oriented programming, and a form of typestate supporting non-uniform objects, i.e. objects that dynamically change the set of available methods. We define syntax, operational se-mantics, a sound type system, and a sound and complete type checking algorithm for a small distributed class-based object-oriented language with structural subtyping. Static typing guarantees that both sequences of messages on channels, and sequences of method calls on objects, conform to type-theoretic specifications, thus ensuring type-safety. The language includes expected features of session types, such as delegation, and expected features of object-oriented programming, such as encapsulation of local state.
A Role for Neurokinin B in Pulsatile GnRH Secretion in the Ewe

The recent description of infertility in humans with loss-of-function mutations in genes for neurokinin B (NKB) or its receptor (NK3R) has focused attention on the importance of this tachykinin in the control of GnRH secretion. In a number of species, NKB neurons in the arcuate nucleus also produce two other neuropeptides implicated in the control of GnRH secretion: (1) kisspeptin, which is also essential for fertility in humans, and (2) dynorphin, an inhibitory endogenous opioid peptide. A number of characteristics of this neuronal population led to the hypothesis that they may be responsible for driving synchronous release of GnRH during episodic secretion of this hormone, and there is now considerable evidence to support this hypothesis in sheep and goats. In this article, we briefly review the history of work on the NKB system in sheep and then review the anatomy of NKB signaling in the ewe. We next describe evidence from a number of species that led to development of a model for the role of these neurons in episodic GnRH secretion. Finally, we discuss recent experiments in sheep and goats that tested this hypothesis and led to a modified version of the model, and then broaden our focus to briefly consider the possible roles of NKB in other species and systems.
Flexible, symmetry-directed approach to assembling protein cages

Significance The ability to organize biological molecules into new hierarchical forms represents an important goal in synthetic biology. However, designing new quaternary interactions between protein subunits has proved technically challenging and has generally required extensive redesign of protein−protein interfaces. Here, we demonstrate a conceptually simple way to assemble a protein into a well-defined geometric structure that uses coiled-coil sequences as “off-the-shelf” components. This approach is inherently modular and adaptable to a wide range of proteins and symmetries, opening up avenues for the construction of biological structures with diverse geometries and wide-ranging functionalities. The assembly of individual protein subunits into large-scale symmetrical structures is widespread in nature and confers new biological properties. Engineered protein assemblies have potential applications in nanotechnology and medicine; however, a major challenge in engineering assemblies de novo has been to design interactions between the protein subunits so that they specifically assemble into the desired structure. Here we demonstrate a simple, generalizable approach to assemble proteins into cage-like structures that uses short de novo designed coiled-coil domains to mediate assembly. We assembled eight copies of a C3-symmetric trimeric esterase into a well-defined octahedral protein cage by appending a C4-symmetric coiled-coil domain to the protein through a short, flexible linker sequence, with the approximate length of the linker sequence determined by computational modeling. The structure of the cage was verified using a combination of analytical ultracentrifugation, native electrospray mass spectrometry, and negative stain and cryoelectron microscopy. For the protein cage to assemble correctly, it was necessary to optimize the length of the linker sequence. This observation suggests that flexibility between the two protein domains is important to allow the protein subunits sufficient freedom to assemble into the geometry specified by the combination of C4 and C3 symmetry elements. Because this approach is inherently modular and places minimal requirements on the structural features of the protein building blocks, it could be extended to assemble a wide variety of proteins into structures with different symmetries.
Low Prevalence of Primary HIV Resistance in Western Massachusetts

Most studies of primary antiretroviral (ARV) resistance have been conducted in large metropolitan areas with reported rates of 8% to 25%. We collected data on 99 HIV-1-infected antiretroviral-naive patients from several sites in Springfield, MA, who underwent genotypic resistance assay between 2004 and 2008. Only major resistance mutations per International AIDS Society-USA (IAS-USA) drug resistance mutations list were considered. The prevalence of resistance was 5% (5 of 99). Three patients had one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation: 103N, 103N, and 190A, 1 patient had a protease inhibitor (PI) mutation: 90M; and 1 patient had 3-class resistance with NNRTI: 181C, 190A, PI: 90M, and nucleoside analogue reverse transcriptase inhibitor (NRTI): 41L, 210W. Mean time from HIV diagnosis to resistance testing was shorter in patients with resistance versus those without: 9 (range 0.3-42 months) versus 27 (range 0.1-418 months), P = . 11. There was a trend to lower mean CD4 count in those with resistance, 170 versus 318 cells/mm3, P = . 06. No differences were noted in gender, age, HIV risk category, or HIV RNA level. The low prevalence of primary resistance may be explained by differences in demographic and risk factors or may reflect the time from infection to resistance testing. Our findings emphasize the importance of continued resistance surveillance.
High Quality Range Data Acquisition Using Time-of-Flight Camera and Stereo Vision

Time-of-flight range camera (referred to as TOF camera) has many advantages: compact, easy to use and can obtain three-dimensional depth data of any scene in real-time, which makes it increasingly widely used in various applications. However, TOF camera produces very noisy depth map and often performs poorly on the rich-textured scenes, such as textiles, in which situations stereo vision excels. To solve this problem and use the merits of two methods respectively, we propose a method for jointly using TOF cameras and stereo vision to produce a high quality depth map for surfaces that have rich texture. We choose textiles as experimental object, and the result shows that our method significantly improves the quality of the textile's depth data captured from TOF camera. So we also expand the scope of application of TOF cameras.
A Ka Band Transceiver Using LTCC Technology

A Ka band transceiver based on low temperature co-fired ceramics (LTCC) technology is presented in this paper. All the passive elements as well as naked millimeter-wave MMICs of the module are integrated in standard multi-layer LTCC, and encapsulated in metallic package with the size of 30 mm X 30 mm X 4. 5 mm. The measured results demonstrate the feasibility of developing highly miniaturized and hermetical package transceivers at Ka band.
Protein phosphorylation: hormones, drugs, and bioregulation

Reversible protein phosphorylation is widely recognized as an important mechanism for the regulation of cell function by a variety of physiological stimuli. Exposure of cells to hormones, neurotransmitters, and growth factors initiates a cascade of events facilitated by intracellular second messengers and mediated in many cases by protein kinases and/or phosphatases. The subsequent covalent modification of target proteins and the associated changes in their function account for the physiological response. Considerable evidence points to crosstalk between multiple membrane‐associated signaling processes leading to coordinated regulation of cellular processes. The role of protein phosphorylation at multiple points in the pathways that integrate these signals is becoming increasingly apparent. Pharmacological modulation of cellular protein phosphorylation has yielded useful information on the molecular events involved. This review surveys some of the recent progress in hormonal regulation of cell function, focusing on examples that may provide new insight into the role of protein phosphorylation in the coordinated control of cellular processes by physiological stimuli. —Shenolikar, S. Protein phosphorylation: hormones, drugs, and bioregulation. FASEB J. 2: 2753‐2764; 1988.
Detection of apoptosis by the TUNEL technique in clinically localised prostatic cancer before and after combined endocrine therapy.

AIMS: Apoptosis in prostate cancer was evaluated after three months of combined endocrine therapy to investigate the association with tumour grade, tumour stage, and the immunohistochemical detection of p53 and bcl-2 in tumour cells before and after therapy. METHODS: Twenty six formalin fixed, paraffin wax embedded core biopsies and corresponding prostatectomy specimens, excised after three months of combined endocrine therapy, were analysed for the presence of apoptotic cells by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method, and for p53 and bcl-2 overexpression by immunohistochemistry. RESULTS: All 26 adenocarcinomas were clinically localised at diagnosis. In biopsies performed before combined endocrine therapy, the apoptotic indices varied between 0.09% and 1.73%, while the tumour grade fell between Gleason score 1 and 8. The mean (SD) apoptotic count pretherapy was 0.71% (0.50). There was a significant association between elevated apoptotic counts and higher Gleason scores in the biopsies (p = 0.005). After three months of therapy, the percentage of apoptotic tumour cells increased independently of tumour stage, while a significant association with Gleason grade was found (p = 0.0018) and all the tumours had Gleason scores of < 7. In eight cases the apoptotic index was more than twice its pretherapy value. The remaining tumours showed less of an increase in the apoptotic index (five cases) or a reduction in the percentage of apoptotic cells. The overall moderate increase in apoptotic index after combined endocrine therapy was not statistically significant (p = 0.8). Immunoreactivity to p53 was absent in all cases, before and after therapy, while a slight increase in the number of cells overexpressing bcl-2 was observed in five of the 13 tumours (38.1%) with reduced apoptotic indices after therapy. CONCLUSIONS: After three months of combined endocrine treatment a minority of clinically localised prostate neoplasms showed regressive epithelial alterations, associated with an increase in apoptotic tumour cells; an increase in cells overexpressing bcl-2 was observed in five of the 13 tumours with reduced apoptotic indices.