Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating Transcription Factor-1-mediated Hepatocyte Growth Factor-induced Down-regulation of Thrombospondin-1 Expression Leads to Thyroid Cancer Cell Invasion*

Hepatocyte growth factor (HGF) plays a major role in the pathogenesis of a variety of human epithelial tumors including papillary carcinoma of the thyroid. Previous reports demonstrated that HGF, acting through the Met receptor, repressed thrombospondin-1 (TSP-1) expression. To study the mechanisms by which HGF down-regulated TSP-1 expression, we transiently transfected a panel of deleted human TSP-1 promoter reporter plasmids into papillary thyroid carcinoma cells. We identified a region between –1210 and –1123 bp relative to the transcription start site that is responsive to HGF treatment and harbors a cAMP-responsive element (CRE) at position –1199 (TGACGTCC). Overexpression of various members of the CRE-binding protein family identified activating transcription factor-1 (ATF-1) as the transcription factor responsible for HGF-induced repression of TSP-1 promoter activity. This inhibition was associated with a concomitant increase in the abundance of nuclear ATF-1 protein. Gel shift and antibody supershift studies indicated that ATF-1 was involved in DNA binding to the TSP-1-CRE site. Finally, we utilized small hairpin RNA to target ATF-1 and showed that these small interfering RNA constructs significantly inhibited ATF-1 expression at both the RNA and the protein level. ATF-1 knockdown prevented HGF-induced down-regulation of TSP-1 promoter activity and protein expression and also reduced HGF-dependent tumor cell invasion. Taken together, our results indicate that HGF-induced down-regulation of TSP-1 expression is mediated by the interaction of ATF-1 with the CRE binding site in the TSP-1 promoter and that this transcription factor plays a crucial role for tumor invasiveness in papillary carcinoma of the thyroid triggered by HGF.
A Comparison Study of Heuristics for Mapping Parallel Algorithms to Message-passing Multiprocessors

This paper presents a comparison study of popular clustering and mapping heuristics which are used to map task-flow graphs to message-passing multiprocessors. Tb this end, we use task-graphs which arc representative of important scientific algorithms running on data-sets of practical interest. The annotation which assigns weights to nodes and edges of the task-graphs is realistic It reflects current trends in processor, communication channel, and message-passing interface technology and takes into consideration hardware characteristics of state-of-the-art multiprocessors. Our experiments show that applying realistic models for task-graph annotation affects the effectiveness and functionality of clustering and mapping techniques. Therefore, new heuristics are necessary that will take into account more practical models of communication costs. We present modifications to existing clustering and mapping algorithms which improve their efficiency and running-time for the practical models adopted.
Planning quasi-static fingertip manipulations for reconfiguring objects

We address the global motion planning aspects of dexterous manipulation by a multifingered robotic hand. The specific task we address is: starting from a given initial grasp of a three-dimensional (3-D) object O, find feasible quasistatic trajectories (rolling/sliding motions and forces) for the fingertips to move O to a desired final configuration. We call this the reconfiguration problem. Our planner is based on a two-level algorithm combining a graph search on the configuration space of the object and a local planner that solves for instantaneous quasistatic motions of the entire manipulation system. The planner is used for simulating several complex reconfiguration tasks for smooth objects demonstrating the promise of our approach.
Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial.

CONTEXT Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. OBJECTIVE To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. INTERVENTION Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). MAIN OUTCOME MEASURES Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. RESULTS A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P < .001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). CONCLUSIONS The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00003216.
TTF-1 Expression in Pulmonary Adenocarcinomas

Tissue-specific gene expression is mediated largely by transcription factors, and a master regulatory gene is thus a potential marker of cellular lineage. Using normal fetal through adult pulmonary tissues and 64 consecutive lung adenocarcinomas, we examined the expression of thyroid transcription factor (TTF-1), which plays a crucial role in normal lung function and morphogenesis. TTF-1 was expressed consistently throughout the life stages and uniformly in the terminal respiratory unit, which is comprised of peripheral airway cells and small-sized bronchioles. Furthermore, the expression was maintained in 72% of adenocarcinomas that exhibited high correlation with surfactant apoprotein (p <0.001) and morphologic resemblance to terminal respiratory unit cells (p <0.001). The staining pattern was also uniform in the adenocarcinomas despite histologic and microenvironmental diversity in individual tumors and their metastatic foci. This consistency and uniformity, therefore, suggested that TTF-1 expression could be used as a lineage marker of terminal respiratory unit. We also identified interesting distinctions between TTF-1-positive and -negative adenocarcinomas based on their clinicopathologic features and expression of various cancer-associated genes. TTF-1-positive adenocarcinomas had statistically significant prevalence of female (p <0.01), nonsmoker (p <0.05), negative p53 staining (p <0.01), less frequent RB loss (p <0.05), and preserved expression of p27 (p <0.01). The results supported the TTF-1 lineage marker and suggested that molecular pathogenesis may in part be characterized by cellular lineage.
The t(8;21) chromosomal translocation in acute myelogenous leukemia modifies intranuclear targeting of the AML1/CBFα2 transcription factor

Targeting of gene regulatory factors to specific intranuclear sites may be critical for the accurate control of gene expression. The acute myelogenous leukemia 8;21 (AML1/ETO) fusion protein is encoded by a rearranged gene created by the ETO chromosomal translocation. This protein lacks the nuclear matrix-targeting signal that directs the AML1 protein to appropriate gene regulatory sites within the nucleus. Here we report that substitution of the chromosome 8-derived ETO protein for the multifunctional C terminus of AML1 precludes targeting of the factor to AML1 subnuclear domains. Instead, the AML1/ETO fusion protein is redirected by the ETO component to alternate nuclear matrix-associated foci. Our results link the ETO chromosomal translocation in AML with modifications in the intranuclear trafficking of the key hematopoietic regulatory factor, AML1. We conclude that misrouting of gene regulatory factors as a consequence of chromosomal translocations is an important characteristic of acute leukemias.
Elliptic Curve-Based Secure Multidimensional Aggregation for Smart Grid Communications

In smart grid, data aggregation is considered as an essential paradigm in assessing information about current energy usage. To achieve the privacy-preserving goal, several homomorphic-based solutions have been proposed. However, these solutions either consider one-dimensional information or use costly pairing computation in order to ensure source authentication. In fact, smart grid data are likely to be multidimensional (e.g., time, purpose, and so on) for more accurate control. In addition, the aggregation node in smart grid needs to verify data that come from several smart meters in a residential area; hence, the verification must be cost-efficient. In this paper, we propose a scheme that considers multidimensional aggregation with privacy preserving and an efficient verification of smart grid data. The proposal is based on elliptic curve cryptography along with homomorphic encryption and without pairings. The performance analysis shows the efficiency of the scheme for smart grid communications in comparison with existing schemes. For instance, we show that, when an aggregator node is responsible of 600 smart meters, it spends approximately 14 s to verify the data in pairing-based schemes, while only 0.3 s is needed for verification within the proposed scheme.
Novel miniaturized UWB antenna with triple band-notched characteristics utilizing SRR and folded U-shaped slot

In this paper, a novel miniaturized antenna for Ultra-Wideband (UWB) is presented. The prospective antenna is fed using 50 ohm coplanar waveguide (CPW). A wide impedance bandwidth is achieved covering the band from 3.1 GHz to more than 20 GHz with reflection coefficient superior to −10dB. Three frequency notches are implemented to ensure coexistence with the narrow band applications sharing some of these frequency bands of WiMAX, WLAN and X-band satellite communication. Split ring resonator (SRR) is embedded in coplanar ground for both frequency bands rejection of IEEE 802.16 WiMAX (3.3–3.8 GHz) and IEEE 802.11 WLAN (5.15–5.825GHz). Folded U-shaped slot is etched in feed line for frequency band rejection of (7.25–8.395) GHz for X-band satellite communication. The proposed antenna has a total size of 24 × 18.5 × 1.5 mm3. Omnidirectional radiation pattern with stable radiation characteristics is acquired. Good agreement is achieved between simulated and measurement results. To investigate the performance of the proposed antenna in terms of achieving wideband operations, the commercially available simulation software CST STUDIO SUITE ver.2014 was used for numerical analysis.
Timing analysis with crosstalk as fixpoints on complete lattice

Increasing delay variation due to crosstalk has a dramatic impact on deep sub-micron technologies. It is now necessary to include crosstalk in timing analysis. But timing analysis with crosstalk is a chicken-and-egg problem since crosstalk effect in turn depends on timing behavior of a circuit. In this paper, we establish a theoretical foundation for timing analysis with crosstalk. We show that solutions to the problem are fixpoints on a complete lattice. Based on that, we prove in general the convergence of any iterative approach. We also show that, starting from different initial solutions, an iterative approach will reach different fixpoints. The current prevailing practice, which starts from the worst case solution, will always reach the greatest fixpoint (which is the loosest solution). In order to reach the least fixpoint, we need to start from the best case solution. Based on chaotic iteration and heterogeneous structures of coupled circuits, we also design techniques to speed up iterations.
The SM protein Sly1 accelerates assembly of the ER–Golgi SNARE complex

Significance Every vesicle fusion reaction is driven by soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) proteins that zipper into tight complexes between membranes. Members of the Sec1/Munc18 (SM) family tightly regulate this process through interactions with a member of the syntaxin SNARE subfamily. However, seemingly different interaction modes have been found for different SM proteins and syntaxins. Here we show that the ER–Golgi SM protein Sly1 interacts not only with the N-peptide of the syntaxin Sed5, as previously thought, but also with its remainder. This corroborates the idea that SM proteins and syntaxins generally make use of two spatially separated binding sites. Remarkably, binding of Sly1 relaxes the autoinhibitory closed conformation of Sed5 and thereby accelerates SNARE complex formation. Soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins constitute the core of an ancient vesicle fusion machine that diversified into distinct sets that now function in different trafficking steps in eukaryotic cells. Deciphering their precise mode of action has proved challenging. SM proteins are thought to act primarily through one type of SNARE protein, the syntaxins. Despite high structural similarity, however, contrasting binding modes have been found for different SM proteins and syntaxins. Whereas the secretory SM protein Munc18 binds to the ‟closed conformation” of syntaxin 1, the ER–Golgi SM protein Sly1 interacts only with the N-peptide of Sed5. Recent findings, however, indicate that SM proteins might interact simultaneously with both syntaxin regions. In search for a common mechanism, we now reinvestigated the Sly1/Sed5 interaction. We found that individual Sed5 adopts a tight closed conformation. Sly1 binds to both the closed conformation and the N-peptide of Sed5, suggesting that this is the original binding mode of SM proteins and syntaxins. In contrast to Munc18, however, Sly1 facilitates SNARE complex formation by loosening the closed conformation of Sed5.
Stabilization of Uncertain Discrete-Time Linear System With Limited Communication

This technical note proposes a procedure to control an uncertain discrete-time networked system using an aperiodic stabilizing input information. The system is primarily affected by the time-varying, norm bounded, mismatched parametric uncertainty. Aperiodic exchange of information is done due to bandwidth constraint of the communication network. An event-triggered based robust control strategy is adopted to reduce the effects of system uncertainty in such bandwidth constrained networks. In event-triggered control, the control input is computed and actuated at the system end only when a pre-specified event condition is violated. The robust control input is derived to stabilize the uncertain system by solving an optimal control problem based on a virtual nominal dynamics and a modified cost-functional. It is shown that the robust control law with aperiodic information ensures input-to-state stability (ISS) of the original system in the presence of mismatched uncertainty. Deriving the event-triggering condition for a discrete-time uncertain system and ensuring the stability of such system analytically are the key contributions of this technical note. A numerical example is given to prove the efficacy of the proposed event-based control algorithm over the conventional periodic one.
Unusual Atrioventricular Reentry Tachycardia in Congenitally Corrected Transposition of Great Arteries: A Novel Site for Catheter Ablation

A 19-year-old male with congenitally corrected transposition of the great arteries (ccTGA; S, L, L–situs solitus, l-loop, l-transposition)1,2 presented with recurrent frequent palpitations, fatigue, and effort intolerance. Previous history was significant for initial presentation with supraventricular tachycardia (SVT) at the age of 14 years. Transthoracic echocardiography at that time led to diagnosis of ccTGA. He reportedly underwent a posteroseptal accessory pathway ablation, and subsequently a second ablation the same year for recurrent SVT, again targeting a posteroseptal pathway. At the age of 17 years, he had a third procedure and reportedly linear ablation between the right atrioventricular valve (mitral), and inferior vena cava was performed for inducible right atrial flutter. Physical examination was unremarkable except for loud aortic closure on cardiac auscultation. The baseline ECG showed the presence of septal Q waves and the absence of lateral Q waves, findings characteristic of ccTGA (Figure 1A). 1 The chest radiograph showed mesocardia without cardiomegaly or pulmonary congestion. Transthoracic echocardiography showed ccTGA, no atrial or ventricular septal defect, no pulmonary stenosis, normally functioning competent atrioventricular valves, and preserved function of both ventricles. Ambulatory monitoring revealed tachycardia, sometimes regular but at other times with an alternating variation in QRS axis and RR interval (Figure 1B). He was brought to the electrophysiology laboratory, and catheters were positioned in standard positions, including high right atrium, His-bundle, subpulmonic ventricle, and coronary sinus (CS). Dissociated signals were noted in the posteroseptal region/CS ostium, presumably related to previous ablations. With premature atrial beats, a distinctly different QRS complex with loss of notching in the inferior leads and a slightly more superior axis was noted. This second more superiorly directed QRS morphology was associated with a shortening in the recorded HV interval. There was no VA conduction. SVT was easily inducible with atrial extrastimuli and …
Pro-apoptotic gene expression mediated by the p38 mitogen-activated protein kinase signal transduction pathway

Neurotrophic factor deprivation causes apoptosis by a mechanism that requires macromolecular synthesis. This fact suggests that gene expression is necessary to achieve cell death. To identify mRNA that is expressed in apoptotic cells we used subtractive hybridization with cDNA prepared from neuronal pheochromocytoma cells. Monoamine oxidase (MAO) expression was increased in cells during nerve growth factor withdrawal-induced apoptosis. The increased apoptosis and induction of MAO was prevented by inhibition of the p38 mitogen-activated protein (MAP) kinase pathway. MAO may contribute to the apoptotic process because inhibition of MAO activity suppressed cell death. Together, these data indicate that MAO may be a target of pro-apoptotic signal transduction by the p38 MAP kinase pathway.
Evaluation of F127/chitosan hydrogel as a scaffold for bone repair

An in situ gelled scaffold for bone tissue engineering to restore the function of bone tissues is developed. The gel is comprised of Pluronic F127 and chitosan. The gelation temperature (Tgel), and viscoelastic properties and mucoadhesive force of the systems were investigated by means of rheological analyses. At specific concentrations, the hydrogel exhibited a Tgel close to the body temperature due to the addition of chitosan. Mucoadhesion experiments showed a rheological synergism between F127/chitosan gels and mucin dispersion, and a change in the flow behavior. In vitro release results indicated that the optimized gel was able to prolong and control acyclovir release for more than 20 min. Based on cell proliferation assay, the gel exhibited biocompatibility for osteoblasts.
Tense and plural formation in Welsh-English bilingual children with and without language impairment.

BACKGROUND Grammatical morphology has been shown to be problematic for children with specific language impairment (SLI) or developmental language disorder (DLD). Most research on this topic comes from widely spoken languages, such as English. Despite Welsh being the most extensively spoken indigenous in the UK after English, and Wales being the only official bilingual country in the UK, our knowledge about the morphosyntactic areas of Welsh that may pose problems for Welsh-speaking children with SLI is limited. Currently, Welsh-speaking speech and language therapists (SLTs) are heavily reliant on the use of informally translated English assessments. This can inadvertently result in a failure to take aspects of Welsh morphosyntax into account that are critical for the assessment and treatment of Welsh-speaking children. AIMS This is the first study to examine how Welsh-English bilingual children of early school age with typical development (bi-TD) and with SLI (bi-SLI) perform on production tasks targeting verbal and nominal morphology in Welsh. We targeted areas of Welsh morphosyntax that could potentially be vulnerable for Welsh-speaking children with or at risk of language impairment, such as tense marking and plural formation, and assessed their diagnostic potential. METHODS & PROCEDURES Twenty-eight Welsh-dominant bilingual children participated in the study: 10 bi-SLI and 18 bi-TD. They were administered three elicitation tasks targeting the production of verbal (compound and synthetic past tense) and nominal (plural) morphology in Welsh. OUTCOMES & RESULTS The bi-SLI children performed worse than their bi-TD peers across all three tasks. They produced more uninflected verbs in the elicited-production task and were less likely to be prompted to produce the synthetic past, which is a concatenating, low-frequency form of the past tense. They also over-regularized less in the context of plural nouns, and when they did, they opted for high-frequency suffixes. CONCLUSIONS & IMPLICATIONS By focusing on aspects of morphosyntactic development which are unique to Welsh, we have increased existing about how verbal and nominal morphology are acquired in Welsh-speaking bi-SLI and bi-TD children. The present results point towards productivity problems for Welsh-speaking bi-SLI children who are adversely influenced by low-frequency structures and fail to over-regularize in the context of verbal and nominal concatenating morphology. From a clinical perspective, targeting synthetic past-tense forms through a prompting task may be a promising assessment and intervention tool that future studies could explore further.