Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Tumor Angiogenesis by the Matrix Metalloproteinase–Activated Anthrax Lethal Toxin in an Orthotopic Model of Anaplastic Thyroid Carcinoma

Patients with anaplastic thyroid carcinoma (ATC) typically succumb to their disease months after diagnosis despite aggressive therapy. A large percentage of ATCs have been shown to harbor the V600E B-Raf point mutation, leading to the constitutive activation of the mitogen-activated protein kinase pathway. ATC invasion, metastasis, and angiogenesis are in part dependent on the gelatinase class of matrix metalloproteinases (MMP). The explicit targeting of these two tumor markers may provide a novel therapeutic strategy for the treatment of ATC. The MMP-activated anthrax lethal toxin (LeTx), a novel recombinant protein toxin combination, shows potent mitogen-activated protein kinase pathway inhibition in gelatinase-expressing V600E B-Raf tumor cells in vitro. However, preliminary in vivo studies showed that the MMP-activated LeTx also exhibited dramatic antitumor activity against xenografts that did not show significant antiproliferative responses to the LeTx in vitro. Here, we show that the MMP-activated LeTx inhibits orthotopic ATC xenograft progression in both toxin-sensitive and toxin-resistant ATC cells via reduced endothelial cell recruitment and subsequent tumor vascularization. This in turn translates to an improved long-term survival that is comparable with that produced by the multikinase inhibitor sorafenib. Our results also indicate that therapy with the MMP-activated LeTx is extremely effective against advanced tumors with well-established vascular networks. Taken together, these results suggest that the MMP-activated LeTx-mediated endothelial cell targeting is the primary in vivo antitumor mechanism of this novel toxin. Therefore, the MMP-activated LeTx could be used not only in the clinical management of V600E B-Raf ATC but potentially in any solid tumor. Mol Cancer Ther; 9(1); 190–201
The Time Course of Transmitter at Glycinergic Synapses onto Motoneurons

The concentration of transmitter in the synaptic cleft and its clearance time are one of the main determinants of synaptic strength. We estimated the time course of glycine at rat lumbar motoneurons synapses in spinal cord slices by recording synaptic currents in the presence of a low-affinity competitive antagonist at glycine receptors [2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium (SR-95531)]. Data were analyzed by using the established activation mechanism for glycine receptors and our measurements of SR-95531 binding rates. We show that this technique alone is not sufficient to determine simultaneously the peak concentration of transmitter and its clearance time. However, we found that block of the glial glycine transporter prolongs the glycine transient. This observation puts additional constraints on the range of possible values of the time course of glycine, indicating that glycine reaches a peak concentration of 2.2–3.5 mm and is cleared from the cleft with a time constant of 0.6–0.9 ms.
Genomic structure of the mouse Ap3b1 gene in normal and pearl mice.

The mouse hypopigmentation mutant pearl is an established model for Hermansky-Pudlak syndrome (HPS), a genetically heterogenous disease with misregulation of the biogenesis/function of melanosomes, lysosomes, and platelet dense granules. The pearl (Ap3b1) gene encodes the beta3A subunit of the AP-3 adaptor complex, which regulates vesicular trafficking. The genomic structure of the normal Ap3b1 gene includes 25 introns and a putative promoter sequence. The original pearl (pe) mutation, which has an unusually high reversion rate on certain strain backgrounds, has been postulated to be caused by insertion of a transposable element. Indeed, the mutation contains a 215-bp partial mouse transposon at the junction point of a large tandem genomic duplication of 6 exons and associated introns. At the cDNA level, three pearl mutations (pearl, pearl-8J, and pearl-9J) are caused by deletions or duplications of a complete exon(s).
Tissue specific CTCF occupancy and boundary function at the human growth hormone locus

The robust and tissue-specific activation of the human growth hormone (hGH) gene cluster in the pituitary and placenta constitutes an informative model for analysis of gene regulation. The five-gene hGH cluster is regulated by two partially overlapping sets of DNase I hypersensitive sites (HSs) that constitute the pituitary (HSI, II, III and V) and placental (HSIII, IV, and V) locus control regions (LCRs). The single placenta-specific LCR component, HSIV, is located at −30 kb to the cluster. Here we generate a series of hGH/BAC transgenes specifically modified to identify structural features of the hGH locus required for its appropriate placental expression. We find that placental specificity is dependent on the overall multigene configuration of the cluster whereas the distance between the cluster and its LCR impacts the level of placental expression. We further observe that a major function of the placental hGH LCR is to insulate the transgene locus from site-of-integration effects. This insulation activity is linked to placenta-specific occupancy of the chromatin architectural protein, CTCF, at HSIV. These data reveal a remarkable combination of structural configurations and regulatory determinants that must work in concert to insure robust and tightly controlled expression from a complex multigene locus.
Efficiency of the gossip algorithm for wireless sensor networks

Gossip is a well-known technique for distributed computing in an arbitrarily connected network of nodes. The gossip algorithm, which is very simple to implement, takes into account strong limitations in computational, communication and energy resources that usually characterize nodes in sensor networks. In gossip, the computational burden is distributed among the nodes, and computation and communication are managed in a very quick and efficient way: in essence, each node acquires its own measure and, starting from it, exchanges information with its neighbors, according with a connection probability distribution. In this paper, we study the performance of gossip algorithms, aiming to test the agreement between analytical results on the averaging time and the actual convergence time for specific scenarios, estimated through numerical simulations. Furthermore, we apply an optimization technique, recently appeared in the literature, that theoretically allow to accelerate convergence. Numerical simulations permit to assess the effects of optimization in real cases, thus evaluating the actual improvement in performance it achieves.
‘You're not a teacher, you're a man’: the need for a greater focus on gender studies in teacher education

If teachers are to play a positive educative role in addressing societal gender-related issues that impact on social justice and inclusiveness, teacher education institutions have to ensure that their graduating teachers are well equipped with the necessary understandings and skills to enact this role. This research draws on interviews with men primary school teachers in New Zealand, Sweden and the UK. It investigates their remembered experiences during teacher education relating to gender discourse and whether the education they received, if any, has influenced their classroom practices. Across the three countries, the men had varying levels of recall, ranging from comprehensive gender-related education to none whatsoever. In Sweden, a governmental emphasis on gender equality in society appeared to have influenced the teachers' attitudes and practices regardless of the amount of teacher education relating to gender that they remembered. The teachers' comments suggest that those of us engaged in teacher education need to address any apparent gaps in gender studies at pre-service level. Both men and women teacher education students require comprehensive gender studies if they are to recognise and realise their potential to deconstruct traditional stereotypes and contribute to social justice and inclusiveness.
Racial and Ethnic Differences in Family Caregiving in California

Abstract Family caregivers are the main source of long-term care for older persons in the United States. At the same time, cultural values and beliefs shape decisions surrounding who provides care and whether families use formal support interventions to assist the caregiver. The current article examines how the family caregiving experience differs among racial and ethnic groups in terms of caregiver characteristics, service utilization, caregiver strain, and coping mechanisms. Telephone interviews were conducted in English and Spanish with a random sample of 1,643 respondents in California who provide care to someone age 50 or over. Bivariate analyses showed evidence of ethnic differences in the demographic characteristics of caregivers, intensity of care provided, caregiver health, level of financial strain, religious service attendance, formal service utilization and barriers to formal services. Odds ratios showed that White and African American caregivers were about two times as likely to use formal caregiver services as were Asian/Native Hawaiian/Pacific Islander and Latina American caregivers. Implied by these findings is the need for further understanding of caregiver service needs among diverse racial and ethnic groups.
Mezlocillin pharmacokinetics in patients with normal and impaired renal functions

The pharmacokinetics of intravenous bolus doses of 1.0 g of mezlocillin were studied in 13 persons with normal and reduced renal functions. In renal failure a moderate increase was observed for the terminal serum half-life(t1/2 beta). This changed from a mean of 1.1 h at a glomerular filtration rate of 100 ml/min to 1.6 h at 10 ml/min. The difference was not statistically significant. The excretion of unchanged drug in urine during 24 h was reduced from a mean of 59.4% (range, 52 to 77) in subjects with glomerular filtration rate above 50 ml/min to 10% (range, 7.9 to 12.1) in two patients with glomerular filtration rate of 10 to 20 ml/min. The volume of distribution during the beta-phase, Vd,b, was 14% of the body weight. Much of the antibiotic was metabolized, and this proportion increased upon reduction in renal function.
Relationship between coronary artery disease and non-HDL-C, and effect of highly purified EPA on the risk of coronary artery disease in hypercholesterolemic patients treated with statins: sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

AIM The present study examined the importance of reducing non-high-density lipoprotein cholesterol (non-HDL-C) for the primary prevention of the occurrence of coronary artery disease (CAD) in the JELIS, and the effects of EPA. METHODS The patients were distributed into 4 subgroups using the lipid management goal for LDL-C recommended by the Japan Atherosclerosis Society guideline (2007) and the goal for non-HDL-C defined as 30 mg/dL higher than LDL-C: A) achieved both goals; B) achieved the LDL-C but not non-HDL-C goal; C) achieved the non-HDL-C but not LDL-C goal; and D) did not attain either goal. The incidences of CAD in the 4 subgroups were compared, and the effects of eicosapentaenoic acid (EPA) on the risk of CAD in these subgroups were examined. RESULTS In the non-EPA group, the incidence of CAD in patients who did not achieve the goals for LDL-C or non-HDL-C was higher than in patients who achieved those goals. Patients in subgroups B, C, and D were at higher risk for CAD than those in subgroup A (B, HR 2.31; C, HR 1.90; D, HR 2.47). EPA reduced the risk of CAD by 38% in subgroups B, C, and D (p= 0.007). CONCLUSION We reconfirmed non-HDL-C as a predictor of the risk for CAD and a residual risk marker of CAD after LDL-C-lowering therapy. EPA was useful to reduce the occurrence of CAD in patients who did not achieve the goals for LDL-C and/or non-HDL-C.
A Survey of Methods for Generating a Test Sequence for Conformance Testing of Finite State Machine

Finite state machines testing problems has been studied due to its applications to conformance testing of communication protocol; we will focus on the primary problems of conformance testing (or fault detection problem) based on knowing where we are during the experiment, using status message, reset and distinguishing sequence. Given a specification machine we have its state transition and output functions in the form of a transition diagram or "black box" which we can only observe its input/output behaviour, and we will design a test to determine whether implementation conforms to the specification by generating and using test sequence called checking sequence. We discuss three methods for generating checking sequence: Status Message and Reset, Distinguishing Sequence Method and Using Separating Sequences Instead of Status Massages. Finally, we will review a small comparison between those methods about how we can choose between them.
Machiavellianism and psychopathy: An East-West note

Western theory and research has found a positive relationship between the Machiavellian personality (Mach) and the Primary Psychopath (PP). Joint symptoms include affective poverty, lack of remorse/guilt, and manipulativeness. We explored the Mach-PP relationship in a culture which changed radically after 1990 from socialism to capitalism.
Mycobacterium tuberculosis Resists Stress by Regulating PE19 Expression

ABSTRACT Mycobacterium tuberculosis requires the phosphate-sensing signal transduction system Pst/SenX3-RegX3 to resist host immune responses. A ΔpstA1 mutant lacking a Pst phosphate uptake system component is hypersensitive to diverse stress conditions in vitro and is attenuated in vivo due to constitutive expression of the phosphate starvation-responsive RegX3 regulon. Transcriptional profiling of the ΔpstA1 mutant revealed aberrant expression of certain pe and ppe genes. PE and PPE proteins, defined by conserved N-terminal domains containing Pro-Glu (PE) or Pro-Pro-Glu (PPE) motifs, account for a substantial fraction of the M. tuberculosis genome coding capacity, but their functions are largely uncharacterized. Because some PE and PPE proteins localize to the cell wall, we hypothesized that overexpression of these proteins sensitizes M. tuberculosis to stress by altering cell wall integrity. To test this idea, we deleted pe and ppe genes that were overexpressed by ΔpstA1 bacteria. Deletion of a single pe gene, pe19, suppressed hypersensitivity of the ΔpstA1 mutant to both detergent and reactive oxygen species. Ethidium bromide uptake assays revealed increased envelope permeability of the ΔpstA1 mutant that was dependent on PE19. The replication defect of the ΔpstA1 mutant in NOS2−/− mice was partially reversed by deletion of pe19, suggesting that increased membrane permeability due to PE19 overexpression sensitizes M. tuberculosis to host immunity. Our data indicate that PE19, which comprises only a 99-amino-acid PE domain, has a unique role in the permeability of the M. tuberculosis envelope that is regulated to resist stresses encountered in the host.
Continuous Curvature Trajectory Generation with Obstacle Avoidance for Car-Like Robots

This paper presents an extension of cubic curvature polynomial trajectory planning to include a mechanism for obstacle avoidance. Cubic polynomials have been used to describe curvature continuous trajectories for car like robots. From known start and end robot postures, (position, orientation and curvature) a continuous trajectory can be decided. We extend cubic polynomial trajectories to fourth order polynomials, and introduce a cost function, describing accumulated distance to obstacles along a trajectory, to the robot posture vector. Such trajectories, generated by a gradient descent method, satisfy continuity constraints and avoid obstacles. The method is implemented on a mobile robot system and experiments in real time trajectory planning and execution are conducted
Do infrastructure reforms reduce the effect of corruption ? Evidence from electricity firms in Latin America ∗

This paper investigates whether corruption affects firms’ efficiency and how this relationship is affected by institutional reforms. In particular, we consider the impact of corruption and institutional governance on a panel of 199 electricity distribution firms across 16 different countries in Latin America between 1995 and 2005. We find evidence that corruption, a lack of good regulatory governance and public ownership are each associated with less efficient firms. Indeed, the analysis suggests that the creation of an Independent Regulatory Agency (IRA) may increase efficiency if regulatory governance is strong, but decrease efficiency if governance is weak. Moreover, both the creation of a well-governed IRA and privatisation appear to significantly reduce the effect of corruption on efficiency. These results broadly survive a range of robustness checks including separately instrumenting for corruption, ownership and regulatory governance. Overall, we conclude that the creation of well governed sector-specific institutions can help to counter the adverse effects of high levels of corruption present in many developing countries. JEL: D73; L51; L98
An Isometric Predictor for Maximum Acceptable Weight of Lift for Chinese Men

The aim of this study was to examine the practicality of the modified isometric strength tests to predict the maximum acceptable weight of lift (MAWL) of Chinese men. The modified strength tests allow the participant to pull on the load cell in front of the body and to apply force in a functional free posture. Both the modified and the standard strength data of each participant were used as predictors for the MAWLs. The prediction models were constructed and evaluated under task conditions of two lifting ranges, two box sizes, and three lifting frequencies. To realize the effect of modifications, testing posture was recorded and the joint angles were calculated. A stepwise multiple regression analysis indicated that modified composite strength (MCS), chest circumference, and acromial height accounted for 86% to 91% of the variance. Because the strength of the upper extremity body was also recruited in the test, the weak upper extremity strength of the Chinese participants would therefore be better reflected. Evidence for the existence of a close match between MAWL and MCS values, as well as the task conditions for its existence, suggest that a simple isometric strength measure is a good predictor for the MAWL.
Pancreas Transplantation: Does Age Increase Morbidity?

Introduction. Pancreas transplantation (PTx) is the only definitive intervention for type 1 diabetes. Medical advancements in diabetes care have led to an aging PTx candidate pool. We report our experience with patients ≥50 years of age undergoing PTx. Methods. We reviewed 136 consecutive PTx patients at our institution from 1996–2010; 17 were ≥50 years of age. We evaluated demographics, surgical complications, acute rejection (AR) rates, nonsurgical infections, and survival outcomes. Results. Demographic data was similar (P > .05) between groups, excluding age. The two groups had comparable major and minor surgical complication rates (P = .10 and P = .25, resp.). The older group had a lower 1-year and overall AR rate (P = .04 and P = .03, resp.). The incidence of non-surgical infections and overall patient and graft survival was similar between groups (P > .05). Conclusion. Older patients with type 1 diabetes are feasible candidates for PTx, as surgical morbidity, incidence of infections, and AR rates are low.
An Iterative Locally Auto-Weighted Least Squares Method for Microarray Missing Value Estimation

Microarray data often contain missing values which significantly affect subsequent analysis. Existing LLSimpute-based imputation methods for dealing with missing data have been shown to be generally efficient. However, all of the LLSimpute-based methods do not consider the different importance of different neighbors of the target gene in the missing value estimation process and treat all the neighbors equally. In this paper, a locally auto-weighted least squares imputation (LAW-LSimpute) method is proposed for missing value estimation, which can automatically weight the neighboring genes based on the importance of the genes. Then, an accelerating strategy is added to the LAW-LSimpute method in order to improve the convergence. Furthermore, an iterative missing value estimation framework of LAW-LSimpute (ILAW-LSimpute) is designed. Experimental results show that the ILAW-LSimpute method is able to reduce the estimation error.
Advanced Broadband Millimetre-Wave Characterization Techniques of Dielectrics

The paper presents a broadband CW imaging technique using an unfocused free space reflection measurement setup in W-Band (75-100 GHz). The goal is to achieve a spatial highly resolved 3D-image of a dielectric device under test (DUT) in order to detect cracks or other defects up to a size of 1-2mm. After the data collection, numerical post processing is applied to the unfocused rawdata in order to achieve a highly resolved 3D-reconstruction of the DUT. Two approaches are realized, the first one is a special Synthetic Aperture Radar (SAR) algorithm called Range Migration Algorithm (RMA). The second one is a deconvolution algorithm based upon a constrained least squares (CLS) method. Latter reconstruction techniques require coherent signal detection. Therefore a heterodyne frequency stepped measurement setup was developed. This setup is realised with a commercial network vector analyzer (VNA) which allows a fast and accurate measurement of a broadband frequency response of the DUT. The data collection is either realized in a planar or cylindrical scanning geometry. Both cases are examined. Furthermore spectral estimation techniques are applied to the broadband measurement data to overcome the limitations of the range resolution, achieved by conventional processing techniques.
Functional linear instrumental regression under second order stationarity

We consider the problem of estimating the slope parameter in functional linear instrumental regression, where in the presence of an instrument W, i.e., an exogenous random function, a scalar response Y is modeled in dependence of an endogenous random function X. Assuming second order stationarity jointly for X and W a nonparametric estimator of the functional slope parameter and its derivatives is proposed based on an n-sample of (Y,X,W). In this paper the minimax optimal rate of convergence of the estimator is derived assuming that the slope parameter belongs to the well-known Sobolev space of periodic functions. We discuss the cases that the cross-covariance operator associated to the random functions X and W is finitely, infinitely or in some general form smoothing.
Two-Step Time of Arrival Estimation for Pulse-Based Ultra-Wideband Systems

In cooperative localization systems, wireless nodes need to exchange accurate position-related information such as time-of-arrival (TOA) and angle-of-arrival (AOA), in order to obtain accurate location information. One alternative for providing accurate position-related information is to use ultra-wideband (UWB) signals. The high time resolution of UWB signals presents a potential for very accurate positioning based on TOA estimation. However, it is challenging to realize very accurate positioning systems in practical scenarios, due to both complexity/cost constraints and adverse channel conditions such as multipath propagation. In this paper, a two-step TOA estimation algorithm is proposed for UWB systems in order to provide accurate TOA estimation under practical constraints. In order to speed up the estimation process, the first step estimates a coarse TOA of the received signal based on received signal energy. Then, in the second step, the arrival time of the first signal path is estimated by considering a hypothesis testing approach. The proposed scheme uses low-rate correlation outputs and is able to perform accurate TOA estimation in reasonable time intervals. The simulation results are presented to analyze the performance of the estimator.