Miracle-dz/UniFAR-FTUs huggingface dataset:
Tests for gene‐environment interaction from case‐control data: a novel study of type I error, power and designs

To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non‐multiplicative gene‐environment effects from case‐control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case‐control method; (ii) the case‐only method, which requires an assumption of gene‐environment independence for the underlying population; (iii) a two‐step method that decides between the case‐only and case‐control estimators depending on a statistical test for the gene‐environment independence assumption and (iv) a novel empirical‐Bayes (EB) method that combines the case‐control and case‐only estimators depending on the sample size and strength of the gene‐environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene‐environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene‐environment interactions from case‐control studies. In particular, the EB procedure, unlike the case‐only or two‐step methods, can closely maintain a desired Type I error under realistic scenarios of gene‐environment dependence and yet can be substantially more powerful than the traditional case‐control analysis when the gene‐environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non‐traditional case‐control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N‐acetyl transferase type 2 and glutathione s‐transferase M1, with smoking and dietary exposures, in a large case‐control study of colorectal cancer. Genet. Epidemiol. 2008. Published 2008 Wiley‐Liss, Inc.
Adaptive noise smoothing for speech enhancement filters

Noise estimation is one of the main keys for successful speech enhancement processing. Traditional noise estimators based on inter-frame smoothing of the estimated power spectrum (PSD) of the background noise leads to artificial artifacts on the residual noise well known as `musical noise'. In this paper we show the relationship of the estimated noise PSD and the denoised speech quality. This study leads to the development of a new technique to smooth the estimated noise power spectrum over frequency bins of the same frame. The smoothing processing is governed adaptively by the PSD of the noisy speech and the estimated noise. Compared to traditional inter-frame smoothing, experimental results show that this intraframe smoothing has a good impact on the denoised speech and the problem of musical noise is well reduced.
The Role of the Base Stack on the AC Performance of GaN Hot Electron Transistor

In this letter, we provide guidelines for the design of the base stack of a GaN-base HET suitable for high-frequency operation, through full band cellular Monte Carlo device simulations. The experimental curves are matched by our model and the transmission coefficient through the base is confirmed to be 0.2. We found that upon moderate reduction of the base thickness and collector barrier height, the transmission coefficient reaches values well above 0.5, hence allowing current amplification. The cutoff frequency of the scaled devices is then calculated from the short circuit current gain and is found to be larger than 100 GHz. Moreover, the cutoff frequency is seen to increase roughly proportionally to the transmission coefficient. This result, and the calculation of the base capacitance, suggests that the cutoff frequency can be well described by the intrinsic delay time Cb/gm.
Activation of the Integrated Stress Response Regulates Lovastatin-induced Apoptosis*

Lovastatin, a potent inhibitor of mevalonate synthesis, can readily induce apoptosis in a subset of human tumor types including head and neck squamous cell carcinomas (HNSCC). We recently identified activation of transcription factor (ATF) 4 as a lovastatin induced gene in HNSCC cells. ATF4 plays a significant role in regulating cellular responses to a wide variety of stress inducers known as the integrated stress response (ISR). These cell stresses lead to the phosphorylation of eukaryotic initiation factor (eIF) 2α shutting down global protein translation. However, the translation of ATF4 is enhanced. In this study, lovastatin treatment induced eIF2α phosphorylation and inhibited global protein translation. ATF4 expression was induced followed by increased ATF3 and CHOP expression, targets of ATF4 activity, in SCC25 HNSCC cells. In CHOP–/– murine embryonic fibroblasts (MEFs), lovastatin-induced apoptosis was attenuated indicating a role for CHOP in this response. Furthermore, the eIF2α kinase GCN2 mediates lovastatin induction of ATF4 and lovastatin-induced apoptosis was also attenuated in GCN2–/– MEFs. The pro-drug version of lovastatin has potential proteasome inhibitory activity and recently a variety of well established proteasome inhibitors were shown to activate the ISR. In this study, neither the pro-drug nor the active forms of lovastatin had any significant effect on proteasome activity. Therefore, lovastatin, by targeting mevalonate synthesis, is a potent inducer of the ISR through a novel and as yet unrecognized mechanism.
Highly Variable Rates of Genome Rearrangements between Hemiascomycetous Yeast Lineages

Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.
APRENDIZAGENS PARA ALFABETIZAR E LETRAR NO PIBID LEARNING TO TEACH READING AND WRITING IN AN INITIAL TEACHER EDUCATION PROGRAM (PIBID)

This article aims to analyze the contributions and possibilities of a program to support teacher education in a public university in Sao Carlos, Sao Paulo, Brazil. It focuses on learning to teach literacy practices, through the actions of student teachers in a Pedagogy course in their actions envolving to teach reading and writing to first to fifth graders of elementary school during 2010 and 2011. The research was conducted in a qualitative approach and included analysis of interviews with student teachers, diary with field notes
ID3-SD: an algorithm for learning characteristic decision trees by controlling the degree of generalization

Decision trees constructed by ID3-like algorithms suffer from an inability of detecting instances of categories not present in the set of training examples, i.e., they are discriminative representations. Instead, such instances are assigned to one of the classes actually present in the training set, resulting in undesired misclassifications. In this report, twomethods of reducing this problemby learning characteristic representations are presented. The central idea behind both methods is to augment each leaf of the decision tree with a subtree containing additional information concerning each feature’s values in that leaf. This is accomplished by computing two limits (lower and upper) for every feature from the training instances belonging to the leaf. A subtree is then constructed from these limits that tests every feature; if the value is below the lower limit or above the upper limit for some feature, the instance will be rejected, i.e., regarded as belonging to a novel class. This subtree is then appended to the leaf. The first method presented corresponds to creating a maximum specific description, whereas the second is a novel method called ID3-SD that makes use of the information about the statistical distribution of the feature values that can be extracted from the training examples. An important property of the novel method is that the gap between the limits (i.e., the degree of generalization) can be controlled. The two methods are then evaluated empirically in three different domains: the classic Iris database, a wine database, and a novel database from a coin-sorting machine. It is concluded that the dynamical properties of the ID3-SD method makes it preferable in many applications. Finally, we argue that thismethod in fact is general in that it, in principle, can be applied to any empirical learning algorithm, i.e., it is not restricted to decision tree algorithms. (Less)
Osteogenic stem cells and orthopedic engineering: summary and update.

The use of osteogenic stem cells or osteoprogenitors to reconstruct skeletal tissues is a popular area of research investigation with high potential for successful use of tissue-engineering principles in orthopedics. Recent studies demonstrate the migration of marrow-derived stem cells to skeletal sites and the proliferation and differentiation at local tissue sites and support possibilities for assessing the successful uses of human osteoprogenitors in the treatment of bone deficiency diseases. In addition, the development of gene therapy procedures in these and other conditions is now considered an achievable goal with the use of these primitive marrow cells.
On-line optimization-based coordination of multiple unmanned vehicles

The objective of this work is to investigate on-line optimization-based coordination strategies for robot teams to efficiently accomplish a mission (e.g., reach a set of assigned targets) while avoiding collisions. The multi-robot coordination problem is addressed by solving an on-line receding-horizon mixed-integer program to find some suitable inputs for the vehicles. Simulations results verify the feasibility of our approach.
Antitumor Activity of Targeted and Cytotoxic Agents in Murine Subcutaneous Tumor Models Correlates with Clinical Response

Purpose: Immunodeficient mice transplanted with subcutaneous tumors (xenograft or allograft) are widely used as a model of preclinical activity for the discovery and development of anticancer drug candidates. Despite their widespread use, there is a widely held view that these models provide minimal predictive value for discerning clinically active versus inactive agents. To improve the predictive nature of these models, we have carried out a retrospective population pharmacokinetic–pharmacodynamic (PK–PD) analysis of relevant xenograft/allograft efficacy data for eight agents (molecularly targeted and cytotoxic) with known clinical outcome. Experimental Design: PK–PD modeling was carried out to first characterize the relationship between drug concentration and antitumor activity for each agent in dose-ranging xenograft or allograft experiments. Next, simulations of tumor growth inhibition (TGI) in xenografts/allografts at clinically relevant doses and schedules were carried out by replacing the murine pharmacokinetics, which were used to build the PK–PD model with human pharmacokinetics obtained from literature to account for species differences in pharmacokinetics. Results: A significant correlation (r = 0.91, P = 0.0008) was observed between simulated xenograft/allograft TGI driven by human pharmacokinetics and clinical response but not when TGI observed at maximum tolerated doses in mice was correlated with clinical response (r = 0.36, P = 0.34). Conclusions: On the basis of these analyses, agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, are more likely to lead to responses in the clinic. A proposed strategy for the use of murine subcutaneous models for compound selection in anticancer drug discovery is discussed. Clin Cancer Res; 18(14); 3846–55. ©2012 AACR.
A finite-set model predictive position controller for the permanent magnet synchronous motor

In this work a position controller for the permanent magnet synchronous motor is developed. The design is based on ideas of time-optimal control and predictive control and considers constraints for both torque and speed. The proposed controller takes the form of a state feedback. Its inputs are the position reference and the system state, and its output is the switching state to be applied by the power converter in the next sampling instant. The design procedure starts by solving a time-optimal control problem for a simple system: the triple integrator. The solution is then used to devise a state feedback rule for the motor. Although the control scheme does not have a completely cascaded structure, the approach taken establishes a hierarchy, with the error in the position having the highest priority. This separates the controller in two main building blocks, which work at different abstraction levels. The purpose of the first block is to generate references for the relevant states of the motor (speed and torque), based on long term predictions, which are realized using the triple integrator model. The second block is a receding horizon controller with a prediction horizon of one time step and a specially devised cost function, for the simultaneous control of speed, torque and stator currents. The performance of the controller is verified with experimental results.
Palliative first-line treatment with weekly high-dose 5-fluorouracil and sodium folinic acid (s-FA) (AIO-schedule) as 24h-infusion plus biweekly oxaliplatin (ox) in patients with definitively non-resectable metastatic colorectal cancer (CRC) following secondary (sec.) metastatic resection: An interd

e15073 Background: In an interdisciplinary phase II trial performed from 1995 to 1997 and based on a 5-FU monotherapy it was possible to achieve both a sec. metastatic resection after downsizing in 9 patients (17%) and a R0 resection offering curative option in 6 patients (11%) out of a total collective of 53 treated patients (Wein et al, Ann Oncol 2001). The objective of this phase II trial is to verify whether a combination therapy based on ox may improve the curative option in terms of a sec. metastatic resection in a patient cohort with identical inclusion - and exclusion criteria. METHODS Prospective evaluation of 50 patients. ; palliative chemotherapy: ox (oxaliplatin, 85 mg/m2 i.v. as a 2h-infusion (inf.); d 1, 15, 29 qd 57) followed by 5-FU (2000 mg/m2 i.v. as a 24h- inf.; d 1, 8, 15, 22, 29, 36 qd 57) together with s-FA (Oncofolic, 500 mg/m2 i.v. as a 24h-inf.; d 1, 8, 15, 22, 29, 36 qd 57) via a miniature pump system. RESULTS Last date of evaluation: Sep/30/2008; median age: 63 years; chemoth. appl. : total number: 935; higher grade toxicity (grade 3+4): diarrhea 20,0 %, nausea 4,0 %; vomitus 6,0 %; hand-foot-syndrome 2,0 %; fever/infection 2,0 %; response: CR: 2,0 %; PR: 52,0 %; SD: 32,0 %; PD: 12,0 %; not evaluable: 2,0 %; tumor control (CR, PR, SD): 86,0 %; sec. metastatic resection: R0: 28,0 %; R1: 2,0 %; R2 8,0 %; TTP (n = 50): 9,8 months. CONCLUSION Combination chemotherapy with weekly 5-FU and s-FA (AIO) plus bi-weekly ox on an outpatient basis is an effective palliative treatment schedule offering a high rate of curative metastatic resection with solely low grade toxicity and no higher grade neurotoxic side effects. Final results in terms of median survival remain to be seen whereas they are certainly influenced by the second line therapy. No significant financial relationships to disclose.
Weekly diffusion-weighted imaging of normal-appearing white matter in MS

Article abstract To elucidate the dynamics and the nature of normal-appearing white matter (NAWM) changes preceding new lesion formation in MS, the authors obtained weekly diffusion-weighted images for 12 weeks from 6 patients. NAWM areas subsequently involved by enhancement had a significant increase in mean diffusivity values starting 6 weeks before the appearance of enhancement (p values ranging between < 0.0001 and 0.04). This suggests that focal edema and demyelination play a part in the NAWM changes preceding new lesion formation in MS.
Stimulated exocytosis of endosomes in goldfish retinal bipolar neurons

After exocytosis, synaptic vesicle components are selectively retrieved by clathrin‐mediated endocytosis and then re‐used in future rounds of transmitter release. Under some conditions, synaptic terminals in addition perform bulk endocytosis of large membranous sacs. Bulk endocytosis is less selective than clathrin‐mediated endocytosis and probably internalizes components normally targeted to the plasma membrane. Nonetheless, this process plays a major role in some tonic ribbon‐type synapses, which release neurotransmitter for prolonged periods of time. We show here, that large endosomes formed after strong and prolonged stimulation undergo stimulated exocytosis in retinal bipolar neurons. The result suggests how cells might return erroneously internalized components to the plasma membrane, and also demonstrates that synaptic vesicles are not the only neuronal organelle that stains with styryl dyes and undergoes stimulated exocytosis.
Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study.

BACKGROUND Recruitment of circulating leukocytes at sites of atherosclerosis is mediated through a family of adhesion molecules. The function of circulating forms of these adhesion molecules remains unknown, but their levels may serve as molecular markers of subclinical coronary heart disease (CHD). METHODS AND RESULTS To determine the ability of circulating vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intercellular adhesion molecule-1 (ICAM-1) to serve as molecular markers of atherosclerosis and predictors of incident CHD, we studied 204 patients with incident CHD, 272 patients with carotid artery atherosclerosis (CAA), and 316 control subjects from the large, biracial Atherosclerosis Risk In Communities (ARIC) study. Levels of VCAM-1 were not significantly different among the patients with incident CHD, those with CAA, and control subjects. Higher levels of E-selectin and ICAM-1 were observed for the patients with CHD (means [ng/mL]: E-selectin, 38.4; ICAM-1, 288.7) and those with CAA (E-selectin, 41.5; ICAM-1, 283.6) compared with the control subjects (E-selectin, 32.8; ICAM-1, 244.2), but the distributions were not notably different between the patients with CHD and CAA. Results of logistic regression analyses indicated that the relationship of ICAM-1 and E-selectin with CHD and CAA was independent of other known CHD risk factors and was most pronounced in the highest quartile. The odds of CHD and CAA were 5.53 (95% CI, 2.51-12.21) and 2.64 (95% CI, 1.40-5.01), respectively, for those with levels of ICAM-1 in the highest quartile compared with those in the lowest quartile. Odds of CAA were 2.03 (95% CI, 1.14-3.62) for those with levels of E-selectin in the highest quartile compared with those in the lowest quartile. CONCLUSIONS These data indicate that plasma levels of ICAM-1 and E-selectin may serve as molecular markers for atherosclerosis and the development of CHD.
Minimization of Congestion using Backpressure Routing Algorithm in Wireless Networks

: Back-pressure-type algorithms have recently received much attention for jointly routing and scheduling over multi-hop wireless networks. However, this approach has a significant weakness in routing because it explores and exploits all feasible paths between each source and destination. While this extensive exploration is essential in order to maintain stability when the network is heavily loaded, under light or moderate loads, packets may be sent over unnecessarily long routes, and the algorithm could be very inefficient in terms of end-to-end delay and routing convergence times. We develop a improvised backpressure routing algorithm that maximizes network throughput and expends an average power that can be pushed arbitrarily close to the minimum average power required for network stability, with a corresponding tradeoff in network delay . This paper proposes a new routing/scheduling back-pressure algorithm that not only guarantees network stability, but also adaptively selects a set of optimal routes based on shortest-path information in order to minimize average path lengths between each source and destination pair . On the other-hand, the proposed algorithm adaptively selects a set of routes according to the traffic load so that long paths are used only when necessary, thus resulting in much smaller end-to-end packet delays as compared to the traditional back-pressure algorithm.
Real-time full-body motion reconstruction and recognition for off-the-shelf VR devices

Almost all VR multi-person applications have the requirement of reconstructing the whole-body motions in real-time in order to create deeper immersion. In fact, if we can ensure that the motion we reconstruct is natural, we can improve upon the comfort and number of wearing sensors at the cost of reconstruction precision because all users in VR are blindfolded. In this paper, we introduce a novel real-time motion reconstruction and recognition method in VR only using the positions and orientations of user's head and two hands. To reconstruct natural motions according to rare sensors, we divide the whole body into the upper body and the lower body. The upper body reconstruction algorithm based on inverse kinematics which is more accurate and the lower body based on animation blending which only needs a small number of prepared animations. Meanwhile, a natural action recognition algorithm based on neural network will run in need to detect the target motions we have trained. We show that our method can reconstruct various full-body motions, such as walking in any direction, jogging, jumping, crouching and turning. Our method has the ability to reconstruct natural human motions which can be used in almost all VR multi-person interactive applications. The configuration of sensors we attached on the head and hands is very popular in VR well-known devices, so the method can be easily integrated into off-the-shelf VR devices.