Miracle-dz/UniFAR-FTUs huggingface dataset:
The zinc finger protein Zn 72 D and DEAD box helicase Belle interact and control maleless mRNA and protein levels

Background: The Male Specific Lethal (MSL) complex is enriched on the single X chromosome in male Drosophila cells and functions to upregulate X-linked gene expression and equalize X-linked gene dosage with XX females. The zinc finger protein Zn72D is required for productive splicing of the maleless (mle) transcript, which encodes an essential subunit of the MSL complex. In the absence of Zn72D, MLE levels are decreased, and as a result, the MSL complex no longer localizes to the X chromosome and dosage compensation is disrupted. To understand the molecular basis of Zn72D function, we identified proteins that interact with Zn72D. Results: Among several proteins that associate with Zn72D, we found the DEAD box helicase Belle (Bel). Simultaneous knockdown of Zn72D and bel restored MSL complex localization to the X chromosome and dosage compensation. MLE protein was restored to 70% of wild-type levels, although the level of productively spliced mle transcript was still four-fold lower than in wild-type cells. The increase in production of MLE protein relative to the amount of correctly spliced mle mRNA could not be attributed to an alteration in MLE stability. Conclusion: These data indicate that Zn72D and Bel work together to control mle splicing and protein levels. Thus Zn72D and Bel may be factors that coordinate splicing and translational regulation. Background There is increasing evidence linking the processes involved in gene expression, such as transcription, splicing, mRNA localization, and translation. For example, splicing factors, such as hnRNP proteins and the serine/ arginine-rich (SR) protein SF2/ASF, can remain associated with mature transcripts, shuttle to the cytoplasm, and regulate translation [1-4]. For the Drosophila oskar transcript, splicing of the first intron is required for proper localization of the transcript to the posterior end of the oocyte, where it is locally translated [5]. Correct localization of this transcript also depends on the exon junction complex components Y14 and Mago nashi [6-8]. Despite evidence for coordination of splicing, mRNA localization, and translation, the mechanisms underlying this coordination remain poorly characterized. We previously demonstrated that the Drosophila zinc finger protein Zn72D is required for proper splicing of the maleless (mle) transcript. The MLE protein is an essential Published: 22 April 2009 BMC Molecular Biology 2009, 10:33 doi:10.1186/1471-2199-10-33 Received: 29 October 2008 Accepted: 22 April 2009 This article is available from: http://www.biomedcentral. com/1471-2199/10/33 © 2009 Worringer et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. BMC Molecular Biology 2009, 10:33 http://www.biomedcentral. com/1471-2199/10/33
Apps Can Quickly Destroy Your Mobile's Flash: Why They Don't, and How to Keep It That Way

Although flash cells wear out, a typical SSD has enough cells and sufficiently sophisticated firmware that its lifetime generally exceeds the expected lifetime of its host system. Even under heavy use, SSDs last for years and can be replaced upon failure. On a smartphone, in contrast, the hardware is more limited and we show that, under heavy use, one can easily, and more quickly, wear out smartphone flash storage. Consequently, a simple, unprivileged, malicious application can render a smartphone unbootable ("bricked") in a few weeks with no warning signs to the user. This bleak result becomes more worrisome when considering the fact that smartphone users generally believe it is safe to try out new applications. To combat this problem, we study the I/O behavior of a wide range of Android applications. We find that high-volume write bursts exist, yet none of the applications we checked sustains an average write rate that is high enough to damage the device (under reasonable usage assumptions backed by the literature). We therefore propose a rate-limiting algorithm for write activity that (1) prevents such attacks, (2) accommodates "normal" bursts, and (3) ensures that the smartphone drive lifetime is longer than a preconfigured lower bound (i.e., its warranty). In terms of user experience, our design only requires that, in the worst case of an app that issues continuous, unsustainable, and unusual writes, the user decides whether to shorten the phone's life or rate limit the problematic app.
Increase in the ileal absorption rate of sodium taurocholate in germ-free or conventional rats given an amylomaize-starch diet

1. Twenty germ-free and twenty conventional male Fischer 344 rats, 3 months old, were fed ad lib. diets based either on normal or on amylomaize starch for 1 month. The absorption rate of sodium taurocholate. 25 mmol/l, was determined in vivo in jejunal or ileal segments. Each determination included five rats. 2. Jejunal absorption rate was not modified either by the amylomaize-based diet or by the digestive microflora. 3. Ileal absorption rate was slightly higher in germ-free than in conventional rats. 4. Ileal absorption rate was largely increased by the amylomaize-based diet. This increase was slightly larger in germ-free rats than in conventional rats. 5. It is suggested that dietary amylomaize starch has an action on the active absorption process of bile acid.
HRM and innovation: looking across levels

Studies are starting to explore the role of HRM in fostering organizational innovation but empirical evidence remains contradictory and theory fragmented. This is partly because extant literature by and large adopts a unitary level of analysis, rather than reflecting on the multi-level demands that innovation presents. Building on an emergent literature focused on HRM’s role in shaping innovation, we shed light on the question of whether, and how, HRM might influence employees’ innovative behaviours in the direction of strategically important goals. Drawing upon institutional theory, our contributions are three-fold: to bring out the effect of two discrete HRM configurations- one underpinned by a control and the other by an entrepreneurial ethos, on attitudes and behaviours at the individual level; to reflect the way in which employee innovative behaviours arising from these HRM configurations coalesce to shape higher-level phenomena, such as organizational-level innovation; and to bring out two distinct patterns of bottom-up emergence, one driven primarily by composition and the other by both composition and compilation.
Visualizing Problem Solving in a Strategy Game for Teaching Programming

Lack of problem solving skill has been identified as the major cause of students’ failure in introductory programming courses. This paper presents a strategy game, COPS, which helps students improve their problem solving ability by building program flowcharts as a jigsaw puzzle. For each move, pseudocode equivalents are immediately generated by the system. Students therefore have two visual representations of the problem solution and can more easily follow the logic in their solution. COPS provides dynamic feedback using visual and textual aids to guide students throughout the process. The results of two studies done with secondary school students in Trinidad and Tobago using COPS had positive results.
The ERK/MAPK pathway, as a target for the treatment of neuropathic pain

Peripheral nerve injury produces neuropathic pain as well as phosphorylation of mitogen activated protein kinase (MAPK) family in dorsal root ganglia (DRG) and dorsal horn. Following nerve injury, phosphorylation of extracellular signal-regulated protein kinase (ERK), an important member of this family, is sequentially increased in neurons, microglia and astrocytes of the dorsal horn and gracile nucleus, and in injured large DRG neurons. Nerve injury-induced phosphorylation of ERK occurs early and is long-lasting. In several animal models of neuropathic pain, MEK inhibitors, known to suppress the synthesis of ERK, have proven effective to alleviate pain at various time points. Thus, the regulation of ERK/MAPK can be considered as a promising therapeutic target for the treatment of neuropathic pain.
Deep-Ultraviolet Raman Spectroscopy for Cancer Diagnostics: A Feasibility Study with Cell Lines and Tissues

Background Deep-ultraviolet resonance Raman spectroscopy (UVRS) offers significant advantages over visible and near-infrared Raman spectroscopy for biological applications, including cancer identification. Cancer is the second-leading cause of death in the United States. Early diagnostics plays a crucial role in providing the best chances for an afflicted individual to seek successful treatment opportunities. Current methods for diagnosing various forms of cancer are both expensive and invasive. As such, the objective of this study is to explore the feasibility of UVRS for discrimination of cancerous tissues and cancer cells from normal samples. The safety issues of using ultraviolet light for human applications are analyzed. Methods Cancerous brain tissues from nonobese diabetic/severe combined immunodeficiency (NOD-SCID) model mice injected with 435-tdT cells (human adenocarcinoma breast cancer cells) at known locations and adjacent normal brain tissues as well as normal and cancer (adenocarcinoma PC-3) prostate cells were studied using UVRS. The obtained Raman spectra of the healthy and cancerous samples are compared in order to identify biochemical differences between them. Results The obtained spectra reflect biochemical differences which occur between the healthy and malignant samples in both brain and prostate cancers. UVRS provides distinctive resonance signatures of major biochemical components, including proteins and nucleic acids, and it does not suffer from fluorescence interference, nor does it require high laser power levels for excitation. These advantages allow for clear and effective spectral discrimination between samples. Conclusion Our results suggest UVRS should be considered for cancer identification, and is safe for use within humans. The proposed innovative approach has significant potential for cancer imaging and real-time tissue discrimination during surgery.
Focal adhesion kinase and tumour angiogenesis

Angiogenesis, the formation of new blood vessels from pre‐existing ones, is essential for tumour development. It is initiated and regulated by growth factors via their surface receptors, which activate several intracellular signalling pathways in endothelial cells. Cell adhesion molecules, such as integrins, also regulate angiogenesis. Despite these facts, inhibitors of endothelial cell growth factor receptors or integrins have not been as effective as initially hoped in the long‐term inhibition of angiogenesis in cancer patients. Signalling downstream of growth factor receptors and integrins converge on the ubiquitously expressed non‐receptor tyrosine kinase focal adhesion kinase (FAK). FAK is involved in endothelial cell proliferation, migration and survival, is up‐regulated in many cancers and has recently been shown to control tumour angiogenesis. Indeed, FAK inhibitors are presently being developed for the treatment of cancer. However, recent studies have indicated the complexities of understanding the precise role for FAK in angiogenesis. Here we have summarized some of the key features of FAK, addressed some of the apparently contradictory roles of this molecule in angiogenesis and provided some perspectives for future studies. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A Novel Magnetic Flux Weakening Method of Permanent Magnet Synchronous Motor for Electric Vehicles

In this paper, a novel field weakening control method for permanent magnet synchronous motor is proposed to improve maximum speed range and maximum power, which are important parameters for electric vehicle application. Unlike general field weakening control method in which current vector is used to decrease linkage magnetic flux, the proposed method can decrease linkage magnetic flux by creating a difference gap between a stator and a rotor in axial direction without moving the current vector. This method is effective in increasing the maximum speed and the output power of permanent magnet synchronous motor, including surface permanent magnet-type rotor and interior permanent magnet-type rotor. Three-dimensional finite element method is adopted for the analysis of the proposed method in order to calculate d-axis and q-axis inductances as well as linkage magnetic flux according to axial gap. Motor performances according to speed are also compared with one another.
Contextual loss functions for optimization of convolutional neural networks generating pseudo CTs from MRI

Predicting pseudo CT images from MRI data has received increasing attention for use in MRI-only radiation therapy planning and PET-MRI attenuation correction, eliminating the need for harmful CT scanning. Current approaches focus on voxelwise mean absolute error (MAE) and peak signal-to-noise-ratio (PSNR) for optimization and evaluation. Contextual losses such as structural similarity (SSIM) are known to promote perceptual image quality. We investigate the use of these contextual losses for optimization. Patch-based 3D fully convolutional neural networks (FCN) were optimized for prediction of pseudo CT images from 3D gradient echo pelvic MRI data and compared to ground truth CT data of 26 patients. CT data was non-rigidly registered to MRI for training and evaluation. We compared voxelwise L1 and L2 loss functions, with contextual multi-scale L1 and L2 (MSL1 and MSL2), and SSIM. Performance was evaluated using MAE, PSNR, SSIM and the overlap of segmented cortical bone in the reconstructions, by the dice similarity metric. Evaluation was carried out in cross-validation. All optimizations successfully converged well with PSNR between 25 and 30 HU, except for one of the folds of SSIM optimizations. MSL1 and MSL2 are at least on par with their single-scale counterparts. MSL1 overcomes some of the instabilities of the L1 optimized prediction models. MSL2 optimization is stable, and on average, outperforms all the other losses, although quantitative evaluations based on MAE, PSNR and SSIM only show minor differences. Direct optimization using SSIM visually excelled in terms subjective perceptual image quality at the expense of a voxelwise quantitative performance drop. Contextual loss functions can improve prediction performance of FCNs without change of the network architecture. The suggested subjective superiority of contextual losses in reconstructing local structures merits further investigations.
In-vitro prostate cancer biomarker detection by directed conjugation of anti-PSCA antibody to super paramagnetic iron oxide nanoparticless

Background: The main property of a successful conjugation of antibodies to nanoparticles is keeping the potency of antibody for binding the antigen, and an oriented conjugation can do that. Under such ground, this study was carried out to explore the efficiency of two conjugation methods in binding iron nanoparticles to an antibody produced against PSCA (prostate stem cell antigen) using in vitro labeling of PC3 cells. Methods: In this experimental study, we conjugated dextran-superparamagnetic iron oxide nanoparticles (dexSPIONs) to anti-PSCA antibody by two different methods, including targeting carbohydrate moieties in FC domain and the free amine group of amino acid side chains. Ultimately, Iron staining was done by anti-PSCA antibody-dexSPIONs in PC3 cells to detect antibody binding to the cells. Results: A strong blue dye was induced by iron staining in conjugated dexSPIONs on the membrane of PC3 cells by the former method than the second one. Moreover, cells treated with 20 nm diameters of dexSPIONs showed higher resolution of blue color than those treated with 100 nm nanoparticles. Conclusion: This oriented conjugation method promoted the efficiency of targeting tumor antigens, and the presence of iron particles might enhance MRI image intensity in vivo by targeting PSCA-overexpressing cells in future studies.
A Novel CMOS Compatible Top-Floating-Gate Flash EEPROM Cell

A novel nonvolatile memory (NVM) Top-floating-gate (TFG) flash device is demonstrated in a CMOS technology which can be implemented as a stand alone device, or with additional benefit as an embedded device. This device differs in both structure and operation to typical split-gate or stacked-gate approaches. The TFG device uniquely offers low development cost, low power compliance and high reliability. It can be fabricated using routine CMOS processing making it clearly competitive to options typically used in the industry. The structure and operation of this novel device structure is described. This is followed by a description of the processing required and electrical results.
Influence of Fc&ggr;RIIIA genetic polymorphism on T-lymphocyte depletion induced by rabbit antithymocyte globulins in kidney transplant patients

Introduction Polyclonal antithymocyte globulins (ATG) have been used in transplantation for several decades, but the sources of the interindividual variability of their effect are poorly understood. An influence of the FCGR3A-158V/F genetic polymorphism on the horse ATG concentration–effect relationship was reported in kidney transplant patients. The objective of the present study was to confirm the influence of the FCGR3A polymorphism on the extent of lymphocyte depletion in kidney transplant patients treated with rabbit antithymocyte globulin (r-ATG). Materials and methods Of the 194 transplant patients treated with r-ATG between 1998 and 2002 in our institution, 69 patients were eligible and included in this retrospective study. Biomarkers of response were CD3 and CD4 counts. Dose–effect data were analyzed using a population approach, and a two-compartment turnover model with stimulation of lymphocyte ‘output’. Since r-ATG concentrations were not available, a K-PD model was used. The influence of FCGR3A genotype on estimated parameters was investigated. Results The r-ATG infusion rate leading to a 50% stimulation of CD3+ output (EDK50), which is inversely related to patient sensitivity to r-ATG treatment, decreased with the number of V alleles (P=0.0016). Conclusion The genetic polymorphism of FCGR3A influences r-ATG effect on CD3 count in kidney transplant patients, those with the V allele being more sensitive to antilymphocyte serum. These results also suggest that r-ATG act, at least in part, by antibody-dependent cellular cytotoxicity.
A prospective study of concomitant GLP-1 analogue and insulin use in type 2 diabetes in clinical practice.

BACKGROUND A small number of studies have shown a significant reduction in HbA1c, weight and total daily insulin dose when a glucagon-like-peptide-1 (GLP-1) analogue was added in type 2 diabetes patients already on insulin treatment. Therefore, in a clinical setting, we investigated the effect of adding GLP-1 analogues in patients with type 2 diabetes already using insulin with respect to glycaemic control, body weight and insulin dose. METHODS In this prospective hospital-based study, we included 125 patients suffering from type 2 diabetes, treated with insulin and with a body mass index ≥ 35 kg/m2, who had started on GLP-1 analogues (liraglutide/exenatide). HbA1c, body weight, daily insulin dose, and side effects were registered at baseline, and after three, six and 12 months. RESULTS HbA1c and weight decreased significantly at all the timepoints (p ≤ 0.001 compared with baseline; HbA1c: -5.5 mmol/mol (-0.5%) and weight: -14.3 kg after 12 months), with the largest decrease in the first three months. No significant correlation was found between weight loss and HbA1c reduction, and between duration of diabetes and both weight loss and HbA1c reduction. After six and 12 months, the total daily insulin dose decreased significantly (p < 0.001, -75.4 IU after 12 months). Moreover, 34% of the patients were able to stop using insulin therapy after 12 months. CONCLUSION By adding a GLP-1 analogue in obese patients with type 2 diabetes already on insulin therapy, a significant reduction of HbA1c levels and body weight, and a significant reduction in insulin dose or complete discontinuation of insulin can be achieved.
Chronic Lymphocytic Leukemia Treatment Options for Patients With Refractory Disease

Patients with purine analogue–refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zetachain–associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL. Cancer 2009;115:3830–41. VC 2009 American Cancer Society.
Realization of Low Profile Leaky Wave Antennas Using the Bending Technique for Frequency Scanning and Sensor Applications

This paper proposes an efficient transmission line modulation by using the bending technique to realize low profile leaky wave antennas in the Ku-band for frequency scanning and sensor applications. The paper focuses mainly on the bending effects of the transmission line in terms of the sharpness of edges. The right-hand/left-hand transmission line can be designed in the form of zig-zag pattern with sharp corners and only the right-hand transmission line in the form of sinusoidal patterns with smooth corners. In this presentation, we demonstrate that transmission lines of this kind can be used to realize highly efficient leaky wave antennas with broadband impedance matching and high gain characteristics in the Ku-band. Dispersion analysis and ladder network analysis have been performed for investigating the performance of the proposed designs. The sharpness of the bends periodically distributed along the body of the antenna has been used to our advantage for frequency scanning in the left-hand and right-hand quadrants at different frequencies. The proposed bending technique has been proven to be instrumental in achieving the desired characteristics of low profile leaky wave antennas.
A chemoprobe tracks its target

Small-molecule inhibitors of histone-modifying enzymes have significant clinical utility for managing diseases such as cancer. These inhibitors are usually identified and monitored through their effects on the gain or loss of specific histone marks. In cells, multiple related enzymes can place or remove a specific mark; therefore, relying on an indirect measure of inhibitor engagement can be misleading. Mascaró et al. describe a luminescence-based ELISA approach that directly monitors binding of inhibitors to the histone lysine demethylase KDM1A.