Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimized models for design of efficient miR30-based shRNAs

Small hairpin RNAs (shRNAs) became an important research tool in cell biology. Reliable design of these molecules is essential for the needs of large functional genomics projects. To optimize the design of efficient shRNAs, we performed comparative, thermodynamic, and correlation analyses of ~18,000 miR30-based shRNAs with known functional efficiencies, derived from the Sensor Assay project (Fellmann et al., 2011). We identified features of the shRNA guide strand that significantly correlate with the silencing efficiency and performed multiple regression analysis, using 4/5 of the data for training purposes and 1/5 for cross validation. A model that included the position-dependent nucleotide preferences was predictive in the cross-validation data subset (R = 0.39). However, a model, which in addition to the nucleotide preferences included thermodynamic shRNA features such as a thermodynamic duplex stability and position-dependent thermodynamic profile (dinucleotide free energy) was performing better (R = 0.53). Software “miR_Scan” was developed based upon the optimized models. Calculated mRNA target secondary structure stability showed correlation with shRNA silencing efficiency but failed to improve the model. Correlation analysis demonstrates that our algorithm for identification of efficient miR30-based shRNA molecules performs better than approaches that were developed for design of chemically synthesized siRNAs (Rmax = 0.36).
Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study

Background The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. Methods Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR) after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease. Results Thirty-three patients were enrolled. The median age was 62 (range: 35–77) years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8–57.0) and the response rate (complete response and partial response) was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m2. Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment-related deaths. Conclusion Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.
Active Learning of Event Detection Patterns

Retraining an event extraction system for a new class of events requires considerable effort. A given type of event may appear in many linguistic forms, and mentions of the event type may be relatively infrequent in running text; together, this means that, with sequential annotation, a large amount of text must be annotated to train a system of reasonable performance. Semi-supervised training can greatly reduce the labor, but its effectiveness over different event classes is very uneven. We show that an active learner adapted from the semi-supervised method can achieve very good performance, exceeding that of a tagger trained on 300,000 words of text, with a reasonable amount of effort (answering several hundred questions).
A conditional allele of the novel repeat-containing yeast nucleoporin RAT7/NUP159 causes both rapid cessation of mRNA export and reversible clustering of nuclear pore complexes

In a screen for Saccharomyces cerevisiae genes required for nucleocytoplasmic transport of messenger RNA, we identified the RAT7 gene (ribonucleic acid trafficking), which encodes an essential protein of 1,460 amino acids. Rat7p is located at the nuclear rim in a punctate pattern characteristic of nucleoporins. Furthermore, the central third of Rat7p contains 22 XXFG and three XFXFG degenerate repeats that are similar to signature GLFG and XFXFG repeats present in a majority of yeast and some mammalian nucleoporins sequenced to date. Shift of a strain bearing the temperature-sensitive rat7-1 allele from 23 degrees C to 37 degrees C resulted in rapid (within 15 minutes) cessation of mRNA export, but did not cause concomitant cytoplasmic accumulation of a reporter protein bearing a nuclear localization signal. This suggests that Rat7p may play a direct role in nucleocytoplasmic export of RNA. Immunofluorescence and thin section electron microscopy revealed that in rat7-1 cells grown at 23 degrees C, the majority of nuclear pore complexes (NPCs) were clustered on one side of the nucleus. No ultrastructural abnormalities of the nuclear envelope were seen. Interestingly, shifting rat7-1 cells to 37 degrees C for 1 h caused the NPCs to disperse, restoring near wild-type NPC distribution. After this temperature shift, the mutant Rat7p was no longer detectable by immunofluorescence.
The power of phylogenetic comparison in revealing protein function.

Positive selection, that is, fixation of advantageous mutations driven by natural selection, has been an exciting topic to evolutionary biologists, because adaptive changes in genes and genomes are ultimately responsible for evolutionary innovations and species differences. In recent years, detecting signals of natural selection has also become a powerful approach for molecular biologists, biochemists, and virologists to understand the functions of new genes. In a recent issue of PNAS, Sawyer et al. (1) described a remarkable study in which phylogenetic sequence comparison identified a small segment of the primate TRIM5α protein to be under positive selection, and functional analysis using mutagenesis confirmed the importance of the segment in species-specific retroviral inhibition. TRIM5α is a protein in the cellular antiviral defense system in primates and can restrict retroviruses such as HIV-1 and simian immunodeficiency virus in a species-specific manner. The protein was identified recently because the rhesus monkey TRIM5α restricts reverse transcription of HIV-1, whereas the native human TRIM5α does not (2). Sawyer et al. (1) sequenced the TRIM5 α gene from a number of primate species, including hominoids and Old and New World monkeys. Their phylogenetic analysis estimating evolutionary rates identified amino acid positions in the protein at which natural selection appears to have actively promoted amino acid substitutions. In particular, a 13-aa “patch” in the SPRY domain had a concentration of positively selected sites, implicating it as an antiviral interface. By creating chimeric TRIM5 α genes, Sawyer et al. demonstrated that this patch is responsible for most of the species-specific antiretroviral activity. Previous studies using phylogenetic approaches have identified a number of genes under positive selection, especially genes involved in host–pathogen interactions. However, this study is unique in that there was no a priori information, structural or otherwise, concerning which part of the protein acts as the interaction interface …
Robust optimization of cognitive radio networks powered by energy harvesting

We consider a cognitive radio network, where primary users (PUs) share their spectrum with energy harvesting (EH) enabled secondary users (SUs), conditioned on a limited SUs' interference at PU receivers. Due to the lack of information exchange between SUs and PUs, the SU-PU interference channels are subject to uncertainty in channel estimation. Besides channel uncertainty, SUs' EH profile is also subject to spatial and temporal variations, which enforce an energy causality constraint on SUs' transmit power control and affect SUs' interference at PU receivers. Considering both the channel and EH uncertainties, we propose a robust design for SUs' power control to maximize SUs' throughput performance. Our robust design targets at the worst-case interference constraint to provide a robust protection for PUs, while guarantees a transmission probability to reflect SUs' minimum QoS requirements. To make the non-convex throughput maximization problem tractable, we develop a convex approximation for each robust constraint and successfully design a successive approximation approach that converges to the global optimum of the throughput objective. Simulations show that SUs will change transmission strategies according to PUs' sensitivity to interference, and we also exploit the impact of SUs' EH profile (e.g., mean, variance, and correlation) on SUs' power control.
Information flow inference for free

This paper shows how to systematically extend an arbitrary type system with dependency information, and how soundness and non-interference proofs for the new system may rely upon, rather than duplicate, the soundness proof of the original system. This allows enriching virtually any of the type systems known today with information flow analysis, while requiring only a minimal proof effort.Our approach is based on an untyped operational semantics for a labelled calculus akin to core ML. Thus, it is simple, and should be applicable to other computing paradigms, such as object or process calculi.The paper also discusses access control, and shows it may be viewed as entirely independent of information flow control. Letting the two mechanisms coexist, without interacting, yields a simple and expressive type system, which allows, in particular, "selective" declassification.
Analysis of the Ideal Conditions for the Differentiation of Embryonic Stem Cells

Embryonic stem (ES) cells have the potential to differentiate into any type of body cell. For our experiment, we used mice embryonic stem cells. We aimed to create the ideal two-dimensional film to model a future three-dimensional scaffold that could be implanted into humans to repair damaged bone. We created a film that could endure normal human bone stress and strain while making a surface where the cells could attach and eventually differentiate. We made a solution of chitosan and sodium alginate, two nontoxic, biodegradable polymers, and combined it with hydroxyapatite, an inorganic human bone salt. Using this solution, we made twodimensional films which served as sites of attachment for stem cells. The film was tested for its strength using an Instron tensile strength tester. Young’s Modulus, which is a mechanical property for evaluating the elasticity of a material, was calculated. Our average Young’s modulus value was 3.3 gigapascals and the greatest stress was 70 megapascals. Thus, our substitute was strong enough to act as human bone. To test cell attachment, we used the same solution used to create films which we placed on two six-by-four welled plates. We examined two factors that affect cell-to-film adhesion: media and cell concentration. One plate contained cells in growth medium, which promoted stem cell differentiation. The other plate contained culture medium, which optimized stem cell proliferation. Half of each plate contained 10,000 cells per well, while the other half contained 20,000 cells per well. The cells were then stained and fixed after one week of incubation. Although only one trial was performed, we concluded that the optimal tested condition for cell adhesion to film was the 20,000 cell concentration combined with a culture medium. While further research must be conducted before conclusions may be drawn, our results show promising results for the future of stem cell bone research.
Aggregation of Gradual Trust and Distrust

Trust and distrust are two increasingly important metrics in social networks, reflecting users' attitudes and relationships towards each other. In this paper, we study the indirect derivation of these metrics' values for users that do not know each other, but are connected through the network. In particular, we focus on the aggregation step that is required for fusing trust and distrust information obtained via multiple network paths.
Endocannabinoid–Dopamine Interactions in Striatal Synaptic Plasticity

The nigrostriatal dopaminergic system is implicated in action control and learning. A large body of work has focused on the contribution of this system to modulation of the corticostriatal synapse, the predominant synapse type in the striatum. Signaling through the D2 dopamine receptor is necessary for endocannabinoid-mediated depression of corticostriatal glutamate release. Here we review the known details of this mechanism and discuss newly discovered signaling pathways interacting with this system that ultimately exert dynamic control of cortical input to the striatum and striatal output. This topic is timely with respect to Parkinson’s disease given recent data indicating changes in the striatal endocannabinoid system in patients with this disorder.
Immuno-localization of the insulin regulatable glucose transporter in brown adipose tissue of the rat

Antibodies specific for the insulin-regulatable glucose transporter (GLUT 4) were used to immunolocalize this protein in brown adipose tissue from basal- and insulin-treated rats. Cryosections of fixed tissue were incubated with antibodies, which were subsequently labeled with Protein A/gold and examined by EM. Antibodies against albumin and cathepsin D were also used with gold particles of different sizes to identify early and late endosomes, respectively. Under basal conditions 99% of the GLUT 4 labeling was located within the cell. Labeling was predominantly in the trans-Golgi reticulum and tubulo-vesicular structures elsewhere in the cytoplasm. In insulin-stimulated cells approximately 40% of the GLUT 4 labeling was at the cell surface, where it was randomly distributed, except for occasional clustering in coated pits. Moreover, after insulin treatment, GLUT 4 was also enriched in early endosomes. We conclude that translocation of GLUT 4 to the cell surface is the major mechanism by which insulin increases glucose transport. In addition, these results suggest that in the presence of insulin GLUT 4 recycles from the cell surface, probably via the coated pit-endosome pathway that has been characterized for cell surface receptors, and also that insulin causes the redistribution of GLUT 4 by stimulating exocytosis from GLUT 4-containing tubulo-vesicular structures, rather than by slowing endocytosis of GLUT 4.
Demo: Yalut -- user-centric social networking overlay

Yalut is a novel user-centric hybrid content sharing overlay for social networking. Yalut enables the users to retain control over their own data and preserve their privacy, whilst still using the popular centralized services. In this demonstration, we show the feasibility of Yalut by integrating the service with the popular social networking apps on Android devices, Mac and Windows desktop platforms. We show that it is possible to provide the benefits of distributed content sharing on top of the existing centralized services with minimal changes to the content sharing process.
CompUTE: a runtime infrastructure for device composition

In this paper, we present the idea of a composite device, which is one device made up of a composition of several separate devices working together in concert. We present the CompUTE architecture as a runtime infrastructure for device composition. This architecture is implemented in the CompUTE . net platform, which enables device composition between Windows XP devices based on an 'extended desktop' metaphor. We discuss how the CompUTE . net platform enables users to merge multiple computers into one composite device with an enlarged desktop area and several keyboards and mice. Each user is equipped with a unique cursor, which works across all connected devices and she can drag and drop any application window and files between the connected devices. User can also work collaboratively on the composite device. We reports from a usability study involving 24 participants who found the CompUTE . net platform very useful, easy to use, and easy to learn.
Adopt-a-robot: A story of attachment (Or the lack thereof)

Robots have diffidently started to invade human spaces, but are still limited to very rudimentary forms such as robot vacuum cleaners and various entertainment platforms. Dramatic changes with respect to the number of robots in homes and offices, however, can be foreseen for the near future as sensing, computing and associated technologies mature. Currently, it is not known how we humans will treat machine companions when they will be with us over prolonged periods of time and share our personal space. In this exploratory study we investigated whether participants would form a bond with a small, basic research robot in an adoption scenario whereby the robot's initial interaction abilities were upgraded in two steps. We were particularly interested in investigating whether any increases in attachment would be related to the 2 steps of progressively heightened technical sophistication of the robot over a prolonged (six month) period of time.
A push recovery strategy for a passively compliant humanoid robot using decentralized LQR controllers

This paper presents a control scheme that is directed towards the performance of push recovery on the compliant humanoid robot, COMAN. The novelty offered by this work is related to the use of a decentralized controller based on an initial Limited Quadratic Regulator (LQR) design on a humanoid robot in addition to the regulation of the actual joint positions instead of the motor positions. Moreover, the ankle-knee strategy is examined through the use of a compliant double inverted pendulum model. A key feature of the propounded approach lies in the controller's ability to regulate the system's inherently compliant dynamics through considering not only the motor-related variables but also those of the link-side, appearing after the passive compliant element. Consequently, this leads to a control method that is capable of stabilizing the robot by means of increasing the damping on the link, which is essential given the system's oscillatory behaviour once it has been perturbed.
DETAILED IMAGE SEGMENTATION USING NORMALISED CUTS AND WEIGHTED CO- EFFICIENT

Image segmentation is one of the vital steps in th e processing of image which includes dividing the image pixels in to salient image regions. These may be the regions cor responding to individual surfaces, objects, or natural parts of o bjects which could be used for object recognition, occlusion bou ndary estimation within motion or stereo systems, image c ompression or image editing. Normalized cut method of image segmentation is one of the intensively used image segmentation a pproach which deals with clustering a set of elements based only on the values of a similarity measure between all possible pairs of elements. Along with this method if weighted graph based analysis of clustered image is used, that would help in reducing the comp utational complexity and provides new vision in image segmentation. In this paper weighted graphical co-efficient and normalized cut methods are combined to get the optimal segmentation results. Once the image is segmented using normalized cut method, clusters are analyzed using weighted pixel paramete rs and by taking their co- efficient into consideration.
Neocognitron as a tool for optical marks recognition

Paper describes an investigation of simplified neocognitron neural network model as a tool for practical recognition of handwritten mark images. Simplification of neocognitron structure from only two stages and fixed number of feature-extraction planes is proposed, the overall stages of solving practical image processing problem are described. Recognition properties of simplified net are investigated, it is shown that for particular task simple structure of net may be the same effective (up to 98% of correct recognition) as traditional four-stages one.
Vibrapass: secure authentication based on shared lies

Authentication in public spaces is a risky task. Frauds on cash machines (ATMs) are not uncommon nowadays. The biggest group of attacks is observation attacks, which focus on recording the input done by the users. In this work, we present VibraPass, a system created to be resilient against observation attacks using tactile feedback provided by the users' own mobile devices. In this way, secret information is shared between the terminal and the users to add an over-head of 'lies' to the input which makes it hard for attackers to steal the real PIN or password. We present an evaluation, which shows that VibraPass has the potential to replace current authentication systems due to increased security combined with reasonable input speed and error rates.
Design of a Flexible Open Platform for High Performance Active Networks

This paper describes an architecture for a high performance active router. The system is designed as an open research platform, with a range of configuration options and possibilities for extension in both the software and hardware dimensions. The system is built around a scalable switch fabric and includes a general-purpose processor subsystem at each port, enabling flexible packet processing and deployment of flow-specific active plugins. Such a research platform is becoming an indispensable tool for effective systems research in networking and distributed systems.
The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser358 in adipocytes

SIK2 (salt-inducible kinase 2) is a member of the AMPK (AMP-activated protein kinase) family of kinases and is highly expressed in adipocytes. We investigated the regulation of SIK2 in adipocytes in response to cellular stimuli with relevance for adipocyte function and/or AMPK signalling. None of the treatments, including insulin, cAMP inducers or AICAR (5-amino-4-imidazolecarboxamide riboside), affected SIK2 activity towards peptide or protein substrates in vitro. However, stimulation with the cAMP-elevating agent forskolin and the β-adrenergic receptor agonist CL 316,243 resulted in a PKA (protein kinase A)-dependent phosphorylation and 14-3-3 binding of SIK2. Phosphopeptide mapping of SIK2 revealed several sites phosphorylated in response to cAMP induction, including Ser358. Site-directed mutagenesis demonstrated that phosphorylation of Ser358, but not the previously reported PKA site Ser587, was required for 14-3-3 binding. Immunocytochemistry illustrated that the localization of exogenously expressed SIK2 in HEK (human embryonic kidney)-293 cells was exclusively cytosolic and remained unchanged after cAMP elevation. Fractionation of adipocytes, however, revealed a significant increase of wild-type, but not Ser358Ala, HA (haemagglutinin)–SIK2 in the cytosol and a concomitant decrease in a particulate fraction after CL 316,243 treatment. This supports a phosphorylation-dependent relocalization in adipocytes. We hypothesize that regulation of SIK2 by cAMP could play a role for the critical effects of this second messenger on lipid metabolism in adipocytes.