Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimization of Duplex Stability and Terminal Asymmetry for shRNA Design

Prediction of efficient oligonucleotides for RNA interference presents a serious challenge, especially for the development of genome-wide RNAi libraries which encounter difficulties and limitations due to ambiguities in the results and the requirement for significant computational resources. Here we present a fast and practical algorithm for shRNA design based on the thermodynamic parameters. In order to identify shRNA and siRNA features universally associated with high silencing efficiency, we analyzed structure-activity relationships in thousands of individual RNAi experiments from publicly available databases (ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/). Using this statistical analysis, we found free energy ranges for the terminal duplex asymmetry and for fully paired duplex stability, such that shRNAs or siRNAs falling in both ranges have a high probability of being efficient. When combined, these two parameters yield a ∼72% success rate on shRNAs from the siRecords database, with the target RNA levels reduced to below 20% of the control. Two other parameters correlate well with silencing efficiency: the stability of target RNA and the antisense strand secondary structure. Both parameters also correlate with the short RNA duplex stability; as a consequence, adding these parameters to our prediction scheme did not substantially improve classification accuracy. To test the validity of our predictions, we designed 83 shRNAs with optimal terminal asymmetry, and experimentally verified that small shifts in duplex stability strongly affected silencing efficiency. We showed that shRNAs with short fully paired stems could be successfully selected by optimizing only two parameters: terminal duplex asymmetry and duplex stability of the hypothetical cleavage product, which also relates to the specificity of mRNA target recognition. Our approach performs at the level of the best currently utilized algorithms that take into account prediction of the secondary structure of the target and antisense RNAs, but at significantly lower computational costs. Based on this study, we created the si-shRNA Selector program that predicts both highly efficient shRNAs and functional siRNAs (ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/).
31 Questions and Answers

Few people have contributed as much to artificial intelligence (AI) as has Judea Pearl. Among his several hundred publications, several stand out as among the historically most significant and influential in the theory and practice of AI. With my few pages in this celebratory volume, I join many of his colleagues and former students in showing our gratitude and respect for his inspiration and exemplary career. He is a towering figure in our field. Certainly one key to Judea’s many outstanding achievements (beyond dedication and hard work) is his keen ability to ask the right questions and follow them up with insightful intuitions and penetrating mathematical analyses. His overarching question, it seems to me, is “how is it that humans can do so much with simplistic, unreliable, and uncertain information? ” The very name of his UCLA laboratory, the Cognitive Systems Laboratory, seems to proclaim his goal: understanding and automating the most cognitive of all systems, namely humans. In this essay, I’ll focus on the questions and inspirations that motivated his ground-breaking research in three major areas: heuristics, uncertain reasoning, and causality. He has collected and synthesized his work on each of these topics in three important books [Pearl 1984; Pearl 1988; Pearl 2000].
Athletic Aggression: Perceived Legitimacy and Behavioral Intentions in Girls’ High School Basketball

The present study examined the stability of athletes' legitimacy judgments and behavioral intentions over the course of a basketball season and the relationship between these factors to actual behavior. The 49 female basketball players responded to a questionnaire that was derived from Bredemeier's (1985) Continuum of Injurious Acts. The preseason legitimacy rating of aggressive actions made by first-year basketball players were significantly higher than those made by more experienced players, but by the end of the season the first-year participants' ratings had dropped to a level comparable to their more experienced teammates. Preseason legitimacy judgments were found to predict player aggression during the season. Interpretation of the findings and recommendations for future direction in this area are discussed.
The Influence of the Spouse on American Expatriate Adjustment and Intent to Stay in Pacific Rim Overseas Assignments

Past international human resource management literature has suggested that most American multinationalfirms that employ expatriate managers have difficulty successfully retaining these managers in overseas assignments. Although some scholars have suggested that the inability of the spouse to adjust is one of the major reasons expatriate managers return early from their overseas assignments, few researchers have attempted to verify empirically a relationship between the spouse's adjustment and the adjustment and intentions to stay or leave of the expatriate manager. This study found that a favorable opinion about the overseas assignment by the spouse is positively related to the spouse's adjustment and the novelty of the foreign culture has a negative relationship with the spouse's adjustment. Additionally, the adjustment of the spouse is highly correlated to the adjustment of the expatriate manager and the adjustment of the spouse and the expatriate are positively related to the expatriate's intention to stay in the overseas assignment.
miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers, including inflammation. Here, new data show that deleting microRNA-155 (miR-155) affects both mechanisms and improves repair and functional recovery after SCI. Macrophages lacking miR-155 have altered inflammatory capacity, which enhances neuron survival and axon growth of cocultured neurons. In addition, independent of macrophages, adult miR-155 KO neurons show enhanced spontaneous axon growth. Using either spinal cord dorsal column crush or contusion injury models, miR-155 deletion improves indices of repair and recovery. Therefore, miR-155 has a dual role in regulating spinal cord repair and may be a novel therapeutic target for SCI and other CNS pathologies.
Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease

Human umbilical vein endothelial cells (HUVECs) were used to gain insight into the molecular mechanism whereby the major extracellular protease from group A streptococci damages host tissue. HUVECs exposed to streptococcal cysteine protease (SCP) for various times exhibited cytopathic effect and cell detachment from the culture vessel. Gelatin substrate zymography showed that a time- and concentration-dependent increase in the level of activity of an approximately 66-kDa gelatinase occurred in culture medium taken from cells exposed to enzymatically active SCP. This gelatinase comigrated in gelatin zymograms with the activated form of purified recombinant matrix metalloprotease 2 (MMP-2) and had type IV collagenase activity. In contrast, medium taken from cells exposed to inactivated (boiled) SCP and cells exposed to SCP inhibited by treatment with N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethyl ketone lacked the 66-kDa gelatinase. Appearance of the 66-kDa gelatinase activity was also prevented by 1,10-phenanthroline, a zinc chelator and MMP inhibitor. Inasmuch as proteolytically active SCP is required for the emergence of this gelatinase and MMP activation occurs by proteolytic processing, the 66-kDa gelatinase may be a proteolytic cleavage product of a latent MMP expressed extracellularly by HUVECs. Direct SCP treatment of culture supernatant taken from HUVECs not exposed to SCP also produced the 66-kDa gelatinase. The data show that SCP activates an MMP produced by human endothelial cells, a process that may contribute to endothelial cell damage, tissue destruction, and hemodynamic derangement observed in some patients with severe, invasive group A streptococcal infection.
STAT3 activation contributes directly to Epstein‐Barr virus–mediated invasiveness of nasopharyngeal cancer cells in vitro

Nasopharyngeal cancer (NPC) is an Epstein‐Barr virus (EBV)‐associated head and neck cancer prevalent in Asia. Although with reasons not fully understood, the intrinsic invasiveness of NPC is believed to be EBV‐linked. Recently, EBV was found to induce STAT3 activation. Constitutive STAT3 activation correlated with advanced clinical staging in NPC. We hypothesized that STAT3 activation by EBV directly contributes to the intrinsic invasiveness of NPC cells. Phospho‐STAT3‐Tyr705 was detected in high percentage of NPC tumors (7/10 cases). Using a paired NPC cell line model, HONE‐1 and the EBV‐infected counterpart, HONE‐1‐EBV, we found that HONE‐1‐EBV expressed a higher level of phospho‐STAT3‐Tyr705 and was ∼11‐fold more invasive than HONE‐1. In HONE‐1‐EBV, STAT3 siRNA targeting inhibited both spontaneous and serum‐induced invasion, as well as cell growth. Conversely, activation of STAT3 (by expressing an activated STAT3 mutant, namely STAT3C) in the parental HONE‐1, mimicking EBV‐induced STAT3 activation, significantly enhanced its invasiveness and proliferation, which was accompanied by increased expression of markers of mesenchymal status, proliferation and anti‐apoptosis. Our results demonstrated that EBV‐induced STAT3 activation is responsible for NPC cell proliferation and invasion. This was further confirmed by a small molecule inhibitor of JAK/STAT3, JSI‐124. JSI‐124 inhibited STAT3 activation in HONE‐1‐EBV, with subsequent growth inhibition, induction of PARP cleavage, abrogation of anchorage‐independent growth and invasion. We found that EBV‐independent activation of STAT3 by a growth factor, EGF, also contributed to NPC invasion. In conclusion, EBV‐induced STAT3 activation directly contributes to the intrinsic invasiveness of NPC cells and STAT3 targeting may be beneficial in treating aggressive NPC. © 2009 UICC
Residential differentiation in Victorian cities: a reassessment

The extent to which residential differentiation existed in mid-Victorian Liverpool and Leeds is reassessed in an attempt to reconcile conflicting interpretations of residential separation that have been put forward by various research workers. It is suggested that patterns of residential differentiation assume greater value when viewed in the context of their significance and meaning for Victorian society. Examples of the economic, environmental and social significance of residential differentiation are discussed as illustrations of the themes that may be explored: it is stressed that the impact of differentiation varied greatly over space and time, and that residential separation could assume different kinds of significance at various levels of Victorian society. Although comprehensive data sources may be difficult to obtain attempts to link the pattern and process of residential differentiation to its significance and meaning are likely to pay substantial dividends by furthering our understanding of Victorian urban society.
Histamine production during the anti-allograft response. Demonstration of a new lymphokine enhancing histamine synthesis

Histamine production is greatly increased during culture of allograft recipient spleen cells in the presence of immunizing cells (secondary mixed leukocyte cultures [MLC]) as compared to that found in primary MLC (i.e., without previous allograft). This phenomenon appears after 24 h of culture and reaches its maximum at 48 h. Optimal increased histamine production is observed when MLC is performed with spleen cells removed from mice during rejection. This increased production of histamine during secondary MLC results from the action of a lymphokine: the histamine-producing cell stimulating factor (HCSF). This factor is released by T lymphocytes. Its production requires specific stimulation of the recipient lymphocytes because increase in histamine production during secondary MLC can be only observed when recipient cells are cultured with stimulating cells bearing at least one homology at K or D loci with immunizing cells. HCSF acts on a cell which is present in bone marrow, spleen, blood, and peritoneal cells but absent in thymus or lymph node cells. This target cell is found in the less-dense layer of a discontinuous Ficoll-gradient of bone marrow cells. HCSF is heat stable, destroyed by trypsin treatment, and has a molecular weight between 50,000 and 100,000. It acts on its target cells by increasing histidine decarboxylase activity.
A KINETIC DESCRIPTION OF PARTICLE FRAGMENTATION

This paper is concerned with the formulation and analysis of particle fragmentation by a mathematical approach of the kinetic theory. We consider a fairly general model which may require a description of the internal configuration of each particle, like internal energy. The fragmentation process is assumed to occur due to the configuration of the corresponding particle; an easy modification would allow one to consider the interaction with some external medium (typically a fluid) but we do not deal with fragmentation processes induced by particles collision here. The proposed model is therefore linear and may be analyzed with the use of correct entropies.
Towards formal analysis of security protocols

The pioneering and well-known work of M. Burrows, M. Abadi and R. Needham (1989), (the BAN logic) which dominates the area of security protocol analysis is shown to take an approach which is not fully formal and which consequently permits approval of dangerous protocols. Measures to make the BAN logic formal are then proposed. The formalisation is found to be desirable not only for its potential in providing rigorous analysis of security protocols, but also for its readiness for supporting a computer-aided fashion of analysis. <<ETX>>
Enhancing fish tank VR

Fish tank VR systems provide head coupled perspective projected stereo images on a display device of limited dimensions that resides at a fixed location. Therefore, fish tank VR systems provide only a limited virtual workspace. As a result, such systems are less suited for displaying virtual worlds that extend beyond the available workspace and depth perception problems arise when displaying objects (virtually) located on the edge of the workspace in between the viewer and the display screen. In this paper we present two techniques to reduce this disadvantage: cadre viewing and amplified head rotations. The first aims to eliminate the problems in depth perception for objects with negative parallax touching the screen surround. Subjective observations from an informal user study indicate a reduction of confusion in depth perception. The second provides a transparent navigation technique to allow users to view larger portions of the virtual world without the need for an additional input device to navigate. A user study shows it performs equally well when compared to a technique based on the use of an additional spatial input device.
Post‐marketing studies: the Italian CRONOS project

As scientific coordinators of the CRONOS project, we were very surprised to read the letter from Bianchetti et al. (2003) presented as a comment on the paper of Winblad et al. (2001) two years after its publication. The title of the letter refers to the Italian CRONOS project even if the authors simply present a case series of 420 AD patients of the area Brescia-Cremona. From this point of view, considerations made by Bianchetti et al. cannot be generalized to the CRONOS project. As for the results of the Brescia-Cremona case series, they are presented in a misleading way. In fact, the authors do not report the number of patients still on treatment at the end of the nine-month observation period. Thus, changes in MMSE scores seem to derive from the entire population and not from the proportion of patients able to complete the study. Moreover, the authors show to be not fully aware of the aims of the CRONOS project and, in general, of the post-marketing surveillance studies. It’s widely held that randomized controlled clinical trials are the ‘gold standard’ to assess drug efficacy as it’s held that knowledge on drug toxicity and effectiveness must rely mainly on observational studies. In fact, typical trial procedures assure internal validity of results but often limit their generalizability. Pre-registrative trials (explanatory trials) are always conducted on the minimum number of patients and in the minimum time necessary to observe the outcome. As a consequence, infrequent or long term adverse drug reactions can hardly be observed. Patients are enrolled through restrictive eligibility criteria (as lack of serious concomitant illnesses) and receive better care, even in the placebo arm, than any patient in the real world. When a new drug is marketed the doubt remains if it will ‘work’ in the same way in the everyday practice and if the benefit/risk profile will remain still favourable. Even more attention is required for drugs with new mechanism of action for serious pathologies such as AchE-I for dementia and TNF-blockers in rheumatology. These kind of drugs are generally introduced fast to the market and, then, it is mandatory for National Health Authorities to follow their use and effects in the real world. Recently, to improve knowledge on new drug therapies, Italian Health Authorities have promoted and funded several multicenter observational studies. These efforts were aimed to: characterize the population of patient treated; monitor effectiveness and drug safety in the field practice; identify variables which may predict the best response to therapies. CRONOS, for which we are completing the final data analysis, is one of these nationwide projects.
A qualitative exploration of higher self-efficacy string students preparing for a competition

This study examined and qualitatively described the music practice behaviors, strategies, and thoughts of four high school string students who indicated a high string playing self-efficacy. Concepts of practice, motivation, achievement, and self-efficacy were linked together to analyze tendencies and summarize strategies. These students were chosen from previous research where eight high and eight low self-efficacy string students were narrowed and compared after 101 string students’ self-efficacy scores were determined and 65 of those correlated to achievement. Each of the four students for the current study was videotaped practicing, interviewed, and given a two-week practice journal. Triangulation was used for reliability. The participants in this study were higher self-efficacy students who had common elements that enabled them to succeed, such as studying with expert teachers, practicing outside of orchestra at school and home, and owning a quality instrument. Practice strategies varied and were qual.
Establishing semantic relationships across languages using word vectors

In this paper, we improvise an existing word vector based machine translation system to measure semantic relatedness across languages and apply it to the language pair of English and Hindi. We also evaluate the model using human scored word relatedness datasets. Unlike most systems performing a similar task, the system does not make use of parallel corpora, which are cumbersome and not practical to build between all possible pairs of languages. The system learns a linear transformation between multidimensional word vector spaces of a pair of languages using a set of known translations, called a bilingual dictionary. An approach to reduce the effort in building a usable bilingual dictionary in the system is also proposed.
Comparative double blind clinical trial of phenytoin and sodium valproate as anticonvulsant prophylaxis after craniotomy: efficacy, tolerability, and cognitive effects

OBJECTIVE To determine the efficacy, tolerability, and impact on quality of life and cognitive functioning of anticonvulsant prophylaxis with phenytoin or sodium valproate in patients after craniotomy. METHODS A prospective, stratified, randomised, double blind single centre clinical trial was performed, comparing two groups of 50 patients each, who underwent craniotomy for different pathological conditions and who were treated for 1 year after surgery with either 300 mg phenytoin/day or 1500 mg sodium valproate/day. During the study period patients were seen in the outpatient clinic at 1.5, 3, 6, and 12 months, when medical history, adverse events, and drug plasma concentrations were evaluated. Neuropsychological functioning and quality of life were assessed on the last three visits. In cases of a seizure an EEG was performed, drug plasma concentration assessed, and medication subsequently increased. RESULTS Of the 100 included patients 14 (seven in each group) experienced one or more postoperative seizures. Severity of the seizures was comparable in the two groups. In all patients, drug plasma concentrations were in the low or subtherapeutic ranges at the time of the first postoperative seizure. Five patients in the phenytoin group and two in the valproate group had to stop their treatment due to drug related adverse events. Sixty patients completed the 12 month period. Analysis of neuropsychological and quality of life data showed no significant differences. CONCLUSION For efficacy, tolerability, impact on cognitive functioning, and quality of life, no major differences were found between phenytoin and valproate prophylaxis. Valproate is an alternative for anticonvulsant prophylaxis in patients after craniotomy.