Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in the SF1-U2AF59-U2AF23 Complex Cause Exon Skipping in Schizosaccharomyces pombe*

To identify genes involved in the mechanism to ensure ordered 5′ to 3′ exon joining in constitutively spliced pre-mRNAs, we screened for mutants that cause exon skipping in the fission yeast Schizosaccharomyces pombe using a reporter plasmid, which contains the ura4+ gene with the nda3 intron 1-exon 2-intron 2 sequence. The reporter plasmid was designed to produce the functional ura4+ mRNA, when the central nda3 exon is skipped during the splicing reaction. We mutagenized cells harboring the plasmid by UV irradiation and isolated 34 ura+ mutants that grew on minimal medium. Of those, eight mutants were found to be temperature sensitive (ts) for growth. Complementation analyses revealed that the ts mutants belong to three distinct complementation groups named ods (ordered splicing) 1, 2, and 3. RT-PCR analyses showed that products of exon skipping were actually generated in the ods mutants. We cloned the genes responsible for the ods mutations, and found that ods1+, ods2+, and ods3+ encode splicing factors Prp2p/U2AF59, U2AF23, and SF1, respectively, which form a SF1-U2AF59-U2AF23 complex involved in recognition of the branch-point and 3′ splice site sequences in a pre-mRNA. We also showed that mutations in the SF1-U2AF59-U2AF23 binding sequences in the reporter plasmid result in exon skipping in wild-type S. pombe cells. In addition, drugs that decrease the rate of transcription elongation were found to suppress the exon skipping in the ods mutants. These results suggest that co-transcriptional recognition of a nascent pre-mRNA by the SF1-U2AF59-U2AF23 complex is essential for ordered exon joining in constitutive splicing in S. pombe.
Adversarial Multi-Armed Bandit Approach to Stochastic Optimization

We first present a sampling-based algorithm for solving stochastic optimization problems based on the Exp3 algorithm by Auer et al for "adversarial multi-armed bandit problems. " The value returned by the algorithm is an upper-bound estimate of the sample-average-maximum for a sample average approximation (SAA) problem induced by the sampling process of the algorithm, and the estimate converges to the optimal objective-function value as the number of samples goes to infinity. We then recursively extend the Exp3-based algorithm for solving a given finite-horizon Markov decision process (MDP) and analyze its finite-time performance in terms of the expected bias relative to the maximum value of the induced recursive SAA problem, showing that the upper bound of the expected bias approaches zero as the sampling size per stage goes to infinity, leading to the convergence to the optimal value of the original MDP problem in the limit
Context-dependent female mate choice maintains variation in male sexual activity

The existence of individual variation in males' motivation to mate remains a conundrum as directional selection should favour high mating frequencies. Balancing selection resulting from (context-dependent) female mate choice could contribute to the maintenance of this behavioural polymorphism. In dichotomous choice tests, mosquitofish (Gambusia holbrooki) females preferred virtual males showing intermediate mating frequencies, reflecting females' tendencies to avoid harassment by highly sexually active males. When tested in the presence of a female shoal—which protects females from male harassment—focal females showed significantly stronger preferences for high sexual activity. A trade-off between (indirect) benefits and (direct) costs of mating with sexually active males probably explains context-dependent female mate choice, as costs depend on the social environment in which females choose their mates. No preference was observed when we tested virgin females, suggesting that the behavioural pattern described here is part of the learned behavioural repertoire of G. holbrooki females.
Fresh Osteochondral Allografts for Patellofemoral Arthritis: Long-term Followup

Treatment of patellofemoral osteoarthritis in young patients is a challenge for orthopaedic surgeons. Concern about loosening and wear in active young people render arthroplasty more suitable for older patients. Osteochondral allografts may be a good alternative, but reports of experience with such grafts in patellofemoral joints are limited. We retrospectively reviewed our results with fresh osteochondral allografts. Our hypothesis was that these grafts provide relief from osteoarthritis, improve knee function, and delay prosthetic knee replacement. From 1986 to 1999, 14 fresh patellofemoral or patellar allografts were implanted in knees of 11 patients younger than 55 years and diagnosed with advanced secondary osteoarthritis. At last followup (average, 10 years; range, 2.5-17.5 years), eight grafts were in place, four for more than 10 years and two for more than 5 years. Of the nonsurviving allografts, three survived more than 10 years. Radiographs of the knees with intact allografts showed mild or no degenerative changes. Average Knee Society scores improved (preoperative to last followup), with knee scores improving from 46 points (range, 38-60 points) to 82 points (range, 35-100 points) and functional scores from 30 points (range, 10-60 points) to 75 points (range, 20-100 points). Fresh osteochondral allografts can provide relief from the arthritic condition, improve knee function, and delay prosthetic knee replacement.Level of Evidence: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.
Chip‐based microfluidic devices coupled with electrospray ionization‐mass spectrometry

We present the current status of the development of microfluidic devices fabricated on different substrates for coupling with electrospray ionization‐mass spectrometry (ESI‐MS). Until now, much success has been gained in fabricating the ESI chips, which show better performances due to miniaturization when compared with traditional methods. Integration of multiple steps for sample preparation and ESI sample introduction, however, remains a great challenge. This review covers the main technical development of electrospray device that were published from 1997 to 2004. This article does not attempt to be exclusive. Instead, it focuses on the publications that illustrated the breath of the development and applications of microchip devices for MS‐based analysis.
Fast Blind Adaptive Beamforming Algorithm With Interference Suppression

A fast blind adaptive beamforming algorithm is proposed in code-division multiple-access wireless systems based on an array pattern synthesis approach. By incorporating an interference suppression mechanism in the iterative procedure, the proposed algorithm outperforms conventional blind algorithms. Two practical adaptive beamforming algorithms are further presented, which provide fast convergence speed with low complexity. The simulation results demonstrate the effectiveness of the proposed adaptive beamforming algorithms in various signal environments.
Wave-front aberration modeling based on wavelet methods

Wave-front aberration has serious adverse influence on the efficiency of optical system whose modeling problem is of great importance for further research. In this paper, wavelet method, which has a broad application in signal analysis, is used to model wave-front aberration. As the basis of wavelet method, the selection of basis function is the primary step for signal reconstruction, and two types of wave-front aberration are studied in this paper. First, for general wave-front aberration, a selection algorithm is given by comparing the minimum Mean Square Error (MSE). Secondly we take into account the primary wave-front aberration represented by finite Zernike polynomials, a simplified selection algorithm is proposed via minimum Maximum Mean Error Ratio (MMER) criterion. Numerical results shows that basis function selection algorithm via minimum MMER criterion can ensure the modeling accuracy, and it costs much smaller calculation than minimum MSE criterion.
Preventing domestic violence

Papers pp 271, 274 Domestic violence can be physical, sexual, or psychological. Physical and sexual violence by an intimate partner are common problems, affecting 20-50% of women at some stage in life in most populations surveyed globally.1 Between 3% and 50% of women have experienced it in the past year.1 Domestic violence has a profound impact on the physical and mental health of those who experience it. As well as injuries, it is associated with an increased risk of a range of physical and mental health problems and is an important cause of mortality from injuries and suicide.2 Review of international literature on risk of domestic violence shows that although it is greatest in relationships and communities where the use of violence in many situations is normative, notably when witnessed in childhood, it is substantially a product of gender inequality and the lesser status of women compared with men in society.3 Except for poverty, few social and demographic characteristics define risk groups. Poverty increases vulnerability through increasing relationship conflict, reducing women's economic and educational power, and reducing the ability of men to live in a manner that they regard as successful. Violence is used frequently to resolve a crisis of male identity. Domestic violence is often associated …
Prevalence of asymptomatic incidental aneurysms: review of 4568 arteriograms.

OBJECT The prevalence of unruptured cerebral aneurysms is unknown, but is estimated to be as high as 5%. The goal of this study was to determine the prevalence of asymptomatic incidental aneurysms. METHODS The authors studied all cerebral arteriography reports produced at a single institution, the University of Virginia, between April 1969 and January 1980. A review of 3684 arteriograms demonstrated 24 cases of asymptomatic aneurysms, yielding a prevalence rate of 0.65%. The majority (67%) of the 24 patients harboring unruptured aneurysms were women. More than 90% of the unruptured aneurysms were located in the anterior circulation and in locations similar to those found in patients with ruptured aneurysms. Nearly 80% of the aneurysms were smaller than 1 cm in their greatest diameter. The frequency of asymmetrical unruptured aneurysms (0.6-1.5%) was constant throughout all relevant age ranges (35-84 years). CONCLUSIONS While keeping in mind appropriate caveats in extrapolating from these data, the prevalence rate of asymptomatic unruptured aneurysms found in the present study allows an estimation of the yearly rate of rupture of these lesions. The authors suggest that this yearly rate of rupture falls within the range of 1 to 2%.
Optimal design of pulsed arterial spin labeling MRI experiments

Quantitative measurement of cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI requires the acquisition of multiple inversion times (TIs) and the application of an appropriate kinetic model. The choice of these sampling times will have an impact on the precision of the estimated parameters. Here, optimal sampling schedule (OSS) design techniques, based on the Fisher Information approach, are applied in order to derive an optimal sampling scheme for pulsed arterial spin labeling (PASL) experiments. Such an approach should improve the precision of parameter estimation from experimental data, and provide a formal framework for optimally selecting a limited number of samples. In this study, we aimed to optimize the estimation precision of CBF and bolus arrival time from the PASL data. The performance of OSS was compared to a more standard evenly distributed sampling schedule (EDS) using both simulated and measured experimental data sets. It was found that OSS was able to significantly improve the precision of parameter estimation in PASL studies that sought to estimate either both CBF and bolus arrival time, or CBF alone. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
Regulated Phosphorylation of a Major UDP-glucuronosyltransferase Isozyme by Tyrosine Kinases Dictates Endogenous Substrate Selection for Detoxification*

Whereas UDP-glucuronosyltransferase-2B7 is widely distributed in different tissues, it preferentially detoxifies genotoxic 4-OH-estradiol and 4-OH-estrone (4-OHE1) with barely detectable 17β-estradiol (E2) conversion following expression in COS-1 cells. Consistent with the UDP-glucuronosyltransferase requirement for regulated phosphorylation, we discovered that 2B7 requires Src-dependent tyrosine phosphorylation. Y236F-2B7 and Y438F-2B7 mutants were null and 90% inactive, respectively, when expressed in COS-1. We demonstrated that 2B7 incorporated immunoprecipitable [33P]orthophosphate and that 2B7His, previously expressed in SYF-(Src,Yes,Fyn)−/− cells, was Src-supported or phosphorylated under in vitro conditions. Unexpectedly, 2B7 expressed in SYF−/− and SYF+/− cells metabolized 4-OHE1 at 10- and 3-fold higher rates, respectively, than that expressed in COS-1, and similar analysis showed that E2 metabolism was 16- and 9-fold higher than in COS-1. Because anti-Tyr(P)-438–2B7 detected Tyr(P)-438–2B7 in each cell line, results indicated that unidentified tyrosine kinase(s) (TKs) phosphorylated 2B7 in SYF−/−. 2B7-transfected COS-1 treated with increasing concentrations of the Src-specific inhibitor PP2 down-regulated 4-OHE1 glucuronidation reaching 60% maximum while simultaneously increasing E2 metabolism linearly. This finding indicated that increasing PP2 inhibition of Src allows increasing E2 metabolism caused by 2B7 phosphorylation by unidentified TK(s). Importantly, 2B7 expressed in SYF−/− is more competent at metabolizing E2 in cellulo than 2B7 expressed in COS-1. To confirm Src-controlled 2B7 prevents toxicity, we showed that 2B7-transfected COS-1 efficiently protected against 4-OH-E1-mediated depurination. Finally, our results indicate that Src-dependent phosphorylation of 2B7 allows metabolism of 4-OHE1, but not E2, in COS-1, whereas non-Src-phosphorylated 2B7 metabolizes both chemicals. Importantly, we determined that 2B7 substrate selection is not fixed but varies depending upon the TK(s) that carry out its required phosphorylation.
The pCa‐tension and force‐velocity characteristics of skinned fibres isolated from fish fast and slow muscles

1. Single fast fibres and small bundles of two to six slow fibres were dissected from the myotomal muscles of the cod, Gadus morhua, and the dogfish, Scyliorhinus canicula. Fibres were chemically skinned with the non‐ionic detergent Brij 58.
Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6

The dominantly inherited spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive gait ataxia, upper limb incoordination, and dysarthria. We studied a six‐generation kindred of Norwegian ancestry with pure cerebellar ataxia inherited in an autosomal dominant pattern. All affected family members had a slowly progressive cerebellar ataxia, with an age of onset range from 26 to 60 years. Brain magnetic resonance imaging study of 11 affected patients showed that atrophy was confined to the cerebellum. After excluding all the known SCAs using linkage analysis or direct mutation screen, we conducted a genomewide genetic linkage scan. With the aid of a novel linkage analysis strategy, we found linkage between the disease locus and marker D19S591 and D19S1034. Subsequent genetic and clinical analysis identified a critical region of 15.55cM interval on chromosome 19p13.3, flanked by markers D19S886 and D19S894, and have established a new genetic locus designated SCA26. The SCA26 locus is adjacent to the genes for Cayman ataxia and SCA6. The region consists of 3.3 million base pairs (Mb) of DNA sequences with approximately 100 known and predicted genes. Identification of the responsible gene for SCA26 ataxia will provide further insight into mechanisms of neurodegeneration. Ann Neurol 2005;57:349–354
Akt inhibition improves irinotecan treatment and prevents cell emergence by switching the senescence response to apoptosis

Activated in response to chemotherapy, senescence is a tumor suppressive mechanism that induces a permanent loss of proliferation. However, in response to treatment, it is not really known how cells can escape senescence and how irreversible or incomplete this pathway is. We have recently described that cells that escape senescence are more transformed than non-treated parental cells, they resist anoikis and rely on Mcl-1. In this study, we further characterize this emergence in response to irinotecan, a first line treatment used in colorectal cancer. Our results indicate that Akt was activated as a feedback pathway during the early step of senescence. The inhibition of the kinase prevented cell emergence and improved treatment efficacy, both in vitro and in vivo. This improvement was correlated with senescence inhibition, p21waf1 downregulation and a concomitant activation of apoptosis due to Noxa upregulation and Mcl-1 inactivation. The inactivation of Noxa prevented apoptosis and increased the number of emergent cells. Using either RNA interference or p21waf1-deficient cells, we further confirmed that an intact p53-p21-senescence pathway favored cell emergence and that its downregulation improved treatment efficacy through apoptosis induction. Therefore, although senescence is an efficient suppressive mechanism, it also generates more aggressive cells as a consequence of apoptosis inhibition. We therefore propose that senescence-inducing therapies should be used sequentially with drugs favoring cell death such as Akt inhibitors. This should reduce cell emergence and tumor relapse through a combined induction of senescence and apoptosis.
Enhanced Area of Secondary Hyperalgesia in Women with Multiple Stressful Life Events: A Pilot Study.

OBJECTIVE Stressful life events are associated with increased pain severity and chronicity. However, the mechanism underlying this association remains disputed. Recent animal studies suggest that chronic stress increases pain sensitivity and persistence by enhancing peripheral and central sensitization mechanisms. To test this hypothesis in humans, the authors examined whether sensitization is enhanced in healthy women reporting more stressful life events using the topical capsaicin test. METHODS Thirty-two healthy young women reporting varying levels of stressful life events were invited for laboratory pain testing. Capsaicin was applied topically to the volar forearm. Measurements included capsaicin-induced spontaneous pain and area of secondary hyperalgesia in the region surrounding capsaicin application. Physiological (heart rate and skin conductance) and self-reported affective (emotional valence and arousal) states were also measured. RESULTS The results indicate that more stressful life events predicted a linear increase in the area of secondary hyperalgesia (β = 0.40, p = 0.023, R2 = 0.16), but not the intensity of secondary hyperalgesia nor capsaicin-induced spontaneous pain. These findings suggest that life stressors may be associated with heightened central sensitization manifested by an increased area of secondary hyperalgesia. Additionally, life stressors were related to greater sympathetic cardiac, but not to affective responses to capsaicin-induced pain. CONCLUSION This study shows that women reporting more stressful life events show a larger area of secondary mechanical hyperalgesia. These preliminary findings suggest that life stressors may facilitate pain processing by enhancing central sensitization.
A Modularized Equalization Method Based on Magnetizing Energy for a Series-Connected Lithium-Ion Battery String

A single charge equalizer using the multi-winding transformer (SCEMT) is useful for the precise and fast equalization. Since this type of equalizer requires voltage sensing circuits for each battery cell, the size and cost of the overall equalizer system increase. In this paper, a novel switching method, which does not require voltage sensing circuits, is proposed for the SCEMT. However, due to the problems related to the implementation of multiwinding in a single transformer, the SCEMT is definitely difficult to apply to long series-connected lithium-ion battery string. In order to overcome these drawbacks, a novel module charge equalizer based on the configuration of the SCEMT is developed. Unlike the conventional module charge equalizer using additional components, the proposed novel module charge equalizer utilizes the magnetizing energy of the multiwinding transformer for the equalization among modules. Therefore, proposed module charge equalizer does not suffer from the size, cost, and loss related to the modularization. The validity of the proposed module charge equalizer is verified through experimental results.
Development of the Mobile Phone Attachment Scale

Existing instruments that assess the individual's relationship with technology tend to focus on negative constructs and assume that a high use of technology reflects pathology. Since technology use can be beneficial, there is a need for a more balanced instrument. An initial survey to assess the individual's relationship with their mobile phone was developed, checked for face validity and the resulting survey was administered online to students at local colleges. 146 adults (mean age=25.5 years) completed surveys. Principal Component Analysis with varimax rotation produced a final 27-item scale with factor loadings from . 50 to . 81, representing 4 components: "Usefulness", "Anxious Attachment", "Addiction" and "24/7" (continuous use). This study produced an instrument to assess multiple aspects of the individuals' relationship to their mobile phone. Additional work is needed to validate this measure in other populations, with larger samples, and to assess its predictive ability in mHealth interventions delivered through mobile phones.
Posttraumatic stress disorder and metabolic syndrome: retrospective study of repatriated prisoners of war.

OBJECTIVE We conducted a retrospective study of metabolic data for Vietnam-era repatriated prisoners of war (RPWs) and a comparison group to determine if metabolic syndrome (MbS) was more common in those individuals with clinically diagnosed, current or lifetime posttraumatic stress disorder (PTSD) as suggested in a recent report. METHODS The metabolic data of our patients nearest the time of psychiatric evaluation (1998-2004) for PTSD were analyzed using both an analysis of variance and logistic regression. RESULTS Although we found elevated triglyceride levels (40 mg/dl higher) in RPWs with PTSD who met MbS criteria, overall the prevalence of MbS was the same in RPWs with and without PTSD and comparison group. Moreover, current PTSD symptom severity did not increase the likelihood of MbS. CONCLUSIONS Our results from these repatriates who actively participate in a 37-year medical follow up program do not support the conclusion that MbS occurs more commonly in individuals with current PTSD.