Miracle-dz/UniFAR-FTUs huggingface dataset:
Different nuclease requirements for exosome-mediated degradation of normal and nonstop mRNAs

Two general pathways of mRNA decay have been characterized in yeast. In one pathway, the mRNA is degraded by the cytoplasmic form of the exosome. The exosome has both 3′ to 5′ exoribonuclease and endoribonuclease activity, and the available evidence suggests that the exonuclease activity is required for the degradation of mRNAs. We confirm here that this is true for normal mRNAs, but that aberrant mRNAs that lack a stop codon can be efficiently degraded in the absence of the exonuclease activity of the exosome. Specifically, we show that the endo- and exonuclease activities of the exosome are both capable of rapidly degrading nonstop mRNAs and ribozyme-cleaved mRNAs. Additionally, the endonuclease activity of the exosome is not required for endonucleolytic cleavage in no-go decay. In vitro, the endonuclease domain of the exosome is active only under nonphysiological conditions, but our findings show that the in vivo activity is sufficient for the rapid degradation of nonstop mRNAs. Thus, whereas normal mRNAs are degraded by two exonucleases (Xrn1p and Rrp44p), several endonucleases contribute to the decay of many aberrant mRNAs, including transcripts subject to nonstop and no-go decay. Our findings suggest that the nuclease requirements for general and nonstop mRNA decay are different, and describe a molecular function of the core exosome that is not disrupted by inactivating its exonuclease activity.
The Identification of Two Arabinosyltransferases from Tomato Reveals Functional Equivalency of Xyloglucan Side Chain Substituents1[W][OPEN]

Expression of xyloglucan arabinofuranosyltransferases, identified from tomato using a comparative genomics approach, rescues growth and mechanical defects of an Arabidopsis mutant deficient for xyloglucan galactosylation. Xyloglucan (XyG) is the dominant hemicellulose present in the primary cell walls of dicotyledonous plants. Unlike Arabidopsis (Arabidopsis thaliana) XyG, which contains galactosyl and fucosyl substituents, tomato (Solanum lycopersicum) XyG contains arabinofuranosyl residues. To investigate the biological function of these differing substituents, we used a functional complementation approach. Candidate glycosyltransferases were identified from tomato by using comparative genomics with known XyG galactosyltransferase genes from Arabidopsis. These candidate genes were expressed in an Arabidopsis mutant lacking XyG galactosylation, and two of them resulted in the production of arabinosylated XyG, a structure not previously found in this plant species. These genes may therefore encode XyG arabinofuranosyltransferases. Moreover, the addition of arabinofuranosyl residues to the XyG of this Arabidopsis mutant rescued a growth and cell wall biomechanics phenotype, demonstrating that the function of XyG in plant growth, development, and mechanics has considerable flexibility in terms of the specific residues in the side chains. These experiments also highlight the potential of reengineering the sugar substituents on plant wall polysaccharides without compromising growth or viability.
Pathogen selection drives nonoverlapping associations between HLA loci

Significance Human leukocyte antigens (HLA), first identified in tissue-matching for transplantation, play a critical role in immunity. HLAs are extraordinarily diverse, but certain sets of HLA genes are more likely to be found together than others. Here, we show that associations between HLA genes can arise through their coevolutionary interaction with pathogens. Technological advances are making it easier to determine HLA types, but DNA sequence alone cannot fully predict an HLA’s functional properties. Our work offers a new evolutionary approach to tackling this problem. Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host–pathogen systems.
Content-based audio search: from fingerprinting to semantic audio retrieval

This dissertation is about audio content-based search. Specifically, it is on exploring promising paths for bridging the semantic gap that currently prevents widedeployment of audio content-based search engines. Music search sound engines rely on metadata, mostly human generated, to manage collections of audio assets. Even though time-consuming and error-prone, human labeling is a common practice. Audio content-based methods, algorithms that automatically extract description from audio files, are generally not mature enough to provide the user friendly representation that users demand when interacting with audio content. Mostly, content-based methods provide low-level descriptions, while high-level or semantic descriptions are beyond current capabilities. This dissertation has two parts. In a first part we explore the strengths and limitation of a pure low-level audio description technique: audio fingerprinting. We prove by implementation of different systems that automatically extracted low-level description of audio are able to successfully solve a series of tasks such as linking unlabeled audio to corresponding metadata, duplicate detection or integrity verification. We show that the different audio fingerprinting systems can be explained with respect to a general fingerprinting framework. We then suggest that the fingerprinting framework, which shares many functional blocks with content-based audio search engines, can eventually be extended to allow for content-based similarity type of search, such as find similar or “query-by-example”. However, low-level audio description cannot provide a semantic interaction with audio contents. It is not possible to generate a verbose and detailed descriptions in unconstraint domains, for
Retirement, Personality, and Well‐Being

This study investigates how two sources of individual heterogeneity — personality and gender — impact the well-being effects of retirement. Using data on older men and women from the British Household Panel Survey and its continuation, Understanding Society, we estimate the causal effect of retirement on satisfaction with overall life and domains of life in the presence of personality characteristics. As retirement is often considered to be a choice and thus may be endogenous to individual-level characteristics, we use the eligibility ages for basic state pension in the United Kingdom as instruments for retirement. We find that retirement increases leisure satisfaction of both males and females but not necessarily life satisfaction and income satisfaction. We further show that certain personality characteristics affect the well-being of female retirees. For males, however, personality does not seem to matter in how they cope with retirement.
Molecular Cloning and Expression of cDNA Encoding Rat Brain Cytosolic Acyl-Coenzyme A Thioester Hydrolase (*)

The cDNA encoding rat brain cytosolic acyl-CoA thioester hydrolase (ACT) has been cloned and sequenced, and the primary structure of the enzyme has been deduced. A partial amino acid sequence (38 amino acids) of the enzyme was determined using the peptides generated after CNBr digestion of the purified enzyme. Primers synthesized on the basis of this information were used to isolate two cDNA clones, each encoding the full length of the enzyme. The nucleotide sequences of these clones contained an open reading frame encoding a 358-amino acid polypeptide with a calculated molecular mass of 39.7 kDa, similar to that determined for the purified enzyme (40.9 kDa). The deduced ACT sequence showed no homology to the known sequences of any other thioesterases nor to any other known protein sequence. However, there was a strong homology to a number of expressed sequence tag human brain cDNA clones. The identity of the ACT cDNA was confirmed by the expression of ACT activity in Escherichia coli. There was a 10-15-fold increase in ACT-specific activity in the bacterial extracts after induction with isopropyl thiogalactoside, and the properties of the expressed enzyme (fusion protein) were the same as those of the purified rat brain ACT. Northern blot analysis showed that a 1.65-kilobase ACT transcript was present in rat brain and testis but not in any other rat tissues examined. However, the ACT mRNA was induced in the liver of rats that were fed Wy-14,643, a peroxisome proliferator and inducer of rodent liver cytosolic acyl-CoA thioesterase. These results indicate that the induced rat liver ACT is homologous to the constitutive rat brain ACT.
The Sāda in History: A critical essay on Ḥaḍramī historiography

In attempting to write a religious and political history of Ḥaḍramawt in the Middle Ages one inevitably encounters a number of methodological and historiographical problems some of which will be addressed in the present article. The first arises from the overall scarcity of historical documentation on the period in question. More importantly, the sources that are available are riddled with underlying agendas and biases, which often hinge on considerations of genealogy and clannish honour. These genealogical or clannish agendas and biases are evident in the sources dealing with practically every aspect of Ḥaḍrami history. However, they are especially conspicuous in the historical texts which describe the spread of the Shāfi'ī school of law in Ḥaḍramawt, the cult of local saints and the origins of local religious and educational institutions. In my recent study of Ḥaḍramī shrines and seasonal pilgrimages, I have brought out the genealogical underpinnings of the theological polemic around the cult of local holy men and women - a polemic that grew especially intense in the first decades of our century and flared up with a vengeance during the recent civil war between the Northern and Southern parts of unified Yemen. In this paper I will demonstrate how these hidden agendas have manifested themselves in the historical accounts of Ḥaḍramī Islam with special reference to the rise of the Shāfi'ī madhhab and the dissemination of Ṣūfism.
TASTE MASKING OF PRIFINIUM BROMIDE IN ORODISPERSIBLE TABLETS

Objective: In previous work, Prifinium Bromide had been successfully formulated as oro-dispersible tablets. However, Prifinium Bromide, a quaternary ammonium compound, has a bitter taste; therefore, taste masking was necessary to produce acceptable oro-dispersible tablets and enhance patients' compliance. Methods: In this work, several attempts had been made to mask the bitterness of this drug. β-cyclodextrin inclusion complexes, solid dispersions of the drug in ethyl cellulose and methyl cellulose as well as loading the drug on Eudragit E100 have all been used. The selected granules were used to prepare oro-dispersible tablets and were evaluated. Results: Drug-Eudragit granules E3 prepared by mass extrusion method gave less than 10% of drug in simulated saliva fluid and almost complete release in simulated gastric fluid after 2 minutes. Therefore, it was used to prepare oro-dispersible tablets formulas. In vitro disintegration time of formula T2 was 45.5 ± 7.7 seconds showed a complete drug release of Prifinium Bromide in phosphate buffer (pH 6.8) and (94%) in SGF (pH 2.1). Conclusion: Loading of Prifinium Bromide on Eudragit E100 using mass extrusion method was the best method to overcome the disagreeable taste of the drug. They gave the least amount of drug released in simulated saliva fluid and passed the quality control tests of tablets after formulation as oro-dispersible tablets. They also gave good taste when tested in vivo.
Active Electrostatic Compensation of Micromechanical Resonators Under Random Vibrations

This letter presents a method of using electrostatic tuning to actively diminish the phase noise in a micromechanical oscillator that is caused by external vibrations. An accelerometer measures the acceleration applied to a micromechanical resonator and generates a compensation signal that is added to the bias voltage to remove the induced phase error. The proposed method achieves an 80.6% reduction of the acceleration sensitivity on average for a sinusoidal acceleration from 50 to 250 Hz with single-anchored double-ended tuning fork resonators. The rejection of phase noise due to random vibrations in the band from 15 to 80 Hz is also demonstrated.
The future of DNA sequencing.

This article describes the emerging technologies for rapid sequencing of DNA. Technologies discussed include the use of ultrathin gels, replaceable or reusable gels, automated systems, new types of primers to replace the current shotgun method of DNA sequencing, mass spectrometric direct sequencing technologies, and sequencing by hybridization.
Reducing in-hospital delay to 20 minutes in stroke thrombolysis

Objectives: Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset. We analyzed the effect of interventions aimed to reduce treatment delays in our single-center observational series. Methods: All consecutive ischemic stroke patients treated with IV alteplase (tissue plasminogen activator [tPA]) were prospectively registered in the Helsinki Stroke Thrombolysis Registry. A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011. In-hospital delays were analyzed as annual median door-to-needle time (DNT) in minutes, with interquartile range. Results: A total of 1,860 patients were treated between June 1995 and June 2011, which included 174 patients with basilar artery occlusion (BAO) treated mostly beyond 4.5 hours from symptom onset. In the non-BAO patients, the DNT was reduced annually, from median 105 minutes (65–120) in 1998, to 60 minutes (48–80) in 2003, further on to 20 minutes (14–32) in 2011. In 2011, we treated with tPA 31% of ischemic stroke patients admitted to our hospital. Of these, 94% were treated within 60 minutes from arrival. Performing angiography or perfusion imaging doubled the in-hospital delays. Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival. Conclusions: With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes. The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that, while the patient is being transported.
The psychological costs of unsustainable housing commitments

Background. The extended recession and stagnant housing market in the 1990s following the boom of the late 1980s resulted in more than half a million housing repossessions. This study explores the impact of unsustainable housing commitments on psychological well-being. We test the hypotheses that housing payment problems and housing arrears have adverse impacts on heads of households' psychological well-being over and above those caused by financial hardship more generally. Method. Data came from the British Household Panel Survey 1991–2003 and the samples for analysis consist of: (1) 5651 male head of households producing 26618 person-year observations, and (2) 2534 female head of households producing 9091 person-year observations. Summary statistics and multivariate, fixed effects regression models are used. Mental health was measured by the 12-item General Health Questionnaire. Results. For male heads of households housing payment problems and entering arrears have significant detrimental effects on mental well-being and for female heads of households longer-term housing payment problems and arrears have significant detrimental effects on mental well-being. The sizes of these effects are in addition to and larger in magnitude than those associated with financial hardship more generally. The net effects appear to be relatively stable over the time of the panel data. Conclusions. This study provides evidence that housing payment problems have independent psychological costs over and above those associated with general financial hardship. The magnitude of the effect is similar to that shown for marital breakdown and job loss.
Frame recursive dynamic mean bias removal technique for robust environment-aware speech recognition in real world applications

In this paper, we investigated and simulated the frame recursive dynamic mean bias removing technique in the cepstral domain with a time smoothing parameter in order to improve the robustness of automatic speech recognition (ASR) in realtime environments. The objective of this simulation was to examine the suitability of the frame recursive cepstral mean bias removal technique as a part of an effort to develop single channel joint additive noise and channel distortion compensation (JAC) algorithm in feature space for real-world applications. The Aurora2 speech corpus was used in this simulation. The simulation results show that the frame recursive dynamic mean bias removal technique performs better in real-time scenarios compared to conventional approaches (non real-time) to improve the robustness of ASR under noisy conditions.
Prevalence of alcohol use disorders among American surgeons.

OBJECTIVES To determine the point prevalence of alcohol abuse and dependence among practicing surgeons. DESIGN Cross-sectional study with data gathered through a 2010 survey. SETTING The United States of America. PARTICIPANTS Members of the American College of Surgeons. MAIN OUTCOME MEASURES Alcohol abuse and dependence. RESULTS Of 25,073 surgeons sampled, 7197 (28.7%) completed the survey. Of these, 1112 (15.4%) had a score on the Alcohol Use Disorders Identification Test, version C, consistent with alcohol abuse or dependence. The point prevalence for alcohol abuse or dependence for male surgeons was 13.9% and for female surgeons was 25.6%. Surgeons reporting a major medical error in the previous 3 months were more likely to have alcohol abuse or dependence (odds ratio, 1.45; P < .001). Surgeons who were burned out (odds ratio, 1.25; P = .01) and depressed (odds ratio, 1.48; P < .001) were more likely to have alcohol abuse or dependence. The emotional exhaustion and depersonalization domains of burnout were strongly associated with alcohol abuse or dependence. Male sex, having children, and working for the Department of Veterans Affairs were associated with a lower likelihood of alcohol abuse or dependence. CONCLUSIONS Alcohol abuse and dependence is a significant problem in US surgeons. Organizational approaches for the early identification of problematic alcohol consumption followed by intervention and treatment where indicated should be strongly supported.
Power Loss and Switching Noise Reduction Techniques for Single-Inductor Multiple-Output Regulator

A new gate drive circuit to reduce the power loss and switching noise of single-inductor-multiple-output regulators is presented. Efficiency degradation and switching noise induced by the cross-talk of the voltages and currents within the power stage and buffer are analyzed. A shoot-through-current (STC) controlled buffer with four-transistor (4T) inverters is presented, and the 4T inverter enables internal STC control and generates two outputs with dead-time. To further isolate the cross-talk, two separate high voltage selectors (HVS) with the proposed buffer are used to power the buffer and the power P-MOSFET body, respectively. Simulation results show that the peak and average currents of the proposed buffer are smaller and much less sensitive to the buffer size than those of the traditional inverter based buffer. Two single-inductor-dual-output boost converters with and without the proposed techniques have been fabricated in a 0.35- μm CMOS process. Experimental results show that the maximum efficiency is increased from 87.8% to 91.6% with the proposed technique.
Determination of the maximum specific uptake capacities for glucose and oxygen in glucose-limited fed-batch cultivations of Escherichia coli.

A simple pulse-based method for the determination of the maximum uptake capacities for glucose and oxygen in glucose limited cultivations of E. coli is presented. The method does not depend on the time-consuming analysis of glucose or acetate, and therefore can be used to control the feed rate in glucose limited cultivations, such as fed-batch processes. The application of this method in fed-batch processes of E. coli showed that the uptake capacity for neither glucose nor oxygen is a constant parameter, as often is assumed in fed-batch models. The glucose uptake capacity decreased significantly when the specific growth rate decreased below 0.15 h(-1) and fell to about 0.6 mmol g(-1) h(-1) (mmol per g cell dry weight and hour) at the end of fed-batch fermentations, where specific growth rate was approximately 0.02 h(-1). The oxygen uptake capacity started to decrease somewhat earlier when specific growth rate declined below 0.25 h(-1) and was 5 mmol g(-1) h(-1) at the end of the fermentations. The behavior of both uptake systems is integrated in a dynamic model which allows a better fitting of experimental values for glucose in fed-batch processes in comparison to generally used unstructured kinetic models.
Metrics in the development and maintenance of software: an application in a large scale environment

The importance of metrics in software projects is well known. Assessing and controlling quality and productivity in large scale environments requires the establishment of software measurement systems for both products and processes. Product and process measurements should be considered simultaneously to assess software projects effectively. Unfortunately, measurement programs are rarely carried out extensively in practice or they just provide a limited set of sample data. This paper reports experience with software measurement systems gained in a large scale environment and describes an approach whereby product and process measurements can be jointly used to assess and control project evolution. In the paper, data collection and data analysis techniques are presented to describe a solution for a real organization. Insights into how to make decisions about software projects and set the goals for improvement are made. Copyright © 2000 John Wiley & Sons, Ltd.