Miracle-dz/UniFAR-FTUs huggingface dataset:
An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans

Two small temporal RNAs (stRNAs), lin-4 andlet-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed withlet-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.
Hedge Fund Activism April

This paper examines a large, nearly universal sample of hedge fund activism between January 1, 2003 and December 31, 2005. Hedge fund activism is when a hedge fund files a 13D filing after taking an initial stake of 5 percent or more in the company, and clearly states in the filing’s “purpose” section that it intends to proactively influence management’s future decisions. We find that hedge funds have engaged in successful and profitable activist campaigns against a large group of publicly-traded companies. Over 60 percent of the time, they are successful in getting existing management to acquiesce to their demands, be it representation on the firm’s board, a change in strategic operations, share repurchases by the firm, scuttling an existing merger proposal, or being acquired by another firm (sometimes the hedge fund itself). We also present evidence that the paradigm of shareholder activism does not apply to hedge funds. First, unlike previous studies on blockholder activism, hedge funds target profitable and healthy firms, firms with above-average cash holdings. Second, they earn significantly higher abnormal stock returns around the initial 13D filing date than a sample of control firm. Third, they do not improve the accounting performances of firms in the year after the initial purchase – in fact, both EPS and ROA decline in the fiscal year after the activism. Fourth, they appear to extract cash from the firm through increasing the debt capacity of the target firm and paying themselves higher dividends. Examination of proxy fights and threats accompanying the activist campaign suggests that hedge fund managers achieve their goals by posing a credible threat of engaging the target in a costly proxy solicitation contest.
Evolutionary conservation of an atypical glucocorticoid‐responsive element in the human tyrosine hydroxylase gene

The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at −7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein‐1 (AP‐1)‐like motif in the rat TH gene. We cloned this hTH‐CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH‐CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5′‐TGACTAA at −7243 bp completely abolished the Dex‐stimulated Luc activity of hTH‐CRII construct. The AP‐1 agonist, tetradeconoyl‐12,13‐phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP‐1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid‐responsive element in a 7 bp AP‐1‐like motif in the promoter region at −7.24 kb of the human TH gene.
Alternating repetition time balanced steady state free precession

A novel balanced SSFP technique for the separation or suppression of different resonance frequencies (e.g., fat suppression) is presented. The method is based on applying two alternating and different repetition times, TR1 and TR2. This RF scheme manipulates the sensitivity of balanced SSFP to off‐resonance effects by a modification of the frequency response profile. Starting from a general approach, an optimally broadened stopband within the frequency response function is designed. This is achieved with a TR2 being one third of TR1 and an RF‐pulse phase increment of 90°. With this approach TR2 is too short (∼1 ms) to switch imaging gradients and is only used to change the frequency sensitivity. Without a significant change of the spectral position of the stopband, TR1 can be varied over a range of values (∼2.5–4.5 ms) while TR2 and phase cycling is kept constant. On‐resonance spins show a magnetization behavior similar to balanced SSFP, but with maximal magnetization at flip angles about 10° lower than in balanced SSFP. The total scan time is increased by about 30% compared to conventional balanced SSFP. The new technique was applied on phantoms and volunteers to produce rapid, fat suppressed images. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Mass screening for silent atrial fibrillation in high risk patients - preliminary results from the STROKESTOP trial

Background: Atrial fibrillation (AF) is a frequent source of cardiac emboli in patients with ischemic stroke. AF may be asymptomatic and therefore undiagnosed. As oral anticoagulation (OAC) treatment is highly effective for stroke prevention, screening for silent AF seems suitable in risk populations. Above the age of 75, the current guidelines recommend OAC for AF, even in the absence of other risk factors. We hypothesize that AF screening in this age group will reduce stroke incidence. Methods: All inhabitants in Stockholm County and Region Halland, Sweden age 75-76 years (n=25 415) are randomized in a 1:1 fashion either to be invited to a screening program for AF or to act as a control group. In the screening group, participants are invited to undergo intermittent ambulatory ECG recordings during two weeks. Participants in whom AF is detected are offered OAC treatment. Screening-and control groups will be followed prospectively for 5 years with regard to thromboembolic events, bleeding and mortality. Results: During a 10- month period, 10 503 inhabitants in the screening arm had been invited and 4783 (46%) participated. Previously undiagnosed AF was found in 131 (3%) of participants and another 85 (2%) have been identified with previously known AF but without OAC treatment. The total prevalence of AF in the screening group exceeds 11%. Participation in the screening program is lower in urban Stockholm (45%) in comparison to rural areas (64%). More than 90% of the patients with undiagnosed AF were started on OAC. Conclusion: Population based AF screening in a 75-year old population identifies 5% of the population as new candidates for OAC treatment due to AF. There is considerable local and regional variation in participation in the screening program.
Ligand-assisted Aggregation of Proteins

A comprehensive series of solution and crystallographic studies reveal how simple, achiral, bivalent ligands of the cyclic pyruvate of glycerol promote face-to-face complex formation of the pentraxin, serum amyloid P component (SAP) into decamers. SAP, a protein of the human innate immune system, is universally present in amyloids, including cerebral amyloid deposits found in the brain of Alzheimer disease patients. Removal of SAP through a specific aggregation mechanism mediated by multivalent ligands appears to provide therapeutic benefit in the progression of this disease. Crystallographic studies reveal that in our novel series of ligands only the methyl and carboxylate moieties of the pyruvate ketal directly interact with the protein, but the geometric constraints imposed by the tether dictate which of two chair conformations are adopted by the pyruvate dioxane ring. Solution studies, as interpreted through a simple thermodynamic model, account for the distribution of pentameric and decameric bound states at different ligand concentrations and indicate that differences in the flexibility of the tether determine the geometry and stability of the specific aggregates formed between SAP and two different bivalent ligands. The factors affecting the design of ligands promoting face-to-face protein dimerization as well as potential biological implications are discussed.
Image denoising based on learning over-complete dictionary

The sparse and redundant representations of signal theory have aroused extensive and deep research in recent years, and been widely applied to image processing. Aiming to study the performance and suitability of the sparse and redundant representations in image denoising, our paper introduces a sparse and redundant representations algorithm based on over-complete learned dictionary to process different types of images. We use the K-SVD denoising framework and modify its initial dictionary, and then mainly focus on using it to study its denoising performance and suitability for different types of images, and then compare it with some other image denoising algorithms. As to the remote sensing images denoising, the experiment results show that the K-SVD algorithm can leads to the state-of-art denoising performance at low noisy levels, but for high noisy levels, its performance isn't good on PSNR and visual effect, that is it cannot retain the local details of images.
The Promoter for Constitutive Expression of the Human ICln Gene CLNS1A *

The ICln protein is expressed ubiquitously in mammals. Experiments designed to knock down the ICln protein in NIH 3T3 fibroblasts as well as in epithelial cells led to the conclusion that this protein is crucially involved in volume regulation after cytoplasmic swelling. Reconstitution of the ICln protein in lipid bilayers revealed the ion channel nature of ICln. Here we describe a new human promoter sequence, composed of 89 nucleotides, which is responsible for a highly constitutive expression of the ICln protein. The promoter sequence lacks a TATA box, and the transcription can be effected at multiple sites. In addition to the starting sites, upstream sequence elements are mandatory for an efficient transcription of the ICln gene (CLNS1A). These new nucleotide elements were defined by site-directed mutagenesis.
A Differential-Algebraic Riccati Equation for Applications in Flow Control

We investigate existence and structure of solutions to quadratic control problems with semiexplicit differential-algebraic constraints as they appear in the modeling of flows. We introduce a decoupled representation of the state and the formal adjoint equations to identify the conditions for the existence of solutions. We derive a differential-algebraic Riccati equation formulated in the original coefficients for the efficient numerical computation of the optimal solution.
Developmentally regulated expression during gametogenesis of the murine gene meg1 suggests a role in meiosis

Previous studies have shown that in adult male mice, expression of the meg1 gene is restricted to meiotic and early postmeiotic testicular germ cells. We have now analyzed the expression of meg1 during postnatal testicular development and the comparable meiotic stages in the female. The 0.75 kb transcript for meg1 begins to accumulate in testes at d8‐9 of postnatal (pn) development, coincident with the entry of germ cells into meiosis, and is expressed most abundantly at pn d14 and subsequent stages, when the spermatocytes have entered pachytene. In situ hybridization analysis shows that meg1 is expressed at very low levels in leptotene cells and increases as the cells progress through zygotene and pachytene stages. In the embryonic ovary, meg1 is not detected until after day 15 of gestation when the cells have entered the pachytene stage of meiosis I. In situ hybridization analysis suggests that meg1 transcripts are expressed at higher levels in degenerating rather than in healthy pachytene stage oocytes; meg1 is not expressed in any cells of the adult ovary, regardless of the stage of follicular development. These results suggest that meg1 is indeed a meiosis‐associated gene in both male and female germ cells through the pachytene stage of meiosis I and appears to exhibit sex‐specific differences in its expression thereafter. © 1994 Wiley‐Liss, Inc.
Developing Reusable and Reconfigurable Real-Time Software using Aspects and Components

Our main focus in this thesis is on providing guidelines, methods, and tools for design, configuration, and analysis of configurable and reusable real-time software, developed using a combination of aspect-oriented and component-based software development. Specifically, we define a reconfigurable real-time component model (RTCOM) that describes how a real-time component, supporting aspects and enforcing information hiding, could efficiently be designed and implemented. In this context, we outline design guidelines for development of real-time systems using components and aspects, thereby facilitating static configuration of the system, which is preferred for hard real-time systems. For soft real-time systems with high availability requirements we provide a method for dynamic system reconfiguration that is especially suited for resourceconstrained real-time systems and it ensures that components and aspects can be added, removed, or exchanged in a system at run-time. Satisfaction of real-time constraints is essential in the real-time domain and, for real-time systems built of aspects and components, analysis is ensured by: (i) a method for aspectlevel worst-case execution time analysis; (ii) a method for formal verification of temporal properties of reconfigurable real-time components; and (iii) a method for maintaining quality of service, i.e., the specified level of performance, during normal system operation and after dynamic reconfiguration. We have implemented a tool set with which the designer can efficiently configure a real-time system to meet functional requirements and analyze it to ensure that non-functional requirements in terms of temporal constraints and available memory are satisfied. In this thesis we present a proof-of-concept implementation of a configurable embedded real-time database, called COMET. The implementation illustrates how our methods and tools can be applied, and demonstrates that the proposed solutions have a positive impact in facilitating efficient development of families of realtime systems.
Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.

Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2. 1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy. Comparable to rucaparib development, other PARP inhibitors, such as olaparib, niraparib, veliparib and talazoparib, are developing CDx tests for targeted therapy. PARP inhibitor clinical trials and CDx assays are discussed in this review, as are potential PARP inhibitor combination therapies and likely resistance mechanisms.
Selected Aspects of Perinatal Casualties

Presented in part at the Third Annual Conference on Neonatal-Perinatal Medicine, Reno, Nevada, May 18-20, 1978. * Professor and Chairman, Maternal and Child Health Program, and Family Health Program, University of California School of Public Health, Berkeley, California. THE relatively high infant and perinatal morbidity and mortality rates in the United States today still represent one of our country’s major public health problems. Because of this, it is timely to review certain aspects of the present status, analyze recent national efforts, and comment on possible future directions and emphases.
Potassium currents in rat prevertebral and paravertebral sympathetic neurones: control of firing properties.

1. Intracellular recordings were made from rat sympathetic neurones in isolated superior cervical ganglia (SCG), coeliac ganglia (CG) and superior mesenteric ganglia (SMG). 2. Based on their response to a maintained depolarizing current stimulus, neurones were classified as ‘phasic’ or ‘tonic’. All neurones in the SCG were phasic, 85% of the neurones in the SMG and 58% of the neurones in the CG were tonic, and the remainder were phasic. 3. The voltage response of phasic and tonic neurones around threshold to a constant current step was markedly different. The response of phasic neurones was biphasic with an initial depolarizing response followed by significant repolarization of the membrane potential. In contrast, tonic neurones became more depolarized during a prolonged current step. 4. The underlying currents were studied using single‐electrode voltage‐clamp recording. The M‐current was present in all phasic neurones, but was very weak or absent in tonic neurones. 5. An A‐current was apparent in both phasic and tonic neurones. The voltage‐dependent activation, steady‐ state inactivation, and current density of the A‐current were all similar in phasic and tonic cells. 6. A low‐ threshold, slowly inactivating outward current (D2‐current) was observed exclusively in tonic neurones. The slow inactivation of this current appeared to underlie the slow depolarizing ramp seen in response to a maintained depolarizing current step. 7. Computer simulations, based on the voltage‐clamp data, suggested that the different firing properties of phasic and tonic neurones could be accounted for by differential expression of the M‐current.
Akt , AS 160 , metabolic risk factors and aerobic fitness in middle-aged women

Aims: This study investigated the association between the basal (rest) insulin-signaling proteins, Akt, and the Akt substrate AS160, metabolic risk factors, inflammatory markers and aerobic fitness, in middle-aged women with varying numbers of metabolic risk factors for type 2 diabetes. Methods: Sixteen women (n=16) aged 51.3±5.1 (mean ±SD) years provided muscle biopsies and blood samples at rest. In addition, anthropometric characteristics and aerobic power were assessed and the number of metabolic risk factors for each participant was determined (IDF criteria). Results: The mean number of metabolic risk factors was 1.6±1.2. Total Akt was negatively correlated with IL-1β (r = −0.45, p = 0.046), IL-6 (r = −0.44, p = 0.052) and TNF-α (r = −0.51, p = 0.025). Phosphorylated AS160 was positively correlated with HDL (r = 0.58, p= 0.024) and aerobic fitness (r = 0.51, p=0.047). Furthermore, a multiple regression analysis revealed that both HDL (t=2.5, p=0.032) and VO2peak (t=2.4, p=0.037) were better predictor for phosphorylated AS160 than TNF-α or IL-6 (p>0.05). Conclusions: Elevated inflammatory markers and increased metabolic risk factors may inhibit insulin-signaling protein phosphorylation in middle-aged women, thereby increasing insulin resistance under basal conditions. Furthermore, higher HDL and fitness levels are associated with an increase AS160 phosphorylation, which may in turn reduce insulin resistance.
Exhaled nitric oxide is reduced after sputum induction in asthmatic children

Exhaled nitric oxide (ENO) and eosinophil sputum markers are considered noninvasive markers of airway inflammation in asthma. The aim of this study was to evaluate whether the procedure of sputum induction can affect the level of ENO. We measured ENO before and after sputum induction by inhalation of hypertonic saline solution in 22 asthmatic children and 9 healthy controls.
ASPHERICITY, INTERACTION, AND DUST IN THE TYPE II-P/II-L SUPERNOVA 2013EJ IN MESSIER 74

SN 2013ej is a well-studied core-collapse supernova (SN) that stemmed from a directly identified red supergiant (RSG) progenitor in galaxy M74. The source exhibits signs of substantial geometric asphericity, X-rays from persistent interaction with circumstellar material (CSM), thermal emission from warm dust, and a light curve that appears intermediate between supernovae of Types II-P and II-L. The proximity of this source motivates a close inspection of these physical characteristics and their potential interconnection. We present multiepoch spectropolarimetry of SN 2013ej during the first 107 days and deep optical spectroscopy and ultraviolet through infrared photometry past ∼800 days. SN 2013ej exhibits the strongest and most persistent continuum and line polarization ever observed for a SN of its class during the recombination phase. Modeling indicates that the data are consistent with an oblate ellipsoidal photosphere, viewed nearly edge-on and probably augmented by optical scattering from circumstellar dust. We suggest that interaction with an equatorial distribution of CSM, perhaps the result of binary evolution, is responsible for generating the photospheric asphericity. Relatedly, our late-time optical imaging and spectroscopy show that asymmetric CSM interaction is ongoing, and the morphology of broad Hα emission from shock-excited ejecta provides additional evidence that the geometry of the interaction region is ellipsoidal. Alternatively, a prolate ellipsoidal geometry from an intrinsically bipolar explosion is also a plausible interpretation of the data but would probably require a ballistic jet of radioactive material capable of penetrating the hydrogen envelope early in the recombination phase. Finally, our latest space-based optical imaging confirms that the late interaction-powered light curve dropped below the stellar progenitor level, confirming the RSG star’s association with the explosion.
Arctangent-Based Extended State Observer with Terminal Attractor

Aiming at the numerous adjustable parameters, poor chattering attenuation ability and unsystematic parameter tuning method of arctangent-based extended state observer (AESO), an arctangent-based extended state observer with terminal attractor (AESOT) is designed. By introducing the terminal attractor in sliding mode control, ESO could obtain a better interference rejection ability and a fewer quantity of adjustable parameters. Then, the parameter tuning method of AESOT is summarized by frequency domain analysis. Finally, the simulations include the testing for the estimated ability with the measurement noise and a typical application for AESOT in aircraft pitch angle controller. The simulation results show that the estimated ability, disturbance rejection ability and chattering attenuation ability for the second-order signal and disturbing signal of AESOT are better. And AESOT can be applied in the pitch angle controller.