Miracle-dz/UniFAR-FTUs huggingface dataset:
EVOLUTION OF β‐GLUCURONIDASE REGULATION IN THE GENUS MUS

Despite the central role suggested for regulatory mutations in many evolutionary scenarios, there is relatively little information available about the type and extent of regulatory differences between species, or to what extent differences between species are independent of variation within species. To address this issue we have studied the regulatory system of β‐glucuronidase, a gene implicated in a murine androgen‐inducible pheromone‐signalling system. We examined the changes in β‐glucuronidase hormonal regulation which have occurred during the radiation of a group of 12 closely related species of mice by assaying β‐glucuronidase activity in six different tissues after treatment with estrogen, and with androgen alone and in combination with either estrogen or growth hormone. We also examined in some detail the extent of variation in regulatory responses within species. We found extensive variation in regulatory phenotypes both within and among the species surveyed, suggesting that many of the species examined are currently polymorphic for various regulatory factors that affect inducibility of β‐glucuronidase. The variation we observed reflects changes in the ability of the β‐glucuronidase gene to respond to hormonal influences, rather than changes in aspects of the hormonal signalling system exterior to the gene. The marked differences among species in the renal and uterine responses to hormonal induction of β‐glucuronidase are not easily related to the phylogeny of the genus Mus. If hormonal induction of the gene for β‐glucuronidase is subject to natural selection, it appears to be subject to widely fluctuating selective forces. We review evidence that the apparently disorderly evolution of the hormonal responsiveness of β‐glucuronidase does not appear to be a unique property of this regulatory system. In contrast to the evolution of many protein sequences, which are tightly correlated with phylogeny and proceed at a relatively constant rate, some, perhaps many, regulatory phenotypes are in rapid evolutionary flux, providing an extensive range of phenotypes upon which selection can act.
Glycemic variability and its responses to intensive insulin treatment in newly diagnosed type 2 diabetes.

BACKGROUND Recent data show that blood glucose (BG) variability is an HbA1c-independent risk factor for diabetic complications. This study investigated the characteristics of BG variability in type 2 diabetic patients and the effect of intensive treatment. MATERIAL/METHODS Forty-eight subjects with normal glucose regulation and 69 patients with newly diagnosed type 2 diabetes were monitored using the continuous glucose monitoring system. A subset of the type 2 diabetic patients (n=23) whose HbA1c was >8.5% was monitored a second time following 2 to 3 weeks of treatment with multiple daily injections. The mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and the incremental areas above preprandial glucose values (AUCpp) were used for assessing intra-day, inter-day, and postprandial BG variability. RESULTS In type 2 diabetic patients, the MAGE, MODD, and AUCpp levels were all higher than those of subjects with normal glucose regulation (P<0.001). Multivariant regression analysis indicated that AUCpp was the main independent factor influencing MAGE (Adjusted R2=0.56), while postprandial hyperglycemia was most prominent following breakfast and less evident during lunch and dinner. After intensive treatment, significant decreases in MAGE, MODD, and AUCpp were observed (41%, 29%, and 49%, respectively, P<0.001). AUCpp after breakfast was higher than after lunch and dinner (P<0.05). In 65.2% of the subjects, peak intra-day values occurred 103+/-30 minutes after breakfast. CONCLUSIONS Minimizing glycemic variability in type 2 diabetic patients, especially postprandial glucose excursions following breakfast, may be an important aspect of glucose management.
Field Tests of the Hybrid Remotely Operated Vehicle (HROV) Light Fiber Optic Tether

The Hybrid Remotely Operated Vehicle (HROV), being designed and built by Woods Hole Oceanographic Institution (WHOI) with the support of the Space and Naval Warfare Systems Center San Diego (SSC San Diego), will provide a new level of accessibility for deep ocean research. HROV will be primarily an autonomous vehicle but will be reconfigurable to a teleoperated system by the installation of a fiber optic data link and a manipulator based work system. Development of the fiber optic link has been supported by both simulation and a series of field tests over the past 3 years. The November 2004 tests consisted of deploying two different types of fiber optic cable from an Oceanographic elevator deployed from a ship to 2000 m depth. Data collected from this test demonstrated the feasibility of using both the Fiber Optic Microcable (FOMC) and plain buffered optical fiber as a tether for the HROV. The December 2005 tests demonstrated the utility of the buffered optical fiber operating on an underwater vehicle using the WHOI ABE vehicle as a substitute for the future HROV. Five dives were made to 2000 m with real-time communication from the vehicle to the surface via the fiber. The May 2006 tests focused on the employment of a cable depressor and deployment system. Using a deep elevator as a substitute for HROV, the fiber was deployed from both the depressor and the elevator to a depth of 4200 m. Over the course of 4 deployments, over 16 km of fiber was deployed, operating for a total of 33 hours, demonstrating the feasibility of the planned approach
Oral formulations of L dopa and continuous dopaminergic stimulation

We read with interest the article by Hauser et al and your editorial on efforts to obtain continuous delivery of Ldopa (CDS). The authors described a novel formulation of L-dopa that has the capacity to provide sustained benefit over a number of hours. The use of this drug resulted in a reduction in dosing frequency but at the cost of higher doses of L-dopa. This was associated with a reduction in the number of ‘‘off’’ periods and an increase ‘‘on’’ time without troublesome dyskinesia. We recently published a similar study, but without measuring L-dopa levels. We used readily available preparations of L-dopa and combined conventional-release L-dopa with slow-release L-dopa with the addition of a COMT inhibitor. We were able to similarly reduce the number of daily doses to 3. This resulted in maintenance of normal mobility, as measured by the Timed Up and Go test, and no troublesome extra movements during ‘‘on’’ time. Theoretically it is feasible to achieve sustained dopaminergic release by combining the 2 preparations of L-dopa. In midto advanced-stage Parkinson’s disease, immediaterelease L-dopa typically works for 1.5–2.5 hours, and as the plasma level reduces, that of controlled release (CR) increases. The duration of action of CR can extend for a further 3–5 hours. The addition of entacapone can also augment the longer duration of action, as entacapone has a dual peak, which may coincide with the immediate-release form and the CR form. Tolcapone, which has a longer half-life than entacapone, would also increase the duration of action of both L-dopa preparations. The key to success with this combination is to optimize the dose for the patient on an individual basis, by microtitration, prior to titration of the dosage interval. In addition, the dose of the CR preparation needs to be adjusted upward to match the conventionalrelease dose because of the reduced bioavailability of the CR preparations. In our study microtitration of the dose, as well as the titration of dosage interval, was performed by trained nurses who first adjusted the dose amount and then the medication dosage interval based on the hourly measures of mobility using the Timed Up and Go test and the magnitude of tremor and dyskinesia. This titration method would obviate any escalation of 1 dose on the other, as would occur on a fixed schedule and therefore minimize the level of troublesome dyskinesia. Our subjects were also trained to titrate the dosage interval themselves according to their particular needs, thereby minimizing dyskinesia with long-term use. A majority of patients (78%) continued to use the combination postdischarge up to a maximum follow-up of 130 weeks. We agree that a trial investigating such a combination as an alternative method of providing CDS is warranted. Our point, however, is that this does not necessarily need to wait for the development of a different formulation of levodopa because the current forms, if combined and titrated appropriately, may be able to provide a similar outcome.
Very low threshold whispering-gallery-mode microsphere laser.

Laboratoire Kastler Brossel, Ecole Normale Supe´rieure, 24 rue Lhomond, 75231 Paris Cedex 05, France~Received 15 April 1996! We report on the realization of a whispering-gallery-mode laser based on neodymium-doped silica micro-spheres. Absorbed pump powers at threshold are as low as 200 nW. The linear variation of the threshold withthe loss factor of the cavity mode has also been observed. We discuss the potential of this system as apermanent microlaser operating with a few active ions at liquid-helium temperature. @S1050-2947~96! 50309-4#PACS number~s! : 42.55. 2f, 42.60. 2v
Impact of tobacco smoking on response to tumour necrosis factor-alpha inhibitor treatment in patients with ankylosing spondylitis: results from the Danish nationwide DANBIO registry.

OBJECTIVES To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses in patients with AS treated with their first tumour necrosis factor-alpha inhibitor (TNFi) therapy in routine care. METHODS Observational cohort study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, Cox and logistic regression analyses by smoking status (current/never/previous) were calculated for treatment adherence and BASDAI 50%/20 mm-response. Additional stratified analyses were performed for gender and TNFi-type. RESULTS Of 1576 AS patients included in the study, 1425(90%) had known smoking status (current/never/previous: 43%/41%/16%). The median follow-up time was 2.02 years (IQR 0.69-5.01). At baseline, current smokers compared with never smokers had longer disease duration (4 years (1-12)/2 years (0-10)), higher BASDAI (61 mm (47-73)/58 mm (44-70)), BASFI (53 mm (35-69)/46 mm (31-66)) and BASMI (40 mm (20-60)/30 mm (10-50)) scores (all P < 0.01). Current and previous smokers had shorter treatment adherence than never smokers (current: 2.30 years (1.81-2.79) (median (95% CI)); previous: 2.48 years (1.56-3.40), never: 4.12 years (3.29-4.95)), P < 0.0001). Similar results were found in multivariate analyses (current versus never smokers, HR 1.41 (95% CI 1.21-1.65), P < 0.001), most pronounced among men. Current smokers had poorer 6 months' BASDAI50%/20 mm-response rate than never smokers (42%/58%, P < 0.001). In multivariate analyses, current smokers had lower odds of achieving BASDAI50%/20 mm-response than never smokers, both overall (OR 0.48 (95% CI 0.35-0.65), P < 0.0001) and for the different TNFi-types (adalimumab 0.45 (0.27-0.76)/etanercept 0.24 (0.10-0.61)/infliximab 0.57 (0.34-0.95)). CONCLUSION In this study of TNFi-treated AS patients in clinical practice, current and previous smokers had significantly poorer patient-reported outcomes at baseline, shorter treatment adherence and poorer treatment response compared with never smokers.
Inflation of the esophagus and vocal tract filtering in ring doves

SUMMARY Ring doves vocalize with their beaks and nostrils closed, exhaling into inflatable chambers in the head and neck region. The source sound produced at the syrinx contains a fundamental frequency with prominent second and third harmonic overtones, but these harmonics are filtered out of the emitted signal. We show by cineradiography that the upper esophagus, oral and nasal cavities collect the expired air during vocalization and that the inflated esophagus becomes part of the suprasyringeal vocal tract. The level of the second and third harmonics, relative to the fundamental frequency (f0), is reduced in the esophagus and emitted vocalization compared with in the trachea, although these harmonics are still considerably higher in the esophagus than in the emitted signal. When the esophagus is prevented from fully inflating, there is a pronounced increase in the level of higher harmonics in the emitted vocalization. Our data suggest that the trachea and esophagus act in series as acoustically separate compartments attenuating harmonics by different mechanisms. We hypothesize that the trachea behaves as a tube closed at the syringeal end and with a variable, restricted opening at the glottal end that lowers the tracheal first resonance to match the f0 of the coo. The inflated esophagus may function as a Helmholtz resonator in which the elastic walls form the vibrating mass. Such a resonator could support the f0 over a range of inflated volumes.
Mitochondrial decay in ageing: ‘Qi‐invigorating’ schisandrin B as a hormetic agent for mitigating age‐related diseases

1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary role for mitochondrial reactive oxygen species (ROS) in the ageing process. The reductive hot spot hypothesis of mammalian ageing serves as a supplement to the MFRTA by explaining how the relatively few cells that have lost oxidative phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the rest of the body and result in the development of age‐related diseases.
Low-Loss Circularly Polarized Periodic Leaky-Wave Antenna

This letter presents a periodic leaky-wave array antenna with circular polarization at millimeter-wave frequencies. The antenna is designed on the low-loss planar Goubau transmission line to maximize the radiation efficiency of the antenna. The unit cell of the array is formed by four dipoles located on both faces of the Goubau line's substrate. A prototype has been fabricated and measured. Experimental results show an impedance bandwidth above 15% for |S11| <; -10 dB and a 3-dB axial-ratio bandwidth of 7.6%. The radiation efficiency and maximum gain of the prototype are above 90% and 15.6 dBi, respectively, from 38 to 41 GHz. The maximum gain and the minimum axial ratio present the characteristic steering behavior of leaky-wave antennas.
Exclusion of maternal uniparental disomy of chromosome 14 in patients referred for Prader-Willi syndrome using a multiplex methylation polymerase chain reaction assay

Uniparental disomy (UPD) is the inheritance of both homologues of a chromosome from one parent. For most of the autosomes, there is no definitive clinical consequence of this abnormal inheritance. However, UPDs of chromosomes 6, 7, 11, 14, and 15 are associated with abnormal phenotypes owing to overexpression or underexpression of imprinted genes on those chromosomes.1,2 Maternal UPD(14) (matUPD(14)) has been described in over 20 cases and is primarily characterised by intrauterine growth retardation and precocious puberty. Additional features can include hypotonia at birth, feeding difficulties in early infancy, short stature, musculoskeletal findings including small hands and feet and scoliosis, mild developmental delay, and early childhood obesity. Most patients with matUPD(14) are described with minor facial dysmorphism including frontal bossing, short philtrum, and high arched palate. Paternal UPD(14) (patUPD(14)) is less common, more severe, and is characterised by polyhydramnios, facial and skeletal anomalies, and severe developmental delay.3,4 Recently, Wylie et al 5 described reciprocally imprinted genes DLK1 and MEG3, positioned ~90 kb apart at 14q32, which are candidate genes for the UPD(14) phenotypes. DLK1 , a cell surface transmembrane protein, is paternally expressed, and MEG3 , which lacks an open reading frame, is maternally expressed.5 Dlk1 knockout mice show features of matUPD(14), providing evidence that many of the phenotypic consequences of matUPD(14) may be attributed to a lack of DLK1 expression in these patients.6 UPD(14) is usually ascertained through a combination of clinical features and a karyotype suggestive of UPD, such as confined placental mosaicism for trisomy 14, a non-homologous Robertsonian or reciprocal translocation involving chromosome 14, or an isochromosome 14. These karyotypes are consistent with, or predispose to, monosomy or trisomy rescue events, which are the most common mechanisms leading to UPD.2 Recently, three patients with matUPD(14) were described who were originally …
ENHANCED SELECTION FOR MHC DIVERSITY IN SOCIAL TUCO‐TUCOS

Abstract To explore the effects of behavior and demography on balancing selection at major histocompatibility complex (MHC) loci, we examined allelic diversity at exon 2 of the MHC class II DQ(3 locus in a social and a solitary species of tuco‐tuco (Rodentia: Ctenomyidae: Ctenomys), both of which occur in the same valley in southwestern Argentina. By comparing patterns of diversity at this MHC gene to the diversity evident at fifteen microsatellite loci, we demonstrate that balancing selection at the DQ(3 locus is enhanced in the social species compared to its solitary congener. These findings have intriguing implications for the role of behavioral and demographic parameters in maintaining diversity at MHC loci.
Does This Patient With Chest Pain Have Acute Coronary Syndrome?: The Rational Clinical Examination Systematic Review.

IMPORTANCE About 10% of patients with acute chest pain are ultimately diagnosed with acute coronary syndrome (ACS). Early, accurate estimation of the probability of ACS in these patients using the clinical examination could prevent many hospital admissions among low-risk patients and ensure that high-risk patients are promptly treated. OBJECTIVE To review systematically the accuracy of the initial history, physical examination, electrocardiogram, and risk scores incorporating these elements with the first cardiac-specific troponin. STUDY SELECTION MEDLINE and EMBASE were searched (January 1, 1995-July 31, 2015), along with reference lists from retrieved articles, to identify prospective studies of diagnostic test accuracy among patients admitted to the emergency department with symptoms suggesting ACS. DATA EXTRACTION AND SYNTHESIS We identified 2992 unique articles; 58 met inclusion criteria. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, and likelihood ratio (LR) of findings for the diagnosis of ACS. The reference standard for ACS was either a final hospital diagnosis of ACS or occurrence of a cardiovascular event within 6 weeks. RESULTS The clinical findings and risk factors most suggestive of ACS were prior abnormal stress test (specificity, 96%; LR, 3.1 [95% CI, 2.0-4.7]), peripheral arterial disease (specificity, 97%; LR, 2.7 [95% CI, 1.5-4.8]), and pain radiation to both arms (specificity, 96%; LR, 2.6 [95% CI, 1.8-3.7]). The most useful electrocardiogram findings were ST-segment depression (specificity, 95%; LR, 5.3 [95% CI, 2.1-8.6]) and any evidence of ischemia (specificity, 91%; LR, 3.6 [95% CI,1.6-5.7]). Both the History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) risk scores performed well in diagnosing ACS: LR, 13 (95% CI, 7.0-24) for the high-risk range of the HEART score (7-10) and LR, 6.8 (95% CI, 5.2-8.9) for the high-risk range of the TIMI score (5-7). The most useful for identifying patients less likely to have ACS were the low-risk range HEART score (0-3) (LR, 0.20 [95% CI, 0.13-0.30]), low-risk range TIMI score (0-1) (LR, 0.31 [95% CI, 0.23-0.43]), or low to intermediate risk designation by the Heart Foundation of Australia and Cardiac Society of Australia and New Zealand risk algorithm (LR, 0.24 [95% CI, 0.19-0.31]). CONCLUSIONS AND RELEVANCE Among patients with suspected ACS presenting to emergency departments, the initial history, physical examination, and electrocardiogram alone did not confirm or exclude the diagnosis of ACS. Instead, the HEART or TIMI risk scores, which incorporate the first cardiac troponin, provided more diagnostic information.
Tutorial on Metrics of User Engagement: Applications to News, Search and E-Commerce

User engagement plays a central role in companies operating online services, such as search engines, news portals, e-commerce sites, and social networks. A main challenge is to leverage collected knowledge about the daily online behavior of millions of users to understand what engage them short-term and more importantly long-term. The most common way that engagement is measured is through various online metrics, acting as proxy measures of user engagement. This tutorial will review these metrics, their advantages and drawbacks, and their appropriateness to various types of online services. As case studies, we will focus on three types of services, news, search and e-commerce. We will also briefly discuss how to develop better machine learning models to optimize online metrics, and design experiments to test these models.
A Novel Compact Printed Rectenna for Data Communication Systems

A novel design of a two-port printed microstrip rectenna with compact structure for communication systems is presented. An aperture-coupled dual polarization patch antenna is utilized as the receiving antenna. The vertical feed port receives the microwave energy and transfers it to the rectifying circuit for dc power generation, while the horizontal feed port is used for data communication, with high isolation between the two ports. This patch antenna includes harmonic suppression functionality, which is essential for high microwave—direct current (mw-dc) conversion efficiency. A co-simulation procedure using HFSS and ADS for the analysis of the rectenna and the rectifying circuit design is used. This design assumes low input power for the rectifying circuit to comply with safety standards. A mw-dc conversion efficient of 63% is measured with a 900 <formula formulatype="inline"><tex Notation="TeX">$\Omega$</tex> </formula> load, 5.78 GHz operation frequency, and 25 mW receiving power. For the communication port, the measured reflection coefficient is <formula formulatype="inline"><tex Notation="TeX">$-$</tex></formula>18 dB at 6.1 GHz center frequency, the gain is 7.0 dBi, and the cross polarization in the broadside direction is <formula formulatype="inline"><tex Notation="TeX">$-$</tex> </formula>15 dB.
L’enseignement des fractions en France et en Nouvelle- Zélande

Ce travail examine les connaissances mathematiques utilisees dans la vie courante et enseignees a l'ecole en Nouvelle-Zelande et en France en particulier concernant les fractions. Dans les pays anglo-saxons, les fractions sont abondamment utilisees, et les nombres mixtes du type 3 ½ pour 3,5 sont encore manipules. Alors qu'en France, pionniere en matiere de decimalisation, les ecritures decimales sont utilisees beaucoup plus volontiers. Ceci revele une culture mathematique differente qui aboutit a l'utilisation de notations mathematiques differentes, aussi bien dans la vie quotidienne que dans les programmes scolaires. Afin de situer notre propos, nous developpons tout d'abord certains aspects historiques concernant les fractions et les nombres decimaux. Nous examinons ensuite les differences entre la culture anglo-saxonne et francaise : d'une part en etudiant les aspects culturels et langagiers des fractions puis d'autre part en considerant les aspects didactiques de cette notion. Cette etude montre que si a priori les similitudes sont nombreuses entre l'enseignement de fractions en France et en Nouvelle-Zelande, il existe des points divergents, en particulier la programmation des instructions officielles.