Next-generation plasmids for transgenesis in zebrafish and beyond

Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible, modular system. Here, we established several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene-regulatory element testing, we generated Gateway middle entry vectors harboring the small mouse beta-globin minimal promoter coupled to several fluorophores, CreERT2, and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein mCerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3' vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Lastly, we established Tol2 destination vectors carrying the zebrafish exorh promoter driving different fluorophores as a pineal gland-specific transgenesis marker active prior to hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish, and other models

Next-generation plasmids for transgenesis in zebrafish and beyond

Transgenesis is an essential technique for any genetic model. Tol2-based transgenesis paired with Gateway-compatible vector collections has transformed zebrafish transgenesis with an accessible, modular system. Here, we established several next-generation transgenesis tools for zebrafish and other species to expand and enhance transgenic applications. To facilitate gene-regulatory element testing, we generated Gateway middle entry vectors harboring the small mouse betaglobin minimal promoter coupled to several fluorophores, CreERT2, and Gal4. To extend the color spectrum for transgenic applications, we established middle entry vectors encoding the bright, blue-fluorescent protein Cerulean and mApple as an alternative red fluorophore. We present a series of p2A peptide-based 3' vectors with different fluorophores and subcellular localizations to co-label cells expressing proteins of interest. Lastly, we established Tol2 destination vectors carrying the zebrafish exorh promoter driving different fluorophores as a pineal gland-specific transgenesis marker active prior to hatching and through adulthood. exorh-based reporters and transgenesis markers also drive specific pineal gland expression in the eye-less cavefish (Astyanax). Together, our vectors provide versatile reagents for transgenesis applications in zebrafish, cavefish, and other models

Becoming Physically Active After Bariatric Surgery is Associated With Improved Weight Loss and Health-Related Quality of Life

The purpose of this study was to determine whether pre- to postoperative increases in physical activity (PA) are associated with weight loss and health-related quality of life (HRQoL) following bariatric surgery. Participants were 199 Roux-en-Y gastric bypass (RYGB) surgery patients. The International Physical Activity Questionnaire (IPAQ) was used to categorize participants into three groups according to their preoperative and /1-year postoperative PA level: (i) Inactive/Active (\u3c200-min/week/≥200-min/week), (ii) Active/Active (≥200-min/week/greater ≥200-min/week) and (iii) Inactive/Inactive (\u3c200-min/week/\u3c200-min/week). The Medical Outcomes Study Short Form-36 (SF-36) was used to assess HRQoL. Analyses of covariance were conducted to examine the effects of PA group on weight and HRQoL changes. Inactive/Active participants, compared with Inactive/Inactive individuals, had greater reductions in weight (52.5 ± 15.4 vs. 46.4 ± 12.8 kg) and BMI (18.9 ± 4.6 vs. 16.9 ± 4.2 kg/m2). Weight loss outcomes in the Inactive/Active and Active/Active groups were similar to each other. Inactive/Active and Active/Active participants reported greater improvements than Inactive/Inactive participants on the mental component summary (MCS) score and the general health, vitality and mental health domains (P \u3c 0.01). Although the direction of causation is not clear, these findings suggest that RYGB patients who become active postoperatively achieve weight losses and HRQoL improvements that are greater than those experienced by patients who remain inactive and comparable to those attained by patients who stay active. Future randomized controlled trials should examine whether assisting patients who are inactive preoperatively to increase their PA postoperatively contributes to optimization of weight loss and HRQoL outcomes

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain

<p>Abstract</p> <p>Background</p> <p>Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients.</p> <p>Methods</p> <p>We studied 103 patients, mean 56.7 ± 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization.</p> <p>Results</p> <p>In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%.</p> <p>Conclusion</p> <p>AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.</p

The Accuracy of the Electrocardiogram during Exercise Stress Test Based on Heart Size

BACKGROUND: Multiple studies have shown that the exercise electrocardiogram (ECG) is less accurate for predicting ischemia, especially in women, and there is additional evidence to suggest that heart size may affect its diagnostic accuracy. HYPOTHESIS: The purpose of this investigation was to assess the diagnostic accuracy of the exercise ECG based on heart size. METHODS: We evaluated 1,011 consecutive patients who were referred for an exercise nuclear stress test. Patients were divided into two groups: small heart size defined as left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart size defined as LVEDV ≥65 mL (Group B) and associations between ECG outcome (false positive vs. no false positive) and heart size (small vs. normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. LVEDV calculations were performed via a computer-processing algorithm. SPECT myocardial perfusion imaging was used as the gold standard for the presence of coronary artery disease (CAD). RESULTS: Small heart size was found in 142 patients, 123 female and 19 male patients. There was a significant association between ECG outcome and heart size (χ(2) = 4.7, p = 0.03), where smaller hearts were associated with a significantly greater number of false positives. CONCLUSIONS: This study suggests a possible explanation for the poor diagnostic accuracy of exercise stress testing, especially in women, as the overwhelming majority of patients with small heart size were women

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Final report on LDRD project 52722 : radiation hardened optoelectronic components for space-based applications.

This report describes the research accomplishments achieved under the LDRD Project 'Radiation Hardened Optoelectronic Components for Space-Based Applications.' The aim of this LDRD has been to investigate the radiation hardness of vertical-cavity surface-emitting lasers (VCSELs) and photodiodes by looking at both the effects of total dose and of single-event upsets on the electrical and optical characteristics of VCSELs and photodiodes. These investigations were intended to provide guidance for the eventual integration of radiation hardened VCSELs and photodiodes with rad-hard driver and receiver electronics from an external vendor for space applications. During this one-year project, we have fabricated GaAs-based VCSELs and photodiodes, investigated ionization-induced transient effects due to high-energy protons, and measured the degradation of performance from both high-energy protons and neutrons

Calibration of the CMS Drift Tube Chambers and Measurement of the Drift Velocity with Cosmic Rays

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