Engineering near infrared single photon emitters in ultrapure silicon carbide

Quantum emitters hosted in crystalline lattices are highly attractive candidates for quantum information processing, secure networks and nanosensing. For many of these applications it is necessary to have control over single emitters with long spin coherence times. Such single quantum systems have been realized using quantum dots, colour centres in diamond, dopants in nanostructures and molecules . More recently, ensemble emitters with spin dephasing times on the order of microseconds and room-temperature optically detectable magnetic resonance have been identified in silicon carbide (SiC), a compound being highly compatible to up-to-date semiconductor device technology. So far however, the engineering of such spin centres in SiC on single-emitter level has remained elusive. Here, we demonstrate the control of spin centre density in ultrapure SiC over 8 orders of magnitude, from below $10^{9}$ to above $10^{16} \,$cm$^{-3}$ using neutron irradiation. For a low irradiation dose, a fully photostable, room-temperature, near infrared (NIR) single photon emitter can clearly be isolated, demonstrating no bleaching even after $10^{14}$ excitation cycles. Based on their spectroscopic fingerprints, these centres are identified as silicon vacancies, which can potentially be used as qubits, spin sensors and maser amplifiers.Comment: 5 pages, 4 figure

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Pleckstrin homology domain leucine-rich repeat protein phosphatases set the amplitude of receptor tyrosine kinase output

Growth factor receptor levels are aberrantly high in diverse cancers, driving the proliferation and survival of tumor cells. Understanding the molecular basis for this aberrant elevation has profound clinical implications. Here we show that the pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) suppresses receptor tyrosine kinase (RTK) signaling output by a previously unidentified epigenetic mechanism unrelated to its previously described function as the hydrophobic motif phosphatase for the protein kinase AKT, protein kinase C, and S6 kinase. Specifically, we show that nuclear-localized PHLPP suppresses histone phosphorylation and acetylation, in turn suppressing the transcription of diverse growth factor receptors, including the EGF receptor. These data uncover a much broader role for PHLPP in regulation of growth factor signaling beyond its direct inactivation of AKT: By suppressing RTK levels, PHLPP dampens the downstream signaling output of two major oncogenic pathways, the PI3 kinase/AKT and the Rat sarcoma (RAS)/ERK pathways. Our data are consistent with a model in which PHLPP modifies the histone code to control the transcription of RTKs

TRIGA-SPEC: A setup for mass spectrometry and laser spectroscopy at the research reactor TRIGA Mainz

The research reactor TRIGA Mainz is an ideal facility to provide neutron-rich nuclides with production rates sufficiently large for mass spectrometric and laser spectroscopic studies. Within the TRIGA-SPEC project, a Penning trap as well as a beam line for collinear laser spectroscopy are being installed. Several new developments will ensure high sensitivity of the trap setup enabling mass measurements even on a single ion. Besides neutron-rich fission products produced in the reactor, also heavy nuclides such as 235-U or 252-Cf can be investigated for the first time with an off-line ion source. The data provided by the mass measurements will be of interest for astrophysical calculations on the rapid neutron-capture process as well as for tests of mass models in the heavy-mass region. The laser spectroscopic measurements will yield model-independent information on nuclear ground-state properties such as nuclear moments and charge radii of neutron-rich nuclei of refractory elements far from stability. This publication describes the experimental setup as well as its present status.Comment: 20 pages, 17 figure

Influences of physical oceanographic processes on chlorophyll distributions in coastal and estuarine waters of the South Atlantic Bight

Coastal and estuarine waters of the South Atlantic Bight are highly productive, with primary production of 600-700 gC/m2/y. While controls and fate of this production are conceptually well understood, the importance of meteorology and physical circulation processes on phytoplankton has not received equivalent attention. Here, we describe the effects of wind stress and tidal currents on temporal and spatial distributions of phytoplankton biomass represented as chlorophyll a (chl a). Moored instruments were deployed and shipboard sampling was conducted in the North Edisto estuary (South Carolina) and adjacent inner shelf waters during four, two-week field studies in May and August 1993, and June and September 1994. Local wind regimes induced upwelling- and downwelling-favorable conditions which strengthened or reduced vertical density stratification in the coastal frontal zone, respectively, and shifted the location of the front. Chl a in shelf waters was more or less homogenous independent of the wind regime, while chl a on the estuary delta was generally vertically stratified. Within the estuary, chl a concentrations were positively correlated with the alongshore component of wind stress; chl a was not correlated with the weaker cross-shelf component of wind stress. Highest chl a occurred during strong downwelling-favorable events. The quick response time to wind forcing (6-12 hrs) implied a direct effect on chl a distributions and not a stimulation of growth processes. The source of the elevated chl a in response to wind forcing was apparently resuspension of settled and epibenthic algal cells. Tidal currents also influenced the vertical distribution and concentration of chl a. Time series sampling on the estuary delta showed that, with increasing velocity of ebb and flood tide currents, the relative contributions of pennate and centric diatoms with attached detritus and sand grains also increased, indicating that tidal resuspension of settled and epibenthic microalgae also occurred. Vertical stratification of chl a (highest concentrations near the bottom) began to degrade upon mixing by tidal currents with velocities as low as 10 cm/sec. Homogenization of 5-7 m water columns was fully achieved at velocities of 20-30 cm/sec. The data document the direct and comparatively immediate (timescales of minuteshours) impact of tidal and wind energy on concentrations and distribution patterns of phytoplankton in coastal and estuarine waters of the South Atlantic Bight

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

COMPARISON OF DIFFERENT STYLES OF SWINE FINISHING FACILITIES WITHIN A UNIFORM PRODUCTION SYSTEM

Swine originating from one farrowing and nursery source were grown in five different finishing facility types. Three of the facilities were considered contemporary styles and two facilities were based on older technologies. The total data set included information collected on 46,408 pigs from 25 groups. The three contemporary facility styles included a fully slatted, hybrid ventilated facility; a fully slatted tunnel ventilated facility; and a partially slatted naturally ventilated facility. These newer facilities were compared to an older, less environmentally controlled facility and an outdoor feeding lot. No significant differences were observed in production performance of the three styles of newer buildings (p \u3e 0.05). Significant differences were found in feed efficiency (p \u3c 0.05), days to market (p \u3c 0.10), and yield (p \u3c 0.05) among all (new and old) facility types. Feed efficiency and yield were found to be significantly better in the newer rather than the older facilities (p \u3c 0.05). Average daily gain (ADG) for the new facilities was found to be significantly different (p \u3c 0.05) by season of the year. The variation in death loss, feed efficiency, and ADG appeared to be relatively consistent among the different styles of finishing facilities. A basic cost analysis showed that the production cost differences among the three styles of contemporary finishing facilities is small and therefore decisions on the type of building should be based more on management preferences than cost savings

Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study

BackgroundBiliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT). However, standardized practices for BTC are lacking, and there is a need to assess the impact of current MDT treatment decisions on BTC outcomes. The purpose of this study was to investigate the role of the treatment plan proposed by the first MDT conference on survival in patients with BTC, and to identify risk factors for poor survival in this population.MethodThis nationwide, multicenter, retrospective cohort study examined data from the Danish Liver Cancer Group (2013–2020) with confirmed BTC diagnoses. Multiple imputation was used to handle missing data. Survival and variable-survival rate relationships were analyzed using the Kaplan-Meier estimator, and the Cox regression model, respectively.ResultsEligible BTC-confirmed cases: n=1923. The overall median survival was 7.7 months (95 % CI: 7.1–8.5), with a 5-year survival rate of 16.3 %. Patients over 70 years of age, with ECOG-PS 3 or 4, non-operable cases, and with unresectable tumors had lower survival rates. Surgery as the first therapeutic option showed the highest median survival (33.1 months, 95 % CI: 27.2–41.6; p < 0.0001). Multivariable analysis showed that poor ECOG-PS, palliative and neoadjuvant chemotherapy, stereotactic radiotherapy, and best supportive care significantly increased mortality risk in patients with BTC (p=0.05).ConclusionAmong the therapeutic options prescribed by the MDT for patients with BTC, surgery offered the best survival rates, likely due to patient-related prognostic factors. High ECOG-PS was linked to an increased mortality risk regardless of age, highlighting the importance of this criterion in treatment decisions

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Diverse motif ensembles specify non-redundant DNA binding activities of AP-1 family members in macrophages

Mechanisms by which members of the AP-1 family of transcription factors play non-redundant biological roles despite recognizing the same DNA sequence remain poorly understood. To address this question, here we investigate the molecular functions and genome-wide DNA binding patterns of AP-1 family members in primary and immortalized mouse macrophages. ChIP-sequencing shows overlapping and distinct binding profiles for each factor that were remodeled following TLR4 ligation. Development of a machine learning approach that jointly weighs hundreds of DNA recognition elements yields dozens of motifs predicted to drive factor-specific binding profiles. Machine learning-based predictions are confirmed by analysis of the effects of mutations in genetically diverse mice and by loss of function experiments. These findings provide evidence that non-redundant genomic locations of different AP-1 family members in macrophages largely result from collaborative interactions with diverse, locus-specific ensembles of transcription factors and suggest a general mechanism for encoding functional specificities of their common recognition motif