A Light‐Induced Decarboxylative‐Elimination of Substituted Maleimides as a Strategy Towards Triggered Photorelease

Herein we report on photodecarboxylations of various substituted maleimides, resulting in an elimination reaction. Furthermore, we establish facile wavelength tunability through modulation of the maleimide double bond substituents. We envisage that these versatile reagents, which are readily constructed and diversified by nucleophilic substitution reactions on bromomaleimides, will offer new opportunities for triggered photorelease

DNA hybridization to mismatched templates: a chip study

High-density oligonucleotide arrays are among the most rapidly expanding technologies in biology today. In the {\sl GeneChip} system, the reconstruction of the target concentration depends upon the differential signal generated from hybridizing the target RNA to two nearly identical templates: a perfect match (PM) and a single mismatch (MM) probe. It has been observed that a large fraction of MM probes repeatably bind targets better than the PMs, against the usual expectation from sequence-specific hybridization; this is difficult to interpret in terms of the underlying physics. We examine this problem via a statistical analysis of a large set of microarray experiments. We classify the probes according to their signal to noise ($S/N$) ratio, defined as the eccentricity of a (PM, MM) pair's `trajectory' across many experiments. Of those probes having large $S/N$ ($>3$) only a fraction behave consistently with the commonly assumed hybridization model. Our results imply that the physics of DNA hybridization in microarrays is more complex than expected, and they suggest new ways of constructing estimators for the target RNA concentration.Comment: 3 figures 1 tabl

Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient’s clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.

Microfungal composition in an Astelia-Donatia cushion Peatland in Tierra del Fuego, Argentina

En el Hemisferio Sur las turberas almacenan grandes cantidades de carbono en el suelo. A pesar de su importancia en el ciclo global del carbono, se sabe poco acerca de los procesos de descomposición y su diversidad fúngica. El presente estudio se realizó para describir la composición de hongos filamentosos en dos profundidades de una turbera compacta donde las especies vegetales predominantes son Astelia (Asteliaceae) y Donatia (Donatiaceae) en Moat, Tierra del Fuego, Argentina. De 48 muestras procesadas, se obtuvieron 338 aislamientos. Mediante el uso de diferentes metodologías de cultivo, a través de observación microscópica y por métodos moleculares identificamos 38 especies fúngicas y 18 géneros de Ascomycetes y Zygomycetes. Los aislamientos de Ascomycetes fueron los más abundantes, con dominancia de Penicillium y Trichoderma. Se describe la composición fúngica y se comparó la diversidad y equitatividad de las especies a dos profundidades de muestreo. No se encontraron diferencias significativas entre la composición de especies, la diversidad y equitatividad. La turbera estudiada es un ecosistema que presenta alta diversidad de especies fúngicas filamentosas, algunas de ellas descritas en otras turberas en todo el mundo.Southern Hemisphere peatlands store substantial amounts of soil carbon. Despite their importance in the global carbon cycle, little is known about decomposition processes and the associated fungal diversity. The present study describes the composition of fungal assemblage in two depths from a cushion peatland of predominating Astelia (Asteliaceae) and Donatia (Donatiaceae) species in Moat, Tierra del Fuego. From 48 samples processed, we obtained 338 isolates. Using different culturing methodologies, through direct and microscopic observation and using molecular methods we identified 38 fungal species and 18 genera of Ascomycetes and Zygomycetes. Isolates belonging to Ascomycetes were the most abundant, with dominance of Penicillium and Trichoderma. We described fungal composition and compared species diversity and evenness across two dephts. No differences in the diversity index and evenness were found between depths. The studied peat is an ecosystem that has a great diversity of filamentous fungal species, some of which are described in other peatlands worldwide.Instituto de Botánica "Dr. Carlos Spegazzini

Microfungal composition in an Astelia-Donatia cushion Peatland in Tierra del Fuego, Argentina

En el Hemisferio Sur las turberas almacenan grandes cantidades de carbono en el suelo. A pesar de su importancia en el ciclo global del carbono, se sabe poco acerca de los procesos de descomposición y su diversidad fúngica. El presente estudio se realizó para describir la composición de hongos filamentosos en dos profundidades de una turbera compacta donde las especies vegetales predominantes son Astelia (Asteliaceae) y Donatia (Donatiaceae) en Moat, Tierra del Fuego, Argentina. De 48 muestras procesadas, se obtuvieron 338 aislamientos. Mediante el uso de diferentes metodologías de cultivo, a través de observación microscópica y por métodos moleculares identificamos 38 especies fúngicas y 18 géneros de Ascomycetes y Zygomycetes. Los aislamientos de Ascomycetes fueron los más abundantes, con dominancia de Penicillium y Trichoderma. Se describe la composición fúngica y se comparó la diversidad y equitatividad de las especies a dos profundidades de muestreo. No se encontraron diferencias significativas entre la composición de especies, la diversidad y equitatividad. La turbera estudiada es un ecosistema que presenta alta diversidad de especies fúngicas filamentosas, algunas de ellas descritas en otras turberas en todo el mundo.Southern Hemisphere peatlands store substantial amounts of soil carbon. Despite their importance in the global carbon cycle, little is known about decomposition processes and the associated fungal diversity. The present study describes the composition of fungal assemblage in two depths from a cushion peatland of predominating Astelia (Asteliaceae) and Donatia (Donatiaceae) species in Moat, Tierra del Fuego. From 48 samples processed, we obtained 338 isolates. Using different culturing methodologies, through direct and microscopic observation and using molecular methods we identified 38 fungal species and 18 genera of Ascomycetes and Zygomycetes. Isolates belonging to Ascomycetes were the most abundant, with dominance of Penicillium and Trichoderma. We described fungal composition and compared species diversity and evenness across two dephts. No differences in the diversity index and evenness were found between depths. The studied peat is an ecosystem that has a great diversity of filamentous fungal species, some of which are described in other peatlands worldwide.Instituto de Botánica "Dr. Carlos Spegazzini

Primary results of long-term outcomes in the MOMENTUM 3 pivotal trial and continued access protocol study phase: a study of 2200 HeartMate 3 left ventricular assist device implants

AIM: The MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal-flow pump, over the HeartMate II axial-flow pump. We now evaluate HM3 LVAD outcomes in a single-arm prospective continuous access protocol (CAP) post-pivotal trial study. METHODS AND RESULTS: We enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2-year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71-1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra-aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68-1.16, P = 0.38). In a pooled analysis, the 2-year primary endpoint was similar between INTERMACS profiles 1-2 (\u27unstable\u27 advanced heart failure), profile 3 (\u27stable\u27 on inotropic therapy), and profiles 4-7 (\u27stable\u27 ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88-0.98, P = 0.006), with consequent decrease in hospitalization. CONCLUSIONS: The primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial

HVAD to HeartMate 3 left ventricular assist device exchange: Best practices recommendations

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices

Microfungal composition in an Astelia-Donatia cushion Peatland in Tierra del Fuego, Argentina

En el Hemisferio Sur las turberas almacenan grandes cantidades de carbono en el suelo. A pesar de su importancia en el ciclo global del carbono, se sabe poco acerca de los procesos de descomposición y su diversidad fúngica. El presente estudio se realizó para describir la composición de hongos filamentosos en dos profundidades de una turbera compacta donde las especies vegetales predominantes son Astelia (Asteliaceae) y Donatia (Donatiaceae) en Moat, Tierra del Fuego, Argentina. De 48 muestras procesadas, se obtuvieron 338 aislamientos. Mediante el uso de diferentes metodologías de cultivo, a través de observación microscópica y por métodos moleculares identificamos 38 especies fúngicas y 18 géneros de Ascomycetes y Zygomycetes. Los aislamientos de Ascomycetes fueron los más abundantes, con dominancia de Penicillium y Trichoderma. Se describe la composición fúngica y se comparó la diversidad y equitatividad de las especies a dos profundidades de muestreo. No se encontraron diferencias significativas entre la composición de especies, la diversidad y equitatividad. La turbera estudiada es un ecosistema que presenta alta diversidad de especies fúngicas filamentosas, algunas de ellas descritas en otras turberas en todo el mundo.Southern Hemisphere peatlands store substantial amounts of soil carbon. Despite their importance in the global carbon cycle, little is known about decomposition processes and the associated fungal diversity. The present study describes the composition of fungal assemblage in two depths from a cushion peatland of predominating Astelia (Asteliaceae) and Donatia (Donatiaceae) species in Moat, Tierra del Fuego. From 48 samples processed, we obtained 338 isolates. Using different culturing methodologies, through direct and microscopic observation and using molecular methods we identified 38 fungal species and 18 genera of Ascomycetes and Zygomycetes. Isolates belonging to Ascomycetes were the most abundant, with dominance of Penicillium and Trichoderma. We described fungal composition and compared species diversity and evenness across two dephts. No differences in the diversity index and evenness were found between depths. The studied peat is an ecosystem that has a great diversity of filamentous fungal species, some of which are described in other peatlands worldwide.Instituto de Botánica "Dr. Carlos Spegazzini

Search for supersymmetry in events with b-quark jets and missing transverse energy in pp collisions at 7 TeV

Results are presented from a search for physics beyond the standard model based on events with large missing transverse energy, at least three jets, and at least one, two, or three b-quark jets. The study is performed using a sample of proton-proton collision data collected at sqrt(s) = 7 TeV with the CMS detector at the LHC in 2011. The integrated luminosity of the sample is 4.98 inverse femtobarns. The observed number of events is found to be consistent with the standard model expectation, which is evaluated using control samples in the data. The results are used to constrain cross sections for the production of supersymmetric particles decaying to b-quark-enriched final states in the context of simplified model spectra.Comment: Submitted to Physical Review