Functional group tolerant hydrogen borrowing C-alkylation

Hydrogen borrowing is an attractive and sustainable strategy for carbon–carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed

Cambio climático: causas, consecuencias, negligencia empresarial, pseudociencia y un llamamiento a la acción

Chief Seattle famously said, “The earth is our mother. Whatever befalls the earth befalls the sons of the earth. The earth does not belong to man, man belongs to the earth. All things are connected like the blood that unites us all. Man did not weave the web of life; he is merely a strand in it. Whatever he does to the web, he does to himself.” Well, the web is fraying, and our mother is dying. Global warming is a scientific fact; is getting worse; and is destroying the planet’s web of life, sickening and killing people and costing trillions of dollars.El Jefe Seattle dejó un mensaje claro para nosotros, el futuro:  La tierra es nuestra madre. Todo lo que le ocurre a la tierra les ocurre a los hijos de la tierra. La tierra no pertenece al hombre, el hombre pertenece a la tierra. Todas las cosas están conectadas como una sangre que nos es común. El hombre no tejió la red de la vida; es sólo una hebra de ella. Lo que le hace a la red, se lo hace a sí mismo.  Pues bien, la red se está deshilachando y nuestra madre se está muriendo. El calentamiento global es un hecho científico; está empeorando y está destruyendo la red de vida del planeta, enfermando y matando gente y costando billones de dólares

Functional group tolerant hydrogen borrowing C-alkylation

Hydrogen borrowing is an attractive and sustainable strategy for carbon–carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed

Participating in the Communication of Science: Identifying Relationships Between Laboratory Space Designs and Students’ Activities

Learning spaces can play a powerful role in shaping and supporting the activities of the students and teachers who use them: they can be agents for change when the success of new pedagogical approaches depends on shifting entrenched practices. The laboratory is a key site for science education. It is here that discipline knowledge and generic competences are fused and honed, in the very act of ‘doing science’. This paper focuses on communication of science. It looks at how students learn to participate in science communication, and acquire both scientific and more generic communication skills, while engaged in laboratory-based activities. This paper reports some findings of ethnographic research that involved observing student activity in laboratories. This opportunity to examine differences in patterns of communicative activity arose from a relocation to new purpose-designed laboratory spaces. Ethnographic research is appropriate for gathering data about space usage. It helps trace relations between student activity, characteristics of the spaces in which the activity is unfolding, the social organisation of the work being done, and the disciplinary practices that underpin the tasks that students are set. Our research identifies the importance of sightlines, communication tools and instructor behaviours in promoting students’ communicative activity. Addendum: Figure 2 has been replaced to ensure ethics requirements are followed

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Pulp properties resulting from different pretreatments of wheat straw and their influence on enzymatic hydrolysis rate

Wheat straw was subjected to three different processes prior to saccharification, namely alkaline pulping, natural pulping and autohydrolysis, in order to study their effect on the rate of enzymatic hydrolysis. Parameters like medium concentration, temperature and time have been varied in order to optimize each method. Milling the raw material to a length of 4 mm beforehand showed the best cost–value-ratio compared to other grinding methods studied. Before saccharification the pulp can be stored in dried form, leading to a high yield of glucose. Furthermore the relation of pulp properties (i.e. intrinsic viscosity, KLASON-lignin and hemicelluloses content, crystallinity, morphology) to cellulose hydrolysis is discussed

Learning How to Ask - Does a one-day training increase trauma inquiry in routine substance use disorder practice? Results of a cluster-randomized controlled trial

Aims To examine the effectiveness of a one-day skills training program for increasing trauma inquiry in routine substance use disorder treatment. Design Cluster-randomized two-armed controlled trial, with 12 substance use disorder (SUD) organizations operating 25 counseling centers, randomly assigned to training in trauma inquiry (13 counseling centers of 8 SUD organizations) or no training (12 counseling centers of 4 SUD organizations). Setting SUD counseling centers in Northern Germany. Cases N = 5204 SUD counseling services. Intervention The professionals assigned to the intervention group received a one-day training in trauma inquiry plus a 1.5-hour refresher session 3 months later. Professionals in the control group received no training. Measures Over a 12-month period, professionals documented for each counseling service whether they asked the client about four traumatic events: physical abuse, emotional abuse, sexual abuse and neglect. Analysis Primary outcomes were rates of asking about physical abuse, sexual abuse, emotional abuse and neglect in the 6 months after training. These were compared across conditions, while adjusting for baseline probabilities in the 6 months before the intervention, using mixed-effects logistic regression. Findings In the 6 months after training, the rate of asking about physical abuse was 18% higher in the SUD counseling services of trained professionals, relative to services of untrained professionals (OR = 1.18, 95% CI = [1.01–1.37, p = .035]). No effect was found for asking about sexual abuse, emotional abuse and neglect. Conclusion A one-day training program in trauma inquiry, combined with a brief refresher session, was effective in increasing inquiries about physical abuse in routine counseling practice. The training was ineffective in increasing inquiries about sexual abuse, emotional abuse and neglect. The effectiveness of a one-day training of trauma inquiry might be increased by a longer training, or by combining it with additional elements, such as ongoing supervision

Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry

Rationale Progressive fibrosing interstitial lung disease (PF-ILD) is characterized by progressive physiologic, symptomatic, and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain. Methods Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015-2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation, or any 2 of: relative FVC decline ≥5 and <10%, worsening respiratory symptoms, or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression. Results Of 2,746 patients with fibrotic ILD (mean age 65±12 years, 51% female), 1,376 (50%) met PFILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD), and 402 (45%) with connective tissue diseaseassociated ILD (CTD-ILD). Compared to IPF, time to progression was similar in patients with HP (hazard ratio [HR] 0.96, 95% confidence interval, CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilized in 49%, 61%, and 37% of patients with CHP, CTD-ILD, and U-ILD respectively. Increasing age, male sex, gastroesophageal reflux disease, and lower baseline pulmonary function were independently associated with progression. Interpretation Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategie

Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry

A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information

10Kin1day: a bottom-up neuroimaging initiative

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain