The synthesis and properties of the hybrid organic/inorganic germanium perovskite compounds, AGeI3, are reported (A = Cs, organic cation). The systematic study of this reaction system led to the ...isolation of 6 new hybrid semiconductors. Using CsGeI3 (1) as the prototype compound, we have prepared methylammonium, CH3NH3GeI3 (2), formamidinium, HC(NH2)2GeI3 (3), acetamidinium, CH3C(NH2)2GeI3 (4), guanidinium, C(NH2)3GeI3 (5), trimethylammonium, (CH3)3NHGeI3 (6), and isopropylammonium, (CH3)2C(H)NH3GeI3 (7) analogues. The crystal structures of the compounds are classified based on their dimensionality with 1–4 forming 3D perovskite frameworks and 5–7 1D infinite chains. Compounds 1–7, with the exception of compounds 5 (centrosymmetric) and 7 (nonpolar acentric), crystallize in polar space groups. The 3D compounds have direct band gaps of 1.6 eV (1), 1.9 eV (2), 2.2 eV (3), and 2.5 eV (4), while the 1D compounds have indirect band gaps of 2.7 eV (5), 2.5 eV (6), and 2.8 eV (7). Herein, we report on the second harmonic generation (SHG) properties of the compounds, which display remarkably strong, type I phase-matchable SHG response with high laser-induced damage thresholds (up to ∼3 GW/cm2). The second-order nonlinear susceptibility, χS (2), was determined to be 125.3 ± 10.5 pm/V (1), (161.0 ± 14.5) pm/V (2), 143.0 ± 13.5 pm/V (3), and 57.2 ± 5.5 pm/V (4). First-principles density functional theory electronic structure calculations indicate that the large SHG response is attributed to the high density of states in the valence band due to sp-hybridization of the Ge and I orbitals, a consequence of the lone pair activation.
Forest dynamics are the processes of recruitment, growth, death, and turnover of the constituent tree species of the forest community. These processes are driven by disturbances both natural and ...anthropogenic. McDowell et al. review recent progress in understanding the drivers of forest dynamics and how these are interacting and changing in the context of global climate change. The authors show that shifts in forest dynamics are already occurring, and the emerging pattern is that global forests are tending toward younger stands with faster turnover as old-growth forest with stable dynamics are dwindling.
For children with cerebral malaria, mortality is high, and in survivors, long-term neurologic and cognitive dysfunctions are common. While specific clinical factors are associated with death or ...long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes, is less well characterized.
In this prospective cohort study of 149 children age 6 months to 12 years who survived cerebral malaria in Kampala, Uganda, we evaluated whether depth of coma, number of clinical seizures, or EEG features during hospitalization were associated with mortality during hospitalization, short-term and long-term neurologic deficits, or long-term cognitive outcomes (overall cognition, attention, memory) over the 2-year follow-up.
Higher Blantyre or Glasgow Coma Scores (BCS and GCS, respectively), higher background voltage, and presence of normal reactivity on EEG were each associated with lower mortality. Among clinical and EEG features, the presence of >4 seizures on admission had the best combination of negative and positive predictive values for neurologic deficits in follow-up. In multivariable modeling of cognitive outcomes, the number of seizures and specific EEG features showed independent association with better outcomes. In children younger than 5 years throughout the study, seizure number and presence of vertex sharp waves were independently associated with better posthospitalization cognitive performance, faster dominant frequency with better attention, and higher average background voltage and faster dominant background frequency with better associative memory. In children younger than 5 years at CM episode but 5 years or older at cognitive testing, seizure number, background dominant frequency, and the presence of vertex sharp waves were each associated with changes in cognition, seizure number and variability with attention, and seizure number with working memory.
In children with cerebral malaria, seizure number is strongly associated with the risk of long-term neurologic deficits, while seizure number and specific EEG features (average background voltage, dominant rhythm frequency, presence of vertex sharp waves, presence of variability) are independently associated with cognitive outcomes. Future studies should evaluate the predictive value of these findings.
The hybrid two-dimensional (2D) halide perovskites have recently drawn significant interest because they can serve as excellent photoabsorbers in perovskite solar cells. Here we present the large ...scale synthesis, crystal structure, and optical characterization of the 2D (CH3(CH2)3NH3)2(CH3NH3) n−1Pb n I3n+1 (n = 1, 2, 3, 4, ∞) perovskites, a family of layered compounds with tunable semiconductor characteristics. These materials consist of well-defined inorganic perovskite layers intercalated with bulky butylammonium cations that act as spacers between these fragments, adopting the crystal structure of the Ruddlesden–Popper type. We find that the perovskite thickness (n) can be synthetically controlled by adjusting the ratio between the spacer cation and the small organic cation, thus allowing the isolation of compounds in pure form and large scale. The orthorhombic crystal structures of (CH3(CH2)3NH3)2(CH3NH3)Pb2I7 (n = 2, Cc2m; a = 8.9470(4), b = 39.347(2) Å, c = 8.8589(6)), (CH3(CH2)3NH3)2(CH3NH3)2Pb3I10 (n = 3, C2cb; a = 8.9275(6), b = 51.959(4) Å, c = 8.8777(6)), and (CH3(CH2)3NH3)2(CH3NH3)3Pb4I13 (n = 4, Cc2m; a = 8.9274(4), b = 64.383(4) Å, c = 8.8816(4)) have been solved by single-crystal X-ray diffraction and are reported here for the first time. The compounds are noncentrosymmetric, as supported by measurements of the nonlinear optical properties of the compounds and density functional theory (DFT) calculations. The band gaps of the series change progressively between 2.43 eV for the n = 1 member to 1.50 eV for the n = ∞ adopting intermediate values of 2.17 eV (n = 2), 2.03 eV (n = 3), and 1.91 eV (n = 4) for those between the two compositional extrema. DFT calculations confirm this experimental trend and predict a direct band gap for all the members of the Ruddlesden–Popper series. The estimated effective masses have values of m h = 0.14 m 0 and m e = 0.08 m 0 for holes and electrons, respectively, and are found to be nearly composition independent. The band gaps of higher n members indicate that these compounds can be used as efficient light absorbers in solar cells, which offer better solution processability and good environmental stability. The compounds exhibit intense room-temperature photoluminescence with emission wavelengths consistent with their energy gaps, 2.35 eV (n = 1), 2.12 eV (n = 2), 2.01 eV (n = 3), and 1.90 eV (n = 4) and point to their potential use in light-emitting diodes. In addition, owing to the low dimensionality and the difference in dielectric properties between the organic spacers and the inorganic perovskite layers, these compounds are naturally occurring multiple quantum well structures, which give rise to stable excitons at room temperature.
Purpose Molecular testing of colorectal cancers (CRCs) to improve patient care and outcomes of targeted and conventional therapies has been the center of many recent studies, including clinical ...trials. Evidence-based recommendations for the molecular testing of CRC tissues to guide epidermal growth factor receptor (EGFR) -targeted therapies and conventional chemotherapy regimens are warranted in clinical practice. The purpose of this guideline is to develop evidence-based recommendations to help establish standard molecular biomarker testing for CRC through a systematic review of the literature. Methods The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) convened an Expert Panel to develop an evidence-based guideline to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for patients with CRC. A comprehensive literature search that included over 4,000 articles was conducted to gather data to inform this guideline. Results Twenty-one guideline statements (eight recommendations, 10 expert consensus opinions and three no recommendations) were established. Recommendations Evidence supports mutational testing for genes in the EGFR signaling pathway, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize molecular testing for predictive and prognostic molecular biomarkers involve selection of assays, type of specimens to be tested, timing of ordering of tests and turnaround time for testing results. Additional information is available at: www.asco.org/CRC-markers-guideline and www.asco.org/guidelineswiki.
Abstract
There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming ...skills. Here we present iLINCS (
http://ilincs.org
), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling.
1. Animals produce sounds for diverse biological functions such as defending territories, attracting mates, deterring predators, navigation, finding food and maintaining contact with members of their ...social group. Biologists can take advantage of these acoustic behaviours to gain valuable insights into the spatial and temporal scales over which individuals and populations interact. Advances in bioacoustic technology, including the development of autonomous cabled and wireless recording arrays, permit data collection at multiple locations over time. These systems are transforming the way we study individuals and populations of animals and are leading to significant advances in our understandings of the complex interactions between animals and their habitats. 2. Here, we review questions that can be addressed using bioacoustic approaches, by providing a primer on technologies and approaches used to study animals at multiple organizational levels by ecologists, behaviourists and conservation biologists. 3. Spatially dispersed groups of microphones (arrays) enable users to study signal directionality on a small scale or to locate animals and track their movements on a larger scale. 4. Advances in algorithm development can allow users to discriminate among species, sexes, age groups and individuals. 5. With such technology, users can remotely and non-invasively survey populations, describe the soundscape, quantify anthropogenic noise, study species interactions, gain new insights into the social dynamics of sound-producing animals and track the effects of factors such as climate change and habitat fragmentation on phenology and biodiversity. 6. There remain many challenges in the use of acoustic monitoring, including the difficulties in performing signal recognition across taxa. The bioacoustics community should focus on developing a common framework for signal recognition that allows for various species' data to be analysed by any recognition system supporting a set of common standards. 7. Synthesis and applications. Microphone arrays are increasingly used to remotely monitor acoustically active animals. We provide examples from a variety of taxa where acoustic arrays have been used for ecological, behavioural and conservation studies. We discuss the technologies used, the methodologies for automating signal recognition and some of the remaining challenges. We also make recommendations for using this technology to aid in wildlife management.
Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic ...progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4
T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.
KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating ...mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRAS
-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.
Forest transitions (FT) have been observed in many developed countries and more recently in the developing world. However, our knowledge of FT from tropical regions is mostly derived from case ...studies from within a particular country, making it difficult to generalize findings across larger regions. Here we overcome these difficulties by conducting a recent (2001-2010) satellite-based analysis of trends in forest cover across Central America, stratified by biomes, which we related to socioeconomic variables associated with human development. Results show a net decrease of woody vegetation resulting from 12,201 km² of deforestation of moist forests and 6,825 km² of regrowth of conifer and dry forests. The Human Development Index was the socioeconomic variable best associated with forest cover change. The least-developed countries, Nicaragua and Guatemala, experienced both rapid deforestation of moist forests and significant recovery of conifer and dry forests. In contrast, the most developed countries, Panama and Costa Rica, had net woody vegetation gain and a more stable forest cover configuration. These results imply a good agreement with FT predictions of forest change in relation to socioeconomic development, but strong asymmetry in rates and directions of change largely dependent upon the biome where change is occurring. The FT model should be refined by incorporating ecological and socioeconomic heterogeneity, particularly in multicountry and regional studies. These asymmetric patterns of forest change should be evaluated when developing strategies for conserving biodiversity and environmental services.
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