Design Principles for Two-Dimensional Molecular Aggregates Using Kasha's Model: Tunable Photophysics in Near and Short-Wave Infrared

Technologies which utilize near-infrared (700 – 1000 nm) and short-wave infrared (1000 – 2000 nm) electromagnetic radiation have applications in deep-tissue imaging, telecommunications and satellite telemetry due to low scattering and decreased background signal in this spectral region. It is therefore necessary to develop materials that absorb light efficiently beyond 1000 nm. Transition dipole moment coupling (e.g. J-aggregation) allows for redshifted excitonic states and provides a pathway to highly absorptive electronic states in the infrared. We present aggregates of two cyanine dyes whose absorption peaks redshift dramatically upon aggregation in water from ~800 nm to 1000 nm and 1050 nm respectively with sheet-like morphologies and high molar absorptivities (e ~ 105 M-1cm-1). We use Frenkel exciton theory to extend Kasha’s model for J and H aggregation and describe the excitonic states of 2-dimensional aggregates whose slip is controlled by steric hindrance in the assembled structure. A consequence of the increased dimensionality is the phenomenon of an intermediate “I-aggregate”, one which redshifts yet displays spectral signatures of band-edge dark states akin to an H-aggregate. We distinguish between H-, I- and J-aggregates by showing the relative position of the bright (absorptive) state within the density of states using temperature dependent spectroscopy. I-aggregates hold potential for applications as charge injection moieties for semiconductors and donors for energy transfer in NIR and SWIR. Our results can be used to better design chromophores with predictable and tunable aggregation with new photophysical properties

Checks and Balances in Autoimmune Vasculitis

Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system. The use of immune checkpoint inhibitors (ICIs) to treat cancer has proven to be effective producing durable antitumor responses in multiple cancer types. However, one of the disadvantages derived from the use of these agents is the appearance of inflammatory manifestations termed immune-related adverse events (irAEs). These irAEs are often relatively mild, but more severe irAEs have been reported as well including several forms of vasculitis. In this article, we argue that age-related changes in expression and function of immune checkpoint molecules lead to an unstable immune system, which is prone to tolerance failure and autoimmune vasculitis development. The topic is introduced by a case report from our hospital describing a melanoma patient treated with ICIs and who subsequently developed biopsy-proven giant cell arteritis. Following this case report, we present an in-depth review on the role of immune checkpoint pathways in the development and progression of autoimmune vasculitis and its relation with an aging immune system

Backgrounds and sensitivity of the NEXT double beta decay experiment

NEXT (Neutrino Experiment with a Xenon TPC) is a neutrinoless double-beta (ßß0¿ßß0¿) decay experiment that will operate at the Canfranc Underground Laboratory (LSC). It is an electroluminescent high-pressure gaseous xenon Time Projection Chamber (TPC) with separate read-out planes for calorimetry and tracking. Energy resolution and background suppression are the two key features of any neutrinoless double beta decay experiment. NEXT has both good energy resolution (<1% FWHM) at the Q value of 136Xe and an extra handle for background identification provided by track reconstruction. With the background model of NEXT, based on the detector simulation and the evaluation of the detector radiopurity, we can determine the sensitivity to a measurement of the ßß2¿ßß2¿ mode in NEW and to a ßß0¿ßß0¿ search in NEXT100. In this way we can predict the background rate of 5×10-4 counts/(keV kg yr)5×10-4 counts/(keV kg yr), and a sensitivity to the Majorana neutrino mass down to 100 meV after a 5-years run of NEXT100

Esofagitis eosinofílica, eficacia de las alternativas terapéuticas en el adulto: revisión sistemática

Fundamentos: La esofagitis eosinofílica es hoy en día la principal causa de disfagia en el adulto. La elección de la terapia se debe consensuar con el paciente. El objetivo de este trabajo fue revisar la bibliografía científica para conocer la eficacia de las distintas opciones terapéuticas de la esofagitis eosinofílica en el adulto. Métodos: Se realizó una búsqueda de artículos durante el mes de febrero de 2023 en las bases de datos de PubMed, Web of Science, Scopus y Scielo, empleando los términos de búsqueda eosinophilic esophagitis, therapeutics y treatment, seleccionándose los ensayos clínicos y estudios observacionales publicados en los últimos diez años en adultos. Resultados: Se obtuvieron un total de 1.138 artículos, de los cuales 41 fueron seleccionados tras aplicar los criterios de elegibilidad. De las terapias disponibles, el tratamiento más frecuentemente analizado fueron los corticoides deglutidos, seguido de las dietas de eliminación y de los inhibidores de la bomba de protones, predominando los ensayos clínicos. Los estudios arrojan resultados sobre la eficacia de estas terapias en la remisión histológica y clínica, tanto en la inducción como a largo plazo. Conclusiones: Existen fundamentalmente tres terapias en la esofagitis eosinofílica en el adulto, siendo todas superiores frente a placebo en respuesta histológica y clínica

PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions

Group 2 innate lymphoid cells (ILC2s) play a critical role in protection against helminths and in diverse inflammatory diseases by responding to soluble factors such as the alarmin IL-33, that is often overexpressed in cancer. Nonetheless, regulatory factors that dictate ILC2 functions remain poorly studied. Here, we show that peroxisome proliferator-activated receptor gamma (PPARγ) is selectively expressed in ILC2s in humans and in mice, acting as a central functional regulator. Pharmacologic inhibition or genetic deletion of PPARγ in ILC2s significantly impair IL-33-induced Type-2 cytokine production and mitochondrial fitness. Further, PPARγ blockade in ILC2s disrupts their pro-tumoral effect induced by IL-33-secreting cancer cells. Lastly, genetic ablation of PPARγ in ILC2s significantly suppresses tumor growth in vivo. Our findings highlight a crucial role for PPARγ in supporting the IL-33 dependent pro-tumorigenic role of ILC2s and suggest that PPARγ can be considered as a druggable pathway in ILC2s to inhibit their effector functions. Hence, PPARγ targeting might be exploited in cancer immunotherapy and in other ILC2-driven mediated disorders, such as asthma and allergy

Value of Serum NEUROG1 Methylation for the Detection of Advanced Adenomas and Colorectal Cancer

Aberrant DNA methylation detected in liquid biopsies is a promising approach for colorectal cancer (CRC) detection, including premalignant advanced adenomas (AA). We evaluated the diagnostic capability of serum NEUROG1 methylation for the detection of AA and CRC. A CpG island in NEUROG1 promoter was assessed by bisulfite pyrosequencing in a case-control cohort to select optimal CpGs. Selected sites were evaluated through a nested methylation-specific qPCR custom assay in a screening cohort of 504 asymptomatic family-risk individuals. Individuals with no colorectal findings and benign pathologies showed low serum NEUROG1 methylation, similar to non-advanced adenomas. Contrarily, individuals bearing AA or CRC (advanced neoplasia-AN), exhibited increased NEUROG1 methylation. Using >1.3518% as NEUROG1 cut-off (90.60% specificity), 33.33% of AN and 32.08% of AA were identified, detecting 50% CRC cases. Nonetheless, the combination of NEUROG1 with fecal immunochemical test (FIT), together with age and gender through a multivariate logistic regression resulted in an AUC = 0.810 for AN, and 0.796 for AA, detecting all cancer cases and 35-47% AA (specificity 98-95%). The combination of NEUROG1 methylation with FIT, age and gender demonstrated a convenient performance for the detection of CRC and AA, providing a valuable tool for CRC screening programs in asymptomatic individuals

Analysis of High-order Social Interaction of Female Mice on the International Space Station

Social interactions are adaptive responses to environmental pressures that have evolved to facilitate the success of individual animals and their progeny. Quantifying social behavior in social animals is therefore one method of evaluating an animal's health, wellbeing and their adjustment to changes in their environment. The interaction between environment and animal can influence numerous other physiological and psychological responses that may enhance, deter or shift an animals social paradigm. For this study, we utilized flight video from the Rodent Research Hardware and Operations Validation mission (Rodent Research-1; RR1) on the International Space Station (ISS). Female mice spent 37 days in microgravity on the ISS and video was captured during the final 33 days. In a previous analysis of individual behavior, we also reported an observed spontaneous ambulatory behavior which we termed circling or 'race tracking,' and we anecdotally observed an increase in group organization around this behavior. In this analysis we further examined this behavior, and other social interactions, to determine if (1) animals joining in on this behavior were induced by other cohort members already participating in this circling behavior, (2) rates of joining varied by number already participating

On the Usefulness of Modern Animism: Co-Creating Architecture with Soils as Ontopolitical Practice

In opposition to the general understanding of animism as an irrational religious set of beliefs, the—secular—modern animism embodied in this practice of built and grown architecture is operative. It conceives of places—ecosystems—as beings with agency that we garden with to nurture and express their resilience. It is a useful ontology for ecological practice; this architectural animism is ontopolitical; it co-creates a common world. At a recent symposium, a number of projects were presented as architectural soils and to give a voice to these earthly beings, the method was to write a letter from them to me. This first letter with the response in this article forms the beginning of an animistic correspondence. The medium places the reader in a pluriverse, in between the multiple voices of various “actants.” The text is isomorphic to the embodied dialogue of this earthy practice. It is useful both to nurture societal awareness—empathy and care—towards these fragmentary ecosystemic beings, and as research method to conceive them, and our relationship

Systematics, biogeography, and diversification of Scytalopus tapaculos (Rhinocryptidae), an enigmatic radiation of Neotropical montane birds

Copyright © American Ornithological Society 2020. All rights reserved. For permissions, e-mail: [email protected]. We studied the phylogeny, biogeography, and diversification of suboscine passerines in the genus Scytalopus (Rhinocryptidae), a widespread, species-rich, and taxonomically challenging group of Neotropical birds. We analyzed nuclear (exons, regions flanking ultraconserved elements) and mitochondrial (ND2) DNA sequence data for a taxonomically and geographically comprehensive sample of specimens collected from Costa Rica to Patagonia and Brazil. We found that Scytalopus is a monophyletic group sister to Eugralla and consists of 3 main clades roughly distributed in (1) the Southern Andes, (2) eastern Brazil, and (3) the Tropical Andes and Central America. The clades from the Southern Andes and eastern Brazil are sister to each other. Despite their confusing uniformity in plumage coloration, body shape, and overall appearance, rates of species accumulation through time in Scytalopus since the origin of the clade in the Late Miocene are unusually high compared with those of other birds, suggesting rapid non-adaptive diversification in the group. We attribute this to their limited dispersal abilities making them speciation-prone and their occurrence in a complex landscape with numerous barriers promoting allopatric differentiation. Divergence times among species and downturns in species accumulation rates in recent times suggest that most speciation events in Scytalopus predate climatic oscillations of the Pleistocene. Our analyses identified various cases of strong genetic structure within species and lack of monophyly of taxa, flagging populations which likely merit additional study to clarify their taxonomic status. In particular, detailed analyses of species limits are due in S. parvirostris, S. latrans, S. speluncae, the S. atratus complex, and the Southern Andes clade