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Recent advances in electrode materials, manufacturing processes, and safety features are enabling Li-ion battery (LIB) designs to better support energy storage needs for the emerging all-electric aviation market. Increases in cell specific energy, improved fast charge and discharge rate capability, and extended cycle-life are required for the next-generation aviation platforms that consist of more-electric, hybrid, and all-electric aircraft designed to reduce generated flight noise and carbon emissions. The success of these emerging Advanced Air Mobility (AAM) markets is highly dependent upon implementing a safe and reliable energy storage system compliant with aircraft system requirements. This work discusses state-of-the-art (SOA) and emerging LIB technology readiness to meet the derived marketplace performance and imposed regulatory requirements for all-electric aircraft. A special focus on advanced LIB safety design guidelines intended to meet the intent of the FAA DO-311A minimum operational performance standard for rechargeable lithium batteries and battery systems installed on aircraft is emphasized.

Background It has been well established that individuals who identify as lesbian, gay, bisexual, transgender, and queer are at increased risk for mental health pathology, including eating disorders/disordered eating behaviors (ED/DEB). However, less is understood about the unique experiences of transgender and gender diverse (TGD) people who struggle with ED/DEB. Aims The purpose of this literature review is to examine the literature regarding the unique risk factors for TGD individuals who experience ED/DEB through a lens informed by the minority stress model. Additionally, guidance around the assessment and clinical management of eating disorders for TGD individuals will be presented. Results TGD people are at increased risk for developing ED/DEB due to a number of factors including: gender dysphoria, minority stress, the desire to pass, and barriers to gender affirming care. Conclusion While guidance around assessment and treatment of ED/DEB for TGD individuals is still limited, adhering to a gender affirmative care model is essential.

The adhesion of initial colonizers such asStreptococcus mutansto collagen is critical for dentinal and root caries progression. One of the most described pathological and aging-associated changes in collagen – including dentinal collagen – is the generation of advanced glycation end-products (AGEs) such as methylglyoxal (MGO)-derived AGEs. Despite previous reports suggesting that AGEs alter bacterial adhesion to collagen, the biophysics driving oral streptococcal attachment to MGO-modified collagen remains largely understudied. Thus, the aim of this work was to unravel the dynamics of the initial adhesion ofS. mutansto type-I collagen in the presence and absence of MGO-derived AGEs, by employing bacterial cell force-spectroscopy with atomic force microscopy (AFM). Type-I collagen gels were treated with 10mM MGO to induce AGE formation, which was characterized with microscopy and ELISA. Subsequently, AFM cantilevers were functionalized with livingS. mutansUA 159 orS. sanguinisSK 36 cells and probed against collagen surfaces to obtain force-curves displaying bacterial attachment in real-time, from which the adhesion force, number of events, Poisson analysis, and contour and rupture lengths for each individual detachment event were computed. Furthermore, in-silico docking studies between the relevantS. mutansUA 159 collagen-binding protein SpaP and collagen were computed, in the presence and absence of MGO. Overall, results showed that MGO modification increased both the number and adhesion force of single-unbinding events betweenS. mutansand collagen, without altering the contour or rupture lengths. Both experimental and in-silico simulations suggest that this effect is due to increased specific and non-specific forces and interactions betweenS. mutansUA 159 and MGO-modified collagen substrates. In summary, these results suggest that collagen alterations due to glycation and AGE formation may play a role in early bacterial adherence to oral tissues, associated with conditions such as aging or chronic hyperglycemia, amongst others.

For many transgender individuals, pursuing gender-affirming surgery (GAS) to minimize gender incongruence—commonly referred to as gender dysphoria—is a medically necessary element of comprehensive ...

Funder: Croucher Foundation; Id: http://dx.doi.org/10.13039/501100001692, The bacterial heterodimeric ATP-binding cassette (ABC) multidrug exporter PatAB has a critical role in conferring antibiotic resistance in multidrug-resistant infections by Streptococcus pneumoniae. As with other heterodimeric ABC exporters, PatAB contains two transmembrane domains that form a drug translocation pathway for efflux and two nucleotide-binding domains that bind ATP, one of which is hydrolysed during transport. The structural and functional elements in heterodimeric ABC multidrug exporters that determine interactions with drugs and couple drug binding to nucleotide hydrolysis are not fully understood. Here, we used mass spectrometry techniques to determine the subunit stoichiometry in PatAB in our lactococcal expression system and investigate locations of drug binding using the fluorescent drug-mimetic azido-ethidium. Surprisingly, our analyses of azido-ethidium-labelled PatAB peptides point to ethidium binding in the PatA nucleotide-binding domain, with the azido moiety crosslinked to residue Q521 in the H-like loop of the degenerate nucleotide-binding site. Investigation into this compound and residue’s role in nucleotide hydrolysis pointed to a reduction in the activity for a Q521A mutant and ethidium-dependent inhibition in both mutant and wild type. Most transported drugs did not stimulate or inhibit nucleotide hydrolysis of PatAB in detergent solution or lipidic nanodiscs. However, further examples for ethidium-like inhibition were found with propidium, novobiocin and coumermycin A1, which all inhibit nucleotide hydrolysis by a non-competitive mechanism. These data cast light on potential mechanisms by which drugs can regulate nucleotide hydrolysis by PatAB, which might involve a novel drug binding site near the nucleotide-binding domains.

Objective: To evaluate the outcomes of patients with sepsis-associated organ dysfunction and septic shock who receive fluid resuscitation with balanced and unbalanced solutions in a middle-income country. Design: An observational, analytical cohort study with propensity score matching (PSM) in children admitted to a pediatric intensive care unit (PICU). Patients from one month to 17 years old who required fluid boluses due to hemodynamic instability were included. The primary outcome was the presence of acute kidney injury and the secondary outcomes were the need to begin continuous renal replacement therapy (CRRT), metabolic acidosis, PICU length of stay and mortality. Measurements and Main Results: Out of the 1,074 admissions to the PICU during the study period, 99 patients had sepsis-associated organ dysfunction and septic shock. Propensity score matching was performed including each patient´s baseline characteristics. The median age was 9.9 months (IQR 4.9-22.2) with 55.5% of the patients being male. Acute kidney injury was seen less frequently in children who received a balanced solution than in those who received an unbalanced solution (20.3% vs 25.7% P = 0.006 ORa, 0.75; 95% CI, 0.65-0.87), adjusted for disease severity. In addition, the group that received balanced solutions had less need for CRRT (3.3 % vs 6.5%; P = 0.02 ORa 0.48; 95% CI, 0.36-0.64) and a shorter PICU stay (6 days IQR 4.4-20.2 vs 10.2 days IQR 4.7-26; P < 0.001) than the group with unbalanced solutions. We found no difference in the frequency of metabolic acidosis ( P = 0.37), hyperchloremia ( P = 0.11) and mortality ( P = 0.25) between the 2 groups. Conclusion: In children with sepsis-associated organ dysfunction and septic shock, the use of unbalanced solutions for fluid resuscitation is associated with a higher frequency of acute kidney injury, a greater need for continuous renal support and a longer PICU stay compared to the use of balanced solutions, in a middle-income country.

The P2X4 receptor (P2X4R) is an ATP-gated cation channel. Here, we used fast-scan atomic force microscopy (AFM) to visualize changes in the structure and mobility of individual P2X4Rs in response to activation. P2X4Rs were purified from detergent extracts of transfected cells and integrated into lipid bilayers. Activation resulted in a rapid (2 s) and substantial (10-20 nm2 ) increase in the cross-sectional area of the extracellular region of the receptor and a corresponding decrease in receptor mobility. Both effects were blocked by the P2X4R antagonist 5-BDBD. Addition of cholesterol to the bilayer reduced receptor mobility, although the ATP-induced reduction in mobility was still observed. We suggest that the observed responses to activation may have functional consequences for purinergic signalling.

Biofilm-mediated oral diseases such as dental caries and periodontal disease remain highly prevalent in populations worldwide. Biofilm formation initiates with the attachment of primary colonizers onto surfaces, and in the context of caries, the adhesion of oral streptococci to dentinal collagen is crucial for biofilm progression. It is known that dentinal collagen suffers from glucose-associated crosslinking as a function of aging or disease; however, the effect of collagen crosslinking on the early adhesion and subsequent biofilm formation of relevant oral streptococci remains unknown. Therefore, the aim of this work was to determine the impact of collagen glycation on the initial adhesion of primary colonizers such as Streptococcus mutans UA159 and Streptococcus sanguinis SK 36, as well as its effect on the early stages of streptococcal biofilm formation in vitro. Type I collagen matrices were crosslinked with either glucose or methylglyoxal. Atomic force microscopy nanocharacterization revealed morphologic and mechanical changes within the collagen matrix as a function of crosslinking, such as a significantly increased elastic modulus in crosslinked fibrils. Increased nanoadhesion forces were observed for S. mutans on crosslinked collagen surfaces as compared with the control, and retraction curves obtained for both streptococcal strains demonstrated nanoscale unbinding behavior consistent with bacterial adhesin-substrate coupling. Overall, glucose-crosslinked substrates specifically promoted the initial adhesion, biofilm formation, and insoluble extracellular polysaccharide production of S. mutans, while methylglyoxal treatment reduced biofilm formation for both strains. Changes in the adhesion behavior and biofilm formation of oral streptococci as a function of collagen glycation could help explain the biofilm dysbiosis seen in older people and patients with diabetes. Further studies are necessary to determine the influence of collagen crosslinking on the balance between acidogenic and nonacidogenic streptococci to aid in the development of novel preventive and therapeutic treatment against dental caries in these patients.

Throughout the last decade, extracellular vesicles (EVs) have become increasingly popular in several areas of regenerative medicine. Recently, Apis mellifera royal jelly EVs (RJ EVs) were shown to display favorable wound healing properties such as stimulation of mesenchymal stem cell migration and inhibition of staphylococcal biofilms. However, the sustained and effective local delivery of EVs in non-systemic approaches – such as patches for chronic cutaneous wounds – remains an important challenge for the development of novel EV-based wound healing therapies. Therefore, the present study aimed to assess the suitability of type I collagen -a well-established biomaterial for wound healing – as a continuous delivery matrix. RJ EVs were integrated into collagen gels at different concentrations, where gels containing 2 mg/ml collagen were found to display the most stable release kinetics. Functionality of released RJ EVs was confirmed by assessing fibroblast EV uptake and migration in a wound healing assay. We could demonstrate reliable EV uptake into fibroblasts with a sustained pro-migratory effect for up to 7 d. Integrating fibroblasts into the RJ EV-containing collagen gel increased the contractile capacity of these cells, confirming availability of RJ EVs to fibroblasts within the collagen gel. Furthermore, EVs released from collagen gels were found to inhibit Staphylococcus aureus ATCC 29213 biofilm formation. Overall, our results suggest that type I collagen could be utilized as a reliable, reproducible release system to deliver functional RJ EVs for wound healing therapies.

A dual-rail hybrid analog/digital low-dropout regulator (DRLDO) targeting heterogeneous integration in a multichip package (MCP) platform is presented. Different from the classic single-input–single-output low-dropout regulator (LDO) topology, which incurs an efficiency penalty due to a large dropout voltage, this DRLDO architecture breaks the tradeoff of power-supply rejection and high efficiency by exploiting two rails available in a typical MCP system on a chip. One rail is the larger dropout ac branch rail which helps with power-supply rejection while the other is the low-dropout dc branch that helps with maximizing efficiency. The hybrid combination of analog and digital branches achieves both high efficiency and high power-supply rejection ratio (PSRR) simultaneously. Moreover, a dynamic current steering mechanism actively regulates the current contribution between the two rails and flexibly tunes the PSRR and power conversion efficiency performances. Measurements on a 22-nm CMOS chip demonstrate up to −46-dB PSRR and 89% efficiency across a 0–80-mA load from 1.8-V HV and 1.05-V LV dual-input rails. It improves the efficiency of the conventional analog LDO (ALDO) in MCP applications up to 32% while still maintaining −20-dB PSRR performance.

Recent advances in atomic force microscopy (AFM) have allowed the characterisation of dental-associated biomaterials and biological surfaces with high-resolution and minimal sample preparation. In this context, the topography of dental enamel – the hardest mineralised tissue in the body – has been explored with AFM-based approaches at the micro-scale. With age, teeth are known to suffer changes that can impact their structural stability and function; however, changes in enamel structure because of ageing have not yet been explored with nanoscale resolution. Therefore, the aim of this exploratory work was to optimise an approach to characterise the ultrastructure of dental enamel and determine potential differences in topography, hydroxyapatite (HA) crystal size, and surface roughness at the nanoscale associated to ageing. For this, a total of six teeth were collected from human donors from which enamel specimens were prepared. By employing AC mode imaging, HA crystals were characterised in both transversal and longitudinal orientation with high-resolution in environmental conditions. Sound superficial enamel displayed the presence of a pellicle-like coating on its surface, that was not observable on cleaned specimens. Acidetching exposed crystals that were imaged and morphologically characterised in highresolution at the nanoscale in both the external and internal regions of enamel in older and younger specimens. Our results demonstrated important individual variations in HA crystal width and roughness parameters across the analysed specimens; however, an increase in surface roughness and decrease in HA width was observed for the pooled older external enamel group compared to younger specimens. Overall, high-resolution AFM was an effective approach for the qualitative and quantitative characterisation of human dental enamel ultrastructure at the nanometre range. Future work should focus on exploring the ageing of dental enamel with increased sample sizes to compensate for individual differences as well as other potential confounding factors such as behavioural habits and mechanical forces.

Seriously ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hospitalized in intensive care units (ICUs) are commonly given a combination of drugs, a process known as multi-drug treatment. After extracting data on drug-drug interactions with clinical relevance from available online platforms, we hypothesize that an overall interaction map can be generated for all drugs administered. Furthermore, by combining this approach with simulations of cellular biochemical pathways, we may be able to explain the general clinical outcome. Finally, we postulate that by applying this strategy retrospectively to a cohort of patients hospitalized in ICU, a prediction of the timing of developing acute kidney injury (AKI) could be made. Whether or not this approach can be extended to other diseases is uncertain. Still, we believe it represents a valuable pharmacological insight to help improve clinical outcomes for severely ill patients.

The human skin changes with time, presenting different appearances and even properties. Peripheral vascularization is one of the crucial factors that affect skin growth. The variation of vascularization with age is a topic that always arouses great interest. The quality of the skin, concerning age, can be an important factor in interventions for functional skin improvement and understanding the skin-related aging process. In particular, the statistical distribution of the size of peripheral vascularization components and their indicators of evolution with age is a quantifier that is not common in conventional medicine. Their introduction is the main objective of this report. In this work, we use optical coherent tomography angiography to investigate skin microvasculature changes in men and women from different age groups. Using our algorithms, we were able to assess the vessel density and the distribution of average vessel caliber as a function of age. The vessel’s density distribution shifts to smaller vessels’ diameters values according to aging. This finding may indicate a way of evaluating physiological skin aging and proposing alternatives for its delay. Some possible consequences of these findings are also discussed.

Methylglyoxal (MGO) is an important molecule derived from glucose metabolism with the capacity of attaching to collagen and generating advanced glycation end-products (AGEs), which accumulate in tissues over time and are associated to aging and diseases. However, the accumulation of MGO-derived AGEs in dentin and their effect on the nanomechanical properties of dentinal collagen remain unknown. Thus, the aim of the present study was to quantify MGO-based AGEs in the organic matrix of human dentin as a function of age and associate these changes with alterations in the nanomechanical and ultrastructural properties of dentinal collagen. For this, twelve healthy teeth from 50 year-old patients were collected and prepared to obtain crown and root dentin discs. Following demineralization, MGO-derived AGEs were quantified with a competitive ELISA assay. In addition, atomic force microscopy (AFM) nano-indentation was utilized to measure changes in elastic modulus in both peritubular (PT) and intertubular (IT) collagen fibrils. Finally, principal component analysis (PCA) was carried out to determine aging profiles for both crown and root dentin. Results showed increased presence of MGO AGEs in the organic matrix of dentin in the >50 year-old compared to 50 year-old group associated to ultrastructural changes in the organic matrix determined by AFM analysis. Furthermore, PCA loading plots suggested different ‘aging profiles’ in both crown and root dentin, which could potentially have important therapeutic implications in restorative and adhesive dentistry approaches. Overall, these results demonstrate that the organic matrix of human dentin undergoes aging-related changes due to MGO-derived AGEs with important changes in nanomechanical behavior of collagen that may impact diagnostic and restorative procedures in the elderly.

This work presents an experimental and theoretical study about the optical properties of the wings of butterfly Greta oto. UV-Vis spectroscopy was used to obtain the optical response of the sample as function of the incident light angle. It was possible to observe a shift in the maximum of the reflectance spectra towards lower values of lambda when the angle of incident light increases. The theoretical modeling allows us to relate photonic behavior with the optical properties of the wings of butterfly Greta oto. In particular, photonic behavior could be associated with the iridescent phenomenon on the butterfly wings.

* Abbreviations: GAC — : gender-affirmative medical care GnRHa — : gonadotropin-releasing hormone analogue TGD — : transgender and gender-diverse Transgender and gender-diverse (TGD) youth experience barriers to accessing health care and are at risk for poorer overall health compared with cisgender peers. In the last year, dozens of US legislative bills have been proposed to restrict the rights of TGD youth.1 A subset of these bills aims to restrict access to essential treatment of youth diagnosed with gender dysphoria, even when they meet rigorous criteria, as determined by a multidisciplinary evaluation (Table 1).1,2 Other proposed legislation would criminalize clinicians who provide gender-affirmative medical care (GAC) for TGD adolescents, with one bill currently under consideration in Oklahoma classifying providing GAC as a felony punishable by 3 years to life in prison.1 Clinicians and parents fear that legislation eliminating access to GAC will lead to worsening mental health and increased suicidality for their TGD children.3 View this table: TABLE 1 Bills Proposed During the 2021 US State Legislative Session to Date Despite these objections, in December 2020, the Bell versus Tavistock ruling in the United Kingdom mandated … Address correspondence to Jessica Kremen, MD, Division of Endocrinology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: jessica.kremen{at}childrens.harvard.edu

The necrotic streak of the fique (Furcraea spp.) or “Macana” disease is considered the most limiting disease for this crop in Colombia, whose causal agent is the Furcraea Necrotic Streak Virus - FSNV (RNA +). Currently, there are no strategies to control the disease, being necessary to develop methods for early detection of this disease in the planting material before being taken to the field. In this study, polyclonal antibodies produced in egg yolk (IgY) were assesses for detection FSNV. Two immunoenzymatic methodologies were standardized: Dot Blot Immunobinding Assay (DBIA) and Enzyme Linked Immunosorbent Assay (ELISA), determining their specificity and sensitivity. The detection limit by DBIA corresponded to 8 µg/mL of purified virus suspension using 10 µg/mL of primary antibody. In the ELISA test, the primary antibody concentration of 3 µg/mL (1:800 dilution) detected the antigen at concentrations between 10 and 70 µg/mL. The polyclonal antibody anti-FNSV IgY allowed the detection of FNSV in samples of purified virus and extracts of roots and leaves of fique plants with symptoms of “Macana” disease and did not produce any signal with the control samples. Results showed the potential of using egg yolk IgY for immunological test as a novel approach for the early detection of FNSV in fique plants.

Summary Optimized time-domain pre-migration reprocessing and advanced full-azimuth (FAZ) depth imaging of a 3D rich-azimuth land seismic dataset from the mature Middle Magdalena Valley Basin, onshore Colombia, resulted in a step-change in pre-stack time and depth migrated image quality and resolution, without the need for excessive post-migration processing and amplitude gains, and reliably tied to well logs at Eocene reservoir level. We present a case study in which successful deployment of new-generation processing and imaging techniques, QC processes and advanced depth migration algorithms with Q-compensation was carefully integrated to achieve all imaging and exploration goals. High-frequency absorption was not even reported nor resolved in any legacy processing passes, which illustrates that imaging challenges need to be identified before geophysical solutions can be planned and implemented. Strong Quality Control is vital. The enhanced reflection PSDM image was complemented by depth-domain dip-angle diffraction imaging, adding value to fault characterization in conventional and unconventional (Cretaceous) target intervals. The obtained results provide geologists and interpreters with insight into the Eocene reservoir in the Middle Magdalena Valley, Colombia. Diffraction imaging, applied onshore, is capable to show details otherwise considered subseismic, related to small faults, fractured zones, and other subtle seismic features.

A cognitive model is a computational model of internal information processing mechanisms of the brain for the purposes of comprehension and prediction. CARINA metacognitive architecture runs cognitive models. However, CARINA does not currently have mechanisms to store and learn from cognitive models executed in the past. Semantic knowledge representation is a field of study which concentrates on using formal symbols to a collection of propositions, objects, object properties, and relations among objects. In CARINA Beliefs are a form of represent the semantic knowledge. The aim of this chapter is to formally describe a CARINA-based cognitive model through of denotational mathematics and to represent these models using a technique of semantic knowledge representation called beliefs. All the knowledge received by CARINA is stored in the semantic memory in the form of beliefs. Thus, a cognitive model represented through beliefs will be ready to be stored in semantic memory of the metacognitive architecture CARINA. Finally, an illustrative example is presented.

Purpose To investigate the safety of photobiomodulation therapy (PBM) in tumors and its potential as a radiosensitizer when combined with radiotherapy. Methods We have performed in vitro experiments in A431 cells to assess proliferation and cell cycle after PBM, as well as clonogenic assay and H2AX-gamma immunolabeling to quantify double strand breaks after the combination of PBM and radiation. In vivo experiments in xenografts included Kaplan-Meier survival analysis, optical coherence tomography (OCT) and histological analysis. Results PBM did not induce proliferation in vitro, but increased the G2/M fraction by 27% 24h after illumination, resulting in an enhancement of 30% in radiation effect in the clonogenic assay. The median survival of the PBM-RT group increased by 4 days and the hazard ratio was 0.417 (CI 95%: 0.173–1.006) when compared to radiation alone. OCT analysis over time demonstrated that PBM increases tumor necrosis due to radiation, and histological analysis showed that illumination increased cell differentiation and angiogenesis, which may play a role in the synergetic effect of PBM and radiation. Conclusion PBM technique may be one of the most appropriate approaches for radiosensitizing tumors while protecting normal tissue because of its low cost and low training requirements for staff.

The growth of detrimental biofilms on metal surfaces affects their structural performance and lifespan. Microtopographic texturization has emerged as an approach to suppress biofilm growth by preventing the initial stages of bacterial adhesion. This work studies the effects of linear pattern copper texturization on the initial adhesion steps of the biofilm-forming and copper-resistant bacterium Variovorax sp. Linear patterns with 4.7, 6.8, 14, and 18 μm periodicity were produced by direct laser interference patterning (DLIP) on copper coupons. Surface features were characterized by microscopic and spectroscopic techniques, and bacterial adhesion behavior was characterized by epifluorescence microscopy and functionalization of atomic force microscopy tips. We found a periodicity of 4.7 μm as the most efficient pattern to suppress Variovorax sp. initial adhesion by 31.1 % with respect to the nontextured surface. Preferential settlement in hummocks over hollows was observed for patterns with 14 and 18 μm periodicity, with adhesion events showing higher frequency in these topographies than patterns with periodicities of 4.7 and 6.8 μm. Our results highlight an understanding of the initial bacteria-copper adhesion and settlement behavior, thus contributing to the potential development of innocuous strategies for controlling biofilm growth on copper-based materials.

A dual-rail hybrid analog/digital LDO achieves both high efficiency and tunable high PSRR simultaneously using a dynamic current steering mechanism. Measurements on a 22nm CMOS test chip demonstrate up to −46dB PSRR and 89% efficiency across 0–80mA load from1.8V/1.05V dual-input rails.

Objective: This study aimed to determine the association between venous–arterial CO2 difference (Pv-aCO2) and clinical outcomes of interest in children with severe sepsis and septic shock. Design: An analytical observational study of a prospective cohort was conducted. Setting: The study was carried out from January 2015 to January 2018 in the pediatric intensive care unit of a referral hospital. Materials and methods: Of a total of 1159 patients who were admitted to pediatric critical care, 375 had severe sepsis and septic shock, of which 67 fulfilled the inclusion criteria. Arterial and venous gases were drawn simultaneously with a transthoracic echocardiogram, Pv-aCO2, and other measures of tissue perfusion such as arterial lactate, venous, and evolution to multiple organ failure. Measurements and main results: Half (53.7%) of the patients were under 24 months old, with a slight predominance of male patients. The main site of infection was the lungs in 56% of the cases, with a 91.2% survival rate. Patients who died had a higher venous lactate level (interquartile range 16.2–33.6, p = 0.02). However, there was no correlation between myocardial dysfunction seen on echocardiogram and a Pv-aCO2 greater than 6 mm Hg in children with severe sepsis and septic shock (r = 0.13). Pv-aCO2 and central venous saturation had low sensitivity to detect multiple organ failure and poor correlation with the number of compromised systems (r = 0.8). Conclusion: Pv-aCO2 was not associated with myocardial dysfunction, measured by echocardiogram, in children with severe sepsis and septic shock. It also did not correlate with the number of organs involved or mortality.

The application of isogeometric analysis requires a full parametrization map of the physical domain. This map is suitable for the analysis only if it is injective. In this paper we give a necessary condition for the injectivity of a B-spline biquadratic map. Moreover, sufficient injectivity conditions, which are easy to check in the practice, are introduced. A method for parametrizing planar regions using a biquadratic map is also proposed. The method is simpler than others reported in the literature, since it is based on the solution of an optimization problem without restrictions and only requires the construction of a quadrilateral mesh with optimal geometric properties. Finally we show that the proposed method can be successfully used to obtain high quality parametrizations of simply connected planar regions with irregular boundary.

Key points Extracellular ATP, in association with [Ca2+]i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Abstract Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca2+]i-dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca2+]i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml−1) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an antagonist used to block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing extracellular ATP levels (0.1–100 μm) increased CBF, maintaining a sustained response that was suppressed in the presence of carbenoxolone. We also show that high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal CBF by reducing [Ca2+]i and hemichannel functionality. In summary, we provide evidence indicating that airway epithelium ATP release is the molecular autocrine mechanism regulating basal ciliary activity and is also the mediator of the ciliary response to chemical stimulation.

Dilute acid hydrolysis (DAH) and auto-hydrolysis (AU) have demonstrated to be optimal pre-treatments for the generation of biofuels from wood. Recent studies have highlighted the importance of ensuring the accessibility of cellulose enzymes during the enzymatic hydrolysis (EH) of pre-treated materials. In this work, the microscopic and nanoscopic structures of Eucalyptus globulus samples pre-treated by AU and DAH were evaluated by different techniques to understand the effect of the ultrastructure of samples on the enzymatic conversion and cellulose accessibility for bioethanol production. Microscopic techniques revealed changes in the physical characteristics of pre-treated fibers, coalescence at microscopic level, and differences in the chemical distribution of lignocellulosic components depending on the severity and type of pre-treatment. The atomic force microscopy-based nanoscopic study of samples showed differences in the effect of the pre-treatments on the ultrastructure of samples, with DAH pre-treatment producing major changes in the secondary cell wall with respect to AU samples at comparable severities, and a positive effect of the DAH ultrastructure changes to increase the EH yield.

The ability of the isolate VG008 of S. frugiperda granulovirus (SpfrGV) to enhance the infectivity of the isolate SfCOL of S. frugiperda multiple nucleopolyhedrovirus (SpfrMNPV) was evaluated on S. frugiperda larvae. Bioassays were performed with mixtures by using different proportions 90%:10% (M1), 95%:5% (M2) and 97.5%:2.5% (M3) of SfCOL:VG008, respectively. All mixtures showed higher insecticidal activity that SfCOL. The mixture M3 showed the highest enhancement of SfCOL reducing 11.40 times the Mean Lethal Concentration and 96 h in the Mean Time to Death. The enhancer activity of proteins derived from VG008 (GVPs) were also evaluated in mixture with SfCOL. The GVPs increased 27% larval mortality caused by SfCOL and damaged the peritrophic membrane of S. litura larvae, suggesting that the key point in this enhancing activity is the initial step of the larva colonization, the midgut infection. M3 was formulated and evaluated under greenhouse conditions in maize plants using different doses. The highest efficacy was obtained with the highest dose of M3 (8 × 1011 OBs/ha), which was similar to that found when formulated SfCOL was applied using an approximately twofold higher dose. The viral mixture M3 was selected as the active ingredient for developing a new biopesticide for a more efficient management of the pest in the field.

Titanium dioxide nanotubes, TiO2 NTs, can be obtained by electrochemical anodization of Titanium sheets. After nanotubes are removed by mechanical stress, residual structures or traces on the surface of titanium sheets can be observed. These traces show iridescent effects. In this paper we carry out both experimental and theoretical study of those interesting and novel optical properties. For the experimental analysis we use angle resolved UV–vis spectroscopy while in the theoretical study is evaluated the photonic spectra using numerical simulations into the frequency-domain and the framework of the wave plane approximation. The iridescent effect is a strong property and independent of the sample. This behavior can be important to design new materials or compounds for several applications such as, cosmetic industry, optoelectronic devices, photocatalysis, sensors, among others.

Approaches for thermal management of lithium-ion (Li-ion) batteries do not always keep pace with advances in energy storage and power delivering capabilities. Root-cause analysis and empirical evidence indicate that thermal runaway (TR) in cells and cell-to-cell thermal propagation are due to adverse changes in physical and chemical characteristics internal to the cell. However, industry widely uses battery management systems (BMS) originally designed for aqueous-based batteries to manage Li-ion batteries. Even the “best” BMS that monitor both voltage and outside-surface temperature of each cell are not capable of preventing TR or TR propagation, because voltage and surface-mounted temperature sensors do not track fast-emerging adverse events inside a cell. Most BMS typically include a few thermistors mounted on select cells to monitor their surface temperature. Technology to track intra-cell changes that are TR precursors is becoming available. Simultaneously, the complex pathways resulting in cell-to-cell TR propagation are being successfully modelled and mapped. Innovative solutions to prevent TR and thermal propagation are being advanced. These include modern BMS for rapid monitoring the internal health of each individual cell and physical as well as chemical methods to reduce the deleterious effects of rapid cell-to-cell heat and material transport in case of TR.

We evaluated the effects of titanium plasma nitriding and oxidation on live endothelial cell viscoelasticity. For this, mechanically polished titanium surfaces and two surfaces treated by planar cathode discharge in nitriding (36N2 and 24H2) and oxidant (36O2 and 24H2). Surfaces were characterized regarding wettability, roughness and chemical composition. Rabbit aortic endothelial cells (RAECs) were cultured on the titanium surfaces. Cell morphology, viability and viscoelasticity were evaluated by scanning electron microscopy (SEM), methyl thiazolyl tetrazolium (MTT) assay and atomic force microscopy (AFM), respectively. Grazing Incidence X-ray Diffraction confirmed the presence of TiN0,26 on the surface (grazing angle theta 1°) of the nitrided samples, decreasing with depth. On the oxidized surface had the formation of TiO3 on the material surface (Theta 1°) and in the deeper layers was noted, with a marked presence of Ti (Theta 3°). Both plasma treatments increased surface roughness and they are hydrophilic (angle < 90°). However, oxidation led to a more hydrophilic titanium surface (66.59° ± 3.65 vs. 76.88° ± 2.68; p = 0.001) due to titanium oxide films in their stoichiometric varieties (Ti3O, TiO2, Ti6O), especially Ti3O. Despite focal adhesion on the surfaces, viability was different after 24 h, as cell viability on the oxidized surface was higher than on the nitrided surface (9.1 × 103 vs. 4.5 × 103cells; p < 0.05). This can be explained by analyzing the viscoelastic property of the cellular cytoskeleton (nuclear and peripheral) by AFM. Surface oxidation significantly increased RAECs viscoelasticity at cell periphery, in comparison to the nucleus (2.36 ± 0.3 vs. 1.5 ± 0.4; p < 0.05), and to the RAECs periphery in contact with nitrided surfaces (1.36 ± 0.7; p < 0.05) and polished surfaces (1.55 ± 0.6; p < 0.05). Taken together, our results have shown that titanium plasma treatment directly increased cell viscoelasticity via surface oxidation, and this mechanobiological property subsequently increased biocompatibility.

Summary Neurotransmitter-gated ion channels are allosteric proteins that switch on and off in response to agonist binding. Most studies have focused on the agonist-bound, activated channel while assigning a lesser role to the apo or resting state. Here, we show that nanoscale mobility of resting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors (AMPA receptors) predetermines responsiveness to neurotransmitter, allosteric anions and TARP auxiliary subunits. Mobility at rest is regulated by alternative splicing of the flip/flop cassette of the ligand-binding domain, which controls motions in the distant AMPA receptor N-terminal domain (NTD). Flip variants promote moderate NTD movement, which establishes slower channel desensitization and robust regulation by anions and auxiliary subunits. In contrast, greater NTD mobility imparted by the flop cassette acts as a master switch to override allosteric regulation. In AMPA receptor heteromers, TARP stoichiometry further modifies these actions of the flip/flop cassette generating two functionally distinct classes of partially and fully TARPed receptors typical of cerebellar stellate and Purkinje cells.

Son illər nanotexnologiyanın sürətli inkişafı və nəticə olaraq insan fəaliyyətinin müxtəlif sahələrində tətbiq edilməsi həyata keçir. Nanomateriallar unikal ölçüsü və morfoloji xüsusiyyətlərinə görə fiziki və kimyəvi cəhətdən emal edilə bilir, sənaye və biotibbi proseslərdə geniş istifadə olunur. TiO2 nanohissəciyi (NH) mühüm ekoloji, texnoloji və biotibbi sahələrdə tətbiq edilir. TiO2 NH insan və heyvan orqanizminə daxil edilməsinin əsas yolları – tənəffüs sistemi, peroral və perkutan hesab edilir. Nəticədə, əsas hədəf orqanları tənəffüs, bağırsaq, immun, dəri sistemləri toxumaları, təsirinə gorə isə daha kritik beyin, sümük iliyi, reproduktiv və ifrazat orqanlarıdır.