Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Expression of mRNA and protein of IL-18 and its receptor in human follicular granulosa cells.

PURPOSE: There is no information available about the IL-18 receptor in ovarian follicles, so the present study attempts to demonstrate the expression of IL-18 and its receptor in human granulosa cells (GCs). METHODS: To evaluate the concentration of IL-18 in serum and follicular fluid (FF), we collected serum and FF from 102 women undergoing oocyte retrieval. Also, to detect expression of IL-18 and its receptor by luteinized GCs, these cells were pooled six times from a total of twenty individual patients with 5-16 follicles each. The IL-18 concentration was determined by ELISA and the expression of IL-18 and its receptor by immunocytochemistry and reverse transcription polymerase chain reaction. RESULTS: Our results showed that the median IL-18 concentration in serum, 159.27 pg/ml (IQR 121.41-210.1), was significantly higher than in FF, 142.1 pg/ml (IQR 95.7-176.5), p < 0.001. Moreover, we found that IL-18 and its receptor are expressed by GCs. CONCLUSION: The presence of IL-18 in FF and the expression of IL-18 and its receptor by GCs suggest an important role for this cytokine in ovarian function.

Follicular fluid PlGF/sFlt-1 ratio and soluble receptor for advanced glycation end-products correlate with ovarian sensitivity index in women undergoing A.R.T.

PURPOSE: Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI. METHODS: In a cross-sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited. The patients were divided according to ovarian sensitivity index (OSI). ICSI cycle outcomes were evaluated for each patient and PlGF, sFlt-1 and sRAGE levels of follicular fluid were assayed using commercial ELISA kits. RESULTS: Follicular fluid (FF) sRAGE levels and PlGF/sFlt-1 ratio were statistically greater in high-responder women than other responders (p < 0.05). Positive correlations were obtained between sRAGE level with the number of oocytes, follicles and OSI level. sRAGE levels with cutoff value of 4.83 (ng/ml) for evaluating the pregnancy outcome showed 81.8 % sensitivity and 60.7 % specificity. Furthermore, there were positive associations between PlGF/sFlt-1 ratio with the number of oocytes, embryos and OSI level. CONCLUSION: In conclusion, the results of current study supported that good ovarian response is independent of pregnancy outcome. Our results showed that FF levels of sRAGE and PlGF/sFlt-1 ratio could be used as markers for determining the high-responder women. Also, FF sRAGE levels could be a good predictor for ART outcome.

A guided wave propagation method for delamination detection in fiber-metal laminates.

This study aimed to assess the delamination detection in FMLs via the finite element (FE) simulations of Lamb wave propagation. An FE model of an FML specimen with [Al/902/Al/902/Al] layup was developed. Delamination damage of 10 and 25 mm diameters was induced between different layers of the FML specimen. The fundamental antisymmetric Lamb wave mode (A0) at 60 kHz and the fundamental symmetric Lamb wave mode (S0) at the frequency of 206 kHz were propagated on the developed FE models. The Lamb wave phase velocity was obtained from the FE models and compared with those obtained from the Lamb wave propagation tests. The sensitivity of the A0 and S0 Lamb wave modes to the delamination and its diameter were examined. The inverse Lamb wave propagation problem was then solved, and the elastic modulus of the FML specimen was estimated in the intact and delamination regions. It was observed that the phase velocity of the S0 Lamb wave mode had a higher sensitivity to the delamination damage compared to that of the A0 Lamb wave mode. The phase velocity of the A0 Lamb wave mode was more sensitive to the delamination diameter. The capability of the proposed simulated Lamb wave propagation method as a virtual lab for detecting delamination in the FMLs was confirmed.

On the structural and electrical properties of MgFe2O4, MgMn0.2Fe1.8O4, and Mn3O4.

Charge carrier transport via donor/acceptor pairs of similar elements is dominant in n-type MgFe2O4 and p-type Mn3O4 spinels. The temperature-independent activation energy in the form of the nearest neighbor hopping model is applied for Fe2+/Fe3+ pairs of cubic MgFe2O4 spinel in the temperature range of 423-523 K (150-250 °C). At such high temperatures, even for this relatively narrow temperature range, the constant energy barrier deviates to a variable range hopping energy barrier in the case of Mn3O4, due to Jahn-Teller active octahedral sites. Replacing 10 mol% of Fe at octahedral sites with Mn has significantly increased the electron hopping energy barrier and electrical conductivity of MgFe2O4, while keeping the nearest neighbor hopping model dominant. The observed high energy barrier is due to donor/acceptor pairs of different elements (Mn/Fe). Due to a lack of structural distortion, deviation from the nearest neighbor hopping mechanism with temperature-independent activation energy was not observed. Rietveld refined XRD patterns and FT-IR spectra are utilized to support the argument on electrical conductivity mechanisms.

A systemic approach to analyze integrated energy system modeling tools: A review of national models.

We reviewed the literature focusing on nineteen integrated Energy System Models (ESMs) to: (i) identify the capabilities and shortcomings of current ESMs to analyze adequately the transition towards a low-carbon energy system; (ii) assess the performance of the selected models by means of the derived criteria, and (iii) discuss some potential solutions to address the ESM gaps. This paper delivers three main outcomes. First, we identify key criteria for analyzing current ESMs and we describe seven current and future low-carbon energy system modeling challenges: the increasing need for flexibility, further electrification, emergence of new technologies, technological learning and efficiency improvements, decentralization, macroeconomic interactions, and the role of social behavior in the energy system transition. These criteria are then translated into required modeling capabilities such as the need for hourly temporal resolution, sectoral coupling technologies (e.g., P2X), technological learning, flexibility technologies, stakeholder behavior, cross border trade, and linking with macroeconomic models. Second, a Multi-Criteria Analysis (MCA) is used as a framework to identify modeling gaps while clarifying high modeling capabilities of MARKAL, TIMES, REMix, PRIMES, and METIS. Third, to bridge major energy modeling gaps, two conceptual modeling suites are suggested, based on both optimization and simulation methodologies, in which the integrated ESM is hard-linked with a regional model and an energy market model and soft-linked with a macroeconomic model.

Voriconazole resistance genes in Aspergillus flavus clinical isolates.

OBJECTIVE: The present study was designed to discover novel biomarkers involved in voriconazole resistance in clinical isolates of Aspergillus flavus. MATERIALS AND METHODS: Two voriconazole non-wild-type and two voriconazole-wild-type A. flavus clinical isolates were selected to evaluate possible molecular mechanism involved in A. flavus resistance to voriconazole using the mutation assessment, Quantitative real- time PCR of cyp51A and cyp51C genes and complementary DNA- amplified fragment length polymorphism technique. RESULTS: No mutations were seen in the cyp51A and cyp51C genes in voriconazole non-wild-type isolates compared to wild- type and reference strains. Regarding to mRNA expression results, no changes were observed in expression fold of cyp51A and cyp51C mRNA expression level in first non- wild- type isolate compared to wild-type isolate. For second isolate cyp51C mRNA expression level was down regulated (5.6 fold). The set of genes including ABC fatty acid transporter XM- 002375835 and aldehydereductase XM- 002376518 and three unknown functional genes were identified. Based on results, the over-expression of AKR1 and ABC fatty acid transporter in the voriconazole non- wild- type isolates suggests these genes could represent a novel molecular marker linked to the voriconazole resistance in A. flavus. CONCLUSION: The results obtained in this study showed a novel finding as the authors identified AKR1 and ABC fatty acid transporter genes as possible voriconazole target genes in Iranian clinical isolates of A. flavus.

Presentation of a Hemangioblastoma in cavernous sinus: An extremely rare case report.

INTRODUCTION: Hemangioblastoma (HB) is a benign vascular tumor that accounts for about 2% of intracranial neoplasms. HB of the cavernous sinus (CS) is extremely rare. Only one report was found in the literature. PRESENTATION OF CASE: We present a 29-year-old female with progressive headache and she had right ptosis and right mild oculomotor nerve palsy. The brain Magnetic Resonance Imaging (MRI) revealed a right extra-axial 4 × 4 cm in right CS position. The patient was operated upon microscopically via sub-temporal approach through a right temporal craniotomy. After the subtotal removal of a highly vascular tumor, the patient was referred for adjuvant therapy with Gamma-knife surgery. DISCUSSION: Surgical removal of HB is the most effective treatment of the central nervous system (CNS) HBs. Tumors invading the CS could cause severe bleeding during surgery and HB-because of its vascular origin-had more risk for severe intraoperative bleeding, and in some cases resulted in surgery stop with subtotal resection of tumor. CONCLUSION: It was recommended to perform a pre-operative brain angiography and selective embolization of these highly vascular lesions that it could result in subsequent complete surgical removal.

Onychomycosis due to dermatophytes species in Iran: Prevalence rates, causative agents, predisposing factors and diagnosis based on microscopic morphometric findings.

OBJECTIVE: Onychomycosis (OM) or fungal nail infection is one of the most common fungal infections, which is increasingly prevalent. OM is caused by dermatophytes spp, yeasts and non-dermatophyte moulds (NDMs). The purpose of this study was to identify and determine the prevalence rates, predisposing factors and causative agents of OM using clinical symptoms and microscopic morphometric findings. MATERIALS AND METHODS: In the present study, 180 patients suspected of OM were evaluated by direct microscopy using KOH 20%, culturing in Mycosel and Sabouraud dextrose agar media and Olysia software for identifying the causative fungi of OM. RESULTS: From 180 referred patients, 118 (65.56%) had OM, of whom 79 (66.94%) were positive for infection with dermatophytes spp. Of the 79 cases, the commonest age group was 61-70 years (21%) with males being 46 (58.23%) and females being 33 (41.77%). Both the fingernail and toenail infections were most prevalent in male patients. Sex, diabetes and age above 60 years were significant predisposing factors for OM development. DLSO was observed as the only clinical pattern of OM and T. rubrum was the commonest dermatophyte isolate (49.34%). CONCLUSION: This study showed that T. rubrum was the most common dermatophyte agent of OM in Iran.

Development an efficient calibrated nonlocal plate model for nonlinear axial instability of zirconia nanosheets using molecular dynamics simulation.

New ceramic materials containing nanoscaled crystalline phases create a main object of scientific interest due to their attractive advantages such as biocompatibility. Zirconia as a transparent glass ceramic is one of the most useful binary oxides in a wide range of applications. In the present study, a new size-dependent plate model is constructed to predict the nonlinear axial instability characteristics of zirconia nanosheets under axial compressive load. To accomplish this end, the nonlocal continuum elasticity of Eringen is incorporated to a refined exponential shear deformation plate theory. A perturbation-based solving process is put to use to derive explicit expressions for nonlocal equilibrium paths of axial-loaded nanosheets. After that, some molecular dynamics (MD) simulations are performed for axial instability response of square zirconia nanosheets with different side lengths, the results of which are matched with those of the developed nonlocal plate model to capture the proper value of nonlocal parameter. It is demonstrated that the calibrated nonlocal plate model with nonlocal parameter equal to 0.37nm has a very good capability to predict the axial instability characteristics of zirconia nanosheets, the accuracy of which is comparable with that of MD simulation.

Gas phase hydrogen deuterium exchange reactions of a model peptide: FT-ICR and computational analyses of metal induced conformational mutations.

We utilized gas phase hydrogen/deuterium (H/D) exchange reactions and ab initio calculations to investigate the complexation between a model peptide (Arg-Gly-Asp[triple bond]RGD) with various alkali metal ions. The peptide conformation is drastically altered upon alkali metal ion complexation. The associated conformational changes depend on both the number and type of complexing alkali metal ions. Sodium has a smaller ionic diameter and prefers a multidentate interaction that involves all three amino acids of the peptide. Conversely, potassium and cesium form different types of complexes with the RGD. The [RGD + 2Cs - H]+ species exhibit the slowest H/D exchange reactivity (reaction rate constant of approximately 6 x 10(-13) cm3molecule(-1)s(-1) for the fastest exchanging labile hydrogen with ND3). The reaction rate constant of the protonated RGD is two orders of magnitude faster than that of the [RGD + 2Cs - H]+. Addition of the first cesium to the RGD reduces the H/D exchange reaction rate constant (i.e., D0) by a factor of seven whereas sodium reduces this value by a factor of thirty. Conversely, addition of the second alkali metal ions has the opposite effect; the rate of D0 disappearance for all [RGD + 2Met - H]+ species (Met[triple bond]Na, K, and Cs) decreases with the alkali metal ion size.

Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy.

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.

In vitro cytotoxic evaluation of some synthesized COX-2 inhibitor derivatives against a panel of human cancer cell lines.

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents.