ARTICLE | doi:10.20944/preprints201903.0127.v1
Subject: Materials Science, Nanotechnology Keywords: focal plane array, thermal source, synchrotron radiation, infrared spectroscopy, hyperspectral imaging, silk, SZ2080
Online: 11 March 2019 (09:38:21 CET)
A focal plane array (FPA) detector was used for hyperspectral imaging in the infrared (IR) spectral region using thermal and synchrotron light sources. FPA Fourier-transform IR (FTIR) imaging microspectroscopy will be able to monitor real time changes at specific absorption bands when combined with high brightness synchrotron source. In this study, several types of samples with unique structural motifs were selected and used for assessing the capability of the FPA-FTIR imaging technique. It was shown that the time required for polariscopy at IR wavelengths can be substantially reduced by the FPA-FTIR imaging approach. By using natural and laser fabricated polymers with sub-wavelength features, alignment of absorbing molecular dipoles was revealed as well as higher order patterns (laser fabricated structures). Micro-spectroscopy of absorber orientation reveals alignment patterns even when they are not spatially resolved.
ARTICLE | doi:10.20944/preprints201905.0314.v1
Subject: Earth Sciences, Space Science Keywords: the Chang’e-4 lunar rover; phase-locked; signal-to-noise ratio; spectral resolution; infrared focal plane components
Online: 27 May 2019 (12:01:44 CEST)
The Chang’e-4 (CE-4) lunar rover, equipped with The Visible and Near-IR Imaging Spectrometer(VNIS) which based on acousto-optic tunable filter spectroscopy, was launched to the far side of the moon on December 8, 2018. The detection band of VNIS ranges from 0.45 to 2.4μm. Because of the weak reflection of infrared radiation from the lunar surface, a static electronic phase-locked acquisition method is adopted in the infrared channel for signal amplification. In this paper, full-link simulations and modeling are conducted of the infrared channel information flow of the instrument. The signal/noise characteristics of VNIS are analyzed in depth, and the signal-to-noise(SNR) ratio prediction and laboratory verification are presented. On January 4, 2019, the VNIS started working successfully and acquired high-resolution spectrum data of the far side of the moon for the first time. Through analysis, the SNR ratio is in line with predictions, and the data obtained by VNIS in orbit are consistent with the information model proposed in this paper.
ARTICLE | doi:10.20944/preprints202103.0181.v1
Subject: Engineering, Automotive Engineering Keywords: focal vibration therapy; vibration frequency; vibration amplitude; vibration intensity
Online: 5 March 2021 (10:10:38 CET)
Focal vibration therapy can provide neurophysiological benefits. Unfortunately, standardized protocols are non-existent. Previous research presents a wide range of protocols with a wide range of effectiveness. This paper is part of a broader effort to identify effective, standardized protocols for focal vibration therapy. The vibration characteristics of four commercially available focal vibration devices that have been used for research and clinically were measured. An accelerometer was used for the measurements. Frequency and peak-to-peak amplitude were measured. Measurements were made when the devices were free and then again when they were strapped to the human body. Vibration frequency ranged from 120 to 225 Hz. Free vibration amplitude ranged from 2.0 to 7.9 g’s (peak-to-peak). When the devices were strapped to the body (constrained), vibration amplitude decreased by up to 65.7%. These results identify effective ranges of focal vibration frequency and amplitude. They illustrate the importance of identifying vibration environment, free or constrained, when quoting vibration characteristics. Finally, the inconsistency of multi-actuator devices is discussed. These results will guide protocol development for focal vibration and potentially better focal vibration devices.
ARTICLE | doi:10.20944/preprints202301.0159.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: mesenchymal stem cells; mechanotransduction; collagen; oxidation; YAP/TAZ; focal adhesion
Online: 9 January 2023 (09:53:23 CET)
ECM provides various mechanical cues that are able to affect the self‑renewal and differentiation of mesenchymal stem cells (MSC). Little is known however how these ques work in a pathological environment, such as acute oxidative stress. To better understand the behavior of human adipose tissue-derived MSC (ADMSC) in such conditions here we provide morphological and quantitative evidence for significantly altered early steps of mechanotransduction when adhering to oxidized collagen (Col-Oxi). This affects both focal adhesion (FA) formation and YAP/TAZ signaling events. Representative morphological images show that ADMSCs spread better within 2 h of adhesion on native collagen (Col), while they tended to round up on Col-Oxi. It correlates also with the less development of the actin cytoskeleton and FA formation, confirmed quantitatively by morpho-metric analysis using ImageJ. As shown by immunofluorescence analysis, oxidation also affected the ratio of cytosolic to nuclear YAP/TAZ activity, concentrating in the nucleus for Col while remaining in the cytosol for Col-Oxi, suggesting abrogated signal transduction. Comparative AFM studies show that native collagen forms relatively coarse aggregates, much thinner with Col-Oxi, possibly reflecting its altered ability to aggregate. On the other hand, the corresponding Young's moduli were only slightly changed, so viscoelastic properties cannot explain the observed biological differences. However, the roughness of the protein layer decreases dramatically, from RRMS equal to 27.95 + 5.1 nm for Col to 5.51 + 0.8 nm for Col-Oxi (p<0.05), which dictates our conclusion that it is the most altered parameter in oxidation. Thus, it appears to be a predominantly topo-graphic response that affects the mechanotransduction of ADMSCs by oxidized collagen.
ARTICLE | doi:10.20944/preprints202203.0314.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: metabolomics; antiseizure medication; ¹H Nuclear Magnetic Resonance; focal epilepsy; response to treatment
Online: 23 March 2022 (09:11:52 CET)
A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.
CASE REPORT | doi:10.20944/preprints202202.0288.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: chronic kidney disease; low birth weight; focal segmental glomerulosclerosis; two-hit theory
Online: 23 February 2022 (08:26:10 CET)
In Japan, the prevalence of low birth weight (LBW) has been estimated to be approximately 10%, which is the highest among developed countries. This high prevalence might affect the prevalence of LBW-associated diseases in the adult population of Japan. Recently, LBW has been recognized as a contributing factor to post-adaptive focal segmental glomerulosclerosis (FSGS) in adulthood; however, few reports to date have evaluated the clinical and pathological characteristics of post-adaptive FSGS. A 13-year-old girl was referred to our hospital owing to mild proteinuria, which was detected at a school urinary screening. She was born at a gestational age of 23 weeks, with a very LBW of 630 g. Dipstick urinalysis revealed grade (2+) proteinuria. Her serum creatinine level was 1.02 mg/dL, and she was diagnosed as having stage 2 chronic kidney disease (CKD). Her serum uric acid level was 7 mg/dL. Her mother and 16-years old brother had hyperuricemia, too. A percutaneous renal biopsy leads to a diagnosis of FSGS. After 3 years of treatment with an angiotensin receptor blocker, her proteinuria decreased. However, her serum creatinine level was 1.07 mg/dL, and she still had stage 2 CKD. We considered that in this patient, the first hit was her LBW, and the second hit was hyperuricemia. The second hit might be associated with the development of CKD. The birth history of patients is not usually confirmed by nephrologists. Our case demonstrates that obtaining information regarding the preterm birth and LBW of patients is important in the diagnosis of noncommunicable diseases, because school urinary screening is not routinely performed in countries other than Japan.
ARTICLE | doi:10.20944/preprints202211.0356.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Focal adhesion kinase; 3D-QSAR; Molecular Dynamics; MM-PB/GBSA; Free energy perturbation
Online: 18 November 2022 (10:13:00 CET)
Precise binding affinity predictions are essential for structure-based drug discovery (SBDD). Focal adhesion kinase (FAK) is a member of the tyrosine kinase protein family and is overexpressed in a variety of human malignancies. Inhibition of FAK using small molecules is a promising therapeutic option for several types of cancer. Here, we conducted computational modeling of FAK targeting inhibitors using 3-dimensional structure-activity relationship (3D-QSAR), molecular dynamics (MD), and hybrid topology-based free energy perturbation (FEP) methods. The structure-activity relationship (SAR) studies between the physicochemical descriptors and inhibitory activities of the chemical compounds were performed with reasonable statistical accuracy using CoMFA and CoMSIA. These are two well-known 3D-QSAR methods based on the principle of supervised machine learning (ML). Essential information regarding residue-specific binding interactions was determined using the MD and MM-PB/GBSA methods. Finally, physics-based relative binding free energy (〖∆∆G〗_RBFE^(A→B)) values of analogous ligands were estimated using the alchemical FEP simulation. An acceptable agreement was observed between the experimental and computed relative binding free energies. The overall results using ML and physics-based hybrid approaches could be useful for the rational optimization of accessible lead compounds with similar scaffolds targeting the FAK receptor.
ARTICLE | doi:10.20944/preprints202204.0082.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Caco2/HT-29 cells; lipopolysaccharide(LPS); mucins; focal adhesion pathway; ECM receptor in-teraction pathway
Online: 8 April 2022 (14:04:17 CEST)
Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.
REVIEW | doi:10.20944/preprints202207.0393.v1
Subject: Medicine & Pharmacology, Urology Keywords: metastatic castration-resistant prostate cancer; cancer vaccines; immunotherapy; focal therapy; combination immunotherapy; tumor immune microenvironment; in vivo vaccination
Online: 26 July 2022 (08:01:20 CEST)
Due to slow progression and susceptibility to radical forms of treatment low-grade PC is associ-ated with high overall survival (OS). With the clinical progression of PC the therapy is getting more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by i.e. immune evasion through Treg cells, synthesis of immunosuppressive mediators, and defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of the tumor and eliminate the immunosuppres-sive properties of TME. In the settings of PC treatment, this can be commonly achieved with radi-ation therapy (RT). Also, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), or irreversible electroporation (IRE) were shown to boost anti-cancer response. Nevertheless, the present guide-lines restrict their application to localized and low-grade PC. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.
ARTICLE | doi:10.20944/preprints202108.0210.v1
Subject: Medicine & Pharmacology, Other Keywords: microscopic polyangiitis; granulomatosis with poliangiitis; eosinophilic granulomatosis with poliangiitis; kidney biopsy; pauci-immune focal and segmental necrotizing and crescentic glomerulonephritis; tubular atrophy and interstitial fibrosis; kidney survival
Online: 10 August 2021 (07:59:00 CEST)
ANCA-associated vasculitis (AAV) pose a significant risk of kidney failure, kidney biopsy remains a key prognostic tool. Pathology classification of the AAV glomerulonephritis (GN) developed by Berden et al showed correlation between GN classes and kidney outcomes; ANCA Renal Risk Score (ARRS) included tubular atrophy and interstitial fibrosis (TA/IF) as an additional parameter for risk assessment. We aimed to evaluate kidney survival across AAV GN classes and ARRS groups. A single-center retrospective study included 85 adult patients with biopsy-proven AAV kidney disease followed in 2000-2020. Primary outcome was kidney survival at the end of 18 [5; 66] months follow-up, kidney death considered as CKD stage 5. We found significant difference in the kidney survival for sclerotic, mixed, crescentic and focal AAV GN classes: 19%, 76.2%, 91.7% and 100% respectively (p=0.009). Kidney survival was 0%, 75.6% and 100% for the high, median and low risk ARRS groups respectively (p<0.001); TA/IF analysis showed kidney survival 49.6% vs 87.7% for widespread and mild TA/IF respectively (р=0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1% respectively, р=0.045). We conclude that unfavorable AAV kidney outcomes associated with sclerotic GN class by Berden’s classification, ARRS high risk group, and anti-MPO-ANCA subtype.