Miracle-dz/UniFAR-FTUs huggingface dataset:
The Constitutive Proteome of Human Aqueous Humor and Race Specific Alterations

Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating ocular homeostasis. Analysis of aqueous humor proteome is challenging, mainly due to low sample volume and protein concentration. In this study, by utilizing state of the art technology, we performed Liquid-Chromatography Mass spectrometry (LC-MS/MS) analysis of 88 aqueous humor samples from subjects undergoing cataract surgery. A total of 2263 unique proteins were identified, which were sub-divided into four categories that were based on their detection in the number of samples: High (n = 152), Medium (n = 91), Low (n = 128), and Rare (n = 1892). A total of 243 proteins detected in at least 50% of the samples were considered as the constitutive proteome of human aqueous humor. The biological processes and pathways enriched in the AH proteins mainly include vesicle mediated transport, acute phase response signaling, LXR/RXR activation, complement system, and secretion. The enriched molecular functions are endopeptidase activity, and various binding functions, such as protein binding, lipid binding, and ion binding. Additionally, this study provides a novel insight into race specific differences in the AH proteome. A total of six proteins were upregulated, and five proteins were downregulated in African American subjects as compared to Caucasians.
Enhanced Antioxidant Capacity of Puffed Turmeric (Curcuma longa L.) by High Hydrostatic Pressure Extraction (HHPE) of Bioactive Compounds

Turmeric (Curcuma longa L.) is known for its health benefits. Several previous studies revealed that curcumin, the main active compound in turmeric, has antioxidant capacity. It has been previously demonstrated that puffing, the physical processing using high heat and pressure, of turmeric increases the antioxidant and anti-inflammatory activities by increasing phenolic compounds in the extract. The current study sought to determine if high hydrostatic pressure extraction (HHPE), a non-thermal extraction at over 100 MPa, aids in the chemical changes and antioxidant functioning of turmeric. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) analyses were conducted and assessed the content of total phenol compounds in the extract. The chemical changes of curcuminoids were also determined by high performance liquid chromatography (HPLC). Among the three variables of ethanol concentration, pressure level, and treatment time, ethanol concentration was the most influential factor for the HHPE of turmeric. HHPE at 400 MPa for 20 min with 70% EtOH was the optimal extraction condition for the highest antioxidant activity. Compositional analysis revealed that 2-methoxy-4-vinylphenol was produced by puffing. Vanillic acid and ferulic acid content increased with increasing HHPE time. Synergistic effect was not observed on antioxidant activity when the turmeric was sequentially processed using puffing and HHPE.
Computational Analysis of Metabolomic Toxicological Data Derived from NMR Spectroscopy

Kelly , Benjamin . M.S., Department of Computer Science & Engineering, Wright State University, 2009 . Computational Analysis of Metabolomic Toxicological Data Derived from NMR Spectroscopy. Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive method of acquiring metabolic profiles from biofluids. The most informative metabolomic features, or biomarkers, may provide keys to the early detection of changes within an organism such as those that result from exposure to a toxin. One major difficulty with typical NMR data, whether it come from a toxicological, medical or other source, is that it features a low sample size relative to the number of variables measured. Thus, traditional pattern recognition techniques are not always feasible. The ”curse of dimensionality” is an important consideration in selecting appropriate statistical and pattern recognition methods for the identification of potential biomarkers. In this thesis, several alternatives for isolating biomarkers are evaluated on NMR-derived toxicological data set and results are compared: the fold test, univariate ranking, the unpaired t-test, and the paired ttest are examined. Potential biomarkers were inspected for differences based on several subjective criteria including ability to identify consistent differences between treatment and control samples and distinguish potential vehicle effects, those effects caused by the method of delivery performed on both treated and control animals. Based on these results, the paired t-test method is preferred, due to its ability to attribute statistical significance, to take into consideration consistency of a single subject over a time course, and to mitigate the low sample, high dimensionality problem. A protocol for the paired t-test is also proposed to remove potential vehicle effects and identify toxic responses above the vehicle effects. Due to the large number of variables to be considered, a correction for multiple testing must be employed. In this thesis, several methods of correction for multiple test is evaluated. An acceptable p-value cutoff for each correction is proposed so that the most appropriate correction can be applied based on the purpose of the metabolomic toxicology experiment. Also in this thesis, a more complex method for identifying biomarkers, Orthogonal Projection to Latent Structures Discriminant Analysis (O-PLS-DA), is compared to the t-test using synthetic data sets based on the characterization of experimental NMR spectra. The ranking of potential biomarkers produced by both methods is compared to the ranking of features used to create the synthetic data. In addition, an O-PLS-DA
Multi-Branch Convolutional Neural Network for Automatic Sleep Stage Classification with Embedded Stage Refinement and Residual Attention Channel Fusion

Automatic sleep stage classification of multi-channel sleep signals can help clinicians efficiently evaluate an individual’s sleep quality and assist in diagnosing a possible sleep disorder. To obtain accurate sleep classification results, the processing flow of results from signal preprocessing and machine-learning-based classification is typically employed. These classification results are refined based on sleep transition rules. Neural networks—i.e., machine learning algorithms—are powerful at solving classification problems. Some methods apply them to the first two processes above; however, the refinement process continues to be based on traditional methods. In this study, the sleep stage refinement process was incorporated into the neural network model to form real end-to-end processing. In addition, for multi-channel signals, the multi-branch convolutional neural network was combined with a proposed residual attention method. This approach further improved the model classification accuracy. The proposed method was evaluated on the Sleep-EDF Expanded Database (Sleep-EDFx) and University College Dublin Sleep Apnea Database (UCDDB). It achieved respective accuracy rates of 85.7% and 79.4%. The results also showed that sleep stage refinement based on a neural network is more effective than the traditional refinement method. Moreover, the proposed residual attention method was determined to have a more robust channel–information fusion ability than the respective average and concatenation methods.
Global Positioning System Analysis of Physical Demands in Small and Large-Sided Games with Floaters and Official Matches in the Process of Return to Play in High Level Soccer Players

The aim of this study was twofold: (i) to analyze the physical demands in the return to play (RTP) process of high-level soccer players in the role of floater in different soccer sided games (SGs) formats (i.e., 4vs4 + 2 and 8vs8 + 1); and (ii) to analyze the differences in physical demands encountered by regular and floater players among the SGs formats and official matches by means of global positioning system technology (GPS APEX pod, North Ireland) was used. Twenty-six highly trained, male soccer players (U16 years) participated in this investigation. Players were classified into two groups: 23 regular and 3 floater players, a total of eight SGs were analyzed, which involved the recording of 80 observations of regular and floater players. Match-play players showed most likely–probable differences in distance covered at high-intensity per minute (D > 14.4/min), at high-speed running per minute (D > 21/min), and peak velocity (Vpeak) in comparison to floaters in the 8vs8 + 1 LSG (large-side-games), and presented most likely differences in accelerations >2/min in comparison to match-play players. Therefore, the use of floaters during the last phase of the RTP (return to play) seems to be a useful strategy for progressive reintroduction into specific training (1) floater in the 4vs4 + 2 SSG; (2) floater in the 8vs8 + 1 LSG; (3) regular player in the 4vs4 + 2 SSG; and (4) regular player in the 8vs8 + 1 LSG before starting full trainings and returning to competition.
Ergosterol‐targeting fusion antifungal peptide significantly increases the Verticillium wilt resistance of cotton

Summary Increasing the targeting ability of antifungal proteins towards specific components of fungal cells has the potential to improve their antifungal activity and reduce harmful effects to nontarget cells. To obtain effective disease resistance genes against cotton Verticillium wilt, we constructed several fusion genes, in which binding domains targeting chitin, sphingolipid or ergosterol in the fungal cell wall or cell membrane were individually fused to the antifungal peptide BbAFP1 from entomopathogenic fungus Beauveria bassiana. Transient expression of fusion genes in cotton cotyledons indicated that the BbAFP1::ErBD fusion peptide with an ergosterol binding domain exhibited better disease resistance against V. dahliae than wild‐type BbAFP1 and other fusion genes. BbAFP1::ErBD and BbAFP1 transgenic cotton were obtained and verified by Southern and Western blotting. Compared with BbAFP1‐expressing cotton, BbAFP1::ErBD‐expressing cotton showed higher disease resistance against V. dahliae, with smaller lesion areas (0.07 cm2 vs. 0.16 cm2) on the leaves and a lower disease index (23.9 vs. 34.5). Overexpression of BbAFP1::ErBD by transgenic tobacco also showed enhanced disease resistance against V. dahliae compared with that of the wild‐type gene. These results indicated that construction of fusion antifungal peptides that target fungal cells is a powerful strategy to obtain new anti‐disease genes, and the obtained fusion gene BbAFP1::ErBD has the potential to defend against plant fungal diseases.
SF3B1-mutant CMML defines a predominantly dysplastic CMML subtype with a superior acute leukemia-free survival.

Malcovati et al 1 recently proposed SF3B1 -mutant ( SF3B1 MT ) myelodysplastic syndrome (MDS) to be a distinct nosologic entity defined by cytopenias, somatic SF3B1 mutation, morphologic dysplasia (with or without ring sideroblasts [RSs]), bone marrow (BM) blasts , 5%, and peripheral blood (PB) blasts , 1%. Select concomitant genetic exclusion criteria are del(5q), monosomy7, inv(3)/abnormal 3q26, complex karyotype, or mutations involving RUNX1 and/or EZH2 . Chronic myelomonocytic leukemia (CMML) is an MDS/myeloproliferative neoplasm (MPN) overlap syndrome characterized by sustained PB monocytosis ( $ 1 3 10 9 /L, $ 10% of white blood cell count [WBC]) further categorized into proliferative (WBC $ 13 3 10 9 /L) and dysplastic (WBC , 13 3 10 9 /L)
Characterizing the kinetics of human ligand-receptor interactions with single molecule sensitivity

Membrane proteins represent about two thirds of the protein targets for existing drugs. Therefore, studies of this class of proteins is a very important part of the drug discovery process. Large drug developing companies put enormous resources on getting new products into the market, motivating new and more efficient means for the characterization of potential drugs. In this thesis a method with single molecule sensitivity is investigated for the characterization of the interaction between a G-Protein Coupled Receptor (GPCR) and one of its natural ligands. GPCRs are estimated to be targeted by more than 40% of the drugs used in clinical medicine, making them the pharmaceutically most important subclass of membrane proteins. In this project the CXCR3 receptor is studied along with its chemokine ligand CXCL10. This receptor-ligand couple plays an important role in our immune system and diseases such as multiple sclerosis and type 1 diabetes are related to the CXCR3 receptor. The approach is to immobilize ligands on a surface and use fluorescently labeled vesicles, derived from membranes of cells expressing the CXCR3 transmembrane protein, in order to visualize the ligand-receptor interaction. The initial evaluation of the surface chemistry was performed with the Quartz Crystal Microbalance with Dissipation monitoring (QCMD) technique. Bind and release events between receptor and ligand were monitored under equilibrium with single event resolution using Total Internal Reflection Fluorescence Microscopy (TIRFM). Kinetic parameters characterizing the interaction were extracted from statistics on these bind and release events. koff and kon for the interaction between the CXCR3 receptor and the CXCL10 ligand were determined to 6:7 10 4 s 1 and 4:0 104 1M 1, respectively. The equilibrium dissociation constant, Kd, was determined implicitly to 16:8 nM and theoretically to 0:3 nM.
The impact of voluntary front-of-pack nutrition labelling on packaged food reformulation: A difference-in-differences analysis of the Australasian Health Star Rating scheme

Background Front-of-pack nutrition labelling (FoPL) of packaged foods can promote healthier diets. Australia and New Zealand (NZ) adopted the voluntary Health Star Rating (HSR) scheme in 2014. We studied the impact of voluntary adoption of HSR on food reformulation relative to unlabelled foods and examined differential impacts for more-versus-less healthy foods. Methods and findings Annual nutrition information panel data were collected for nonseasonal packaged foods sold in major supermarkets in Auckland from 2013 to 2019 and in Sydney from 2014 to 2018. The analysis sample covered 58,905 unique products over 14 major food groups. We used a difference-in-differences design to estimate reformulation associated with HSR adoption. Healthier products adopted HSR more than unhealthy products: >35% of products that achieved 4 or more stars displayed the label compared to <15% of products that achieved 2 stars or less. Products that adopted HSR were 6.5% and 10.7% more likely to increase their rating by ≥0.5 stars in Australia and NZ, respectively. Labelled products showed a −4.0% [95% confidence interval (CI): −6.4% to −1.7%, p = 0.001] relative decline in sodium content in NZ, and there was a −1.4% [95% CI: −2.7% to −0.0%, p = 0.045] sodium change in Australia. HSR adoption was associated with a −2.3% [−3.7% to −0.9%, p = 0.001] change in sugar content in NZ and a statistically insignificant −1.1% [−2.3% to 0.1%, p = 0.061] difference in Australia. Initially unhealthy products showed larger reformulation effects when adopting HSR than healthier products. No evidence of a change in protein or saturated fat content was observed. A limitation of our study is that results are not sales weighted. Thus, it is not able to assess changes in overall nutrient consumption that occur because of HSR-caused reformulation. Also, participation into labelling and reformulation is jointly determined by producers in this observational study, impacting its generalisability to settings with mandatory labelling. Conclusions In this study, we observed that reformulation changes following voluntary HSR labelling are small, but greater for initially unhealthy products. Initially unhealthy foods were, however, less likely to adopt HSR. Our results, therefore, suggest that mandatory labelling has the greatest potential for improving the healthiness of packaged foods.
Handbook of infrared standards II : with spectral coverage of 1.4 μm-4μm and 6.2 μm-7.7 μm

Maps and Wavenumber Tables for the New Spectral Coverage: 1.4 um-4um. Heterodyne Frequency Measurements. Saturation Absorption Spectroscopy: Update of OsO4 Measurements. Methyl Chloride Spectral Maps and Wavenumber Data: 1309cm-1-1594cm-1.
F-box protein CFK1 interacts with and degrades de novo DNA methyltransferase in Arabidopsis.

DNA methylation plays crucial roles in cellular development and stress responses through gene regulation and genome stability control. Precise regulation of DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), the de novo Arabidopsis DNA methyltransferase, is crucial to maintain DNA methylation homeostasis to ensure genome integrity. Compared to the extensive studies on DRM2 targeting mechanisms, little is known regarding the quality control of DRM2 itself. Here, we conducted yeast two hybrid screen assay and identified an E3 ligase, COP9 INTERACTING F-BOX KELCH 1 (CFK1), as a novel DRM2-interacting partner and targets DRM2 for degradation via the ubiquitin-26S proteasome pathway in Arabidopsis thaliana. We also performed whole genome bisulfite sequencing (BS-seq) to determine the biological significance of CFK1-mediated DRM2 degradation. Loss-of-function CFK1 leads to increased DRM2 protein abundance and overexpression of CFK1 showed reduced DRM2 protein levels. Consistently, CFK1 overexpression induces genome-wide CHH hypomethylation and transcriptional de-repression at specific DRM2 target loci. This study uncovered a distinct mechanism regulating de novo DNA methyltransferase by CFK1 to control DNA methylation level.
Spinal spatial integration of nociception and its functional role assessed via the nociceptive withdrawal reflex and psychophysical measures in healthy humans

Animal studies have previously shown that deep dorsal horn neurons play a role in the processing of spatial characteristics of nociceptive information in mammals. Human studies have supported the role of the spinal neurons; however, the mechanisms involved, and its significance, remain to be clarified. The aim of this study was to investigate spatial aspects of the spinal integration of concurrent nociceptive electrical stimuli in healthy humans using the Nociceptive Withdrawal Reflex (NWR) as an objective indication of spinal nociceptive processing. Fifteen healthy volunteers participated in the study. Electrical stimuli were delivered, using five electrodes located across the sole of the foot in a mediolateral disposition, as a single or double simultaneous stimuli with varying Inter‐Electrode Distances (IEDs). The stimulation intensity was set at 1.5× NWR threshold (TA muscle). The size of the NWR was quantified in the 60–180 ms poststimulus window as a primary outcome measure. Psychophysical measures were secondary outcomes. Single stimulation elicited significantly smaller NWRs and perceived intensity than double stimulation (p < .01), suggesting the presence of spatial summation occurring within the spinal processing. During double stimulation, increasing the inter‐electrode distance produced significantly smaller NWR sizes (p < .05) but larger pain intensity ratings (p < .05). By the NWR, spatial summation was shown to affect the nociceptive processing within the spinal cord. The inhibited motor response obtained when simultaneously stimulating the medial and lateral side of the sole of the foot suggests the presence of an inhibitory mechanism with a functional, behaviorally oriented function.
Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype.
Improved Transglycosylation by a Xyloglucan-Active α-l-Fucosidase from Fusarium graminearum

Fusarium graminearum produces an α-l-fucosidase, FgFCO1, which so far appears to be the only known fungal GH29 α-l-fucosidase that catalyzes the release of fucose from fucosylated xyloglucan. In our quest to synthesize bioactive glycans by enzymatic catalysis, we observed that FgFCO1 is able to catalyze a transglycosylation reaction involving transfer of fucose from citrus peel xyloglucan to lactose to produce 2′-fucosyllactose, an important human milk oligosaccharide. In addition to achieving maximal yields, control of the regioselectivity is an important issue in exploiting such a transglycosylation ability successfully for glycan synthesis. In the present study, we aimed to improve the transglycosylation efficiency of FgFCO1 through protein engineering by transferring successful mutations from other GH29 α-l-fucosidases. We investigated several such mutation transfers by structural alignment, and report that transfer of the mutation F34I from BiAfcB originating from Bifidobacterium longum subsp. infantis to Y32I in FgFCO1 and mutation of D286, near the catalytic acid/base residue in FgFCO1, especially a D286M mutation, have a positive effect on FgFCO1 transfucosylation regioselectivity. We also found that enzymatic depolymerization of the xyloglucan substrate increases substrate accessibility and in turn transglycosylation (i.e., transfucosylation) efficiency. The data include analysis of the active site amino acids and the active site topology of FgFCO1 and show that transfer of point mutations across GH29 subfamilies is a rational strategy for targeted protein engineering of a xyloglucan-active fungal α-l-fucosidase.
Efficient Suppression of Abdominal Aortic Aneurysm Expansion in Rats through Systemic Administration of Statin-Loaded Nanomedicine

Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and research has mainly focused on cancer treatments. Here, we developed a statin-loaded polymeric micelle to treat AAAs in rat models. The micelle showed medicinal efficacy by preventing aortic aneurysm expansion in a dose-dependent manner. Furthermore, the micelle-injected group showed decreased macrophage infiltration and decreased matrix metalloproteinase-9 activity in cases of AAA.