Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-Based Virtual Screening to Discover Potential Lead Molecules for the SARS-CoV-2 Main Protease

The COVID-19 disease is caused by a new strain of the coronavirus family (SARS-CoV-2), and it has affected at present millions of people all over the world. The indispensable role of the main protease (Mpro) in viral replication and gene expression makes this enzyme an attractive drug target. Therefore, inhibition of SARS-CoV-2 Mpro as a proposition to halt virus ingression is being pursued by scientists globally. Here we carried out a study with two objectives: the first being to perform comparative protein sequence and 3D structural analysis to understand the effect of 12 point mutations on the active site. Among these, two mutations, viz., Ser46 and Phe134, were found to cause a significant change at the active sites of SARS-CoV-2. The Ser46 mutation present at the entrance of the S5 subpocket of SARS-CoV-2 increases the contribution of other two hydrophilic residues, while the Phe134 mutation, present in the catalytic cysteine loop, can cause an increase in catalytic efficiency of Mpro by facilitating fast proton transfer from the Cys145 to His41 residue. It was observed that active site remained conserved among Mpro of both SARS-CoVs, except at the entrance of the S5 subpocket, suggesting sustenance of substrate specificity. The second objective was to screen the inhibitory effects of three different data sets (natural products, coronaviruses main protease inhibitors, and FDA-approved drugs) using a structure-based virtual screening approach. A total of 73 hits had a combo score >2.0. Eight different structural scaffold classes were identified, such as one/two tetrahydropyran ring(s), dipeptide/tripeptide/oligopeptide, large (approximately 20 atoms) cyclic peptide, and miscellaneous. The screened hits showed key interactions with subpockets of the active site. Further, molecular dynamics studies of selected screened compounds confirmed their perfect fitting into the subpockets of the active site. This study suggests promising structures that can fit into the SARS-CoV-2 Mpro active site and also offers direction for further lead optimization and rational drug design.
Nitrogen isotope fractionation during the reduction of NO3− to NH4+ by Desulfovibrio sp.

Desulfovibrio reduce NO3−to NH4+ via a dissimilatory pathway. In 21 days, four strains of Desulfovibrio reduced 36–48% of the available NO3− to ammonium. During this reductive process extensive nitrogen isotope fractionation occurred: the product NH4+ was enriched in 15N in the initial sample, then became enriched in 14N to a minimum value at approximately 20–25% reaction, and then became isotopically heavier as the reaction proceeded.
Posttraumatic Stress Disorder Is Associated with α Dysrhythmia across the Visual Cortex and the Default Mode Network

Abstract Anomalies in default mode network (DMN) activity and α (8–12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that α oscillations support DMN functioning via interregional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of α deficits in the visual-cortex-DMN system in PTSD. Human patients with PTSD (N = 25) and two control groups, patients with generalized anxiety disorder (GAD; N = 24) and healthy controls (HCs; N = 20), underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical α activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Patients with PTSD (vs GAD/HC) demonstrated attenuated α power in the visual cortex (VC) and key hubs of the DMN [posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC)] at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs S-RS), patients with PTSD further demonstrated reduced α-frequency directed connectivity within the DMN (PCC→mPFC) and, importantly, from the VC to both DMN hubs (VC→PCC and VC→mPFC), linking α deficits in the two systems. These interrelated α deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN α dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations.
DEVELOPMENT OF SYMPTOMS OF BROWN RUST OF BARLEY IN RELATION TO THE DISTRIBUTION OF FUNGAL MYCELIUM, STARCH ACCUMULATION AND LOCALIZED CHANGES IN THE CONCENTRATION OF CHLOROPHYLL

Summary The development of symptoms of brown rust (Puccinia hordei Otth.) of barley was examined in relation to the distribution of fungal mycelium within the leaf, the accumulation of chloroplastic starch and localized changes in the concentration of chlorophyll. Symptom development correlated exactly with the growth and distribution of mycelium within the leaf. Starch accumulated in cells associated with or directly surrounded by fungal mycelium, but rarely in cells beyond the leading edge of the colony. A photographic study of the development of a group of brown rust pustules from the flecking stage to the formation of green islands, using incident light and light transmitted through the leaf, suggested that the yellow colour of the flecks was not caused by chlorophyll breakdown, but that the major loss of chlorophyll occurred from regions between fungal pustules. This conclusion was supported by a study of the density of chlorophyll within different regions of the leaf (using the absorption of red light as a measure of chlorophyll density) and by extraction of chlorophyll from different regions of the leaf. These results are discussed in relation to the controversy surrounding the mode of formation of green islands.
Isolation of Hemicellulose from Corn Fiber by Alkaline Hydrogen Peroxide Extraction

ABSTRACT For the first time, alkaline hydrogen peroxide (AHP) extraction conditions were used to isolate hemicellulose (arabinoxylan) from destarched corn fiber. Yields of the water-soluble hemicellulose B ranged from 35% (24 hr extraction at 25°C) to 42% (2 hr extraction at 60°C). The hemicellulose B resulting from the 2 hr extraction (pH 11.5) was off-white in color, and a very low proportion (1.7%) of water-insoluble hemicellulose A was extracted. AHP treatment caused delignification and facilitated the alkaline extraction of hemicellulose from the lignocellulosic fiber matrix. In the absence of H2O2, yields were reduced by more than one-third when using otherwise identical extraction conditions of time, temperature and pH. In the standard protocol, corn fiber, NaOH solution, and H2O2 were mixed in a 1:25:0.25 (w/v/w) ratio. Extractions were conducted at pH 11.5 at 25°C or 60°C. The pH was adjusted to 11.5 by addition of NaOH at ambient and elevated temperatures. The optimum hemicellulose yield (51.3%;.
Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents.

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results & methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion: In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.
Comparative analysis of first-line treatment regimens for advanced EGFR-mutant non-small cell lung cancer patients with stable brain metastases.

BACKGROUND To compare the survival outcomes of first-line treatment regimens for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with stable brain metastases. METHODS We conducted a systematic review of available data from randomized controlled trials (RCTs) of first-line treatment regimens of NSCLC patients with stable brain metastases. Progression free survival (PFS) and overall survival (OS) were extracted and analysed from the RCT subgroups. A network meta-analysis was constructed using the Bayesian statistical model to synthesize the survival outcomes of all the treatments. RESULTS The analysis included 6 eligible RCT subgroups with 417 patients and 7 treatment regimens osimertinib, afatinib, first-generation EGFR-TKI (gefitinib or erlotinib), erlotinib + bevacizumab, gefitinib + pemetrexed + carboplatin, gemcitabine + cisplatin, and pemetrexed + cisplatin. Of these seven treatment regimens, gefitinib + pemetrexed + carboplatin had the highest potential for favorable PFS and OS, followed by osimertinib, in the treatment of advanced EGFR-mutant NSCLC patients with stable brain metastases. None of the results met the predetermined statistical significance of P<0.05. CONCLUSIONS The regimens of "Gefitinib + pemetrexed + carboplatin" and "Osimertinib" were associated with the most favorable PFS and OS compared to the other therapies in advanced EGFR-mutant NSCLC patients with stable brain metastases, although the difference between these regimens and the others was not statistically significantly different.
Proteome-wide identification of HSP70/HSC70 chaperone clients in human cells

The 70 kDa heat shock protein (HSP70) family of chaperones are the front line of protection from stress-induced misfolding and aggregation of polypeptides in most organisms and are responsible for promoting the stability, folding, and degradation of clients to maintain cellular protein homeostasis. Here, we demonstrate quantitative identification of HSP70 and 71 kDa heat shock cognate (HSC70) clients using a ubiquitin-mediated proximity tagging strategy and show that, despite their high degree of similarity, these enzymes have largely nonoverlapping specificities. Both proteins show a preference for association with newly synthesized polypeptides, but each responds differently to changes in the stoichiometry of proteins in obligate multi-subunit complexes. In addition, expression of an amyotrophic lateral sclerosis (ALS)-associated superoxide dismutase 1 (SOD1) mutant protein induces changes in HSP70 and HSC70 client association and aggregation toward polypeptides with predicted disorder, indicating that there are global effects from a single misfolded protein that extend to many clients within chaperone networks. Together these findings show that the ubiquitin-activated interaction trap (UBAIT) fusion system can efficiently isolate the complex interactome of HSP chaperone family proteins under normal and stress conditions.
Ridge Regression and Extensions for Genomewide Selection in Maize

This paper reviews properties of ridge regres- sion for genomewide (genomic) selection and establishes close relationships with other meth- ods to model genetic correlation among rela- tives, including use of a kinship matrix and the simple matching coeffi cient as computed from marker data. A number of alternative models are then proposed exploiting ties between genetic correlation based on marker data and geostatis- tical concepts. A simple method for automatic marker selection is proposed. The methods are exemplifi ed using a series of experiments with test-cross hybrids of maize (Zea mays L.) con- ducted in fi ve environments. Results underline the need to appropriately model genotype- environment interaction and to employ an inde- pendent estimate of error. It is also shown that accounting for genetic effects not captured by markers may be important.
Isolation and characterisation of deoxynivalenol affinity binders from a phage display library based on single-domain camelid heavy chain antibodies (VHHs)

Abstract Deoxynivalenol (DON), or vomitoxin, is a mycotoxin of the trichothecene group produced by Fusarium species. The present work described construction of a phage display library based on variable domain of heavy chain of HCAbs (VHHs) and panning for binders of DON. Two pair PCR primers designed based on the VHHs conserved domains were used for cloning coding sequences of complementary DNA (cDNA). After total RNA extraction, semi-nested PCR, subcloning and electro transformation, the primary library was generated containing 1.9×107 independent clones. Phage display library was rescued by infection of the primary library with helper phage KM13, and the titre of the library was 5.6×1012 CFU/ml. Three clones with specific DON-binding affinity were obtained after three rounds of panning. Since the library was derived from non-immune animal, it has potential to be used for panning binders of other mycotoxins or low molecular weight haptens. The binders with specific affinity provided new recourses for developing detection methods or tools of mycotoxins in foodstuffs.
Antioxidants: their effects on broiler oxidative stress and its meat oxidative stability

Oxidative rancidity represents one of the major causes of deterioration in food for human consumption. Besides producing unpleasant odours, it is responsible for losses in flavour, texture, consistency, appearance and nutritional value. In a similar way, in living animals, oxidative stress constitutes an important mechanism that leads to biological damage, and is regarded as one of the causes of several pathologies that affect poultry growth. Therefore a better understanding of lipid and protein oxidation processes will allow the use of antioxidants to handle and control them. This is fundamental in order to guarantee the quality and safety of meat for human consumption, and in turn the prevention and/or delay of several oxidation processes would allow its management for an optimal quality and shelf life conservation.
Security challenges for the next generation of highly available systems

Nowadays, highly available (HA) systems are a must, for almost any business process. More recently, the need for HA systems have increased as electronic commerce and other internet-based applications have become widely used with the growing Web usage. Security is a major concern for these systems. Companies want to make sure that their security systems are working flawlessly and efficiently. Making sure that these systems are available to allow the right people access to the right areas of the company is imperative. Traditionally, HA systems consist of proprietary hardware and software components. However, the price/performance advantages of commercial-off-the-shelf (COTS) based clusters have had a compelling affect on HA vendors and their marketplace. The emergence of computational grids makes it feasible to develop cost-effective, large-scale geographically distributed HA systems. Making sure that critical applications on this new generation of HA systems are secured is a challenging proposition. In this article, we have identified a list of challenges for the next generation of grid-based HA systems. We have explored the visualization of security services with their pluggable implementation to address the security needs of these grid-based HA systems. The main advantages of this solution include independence with respect to the underlying security mechanisms; best trade-off between security guarantees and processing capabilities; configurability of security architecture; better portability across heterogeneous platforms; and a smaller application development cycle for the HA functionality in the system.
Loss of rice PARAQUAT TOLERANCE 3 confers enhanced resistance to abiotic stresses and increases grain yield in field

Plants frequently suffer from environmental stresses in nature and have evolved sophisticated and efficient mechanisms to cope with the stresses. To balance between growth and stress response, plants are equipped with efficient means to switch off the activated stress responses when stresses diminish. We previously revealed such an off-switch mechanism conferred by Arabidopsis PQT3, knockout of which significantly enhances resistance to abiotic stresses. To explore whether the rice homolog OsPQT3 is functionally conserved, we generated three knockout mutants with CRISPR-Cas9 technology. The OsPQT3 knockout mutants (ospqt3) display enhanced resistance to oxidative and salt stress with elevated expression of OsGPX1, OsAPX1, and OsSOD1. More importantly, the ospqt3 mutants show significantly enhanced agronomic performance with higher yield compared with the wild type under salt stress in greenhouse as well as in field conditions. We further showed that OsPQT3 was rapidly down regulated in response to oxidative and other abiotic stresses as AtPQT3. Taken together, these results support our previous findings that AtPQT3 acts as an off-switch in stress response, which is well conserved in rice. Therefore, PQT3 locus provides a promising candidate for crop improvement with enhanced stress resistance by gene editing technology.
Update on pollen-food allergy syndrome

ABSTRACT Introduction Allergies affect 20-30% of the population and respiratory allergies are mostly due to pollen grains from anemophilous plants. One to 5% of people suffer from food allergies and clinicians report increasing numbers of pollen-food allergy syndrome (PFAS), such that the symptoms have broadened from respiratory to gastrointestinal, and even to anaphylactic shock in the presence of cofactors. Thirty to 60% of food allergies are associated with pollen allergy while the percentage of pollen allergies associated to food allergy varies according to local environment and dietary habits Areas covered Articles published in peer-reviewed journals, covered by PubMed databank, clinical data are discussed including symptoms, diagnosis, and management. A chapter emphasizes the role of six well-known allergen families involved in PFAS: PR10 proteins, profilins, lipid transfer proteins, thaumatin-like proteins, isoflavone reductases, and β-1,3 glucanases. The relevance in PFAS of three supplementary allergen families is presented: oleosins, polygalacturonases, and gibberellin-regulated proteins. To support the discussion a few original relevant results were added. Expert opinion Both allergenic sources, pollen and food, are submitted to the same stressful environmental changes resulting in an increase of pathogenesis-related proteins in which numerous allergens are found. This might be responsible for the potential increase of PFAS.
Spray-freeze-dried dry powder inhalation of insulin-loaded liposomes for enhanced pulmonary delivery

Nowadays, growing attention has been paid to the pulmonary region as a target for the delivery of peptide and protein drugs, especially macromolecules with systemic effect like insulin, since the pulmonary route exhibits numerous benefits to be an alternative for repeated injection. Furthermore, encapsulation of insulin into liposomal carriers is an attractive way to increase drug retention time and control the drug release in the lung; however, its long-term stability during storage in the reservoir and the process of aerosolization might be suspected when practically applied. Thus, the aim of this study was to design and characterize dry powder inhalation of insulin-loaded liposomes prepared by novel spray-freeze-drying method for enhanced pulmonary delivery. Process variables such as compressed air pressure, pump speed, and concentration were optimized for parameters such as mean particle diameter, moisture content, and fine particle fraction of the produced powders. Influence of different kinds and amounts of lyoprotectants was also evaluated for the best preservation of the drug entrapped in the liposome bilayers after the dehydration–rehydration cycle. The in vivo study of intratracheal instillation of insulin-loaded liposomes to diabetic rats showed successful hypoglycemic effect with low blood glucose level and long-lasting period and a relative pharmacological bioavailability as high as 38.38% in the group of 8 IU/kg dosage.
A Visual-Inertial Odometry Using EKF

Visual-inertial odometry (VIO) is a process of estimating the position and orientation of an mobile platform (e.g., vehicle, robot) using measurements from on-board cameras and IMU sensor. In this paper, a visual-inertial odometry algorithm is presented which can achieves accurate performance. In the proposed method, relative position and orientation between the body frames at different time instants are estimated by MIMU and monoVO separately, then an extended Kalman filter (EKF) is used to combining these estimation for achieving an accurate estimation of the motion. Experiment is conducted to show the effectiveness of the proposed method in real environment. Introduction Visual and inertial measurements offer complementary properties which make them particularly suitable for fusion, in order to address robust and accurate localization and mapping, a primary need for any mobile robotic system [1]. In general, there are two main ways to approaching the visual-inertial estimation problem: nonlinear optimization methods and filtering methods [2]. Although the nonlinear optimization method can achieve higher accuracy, it is difficult to run in real time due to its high computational cost. Based on this reason, an EKF is used for sensor fusion in the proposed method. The EKF framework consists of a prediction step and an updating step. In the prediction step, MIMU provides acceleration and rotational velocity measurements in three axes, and makes the motion prediction. In the updating step, monocular camera provides the angular and ranging measurements between the camera frames at different time instants, and uses these measurements to update the prediction results. In the following, we describe the algorithm in detail. MIMU Dynamic Model An IMU state vector at any time instant can be defined by a 16×1 vector,           T T T T T T W W IMU WI WI WI a g , , , ,        x p q v b b (1) where W WI p and W WI v are the position and velocity of IMU frame {I} with respect to world frame {W}, expressed in {W}. qWI is the unit quaternion describing the rotation from {W} to {I}, ba and bg are 3×1 vectors that describe the biases affecting the accelerometer and gyroscope measurements, respectively. For MIMU, the real angular velocity ω and the real acceleration a are related with gyroscope and accelerometer measurements in the following form: m g m a     ω ω b a a b (2) The dynamic model can be represented by the form: