Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice

Significance Neutralizing antibodies are important for immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and as therapeutics for the prevention and treatment of COVID-19. We identified high-affinity nanobodies against SARS-CoV-2 receptor-binding domain and found that nanobody cocktails consisting of two noncompeting nanobodies were able to block ACE2 engagement with RBD variants present in human populations and potently neutralize both wild-type SARS-CoV-2 and the N501Y D614G variant at low concentrations. Prophylactic administration of nanobody cocktails reduced viral loads in mice infected with the N501Y D614G SARS-CoV-2 virus, showing that nanobody cocktails are useful as prophylactic agents against SARS-CoV-2. Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 104-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.
Potential Value of Customized Video Self-Modelling for Motor Skill Learning in Individuals with Cerebral Palsy: A Case-Study Approach

Cerebral Palsy (CP) is a common physical disability that is managed with a variety of strategies. One non-invasive intervention for people living with CP is a type of video self-modelling (VSM) referred to as positive self-review (PSR). PSR involves watching a video of oneself performing only the best examples of a desired task; this technique has been associated with improved performance and learning for people without disabilities and for those in various clinical populations, including children with spina bifida and stroke patients. PSR may have similar benefits for people living with CP. In this study we examined the effectiveness of PSR for improving a self-selected movement task among individuals living with CP. In this case study approach, eight participants completed a pre-, post-, and second post-test measuring and recording well-being, movement self-consciousness and tendency to consciously monitor movements. Results were mixed, with some participants improving their movement time, well-being ratings and tendency toward self-consciousness and conscious monitoring of movements and others showing no changes or regressions. The effectiveness of VSM appears to depend upon the match between type of task and disability and/or the length of practice. More study is needed.
Simultaneous Anaerobic and Aerobic Ammonia and Methane Oxidation under Oxygen Limitation Conditions

Nitrogen in wastewater leads to eutrophication of the receiving water bodies, and methane is a potent greenhouse gas; it is therefore important that these are removed from wastewater. A potential solution for the simultaneous removal of nitrogenous compounds and methane is the application of a combination of nitrite/nitrate-dependent methane oxidation (N-damo) and anaerobic ammonium oxidation (annamox). ABSTRACT Methane and ammonia have to be removed from wastewater treatment effluent in order to discharge it to receiving water bodies. A potential solution for this is a combination of simultaneous ammonia and methane oxidation by anaerobic ammonia oxidation (anammox) bacteria and nitrite/nitrate-dependent anaerobic methane oxidation (N-damo) microorganisms. When applied, these microorganisms will be exposed to oxygen, but little is known about the effect of a low concentration of oxygen on a culture containing these microorganisms. In this study, a stable coculture containing anammox and N-damo microorganisms in a laboratory scale bioreactor was established under oxygen limitation. Membrane inlet mass spectrometry (MIMS) was used to directly measure the in situ simultaneous activity of N-damo, anammox, and aerobic ammonia-oxidizing microorganisms. In addition, batch tests revealed that the bioreactor also harbored aerobic methanotrophs and anaerobic methanogens. Together with fluorescence in situ hybridization (FISH) analysis and metagenomics, these results indicate that the combination of N-damo and anammox activity under the continuous supply of limiting oxygen concentrations is feasible and can be implemented for the removal of methane and ammonia from anaerobic digester effluents. IMPORTANCE Nitrogen in wastewater leads to eutrophication of the receiving water bodies, and methane is a potent greenhouse gas; it is therefore important that these are removed from wastewater. A potential solution for the simultaneous removal of nitrogenous compounds and methane is the application of a combination of nitrite/nitrate-dependent methane oxidation (N-damo) and anaerobic ammonia oxidation (annamox). In order to do so, it is important to investigate the effect of oxygen on these two anaerobic processes. In this study, we investigate the effect of a continuous oxygen supply on the activity of an anaerobic methane- and ammonia-oxidizing coculture. The findings presented in this study are important for the potential application of these two microbial processes in wastewater treatment.
Ivabradine augments high-frequency dynamic gain of the heart rate response to low- and moderate-intensity vagal nerve stimulation under beta-blockade.

Our previous study indicated that intravenously administered ivabradine (IVA) augmented the dynamic heart rate (HR) response to moderate-intensity vagal nerve stimulation (VNS). Considering an accentuated antagonism, the results were somewhat paradoxical; i.e., the accentuated antagonism indicates that an activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels via the accumulation of intracellular cyclic adenosine monophosphate (cAMP) augments the HR response to VNS, whereas the inhibition of HCN channels by IVA also augmented the HR response to VNS. To remove the possible influence from the accentuated antagonism, we examined the effects of IVA on the dynamic vagal control of HR under beta-blockade. In anesthetized rats (n = 7), the right vagal nerve was stimulated for 10 min according to binary white noise signals between 0 and 10 Hz (V0-10), between 0 and 20 Hz (V0-20), and between 0 and 40 Hz (V0-40). The transfer function from VNS to HR was estimated. Under beta-blockade (propranolol, 2 mg/kg, i.v.), IVA (2 mg/kg, i.v.) did not augment the asymptotic low-frequency gain but increased the asymptotic high-frequency gain in V0-10 (0.53 ± 0.10 vs. 1.74 ± 0.40 beats·min-1·Hz-1, P < 0.01) and V0-20 (0.79 ± 0.14 vs. 2.06 ± 0.47 beats·min-1·Hz-1, P < 0.001). These changes, which were observed under a minimal influence from sympathetic background tone, may reflect an increased contribution of the acetylcholine-sensitive potassium channel (IK,ACh) pathway after IVA, because the HR control via the IK,ACh pathway is faster and acts in the frequency range higher than the cAMP-mediated pathway.
Defining indocyanine green fluorescence to assess anastomotic perfusion during gastrointestinal surgery: systematic review

Abstract Background The aim of this systematic review was to identify all methods to quantify intraoperative fluorescence angiography (FA) of the gastrointestinal anastomosis, and to find potential thresholds to predict patient outcomes, including anastomotic leakage and necrosis. Methods This systematic review adhered to the PRISMA guidelines. A PubMed and Embase literature search was performed. Articles were included when FA with indocyanine green was performed to assess gastrointestinal perfusion in human or animals, and the fluorescence signal was analysed using quantitative parameters. A parameter was defined as quantitative when a diagnostic numeral threshold for patient outcomes could potentially be produced. Results Some 1317 articles were identified, of which 23 were included. Fourteen studies were done in patients and nine in animals. Eight studies applied FA during upper and 15 during lower gastrointestinal surgery. The quantitative parameters were divided into four categories: time to fluorescence (20 studies); contrast‐to‐background ratio (3); pixel intensity (2); and numeric classification score (2). The first category was subdivided into manually assessed time (7 studies) and software‐derived fluorescence–time curves (13). Cut‐off values were derived for manually assessed time (speed in gastric conduit wall) and derivatives of the fluorescence–time curves (Fmax, T1/2, TR and slope) to predict patient outcomes. Conclusion Time to fluorescence seems the most promising category for quantitation of FA. Future research might focus on fluorescence–time curves, as many different parameters can be derived and the fluorescence intensity can be bypassed. However, consensus on study set‐up, calibration of fluorescence imaging systems, and validation of software programs is mandatory to allow future data comparison.
Protein convertase subtilisin/Kexin type 9 inhibits hepatocellular carcinoma growth by interacting with GSTP1 and suppressing the JNK signaling pathway

Objective: Protein convertase subtilisin/Kexin type 9 (PCSK9) has been found to be closely associated with the occurrence and development of numerous tumors. However, the precise role of PCSK9 and its relationship to the development of hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to clarify these issues. Methods: The expression levels of PCSK9 in HCC tissues and HCC cell lines were determined by the quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemical analyses, and the effects of PCSK9 expression on HCC cell biological traits were investigated by overexpressing and downregulating PCSK9 expression in vivo and in vitro. Additionally, the mechanism by which PCSK9 mediated dissociation of glutathione S-transferase Pi 1 (GSTP1) dimers and phosphorylation of the Jun N-terminal kinase (JNK) pathway components were investigated. Results: PCSK9 expression levels were significantly lower in HCC tissues than in adjacent non-tumor samples. In vivo and in vitro experiments suggested that PCSK9 inhibited HCC cell proliferation and metastasis. Further analysis showed that PCSK9 interacted with GSTP1 and promoted GSTP1 dimer dissociation and JNK signaling pathway inactivation in HCC cells. Moreover, the relationships between PCSK9 protein expressions and clinical outcomes were investigated. The PCSK9-lo group displayed a significantly shorter overall survival (OS; median OS: 64.2 months vs. 83.2 months; log-rank statistic: 4.237; P = 0.04) and recurrence-free survival (RFS; median RFS: 26.5 months vs. 46.6 months; log-rank statistic: 10.498; P = 0.001) time than the PCSK9-hi group. Conclusions: PCSK9 inhibited HCC cell proliferation, cell cycle progression, and apoptosis by interacting with GSTP1 and suppressing JNK signaling, suggesting that PCSK9 might act as a tumor suppressor and be a therapeutic target in HCC patients.
New monoclonal antibodies that recognize an unglycosylated, conserved, extracellular region of CD44 in vitro and in vivo, and can block tumorigenesis

CD44 is a transmembrane glycoprotein that binds to hyaluronic acid, plays roles in a number of cellular processes and is expressed in a variety of cell types. It is up-regulated in stem cells and cancer. Anti-CD44 monoclonal antibodies affect cell motility and aggregation, and repress tumorigenesis and metastasis. Here we describe four new anti-CD44 monoclonal antibodies originating from B cells of a mouse injected with a plasmid expressing CD44 isoform 12. The four monoclonal antibodies bind to the terminal, extracellular, conserved domain of CD44 isoforms. Based on differences in western blot patterns of cancer cell lysates, the four anti-CD44 mAbs separated into three distinct categories that include P4G9, P3D2, and P3A7, and P3G4. Spot assay analysis with peptides generated in Escherichia coli support the conclusion that the monoclonal antibodies recognize unglycosylated sequences in the N-terminal conserved region between amino acid 21–220, and analyses with a peptide generated in human embryonic kidney 293 cells, demonstrate that these monoclonal antibodies bind to these peptides only after deglycosylation. Western blots with lysates from three cancer cell lines demonstrate that several CD44 isoforms are unglycosylated in the anti-CD44 target regions. The potential utility of the monoclonal antibodies in blocking tumorigenesis was tested by co-injection of cells of the breast cancer-derived tumorigenic cell line MDA-MB-231 with the anti-CD44 monoclonal antibody P3D2 into the mammary fat pads of mice. All five control mice injected with MDA-MB-231 cells plus anti-IgG formed palpable tumors, while only one of the six test mice injected with MDA-MB-231 cells plus P3D2 formed a tiny tumor, while the remaining five were tumor-free, indicating that the four anti-CD44 mAbs may be useful therapeutically.
Clinical Outcome and Striatal Dopaminergic Function After Shunt Surgery in Patients With Idiopathic Normal Pressure Hydrocephalus

Objective To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Methods Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [123I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years. Results We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery (p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 (p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery (p < 0.01). Conclusions This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH.
Development of multicomponent coupled-cluster theory and its application to nanoclusters and molecular systems

Many theoretical and computational methods are based upon the Born-Oppenheimer approximation. This approximation greatly simplifies the search for a wave function that describes all electrons and nuclei in a chemical system. This is accomplished by assuming that the motion of nuclei and electrons are vastly different; the motion of the two particle types is decoupled. While the BO approximation is ubiquitous in computational and theoretical studies, it is not always justifiable. There are two main cases where this approximation is not valid. The first is when nuclear and electronic motion cannot be decoupled. Decoupling the motion leads to incorrect observations and conclusions drawn. The second case is when a chemical system has more than one type of particle to be treated without the Born-Oppenheimer approximation. For these types of systems, a different and more general interpretation of the Born-Oppenheimer approximation must be made where multiple particle types can be investigated whose motion is not decoupled from one another. In order to investigate systems that are classified in this more inclusive interpretation, new computational theories and methods are needed. To accomplish this task, the multicomponent coupled-cluster method has been developed. In its present form, this new computational method is capable of treating two types of particles without decoupling their motion. The fundamental theories and methods for multicomponent coupled-cluster theory are discussed before the derivation and resulting multicomponent coupled-cluster equations are discussed. This method was then used to study excited electronic states in molecular systems and semiconductor quantum dots via the electron-hole representation. It was also used to calculated ground state energy of the positronium hydride system. These projects sparked further interest in the consequences of the Born-Oppenheimer approximation’s application to chemical systems and how it compares to a non Born-Oppenheimer treatment. Development of multicomponent coupled-cluster theory and its application to nanoclusters and molecular systems
Non-enzymatic glucose electrochemical sensor based on silver nanoparticle decorated organic functionalized multiwall carbon nanotubes

An efficient, fast and stable non-enzymatic glucose sensor was prepared by decorating silver nanoparticles on organic functionalized multiwall carbon nanotubes (AgNPs/F-MWCNTs). MWCNTs were functionalized with organic amine chains and characterized using energy-dispersive X-ray and FT-IR spectroscopy. Moreover, the decorated AgNPs monitored using transmission electron microscopy showed spherical shapes with a mean size of 9.0 ± 2.8 nm. For further study, a glassy carbon electrode (GCE) was modified using the synthesized composite and evaluation of the modification was conducted using cyclic voltammetry and electrochemical impedance spectroscopy. The electrochemical data revealed that modification of the GCE leads to easier electron transfer compared to the bare unmodified GCE due to the presence of the functionalized MWCNTs accompanied with the electrocatalytic effect of the decorated silver nanoparticles. Furthermore, the fabricated modified electrode was applied as a non-enzymatic glucose sensor using electrochemical techniques including cyclic voltammetry and hydrodynamic chronoamperometry. The results obtained from the amperometric analysis of glucose in a 0.1 M NaOH solution indicated an efficient performance of the electrode with a low detection limit of 0.03 μM and a high sensitivity of 1057.3 μA mM−1, as well as a linear dynamic range of 1.3 to 1000 μM. A practical application of this sensor was also examined by analyzing glucose in the presence of common interfering species that exist in a real sample of human blood serum.
Service mesh circuit breaker: From panic button to performance management tool

Site Reliability Engineers are at the center of two tensions: On one hand, they need to respond to alerts within a short time, to restore a non-functional system. On the other hand, short response times is disruptive to everyday life and lead to alert fatigue. To alleviate this tension, many resource management mechanisms are proposed handle overload and mitigate the faults. One recent such mechanism is circuit breaking in service meshes. Circuit breaking rejects incoming requests to protect latency at the expense of availability (successfully answered requests), but in many scenarios achieve neither due to the difficulty of knowing when to trigger circuit breaking in highly dynamic microservice environments. We propose an adaptive circuit breaking mechanism, implemented through an adaptive controller, that not only avoids overload and mitigate failure, but keeps the tail response time below a given threshold while maximizing service throughput. Our proposed controller is experimentally compared with a static circuit breaker across a wide set of overload scenarios in a testbed based on Istio and Kubernetes. The results show that our controller maintains tail response time below the given threshold 98% of the time (including cold starts) on average with an availability of 70% with 29% of requests circuit broken. This compares favorably to a static circuit breaker configuration, which features a 63% availability, 30% circuit broken requests, and more than 5% of requests timing out.
Predicting file lifetimes for data placement in multi-tiered storage systems for HPC

The emergence of Exascale machines in HPC will have the foreseen consequence of putting more pressure on the storage systems in place, not only in terms of capacity but also bandwidth and latency. With limited budget we cannot imagine using only storage class memory, which leads to the use of a heterogeneous tiered storage hierarchy. In order to make the most efficient use of the high performance tier in this storage hierarchy, we need to be able to place user data on the right tier and at the right time. In this paper, we assume a 2-tier storage hierarchy with a high performance tier and a high capacity archival tier. Files are placed on the high performance tier at creation time and moved to capacity tier once their lifetime expires (that is once they are no more accessed). The main contribution of this paper lies in the design of a file lifetime prediction model solely based on its path based on the use of Convolutional Neural Network. Results show that our solution strikes a good trade-off between accuracy and under-estimation. Compared to previous work, our model made it possible to reach an accuracy close to previous work (around 98.60% compared to 98.84%) while reducing the underestimations by almost 10x to reach 2.21% (compared to 21.86%). The reduction in underestimations is crucial as it avoids misplacing files in the capacity tier while they are still in use.
Effect of spray drying conditions on the physicochemical properties of barberry (Berberis vulgaris) extract powder.

Seedless barberry is one of the most popular native fruits in Iran. Conventionally, barberry fruit is dried and consumed as ornamental additive in traditional food. Barberry fruit juice contains high anthocyanins, therefore its spray dried powder can be used as good sources of anthocyanins. Maltodextrin(MD)-Arabic gum(AG) mixture, as carrier in various ratios, were added to the extract to prepare spray dried powder. The drying inlet air temperatures were 160°C and 180°C with air flow rate set to 50 m3/h. The anthocyanins content, product recovery, color, moisture content, dissolution, water activity, and density of spray-dried barberry powder were measured. The results revealed that the product recovery was about 78% when the air temperature set to 160oC and the barberry extract was supplemented with 75:25 ratio of MD:AG. The optimum amount of anthocyanins (390.46 mg/100g) in powder was achieved when the inlet air temperature was 160oC and equal proportions of MD:AG added to the feed. Powder loose and tapped bulk density increased from 0.179 to 0.310 and 0.380 to 0.570 g/cm3 respectively, as level of MD in the ratio increased from 7.5 to 15 g/100 ml. SEM micrographs of the powder indicate an increasing trend in particle size as result of increase of concentration of MD as drying aid. The data obtained in the present work may be used to prepare spray dried barberry extract in a commercial scale.