Thin airfoil dynamic stall at moderate Reynolds numbers is typically linked to the sudden bursting of a small laminar separation bubble close to the leading edge. Given the strong sensitivity of ...laminar separation bubbles to external disturbances, the onset of dynamic stall on a NACA0009 airfoil section subject to different levels of low-amplitude free stream disturbances is investigated using direct numerical simulations. The flow is practically indistinguishable from clean inflow simulations in the literature for turbulence intensities at the leading edge of ${Tu} = 0.02\,\%$. At slightly higher turbulence intensities of ${Tu} = 0.05\,\%$, the bursting process is found to be considerably less smooth and strong coherent vortex shedding from the laminar separation bubble is observed prior to the formation of the dynamic stall vortex (DSV). This phenomenon is considered in more detail by analysing its appearance in an ensemble of simulations comprising statistically independent realisations of the flow, thus proving its statistical relevance. In order to extract the transient dynamics of the vortex shedding, the classical proper orthogonal decomposition method is generalised to include time in the energy measure and applied to the time-resolved simulation data of incipient dynamic stall. Using this technique, the dominant transient spatiotemporally correlated features are distilled and the wave train of the vortex shedding prior to the emergence of the main DSV is reconstructed from the flow data exhibiting dynamics of large-scale coherent growth and decay within the turbulent boundary layer.
Chemical constituents of Asparagus Negi, J S; Singh, P; Joshi, G P ...
Pharmacognosy reviews,
07/2010, Volume:
4, Issue:
8
Journal Article
Peer reviewed
Open access
Asparagus species (family Liliaceae) are medicinal plants of temperate Himalayas. They possess a variety of biological properties, such as being antioxidants, immunostimulants, anti-inflammatory, ...antihepatotoxic, antibacterial, antioxytocic, and reproductive agents. The article briefly reviews the isolated chemical constituents and the biological activities of the plant species. The structural formula of isolated compounds and their distribution in the species studied are also given.
To compare efficacy and safety of two different combination csDMARD therapy in Methotrexate-failed Rheumatoid arthritis patients. In this 24-week open-label, parallel-group non-inferiority, ...single-center clinical trial, Methotrexate-failed Rheumatoid arthritis patients with disease duration < 2 years, were randomized to either of the two treatment regimens–Methotrexate + Leflunomide + Hydroxychloroquine or Methotrexate + Sulfasalazine + Hydroxychloroquine. Primary endpoint was proportion of patients achieving EULAR good response at 12 weeks. Non-inferiority of Leflunomide based therapy was confirmed if the upper limit of the 2-sided 95% confidence interval of treatment difference between the 2 groups was lower than the selected non-inferiority margin of (− 20%) in primary endpoint at 12 weeks. Secondary endpoints were improvement in DAS28, functional outcome and adverse events at 24 weeks. 136 eligible patients were randomized to either Leflunomide or Sulfasalazine group (68 in each group).63 and 59 patients in Leflunomide and 66 and 61 patients in Sulfasalazine group completed 12 and 24 weeks of trial, respectively. In Intension-to-treat analysis, EULAR good response was achieved by 58.8% and 54.4% patients (
p
= 0.7) at the end of 12 weeks, and 61.7% and 64.7% patients (
p
= 0.8) at the end of 24 weeks-in Leflunomide and Sulfasalazine group respectively. At 12 weeks, the difference in EULAR good response with 2-sided 95% confidence interval between 2 groups was 4.4% (− 12%, 20%) in intention-to-treat and 5.8% (− 11%, 23%) in perprotocol analysis.15 and 21 adverse events were recorded in Leflunomide and Sulfasalazine group respectively. Parenteral Methotrexate was required more in Sulfasalazine group due to gastrointestinal intolerance. Leflunomide based csDMARD therapy is non-inferior to Sulfasalazine based csDMARD therapy in Methotrexate-failed Rheumatoid arthritis patients with comparable safety profile. Trial registered at clinicaltrials.gov (NCT02930343) dated 10.09.2016.
Abstract
Background
We aimed to describe the clinical presentation of individuals presenting with prolonged recovery from coronavirus disease 2019 (COVID-19), known as long COVID.
Methods
This was an ...analysis within a multicenter, prospective cohort study of individuals with a confirmed diagnosis of COVID-19 and persistent symptoms >4 weeks from onset of acute symptoms. We performed a multiple correspondence analysis (MCA) on the most common self-reported symptoms and hierarchical clustering on the results of the MCA to identify symptom clusters.
Results
Two hundred thirty-three individuals were included in the analysis; the median age of the cohort was 43 (interquartile range IQR, 36–54) years, 74% were women, and 77.3% reported a mild initial illness. MCA and hierarchical clustering revealed 3 clusters. Cluster 1 had predominantly pain symptoms with a higher proportion of joint pain, myalgia, and headache; cluster 2 had a preponderance of cardiovascular symptoms with prominent chest pain, shortness of breath, and palpitations; and cluster 3 had significantly fewer symptoms than the other clusters (2 IQR, 2–3 symptoms per individual in cluster 3 vs 6 IQR, 5–7 and 4 IQR, 3–5 in clusters 1 and 2, respectively; P < .001). Clusters 1 and 2 had greater functional impairment, demonstrated by significantly longer work absence, higher dyspnea scores, and lower scores in SF-36 domains of general health, physical functioning, and role limitation due to physical functioning and social functioning.
Conclusions
Clusters of symptoms are evident in long COVID patients that are associated with functional impairments and may point to distinct underlying pathophysiologic mechanisms of disease.
The
γ
-ray strength function (
γ
SF) and nuclear level density (NLD) have been extracted for the first time from inverse kinematic reactions with the Oslo method. This novel technique allows ...measurements of these properties across a wide range of previously inaccessible nuclei. Proton–
γ
coincidence events from the
d
(
86
Kr
,
p
γ
)
87
Kr
reaction were measured at iThemba LABS and the
γ
SF and NLD in
87
Kr
was obtained. The low-energy region of the
γ
SF is compared to shell-model calculations, which suggest this region to be dominated by M1 strength. The
γ
SF and NLD are used as input parameters to Hauser–Feshbach calculations to constrain
(
n
,
γ
)
cross sections of nuclei using the TALYS reaction code. These results are compared to
86
Kr
(
n
,
γ
)
data from direct measurements.
•To compute the equivalent properties of polymer nanocomposite.•To predict the effect of CNT on the equivalent properties of nanocomposite.•To predict the influence of holes and inclusions on the ...failure of CNT reinforced epoxy nanocomposite cracked plate.•To predict the influence of flaws on the failure of cracked nanocomposite plate.•To simulate crack growth using XFEM in CNT reinforced epoxy nanocomposites.
In the present study, the effect of holes and inclusions on the stress intensity factor (SIF) in a Carbon NanoTube (CNT) modified polymer nanocomposite (PNC) has been investigated using extended finite element method (XFEM). In order to perform the failure analysis of CNT reinforced nanocomposite two-step procedure is adopted. In the first step, the equivalent properties of the nanocomposites (elastic modulus, fracture energy and fracture toughness) are computed by changing the percentage of weight content of CNTs inside the polymer matrix. Halpin-Tsai equation has been employed to compute the elastic modulus of the material. Whereas, the fracture toughness and fracture energy have been evaluated considering CNT debonding and CNT pull-out as the main toughness criterion. For this purpose, a modified Cottrell-Kelly-Tyson scheme has been chosen in order to account the hollowness of CNTs. In the second step, a thin finite size plate containing an edge crack with multiple holes and inclusions has been taken into consideration. Then, XFEM approach is implemented to perform the failure analysis of cracked nanocomposite plate. The interaction integral approach has been employed to compute the SIF value at the crack tip. The numerical integration has been done using higher order Gaussian quadrature. Few numerical problems have been solved in the presence of discontinuities. It was found that the elastic modulus, fracture toughness and fracture energy improved with increase in weight percent of CNT. The effect of holes was found to be more pronounced than the effect of inclusion on the SIF.
The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor ...genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.
.
Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high ...temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (
s
N
N
=
2.7--4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (
μ
B
>
500
MeV), effects of chiral symmetry, and the equation of state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2024, in the context of the worldwide efforts to explore high-density QCD matter.
Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with ...poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined.
In vitro assessment of BOLA3 regulation and gain- and loss-of-function assays were performed in human pulmonary artery endothelial cells using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3. Polymeric nanoparticle 7C1 was used for lung endothelium-specific delivery of BOLA3 siRNA oligonucleotides in mice. Overexpression of pulmonary vascular BOLA3 was performed by orotracheal transgene delivery of adeno-associated virus in mouse models of PH.
In cultured hypoxic pulmonary artery endothelial cells, lung from human patients with Group 1 and 3 PH, and multiple rodent models of PH, endothelial BOLA3 expression was downregulated, which involved hypoxia inducible factor-2α-dependent transcriptional repression via histone deacetylase 1-mediated histone deacetylation. In vitro gain- and loss-of-function studies demonstrated that BOLA3 regulated Fe-S integrity, thus modulating lipoate-containing 2-oxoacid dehydrogenases with consequent control over glycolysis and mitochondrial respiration. In contexts of siRNA knockdown and naturally occurring human genetic mutation, cellular BOLA3 deficiency downregulated the glycine cleavage system protein H, thus bolstering intracellular glycine content. In the setting of these alterations of oxidative metabolism and glycine levels, BOLA3 deficiency increased endothelial proliferation, survival, and vasoconstriction while decreasing angiogenic potential. In vivo, pharmacological knockdown of endothelial BOLA3 and targeted overexpression of BOLA3 in mice demonstrated that BOLA3 deficiency promotes histological and hemodynamic manifestations of PH. Notably, the therapeutic effects of BOLA3 expression were reversed by exogenous glycine supplementation.
BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic reprogramming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, Fe-S biogenesis, and glycine biology, for diagnostic and therapeutic development.
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