The Intriguing Life of Massive Galaxies: The Connections between α s , β and Merging

In this proceeding paper, we discuss the important underlying connections between the faint end slope α s of the stellar mass function of star-forming galaxies, the logarithmic slope β of the sSFR-mass relation and merging through the continuity approach, as we introduced in Peng et al. (2010, hereafter P10) and (2012, hereafter P12

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study

Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage

Double-Layer Systems at Zero Magnetic Field

We investigate theoretically the effects of intralayer and interlayer exchange in biased double-layer electron and hole systems, in the absence of a magnetic field. We use a variational Hartree-Fock-like approximation to analyze the effects of layer separation, layer density, tunneling, and applied gate voltages on the layer densities and on interlayer phase coherence. In agreement with earlier work, we find that for very small layer separations and low layer densities, an interlayer-correlated ground state possessing spontaneous interlayer coherence (SILC) is obtained, even in the absence of interlayer tunneling. In contrast to earlier work, we find that as a function of total density, there exist four, rather than three, distinct noncrystalline phases for balanced double-layer systems without interlayer tunneling. The newly identified phase exists for a narrow range of densities and has three components and slightly unequal layer densities, with one layer being spin polarized, and the other unpolarized. An additional two-component phase is also possible in the presence of sufficiently strong bias or tunneling. The lowest-density SILC phase is the fully spin- and pseudospin-polarized ``one-component'' phase discussed by Zheng {\it et al.} [Phys. Rev. B {\bf 55}, 4506 (1997)]. We argue that this phase will produce a finite interlayer Coulomb drag at zero temperature due to the SILC. We calculate the particle densities in each layer as a function of the gate voltage and total particle density, and find that interlayer exchange can reduce or prevent abrupt transfers of charge between the two layers. We also calculate the effect of interlayer exchange on the interlayer capacitance.Comment: 35 pages, 19 figures included. To appear in PR

Lenalidomide downregulates ACE2 protein abundance to alleviate infection by SARS-CoV-2 spike protein conditioned pseudoviruses

Dear Editor, The recent health emergency caused by SARS-CoV-2 created a global pandemic. Similar to other CoVs, SARS-CoV-2 utilizes its Spike (S) protein to specifically recognize the human angiotensin converting enzyme 2 (ACE2) membrane receptor for infection. Thus, blocking SARS-CoV-2-S/ACE2 interactions has been investigated as a therapeutic direction in treating SARS-CoV-2, including recombinant hACE2 proteins, ACE2-derived peptides, neutralizing antibodies, engineered ACE2 traps, various heparins, TMPRSS2 inhibitors, and others

Melatonin promoted chemotaxins expression in lung epithelial cell stimulated with TNF-α

BACKGROUND: Patients with asthma demonstrate circadian variations in the airway inflammation and lung function. Pinealectomy reduces the total inflammatory cell number in the asthmatic rat lung. We hypothesize that melatonin, a circadian rhythm regulator, may modulate the circadian inflammatory variations in asthma by stimulating the chemotaxins expression in the lung epithelial cell. METHODS: Lung epithelial cells (A549) were stimulated with melatonin in the presence or absence of TNF-α(100 ng/ml). RANTES (Regulated on Activation Normal T-cells Expressed and Secreted) and eotaxin expression were measured using ELISA and real-time RT-PCR, eosinophil chemotactic activity (ECA) released by A549 was measured by eosinophil chemotaxis assay. RESULTS: TNF-α increased the expression of RANTES (307.84 ± 33.56 versus 207.64 ± 31.27 pg/ml of control, p = 0.025) and eotaxin (108.97 ± 10.87 versus 54.00 ± 5.29 pg/ml of control, p = 0.041). Melatonin(10(-10 )to 10(-6)M) alone didn't change the expression of RNATES (204.97 ± 32.56 pg/ml) and eotaxin (55.28 ± 6.71 pg/ml). However, In the presence of TNF-α (100 ng/ml), melatonin promoted RANTES (410.88 ± 52.03, 483.60 ± 55.37, 559.92 ± 75.70, 688.42 ± 95.32, 766.39 ± 101.53 pg/ml, treated with 10(-10), 10(-9), 10(-8), 10(-7),10(-6)M melatonin, respectively) and eotaxin (151.95 ± 13.88, 238.79 ± 16.81, 361.62 ± 36.91, 393.66 ± 44.89, 494.34 ± 100.95 pg/ml, treated with 10(-10), 10(-9), 10(-8), 10(-7), 10(-6)M melatonin, respectively) expression in a dose dependent manner in A549 cells (compared with TNF-α alone, P < 0.05). The increased release of RANTES and eotaxin in A549 cells by above treatment were further confirmed by both real-time RT-PCR and the ECA assay. CONCLUSION: Taken together, our results suggested that melatonin might synergize with pro-inflammatory cytokines to modulate the asthma airway inflammation through promoting the expression of chemotaxins in lung epithelial cell

Mass and environment as drivers of galaxy evolution in SDSS and zCOSMOS and the origin of the Schechter function

We explore the inter-relationships between mass, star-formation rate and environment in the SDSS, zCOSMOS and other surveys. The differential effects of mass and environment are completely separable to z ~ 1, indicating that two distinct processes are operating, "mass-quenching" and "environment-quenching". Environment-quenching, at fixed over-density, evidently does not change with epoch to z ~ 1, suggesting that it occurs as large-scale structure develops in the Universe. The observed constancy of the mass-function shape for star-forming galaxies, demands that the mass-quenching of galaxies around and above M*, must be proportional to their star-formation rates at all z < 2. We postulate that this simple mass-quenching law also holds over a much broader range of stellar mass and epoch. These two simple quenching processes, plus some additional quenching due to merging, then naturally produce (a) a quasi-static Schechter mass function for star-forming galaxies with a value of M* that is set by the proportionality between the star-formation and mass-quenching rates, (b) a double Schechter function for passive galaxies with two components: the dominant one is produced by mass-quenching and has exactly the same M* as the star-forming galaxies but an alpha shallower by +1, while the other is produced by environment effects and has the same M* and alpha as the star-forming galaxies, and is larger in high density environments. Subsequent merging of quenched galaxies modifies these predictions somewhat in the denser environments, slightly increasing M* and making alpha more negative. All of these detailed quantitative relationships between the Schechter parameters are indeed seen in the SDSS, lending strong support to our simple empirically-based model. The model naturally produces for passive galaxies the "anti-hierarchical" run of mean ages and alpha-element abundances with mass.Comment: 66 pages, 19 figures, 1 movie, accepted for publication in ApJ. The movie is also available at http://www.exp-astro.phys.ethz.ch/zCOSMOS/MF_simulation_d1_d4.mo

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation.</p> <p>Objective</p> <p>To examine whether a dual CCR3 and H₁-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis.</p> <p>Methods</p> <p>Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and α₂-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation.</p> <p>Results</p> <p>Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine.</p> <p>Conclusions</p> <p>AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis.</p> <p>Trial registration</p> <p>EudraCT No: 2005-002805-21.</p

Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index

The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI)

Overview on the pathomechanisms of allergic rhinitis

Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets

Demonstration of a Novel HIV-1 Restriction Phenotype from a Human T Cell Line

Although retroviruses may invade host cells, a productive infection can be established only after the virus counteracts inhibition from different types of host restriction factors. Fv1, APOBEC3G/F, TRIM5alpha, ZAP, and CD317 inhibit the replication of different retroviruses by interfering with viral uncoating, reverse transcription, nuclear import, RNA stability, and release. In humans, although APOBEC3G/3F and CD317 block HIV-1 replication, their antiviral activities are neutralized by viral proteins Vif and Vpu. So far, no human gene has been found to effectively block wild type HIV-1 replication under natural condition. Thus, identification of such a gene product would be of great medical importance for the development of HIV therapies.In this study, we discovered a new type of host restriction against the wild type HIV-1 from a CD4/CXCR4 double-positive human T cell line. We identified a CEM-derived cell line (CEM.NKR) that is highly resistant to productive HIV-1 infection. Viral production was reduced by at least 1000-fold when compared to the other permissive human T cell lines such as H9, A3.01, and CEM-T4. Importantly, this resistance was evident at extremely high multiplicity of infection. Further analyses demonstrated that HIV-1 could finish the first round of replication in CEM.NKR cells, but the released virions were poorly infectious. These virions could enter the target cells, but failed to initiate reverse transcription. Notably, this restriction phenotype was also present in CEM.NKR and 293T heterokaryons.These results clearly indicate that CEM.NKR cells express a HIV inhibitory gene(s). Further characterization of this novel gene product(s) will reveal a new antiretroviral mechanism that directly inactivates wild type HIV-1