Miracle-dz/UniFAR-FTUs huggingface dataset:
C-Fiber Degeneration Enhances Alveolar Macrophage-Mediated IFN-α/β Response to Respiratory Syncytial Virus

Despite continuous advances in medicine, safe and effective drugs against RSV infection remain elusive. As such, host-RSV interactions and host-directed therapies require further research. ABSTRACT Stimulation of unmyelinated C fibers, the nociceptive sensory nerves, by noxious stimuli is able to initiate host responses. Host defensive responses against respiratory syncytial virus (RSV) infection rely on the induction of a robust alpha/beta interferon (IFN-α/β) response, which acts to restrict viral production and promote antiviral immune responses. Alveolar macrophages (AMs) are the major source of IFN-α/β upon RSV infection. Here, we found that C fibers are involved in host defense against RSV infection. Compared to the control mice post-RSV infection, degeneration and inhibition of C fibers by blockade of transient receptor potential vanilloid 1 (TRPV1) lowered viral replication and alleviated lung inflammation. Importantly, AMs were markedly elevated in C-fiber-degenerated (KCF) mice post-RSV infection, which was associated with higher IFN-α/β secretion as measured in bronchoalveolar lavage fluid (BALF) samples. Degeneration of C fibers contributed to the production of vasoactive intestinal peptide (VIP), which modulated AM and IFN-α/β levels to protect against RSV infection. Collectively, these findings revealed the key role of C fibers in regulating AM and IFN-α/β responses against RSV infection via VIP, opening the possibility for new therapeutic strategies against RSV. IMPORTANCE Despite continuous advances in medicine, safe and effective drugs against RSV infection remain elusive. As such, host-RSV interactions and host-directed therapies require further research. Unmyelinated C fibers, the nociceptive sensory nerves, play an important role in regulating the host response to virus. In the present study, from the perspective of neuroimmune interactions, we clarified that C-fiber degeneration enhanced the AM-mediated IFN-α/β response against RSV via VIP, providing potential therapeutic targets for the treatment of RSV infection.
Tracing the first stars and galaxies of the Milky Way

We use 30 high-resolution dark matter halos of the $Caterpillar$ simulation suite to probe the first stars and galaxies of Milky Way-mass systems. We quantify the environment of the high-$z$ progenitors of the Milky Way and connect them to the properties of the host and satellites today. We identify the formation sites of the first generation of Population III (Pop III) stars ($z$ ~ 25) and first galaxies ($z$ ~ 22) with several different models based on a minimum halo mass including a simple model for Lyman-Werner feedback. Through this method we find approximately 23,000 $\pm$ 5,000 Pop III potentially star-forming sites per Milky Way-mass host, though this number is drastically reduced to ~550 star-forming sites when Lyman-Werner feedback is included, as it has critical effects at these length scales. The majority of these halos identified form in isolation (96% at $z$ = 15) and are not subject to external enrichment by neighboring halos (median separation ~1 pkpc at $z$ = 15), though half merge with a system larger than themselves within 1.5 Gyrs. Approximately 55% of the entire population has merged into the host halo by $z$ = 0. Using particle tagging, we additionally trace the Pop III remnant population to $z$ = 0 and find an order of magnitude scatter in their number density at small (i.e. r $ $ 50 kpc) galactocentric radii at $z$ = 0. Using our large number of realizations, we provide fitting functions for determining the number of progenitor minihalo and atomic cooling halo systems that present-day dwarf galaxies and the Magellanic cloud system might have accreted since their formation. We demonstrate that observed dwarf galaxies with stellar masses below 10$^{4.6}$ M$_{\odot}$ are unlikely to have merged with any other star-forming systems.
Emergences of C IV narrow absorption troughs in the quasar SDSS J095254.10+021932.8

In this paper, we report on two C IV narrow absorption systems emerging from the spectrum of the quasar SDSS J095254.10+021932.8, which arelocated at zabs =2.0053 and zabs =1.8011, respectively. These features have velocity offsets of ∼13800 and ∼34700kms −1 with respect to the quasar, and show obviously partial coverage to the background emission sources. The two C IV absorption systems are imprinted on the spectrum obtained by the Sloan Digital Sky Survey (SDSS) III on 2011 March 25, which cannot be observed from the spectrum obtained by SDSS-I/II on 2000 December 30. The time interval of the two SDSS observations is 1186.4d at the quasar rest frame. Because the continuum radiation, broad emission lines and mass accretion rate are stable for the two observations, together with the time interval of observations, we believe that the observed spectral variations are less likely to be caused by the changes in the ionization states of the absorbing gas or by a new outflow, arising from the situation where there was previously no outflow at all. Instead, they probably arise from the motions of multiple streaming gas across the sightline of the quasar.
ON THE ORIGIN OF THE TYPE ii SPICULES: DYNAMIC THREE-DIMENSIONAL MHD SIMULATIONS

Recent high temporal and spatial resolution observations of the chromosphere have forced the definition of a new type of spicule, “type ii's,” that are characterized by rising rapidly, having short lives, and by fading away at the end of their lifetimes. Here, we report on features found in realistic three-dimensional simulations of the outer solar atmosphere that resemble the observed type ii spicules. These features evolve naturally from the simulations as a consequence of the magnetohydrodynamical evolution of the model atmosphere. The simulations span from the upper layer of the convection zone to the lower corona and include the emergence of a horizontal magnetic flux. The state-of-art Oslo Staggered Code is used to solve the full MHD equations with non-gray and non-LTE radiative transfer and thermal conduction along the magnetic field lines. We describe in detail the physics involved in a process which we consider a possible candidate for the driver mechanism that produces type ii spicules. The modeled spicule is composed of material rapidly ejected from the chromosphere that rises into the corona while being heated. Its source lies in a region with large field gradients and intense electric currents, which lead to a strong Lorentz force that squeezes the chromospheric material, resulting in a vertical pressure gradient that propels the spicule along the magnetic field, as well as Joule heating, which heats the jet material, forcing it to fade.
Poor expression of miR‐195‐5p can assist the diagnosis of cerebral vasospasm after subarachnoid hemorrhage and predict adverse outcomes

Patients with spontaneous subarachnoid hemorrhage (SAH) may develop refractory arterial cerebral vasospasm (CVS), which is the leading cause of death in SAH patients. This study explored the clinical diagnostic value of serum miR‐195‐5p levels in CVS after SAH (SAH + CVS) and its relationship with the prognosis of SAH + CVS.
Biochemical and biophysical properties of an unreported T96R mutation causing transthyretin cardiac amyloidosis

Abstract Objectives We presented an unreported T96R mutation induced transthyretin cardiac amyloidosis (ATTR). The biochemical and biophysical properties were explored to support its pathogenicity. Background Understanding the biochemical and biophysical nature of genetically mutated transthyretin (TTR) proteins is key to provide precise medical cares for ATTR patients. Results Genetic testing showed heterozygosity for the T96R pathogenic variant c.347C > G (ATTR p.T116R) after myocardial biopsy confirmed amyloid deposition. Biochemical characterizations revealed slight perturbation of its thermodynamic stability (Cm=3.7 M for T96R, 3.4 M for WT and 2.3 M for L55P (commonly studied TTR mutant)) and kinetic stability (t1/2=39.8 h for T96R, 42 h for WT and 4.4 h in L55P). Crosslinking experiment demonstrated heterozygous subunit exchange between wild-type and TTR T96R protein destabilized the tetramer. Inhibitory effect of tafamidis and diflunisal on TTR T96R fibril formation was slightly less effective compared to WT and L55P. Conclusions A novel T96R mutation was identified for TTR protein. Biochemical and biophysical analyses revealed slightly destabilized kinetic stability. T96R mutation destabilized heterozygous protein but not proteolytic degradation, explaining its pathogenicity. Inhibitory effect of small molecule drugs on T96R mutation was different, suggesting personalized treatment may be required.
Assessment of penetration and permeation of caffeine by confocal Raman spectroscopy in vivo and ex vivo by tape stripping

Tape stripping is an often‐used non‐invasive destructive method to investigate the skin penetration of a substance. In recent years, however, the suitability of confocal Raman spectroscopy (CRS) as a non‐invasive method of non‐destructive examination of the skin has become increasingly apparent. In this study, we compared invasion and depletion penetration and permeation kinetics of a 2% caffeine solution with and without 1,2‐pentanediol as a penetration enhancer measured with CRS and tape stripping.
Dynamic polaron response from variational imaginary time evolution

An variational expression for the zero temperature polaron impedance is obtained by minimizing the free energy in a generalized quadratic Feynman model. The impedance function of the quadratic model serves as the variational parameter. It is shown that a very small change in the energy can be accompanied by a large change in the optical conductivity. This is related to the insensitivity of the Jensen-Feynman free energy to the UV properties of the model. Analytic and numeric results are derived for the Fr\"ohlich polaron in weak and strong coupling. Standard results are recovered at weak coupling but, more importantly, strong coupling inconsistencies are removed.
Brief critical analysis of the Darwin-Fowler method

We present a brief numerical study of the Darwin-Fowler method applied to the analysis of the energy partition of essembles of bosons and fermions. We analyze the assertion of the existence of a "strong maximum" made in the original paper of Darwin and Fowler and other studies and show that although the presumed saddle point along the real axis of the grand canonical parameters may exist it cannot, in general, be characterized as "strong", in the sense of having much larger magnitude than the other points along the path of integration. We show that in some cases the saddle point is not even present and the various approximations of the method can be interpreted as a tricky reformulation of usual thermodynamic relations. The close connection of the method with the formalism of the Laplace transform may produce wrong results if the internal energy of the components of the ensemble is not large enough. Therefore, although useful in many applications the Darwin-Fowler method may not be suitable, in general, for a detailed microscopic analysis of the nuclear structure in connection with the Shell Model approach, as it is usually done in studies of the pre-equilibrium stage of nuclear reactions.
On the influence of non-thermal pressure on the mass determination of galaxy clusters

Aims. Given that in most cases just thermal pressure is taken into account in the hydrostatic equilibrium equation to estimate galaxy cluster mass, the main purpose of this paper is to consider the contribution of all three non-thermal components to total mass measurements. The non-thermal pressure is composed by cosmic rays, turbulence and magnetic pressures. Methods. To estimate the thermal pressure we used public XMM-Newton archival data of five Abell clusters to derive temperature and density profiles. To describe the magnetic pressure, we assume a radial distribution for the magnetic field, B(r) ∝ ρ α . To seek generality we assume α within the range of 0.5 to 0.9, as indicated by observations and numerical simulations. Turbulent motions and bulk velocities add a turbulent pressure, which is considered using an estimate from numerical simulations. For this component, we assume an isotropic pressure, Pturb = 1 ρg(σ 2 + σ 2 ). We also consider the contribution of cosmic ray pressure, Pcr ∝ r −0.5 . Thus, besides the gas (thermal) pressure, we include these three non-thermal components in the magnetohydrostatic equilibrium equation and compare the total mass estimates with the values obtained without them. Results. A consistent description for the non-thermal component could yield a variation in mass estimates that extends from 10% to ∼30%. We verified that in the inner parts of cool core clusters the cosmic ray component is comparable to the magnetic pressure, while in non-cool core clusters the cosmic ray component is dominant. For cool core clusters the magnetic pressure is the dominant component, contributing more than 50% of the total mass variation due to non-thermal pressure components. However, for non-cool core clusters, the major influence comes from the cosmic ray pressure that accounts for more than 80% of the total mass variation due to non-thermal pressure effects. For our sample, the maximum influence of the turbulent component to the total mass variation can be almost 20%. Although all of the assumptions agree with previous works, it is important to notice that our results rely on the specific parametrization adopted in this work. We show that this analysis can be regarded as a starting point for a more detailed and refined exploration of the influence of non-thermal pressure in the intra-cluster medium (ICM).
Two‐sided roles of adipose tissue: Rethinking the obesity paradox in various human diseases from a new perspective

Overweight and obesity, as a result of excess fat accumulation, have become a worldwide public health issue. Recent studies have shown that obesity is closely related to many human diseases, such as cancer, cardiovascular diseases, and type 2 diabetes mellitus, in which adipose tissue plays a dual role. In addition to thermal and mechanical insulation and a critical role in energy storage and heat production, adipose tissue is also a highly plastic endocrine and signaling organ that secretes multiple bioactive molecules for inter‐organ crosstalk. The phenotypic and biological changes of adipose tissue under pathological conditions, especially in obesity, increase the challenge of deciphering the positive or negative effects of adipose tissue in disease. Despite numerous studies on obesity and adipose tissue, the ambiguous role of adipose tissue on specific organs or tissues in different diseases is not fully understood, and the definite mechanisms remain obscure. In this review, we first summarize the basic biological characteristics of adipose tissue in the physiological state and the abnormal remodeling of adipose tissue during obesity. We then discuss the complex and disparate effects of obesity on various human diseases, with a particular focus on the dual roles and underlying mechanisms of adipose tissue, a quintessential player in obesity, in this process. More importantly, rethinking the causes of the “obesity paradox” phenomenon in diseases from the perspective of adipose homeostasis and dysfunction provides a novel strategy for disease treatment by intervening in fat function.
EVOLUTION OF A DWARF SATELLITE GALAXY EMBEDDED IN A SCALAR FIELD DARK MATTER HALO

The cold dark matter (CDM) model has two unsolved issues: simulations overpredict the satellite abundance around the Milky Way (MW) and it disagrees with observations of the central densities of dwarf galaxies which prefer constant density (core) profiles. One alternative explanation known as the scalar field dark matter (SFDM) model, assumes that dark matter is a scalar field of mass (∼10−22 eV/c2); this model can reduce the overabundance issue due to the lack of halo formation below a mass scale of ∼108M⊙ and successfully fits the density distribution in dwarfs. One of the attractive features of the model is predicting core profiles in halos, although the determination of the core sizes is set by fitting the observational data. We perform N-body simulations to explore the influence of tidal forces over a stellar distribution embedded in an SFDM halo orbiting a MW-like SFDM host halo with a disk. Our simulations intend to test the viability of SFDM as an alternative model by comparing the tidal effects that result in this paradigm with those obtained in the CDM for similar mass halos. We found that galaxies in subhalos with core profiles and high central densities survive for 10 Gyr. The same occurs for galaxies in low density subhalos located far from the host disk influence, whereas satellites in low density DM halos and in tight orbits can eventually be stripped of stars. We conclude that SFDM shows consistency with results from the CDM for dwarf galaxies, but naturally offer a possibility to solve the missing satellite problem.
In search of diverse and connected teams: A computational approach to assemble diverse teams based on members’ social networks

Previous research shows that teams with diverse backgrounds and skills can outperform homogeneous teams. However, people often prefer to work with others who are similar and familiar to them and fail to assemble teams with high diversity levels. We study the team formation problem by considering a pool of individuals with different skills and characteristics, and a social network that captures the familiarity among these individuals. The goal is to assign all individuals to diverse teams based on their social connections, thereby allowing them to preserve a level of familiarity. We formulate this team formation problem as a multi-objective optimization problem to split members into well-connected and diverse teams within a social network. We implement this problem employing the Non-dominated Sorting Genetic Algorithm II (NSGA-II), which finds team combinations with high familiarity and diversity levels in O(n2) time. We tested this algorithm on three empirically collected team formation datasets and against three benchmark algorithms. The experimental results confirm that the proposed algorithm successfully formed teams that have both diversity in member attributes and previous connections between members. We discuss the benefits of using computational approaches to augment team formation and composition.
Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

Theories with higher order time derivatives generically suffer from ghost-like instabilities, known as Ostrogradski instabilities. This fate can be avoided by considering ``degenerate'' Lagrangians, whose kinetic matrix cannot be inverted, thus leading to constraints between canonical variables and a reduced number of physical degrees of freedom. In this work, we derive in a systematic way the degeneracy conditions for scalar-tensor theories that depend quadratically on second order derivatives of a scalar field. We thus obtain a classification of all degenerate theories within this class of scalar-tensor theories. The quartic Horndeski Lagrangian and its extension beyond Horndeski belong to these degenerate cases. We also identify new families of scalar-tensor theories with the property that they are degenerate despite the nondegeneracy of the purely scalar part of their Lagrangian.
Zooming in on major mergers: dense, starbursting gas in cosmological simulations

We introduce the `Illustris zoom simulation project', which allows the study of selected galaxies forming in the $\Lambda$CDM cosmology with a 40 times better mass resolution than in the parent large-scale hydrodynamical Illustris simulation. We here focus on the starburst properties of the gas in four cosmological simulations of major mergers. The galaxies in our high-resolution zoom runs exhibit a bursty mode of star formation with gas consumption timescales 10 times shorter than for the normal star formation mode. The strong bursts are only present in the simulations with the highest resolution, hinting that a too low resolution is the reason why the original Illustris simulation showed a dearth of starburst galaxies. Very pronounced bursts of star formation occur in two out of four major mergers we study. The high star formation rates, the short gas consumption timescales and the morphology of these systems strongly resemble observed nuclear starbursts. This is the first time that a sample of major mergers is studied through self-consistent cosmological hydrodynamical simulations instead of using isolated galaxy models setup on a collision course. We also study the orbits of the colliding galaxies and find that the starbursting gas preferentially appears in head-on mergers with very high collision velocities. Encounters with large impact parameters do typically not lead to the formation of starbursting gas.
Bayesian constraints on dark matter halo properties using gravitationally lensed supernovae

Theoretical and observational cosmology have enjoyed a number of significant successes over the last two decades. Cosmic microwave background measurements from the Wilkinson Microwave Anisotropy Probe and Planck, together with large-scale structure and supernova (SN) searches, have put very tight constraints on cosmological parameters. Type Ia supernovae (SNIa) played a central role in the discovery of the accelerated expansion of the Universe, recognised by the Nobel Prize in Physics in 2011.The last decade has seen an enormous increase in the amount of high quality SN observations, with SN catalogues now containing hundreds of objects. This number is expected to increase to thousands in the next few years, as data from next-generation missions, such as the Dark Energy Survey and Large Synoptic Survey Telescope become available. In order to exploit the vast amount of forthcoming high quality data, it is extremely important to develop robust and efficient statistical analysis methods to answer cosmological questions, most notably determining the nature of dark energy.To address these problems my work is based on nested-sampling approaches to parameter estimation and model selection and neural networks for machine-learning. Using advanced Bayesian techniques, I constrain the properties of dark-matter haloes along the SN lines-of-sight via their weak gravitational lensing effects, develop methods for classifying SNe photometrically from their lightcurves, and present results on more general issues associated with constraining cosmological parameters and testing the consistency of different SN compilations.