Miracle-dz/UniFAR-FTUs huggingface dataset:
Microfluidics guided by deep learning for cancer immunotherapy screening

Significance Immune-cell infiltration and cytotoxicity to pathogens and diseased cells are ubiquitous in health and disease. To better understand immune-cell behavior in a 3D environment, we developed an automated high-throughput microfluidic platform that enables real-time imaging of immune-cell infiltration dynamics and killing of the target cancer cells. We trained a deep learning algorithm using clinical data and integrated the algorithm with our microfluidic platform to effectively identify epigenetic drugs that promote T cell tumor infiltration and enhance cancer immunotherapy efficacy both in vitro and in vivo. Our platform provides a unique method to investigate immune-tissue interactions, which can be widely applied to oncology, immunology, neurology, microbiology, tissue engineering, regenerative medicine, translational medicine, and so on.
Novel Synchronization of Pulse-Coupled Oscillators on Time-Varying Networks

In this article I investigate the novel synchronization behaviors of evolving pulse-coupled oscillator networks. Unlike previous models, the time-varying mechanism is inspired by neural network development, where seldom used links die out while heavily used ones get strengthened. Even small network with all-to-all connected topology can have exotic dynamics under this circumstance. The oscillators can coevolve with the network, and finally form a co-synchronized pair. Or if we only allow a fraction of oscillators to send pulses every time, the oscillators can synchronize with the network remain chaotic.
Immune scoring model based on immune cell infiltration to predict prognosis in diffuse large B‐cell lymphoma

Diffuse large B‐cell lymphoma (DLBCL) is genetically heterogeneous in both pathogenesis and clinical symptoms. Most studies on tumor prognosis have not fully considered the role of tumor‐infiltrating immune cells. This study focused on the role of tumor‐infiltrating immune cells in the prognosis of DLBCL.
Molecular Characterization of Clinical Rel Mutations and Consequences for Resistance Expression and Fitness in Staphylococcus aureus

The stringent response (SR) is a universal stress response that acts as a global regulator of bacterial physiology and virulence, and is a contributor to antibiotic tolerance and resistance. In most bacteria, the SR is controlled by a bifunctional enzyme, Rel, which both synthesizes and hydrolyzes the alarmone (p)ppGpp via two distinct catalytic domains. ABSTRACT The stringent response (SR) is a universal stress response that acts as a global regulator of bacterial physiology and virulence, and is a contributor to antibiotic tolerance and resistance. In most bacteria, the SR is controlled by a bifunctional enzyme, Rel, which both synthesizes and hydrolyzes the alarmone (p)ppGpp via two distinct catalytic domains. The balance between these antagonistic activities is fine-tuned to the needs of the cell and, in a “relaxed” state, the hydrolase activity of Rel dominates. We have previously shown that two single amino acid substitutions in Rel (that were identified in clinical isolates from persistent infections) confer elevated basal concentrations of (p)ppGpp and consequent multidrug tolerance in Staphylococcus aureus. Here, we explore the molecular details of how these mutations bring about this increase in cellular (p)ppGpp and investigate the wider cellular consequences in terms of resistance expression, resistance development, and bacterial fitness. Using enzyme assays, we show that both these mutations drastically reduce the hydrolase activity of Rel, thereby shifting the balance of Rel activity in favor of (p)ppGpp synthesis. We also demonstrate that these mutations induce high-level, homogeneous expression of β-lactam resistance and confer a significant fitness advantage in the presence of bactericidal antibiotics (but a fitness cost in the absence of antibiotic). In contrast, these mutations do not appear to accelerate the emergence of endogenous resistance mutations in vitro. Overall, our findings reveal the complex nature of Rel regulation and the multifaceted implications of clinical Rel mutations in terms of antibiotic efficacy and bacteria survival.
Clinical and genetic analysis of patients with segmental overgrowth features and somatic mammalian target of rapamycin (mTOR) pathway disruption: Possible novel clinical issues

Segmental overgrowth syndromes include a group of clinical entities, all characterized by the abundant proliferation of tissues or organs in association with vascular abnormalities. These syndromes show a wide spectrum of severity ranging from limited involvement of only small areas of the body to complex cases with impressive distortions of multiple tissues and organs. It is now clear that somatic mutations in genes of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (in brief “mTOR pathway”) are responsible for such entities. Not all the cells of the body carry the same causative mutation, which is mosaic, appearing from two (or more) distinct cell lineages after fertilization. In this article, we reconsider the clinical spectrum and surveillance programs of patients with segmental overgrowth syndromes, based on the features of six patients with diverse clinical forms of overgrowth and pathogenic variants in genes of the mTOR pathway.
CONSTRAINTS ON THE IONIZING EFFICIENCY OF THE FIRST GALAXIES

Observations of the Lyα forest and of high-redshift galaxies at z ∼ 6–10 imply that there were just enough photons to maintain the universe in an ionized state at z ∼ 5–6, indicating a “photon-starved” end to reionization. The ionizing emissivity must have been larger at earlier times in order to yield the extended reionization history implied by the electron scattering optical depth constraint from Wilkinson Microwave Anisotropy Probe (WMAP). Here we address the possibility that a faint population of galaxies with host halo masses of ∼108–9 M☉ dominated the ionizing photon budget at redshifts z ≳ 9, due to their much higher escape fractions. Such faint, early galaxies, would not have formed in ionized regions due to suppression by heating from the UV background, and would therefore not contribute to the ionizing background at z ≲ 6, after reionization is complete. Our model matches: (1) the low escape fractions observed for high-redshift galaxies, (2) the WMAP constraint of τes ∼ 0.09, (3) the low values for the UVB at z < 6, and (4) the observed star formation rate density inferred from Lyman break galaxies. A top-heavy initial mass function from Pop III stars is not required in this scenario. We compare our model to recent ones in the literature that were forced to introduce an escape fraction that increases strongly toward high redshift and show that a similar evolution occurs naturally if low-mass galaxies possess high escape fractions.
Chiral algebra of the Argyres-Douglas theory from M5 branes

We study chiral algebras associated with Argyres-Douglas theories engineered from M5 brane. For the theory engineered using 6d $(2,0)$ type $J$ theory on a sphere with a single irregular singularity (without mass parameter), its chiral algebra is the minimal model of W algebra of $J$ type. For the theory engineered using an irregular singularity and a regular full singularity, its chiral algebra is the affine Kac-Moody algebra of $J$ type. We can obtain the Schur index of these theories by computing the vacua character of the corresponding chiral algebra.
MIS-TLIF or CLIF for single segmental lumbar degenerative disease

We aimed to compare the effect of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and Crenel lateral interbody fusion (CLIF) on single segmental lumbar degenerative disease. Patients with single segmental lumbar degenerative disease undergoing MIS-TLIF (n = 28) and CLIF (n = 28) were enrolled from April to October 2017. Preoperative medical history, anthropometric data, and clinical data were recorded. Visual analogue scores and Oswestry disability index (ODI) were assessed. Radiography was performed before and after surgery. X-ray films were evaluated according to the Bridwell method, visual analogue scores and ODI scores were evaluated. There were no significant differences in the gender, age, clinical diagnosis, involved segment or preoperative ODI score between 2 groups (P > .05). During 12-month follow-up, MIS-TLIF group had less intraoperative blood loss, drainage, postoperative bedridden time, and hospital stay (P < .05), but more operation time and radiation exposure time compared with CLIF group (P < .05). CLIF group reported less pain than MIS-TLIF group (P > .05). Both groups had similar lumbar fusion rate (P > .05). Overall, CLIF has less complications, less trauma and faster recovery for the treatment of single segmental lumbar degenerate disease when compared with MIS-TLIF. Evaluation of more patients and long-term follow-up are still needed to further validate our findings.
Parental Factors Associated With Internet Gaming Disorder Among First-Year High School Students: Longitudinal Study

Background Parents play central roles in adolescents’ socialization, behavioral development, and health, including the development of internet gaming disorder (IGD). However, longitudinal research on the parental predictors of adolescent IGD is limited. Objective This study aimed to investigate the reciprocal associations between various parental factors and adolescent IGD using 2-wave cross-lagged models. Methods A sample of 1200 year-one high school students in central China completed a baseline assessment in 2018 (mean age 15.6 years; 633/1200, 52.8% male) and a follow-up survey in 2019. IGD was measured using the 9-item DSM-5 IGD Symptoms checklist. Perceptions related to parental variables, including psychological control, parental abuse, parental support, and the parent-child relationship, were also collected from the adolescents. Results Of all the participants, 12.4% (148/1200) and 11.7% (140/1200) were classified as having IGD at baseline (T1) and follow-up (T2), respectively. All 4 cross-lagged models fit the data well (range for the comparative fit index .91-.95; range for the standardized root mean square residual .05-.06). Parental support (β=–.06, P=.02) and parental abuse (β=.08, P=.002) at T1 predicted IGD symptoms at T2, while parental psychological control (β=.03, P=.25) and a positive relationship with parents (β=–.05, P=.07) at T1 had nonsignificant effects on IGD symptoms at T2, when controlling for background variables. In addition, IGD symptoms at T1 did not predict parental factors at T2. Conclusions The findings suggest that parental factors may be significant predictors of adolescent IGD. Health interventions should consider involving parents to increase the effectiveness of treatment to prevent and reduce adolescent IGD.
Mapping metals at high redshift with far-infrared lines

Cosmic metal enrichment is one of the key physical processes regulating galaxy formation and the evolution of the intergalactic medium (IGM). However, determining the metal content of the most distant galaxies has proven so far almost impossible; also, absorption line experiments at $z\sim6$ become increasingly difficult because of instrumental limitations and the paucity of background quasars. With the advent of ALMA, far-infrared emission lines provide a novel tool to study early metal enrichment. Among these, the [CII] line at 157.74 $\mu$m is the most luminous line emitted by the interstellar medium of galaxies. It can also resonant scatter CMB photons inducing characteristic intensity fluctuations ($\Delta I/I_{CMB}$) near the peak of the CMB spectrum, thus allowing to probe the low-density IGM. We compute both [CII] galaxy emission and metal-induced CMB fluctuations at $z\sim 6$ by using Adaptive Mesh Refinement cosmological hydrodynamical simulations and produce mock observations to be directly compared with ALMA BAND6 data ($\nu_{obs}\sim 272$ GHz). The [CII] line flux is correlated with $M_{UV}$ as $\log(F_{peak}/\mu{\rm Jy})=-27.205-2.253\,M_{UV}-0.038\,M_{UV}^2$. Such relation is in very good agreement with recent ALMA observations (e.g. Maiolino et al. 2015; Capak et al. 2015) of $M_{UV}<-20$ galaxies. We predict that a $M_{UV}=-19$ ($M_{UV}=-18$) galaxy can be detected at $4\sigma$ in $\simeq40$ (2000) hours, respectively. CMB resonant scattering can produce $\simeq\pm 0.1\,\mu$Jy/beam emission/absorptions features that are very challenging to be detected with current facilities. The best strategy to detect these signals consists in the stacking of deep ALMA observations pointing fields with known $M_{UV}\simeq-19$ galaxies. This would allow to simultaneously detect both [CII] emission from galactic reionization sources and CMB fluctuations produced by $z\sim6$ metals.
The null energy condition and its violation

A brief review is given of scalar field theories with second-derivative Lagrangians yielding second-order field equations. Some of these theories permit solutions that violate the null energy condition but otherwise show no obvious inconsistencies. The use of these theories in constructing cosmological scenarios and in the context of a laboratory-created universe is illustrated with examples.
Genetically-encoded BRET probes shed light on ligand bias–induced variable ion selectivity in TRPV1 and P2X5/7

Significance Thanks to innovative BRET-based probes, we shed light on ligand-biased ion selectivity, a difficult-to-study ion channel–related pharmacological concept, by performing the dynamic measurements of Ca2+ and K+ concentrations and ionic strength in the nanoenvironment of the TRPV1 channel during drug challenge in real-time live-cell experiments. Our results indicate that some TRPV1 antagonists display differential potencies in inhibiting CAPS-induced Ca2+ and K+ fluxes. We also detect concentration- and time-dependent ligand biases in P2X7 and P2X5 cationic selectivity. These new BRET-based probes now open up avenues for adding value to ion-channel drug discovery platforms by taking ligand bias into account, thus addressing molecular events related to ion channel activation that are intractable using either conventional fluorescent-based probes or patch-clamp techniques.
On the nature of the absorber in IRAS 09104+4109: the X-ray and mid-infrared view

We present a long (≈76 ks) Chandra observation of IRAS 09104+4109, a hyperluminous galaxy, optically classified as a type 2 active galactic nuclei (AGN) hosted in a cD galaxy in a cluster at z = 0.442. We also report on the results obtained by fitting its broad-band spectral energy distribution. The Compton-thick nature of this source (which has been often referred to as an ‘archetype’ of Compton-thick type 2 quasars) was formerly claimed on the basis of its marginal detection in the Phoswich Detection System (PDS) instrument onboard BeppoSAX, being then disputed usingXMM–Newton data. BothChandra analysis and optical/mid-infrared (IR) spectral fitting are consistent with the presence of heavy (≈1–5 × 10 23 cm −2 ), but not extreme (Compton-thick) obscuration. However, using the mid-IR and the [O III] emission as proxies of the nuclear hard X-ray luminosity suggests the presence of heavier obscuration. The 54-month Swift BAT map shows excess hard X-ray emission likely related to a nearby (z = 0.009) type 2 AGN, close enough to IRAS 09104+4109 to significantly enhance and contaminate its emission in the early BeppoSAX PDS data.
On parametric Thue-Morse Sequences and Lacunary Trigonometric Products

One of the fundamental theorems of uniform distribution theory states that the fractional parts of the sequence $(n \alpha)_{n \geq 1}$ are uniformly distributed modulo one (u.d. mod 1) for every irrational number $\alpha$. Another important result of Weyl states that for every sequence $(n_k)_{k \geq 1}$ of distinct positive integers the sequence of fractional parts of $(n_k \alpha)_{k \geq 1}$ is u.d. mod 1 for almost all $\alpha$. However, in this general case it is usually extremely difficult to classify those $\alpha$ for which uniform distribution occurs, and to measure the speed of convergence of the empirical distribution of $(\{n_1 \alpha\}, ., \{n_N \alpha\})$ towards the uniform distribution. In the present paper we investigate this problem in the case when $(n_k)_{k \geq 1}$ is the Thue--Morse sequence of integers, which means the sequence of positive integers having an even sum of digits in base 2. In particular we utilize a connection with lacunary trigonometric products $\prod^{L}_{\ell=0} |\sin \pi 2^{\ell} \alpha |$, and by giving sharp metric estimates for such products we derive sharp metric estimates for exponential sums of $(n_{k} \alpha)_{k \geq 1}$ and for the discrepancy of $(\{n_{k} \alpha\})_{k \geq 1}. $ Furthermore, we comment on the connection between our results and an open problem in the metric theory of Diophantine approximation, and we provide some explicit examples of numbers $\alpha$ for which we can give estimates for the discrepancy of $(\{n_{k} \alpha\})_{k \geq1}$.
Well‐Posedness and Global Behavior of the Peskin Problem of an Immersed Elastic Filament in Stokes Flow

We consider the problem of a one‐dimensional elastic filament immersed in a two‐dimensional steady Stokes fluid. Immersed boundary problems in which a thin elastic structure interacts with a surrounding fluid are prevalent in science and engineering, a class of problems for which Peskin has made pioneering contributions. Using boundary integrals, we first reduce the fluid equations to an evolution equation solely for the immersed filament configuration. We then establish local well‐posedness for this equation with initial data in low‐regularity Hölder spaces. This is accomplished by first extracting the principal linear evolution by a small‐scale decomposition and then establishing precise smoothing estimates on the nonlinear remainder. Higher regularity of these solutions is established via commutator estimates with error terms generated by an explicit class of integral kernels. Furthermore, we show that the set of equilibria consists of uniformly parametrized circles and prove nonlinear stability of these equilibria with explicit exponential decay estimates, the optimality of which we verify numerically. Finally, we identify a quantity that respects the symmetries of the problem and controls global‐in‐time behavior of the system. © 2018 Wiley Periodicals, Inc.
Consulting parents bereaved by childhood cancer: A qualitative study to improve bereavement services

Abstract Twelve Australian parents bereaved by childhood cancer were interviewed about their experiences of, and preferences for, bereavement support, to inform recommendations to improve bereavement care. Reflexive thematic analysis resulted in five themes: Care, empathy, and connection assist with bereavement; Communication makes a difference; Early and ongoing support is desired; Gender matters when grieving the loss of a child; and The pull of peer support. Parents can be assisted through empathy, early and ongoing support, enhanced communication, peer support, and care that is inclusive of all genders. Parents in non-metropolitan areas require increased and flexible support options.
THE ACCRETION DISK AND IONIZED ABSORBER OF THE 9.7 hr DIPPING BLACK HOLE BINARY MAXI J1305−704

We report the results from X-ray studies of the newly discovered black hole candidate MAXI J1305−704 based on Suzaku and Swift observations in the low/hard and high/soft states, respectively. The long Suzaku observation shows two types of clear absorption dips, both of which recur on a dip interval of 9.74 ± 0.04 hr, which we identify with the orbital period. There is also partially ionized absorption in the nondip (persistent) emission in both the high/soft state and, very unusually, the low/hard state. However, this absorption (in both states) has substantially lower ionization than that seen in other high inclination systems, where the material forms a homogeneous disk wind. Here instead the absorption is most likely associated with clumpy, compact structures associated with the dipping material, which we see uniquely in this source likely because we view it at a very large inclination angle. A large inclination angle is also favored, together with a low black hole mass, to explain the high disk temperature seen in the fairly low luminosity high/soft state, as Doppler boosting enhances the disk temperature at high inclination. The disk radius inferred from these data is significantly smaller than that of the soft component seen in the low/hard state, supporting models where the disk is truncated at low luminosities. We find, however, that the lack of variability power on timescales of ∼50 s in the Suzaku low/hard state data is difficult to explain, even with a low-mass black hole.
Hα ACTIVITY OF OLD M DWARFS: STELLAR CYCLES AND MEAN ACTIVITY LEVELS FOR 93 LOW-MASS STARS IN THE SOLAR NEIGHBORHOOD

Through the McDonald Observatory M Dwarf Planet Search, we have acquired nearly 3000 high-resolution spectra of 93 late-type (K5–M5) stars over more than a decade using the High Resolution Spectrograph on the Hobby–Eberly Telescope. This sample provides a unique opportunity to investigate the occurrence of long-term stellar activity cycles for low-mass stars. In this paper, we examine the stellar activity of our targets as reflected in the Hα feature. We have identified periodic signals for six stars, with periods ranging from days to more than 10 years, and find long-term trends for seven others. Stellar cycles with P ⩾ 1 year are present for at least 5% of our targets. Additionally, we present an analysis of the time-averaged activity levels of our sample, and search for correlations with other stellar properties. In particular, we find that more massive, earlier type (M0–M2) stars tend to be more active than later type dwarfs. Furthermore, high-metallicity stars tend to be more active at a given stellar mass. We also evaluate Hα variability as a tracer of activity-induced radial velocity (RV) variation. For the M dwarf GJ 1170, Hα variation reveals stellar activity patterns matching those seen in the RVs, mimicking the signal of a giant planet, and we find evidence that the previously identified stellar activity cycle of GJ 581 may be responsible for the recently retracted planet f in that system. In general, though, we find that Hα is not frequently correlated with RV at the precision (typically 6–7 m s−1) of our measurements.
Łojasiewicz exponents of non-degenerate holomorohic and mixed functions

We consider Łojasiewicz inequalities for a non-degenerate holomorphic function with an isolated singularity at the origin. We give an explicit estimation of the Łojasiewicz exponent in a slightly weaker form than the assertion in Fukui.For a weighted homogeneous polynomial, we give a better estimation in the form which is conjectured by Brzostowski, Krasinski and Oleksik under under some condition (the Łojasiewicz non-degeneracy). We also introduce Łojasiewicz inequality for strongly non-degenerate mixed functions and generalize this estimation for mixed functions.
The postprandial secretion of peptide YY1‐36 and 3‐36 in obesity is differentially increased after gastric bypass versus sleeve gastrectomy

Peptide tyrosine tyrosine (PYY) exists as two species, PYY1‐36 and PYY3‐36, with distinct effects on insulin secretion and appetite regulation. The detailed effects of bariatric surgery on PYY1‐36 and PYY3‐36 secretion are not known as previous studies have used nonspecific immunoassays to measure total PYY. Our objective was to characterize the effect of sleeve gastrectomy (SG) and Roux‐en‐Y gastric bypass (RYGB) on fasting and postprandial PYY1‐36 and PYY3‐36 secretion using a newly developed liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) assay.