Miracle-dz/UniFAR-FTUs huggingface dataset:
Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors

Severe dry mouth in patients with Sjögren’s Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries.
Immunomodulatory Effects of Recombinant Mycobacterium smegmatis Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages

Tuberculosis (TB) causes more than 1.5 million deaths each year, remaining a significant global health problem. Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis) share features, which support the use of the former use in new generation TB vaccine development. In a previous study, the specific humoral and cellular immunogenicity of a recombinant M. smegmatis strain expressing epitopes from M. tuberculosis Ag85B protein (rMs064), was demonstrated in mice. In the current study, the immunomodulatory capacity of rMs064 was determined in a J774A.1 murine macrophage cell line. To determine the immunomodulatory effect of rMs064 in J774A.1 macrophages, the expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) was evaluated. The expression of activation surface markers (MHC-II, CD40, CD80 and CD86) and the production of cytokines (IL-1β, TNF-α, IL-12p70 and IL-6) was also determined in rMs064 infected J774A.1 macrophages. Our findings showed the ability of rMs064 to induce substantial increases in macrophage activation markers expression; MHC class II and CD40, compared with M. smegmatis transformed with the empty vector (rMs012) and uninfected cells. rMs064 induced significant increases in IL-12p70 compared to uninfected cells. The expression of iNOS and CD86, and the production of IL-1β, and TNF-α were increased in rMs064 and rMs012, compared to uninfected cells. rMs064 demonstrated its immunomodulatory ability by stimulating the innate immune response, which supports its further evaluation as a TB vaccine candidate.
A Formal Model for Quality-Driven Decision Making in Self-Adaptive Systems

Maintaining an acceptable level of quality of service in modern complex systems is challenging, particularly in the presence of various forms of uncertainty caused by changing execution context, unpredicted events, etc. Although self-adaptability is a well-established approach for modelling such systems, and thus enabling them to achieve functional and/or quality of service objectives by autonomously modifying their behavior at runtime, guaranteeing a continuous satisfaction of quality objectives is still challenging and needs a rigorous definition and analysis of system behavioral properties. Formal methods constitute a promising and effective solution in this direction in order to rigorously specify mathematical models of a software system and to analyze its behavior. They are also largely adopted to analyze and provide guarantees on the required functional/non-functional properties of self-adaptive systems. Therefore, we introduce a formal model for quality-driven self-adaptive systems under uncertainty. We combine high-level Petri nets and plausible Petri nets in order to model complex data structures enabling system quality attributes quantification and to improve the decision-making process through selecting the most plausible plans with regard to the system's actual context.
Local well-posedness of the Landau–Lifshitz equation with helicity term

We consider the initial value problem for the Landau–Lifshitz equation with a helicity term (chiral interaction term), which arises from the Dzyaloshinskii–Moriya interaction energy. We prove that it is well-posed locally in-time in the space [Formula: see text] for s ≥ 3 with [Formula: see text] and [Formula: see text]. We also show that if we further assume that the solution is homotopic to constant maps, then local well-posedness holds in the space [Formula: see text] for s > 2 with [Formula: see text]. Our proof is based on two different approaches: One is the geometric energy method by McGahagan and the other is via the modified Schrödinger map equation. In the present analysis, we exploit a special structure of the helicity term, which enables us to overcome the difficulty in the quadratic derivative nonlinearity of the helicity term.
Demography and productivity during the recovery time sequence of a wild edible bamboo after large-scale anthropogenic disturbance

Anthropogenic disturbances in forest management practices can affect wild edible plants. Soil scarification is a large-scale disturbance that may cause long-term reduction in productivity of edible dwarf bamboo, Sasa kurilensis, in northern Japan. For their effective and sustainable use, we need to understand the recovery process after such disturbances. At 14 study sites in the Teshio Experimental Forest of Hokkaido University where soil scarification had been conducted between 2 and 44 years prior, the number and stem diameter of old and young (newly emerged, edible) culms was recorded. At sites that were within 11 years of soil scarification, the proportion of old culms (<11%) was lower than in the control area where soil scarification had never been conducted. At sites where more than 15 years had passed since soil scarification, the relative number of old culms was nearly equal to that in control area. Additionally, the number of young culms increased with an increasing number of old culms. These results suggest that recovery of productivity (in term of number) of edible culms may take a few decades. In contrast, the culm diameter of young culms increased linearly with time since soil scarification, but the 95% confidence interval in this relationship suggests that dwarf bamboo can produce thick edible culms soon after soil scarification. These findings will provide useful insights into how to obtain high quality bamboo culms following anthropogenic disturbances in future.
AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke

A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that associates with intracellular molecules to regulate multiple signal transductions. Although the roles of AKAP12 in the central nervous system are still relatively understudied, it was previously shown that AKAP12 regulates blood-retinal barrier formation. In this study, we asked whether AKAP12 also supports the function and integrity of the blood-brain barrier (BBB). In a mouse model of focal ischemia, the expression level of AKAP12 in cerebral endothelial cells was upregulated during the acute phase of stroke. Also, in cultured cerebral endothelial cells, oxygen-glucose deprivation induced the upregulation of AKAP12. When AKAP12 expression was suppressed by an siRNA approach in cultured endothelial cells, endothelial permeability was increased along with the dysregulation of ZO-1/Claudin 5 expression. In addition, the loss of AKAP12 expression caused an upregulation/activation of the Rho kinase pathway, and treatment of Rho kinase inhibitor Y-27632 mitigated the increase of endothelial permeability in AKAP12-deficient endothelial cell cultures. These in vitro findings were confirmed by our in vivo experiments using Akap12 knockout mice. Compared to wild-type mice, Akap12 knockout mice showed a larger extent of BBB damage after stroke. However, the inhibition of rho kinase by Y-27632 tightened the BBB in Akap12 knockout mice. These data may suggest that endogenous AKAP12 works to alleviate the damage and dysfunction of the BBB caused by ischemic stress. Therefore, the AKAP12-rho-kinase signaling pathway represents a novel therapeutic target for stroke.
Development of a CD63 Aptamer for Efficient Cancer Immunochemistry and Immunoaffinity-Based Exosome Isolation

CD63, a member of transmembrane-4-superfamily of tetraspanin proteins and a highly N-glycosylated type III lysosomal membrane protein, is known to regulate malignancy of various types of cancers such as melanoma and breast cancer and serves as a potential marker for cancer detection. Recently, its important role as a classic exosome marker was also emphasized. In this work, via using a magnetic bead-based competitive SELEX (systematic evolution of ligands by exponential enrichment) procedure and introducing a 0.5 M NaCl as elution buffer, we identified two DNA aptamers (CD63-1 and CD63-2) with high affinity and specificity to CD63 protein (Kd = 38.71 nM and 78.43, respectively). Furthermore, CD63-1 was found to be efficient in binding CD63 positive cells, including breast cancer MDA-MB-231 cells and CD63-overexpressed HEK293T cells, with a medium binding affinity (Kd ~ 100 nM) as assessed by flow cytometry. When immunostaining assay was performed using clinical breast cancer biopsy, the CD63-1 aptamer demonstrated a comparable diagnostic efficacy for CD63 positive breast cancer with commercial antibodies. After developing a magnetic bead-based exosome immunoaffinity separation system using CD63-1 aptamer, it was found that this bead-based system could effectively isolate exosomes from both MDA-MB-231 and HT29 cell culture medium. Importantly, the introduction of the NaCl elution in this work enabled the isolation of native exosomes via a simple 0.5M NaCl incubation step. Based on these results, we firmly believe that the developed aptamers could be useful towards efficient isolation of native state exosomes from clinical samples and various theranostic applications for CD63-positive cancers.
Modeling Adverse Conditions in the Framework of Graph Transformation Systems

The concept of adverse conditions addresses systems interacting with an adversary environment and finds use also in the development of new technologies. We present an approach for modeling adverse conditions by graph transformation systems. In contrast to other approaches for graphtransformational interacting systems, the presented main constructs are graph transformation systems. We introduce joint graph transformation systems which involve a system, an interfering environment, and an automaton modeling their interaction. For joint graph transformation systems, we introduce notions of (partial) correctness under adverse conditions, which contain the correctness of the system and a recovery condition. As main result, we show that two instances of correctness, namely k-step correctness (recovery in at most k steps after an environment intervention) and last-minute correctness (recovery until next environment intervention) are expressible in LTL (linear temporal logic), and that a weaker notion of k-step correctness is expressible in CTL (computation tree logic).
Enhancement of Spatial Clustering-Based Time-Frequency Masks using LSTM Neural Networks

Recent works have shown that Deep Recurrent Neural Networks using the LSTM architecture can achieve strong single-channel speech enhancement by estimating time-frequency masks. However, these models do not naturally generalize to multi-channel inputs from varying microphone configurations. In contrast, spatial clustering techniques can achieve such generalization but lack a strong signal model. Our work proposes a combination of the two approaches. By using LSTMs to enhance spatial clustering based time-frequency masks, we achieve both the signal modeling performance of multiple single-channel LSTM-DNN speech enhancers and the signal separation performance and generality of multi-channel spatial clustering. We compare our proposed system to several baselines on the CHiME-3 dataset. We evaluate the quality of the audio from each system using SDR from the BSS\_eval toolkit and PESQ. We evaluate the intelligibility of the output of each system using word error rate from a Kaldi automatic speech recognizer.
The Association of Post-Materialism with Health Care Use. Findings of a General Population Survey in Germany

(1) The aim of this study was to identify the association between post-materialism and health care use (in terms of the frequency of doctor visits and the reason for doctor visits). (2) Data were taken from the German General Social Survey (a representative sample of individuals aged 18 years and over, n = 3338). The Inglehart’s post-materialist index was used to quantify post-materialism. The doctor visits (self-reported) in the past three months served as an outcome measure. The reasons for seeing a doctor served as an additional outcome measure (acute illness; chronic illness; feeling unwell; requesting advice; visit to the doctor’s office without consulting the doctor (e.g., need to get a prescription); preventive medical check-up/vaccination). (3) After adjusting for several covariates, negative binomial regressions revealed that compared with materialism, post-materialism was associated with decreased doctor visits (total sample; women). Moreover, the likelihood of visiting the doctor for reasons of chronic illnesses was lower in post-materialistic women, whereas the likelihood of visiting the doctor for reasons of preventive medical check-up/vaccination was higher in post-materialistic women. (4) Study findings identify an unexplored link between post-materialism and doctor visits in women. One may conclude that in the long-term, the increased likelihood of preventive medical check-ups in post-materialistic women will be beneficial in decreasing the need for doctor visits for reasons of chronic illnesses. However, future research is required to elucidate the underlying mechanisms.
State Masking Over a Two-State Compound Channel

We consider the fundamental limits of reliable communication over a two-state compound channel when the state of the channel needs to be masked. Our model is closely related to an area of study known as covert communication, a setting in which the transmitter wishes to communicate to legitimate receiver(s) while ensuring that the communication is not detected by an adversary. Our main contribution is the establishment of upper and lower bounds on the throughput-key length region when the constraint that quantifies how much the states are masked is defined to be the total variation distance between the channel output distributions of the two states. When length of the key is sufficiently large, we provide sufficient conditions for the bounds to coincide. Our results follow the so-called square-root law and hence are reminiscent of results in covert communications. Numerical examples, including that of a Gaussian channel, are provided to illustrate our results.
The Aerogen® Solo Is an Alternative to the Small Particle Aerosol Generator (SPAG-2) for Administration of Inhaled Ribavirin

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.
Use of a titanium nitride for electrochemical inactivation of marine bacteria

A titanium nitride (TiN) electrode with very low resistance and good electrochemical stability was constructed and used for electrochemical inactivation of the marine Gram-negative bacterium Vibrio alginolyticus. Specific resistance of the TiN electrode, which was formed by reactive sput tering, was 1.1 × 10-4 Ω·cm. When cyclic voltammetry of the TiN electrode-attached V. alginolyticus cells of 4.2 × 105 cells/cm2 was carried out at a scan rate of 20 mV/s in seawater, an anodic peak current appeared around 0.68 V vs Ag/AgCl. In all, 98.7% of V. alginolyticus cells attached onto the electrode were inactivated by applying a potential of 0.8 V vs Ag/AgCl in seawater for 30 min. Changes in pH and chlorine concentration were not observed at 0.8 V vs Ag/AgCl. The TiN electrode was oxidized by applying potential of a 0.8 V vs Ag/AgCl and passivated by formation of TiO2 onto the electrode surface. The TiO2 thin layer formed on the TiN electrode surface did not impede electrochemical inactivation of marine bacteri.
Relationship between structure and aromatic solvent permeability of crosslinked polyurethanes based on hyperbranched polyesters

This work investigates the relationship between structure and aromatic solvent permeability of polyurethanes based on trimethylolpropane (TMP) as a classical crosslinker and self-made hyperbranched polyesters (HBPEs) as newly developed crosslinking agents. For this purpose three groups of samples were synthesized using toluene diisocyanate, poly(tetramethylene glycol) and different pseudo-generation numbers of crosslinkers in the variable hard segment content. The results obtained from characterization tests indicate that replacing TMP by HBPE leads to an increase of crosslink density resulting in significant reduction of sorption capacity and conversely leads to an increase of the diffusion coefficient due to the lower glass transition temperature (Tg) of soft segments. In this way, the toluene permeability of hyperbranched polyurethane (HBPU) is considerably lower than that of classical polyurethane. The HBPUs with sufficient amount of hard segment have the lowest solvent uptake and diffusion coefficient leading to optimal barrier performance. By increasing the generation number of HBPE, the crosslink density of HBPU increases, but the crystallinity as well as Tg of soft segments decrease. These two contradictory changing trends of the structural characteristics cause a slight decrease in sorption coefficient of membranes and an increase of diffusivity. Therefore the barrier performance of HBPUs is weakened with increasing generation number of crosslinkers. © 2015 Society of Chemical Industry
Sample Complexity of Policy Gradient Finding Second-Order Stationary Points

The policy-based reinforcement learning (RL) can be considered as maximization of its objective. However, due to the inherent non-concavity of its objective, the policy gradient method to a first-order stationary point (FOSP) cannot guar- antee a maximal point. A FOSP can be a minimal or even a saddle point, which is undesirable for RL. It has be found that if all the saddle points are strict, all the second-order station- ary points (SOSP) are exactly equivalent to local maxima. Instead of FOSP, we consider SOSP as the convergence criteria to characterize the sample complexity of policy gradient. Our result shows that policy gradient converges to an (ε, √εχ)-SOSP with probability at least 1 − O(δ) after the total cost of O(ε−9/2)sinificantly improves the state of the art cost O(ε−9). Our analysis is based on the key idea that decomposes the parameter space Rp into three non-intersected regions: non-stationary point region, saddle point region, and local optimal region, then making a local improvement of the objective of RL in each region. This technique can be potentially generalized to extensive policy gradient methods. For the complete proof, please refer to https://arxiv.org/pdf/2012.01491. pdf.
Optimal Cosmic Microwave Background Lensing Reconstruction and Parameter Estimation with SPTpol Data

We perform the first simultaneous Bayesian parameter inference and optimal reconstruction of the gravitational lensing of the cosmic microwave background (CMB), using 100 deg2 of polarization observations from the SPTpol receiver on the South Pole Telescope. These data reach noise levels as low as 5.8 μK arcmin in polarization, which are low enough that the typically used quadratic estimator (QE) technique for analyzing CMB lensing is significantly suboptimal. Conversely, the Bayesian procedure extracts all lensing information from the data and is optimal at any noise level. We infer the amplitude of the gravitational lensing potential to be Aϕ=0.949±0.122 using the Bayesian pipeline, consistent with our QE pipeline result, but with 17% smaller error bars. The Bayesian analysis also provides a simple way to account for systematic uncertainties, performing a similar job as frequentist “bias hardening” or linear bias correction, and reducing the systematic uncertainty on A ϕ due to polarization calibration from almost half of the statistical error to effectively zero. Finally, we jointly constrain A ϕ along with A L, the amplitude of lensing-like effects on the CMB power spectra, demonstrating that the Bayesian method can be used to easily infer parameters both from an optimal lensing reconstruction and from the delensed CMB, while exactly accounting for the correlation between the two. These results demonstrate the feasibility of the Bayesian approach on real data, and pave the way for future analysis of deep CMB polarization measurements with SPT-3G, Simons Observatory, and CMB-S4, where improvements relative to the QE can reach 1.5 times tighter constraints on A ϕ and seven times lower effective lensing reconstruction noise.