Stochastic distinguishability of Markovian trajectories.

The ability to distinguish between stochastic systems based on their trajectories is crucial in thermodynamics, chemistry, and biophysics. The Kullback-Leibler (KL) divergence, DKLAB(0,τ), quantifies the distinguishability between the two ensembles of length-τ trajectories from Markov processes A and B. However, evaluating DKLAB(0,τ) from histograms of trajectories faces sufficient sampling difficulties, and no theory explicitly reveals what dynamical features contribute to the distinguishability. This work provides a general formula that decomposes DKLAB(0,τ) in space and time for any Markov processes, arbitrarily far from equilibrium or steady state. It circumvents the sampling difficulty of evaluating DKLAB(0,τ). Furthermore, it explicitly connects trajectory KL divergence with individual transition events and their waiting time statistics. The results provide insights into understanding distinguishability between Markov processes, leading to new theoretical frameworks for designing biological sensors and optimizing signal transduction.

Geometric approach to nonequilibrium hasty shortcuts.

Complex and even non-monotonic responses to external control can be found in many thermodynamic systems. In such systems, nonequilibrium shortcuts can rapidly drive the system from an initial state to a desired final state. One example is the Mpemba effect, where preheating a system allows it to cool faster. We present nonequilibrium hasty shortcuts-externally controlled temporal protocols that rapidly steer a system from an initial steady state to a desired final steady state. The term "hasty" indicates that the shortcut only involves fast dynamics without relying on slow relaxations. We provide a geometric analysis of such shortcuts in the space of probability distributions by using timescale separation and eigenmode decomposition. We further identify the necessary and sufficient condition for the existence of nonequilibrium hasty shortcuts in an arbitrary system. The geometric analysis within the probability space sheds light on the possible features of a system that can lead to hasty shortcuts, which can be classified into different categories based on their temporal pattern. We also find that the Mpemba-effect-like shortcuts only constitute a small fraction of the diverse categories of hasty shortcuts. This theory is validated and illustrated numerically in the self-assembly model inspired by viral capsid assembly processes.

Nonequilibrium Theoretical Framework and Universal Design Principles of Oscillation-Driven Catalysis.

At stationary environmental conditions, a catalyst's reaction kinetics may be restricted by its available designs and thermodynamic laws. Thus, its stationary performances may experience practical or theoretical restraints (e.g., catalysts cannot invert the spontaneous direction of a chemical reaction). However, many works have reported that if environments change rapidly, catalysts can be driven away from stationary states and exhibit anomalous performance. We present a general geometric nonequilibrium theory to explain anomalous catalytic behaviors driven by rapidly oscillating environments where stationary-environment restraints are broken. It leads to a universal design principle of novel catalysts with oscillation-pumped performances. Even though a single free energy landscape cannot describe catalytic kinetics at various environmental conditions, we propose a novel control-conjugate landscape to encode the reaction kinetics over a range of control parameters λ, inspired by the Arrhenius form. The control-conjugate landscape significantly simplifies the design principle applicable to large-amplitude environmental oscillations.

Energy landscape design principle for optimal energy harnessing by catalytic molecular machines.

Under temperature oscillation, cyclic molecular machines such as catalysts and enzymes could harness energy from the oscillatory bath and use it to drive other processes. Using an alternative geometrical approach, under fast temperature oscillation, we derive a general design principle for obtaining the optimal catalytic energy landscape that can harness energy from a temperature-oscillatory bath and use it to invert a spontaneous reaction. By driving the reaction against the spontaneous direction, the catalysts convert low free-energy product molecules to high free-energy reactant molecules. The design principle, derived for arbitrary cyclic catalysts, is expressed as a simple quadratic objective function that only depends on the reaction activation energies, and is independent of the temperature protocol. Since the reaction activation energies are directly accessible by experimental measurements, the objective function can be directly used to guide the search for optimal energy-harvesting catalysts.

Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms.

BACKROUND: Early treatment of oral precancerous lesions is considered as a key strategy for in oral carcinogenesis prevention. Increasing evidence has suggested that the transforming growth factor beta (TGF-ß) signaling pathway is tightly involved in the process of oral-carcinogenesis. In this study, we investigated the inhibition effect and potential mechanism of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) in human oral precancerous cells via TGF-ß pathway. MATERIALS AND METHODS: Here, the dysplastic oral keratinocyte (DOK) cells were incubated with ALA concentration of 1 mM/mL for 4 h and then irradiated with a Helium-Neon (He-Ne) ion laser at 633 nm (200 mW/cm2). The control cells were cultured in Dulbecco's modified Eagle's medium (DMEM) medium. We analyzed the differentially expressed genes and correlated pathways in oral precancerous cells following ALA-PDT using Affymetrix microarrays. TGF-ß pathway was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Bioinformatics analysis was performed to evaluate the expression of TGF-ß1 in human oral cancer samples and adjacent normal samples. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and wound healing assay were used to assess the effects of ALA-PDT plus TGF-ß receptor inhibitor (LY2109761) in DOK cells. RESULTS: The TGF-ß signaling could exert in suppressive effects on DOK cells after ALA-PDT. The cell proliferation and migration rate of DOK cells was significantly reduced and apoptosis and ROS generation induced more effectively by ALA-PDT combined with LY2109761. Furthermore, cell cycle analysis revealed that the combined treatment resulted in G0/G1 phase arrest. CONCLUSIONS: ALA-PDT suppresses the growth of oral precancerous cells by regulating the TGF-ß signaling pathway, and its suppressive effect was enhanced using LY2109761. These results indicate that it could be a promising alternative treatment against oral precancerous lesions.

Emergence and Breaking of Duality Symmetry in Generalized Fundamental Thermodynamic Relations.

Thermodynamics as limiting behaviors of statistics is generalized to arbitrary systems with probability a priori where the thermodynamic infinite-size limit is replaced by a multiple-measurement limit. A duality symmetry between Massieu's and Gibbs's entropy arises in the limit of infinitely repeated observations, yielding the Gibbs equation and Hill-Gibbs-Duhem equation (HGDE) as a dual pair. If a system has a thermodynamic limit satisfying Callen's postulate, entropy being an Eulerian function, the symmetry is lost: the HGDE reduces to the Gibbs-Duhem equation. This theory provides a de-mechanized foundation for classical and nanothermodynamics and offers a framework for distilling emergence from large data, free from underlying details.

Microbial community alteration in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is the most common oral cavity malignancy. The role of the microbial community in TSCC development and progression is unclear. In the present study, 23 patients with TSCC were recruited. Tissue DNA was extracted from cancer and paracancerous normal tissues from all participants. Next-generation 16S rDNA amplicon sequencing and functional prediction were applied for taxonomic analysis. Alpha diversity measurements using the Shannon and Simpson diversity indexes indicated a significant increase in the microbiotic diversity of cancer samples (Shannon index: P = 0.001, Simpson index: P = 0.015); otherwise, no differences were found when using observed operational taxonomic units (OTUs) and Chao1 index (observed OTUs: P = 0.261, Chao1 index: P = 0.054). The dominant phyla of the microbiota included Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Fusobacteria. Multivariate analysis of variance (Adonis) and nonparametric analysis of similarities (ANOSIM) based on unweighted unifrac distances demonstrated differences in the bacterial community structure between the two groups (P = 0.001 for Adonis, P = 0.001 for ANOSIM). Compared with the normal samples, Neisseria, Streptococcus, and Actinomyces levels decreased significantly in cancer samples. Co-occurrence network analysis implied that the bacterial community in cancer was more conserved than that in normal tissue. Matched-pair analysis of cancer and control samples revealed a significant alteration in the relative abundance of specific taxa. These findings will enrich our knowledge of the association between the oral microbial community and TSCC. Further experiments should investigate the potential carcinogenic mechanism of microbial community alterations in TSCC. KEY POINTS: • Microbial community role in tongue squamous cell carcinoma. • Significant alteration of microbiome found between cancer and normal tissues. • Microbial community alteration and potential carcinogenic mechanism.

Oral Treponema denticola Infection Induces Aß1-40 and Aß1-42 Accumulation in the Hippocampus of C57BL/6 Mice.

Accumulation of amyloid-ß (Aß) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aß remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aß1-40 and Aß1-42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both ß-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of ß-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aß accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aß1-42 and Aß1-40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

The Role of Autologous Platelet Concentrates in the Treatment of Medication-Related Osteonecrosis of the Jaw.

ABSTRACT: The frequent refractory response of patients to the treatment of medication-related osteonecrosis of the jaw (MRJON) has attracted clinicians' attention to several treatments. However, they are at best, palliative, and have a higher failure rate than previous treatments. The present meta-analysis was performed to evaluate the clinical effectiveness of autologous platelet concentrates (APCs) combined with surgery in the treatment of MRONJ. The authors conducted a meta-analysis involving a systematic search of PubMed, EMBASE, Wiley Online Library and the Cochrane Library for eligible studies from their inception to November 2019, in accordance with preselected criteria. The inverse variance method was applied to fixed or random effects models based on the heterogeneity of the studies. Thirteen studies that investigated APCs in the treatment of MRONJ were eligible for inclusion in the meta-analysis of 223 patients and 33 lesions. The pooled success rate of APCs combined with surgery for MRONJ was 90% (95%CI, 80%-97%) and the pooled OR was 7.67 (95%CI, 2.10-27.98), indicating the combination was 7.67 times more effective than surgery alone. The results suggest that the use of APCs is a promising therapeutic regimen, as it provided additional benefits to surgery in the treatment of MRONJ. To achieve the benefits, a tension-free primary closure of the soft tissue is recommended as well. Randomized studies with large sample sizes is warranted to confirm our finding.

NAD-dependent methylenetetrahydrofolate dehydrogenase inhibits oral squamous cell carcinoma cell proliferation and promotes apoptosis.

BACKGROUND: NAD-dependent methylenetetrahydrofolate dehydrogenase catalyzes the conversion of 10-formyltetrahydrofolate to formate in embryonic and adult mammalian mitochondria. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is a folate cycle enzyme that is involved in the development of various diseases including cancer. However, the specific mechanisms in oral squamous cell carcinoma (OSCC) are unclear. We analyzed the functional routes of MTHFD1L in OSCC cells. METHODS: MTHFD1L expression in OSCC was analyzed using data from The Cancer Genome Atlas (TCGA) database. Then, the levels of mRNA were measured in OSCC and para-tumor oral tissues using Affymetrix microarrays. Additionally, the effects of short hairpin RNA (shRNA)-induced MTHFD1L silencing on the biological behavior of OSCC were assessed in vitro and in vivo, and the potential molecular mechanisms underlying MTHFD1L activity were also investigated. RESULTS: A TCGA database analysis of RNA sequencing revealed that MTHFD1L levels were higher in tumor tissue than in adjacent tissues. Immunohistochemical staining and Kaplan-Meier survival analysis also indicated that MTHFD1L upregulation is associated with a poor prognosis in OSCC. The knockdown of MTHFD1L suppressed cell proliferation, colony formation, and tumorigenesis, while it induced apoptosis in OSCC. Mechanistically, a microarray analysis showed that MTHFD1L suppressed c-MYC and activated p53 signaling by regulating the protein expression of TP53, GADD45A, FAS and JUN. CONCLUSIONS: MTHFD1L may be involved in OSCC progression via the c-MYC gene and p53 signaling and may serve as a novel target and orientation for tumor therapy.

Nonequilibrium Statistical Mechanics of Continuous Attractors.

Continuous attractors have been used to understand recent neuroscience experiments where persistent activity patterns encode internal representations of external attributes like head direction or spatial location. However, the conditions under which the emergent bump of neural activity in such networks can be manipulated by space and time-dependent external sensory or motor signals are not understood. Here, we find fundamental limits on how rapidly internal representations encoded along continuous attractors can be updated by an external signal. We apply these results to place cell networks to derive a velocity-dependent nonequilibrium memory capacity in neural networks.

Structured silicon for revealing transient and integrated signal transductions in microbial systems.

Bacterial response to transient physical stress is critical to their homeostasis and survival in the dynamic natural environment. Because of the lack of biophysical tools capable of delivering precise and localized physical perturbations to a bacterial community, the underlying mechanism of microbial signal transduction has remained unexplored. Here, we developed multiscale and structured silicon (Si) materials as nongenetic optical transducers capable of modulating the activities of both single bacterial cells and biofilms at high spatiotemporal resolution. Upon optical stimulation, we capture a previously unidentified form of rapid, photothermal gradient-dependent, intercellular calcium signaling within the biofilm. We also found an unexpected coupling between calcium dynamics and biofilm mechanics, which could be of importance for biofilm resistance. Our results suggest that functional integration of Si materials and bacteria, and associated control of signal transduction, may lead to hybrid living matter toward future synthetic biology and adaptable materials.

A Programmable Mechanical Maxwell's Demon.

We introduce and investigate a simple and explicitly mechanical model of Maxwell's demon-a device that interacts with a memory register (a stream of bits), a thermal reservoir (an ideal gas) and a work reservoir (a mass that can be lifted or lowered). Our device is similar to one that we have briefly described elsewhere, but it has the additional feature that it can be programmed to recognize a chosen reference sequence, for instance, the binary representation of π . If the bits in the memory register match those of the reference sequence, then the device extracts heat from the thermal reservoir and converts it into work to lift a small mass. Conversely, the device can operate as a generalized Landauer's eraser (or copier), harnessing the energy of a dropping mass to write the chosen reference sequence onto the memory register, replacing whatever information may previously have been stored there. Our model can be interpreted either as a machine that autonomously performs a conversion between information and energy, or else as a feedback-controlled device that is operated by an external agent. We derive generalized second laws of thermodynamics for both pictures. We illustrate our model with numerical simulations, as well as analytical calculations in a particular, exactly solvable limit.

Entropic constraints on the steady-state fitness of competing self-replicators.

Recent developments in nonequilibrium statistical mechanics suggest that the history of entropy production in a system determines the relative likelihood of competing processes. This presents the possibility of interpreting and predicting the self-organization of complex active systems, but existing theories rely on quantities that are challenging to obtain. Here, we address this issue for a general class of Markovian systems in which two types of self-replicating molecular assemblies (self-replicators) compete for a pool of limiting resource molecules within a nonequilibrium steady state. We derive exact relations that show that the relative fitness of these species depends on a path function, ψ, which is a sum of the entropy production and a relative-entropy term. In the limit of infinite path length, ψ reduces to the entropy production. We demonstrate use of the theory by numerically studying two models inspired by biological systems, including a simplified model of a competition between strains of the yeast prion Sup35 in the presence of driven disaggregation by the ATPase Hsp104.

Biophysical clocks face a trade-off between internal and external noise resistance.

Many organisms use free running circadian clocks to anticipate the day night cycle. However, others organisms use simple stimulus-response strategies ('hourglass clocks') and it is not clear when such strategies are sufficient or even preferable to free running clocks. Here, we find that free running clocks, such as those found in the cyanobacterium Synechococcus elongatus and humans, can efficiently project out light intensity fluctuations due to weather patterns ('external noise') by exploiting their limit cycle attractor. However, such limit cycles are necessarily vulnerable to 'internal noise'. Hence, at sufficiently high internal noise, point attractor-based 'hourglass' clocks, such as those found in a smaller cyanobacterium with low protein copy number, Prochlorococcus marinus, can outperform free running clocks. By interpolating between these two regimes in a diverse range of oscillators drawn from across biology, we demonstrate biochemical clock architectures that are best suited to different relative strengths of external and internal noise.

Self-propulsion of a grain-filled dimer in a vertically vibrated channel.

Steady dissipation of energy is a crucial property that distinguishes active particles from Brownian particles. However, it is not straightforward to explicitly model the dissipative property of existing active particles driven by a vibrating plate. We present a novel active particle that can be explicitly modeled by Newtonian dynamics of a conservative force field plus two asymmetrical dissipative terms. The particle is a dimer consisting of two ping-pong balls connected by a rigid rod, and its two balls are filled with granular particles of the same total mass but of different grain size. This dimer placed on a vibrating plate exhibits 3 types of motion - by tuning the frequency and the amplitude of the vibration, the dimer undergoes either a directed motion toward the small (or large) grain-filled side or an unbiased random motion. We investigate the various modes of motion both experimentally and numerically and show that the directed motion is a result of the asymmetric damping due to the size difference in the filling grains. Furthermore, the numerical simulation reveals that the dimer's dynamics in either directed motion mode resembles a limit cycle attractor that is independent of its initial condition.

Nonequilibrium thermodynamics of the Markovian Mpemba effect and its inverse.

Under certain conditions, it takes a shorter time to cool a hot system than to cool the same system initiated at a lower temperature. This phenomenon-the "Mpemba effect"-was first observed in water and has recently been reported in other systems. Whereas several detail-dependent explanations were suggested for some of these observations, no common underlying mechanism is known. Using the theoretical framework of nonequilibrium thermodynamics, we present a widely applicable mechanism for a similar effect, the Markovian Mpemba effect, derive a sufficient condition for its appearance, and demonstrate it explicitly in three paradigmatic systems: the Ising model, diffusion dynamics, and a three-state system. In addition, we predict an inverse Markovian Mpemba effect in heating: Under proper conditions, a cold system can heat up faster than the same system initiated at a higher temperature. We numerically demonstrate that this inverse effect is expected in a 1D antiferromagnet nearest-neighbors interacting Ising chain in the presence of an external magnetic field. Our results shed light on the mechanism behind anomalous heating and cooling and suggest that it should be possible to observe these in a variety of systems.

[Phonetic parameters analysis of articulated consonant with different denture base].

OBJECTIVE: To compare the phonetic parameters changes of titanium denture base materials to that of conventionally processed poly methyl methacrylate (PMMA) resin. METHODS: Forty-two edentulous patients were included in this study. Each patient received two sets of dentures. One of the upper denture was restored with titanium denture base, the other was restored with conventional PMMA denture base. Consonant /x, sh, r, zh, ch, j, q/ associated with place of articulation and manner of articulation were chosen and all of the processed acoustic specimens were stored at computerized speech lab (CSL). Model 4150 (KAY) for the first concentrated frequency area (CFA-1), voice onset time (VOT) and spectrogram were analyzed. RESULTS: The consonant articulation effect of denture base showed significant difference between the two type of dentures in the CSL. The consonant parameters (/x, sh, r, zh, ch, j, q/) CFA-1 of group A [(3595 +/- 102), (3089 +/- 104), (1876 +/- 116), (4078 +/- 116), (3604 +/- 119), (5432 +/- 118), (4934 +/- 121) Hz] was different from the one of group B [(3644 +/- 101), (3280 +/- 88), (1978 +/- 113), (4214 +/- 193), (3817 +/- 49), (5478 +/- 158), (5020 +/- 183) Hz] (P < 0.05). The consonant parameters VOT of /zh, ch, j/ in group A [(54.67 +/- 1.13), (143.80 +/- 2.24), (62.53 +/- 0.75) ms] was different from those of group B [(52.88 +/- 0.34), (137.55 +/- 2.50), (62.00 +/- 1.54) ms] (P < 0.05). The consonant parameters VOT of /g, k/ in group A [(26.94 +/- 0.33), (114.53 +/- 2.15) ms] was different from those of group B [(28.59 +/- 0.65), (124.40 +/- 3.74) ms] (P < 0.05). A redundant spike as it was located prior to the inherent spike could be observed in the /g, k/ spectrogram of the PMMA denture base group. CONCLUSIONS: Titanium denture base is recommended to provide a satisfying form of articulate position with thinner front palate thickness of the denture base. CFA-1 and VOT based CSL are effective acoustic parameters for articulation testing after denture delivery.

Fracture strength of custom-fabricated Celay all-ceramic post and core restored endodontically treated teeth.

BACKGROUND: The increased use of all-ceramic crown provides a rationale for tooth-colored core. Due to superior mechanical properties, Vita Celay infiltration ceramic developed for crown and bridge works presents the potential for fabricating all-ceramic posts and cores in one piece. This study was conducted to compare the fracture strength of endodontically treated teeth which were thereafter given different types of posts and cores and crowns restoration, respectively. The evaluated post-and-core systems are: custom-fabricated Celay all-ceramic post-core, custom cast metal post-core, and prefabricated stainless steel post (Parapost) with and without 2.0 mm dentine ferrule. METHODS: Sixty freshly extracted human maxillary central incisors were endodontically treated and randomly divided into five groups with 12 samples each. Group A: Celay ceramic post-cores restored teeth with 2.0 mm dentine ferrule. Group B: Celay ceramic post-cores restored teeth with no dentine ferrule. Group C: cast metal post-cores restored teeth with 2.0 mm dentine ferrule. Group D: cast metal post-cores restored teeth with no dentine ferrule. Group E: prefabricated post and composite cores restored teeth with 2.0 mm dentine ferrule. All teeth were restored with Celay ceramic crowns. Each specimen was subjected to a load at a 45-degree angle to the long axis on MTS 810 material testing machine until failure, at crosshead speed of 0.02 cm/minute. Analysis of variance followed by the Newman-Keuls pairwise multiple comparison tests were used to compare the results of the groups tested. RESULTS: There was a statistically significant difference among the five groups (P < 0.01). Celay ceramic post-cores restored teeth with 2.0 mm dentine ferrule [(758.35+/-19.26) N] and cast metal post-cores restored teeth with 2.0 mm dentine ferrule [(756.63+/-66.22) N] had a significantly greater mean fracture strength than the other three groups in which no significant difference was observed. The 2.0 mm dentine ferrule could cause significant fracture resistance alteration of Celay post-core restored teeth. CONCLUSIONS: When covered with Celay ceramic crowns, Celay post-cores restored teeth with 2.0 mm dentine ferrule and cast metal post-cores restored teeth with 2.0 mm dentine ferrule have similar fracture strength. There was a statistically significant difference between the fracture resistance of Celay post-core restored teeth with and without 2.0 mm dentine ferrule.

[Cloning and expression of the succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum Chinese strain in E. coli].

OBJECTIVE: To clone the full-length gene encoding succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum (SjSDISP) Chinese strain and express it in Escherichia coli. METHODS: According to the published incomplete EST (BU804141) of SjSDISP and the sequence of multiclone sites of lambda gt11 vector, 2 pairs of primers were designed and synthesized. Then the 3' and 5'ends of the EST of the SjSDISP from adult Schistosoma japonicum cDNA library were amplified by anchored PCR. After sequencing, a full-length cDNA sequence of the SjSDISP was obtained, and then it was cloned into prokaryotic expression vector pGEX-4T-1. Identified by agarosed gel electrophoresis, endonucleases digestion and PCR, the resultant recombinant plasmid was used for the expression under the temperature-dependent condition and Western blot analysis. RESULTS: A 1,071 bp sequence was obtained. Sequence analysis showed that the fragment contained a complete open reading frame (ORF), encoding 278 amino acid residues. This target fragment was cloned into the prokaryotic expression vector pGEX-4T-1, and expressed in Escherichia coli. SDS-PAGE revealed that the molecular weight of the expressed fusion recombinant product was 56 kD. Western blot showed that the recombinant protein was recognized by polyclonal rabbit antiserum immunized with Schistosoma japonicum adult worm antigen. CONCLUSION: Cloning of the full-length gene encoding SjSDISP and its bacterial expression were successfully done.