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Understanding collective properties of driven particle systems is significantfor naturally occurring aggregates and because the knowledge gained can be usedas building blocks for the design of artificial ones. We model self propellingbiological or artificial individuals interacting through pairwise attractiveand repulsive forces. For the first time, we are able to predict stability andmorphology of organization starting from the shape of the two-body interaction.We present a coherent theory, based on fundamental statistical mechanics, forall possible phases of collective motion.

Understanding collective properties of driven particle systems is significantfor naturally occurring aggregates and because the knowledge gained can be usedas building blocks for the design of artificial ones. We model self propellingbiological or artificial individuals interacting through pairwise attractiveand repulsive forces. For the first time, we are able to predict stability andmorphology of organization starting from the shape of the two-body interaction.We present a coherent theory, based on fundamental statistical mechanics, forall possible phases of collective motion.

This study explores the phase-controlled growth of few-layered 2H-MoTe 2 , 1T'-MoTe 2 , and 2H-/1T'-MoTe 2 heterostructures and their impacts on metal contact properties. Cold-wall chemical vapor deposition (CW-CVD) with varying growth rates of MoO x and reaction temperatures with Te vapors enabled the growth of continuous thin films of either 1T'-MoTe 2 or 2H-MoTe 2 phases on two-inch sapphire substrates. This methodology facilitates the meticulous optimization of chemical vapor deposition (CVD) parameters, enabling the realization of phase-controlled growth of few-layered MoTe 2 thin films and their subsequent heterostructures. The study further investigates the influence of a 1T'-MoTe 2 intermediate layer on the electrical properties of metal contacts on few-layered 2H-MoTe 2 . Bi-layer Ti/Al contacts directly deposited on 2H-MoTe 2 exhibited Schottky behavior, indicating inefficient carrier transport. However, introducing a few-layered 1T'-MoTe 2 intermediate layer between the metal and 2H-MoTe 2 layers improved the contact characteristics significantly. The resulting Al/Ti/1T'-MoTe 2 /2H-MoTe 2 contact scheme demonstrates Ohmic behavior with a specific contact resistance of around 1.7 × 10 -4 Ω cm 2 . This substantial improvement is attributed to the high carrier concentration of the 1T'-MoTe 2 intermediate layer which could be attributed tentatively to the increased tunneling events across the van der Waals gap and enhancing carrier transport between the metal and 2H-MoTe 2 .

This study employs cold-wall chemical vapor deposition to achieve the growth of MoTe 2 thin films on 4-inch sapphire substrates. A two-step growth process is utilized, incorporating MoO 3 and Te powder sources under low-pressure conditions to synthesize MoTe 2 . The resultant MoTe 2 thin films exhibit a dominant 1T' phase, as evidenced by a prominent Raman peak at 161 cm -1 . This preferential 1T' phase formation is attributed to controlled manipulation of the second-step growth temperature, essentially the reaction stage between Te vapor and the pre-deposited MoO x layer. Under these optimized growth conditions, the thickness of the continuous 1T'-MoTe 2 films can be precisely tailored within the range of 3.5-5.7 nm (equivalent to 5-8 layers), as determined by atomic force microscopy depth profiling. Hall-effect measurements unveil a typical hole concentration and mobility of 0.2 cm 2 Vs -1 and 7.9 × 10 21 cm -3 , respectively, for the synthesized few-layered 1T'-MoTe 2 films. Furthermore, Ti/Al bilayer metal contacts deposited on the few-layered 1T'-MoTe 2 films exhibit low specific contact resistances of approximately 1.0 × 10 -4 Ω cm 2 estimated by the transfer length model. This finding suggests a viable approach for achieving low ohmic contact resistance using the 1T'-MoTe 2 intermediate layer between metallic electrodes and two-dimensional semiconductors., (Creative Commons Attribution license.)

In this study, we explored the in vivo effects of Ocimum gratissimum aqueous extracts (OGE) on colorectal cancer (CRC) development provoked by azoxymethane/dextran sodium sulfate (AOM/DSS). The results showed a significant reduction in the tumor load and tumor number for the OGEH group that received continued administration of OGE compared to the AOM/DSS group, with P values of <0.01, but this was not observed in the OGEHs group that received separated administration of OGE. All groups except the control group exhibited aberrant crypt foci (ACF) and adenocarcinoma of lesion pathology in colon, and both conditions were significantly reduced in the OGEH group (P < 0.01) as compared to the AOM/DSS group. Subsequent investigation into whether OGE exhibits eliminative effects on DSS-induced severe colitis (SC) in mice showed that the disease activity index score was significantly reduced in the OGE-treated groups (P < 0.01), also colon colitis histological score was reversed. These data suggest that OGE may be potentially effective in preventing CRC when administered throughout the promotional stages of carcinogenesis by inhibiting inflammatory SC., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We theoretically propose a scheme to generate a strong continuous-variable quantum entangled light source in four-wave mixing (FWM) process by increasing the optical density of atomic medium. By properly choosing the input coupling field Rabi frequency and detuning, the optimized entanglement can be achieved to be better than -17 dB at an optical density of approximately 1, 000, which has been realized in atomic media. Besides, with the optimized one-photon detuning and coupling Rabi frequency, the optimum entanglement degree can be greatly enhanced with the increment of optical density. We also examine the effects of atomic decoherence rate and two-photon detuning on entanglement in a realistic setting, and evaluate the experimental feasibility. We find that the entanglement can be further improved by considering two-photon detuning. In addition, with optimum parameters the entanglement is robust against the decoherence. The strong entanglement provides a promising applications in continuous-variable quantum communications.

Polluted waterbodies such as rivers provide a pathway or reservoir for bacterial resistance. We studied water quality and bacterial antibacterial resistance along the subtropical Qishan River in Taiwan as a case study of environmental resistance spread in a pristine rural area. Human settlement densities increased generally from pristine mountain sites to the more polluted lowlands. Accordingly, as a working hypothesis, we expected the antibacterial resistance level to increase downstream. We collected sediment samples from 8 stations along the Qishan river and where the Qishan river reaches the Kaoping river. The samples were processed in the lab for bacteriological and physicochemical analysis. Antibacterial resistance was tested with common antibacterial. A comparison was made among the sites where isolates began to occur at the upstream (sites 1-6) with the downstream, including site 7 (Qishan town), site 8 (wastewater treatment plant), and site 9 (Kaoping river). The results of multivariate analysis for bacteriological and physicochemical parameters showed increasing water pollution levels downstream of the Qishan river. Bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, Enterobacter sp., Acinetobacter sp., Staphylococcus spp., and Bacillus spp. were analyzed and tested in the study. Their percentage of occurrence varied at each site. The resistance level was determined from the growth inhibition zone diameter (disk diffusion) and the minimum inhibitory concentration (micro-dilution). The results indicated that antibacterial resistance was related to certain environmental factors. Besides, the usage pattern of different classes of antibacterial in different sections could alter trends of their resistance. Bacteria were found with increased resistance to antibacterial used in agriculture through the downstream sites. The WWTP discharging wastewater was demonstrated to be a hotspot of resistance in aquatic environments. In conclusion, bacterial resistance against antibacterial from the Qishan river has become a potential public health threat. This study could assist authorities by providing a reference for risk assessment and management of water quality in Kaohsiung city and southern Taiwan., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 μM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.

Transvaginal mesh (TVM) insertion for the treatment of pelvic organ prolapse (POP) is significantly associated with lower failure rates, although its use remains controversial due to the potential risk of mesh-related complications. In this review, we collected the published literature regarding the use of TVM to treat POP in an attempt to assess both the efficacy and complications related to TVM usage in Taiwan. We searched 25 English language articles using PubMed related to TVM in Taiwan from 2010 to 2019. The present article focuses on the efficacy and complications of TVM and analyzes the data. There were 25 studies on TVM selected for this review. Regarding their success rate, 21 out of the 22 studies (95.5%) had more than a 90% objective success rate. Twenty studies (90.9%) had less than 10% major complications of TVM. Twenty out of the 25 studies (80.0%) had 5% or less mesh exposure. For self-cut TVM and the later single-incision TVM, both the complication rates and exposure rates decreased. The rate of de novo dyspareunia ranged from 2.6% to 14.3%, and the incidence decreased yearly from 2011 to 2019. This review showed both the high treatment efficacy and low complication rate of TVM usage for the short-term treatment of POP in Taiwan. However, a longer-term study is needed to draw a conclusion regarding the safety of this treatment., Competing Interests: Declaration of competing interest There are no conflicts of interest for any of the authors., (Copyright © 2021. Published by Elsevier B.V.)

Quantum entanglement is an essential ingredient for the absolute security of quantum communication. Generation of continuous-variable entanglement or two-mode squeezing between light fields based on the effect of electromagnetically induced transparency (EIT) has been systematically investigated in this work. Here, we propose a new scheme to enhance the degree of entanglement between probe and coupling fields of coherent-state light by introducing a two-photon detuning in the EIT system. This proposed scheme is more efficient than the conventional one, utilizing the ground-state relaxation (population decay or dephasing) rate to produce entanglement or two-mode squeezing which adds far more excess fluctuation or noise to the system. In addition, maximum degree of entanglement at a given optical depth can be achieved with a wide range of the coupling Rabi frequency and the two-photon detuning, showing our scheme is robust and flexible. It is also interesting to note that while EIT is the effect in the perturbation limit, i.e. the probe field being much weaker than the coupling field and treated as a perturbation, there exists an optimum ratio of the probe to coupling intensities to achieve the maximum entanglement. Our proposed scheme can advance the continuous-variable-based quantum technology and may lead to applications in quantum communication utilizing squeezed light.

Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parameters using traditional experimental approaches is impractical due to the vast parameter space; mathematical models provide a more tractable approach to navigate through such a multidimensional space. To this end, we have developed a predictive mathematical model of whole-body NP pharmacokinetics and their tumor delivery in vivo , and have conducted local and global sensitivity analyses to identify the factors that result in low tumor delivery efficiency and high off-target accumulation of NPs. Our analyses reveal that NP degradation rate, tumor blood viscosity, NP size, tumor vascular fraction, and tumor vascular porosity are the key parameters in governing NP kinetics in the tumor interstitium. The impact of these parameters on tumor delivery efficiency of NPs is discussed, and optimal values for maximizing NP delivery are presented., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Cornea is the transparent layer in front of the eye that does not contain blood vessels. Among eye diseases, corneal neovascularization (NV) is one of the major causes of vision loss, since it can also lead to blindness. An herbal extraction containing flavonoid, kaempferol (KA), with antiangiogenic effect was chosen as a candidate drug for inhibited vessel formation. The use of nanomedicine has led to higher drug bioavailability and slow release of the drug as an effective therapeutic formulation in ocular drug delivery. In this study, we prepared gelatin nanoparticles (GNP) with kaempferol encapsulation (GNP-KA) for corneal NV treatment by topical delivery, i.e., eye drops. We found that GNP with/without KA loading was in the size of 85-150 nm, and its zeta potential was around 22-26 mV. The KA entrapment rate of GNP-KA was around 90-98%, and the loading rate was about 4.6%. The TEM results clearly indicated the GNP-KA NPs to be round spheres. The in vitro test involved the adoption of human umbilical vein endothelial cells (HUVECs) for coculture with these nanoparticles. From WST-8 assay, and cell migration examinations, it was evident that GNP-KA had the capacity to inhibit the cell viability and function of HUVECs. The results from in vivo tests such as ocular vessels observation, hematoxylin & eosin (H&E) stain, and metalloproteinases (MMP)/vascular endothelial growth factor (VEGF) quantification revealed the mice's eyes with corneal NV treated by eye drops containing GNP-KA once daily for 7 days had better therapeutic effects with less vessels in-growths in the cornea, compared to the KA solution group by reducing the production of MMP and VEGF in the cornea. Therefore, we expected to achieve a comfortable treatment with a simple method using nanomedicine (GNP-KA) as ophthalmological agent delivered as eye drops., Competing Interests: The authors declare no conflict of interest.

We study the spatiotemporal correlation of terrorist attacks by al-Qaeda, the Islamic State of Iraq and Syria (ISIS), and local insurgents, in six geographical areas identified via k-means clustering applied to the Global Terrorism Database. All surveyed organizations exhibit near-repeat activity whereby a prior attack increases the likelihood of a subsequent one by the same group within 20 km and on average 4 (al-Qaeda) to 10 (ISIS) weeks. Near-response activity, whereby an attack by a given organization elicits further attacks from a different one, is found to depend on the adversarial, neutral, or collaborative relationship between the two. When in conflict, local insurgents respond quickly to attacks by global terror groups while global terror groups delay their responses to local insurgents, leading to an asymmetric dynamic. When neutral or allied, attacks by one group enhance the response likelihood of the other, regardless of hierarchy. These trends arise consistently in all clusters for which data are available. Government intervention and spillover effects are also discussed; we find no evidence of outbidding. Understanding the regional dynamics of terrorism may be greatly beneficial in policy making and intervention design., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Naive human T cells are produced and developed in the thymus, which atrophies abruptly and severely in response to physical or psychological stress. To understand how an instance of stress affects the size and "diversity" of the peripheral naive T cell pool, we derive a mean-field autonomous ODE model of T cell replenishment that allows us to track the clone abundance distribution (the mean number of different TCRs each represented by a specific number of cells). We identify equilibrium solutions that arise at different rates of T cell production, and derive analytic approximations to the dominant eigenvalues and eigenvectors of the mathematical model linearized about these equilibria. From the forms of the eigenvalues and eigenvectors, we estimate rates at which counts of clones of different sizes converge to and depart from equilibrium values-that is, how the number of clones of different sizes "adjusts" to the changing rate of T cell production. Under most physiological realizations of our model, the dominant eigenvalue (representing the slowest dynamics of the clone abundance distribution) scales as a power law in the thymic output for low output levels, but saturates at higher T cell production rates. Our analysis provides a framework for quantitatively understanding how the clone abundance distribution evolves under small changes in the overall T cell production rate.

Nanomedicine holds promise for the treatment of cancer, as it enables tumor-targeted drug delivery. However, reports on translation of most nanomedicine strategies to the clinic so far have been less than satisfactory, in part due to insufficient understanding of the effects of nanoparticle (NP) physiochemical properties and physiological variables on their pharmacological behavior. In this paper, we present a multiscale mathematical model to examine the efficacy of NP delivery to solid tumors; as a case example, we apply the model to a clinically detectable primary pancreatic ductal adenocarcinoma (PDAC) to assess tissue-scale spatiotemporal distribution profiles of NPs. We integrate NP systemic disposition kinetics with NP-cell interactions in PDAC abstractly described as a two-dimensional structure, which is then parameterized with human physiological data obtained from published literature. Through model analysis of delivery efficiency, we verify the multiscale approach by showing that NP concentration kinetics of interest in various compartments predicted by the whole-body scale model were in agreement with those obtained from the tissue-scale model. We also found that more NPs were trapped in the outer well-perfused tumor region than the inner semi-necrotic domain. Further development of the model may provide a useful tool for optimal NP design and physiological interventions.

The human adaptive immune response is known to weaken in advanced age, resulting in increased severity of pathogen-born illness, poor vaccine efficacy, and a higher prevalence of cancer in the elderly. Age-related erosion of the T cell compartment has been implicated as a likely cause, but the underlying mechanisms driving this immunosenescence have not been quantitatively modeled and systematically analyzed. T cell receptor diversity, or the extent of pathogen-derived antigen responsiveness of the T cell pool, is known to diminish with age, but inherent experimental difficulties preclude accurate analysis on the full organismal level. In this paper, we formulate a mechanistic mathematical model of T cell population dynamics on the immunoclonal subpopulation level, which provides quantitative estimates of diversity. We define different estimates for diversity that depend on the individual number of cells in a specific immunoclone. We show that diversity decreases with age primarily due to diminished thymic output of new T cells and the resulting overall loss of small immunoclones.

Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine has made significant progress, but challenges remain that impede its clinical translation. Several biophysical barriers to the transport of nanocarriers to the tumor exist, and a much deeper understanding of nano-bio interactions is necessary to change the status quo. Mathematical modeling has been instrumental in improving our understanding of the physicochemical and physiological underpinnings of nanomaterial behavior in biological systems. Here, we present a comprehensive review of literature on mathematical modeling works that have been and are being employed towards a better understanding of nano-bio interactions for improved tumor delivery efficacy.

We propose an all-optical-control scheme to simultaneously realize parity-time (𝒫𝒯)-symmetric and 𝒫𝒯-antisymmetric susceptibilities along the propagation direction of light by applying an external magnetic field. Through the light-atom interaction within a double-Λ configuration, the resulting position-dependent susceptibilities for the interacting fields can be manipulated through the relative phase between them. In particular, for the probe field, one can switch its refractive index from the 𝒫𝒯-symmetry to 𝒫𝒯-antisymmetry by just varying the phase. Based on the quantum interference among transition channels in a closed loop, analytical formulas are also derived to illustrate the conditions for 𝒫𝒯-symmetry and 𝒫𝒯-antisymmetry.

Considering matter wave bright solitons from weakly coupled Bose-Einstein condensates trapped in a double-well potential, we study the formation of macroscopic non-classical states, including Schrödinger-cat superposition state and maximally path entangled N00N-state. We examine these macroscopic states by Mach-Zehnder interferometer in the context of parity measurements, which has been done to obtain Heisenberg limit accuracy for linear phase shift measurement. We reveal that the ratio of two-body scattering length to intra-well hopping parameter can be measured with the scaling beyond this limit by using nonlinear phase shift with interacting quantum solitons.

To explore resonance phenomena in the nonlinear region, we show by experimental measurements and theoretical analyses that resonance happens in modulation instability from non-instantaneous nonlinearities in photorefractive crystals. With a temporally periodic modulation in the external bias voltage, corresponding to a modulation in the nonlinear strength, an enhancement in the visibility of MI at resonant frequency is reported through spontaneous optical pattern formations. Theoretical curves obtained from a nonlinear non-instantaneous Schrödinger equation give good agreement to experimental data.

Mammary gland ductal elongation is spearheaded by terminal end buds (TEBs), where populations of highly proliferative cells are maintained throughout post-pubertal organogenesis in virgin mice until the mammary fat pad is filled by a mature ductal tree. We have developed a hybrid multiscale agent-based model to study how cellular differentiation pathways, cellular proliferation capacity, and endocrine and paracrine signaling play a role during development of the mammary gland. A simplified cellular phenotypic hierarchy that includes stem, progenitor, and fully differentiated cells within the TEB was implemented. Model analysis finds that mammary gland development was highly sensitive to proliferation events within the TEB, with progenitors likely undergoing 2-3 proliferation cycles before transitioning to a non-proliferative phenotype, and this result is in agreement with our previous experimental work. Endocrine and paracrine signaling were found to provide reliable ductal elongation rate regulation, while variations in the probability a new daughter cell will be of a proliferative phenotype were seen to have minimal effects on ductal elongation rates. Moreover, the distribution of cellular phenotypes within the TEB was highly heterogeneous, demonstrating significant allowable plasticity in possible phenotypic distributions while maintaining biologically relevant growth behavior. Finally, simulation results indicate ductal elongation rates due to cellular proliferation within the TEB may have a greater sensitivity to upstream endocrine signaling than endothelial to stromal paracrine signaling within the TEB. This model provides a useful tool to gain quantitative insights into cellular population dynamics and the effects of endocrine and paracrine signaling within the pubertal terminal end bud., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Author Summary: Cancer treatment efficacy can be significantly enhanced through the elution of drug from nano-carriers that can temporarily stay in the tumor vasculature. Here we present a relatively simple yet powerful mathematical model that accounts for both spatial and temporal heterogeneities of drug dosing to help explain, examine, and prove this concept. We find that the delivery of systemic chemotherapy through a certain form of nano-carriers would have enhanced tumor kill by a factor of 2 to 4 over the standard therapy that the patients actually received. We also find that targeting blood volume fraction (a parameter of the model) through vascular normalization can achieve more effective drug delivery and tumor kill. More importantly, this model only requires a limited number of parameters which can all be readily assessed from standard clinical diagnostic measurements (e.g., histopathology and CT). This addresses an important challenge in current translational research and justifies further development of the model towards clinical translation.

The Goos-Hänchen (GH) shifts in the reflected light are investigated both for p and s polarized partial coherent light beams incident on epsilon-near-zero (ENZ) metamaterials. In contrary to the coherent counterparts, the magnitude of GH shift becomes non-zero for p polarized partial coherent light beam; while GH shift can be relatively large with a small degree of spatial coherence for s polarized partial coherent beam. Dependence on the beam width and the permittivity of ENZ metamaterials is also revealed for partial coherent light fields. Our results on the GH shifts provide a direction on the applications for partial coherent light sources in ENZ metamaterials.

Background: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time., Materials and Methods: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration., Results: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 μg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents., Summary: Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n-hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP: intraperitoneal.

We derive a three-dimensional theory of self-propelled particle swarming in a viscous fluid environment. Our model predicts emergent collective behavior that depends critically on fluid opacity, mechanism of self-propulsion, and type of particle-particle interaction. In "clear fluids" swimmers have full knowledge of their surroundings and can adjust their velocities with respect to the lab frame, while in "opaque fluids" they control their velocities only in relation to the local fluid flow. We also show that "social" interactions that affect only a particle's propensity to swim towards or away from neighbors induces a flow field that is qualitatively different from the long-ranged flow fields generated by direct "physical" interactions. The latter can be short-ranged but lead to much longer-ranged fluid-mediated hydrodynamic forces, effectively amplifying the range over which particles interact. These different fluid flows conspire to profoundly affect swarm morphology, kinetically stabilizing or destabilizing swarm configurations that would arise in the absence of fluid. Depending upon the overall interaction potential, the mechanism of swimming ( e.g., pushers or pullers), and the degree of fluid opaqueness, we discover a number of new collective three-dimensional patterns including flocks with prolate or oblate shapes, recirculating pelotonlike structures, and jetlike fluid flows that entrain particles mediating their escape from the center of mill-like structures. Our results reveal how the interplay among general physical elements influence fluid-mediated interactions and the self-organization, mobility, and stability of new three-dimensional swarms and suggest how they might be used to kinetically control their collective behavior.

ZnO nanorods (NRs) and Ag nanoparticles (NPs) are known to enhance the luminescence of light-emitting diodes (LEDs) through the high directionality of waveguide mode transmission and efficient energy transfer of localized surface plasmon (LSP) resonances, respectively. In this work, we have demonstrated Ag NP-incorporated n-ZnO NRs/p-GaN heterojunctions by facilely hydrothermally growing ZnO NRs on Ag NP-covered GaN, in which the Ag NPs were introduced and randomly distributed on the p-GaN surface to excite the LSP resonances. Compared with the reference LED, the light-output power of the near-band-edge (NBE) emission (ZnO, λ = 380 nm) of our hybridized structure is increased almost 1.5-2 times and can be further modified in a controlled manner by varying the surface morphology of the surrounding medium of the Ag NPs. The improved light-output power is mainly attributed to the LSP resonance between the NBE emission of ZnO NRs and LSPs in Ag NPs. We also observed different behaviors in the electroluminescence (EL) spectra as the injection current increases for the treatment and reference LEDs. This observation might be attributed to the modification of the energy band diagram for introducing Ag NPs at the interface between n-ZnO NRs and p-GaN. Our results pave the way for developing advanced nanostructured LED devices with high luminescence efficiency in the UV emission regime.

The Social Environment and Biomarkers of Aging Study (SEBAS) is a nationally representative longitudinal survey of Taiwanese middle-aged and older adults. It adds the collection of biomarkers and performance assessments to the Taiwan Longitudinal Study of Aging (TLSA), a nationally representative study of adults aged 60 and over, including the institutionalized population. The TLSA began in 1989, with follow-ups approximately every 3 years; younger refresher cohorts were added in 1996 and 2003. The first wave of SEBAS, based on a sub-sample of respondents from the 1999 TLSA, was conducted in 2000. A total of 1023 respondents completed both a face-to-face home interview and, several weeks later, a hospital-based physical examination. In addition to a 12-h (7 pm-7 am) urine specimen collected the night before and a fasting blood specimen collected during the examination, trained staff measured blood pressure, height, weight and waist and hip circumferences. A second wave of SEBAS was conducted in 2006 using a similar protocol to SEBAS 2000, but with the addition of performance assessments conducted by the interviewers at the end of the home interview. Both waves of SEBAS also included measures of health status (physical, emotional, cognitive), health behaviours, social relationships and exposure to stressors. The SEBAS data, which are publicly available at [http://www.icpsr.umich.edu/icpsrweb/NACDA/studies/3792/version/5], allow researchers to explore the relationships among life challenges, the social environment and health and to examine the antecedents, correlates and consequences of change in biological measures and health., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4(-/-) mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN., (© 2015. Published by The Company of Biologists Ltd.)

This study explores the association of child sexual abuse (CSA) with subsequent health risk behaviors among a cross-section of 4354 adolescents and young adults surveyed in urban and rural Taipei. Descriptive analysis and logistic regressions were employed. The overall proportion of CSA was 5.15%, with more females (6.14%) than males (4.16%) likely to experience CSA. CSA was differently associated with multiple adverse health outcomes, after adjusting other factors, such as age, residence, economic status, education, employment status, and household instability. Both males and females with CSA experience were more likely to report drinking, gambling, and suicidal ideation compared with those who had no history of CSA. However, the significant association between CSA and smoking, fighting, and suicidal attempt was not observed among females. Effective interventions are needed to reduce CSA and its adverse effects on adolescent well-being., (© 2015 APJPH.)

An efficient and effective headspace microextraction technique named static headspace knotted hollow fiber microextraction (HS-K-HFME) has been developed for the determination of volatile organic compounds (VOCs) in water samples. The knot-shaped hollow fiber is filled with 25μL of the extraction solvent. The excess solvent forms a large droplet (13μL) and is held in the center of the knot. Even after 20min of extraction time at high temperature (95°C) without cooling, there was still enough volume of extraction solvent for gas chromatography-mass spectrometry (GC-MS) analysis, which extends the choice of solvents for headspace LPME. Moreover, the knot-shaped fiber has a larger extraction contact interface, which increases the rate of mass transfer between the headspace and extraction solvent film attached to the fiber, thus improving the extraction efficiency. The effects of extraction solvent, temperature, stirring rate, salt concentration and extraction time on extraction performance were optimized. The calibration curves exhibited coefficients of determination (R(2)) ranging from 0.9957 to 0.9999 and the limit of detection (LOD) ranged from 0.2 to 10μgL(-1). Relative standard deviations (RSDs) ranged from 4.5% to 11.6% for intraday measurements (n=5). Interday (n=15) values were between 2.2% and 12.9%. The relative recoveries (RRs) ranged from 90.3% to 106.0% for river water and 95.9% to 103.6% for wastewater., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We propose and analyze an efficient way to enhance four-wave mixing (FWM) signals in a four-subband semiconductor quantum well via Fano-type interference. By using Schrödinger-Maxwell formalism, we derive explicitly analytical expressions for the input probe pulse and the generated FWM field in linear regime under the steady-state condition. With the aid of interference between two excited subbands tunneling to the common continuum, the efficiency to generate FWM field is found to be significantly enhanced, up to 35%. More interestingly, a linear growth rate in the FWM efficiency is demonstrated as the strength of Fano-type interference increases in presence of the continuum states, which can be maintained for a certain propagation distance (i.e., 50μm).

Trophocytes and fat cells of honeybees (Apis mellifera) have been used for cellular senescence studies, but the changes in the expression, concentration, and activity of cellular energy-regulated molecules that occur with aging in worker bees is unknown. In this study, energy-regulated molecules were evaluated in the trophocytes and fat cells of young and old workers. The results showed that (i) adenosine monophosphate-activated protein kinase-α2 (AMPK-α2) expression increased with aging, whereas phosphorylated AMPK-α2 expression, the phosphorylated AMPK/AMPK ratio, and AMPK activity decreased with aging; (ii) adenosine diphosphate and adenosine triphosphate concentrations decreased with aging, the AMP concentration was unchanged, the adenosine diphosphate/adenosine triphosphate ratio did not change with aging, and the AMP/adenosine triphosphate ratio increased with aging; (iii) the cyclic AMP concentration decreased with aging, and cyclic AMP-specific phosphodiesterases activity increased with aging; (iv) silent information regulator 2 (Sir2) expression increased with aging, whereas its activity decreased with aging; and (v) peroxisome proliferator-activated receptor-α expression decreased with aging. These results show that the trophocytes and fat cells of young workers have higher cellular energy status and express higher levels of energy-regulated molecules than those of old workers and that aging results in a decline in the energy status of trophocytes and fat cells in worker honeybees., (© The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chemotherapy is mainstay of treatment for the majority of patients with breast cancer, but results in only 26% of patients with distant metastasis living 5 years past treatment in the United States, largely due to drug resistance. The complexity of drug resistance calls for an integrated approach of mathematical modeling and experimental investigation to develop quantitative tools that reveal insights into drug resistance mechanisms, predict chemotherapy efficacy, and identify novel treatment approaches. This paper reviews recent modeling work for understanding cancer drug resistance through the use of computer simulations of molecular signaling networks and cancerous tissues, with a particular focus on breast cancer. These mathematical models are developed by drawing on current advances in molecular biology, physical characterization of tumors, and emerging drug delivery methods (e.g., nanotherapeutics). We focus our discussion on representative modeling works that have provided quantitative insight into chemotherapy resistance in breast cancer and how drug resistance can be overcome or minimized to optimize chemotherapy treatment. We also discuss future directions of mathematical modeling in understanding drug resistance.

The trophocytes and fat cells of honeybees (Apis mellifera) have been used in cellular senescence studies, but the changes of cellular degradation activity with aging in workers are unknown. In this study, cellular degradation activity was evaluated in the trophocytes and fat cells of young and old workers reared in a field hive. The results showed the following: (1) 20S proteosome activity decreased with aging, whereas its expression increased with aging; (2) the expression of microtubule-associated protein 1 light chain 3-II (LC3-II) and the 70 kD heat shock cognate protein (Hsc70) decreased with aging; (3) the size and number of autophagic vacuoles decreased with aging; (4) p62/SQSTM1 and polyubiquitin aggregate expression decreased with aging; (5) lysosomal efficiency decreased with aging; and (6) molecular target of rapamycin (mTOR) expression increased with aging. These results indicate that young workers have higher levels of cellular degradation activity than old workers and that aging results in a decline in the cellular degradation activity in worker honeybees., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Mathematical modeling of drug transport can complement current experimental and clinical investigations to understand drug resistance mechanisms, which eventually will help to develop patient-specific chemotherapy treatments. In this paper, we present a general time- and space-dependent mathematical model based on diffusion theory for predicting chemotherapy outcome. This model has two important parameters: the blood volume fraction and radius of blood vessels divided by drug diffusion penetration length. Model analysis finds that a larger ratio of the radius of blood vessel to diffusion penetration length resulted in to a larger fraction of tumor killed, thereby leading to a better treatment outcome. Clinical translation of the model can help quantify and predict the optimal dosage size and frequency of chemotherapy for individual patients.

Trophocytes and fat cells in honeybees (Apis mellifera) have served as targets for cellular senescence studies, but mitochondrial energy utilization with advancing age in workers is unknown. In this study, mitochondrial energy utilization was evaluated in the trophocytes and fat cells of young and old workers reared in a field hive. The results showed that (1) mitochondrial density increased with advancing age; (2) mitochondrial membrane potential (∆Ψm), nicotinamide adenine dinucleotide oxidized form (NAD(+)) concentration, adenosine triphosphate (ATP) concentration, and NAD(+)/nicotinamide adenine dinucleotide reduced form (NADH) ratio decreased with advancing age; and (3) the expression of NADH dehydrogenase 1 (ND1), ATP synthase, and voltage-dependent anion channel 1 (VDAC1) increased with advancing age, whereas ND1 and ATP synthase did not differ with advancing age after normalization to mitochondrial density and VDAC1. These results show that the trophocytes and fat cells of young workers have higher mitochondrial energy utilization efficiency than those of old workers and that aging results in a decline in mitochondrial energy utilization in the trophocytes and fat cells of worker honeybees.

Lawsonia inermis (Lythraceae) known as henna is one of the most popular and ancient plants used in cosmetics and hair dying. It is cultivated for its leaves but other parts such as seeds, flowers, stem bark and roots are also used in traditional medicine for millennia. Henna tattoo paste also proved to be beneficial for wound healing and in several skin diseases suggesting potent anti-inflammatory activity. To evaluate henna anti-inflammatory activity, 31 compounds, including three 1,5-diphenylpent-3-en-1-yne derivatives, lawsochylin A-C and three methyl naphthalene carboxylates, lawsonaphthoate A-C, were isolated from the stems and leaves of henna utilizing a bioassay-guided fractionation. The structures of the compounds were elucidated by spectroscopic data. Two compounds, lawsochylin A and lawsonaphthoate A showed potent anti-inflammatory activity by inhibition of superoxide anion generation (IC(50)=1.80 and 1.90 μg/ml) and elastase release (IC(50)=1.58 and 3.17 μg/ml) of human neutrophils in response to fMLP or cytochalasin B. Moreover, the known compounds, luteolin, apigenin, 4S-4-hydroxy-α-tetralone, and 2-butoxysuccinic acid, also showed potent inhibition of superoxide anion generation (IC(50)=0.75-1.78 μg/ml) and elastase release (IC(50)=1.62-3.61 μg/ml)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Non-Hodgkin's lymphoma is a disseminated, highly malignant cancer, with resistance to drug treatment based on molecular- and tissue-scale characteristics that are intricately linked. A critical element of molecular resistance has been traced to the loss of functionality in proteins such as the tumor suppressor p53. We investigate the tissue-scale physiologic effects of this loss by integrating in vivo and immunohistological data with computational modeling to study the spatiotemporal physical dynamics of lymphoma growth. We compare between drug-sensitive Eμ-myc Arf-/- and drug-resistant Eμ-myc p53-/- lymphoma cell tumors grown in live mice. Initial values for the model parameters are obtained in part by extracting values from the cellular-scale from whole-tumor histological staining of the tumor-infiltrated inguinal lymph node in vivo. We compare model-predicted tumor growth with that observed from intravital microscopy and macroscopic imaging in vivo, finding that the model is able to accurately predict lymphoma growth. A critical physical mechanism underlying drug-resistant phenotypes may be that the Eμ-myc p53-/- cells seem to pack more closely within the tumor than the Eμ-myc Arf-/- cells, thus possibly exacerbating diffusion gradients of oxygen, leading to cell quiescence and hence resistance to cell-cycle specific drugs. Tighter cell packing could also maintain steeper gradients of drug and lead to insufficient toxicity. The transport phenomena within the lymphoma may thus contribute in nontrivial, complex ways to the difference in drug sensitivity between Eμ-myc Arf-/- and Eμ-myc p53-/- tumors, beyond what might be solely expected from loss of functionality at the molecular scale. We conclude that computational modeling tightly integrated with experimental data gives insight into the dynamics of Non-Hodgkin's lymphoma and provides a platform to generate confirmable predictions of tumor growth.

Background: The present study aimed to (a) characterize 10-year trajectory patterns of depressive symptoms and (b) investigate the association between depressive trajectory and subsequent obesity, metabolic function and cortisol level., Method: In a prospective study of Taiwanese adults aged ≥60 years (n=3922) between 1989 and 1999, depression was assessed using a 10-item short-form of the Center for Epidemiologic Studies Depression Scale and information on body mass index (BMI) was collected by self-report. A subsample (n=445) of the original cohort in 1989 was drawn to assess metabolic variables and cortisol levels in a 2000 follow-up. After trajectory analyses were performed, multinomial logistic regression analyses were used to estimate the association estimates., Results: We identified four distinctive trajectories of depressive symptoms: class 1 (persistent low, 41.8%); class 2 (persistent mild, 46.8%); class 3 (late peak, 4.2%); and class 4 (high-chronic, 7.2%). The results from both complete cases and multiple imputation analyses indicated that the odds of obesity were lower in the class 2, 3 or 4 elderly, as compared with those in class 1, while the odds of underweight were higher. The classes of older adults with more and persistent depressive symptoms showed a trend toward having both a lower BMI (p=0.01) and a higher cortisol level (p=0.04) compared with those with low depressive symptoms., Conclusions: Incremental increases in depressive symptoms over time were associated with reduced risk of obesity and higher cortisol levels., (© Cambridge University Press 2011)

We introduce a novel "mathematical pathology" approach, founded on a biophysical model, to identify robust patient-specific predictors of tumor growth useful in clinical practice to improve the accuracy of diagnosis/prognosis and intervention. In accordance with biological observations, our model simulates the diffusion-limited in situ tumors with a relatively short phase of fast initial growth, followed by a prolonged slow-growth phase where tumor size is constrained primarily by the relative weight of cell mitosis and death. The former phase may only last for a few months, so that at the time of diagnosis, we may assume that most tumors will have entered the phase where their size is changing slowly. Based on this prediction, we hypothesize that the volume of breast with ducts affected by in situ tumors at the time of diagnosis will be closely approximated by a model-derived mathematical function based on the ratio of tumor cell proliferation-to-apoptosis indices and on the extent of diffusion of cell nutrients (diffusion penetration length), which can be measured from immunohistochemical and morphometric analysis of patient histopathology specimens without the need for multiple-time measurements. We tested this idea in a retrospective study of 17 patients by staining breast tumor specimens containing ductal carcinoma in situ for mitosis with Ki-67 and for apoptosis with cleaved caspase-3 and counting cells positive for each marker. We also determined diffusion penetration by measuring the thickness of viable rims of tumor cells within ducts. Using the ensuing ratios, we applied the model to determine a predicted surgical volume or tumor size. We then corroborated our hypothesis by comparing the predicted size of each tumor based on our model with the actual size of the pathological specimen after tumor excision (R2 = 0.74-0.88). In addition, for the 17 cases studied, both histological grade and mammography were not found to correlate with tumor size (R2 = 0.08-0.47). We conclude that our mathematical pathology approach yields a high degree of accuracy in predicting the size of tumors based on the mitotic/apoptotic index and on diffusion penetration. By obtaining these ratios at the time of initial biopsy, pathologists can employ our model to predict the size of the tumor and thereby inform surgeons how much tissue to remove (surgical volume). We discuss how results from the model have implications concerning the current debate on recommendations for screening mammography, while the model itself may contribute to better planning of breast conservation surgery.

Aims/hypothesis: Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised that the inflammatory signals transduced by TLR2 contribute to insulin resistance., Methods: Mice deficient in TLR2 were used to investigate the in vivo roles of TLR2 in initiating and maintaining inflammation-associated insulin resistance and energy homeostasis., Results: We first recapitulated the observation with elevated expression of TLR2 and inflammatory cytokines in white adipose tissue and liver of ob/ob mice. Aged or high-fat-fed TLR2-deficient mice were protected from obesity and adipocyte hypertrophy compared with wild-type mice. Moreover, mice lacking TLR2 exhibited improved glucose tolerance and insulin sensitivity regardless of feeding them regular chow or a high-fat diet. This is accompanied by reductions in expression of inflammatory cytokines and activation of extracellular signal-regulated kinase (ERK) in a liver-specific manner. The attenuated hepatic inflammatory cytokine expression and related signalling are correlated with increased insulin action specifically in the liver in TLR2-deficient mice, reflected by increased insulin-stimulated protein kinase B (Akt) phosphorylation and IRS1 tyrosine phosphorylation and increased insulin-suppressed hepatocyte glucose production., Conclusions/interpretation: The absence of TLR2 attenuates local inflammatory cytokine expression and related signalling and increases insulin action specifically in the liver. Thus, our work has identified TLR2 as a key mediator of hepatic inflammation-related signalling and insulin resistance.

We extend the diffuse interface model developed in Wise et al. (2008) to study nonlinear tumor growth in 3-D. Extensions include the tracking of multiple viable cell species populations through a continuum diffuse-interface method, onset and aging of discrete tumor vessels through angiogenesis, and incorporation of individual cell movement using a hybrid continuum-discrete approach. We investigate disease progression as a function of cellular-scale parameters such as proliferation and oxygen/nutrient uptake rates. We find that heterogeneity in the physiologically complex tumor microenvironment, caused by non-uniform distribution of oxygen, cell nutrients, and metabolites, as well as phenotypic changes affecting cellular-scale parameters, can be quantitatively linked to the tumor macro-scale as a mechanism that promotes morphological instability. This instability leads to invasion through tumor infiltration of surrounding healthy tissue. Models that employ a biologically founded, multiscale approach, as illustrated in this work, could help to quantitatively link the critical effect of heterogeneity in the tumor microenvironment with clinically observed tumor growth and invasion. Using patient tumor-specific parameter values, this may provide a predictive tool to characterize the complex in vivo tumor physiological characteristics and clinical response, and thus lead to improved treatment modalities and prognosis., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The potential impact of employment on maternal health, particularly in relation to gestational hypertension and pre-eclampsia, has been subject to research. However, there is limited evidence on associations between shift work and long working hours on the incidence of these conditions., Aims: To evaluate potential associations between maternal shift work and long working hours during pregnancy and gestational hypertension or pre-eclampsia., Methods: Multistage stratified systematic sampling was used to recruit 24 200 post-partum women from the Taiwan national birth registration database in 2005. Subjects underwent home interview 6 months after their deliveries by structured questionnaire to obtain characteristics of maternal employment and potential confounders. Diagnosis of gestational hypertension and pre-eclampsia was obtained from the birth registration., Results: There was no association between employment status and gestational hypertension or pre-eclampsia. Also, no significant association between gestational hypertension or pre-eclampsia and maternal shift work or long working hours during pregnancy was found in all or primiparous women., Conclusions: There was no convincing evidence that maternal shift work or long working hours had a higher risk of gestational hypertension or pre-eclampsia. However, further research is warranted to confirm these negative findings.

Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of invasiveness and treatment prognosis.