Soft granular particles sheared at a controlled volume: rate-dependent dynamics and the solid-fluid transition.

We study the responses of fluid-immersed soft hydrogel spheres that are sheared under controlled volume fractions. Slippery, deformable particles along with the density-matched interstitial fluid are sandwiched between two opposing rough cones, allowing studies for a wide range of volume fraction φ both above and below the jamming of granular suspension. We utilize sudden cessations of shearing, accompanied by refraction-matched internal imaging, to supplement the conventional flow-curve measurements. At sufficiently high volume fractions, the settling of particles after the cessations exhibits a continuous yet distinct transition over the change of the shear rate. Such changes back out the qualitative difference in the state of flowing prior to the cessations: the quasi-static yielding of a tightly packed network, as opposed to the rapid sliding of particles mediated by the interstitial fluid whose dynamics depends on the driving rate. In addition, we determine the solid-fluid transition using two independent methods: the extrapolation of stress residues and the estimated yield stress from high values of φ, and the settling of particles upon shear cessations as φ goes across the transition. We also verify the power law on values of characteristic stress with respect to the distance from jamming φ - φc, with an exponent close to 2. These results demonstrate a multitude of relaxation timescales behind the dynamics of soft particles, and raise questions on how we extend the existing paradigms of the flow of a densely packed system when the softness is actively involved.

The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor ß (TGF-ß) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

Spreading Waves in a Farmers and Hunter-Gatherers Model of the Neolithic Transition in Europe.

The Neolithic transition began the spread of early agriculture throughout Europe through interactions between farmers and hunter-gatherers about 10,000 years ago. Archeological evidence produced by radiocarbon dating indicates that the expanding velocity of farming is roughly constant all over Europe. Theoretical understanding of such evidence has been performed from mathematical modeling viewpoint. However, the expanding velocity determined by existing modeling approaches is faster than the observed velocity. For understanding this difference, we propose a three-component reaction-diffusion system which consists of two different types of farmers (sedentary and migratory) and hunter-gatherers from the viewpoint of the influence of farming technology. Our purpose is to study the relation between the expanding velocity of farmers and the farming technology parameter (say, [Formula: see text]). In this paper, we mainly focus on the one-dimensional traveling wave solution with minimal velocity and show that the minimal velocity decreases, as [Formula: see text] increases. This can be compatible with the observed velocity when farming technology is developed. Our results suggest that the reason for the slowdown of the Neolithic transition might be related to the increase in the development of farming technology.

Short granular chain under vibration: Spontaneous switching of states.

We study experimentally a short chain of N(≤8) loosely connected spheres bouncing against a horizontal surface that vibrates sinusoidally at intensity Γ. Distinct states are identified: a base state of uniform bouncing in-sync with the substrate prevails at low values of Γ, whereas increasing Γ can induce transitions to two excited states with appreciable storage of energy around one or both ends of the chain. We find that, in a transitional window of Γ, the chain can even switch spontaneously among states, resolving the mystery why different modes of motion can be initiated at the same position in our previous work along a gradient of vibration [Phys. Rev. Lett. 112, 058001 (2014)]. Preliminary interpretations on the parametric dependences and the optimal frequency window for seeing these transitions are offered, based on the microscopic and statistical evidence in our experiments up to date.

Vortex-induced morphology on a two-fluid interface and the transitions.

We investigate experimentally the steady flows in a cylinder containing two immiscible liquids, with the primary fluid being driven by the upper boundary rotating at constant speeds. The system exhibits interesting interplays between the flow fields and the morphology of the interface, with evidence showing that the remarkable flattop structure is a consequence of the vortex breakdown discovered decades ago, and that the deformability of the interface also feedbacks positively to the development of the vortices. Monitoring the topological structure of the flow fields defines the base states and transitions behind the morphology, whereas our survey over different aspect ratios also reveals rich phenomena of surface instabilities accompanying these steady states.

Correction: Real-space evidence of the equilibrium ordered bicontinuous double diamond structure of a diblock copolymer.

Correction for 'Real-space evidence of the equilibrium ordered bicontinuous double diamond structure of a diblock copolymer' by C. Y. Chu et al., Soft Matter, 2015, 11, 1871-1876.

Real-space evidence of the equilibrium ordered bicontinuous double diamond structure of a diblock copolymer.

The ordered bicontinuous double diamond (OBDD) structure has long been believed to be an unstable ordered network nanostructure, which is relative to the ordered bicontinuous double gyroid (OBDG) structure for diblock copolymers. Using electron tomography, we present the first real-space observation of the thermodynamically stable OBDD structure in a diblock copolymer composed of a stereoregular block, syndiotactic polypropylene-block-polystyrene (sPP-b-PS), in which the sPP tetrapods are interconnected via a bicontinuous network with Pn3̄m symmetry. The OBDD structure underwent a thermally reversible order-order transition (OOT) to OBDG upon heating, and the transition was accompanied with a slight reduction of domain spacing, as demonstrated both experimentally and theoretically. The thermodynamic stability of the OBDD structure was attributed to the ability of the configurationally regular sPP block to form helical segments, even above its melting point, as the reduction of internal energy associated with the helix formation may effectively compensate the greater packing frustration in OBDD relative to that in the tripods of OBDG.

Progranulin promotes Temozolomide resistance of glioblastoma by orchestrating DNA repair and tumor stemness.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults with a dismal prognosis. Current therapy of surgical removal combined with Temozolomide (TMZ) and radiation therapy only slightly prolongs the survival of GBM patients. Thus, it is essential to elucidate mechanism underlying its highly malignant properties in order to develop efficacious therapeutic regimens. In this study, we showed that progranulin (PGRN) was overexpressed in most GBM cell lines and the majority of human tumor samples. PGRN overexpression conferred GBM cells with tumorigenic properties and TMZ resistance by upregulating DNA repair (PARP, ATM, BRCA1, Rad51, XRCC1 and so on) and cancer stemness (CD133, CD44, ABCG2) genes, in part via an AP-1 transcription factor, specifically cFos/JunB. Curcumin, an AP-1 inhibitor, was also found to regulate PGRN promoter activity and expression including its downstream effectors aforementioned. These data suggested a feedforward loop between PGRN signaling and AP-1. PGRN depletion significantly decreased unlimited self-renewal and multilineage differentiation and the malignant properties of GBMs cells S1R1, and enhanced their vulnerability to TMZ. In addition, S1R1 depleted of PGRN also lost the ability to form tumor in an orthotopic xenograft mouse model. In conclusion, PGRN had a critical role in the pathogenesis and chemoresistance of GBM and functioned at the top of the hierarchy of cellular machinery that modulates both DNA repair pathways and cancer stemness. Our data suggest that a new strategy combining current regimens with compounds targeting PGRN/AP-1 loop like curcumin may significantly improve the therapeutic outcome of GBM.

Ratcheting and transitions: short granular chain in a gradient of vibration.

We report our experimental work on a one-dimensional gradient of vibration with a short granular chain. The system exhibits transitions of ratcheting dynamics from passive monotonic creeping against the gradient, to rapid stochastic head swinging with a reversed bias in its direction, and to seemingly random fluctuations. The spontaneously emerged spatial pattern reflects bifurcations of the state of the chain. Evidence from counterpart experiments using uniform vibrations confirms a nonmonotonic development of accessible modes behind the transitions, whereas the reversed ratcheting reflects an interesting dialogue between the size of the object and the spatial gradient.

Effects of sebum on drug transport across the human stratum corneum in vivo.

The objective of this study was to investigate the effect of sebum on drug transport across the human stratum corneum (SC) in vivo for two model compounds, 4-cyanophenol (CP) and cimetidine (CM), of different lipophilicity and molecular size by utilizing noninvasive tape-stripping techniques, in conjunction with an unsteady-state diffusion model for data analysis. The results demonstrated that the SC permeability of the relatively hydrophilic CM on the forehead may be as much as four times the permeability on the forearm. The administration of sebum supplementation to the forearm increased the SC permeability of CM more than threefold, but did not have the same effect with regard to CP. Removal of sebum from the forehead demonstrated a small but significant effect (-22%) on the SC permeability of CM. The presence of sebum on the forehead or forearm increased the diffusion of both molecules, but the effect on partition varied between sites and drugs. The change in the SC permeability of the relatively hydrophilic drug using sebum treatment may be attributable to the altered barrier function of the SC due to the disordering structures of the intercellular lipid molecules.

Toluidine blue O photodynamic inactivation on multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: Multidrug-resistant (MDR) Pseudomonas aeruginosa infection is becoming a critical problem worldwide. Currently, only limited therapeutic options are available for the treatment of infections caused by MDR P. aeruginosa, therefore, the development of new alternative treatments is needed. Toluidine blue O (TBO) is an effective antibacterial photosensitizing agent against various bacteria. However, reports on antibacterial photosensitization of MDR bacteria are limited. This study aims to determine the in vitro photobactericidal activity of TBO against MDR P. aeruginosa. STUDY DESIGN/MATERIALS AND METHODS: The efficacy of antibacterial photodynamic inactivation, DNA fragmentation and protein carbonylation of three MDR P. aeruginosa strains and one susceptible strain was compared using TBO as the photosensitizer followed by red light irradiation (630 nm, 90 J/cm(2)) from a light-emitting diode light source. Subsequently, the efficacy of TBO photodynamic inactivation (TBO-PDI) on 60 MDR strains, including 11 with the efflux pump phenotype and 49 with no pump activity, was tested using the minimum lethal drug concentration (MLC) assay. RESULTS: TBO-PDI caused similar bactericidal effect (6-7 logs of killing effect), DNA fragmentation and protein carbonylation in three MDR and one susceptible P. aeruginosa strains. Although the TBO accumulation assay indicated that TBO is a substrate for the efflux pump, TBO-PDI produce similar photobactericidal activity against 60 MDR P. aeruginosa strains, either with or without efflux-pump phenotype, and 19 susceptible strains. CONCLUSION: MDR did not affect the susceptibility of P. aeruginosa strains to TBO-PDI. The efflux pump played an insignificant role in TBO-PDI of MDR P. aeruginosa.

Human sebocytes express prostaglandin E2 receptors EP2 and EP4 but treatment with prostaglandin E2 does not affect testosterone production.

BACKGROUND: Prostaglandins (PG) play an important role in cutaneous homeostasis. Among other skin cells, human sebocytes express cyclooxygenases and can produce PGE(2). Various prostanoid receptors have been demonstrated in epidermis and hair follicles, while limited data are available regarding their expression in sebaceous glands. In addition, the interaction between PGE(2) and androgenesis remains largely unclear. OBJECTIVES: To examine the expression of PGE(2) receptor (EP) and PGF(2alpha) receptor (FP) in human sebocytes and the influence of PGE(2) or PGF(2alpha) on testosterone production. METHODS: A reverse transcription-polymerase chain reaction study was used to detect the expression of EP subtypes and FP. A testosterone radioimmunoassay was used to measure the amount of testosterone in the supernatant of cultured SZ95 sebocytes treated with PGE(2) or PGF(2alpha) alone or in the presence of various androgen precursor substrates. RESULTS: SZ95 sebocytes expressed mainly EP2 and EP4 but not EP3 or FP. Testosterone production was not induced by PGE(2) or PGF(2alpha), alone or in the presence of cholesterol. PGE(2) did not affect androgenesis in cultured sebocytes. CONCLUSIONS: The expression patterns of prostanoid receptors differ between sebocytes, hair follicles and epidermis. The effects of PGE(2) and PGF(2alpha) on the proliferation, lipogenesis and inflammation of sebocytes appear not to be associated with androgenesis.

Aristolochic acid nephropathy due to herbal drug intake manifested differently as Fanconi's syndrome and end-stage renal failure--a 7-year follow-up.

Aristolochic acid (AA) may reduce glomerular or proximal tubular function, or both. We report a married couple taking AA-containing herbal drugs. The man developed Fanconi's syndrome (FS) whereas his wife reached end-stage renal failure (ESRF). He was a 36-year-old alcoholic cirrhotic patient who had taken the Chinese herbal drugs for 6 years, presenting with muscle weakness and laboratory findings of FS; the renal pathological findings were compatible with the diagnosis of aristolochic acid nephropathy (AAN). His 38-year-old wife, who took a lower cumulative amount of the same herbal drug for a shorter duration, developed advanced renal failure and severe anemia with pathological findings of extensive tubular atrophy, interstitial fibrosis but spared glomeruli. AA-I was detected in one of the herbal drugs. The wife has been on hemodialysis for 7 years, but the husband is still at the stage of slowly progressive chronic renal failure and persistent FS. None of their 5 children ever took the herbal drug, and none had renal problems during follow-up. It is important to trace the history of herbal drug intake in all the family members because of the possibility of sharing of drugs within a family. In addition to the effect of cumulative doses of AAs and the potentially higher susceptibility of females to AAN, the roles of liver cirrhosis and related vasodilators in the protection of the renal interstitium from fibrosis are questions that warrant further study.

Clonal spread of SCCmec type IV methicillin-resistant Staphylococcus aureus between community and hospital.

The staphylococcal chromosome cassette (SCC)mec types of 382 hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) isolates in Taiwan were analysed over a 7-year period (1999-2005). There was an abrupt increase in SCCmec type IV in HA-MRSA during 2005. The molecular epidemiology of a subset (n = 69) of HA-MRSA isolates with SCCmec types III, IV or V was characterised and compared with that of community-acquired MRSA (CA-MRSA) (n = 26, collected during 2005). Pulsed-field gel electrophoresis revealed three major pulsotypes (A, B and C) and 15 minor clones. Pulsotypes B and C, which contained isolates carrying SCCmec types IV and V, respectively, included both CA-MRSA and HA-MRSA isolates. Among 24 toxin genes analysed, five genes had significant differential distribution between CA-MRSA and SCCmec type III HA-MRSA. Furthermore, among SCCmec type IV isolates, the seb gene was detected more commonly in HA-MRSA. Analysis of representative members of the three major pulsotypes by multilocus sequence typing revealed two sequence types (STs), namely ST239 (SCCmecIII) and ST59 (SCCmecIV or SCCmecV). This suggests that ST59:SCCmecIV, which is usually community-acquired, has become an important nosocomial pathogen in the hospital studied.

Lamivudine reverses severe acute hepatitis B and pancytopenia after renal transplantation: a case report.

Pancytopenia is rare after acute hepatitis B infection. The use of lamivudine in the treatment of acute hepatitis B-associated pancytopenia in renal transplant recipients has not been documented. Herein we reported a 21-year-old woman who was infected with acute hepatitis B 6 months after renal transplantation, a condition complicated by pancytopenia. Lamivudine reversed the acute hepatitis in 1 month and the pancytopenia after 3 months, without a change in renal function. Lamivudine was maintained for 2 years without a hepatitis flare-up after 4 years.

Decreased B cells and IgA-secreting B cells partially explain the high prevalence of IgA deficiency in dialysis patients.

AIMS: We previously reported 2 hemodialysis (HD) patients with recurrent infections and selective immunoglobulin A deficiency (IgAD). We further demonstrated that serum IgA levels were lower and the prevalence of IgAD was higher in uremic patients. The exact mechanisms of IgAD in uremic patients largely remained unclear. In some patients, it was caused by anti-IgA antibody neutralization and subsequent destruction. We performed the present study to survey if there is any defect in IgA production. MATERIALS AND METHODS: 288 patients were initially included for examination of serum immunoglobulins. 16 normal persons, 16 dialysis patients without IgAD, and 12 dialysis patients with IgAD were enrolled after the initial examination. Blood was drawn into heparinized tubes. WBC counts and lymphocyte percentage were examined by a CBC counter. Lymphocytes were separated by the Ficoll-Paque method. Flow cytometry was utilized to isolate the B cell and IgA-secreting B cell after staining with CD 19 phycoerythrin and FITC-conjugated rabbit anti-human IgA antibody. RESULTS: There is no significant difference between WBC counts or total lymphocyte counts of these 3 groups. However, we found a lower percentage of total lymphocyte counts in dialysis patients, either with or without IgAD. The total B cell numbers were lower in dialysis patients with IgAD. In addition, there were fewer IgA-secreting B cells in dialysis patients with IgAD. CONCLUSION: Decreased B cell and IgA-secreting B cell counts are seen in uremic patients with IgAD. This, in turn, indicates that there might be a defect of IgA production in some patients, rather than IgA destruction by anti-IgA antibodies as seen in some other patients. Further study is needed to investigate the mechanisms of decreased B cells and IgA-secreting B cells.

Granular packings sheared in an annular channel: flow localization and grain size dependence.

We investigate experimentally a quasistatic flow of glass beads in an annular channel, in which particles are packed and sheared from above under a constant normal load. The experiments utilize techniques of refractive-index-matched fluorescent imaging to determine the motion of individual particles and the velocity fields inside the sheared packing. We demonstrated in a previous paper [Phys. Rev. E 70, 031303 (2004)] that an ordering transition has a significant impact on the velocity profile. Here, we report the effects of layer thickness, channel width, and particle size on the internal velocity field. For very thin layers, the grain velocity exhibits a linear vertical profile. As the layer thickness increases, a strongly nonlinear velocity profile emerges, with particle motion that is largely localized to a narrow region (shear band) near the driving surface. Once the packing has reached its steady state, the velocity field is insensitive to the size of grains being used--the velocity profile does not scale with grain size. However, the vertical decay of grain velocity becomes significantly steeper as the horizontal width of the channel decreases. In addition, we demonstrate that changing the direction of shearing generates an anomalous mobility of grains in the deep interior that is sensitive to particle size. The transient grain motion is accompanied by an abrupt volume compaction and a gradual recovery as the shearing proceeds. Reviewing results from this and other works reveals that the velocity profiles of granular shear flows are often geometry specific. We present a heuristic continuum model that qualitatively captures the shear banding observed in this geometry.

A chiral granular gas.

Inspired by rattleback toys, we created small chiral wires that rotate in a preferred direction on a vertically oscillating platform and quantified their motion with experiment and simulation. We demonstrate experimentally that angular momentum of rotation about particle centers of mass is converted to collective angular momentum of center-of-mass motion in a granular gas of these wires, and we introduce a continuum model that explains our observations.

7-84 parathyroid hormone fragments are proportionally increased with the severity of uremic hyperparathyroidism.

AIMS: Recent progress in PTH assay has revealed that the intact PTH assay kit in current use does not differentiate between the truncated 7-84 PTH molecule and the 1-84 PTH molecule. In our series, we examined the effectiveness of a new PTH assay as a noninvasive method of evaluating severity of uremic hyperparathyroidism. METHODS AND MATERIALS: Two hundred and seventy hemodialysis (HD) patients recruited from three HD centers were included and divided into subgroups according to the conventional iPTH assay results. Pre-dialysis blood samples were collected and subjected to two different PTH assays: "intact" PTH assay (iPTH) and "whole" PTH (wPTH) assay. Two biochemical markers of bone remodeling were also examined. RESULTS: In all cases, PTH levels determined by the wPTH assay were in the average 32.3% lower than those determined by the iPTH assay. The difference of the results of the two PTH assay methods, which indicated the portion of 7-84 PTH fragments of the total PTH molecules measured with the iPTH assay, was gradually increased while the severity of uremic hyperparathyroidism increased. Biochemical markers of bone formation/resorption showed a similar change. CONCLUSION: The portion of the 7-84 PTH fragments and markers of increased bone turnover increased in proportion to the severity of uremic hyperparathyroidism. This finding disproves the hypothetical role of 7-84 PTH fragments alone as the noninvasive marker of low-turnover bone disease in HD patients.