Non-Invasive, Continuous, Quantitative Detection of Solvent Content in Vacuum Tray Drying.

A non-invasive capacitance instrument was embedded in the base of a vacuum-drying tray to monitor continuously the residual amount of solvent left in a pharmaceutical powder. Proof of concept was validated with Microcrystalline Cellulose laced with water, as well as water/acetone mixtures absorbed in a spray-dried Copovidone powder. To illustrate the role of impermeability of the base, we derive a model of vapor sorption that reveals the existence of a kinetic limit when solids are thinly spread, and a diffusion limit with greatly diminished effective diffusivity at large powder thickness. By monitoring the residual solvent content of powders, this new in situ technique offers advantages over indirect methods like mass spectrometry of vapor effluents, but without complications associated with probe fouling. To prescribe design guidelines and interpret signals, we model the electric field shed by the probe when a powder holds variable solvent mass fraction in the vertical direction.

Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival. STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: Adult hemodialysis patients treated in hemodialysis 500 facilities participating in the Dialysis Outcomes Practice Patterns Study (DOPPS) between 1999 and 2015 in the US, Japan, and 4 four European countries: Germany, Italy, Spain, and UK. PREDICTORS: Four practice measures at each facility: the percentages of patients with Kt/V>1.2, interdialytic weight gain [IDWG]<5.7%, phosphorus<6 mg/dL, and using AV fistulae. OUTCOMES: Patient survival. ANALYTICAL APPROACH: Mediation analyses, adjusted for case mix, were conducted using 3-year study phase as the exposure and facility practice measures as potential mediators. RESULTS: In Europe, we observed a 13% improvement in overall case-mix adjusted survival per decade. Trends in facility practice measures, especially Kt/V and phosphorus, explained 10% improvement in case-mix survival per decade, representing 77% (10% explained of 13% improvement) of the observed improvement. In Japan, 73% of the observed 12%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially Kt/V and IDWG. In the US, 56% of the observed 47%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially AV fistula use and phosphorus control. LIMITATIONS: Unmeasured changes in the characteristics of the patient population over this period may confound the observed associations. CONCLUSION: The improvements in adjusted hemodialysis patient survival in Europe, Japan, and the US from 1999 to 2015 can be largely explained by improvements in specific facility practices. Future changes in patient survival may be responsive to further evolution in the implementation of common clinical practices.

Statistical Mechanics of Electrowetting.

We derive the ab initio equilibrium statistical mechanics of the gas-liquid-solid contact angle on planar periodic, monodisperse, textured surfaces subject to electrowetting. To that end, we extend an earlier theory that predicts the advance or recession of the contact line amount to distinct first-order phase transitions of the filling state in the ensemble of nearby surface cavities. Upon calculating the individual capacitance of a cavity subject to the influence of its near neighbors, we show how hysteresis, which is manifested by different advancing and receding contact angles, is affected by electrowetting. The analysis reveals nine distinct regimes characterizing contact angle behavior, three of which arise only when a voltage is applied to the conductive liquid drop. As the square voltage is progressively increased, the theory elucidates how the drop occasionally undergoes regime transitions triggering jumps in the contact angle, possibly changing its hysteresis, or saturating it at a value weakly dependent on further voltage growth. To illustrate these phenomena and validate the theory, we confront its predictions with four data sets. A benefit of the theory is that it forsakes trial and error when designing textured surfaces with specific contact angle behavior.

Expression of the monocarboxylate transporter MCT1 is required for virus-specific mouse CD8+ T cell memory development.

Lactate-proton symporter monocarboxylate transporter 1 (MCT1) facilitates lactic acid export from T cells. Here, we report that MCT1 is mandatory for the development of virus-specific CD8+ T cell memory. MCT1-deficient T cells were exposed to acute pneumovirus (pneumonia virus of mice, PVM) or persistent γ-herpesvirus (Murid herpesvirus 4, MuHV-4) infection. MCT1 was required for the expansion of virus-specific CD8+ T cells and the control of virus replication in the acute phase of infection. This situation prevented the subsequent development of virus-specific T cell memory, a necessary step in containing virus reactivation during γ-herpesvirus latency. Instead, persistent active infection drove virus-specific CD8+ T cells toward functional exhaustion, a phenotype typically seen in chronic viral infections. Mechanistically, MCT1 deficiency sequentially impaired lactic acid efflux from activated CD8+ T cells, caused an intracellular acidification inhibiting glycolysis, disrupted nucleotide synthesis in the upstream pentose phosphate pathway, and halted cell proliferation which, ultimately, promoted functional CD8+ T cell exhaustion instead of memory development. Taken together, our data demonstrate that MCT1 expression is mandatory for inducing T cell memory and controlling viral infection by CD8+ T cells.

Comparative Chemometric Manipulations of UV-Spectrophotometric Data for the Efficient Resolution and Determination of Overlapping Signals of Cyclizine and Its Impurities in Its Pharmaceutical Preparations.

BACKGROUND: Cyclizine (CYZ), a commonly used antiemetic drug, has two pharmacopeial toxic impurities, 1-methylpiperazine (MPZ) and diphenylmethanol (DPM). When CYZ parenteral formulations are administered intravenously, both impurities are poisonous, toxic, and harmful to the human body. OBJECTIVE: Cyclizine was determined along with its hazardous impurities MPZ and DPM by green multivariate calibration using UV-spectroscopic data. METHODS: Three multivariate algorithms were used to resolve and quantify overlapped spectral signals: principal component regression (PCR), partial least squares (PLS), and synergistic intervals partial least squares (siPLS). A concentration set containing 16 distinct combinations of CYZ, MPZ, and DPM was randomly prepared, and the absorbance values of the concentration set were determined using the 376 point-wavelength set with an interval of 0.2 nm between 200 and 275 nm. RESULTS: Good linear correlations were established for CYZ, MPZ, and DPM in the concentration ranges of 5.00-25.0, 0.50-2.50, and 0.50-2.50 µg/mL, respectively. The ideal spectral range and associated combinations were chosen based on the lowest root mean error of prediction (RMSEP) and correlation coefficient values (r). The siPLS approach performed better than the PCR and PLS models. The combination of four subintervals, 1, 3, 4, and 7, demonstrated the greatest effect, with RMSEP values of 0.0272, 0.0053, and 0.0315 for CYZ, MPZ, and DPM, respectively, and correlation coefficients of 0.9991, 0.9999, and 0.9997, in order. Various assessment tools were used to evaluate and measure the greenness profile of the established methods. The proposed methods were validated using internal and external validation sets. CONCLUSIONS: The three methods were effectively used to determine CYZ in its pure form and parenteral formulations, as well as its toxic impurities. The acquired results were compared statistically to those obtained using the reported HPLC method. HIGHLIGHTS: Cyclizine and its toxic impurities can be determined spectrophotometrically by using the three developed chemometric models.

Quality by design approach for green HPLC method development for simultaneous analysis of two thalassemia drugs in biological fluid with pharmacokinetic study.

This work implements a combined experimental approach of analytical quality-by-design (AQbD) and green analytical chemistry (GAC) to develop an HPLC method for simultaneous determination of the two thalassemia drugs, deferasirox (DFX) and deferiprone (DFP), in biological fluid for the first time. This integration was designed to maximize efficiency and minimize environmental impacts, as well as energy and solvent consumption. To accomplish this goal, an analytical quality-by-design approach was performed, beginning with quality risk assessment and scouting analysis, followed by Placket-Burman design screening for five chromatographic parameters. Critical method parameters were thoroughly recognized and then optimized by using a two levels-three factors custom experimental design to evaluate the optimum conditions that achieved the highest resolution with acceptable peak symmetry within the shortest run time. The desirability function was used to define the optimal chromatographic conditions, and the optimal separation was achieved using an XBridge® HPLC RP-C18 (4.6 × 250 mm, 5 µm) column with ethanol : acidic water at pH 3.0 adjusted by phosphoric acid in the ratio of (70 : 30, v/v) as the mobile phase at a flow rate of 1 mL min-1 with UV detection at 225 nm at a temperature of 25 °C. Linearity was obtained over the concentration range of 0.30-20.00 µg mL-1 and 0.20-20.00 µg mL-1 for DFX and DFP, respectively, using 20.00 µg mL-1 ibuprofen (IBF) as an internal standard. The established method's greenness profile was evaluated and measured using various assessment tools, and the developed method was green. For the validation of the developed method, FDA recommendations were followed, and all the results obtained met the acceptance criteria. The suggested method was successfully used to study the pharmacokinetic parameters of DFX and DFP in rat plasma. Due to the substantial increase in bioavailability of the two iron chelating drugs, the results from this study strongly recommend their co-administration.

Spectrofluorimetric Approach for Quantification of Cyclizine in the Presence of its Toxic Impurities in Human Plasma; in silico Study and ADMET Calculations.

Cyclizine (CYZ); an antiemetic compound; is widely misused for its euphoric or hallucinatory effects, either by oral or intravenous routes. The concomitant abuse of CYZ among addicted adolescents contributes to neuromuscular disorders that are life-threatening. Consequently, with the company of 1-Methylpiperazine (MPZ) and diphenylmethanol (DPM, Benzhydrol) as pharmacopoeia-reported CYZ impurities, a novel spectrofluorimetric assay for the detection of CYZ, has been established either in human plasma samples or in its parenteral formulation. The native fluorescence of CYZ has been investigated under various conditions. Different parameters affecting relative fluorescence intensity of CYZ including diluting solvent, surfactant, plasma protein solvent, and pH were studied and optimized. The linearity obtained between the fluorescence intensity at emission wavelength 350 nm after excitation at 244 nm and the corresponding CYZ concentrations was in the range 10-1000 ng/mL for measurement of CYZ either in pure form or in human plasma samples, with a appropriate correlation coefficient (r = 0.9999) and 3.10 ng/mL as the limit of detection and 9.41 ng/mL as the limit of quantitation. The suggested procedure was created and validated in accordance with ICH guidelines for quantification of CYZ either in its pure form or its dosage form, and FDA guidelines for the assay of CYZ in human plasma. Finally, in silico study and ADMET predictions were conducted for the studied drug impurities to estimate their pharmacokinetic behaviors. The results showed that both CYZ impurities have higher cellular permeability and maximum tolerated doses, DPM has higher BBB and CNS permeability than MPZ, while MPZ exceeds DPM in total clearance and volume of distribution.

Nanoparticle-enhanced in-line potentiometric ion sensor for point-of-care diagnostics for tropicamide abuse in biological fluid.

Point of care (POC), also identified as on-site testing, has evolved as a rapid and accurate technique for drug of abuse screening and analysis. The aim of this work is to detect tropicamide (TPC) abuse in biological fluids; we selected rat plasma as example. We developed a disposal miniaturized, portable, green, and budget-friendly POC solid-state electrochemical sensor based on potentiometric transduction. To attain that, an innovative microfabricated electrode modified with conducting polymer poly(3-octylthiophene) (POT) has been placed on sensitized printed circuit board (PCB). A two-stage optimization process was implemented to develop the fabricated electrode. The first stage of the optimization process depends on screening various ionophores in order to enhance the sensor selectivity towards tropicamide. Copper nanoparticles exhibited the highest selectivity towards TPC. The second stage was utilizing a polymer as an ion-to-electron transducer layer between the copper nanoparticles impregnated ion sensing membrane and the microfabricated solid-contact ion-selective electrode. This polymer was added to boost the stability of the potential drift (1.2 mV/h) due to the hydrophobic behavior of the POT, which precludes the formation of an aqueous layer at the Cu electrode/polymeric membrane interface and improve the limit of detection (1.1 × 10-8 M). Nernstian potentiometric response was accomplished for TPC with a slope of 58.46 ± 0.43 mV/decade and E0 ∼ 189.39 ± 2.12 over the concentration range 1.0 × 10-7 to 1.0 × 10-2 M. The suggested sensor's intrinsic figure of merits include a quick response time (13 ± 2 s) and long life time (45 days). The proposed sensor has been successfully employed in the selective determination of TPC in pharmaceutical formulations, and biological fluids. When the results were compared to those of the official approach, there was no statistically significant difference. The Eco-Scale tool assessed and measured the greenness profile of the established method.

The Natural History of T Cell Metabolism.

The cells of the immune system, particularly the T lymphocytes, have two main features that distinguish them from the cells of other tissues. They proliferate after activation and have the ability to move in tissues and organs. These characteristics compel them to develop metabolic plasticity in order to fulfil their immune function. This review focuses on the different known mechanisms that allow T cells to adapt their metabolism to the real-life circumstances they operate in, whether it is to exit quiescence, to differentiate into effector cells, or to participate in immune memory formation. Some of the metabolic adaptations to environmental variations that T cells are likely to undergo in their immune monitoring function are also discussed.

Seguimiento del paciente con cardiodesfibrilador automático implantable / Follow-up of the patient with automatic implantable cardioverter-defibrillator

RESUMEN Introducción: Los cardiodesfibriladores mejoran la supervivencia de los pacientes con riesgo de muerte súbita cardíaca. Existen escasos datos en nuestro país acerca de su eficacia en el seguimiento. Objetivo: Describir la evolución en el seguimiento de los pacientes con primoimplante de un cardiodesfibrilador automático. Método: Estudio ambispectivo, longitudinal, en 47 pacientes con primoimplante de un cardiodesfibrilador en el período septiembre de 2007 a diciembre de 2016, con cierre el 31 de diciembre de 2017. La probabilidad acumulada de supervivencia se estimó a través de las curvas de Kaplan-Meier. Resultados: La edad media fue de 57 ± 14,6 años, con predominio del sexo masculino (74,5%) y la indicación en prevención secundaria (83%). Presentaron terapias apropiadas el 57,4% de los pacientes, terapias inapropiadas un 23,4%, proarritmia del cardiodesfibrilador un 14,9% y tormenta arrítmica el 12,8% de los pacientes. Las terapias apropiadas se relacionaron con la fracción de eyección ≤ 35% (p=0,022) y la edad (p=0,031). La supervivencia acumulada libre del primer evento a los cuatro años fue 34,7%. La mortalidad cardiovascular se relacionó con: existencia de cardiopatía estructural (p=0,044), fracción de eyección ≤ 35% (p<0,001), clase funcional III-IV (p=0,046), terapias apropiadas (p=0,014) y tormenta arrítmica (p=0,002). La supervivencia acumulada libre de mortalidad cardiovascular fue de 70,7% al cuarto año. Conclusiones: La supervivencia de los pacientes con cardiodesfibrilador es buena. La mortalidad se asocia a un mayor deterioro del estado cardiovascular y a las terapias del dispositivo.

ABSTRACT Introduction: Implantable cardioverter-defibrillators improve the survival of patients at risk of sudden cardiac death. There is relatively little data in our country about their follow-up effectiveness. Objective: To describe the outcome of patients with primo-implantation of an automatic cardioverter-defibrillator during follow-up. Methods: An ambispective longitudinal cohort study was conducted in 47 patients with primo-implantation of a cardioverter-defibrillator in the period September 2007 to December 2016, ending on December 31, 2017. The cumulative probability of survival was estimated through the Kaplan-Meier curves. Results: Mean age was 57 ± 14.6 years, with male predominance (74.5%) and indication in secondary prevention (83%). Adequate therapies were found in 57.4% of patients, inadequate therapies in 23.4%, implantable cardioverter-defibrillator proarrhythmia in 14.9% and arrhythmic storm in 12.8% of patients. Adequate therapies were related to an ejection fraction ≤ 35% (p=0.022) and age (p=0.031). Cumulative free survival from the first event at four years was 34,7%. Cardiovascular mortality was related to: existence of structural heart disease (p=0.044), ejection fraction ≤ 35% (p<0.001), functional class III-IV (p=0.046), adequate therapies (p=0.014) and arrhythmic storm (p=0.002). Cumulative free survival of cardiovascular mortality was 70.7% at the fourth year. Conclusions: The survival of patients with implantable cardioverter-defibrillator is satisfactory. Mortality is associated with further deterioration of cardiovascular status and with device therapies.

Determination of sofosbuvir with two co-administered drugs; paracetamol and DL-methionine by two chromatographic methods. Application to a pharmacokinetic study.

AIM: Two rapid and sensitive chromatographic methods have been developed and validated for simultaneous analysis of sofosbuvir (SOF) in rat plasma with two co-administered drugs, paracetamol (PAR) and DL-methionine (MET). MATERIALS & METHODS: The first method relied on using TLC-densitometry with a developing system consisted of chloroform: methanol: glacial acetic acid: formic acid in the ratio of 9.5: 1: 1.5: 0.5, by volume. The studied analytes and the internal standard naphazoline hydrochloride were scanned at 210 nm. The second method was HPLC method, whereas the analytes and the internal standard cinnarizine were separated on XTerra® HPLC RP C18 column using gradient elution mode and a mobile phase consisted of methanol: 0.1% aqueous TEA at pH 3 adjusted with orthophosphoric acid at 210 nm. RESULTS: The TLC-densitometry method showed linearity over concentration ranges of 160-3000 ng/band for SOF and PAR, 300-3000 ng/band for MET, but HPLC method was linear and validated over concentration ranges of 150-5000 ng/ml for SOF, 300-5000 ng/ml for both PAR and MET. CONCLUSION: All validation parameters met the acceptance criteria according to US FDA guidelines. Pharmacokinetic study was successfully applied and proved the possibility of co-administration of SOF with PAR and MET.

Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function.

Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronic T cells appeared to rely on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to produce ATP for IFNγ synthesis. Check-point blockade, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1-mediated inhibition appears essential for limiting oxidative metabolism linked to effector function in chronic T cells, thereby promoting survival and functional fitness.

Optimization of RDM-UF for alfalfa wastewater treatment using RSM.

Rotating disk membrane (RDM) module with ultrafiltration (UF) was an effective alternative method to treat alfalfa wastewater and realize protein recovery and agricultural irrigation water production. A scientific investigation has been conducted to comprehend the effect of operation conditions (feed flow rate, shear rate, transmembrane pressure (TMP), and temperature) on alfalfa wastewater treatment with RDM-UF by central composite response surface methodology (CCRSM). First, the filtration behaviors of three types of UF membranes (PES20, UH030P, and PES50) were studied to select the optimized membrane (UH030P). Then, the effects and interactions of four operation conditions were studied and fitting models were established, while data on pollution reduction and protein recovery, membrane fouling behavior, and energy cost evaluation were collected. Furthermore, the optimized operation conditions calculated by CCRSM were Q = 60 L h-1, γ = 220 × 103 s-1, TMP = 5.61 bar, and T = 25 °C. In addition, the concentration test was conducted with these parameters. This work may contribute to the potential application of RDM for membrane wastewater treatment. Graphical abstract Schematic diagram of UF process for alfalfa wastewater treatment and resource recovery.

Stability-Indicating UPLC and TLC-Densitometric Methods for Determination of Benztropine Mesylate and Its Carcinogenic Degradation Product.

Two accurate, precise and highly selective stability-indicating methods were adopted for simultaneous determination of benztropine mesylate (BNZ) in presence of its hepatotoxic and carcinogenic degradation product, benzophenone (BPH) either in pure form or in the pharmaceutical formulation without any preliminary separation steps. The first method is a thin layer chromatography (TLC)-densitometric method that depended on separation of BNZ from its degradate on TLC aluminum plates precoated with silica gel 60 F254 as the stationary phase using a developing system consisted of hexane:methylene chloride:triethylamine (5:5:0.6, by volume) and scanning the separated bands at 235 nm. Linear regression analysis data for the calibration plots of BNZ and BPH showed perfect linear relationships over the concentration range of 1.5-10 and 1-10 µg band-1, respectively. The second method is (UPLC) method, at which the mixture was separated on a reversed phase C8 analytical column (1.9 µm ps, 50 mm × 2.1 i.d.) using a mobile phase of acetonitrile: aqueous sodium dodecyl sulfate (50:50, v/v) Adjusted to pH = 3 with phosphoric acid, at a flow rate of 0.5 mL min-1. Quantification was achieved at 210 nm based on peak area and linear calibration curves over the concentration ranges of (20-200 µg mL-1) and (5-50 µg mL-1) for BNZ and BPH, respectively, were obtained. The investigated methods were successfully applied to available dosage form and method validation has been carried out. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by reported one and no significant differences were obtained regarding both accuracy and precision.

Statistical mechanics of the triple contact line.

We outline a statistical mechanics of the triple gas-solid-liquid contact line on a rough plane. The analysis regards the neighborhood of the line as a solid dotted with cavities. It adopts the simplest mean-field statistical mechanics, in which each cavity is either full or empty, while being connected to near neighbors by thin necks. The theory predicts equilibrium angles for advance and recession in terms of the Young contact angle and the joint statistical distribution of two quantifiable geometrical parameters representing specific neck cross-section and specific cavity opening. It attributes contact angle hysteresis to first-order phase transitions among adjacent cavities, as they collectively imbibe or reject liquid. It also calculates the potential energy barriers that hysteresis erects against overcoming contact line pinning. By determining whether the phase transitions can release latent energy, this ab initio analysis distinguishes six regimes, including two metastable recession states. We compare predictions with data for superhydrophobia on microscopic rods; for hysteresis in the "Wenzel state"; and for variations of the advancing contact angle with surface energies of the liquid.

Metabolic programming in chronically stimulated T cells: Lessons from cancer and viral infections.

T-cell metabolism is central to the shaping of a successful immune response. However, there are pathological situations where T cells are rendered dysfunctional and incapable of eliminating infected or transformed cells. Here, we review the current knowledge on T-cell metabolism and how persistent antigenic stimulation, in the form of cancer and chronic viral infection, modifies both metabolic and functional pathways in T cells.

Treatment of Distal Radial Fractures by Open Reduction and Internal Fixation with a Volar Locking Plate.

The volar locking plate is a popular implant for surgical management of unstable distal radial fractures. We routinely utilize this system for all distal radial fractures except for those with entrapped intra-articular fragments and fractures with a displaced dorsomedial facet fracture (which is hard to capture with the volar approach alone). In this video, we describe in detail the necessary steps for successful placement of the volar locking plate, starting with preoperative planning and ending with expected outcomes. The approach that we utilize is through the flexor carpi radialis tendon sheath and avoids the radial artery. In the video, we describe 4 variations on the application of a volar locking plate: (1) the standard technique after appropriate reduction and provisional fixation with Kirschner wires, (2) regaining length through a shortened distal radial fracture, (3) using the volar plate to assist in the reduction and regain volar tilt, and (4) intraoperative management of coronal shift of the distal fragment. Complications reported for the volar locking plate have decreased with newer low-profile plate designs; however, they still include volar tendon irritation and/or rupture and median neuropathy. Postoperatively, we advise a brief 2-week period of immobilization for wound-healing, which is followed by a period during which a removable wrist splint is used and patients are instructed on the performance of a hand therapy regimen.

Protoporphyrin Treatment Modulates Susceptibility to Experimental Autoimmune Encephalomyelitis in miR-155-Deficient Mice.

We previously identified heme oxygenase 1 (HO-1) as a specific target of miR-155, and inhibition of HO-1 activity restored the capacity of miR-155-/- CD4+ T cells to promote antigen-driven inflammation after adoptive transfer in antigen-expressing recipients. Protoporphyrins are molecules recognized for their modulatory effect on HO-1 expression and function. In the present study, we investigated the effect of protoporphyrin treatment on the development of autoimmunity in miR-155-deficient mice. MiR-155-mediated control of HO-1 expression in promoting T cell-driven chronic autoimmunity was confirmed since HO-1 inhibition restored susceptibility to experimental autoimmune encephalomyelitis (EAE) in miR-155-deficient mice. The increased severity of the disease was accompanied by an enhanced T cell infiltration into the brain. Taken together, these results underline the importance of miR-155-mediated control of HO-1 expression in regulating the function of chronically-stimulated T cells in EAE.

Granular flows on a dissipative base.

We study inclined channel flows of sand over a sensor-enabled composite geotextile fabric base that dissipates granular fluctuation energy. We record strain of the fabric along the flow direction with imbedded fiber-optic Bragg gratings, flow velocity on the surface by correlating grain position in successive images, flow thickness with the streamwise shift of an oblique laser light sheet, velocity depth profile through a transparent side wall using a high-speed camera, and overall discharge rate. These independent measurements at inclinations between 33∘ and 37∘ above the angle of repose at 32.1±0.8∘ are consistent with a mass flow rate scaling as the 3/2 power of the flow depth, which is markedly different than flows on a rigid bumpy boundary. However, this power changes to 5/2 when flows are forced on the sand bed below its angle of repose. Strain measurements imply that the mean solid volume fraction in the flowing layer above the angle of repose is 0.268±0.033, independent of discharge rate or inclination.