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This paper presents the derivation of a general wave dispersion relation for warm magnetized plasma under the two-fluid formalism. The discussion is quite general except for the assumption of low frequency and slow phase speed, for which the displacement current is negligible, under the implicit assumption that the plasma is sufficiently dense to satisfy the condition ω p e > ω c e , where ωpe and ωce denote the plasma oscillation frequency and electron gyro frequency, respectively. The present discussion does not invoke charge neutrality associated with the fluctuations although it is implicitly satisfied. The resulting dispersion relation that includes the fluid thermal effects shows that there are three eigen modes, which include those corresponding to ideal MHD, namely, fast, slow, and kinetic Alfvén waves, as well as higher-frequency modes including the ion and electron cyclotron and lower-hybrid resonances. The fluid effects in the ideal MHD wave branches are influenced by the finite Larmor radius scales, and when the wave number in the cross field direction is comparable to these values, the fluid effects become significant. It is found that the Larmor radius should be interpreted in the sense as ion-acoustic gyro-radius instead of ion thermal gyro radius only. That is, it is found that the electrons also contribute to the non-ideal effect associated with the kinetic Alfvén wave. A comprehensive explanation of the polarization of each mode is also presented. The present findings indicate that the polarity may change its sign only for the kinetic Alfvén mode branch and that such a transition is based on the propagation angle. When such a change does take place, it is found that the kinetic Alfvén wave transits to an ion-acoustic mode. For each branch, it is also found that the electric field along the ambient magnetic field is purely transverse. [ABSTRACT FROM AUTHOR]

The anomalous diffusion of resonant protons in parallel and perpendicular velocity space by kinetic Alfvén waves is discussed. The velocity diffusion coefficient is calculated by employing an autocorrelation function for proton trajectories. It is found that for protons resonant with the waves, the perpendicular diffusion coefficient decays away for a sufficiently long time, but parallel diffusion monotonically increases in time until it saturates at a certain level. This result indicates that a portion of resonant protons can undergo anomalous diffusion along the background magnetic field even if the intensity of the kinetic Alfvén wave is sufficiently low. The present findings imply that under suitable conditions, astrophysical charged-particle acceleration can take place in the parallel direction. [ABSTRACT FROM AUTHOR]

In this paper, we derive the quantum Vlasov equation as a differential equation of the Wigner function directly from the electromagnetic Schrödinger equation and apply it to the plasma waves propagating in the direction parallel to the ambient magnetic field. The upper branches of the L and R waves in the plot of (ω, k) space have dispersion relations similar to those of their respective classical waves, with only minor corrections. The lower R-wave branch also has a dispersion relation similar to that of the classical whistler wave for a small wavenumber k. However, the dispersion curve encounters a region of anomalous dispersion, exhibiting a negative group velocity, as k increases. Furthermore, the branch becomes a damping wave as k increases above a certain critical value and eventually the wave becomes ill-defined for larger k values. [ABSTRACT FROM AUTHOR]

A self-consistent electrostatic odd-symmetric eigenmode (OEM) is analytically found in a solitary type Bernstein-Greene-Kruskal (BGK) equilibrium. The frequency of the OEM is order of the electron bounce frequency and it is spatially odd-symmetric with the scale comparable to that of the solitary BGK equilibrium structure. Such an OEM is consistent with the recent observation from particle-in-cell simulation of the solitary wave [Dokgo et al., Phys. Plasmas 23, 092107 (2016)]. The mode can be driven unstable by trapped electrons within the hole structure of the solitary wave. Such a low frequency, pure electron mode, which may possibly interact resonantly with the ion acoustic mode, provides a possible damping mechanism of the BGK equilibrium. [ABSTRACT FROM AUTHOR]

A possible formation of an electron hole structure associated with an obliquely propagating solitary kinetic Alfvén wave (SKAW) in a strongly magnetized plasma is discussed. It is found that transverse electric field along the magnetic field plays a key role in the electron phase space hole formation. Owing to the presence of trapped electrons, SKAW can propagate in both super-Alfvénic and sub-Alfvénic regimes with different spatial structures. In particular, in the sub- Alfvénic case, the density perturbation possesses a dip at the center accompanied by a pair of humps at the edges. Such a feature may be relevant to satellite observation of solitary structures in the Earth's geomagnetic tail region. [ABSTRACT FROM AUTHOR]

The perpendicular heating and acceleration of ions by linearly polarized Alfvén wave, which is propagating along constant background magnetic field, is studied. The perpendicular diffusion coefficient of ions is calculated through the autocorrelation function based on linear perturbation theory, which unambiguously demonstrates that ion heating is attained by non-resonant wave-particle interaction. It is found that the perpendicular heating and acceleration of ions occur by the Alfvén wave during a relatively short time interval, i.e., approximately 20 ion gyro period (Ωi0t) even though the perturbation amplitude is quite low. Also, it is shown that the temperature anisotropy of ions A, A, where A = T⊥/T∥ − 1, increases with the increasing perturbation amplitude while the parallel ion heating does not occur. Test particle simulation is also carried out in order to investigate the non-resonant perpendicular heating process. [ABSTRACT FROM AUTHOR]

The diffusion of electrons via a linearly polarized, growing electromagnetic (EM) wave propagating along a uniform magnetic field is investigated. The diffusion of electrons that interact with the growing EM wave is investigated through the autocorrelation function of the parallel electron acceleration in several tens of electron gyration timescales, which is a relatively short time compared with the bounce time of electrons between two mirror points in Earth's radiation belts. Furthermore, the pitch-angle diffusion coefficient is derived for the resonant and non-resonant electrons, and the effect of the wave growth on the electron diffusion is discussed. The results can be applied to other problems related to local acceleration or the heating of electrons in space plasmas, such as in the radiation belts. [ABSTRACT FROM AUTHOR]

Background Long-term exposure to sunlight changes skin features like amount of facial wrinkling and skin elasticity, which is useful in estimating skin health and age-related changes. Skin elasticity is evaluated by quantitative methods such as the noninvasive suction device Cutometer®, which is widely used to evaluate regional body-elasticity differences and correlate these findings with the results of other instrumental data. Few field studies have been done with the Ballistometer® device, another noninvasive method for measuring skin elasticity. Method In this study, we measured the skin elasticity of each subject's forehead, cheek, and volar forearm using two devices with different means of obtaining quantitative measurements - Ballistometer® (Diastron Ltd.) and Cutometer® ( CK electronics). Results The results from testing with the Ballistometer® and Cutometer® devices showed that the degree of skin elasticity of the volar forearm is greater than those found on the cheek and forehead. The parameters measured by the Ballistometer® showed high correlation patterns. On the cheek skin, the correlation coefficient between Ballisto-parameters and R parameters (R0, R3, R8) was higher than other skin sites. Conclusion Taken together, R parameters measured by the Cutometer® device have been widely distributed in the evaluation of skin elasticity in research and cosmetics. Although the methodologies are different, the Ballistometer® device is also a useful tool to evaluate skin elasticity. [ABSTRACT FROM AUTHOR]

Nonlinear small-amplitude kinetic Alfvén solitary waves (KASWs) are investigated with their 'anomalous' kinetic viscosity effect on electrons. It is found that the structure of a hump-type KASW solution develops into a shock-type (or double layer) KASW solution for large amplitude KASWs when viscosity exists. For small amplitude KASWs, the Korteweg-de Vries (KdV) equation with an approximate pseudopotential was solved, and it is found that the hump-type KASWs develop into oscillating shock-type (kink-type) KASWs. It is also found that the oscillating scale of this structure is related to the propagation velocity and plasma beta, while the damping scale is inversely proportional to the viscosity. [ABSTRACT FROM AUTHOR]

This work explored the significance of the drying history dependent effect on in situ crystallization in spray drying. Analysis was based on actual single droplet drying kinetics at different drying air temperatures. This paper reports the changes in droplet Tg, T – Tg, solubility, and supersaturation based on actual experimental data as drying progressed. The glass transition analysis suggests that a critical crystallization period might be significant for in situ crystallization in spray drying. This finding highlights the danger in using the final particle condition, delineated by the dyer outlet conditions, as a measure of partial crystallization in spray dried particles. Extended analysis using the nucleation–growth mechanism pointed to the same crystallization phenomenon analogous to the critical crystallization period concept. [ABSTRACT FROM AUTHOR]

Cotton turf and hotwire measurements were used to experimentally assess the highly swirling flow characteristics in a spray dryer fitted with a rotary disc atomizer. The numerical simulation captured key features of the flow field. Analysis revealed that rapid rotation of an atomizing disc tends to centrifugally split the central inlet jet. The flow field exhibited significant long time-scale transient behaviour. However, this centrifugally split jet resulted in a balanced upward recirculation region in the chamber as expected by the jet-feedback mechanism. Detailed analysis using a 'transient air-steady particle' approach revealed that this approach is applicable for such highly swirling transient flows as well. However, caution should be exercised when interpreting the deposition results, particularly in regions of low particle velocities. This is anticipated be an important consideration in future attempts to simulate the predominantly transient flows in spray dryers. [ABSTRACT FROM AUTHOR]

An obliquely propagating solitary kinetic Alfven wave in a low beta dusty plasma (βNd, where lz is the directional cosine and Nd is the dust particle charge density. In the collisional case, the same upper limit of the Mach velocity is found, and the solitary wave turns into an oscillating double layer. The damping scale and the size of the oscillation structure increase with increasing dust particle charge density. The damping scale and the size of the oscillation structure are estimated by using the virial theorem. [ABSTRACT FROM AUTHOR]

Application of an electric or magnetic field can significantly affect the freezing characteristics of water. A DC electric field will tend to induce ice nucleation at a lower degree of supercooling, and there is evidence to show that an AC electric field delays the onset of ice nucleation. Industrial research has shown that a magnetic field can be used to delay nucleation and to induce small, unclustered ice. Smaller ice crystals are essential in the preservation of the structure or bioavailability of frozen materials, particularly biological or food products. On the other hand, larger ice crystals facilitate faster freeze drying because it results in less vapor mass transfer resistance. The end part of this review introduces another application of magnetic field in the form of magnetocaloric freezers. This technology is a potential alternative to heat pump drying for commercial freezing and refrigeration. [ABSTRACT FROM AUTHOR]

Aims: To assess the impact of reaerosolization from liquid impingement methods on airborne virus sampling. Methods and Results: An AGI-30 impinger containing particles [MS2 bacteriophage or 30-nm polystyrene latex (PSL)] of known concentration was operated with sterile air. Reaerosolized particles as a function of sampling flow rate and particle concentration in the impinger collection liquid were characterized using a scanning mobility particle sizer. Reaerosolization from the impinger was also compared to that from a BioSampler. Results show that reaerosolization increases as flow rate increases. While the increased particle concentration in the impinger collection liquid leads to an increase in the reaerosolization of PSL particles, it does not necessarily lead to an increase in the reaerosolization of virus particles. Reaerosolization of virus particles begins to decrease as the particle concentration in the impinger collection liquid rises above 106 PFU ml−1. This phenomenon results from aggregation of viral particles at high concentrations. Compared with micron-sized particles, nanosized virus particles are easier to aerosolize because of reduced inertia. Reaerosolization from the BioSampler is demonstrated to be significantly less than that from the impinger. Conclusions: Reaerosolization from impingement sampling methods is a mode of loss in airborne virus sampling, although it is not as significant a limitation as the primary particle size of the aerosol. Utilizing a BioSampler coupled with short sampling periods to prevent high accumulative concentrations can minimize the impact of reaerosolization. Significance and Impact of the Study: This study confirms reaerosolization of virus particles to be a mode of loss in impingement sampling and identifies methods to minimize the loss. [ABSTRACT FROM AUTHOR]

Abstract: The separation of equimolar mixtures of i-butane and n-butane through poly(1-trimethylsilyl-1-propyne)/MFI composite membranes was studied. Membranes were characterized by XRD and SEM. Addition of 50wt% MFI particles into a PTMSP matrix showed increased permeability and simultaneous improved selectivity in the temperature range 25–200°C. The best improvement was seen at 150°C for the composites, giving almost threefold increase in permeability and 56% higher n-butane/i-butane selectivity over the pure polymer. To our knowledge, this is the first successful demonstration of the incorporation of a molecular sieve into a polymer matrix for butane isomer separations. The composite membranes were also tested for separations of n-hexane/2,2-dimethylbutane and p-xylene/o-xylene. [Copyright &y& Elsevier]

Sleep disorders, autonomic dysfunction, and abnormal cognition are important comorbidities in adult patients with heart failure and are associated with disease progression, morbidity, and mortality. The clinical incidence of these conditions is unknown in children with heart failure. We sought to determine the incidence of symptoms that may be attributable to autonomic dysfunction among children with dilated cardiomyopathy and heart failure. We performed a retrospective chart review of patients with dilated cardiomyopathy seen at our institution between 1999 and 2005. We reviewed charts for symptoms of dysautonomia, sleep problems, or abnormal cognition. From the records of 204 pediatric patients, we identified 69 patients aged 7–18 years with severe dilated cardiomyopathy. Of these, 55 (80%) had symptoms attributable to dysautonomia, 20 (29%) had evidence of sleep disturbance, and 3 (4%) had abnormal cognition. Dysautonomia and sleep disturbances are prevalent in children with heart failure, congruent with studies of adult patients. Based on our data, it is not possible to draw conclusions about any cognitive deficits in this population. Because relatively few subjects’ charts explored symptoms of sleep disturbance, we speculate that sleep symptoms may be underappreciated. [ABSTRACT FROM AUTHOR]

Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild-type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies. [ABSTRACT FROM AUTHOR]

To determine how well tacrolimus (FK506) and cyclosporin A (CsA) are tolerated after HLA-identical blood stem cell transplantation, we performed a retrospective review of 87 adults transplanted consecutively who received FK506 (n = 40) or CsA (n = 47) in a nonrandomized fashion in combination with methylprednisolone for graft-versus-host disease (GVHD) prophylaxis and compared the incidences of complications potentially related to the immunosuppressive agents. Pretransplant demographic characteristics, drug compliance and rates of acute GVHD were comparable for the two groups. Following first discharge, fewer patients in the FK506 group required antihypertensive therapy (32 vs 59%, P = 0.022), but more required insulin (34 vs 10%, P = 0.014). There was also a trend for more hyperkalemia and less moderate-to-severe veno- occlusive disease in the FK506 group. However, nephrotoxicity, neurotoxicity, hemolytic–uremic syndrome, and cytomegaloviral or fungal infections through the first 100 days post-transplant did not differ significantly between the two groups. We conclude that for allogeneic blood stem cell transplant recipients, the incidence of complications related to FK506 and CsA in equally effective dose schedules in combination with methylprednisolone are similar with the exception of the risks of hypertension and hyperglycemia. [ABSTRACT FROM AUTHOR]

Asparaginase is an effective antileukemic agent and is included in most front-line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide; however, allergic reactions to asparaginase may be dose-limiting. We evaluated plasma anti-asparaginase antibody concentrations in a cohort of children with newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity, after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who received asparaginase 10000 IU/m2 i.m. three times weekly for nine doses as part of both multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Twenty-two patients experienced initial allergic reactions to asparaginase during continuation (n=20) or reinduction (n=2) phases and 13 children did not exhibit any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli asparaginase as the antigen. The median anti-asparaginase antibody concentration (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison, median antibody level increased from 0.011 to 0.032 OD at identical time points in patients who did not react to asparaginase (P = 0.02). Both post-induction and post-reinduction anti-asparaginase antibody levels were higher in reacting than in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels were inversely related to the time elapsed between the reaction and sampling (P = 0.011). Although anti-asparaginase antibody levels increased from the post-induction plasma sample to the post-reinduction sample in 28 of 35 patients regardless of whether they exhibited clinical hypersensitivity, patients with hypersensitivity reactions had higher antibody levels than did identically treated control patients at comparable time points in therapy. Therefore, antibody analysis may be of clinical value in predicting future hypersensitivity. [ABSTRACT FROM AUTHOR]

We studied parallel propagating electromagnetic waves in a magnetized quantum electron plasma of finite temperature, as an extension of our previous study on a zero temperature plasma. We obtained simple analytic dispersion relations in the long wavelength limit that included the thermal effect as correction terms to the zero temperature results. As in the zero temperature case, the lower branch of the R wave showed significant damping and became ill-defined at short wavelengths. Quantum effects seemed to give qualitative changes, such as the appearance of anomalous dispersion regions, to the classical dispersion relations when vF/vth≤0.2 for a set of exemplary parameters of vF=0.1c and ωce/ωpe=0.05 was used. We also noted that introduction of the Planck constant in the quantum Vlasov equation changed the shape of the anomalous dispersion region qualitatively, by forming a normal dispersion region in the middle of the original single broad anomalous dispersion region. [ABSTRACT FROM AUTHOR]

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions. [ABSTRACT FROM AUTHOR]

The purpose of this study is to examine the influence of stress on the relationship between shooting performance and cortico-cortical communication. Participants were 16 high school 10 m air pistol athletes whose mean age of 17.8 years (M = 8, F = 8). They were asked to execute shooting under stress condition, and non-stress condition. In both conditions, competitiveness, stress, confidence and relaxation were measured and cortical activity was recorded for analysis of cortico-cortical communication. The result was that stress increased competitiveness and stress, and decreased confidence. However, there was no significant difference in shooting score between both conditions. As the result of coherence analysis, stress treatment reduces neural efficiency by decreasing communication between Cz and T4, responsible for visual-spatial processing and increasing communication between Cz and T3, associated with verbal-analytic processing. The lack of difference in shooting performance between conditions may result from failure to induce stress enough to deteriorate performance. [ABSTRACT FROM AUTHOR]

The effect of the electron viscosity on the kinetic Alfven solitary wave is investigated. It is found that small electron viscosity changes the electron motion along the magnetic field producing a boundary layer, and thus that in a low beta electron-ion plasma(β

Objective: To present national estimates and correlates of lifetime and 12-month DSM-IV eating disorders for Latinos. Method: Data come from the National Latino and Asian American Study (NLAAS), a national epidemiological household survey of Latinos in the United States. Results: Latinos have elevated rates of any binge eating and binge eating disorder but low prevalence of anorexia nervosa and bulimia nervosa. The US born and those living a greater percentage of their lifetime in the US evidenced higher risk for certain eating disorders while severe obesity and low levels of education were significant correlates. Rates of treatment utilization were exceedingly low. Conclusion: Standard eating disorder criteria may not be appropriate for understanding psychological morbidity of eating disorders for Latinos, particularly less acculturated Latinos, due to cultural differences in the presentation of eating disorder symptoms. Criteria for disturbed eating patterns that are more reflective of the illness experience of Latinos should be developed. © 2007 by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

General characteristics of a fishbone mode in KSTAR are investigated. Fishbone activities are observed with a Mirnov coil, an electron cyclotron emission radiometer (from the core to the edge of plasmas) and an beam emission spectroscopy system (core or edge plasmas) which are measuring fluctuations of poloidal magnetic fields, electron temperatures, and densities, respectively. Temporal evolutions of these fluctuations are similar to the observations from other tokamaks. An interesting and notable feature found in KSTAR fishbone modes is that radial coherence structures of electron temperature and density with respect to magnetic fluctuations are non-monotonic that they have a local minimum at r / a ∼ 0.7 and a maximum at r / a ∼ 0.9 in addition to the usual global peak near the q = 1 surface, where r/a is the normalized minor radius and q is the safety factor. Furthermore, the associated temporal evolution of the electron temperatures in slow-time scale, i.e., less than 1 kHz, with the fishbone activities show that there exist a drop in temperature or increase in temperature depending on inside or outside the q = 1 surface, respectively, from the core to the edge plasmas except that there are almost no temperature changes in the intermediate region which seems to be correlated with the non-monotonic coherence profile. Such a non-monotonic structure and the slow temporal evolution of temperatures are explained with barely trapped resonating fast ions with the banana orbit widths of the order of the minor radius, so that they transit the core and the edge regions simultaneously without trespassing the mid-plane intermediate region. [ABSTRACT FROM AUTHOR]

Spray drying conventionally necessitates relatively large or elongated drying chambers. The present study examined the possibility in shrinking the spray drying chamber into narrow tube-like geometry. The key was in utilizing fine droplets which had low transport response time. A narrow copper/steel tube spray dryer (internal diameters between 12.7 and 48.0 mm) was constructed and was fitted with a two-fluid atomizer producing droplets in the size range smaller than 10 µm. Maltodextrin, lactose, and sucrose were spray-dried. The narrow tube approach allowed direct manipulation of the drying conditions via heating or cooling along the wall of the tube. This form of manipulation in the drying conditions, surprisingly, resulted in very distinctly crystalline spray-dried sucrose particles. The tube spray dryer was further modified with a long coiled-up tube, extending the particle residence time with minimal space requirements. Endoscopic analysis revealed that particle deposition within the tube resembled loosely attached particle and granules. The tube spray drying concept can potentially be used to provide precise control of the particle drying history along the length of the drying chamber, not limited to the control of the drying conditions at the inlet or outlet of a spray dryer. [ABSTRACT FROM PUBLISHER]

We report on first evidence of wave activity during neutral beam heating in KSTAR plasmas: 40 kHz magnetic fluctuations with a toroidal mode number of n = 1. Our analysis suggests this a beta-induced Alfv'en eigenmode (BAE) resonant with the q = 1 surface. A kinetic analysis, when coupled with electron temperature measurements from electron cyclotron emission and ion/electron temperature ratios from crystallography, enables calculation of the frequency evolution, which is in agreement with observations. Complementary detailed magnetohydrodynamic (MHD) modelling of the magnetic configuration and wave modes supports the BAE conclusion, by locating an n = 1 mode separated from the continuum in the core region. Finally, we have computed the threshold to marginal stability for a range of ion temperature profiles. These suggest the BAE can be driven unstable by energetic ions when the ion temperature radial gradient is sufficiently large. Our findings suggest that mode existence could be used as a form of inference for temperature profile consistency in the radial interval of the mode, thereby extending the tools of MHD spectroscopy. [ABSTRACT FROM AUTHOR]

A simultaneous convection–dehydration and antisolventprecipitationapproach has been shown to produce uniform microsizedlactose particles from aqueous droplet at atmospheric pressure. Microparticleswith high uniformity having diameters of between 1.0 and 2.4 μmhave been obtained. The precipitation of the microparticles is drivenby a unique self-assembly mechanism that cannot be fully elucidatedby supersaturation alone. Further analysis suggests that structuralchanges in the solvent/antisolvent mixture, due to hydrophobic hydration,could play a role in the precipitation process observed. [ABSTRACT FROM AUTHOR]

The existence condition for bump and dip type, as well as double layer (DL), solutions of electrostatic solitary waves (ESWs) in a nonthermal electron plasma with heavy ions is investigated by a pseudopotential method. It is found that the nonthermality of electrons determines the existence of the DL solution and that the amplitude of ESWs is enhanced by the density of heavy ions. When the heavy ion density is beyond a certain critical value, ESWs and DLs cannot exist. It is also found that both the lower and upper critical Mach numbers are reduced by the presence of heavy ions. [ABSTRACT FROM AUTHOR]

Since autocrine regulation of HGF-Met is implicated in many forms of human cancer, we investigated whether the predisposition to develop ovarian cancer in women with hereditary ovarian cancer syndromes involves changes in the expression of HGF-Met by the tissue of origin of epithelial ovarian cancers, the ovarian surface epithelium (OSE). We compared cultures of normal OSE from women with (FH-OSE) (n=20) and with no (NFH-OSE) (n=48) family histories of ovarian cancer, SV40 Tag immortalized OSE lines (IOSE, n=5) and ovarian cancer cell lines (n=3). Cultures derived from 21/22 women with NFH-OSE and 13/13 women with FH-OSE expressed Met mRNA initially. After two to three passages, Met was downregulated in 37% of NFH-OSE cultures but persisted in 100% of FH-OSE cultures and ovarian cancer lines, like other epithelial differentiation markers that are stabilized in FH-OSE and neoplasia. HGF and Met mRNA were concomitantly expressed by NFH-OSE from only three of 32 women but in FH-OSE from eight of 13 women, and also in five of five IOSE and two of three ovarian cancer lines. Conditioned media from FH-OSE, but not NFH-OSE, contained immunoreactive HGF and induced cohort migration which was inhibited by neutralizing HGF antibody. Several signaling molecules of the PI3K pathway, including Akt2 and p70 S6K, were constitutively activated in FH-OSE from six of six women but in NFH-OSE from only four of eight women. Exogenous HGF was mitogenic in OSE, and that effect was regulated through the MAP kinase (ERK1/ERK2) and FRAP/p70 S6K pathways. The proliferative response to HGF was greater in NFH-OSE than in FH-OSE cultures. The results show that FH-OSE cultures differ from NFH-OSE by increased stability of Met expression and by HGF secretion. Constitutive phosphorylation of kinases and a diminished growth response to HGF suggest the presence of autocrine regulation in FH-OSE. In analogy with other cell types where an autocrine HGF-Met loop has been implicated in tumorigenic... [ABSTRACT FROM AUTHOR]

This study aimed to examine the effects of lipid emulsion on the vasodilation and cardiovascular depression induced by toxic doses of calcium channel blockers. The effects of lipid emulsion on the vasodilation induced by bepridil, verapamil, nifedipine, and diltiazem were investigated in isolated endothelium-denuded rat aortae. The effect of lipid emulsion on the comparable hemodynamic depression induced by the continuous infusion of a toxic dose of either verapamil or diltiazem was examined in an in vivo rat model. The results showed the following decreasing order for the magnitude of lipid emulsion-mediated inhibition of vasodilation: bepridil, verapamil, nifedipine, and diltiazem. Lipid emulsion (0.5-2%) reversed the vasodilation induced by a toxic dose of verapamil, whereas only a higher concentration (2%) reversed the vasodilation induced by a toxic dose of diltiazem. Pretreatment with lipid emulsion alleviated the systolic and mean blood pressure decreases induced by a toxic dose of verapamil, whereas it had no effect on the decrease induced by diltiazem. Taken together, these results suggest that lipid emulsion alleviates the severe vasodilation and systolic blood pressure decrease induced by a toxic dose of verapamil, and this alleviation appears to be associated with the relatively high lipid solubility of verapamil. [ABSTRACT FROM AUTHOR]

Of all the operating conditions in a spray dryer, temperature of the drying medium holds the key parameter in affecting the degree of crystallinity in spray-dried particles. Previous experiments only focus on controlling the drying temperature at the inlet or outlet of drying chamber to delineate the drying history of particles, precluding any detailed studies on particle development throughout the drying duration. Hence, the objective of this work is to address the current limitation by introducing a modified narrow tube spray dryer which enables in situ control of drying history. Essentially, the drying chamber consists of 10 narrow copper tubes with an internal diameter of 1.7 cm. Each individual copper tube can be heated independently to create a unique controlled drying history. Scanning electron microscopy images demonstrate the significant impact of drying history on lactose morphology with possible crystallization by even slight variations in the drying history, which further accentuates the sensitivity of degree of crystallization to temperature. With this newly developed equipment, the detailed drying history conditions can be designed and manipulated to engineer the desired particle properties. [ABSTRACT FROM AUTHOR]

Local infection of the trachea in intubated neonates is one of the main risk factors for development of acquired subglottic stenosis, although its role in the pathogenesis is unclear. Methicillin resistant Staphylococcus aureus (MRSA) is often the cause of critical illness in neonatal patients. Two cases are reported of acquired subglottic stenosis following bacterial infection of the trachea, suggesting an association with the staphylococcal exotoxin, epidermal cell differentiation inhibitor (EDIN). EDIN-producing MRSA were isolated from purulent tracheal secretions from both infants. Acquired subglottic stenosis in both cases was probably caused by delayed wound healing as the result of EDIN inhibition of epithelial cell migration. [ABSTRACT FROM AUTHOR]

Local infection of the trachea in intubated neonates is one of the main risk factors for development of acquired subglottic stenosis, although its role in the pathogenesis is unclear. Methicillin resistant Staphylococcus aureus (MRSA) is often the cause of critical illness in neonatal patients. Two cases are reported of acquired subglottic stenosis following bacterial infection of the trachea, suggesting an association with the staphylococcal exotoxin, epidermal cell differentiation inhibitor (EDIN). EDIN-producing MRSA were isolated from purulent tracheal secretions from both infants. Acquired subglottic stenosis in both cases was probably caused by delayed wound healing as the result of EDIN inhibition of epithelial cell migration. [ABSTRACT FROM AUTHOR]

Ultrafine spherical maltodextrin and maltose particles were successfully produced with the antisolvent vapour precipitation (AVP) technique. Comparison between the two materials confirmed that a key requirement for the process is in inhibiting crystallization of the material. The precipitation process consists of: (1) an initial phase separation forming an emulsion formation, (2) phase inversion and (3) finally a water-maltodextrin shrinkage phase which forms the spherical particles driven by interfacial surface tension. Dehydrating the droplet at different stages of the process resulted in various particle morphologies; porous, smooth, microsphere network and microspheres. Higher ethanol relative humidity, higher ethanol absolute humidity and lower initial weight concentration were found to favour the formation of amorphous microspherical particles upon drying. [ABSTRACT FROM AUTHOR]

Mixing surfactants with whole milk feed before spray drying could be a commercially favorable approach to produce instant whole milk powders in a single step. Pure whole milk powders obtained directly from spray drying often have a high surface fat coverage (up to 98%), rendering them less stable during storage and less wettable upon reconstitution. Dairy industries often coat these powders with lecithin, a food-grade surfactant, in a secondary fluidized-bed drying stage to produce instant powders. This study investigated the changes in wetting behavior on the surface of a whole milk particle caused by the addition of surfactants before drying. Fresh whole milk was mixed with 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin (total solids), and the wetting behavior of the shell formed by each sample was captured using a single-droplet drying device at intermediate drying stages as the shell was forming. The addition of surfactants improved shell wettability from the beginning of shell formation, producing more wettable milk particles after drying. The increase in surfactant loading by 10 times reduced the wetting time from around 30 s to <5 s. At the same loading of 1% (wt/wt; total solids), milk particles with Tween 80 were much more wettable than those with lecithin (<5 s compared with >30 s). We proposed that Tween 80 could adsorb at the oil-water interface of fat globules, making the surface fat more wettable, whereas lecithin tends to combine with milk proteins to form a complex, which then competes for the air-water surface with fat globules. Spray-drying experiments confirmed the greatly improved wettability of whole milk powders by the addition of either 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin; wetting time was reduced from 35 ± 4 s to <15 s. To the best of our knowledge, this is the first time that a dynamic droplet drying system has been used to elucidate the complex interactions between ionic or nonionic surfactants and milk components (both proteins and fat), as well as the resultant effect on the development of milk particle functionality during drying. [ABSTRACT FROM AUTHOR]

Highlights: [•] We had developed new LC–MS/MS method to determine camptothecin derivatives. [•] It can stably determine total forms of CPT-11 and SN-38 by acidifying samples. [•] It can determine CPT-11 and SN-38 in tumor tissues by LLE preparation. [•] It was completely validated for linearity, accuracy, precision and stability. [•] It was successfully applied to the pharmacokinetic study in rabbit plasma and tissues. [ABSTRACT FROM AUTHOR]

Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and myeloma). In patients with leukemia and myeloid disorders, 60 mg was the MTD for weekly as well as biweekly panobinostat. In patients with lymphoma and myeloma, 40 mg was the recommended dose for phase II evaluation (formal MTD not determined) of weekly panobinostat, and 60 mg was the MTD for biweekly panobinostat. Overall, panobinostat-related grade 3-4 adverse events included thrombocytopenia (41.5%), fatigue (21%) and neutropenia (21%). Single-agent activity was observed in several indications, including Hodgkin lymphoma and myelofibrosis. This phase Ia/II study provided a broad analysis of the safety profile and efficacy of single-agent panobinostat in patients with hematologic malignancies. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic β-cells in vivo, we generated a transgenic mouse model using rat insulin promoter (RIP)-driven Cre-loxP recombination system to specifically delete FAK in pancreatic β-cells. These RIPcre(+)fak(fl/fl) mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell viability and proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with attenuated insulin/Akt (also known as protein kinase B) and extracellular signal-related kinase 1/2 signaling and increased caspase 3 activation. FAK-deficient β-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca(2+) influx in response to glucose, but a reduced number of docked insulin granules and insulin exocytosis were found, which was associated with a decrease in focal proteins, paxillin and talin, and an impairment in actin depolymerization. This study is the first to show in vivo that FAK is critical for pancreatic β-cell viability and function through regulation in insulin signaling, actin dynamics, and granule trafficking. [ABSTRACT FROM AUTHOR]

Objective: Type 2 diabetes is characterized by diminished pancreatic β-cell mass and function. Insulin signaling within the β-cells has been shown to play a critical role in maintaining the essential function of the β-cells. Under basal conditions, enhanced insulin-PI3K signaling via deletion of phosphatase with tensin homology (PTEN), a negative regulator of this pathway, leads to increased β-cell mass and function. In this study, we investigated the effects of prolonged β-cell-specific PTEN deletion in models of type 2 diabetes.Research Design and Methods: Two models of type 2 diabetes were employed: a high-fat diet (HFD) model and a db/db model that harbors a global leptin-signaling defect. A Cre-loxP system driven by the rat insulin promoter (RIP) was employed to obtain mice with β-cell-specific PTEN deletion (RIPcre(+) Pten(fl/fl)).Results: PTEN expression in islets was upregulated in both models of type 2 diabetes. RIPcre(+) Pten(fl/fl) mice were completely protected against diabetes in both models of type 2 diabetes. The islets of RIPcre(+) Pten(fl/fl) mice already exhibited increased β-cell mass under basal conditions, and there was no further increase under diabetic conditions. Their β-cell function and islet PI3K signaling remained intact, in contrast to HFD-fed wild-type and db/db islets that exhibited diminished β-cell function and attenuated PI3K signaling. These protective effects in β-cells occurred in the absence of compromised response to DNA-damaging stimuli.Conclusions: PTEN exerts a critical negative effect on both β-cell mass and function. Thus PTEN inhibition in β-cells can be a novel therapeutic intervention to prevent the decline of β-cell mass and function in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Phosphatidylinositol 3-OH kinase (PI3K) has a long-recognized role in beta-cell mass regulation and gene transcription and is implicated in the modulation of insulin secretion. The role of nontyrosine kinase receptor-activated PI3K isoforms is largely unexplored. We therefore investigated the role of the G-protein-coupled PI3Kgamma and its catalytic subunit p110gamma in the regulation of insulin granule recruitment and exocytosis.Research Design and Methods: The expression of p110gamma was knocked down by small-interfering RNA, and p110gamma activity was selectively inhibited with AS605240 (40 nmol/l). Exocytosis and granule recruitment was monitored by islet perifusion, whole-cell capacitance, total internal reflection fluorescence microscopy, and electron microscopy in INS-1 and human beta-cells. Cortical F-actin was examined in INS-1 cells and human islets and in mouse beta-cells lacking the phosphatase and tensin homolog (PTEN).Results: Knockdown or inhibition of p110gamma markedly blunted depolarization-induced insulin secretion and exocytosis and ablated the exocytotic response to direct Ca(2+) infusion. This resulted from reduced granule localization to the plasma membrane and was associated with increased cortical F-actin. Inhibition of p110gamma had no effect on F-actin in beta-cells lacking PTEN. Finally, the effect of p110gamma inhibition on granule localization and exocytosis could be rapidly reversed by agents that promote actin depolymerization.Conclusions: The G-protein-coupled PI3Kgamma is an important determinant of secretory granule trafficking to the plasma membrane, at least in part through the negative regulation of cortical F-actin. Thus, p110gamma activity plays an important role in maintaining a membrane-docked, readily releasable pool of secretory granules in insulinoma and human beta-cells. [ABSTRACT FROM AUTHOR]

Abstract: In addition to protective effects within the adult central nervous system (CNS), in vivo application of N-methyl-d-aspartate inhibitors such as (+) MK-801 have been shown to induce neurodegeneration in neonatal rats over a specific developmental period. We have systematically mapped the nature and extent of MK-801-induced neurodegeneration throughout the neonatal murine brain in order to genetically dissect the mechanism of these effects. Highest levels of MK-801-induced neurodegeneration are seen in the cerebellar external germinal layer; while mature neurons of the internal granule layer are unaffected by MK-801 treatment. Examination of external germinal layer neurons by electron microscopy, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and bromodeoxyuridine (BrdU) labeling, and caspase-3 activation demonstrate that these neurons die through the process of programmed cell death soon after they exit from the cell cycle. Significantly, ablation of caspase-3 activity completely inhibited the MK-801-induced (and developmental) programmed cell death of external germinal layer neurons. Similar to caspase-3, inactivation of muscarinic acetylcholine receptors in vivo using scopolamine inhibited MK-801-induced programmed cell death. By contrast, the GABAergic agonist diazepam, either alone or in combination with MK-801, enhanced programmed cell death within external germinal layer neurons. These data demonstrate that, in vivo, cerebellar granule neurons undergo a dramatic change in intracellular signaling in response to molecules present in the local cellular milieu during their first 24 h following exit from the cell cycle. [Copyright &y& Elsevier]

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. Revisiting of aerosol gene delivery may provide an alternative for safe and effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in the previous study was used as a gene carrier. The potential effects of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) on Akt-related signals and cell cycle regulation were evaluated. Aerosols of UAC–PTEN were delivered into K-rasLA1 lung cancer model mice through the nose-only inhalation system twice a week for total 4 weeks. Delivered PTEN suppressed lung tumor development significantly through nuclear complex formation between PTEN and p53, suppressing Akt-related signals as well as cell cycle regulation. Together, our results suggest that aerosol delivery of UAC–PTEN may be compatible with noninvasive in vivo gene therapy.Cancer Gene Therapy (2008) 15, 275–283; doi:10.1038/sj.cgt.7701116; published online 22 February 2008 [ABSTRACT FROM AUTHOR]

Inadequate pancreatic beta-cell mass resulting from excessive beta-cell apoptosis is a key defect in type 1 and type 2 diabetes. Caspases are the major molecules involved in apoptosis; however, in vivo roles of specific caspases in diabetes are unclear. The purpose of this study is to examine the role of Caspase (Casp)8 in beta-cells in vivo. Using the Cre-loxP system, mice lacking Casp8 in beta-cells (RIPcre(+)Casp8(fl/fl) mice) were generated to address the role of Casp8 in beta-cells in physiological and diabetes models. We show that islets isolated from RIPcre(+)Casp8(fl/fl) mice were protected from Fas ligand (FasL)-and ceramide-induced cell death. Furthermore, RIPcre(+)Casp8(fl/fl) mice were protected from in vivo models of type 1 and type 2 diabetes. In addition to being the central mediator of apoptosis in diabetes models, we show that Casp8 is critical for maintenance of beta-cell mass under physiological conditions. With aging, RIPcre(+)Casp8(fl/fl) mice gradually develop hyperglycemia and a concomitant decline in beta-cell mass. Their islets display decreased expression of molecules involved in insulin/IGF-I signaling and show decreased pancreatic duodenal homeobox-1 and cAMP response element binding protein expression. At the level of individual islets, we observed increased insulin secretory capacity associated with increased expression of exocytotic proteins. Our results show distinct context-specific roles of Casp8 in physiological and disease states; Casp8 is essential for beta-cell apoptosis in type 1 and type 2 diabetes models and in regulating beta-cell mass and insulin secretion under physiological conditions. [ABSTRACT FROM AUTHOR]

Pneumonia is the leading cause of morbidity and mortality after living lobar lung transplantation (LT). Low levels of human leukocyte antigen-DR (HLA-DR) expression on peripheral blood monocytes, have been demonstrated to correlate with risk of infection in surgical, trauma, and adult transplant patients. In addition, interleukin (IL)-10 has been shown to be a negative regulator of HLA-DR expression. This study investigates whether HLA-DR expression and serum IL-10 levels correlate with the development of pneumonia after pediatric LT.Thirteen LT recipients were prospectively monitored with blood samples obtained pre-LT (baseline) and post-LT weeks 1–4. Mean fluorescence intensity (MFI) of HLA-DR on CD14+ monocytes was measured by flow cytometry. IL-10 levels were determined by ELISA from frozen serum collected at the same time points as monocyte HLA-DR expression. Correlates of pneumonia were abstracted from the medical record.Monocyte HLA-DR expression declined in 11 of 13 patients in the first week post-LT. Two patients without an initial decline and four others whose HLA-DR expression recovered by week 2 post-LT, did not develop pneumonia or other infection or rejection. Pneumonia was observed in seven patients, six of whom failed to recover their monocyte HLA-DR expression by 2 weeks post-LT. Six of seven patients with pneumonia recovered, and one patient died of aspergillosis. During weeks 1–4, a statistically significant difference was seen in the profile of mean monocyte HLA-DR expression levels, analyzed as percent of baseline, between the patients with and without pneumonia (P=0.002). The greatest difference between groups over time was seen from post-LT weeks 1–2 (P=0.003). In addition, when comparing the values at each week, a significant difference was seen between the two groups at post-LT week 2 (P=0.006) and week 4 (P=0.05). Analysis of IL-10 concentrations revealed that the overall difference between the groups (patients with and without pneumonia) was statistically significant (P=0.014), with a paradoxical positive correlation between HLA-DR expression at post-LT week 4 and IL-10 concentrations.Persistent low monocyte HLA-DR expression was associated with the risk of post-LT pneumonia in these patients. This measurement may be useful for monitoring risk of infection and stratifying patients into higher and lower risk groups. Increased IL-10 levels may be protective for infection in this group of patients. At present it is unknown whether the predictive power of HLA-DR expression is indicative of a global defect in monocytic function or a specific abnormality. [ABSTRACT FROM AUTHOR]