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Sand concentration and particle size are the main factors that affect the erosion of solid surfaces under the impact of solid particles in liquid–solid two-phase flow. In this study, five sand concentrations (1 wt%, 3 wt%, 5 wt%, 10 wt%, and 20 wt%) and five particle sizes (20 μm, 75 μm, 125 μm, 300 μm, and 425 μm) were used for V-groove Surface mud erosion is simulated. Gambit and Ansys Fluent were used to simulate the anti-erosion performance of the V-shaped groove. The flow field near the V-shape grooved surface was analyzed for the explanation of the erosion behavior. Corresponding experiments were also carried out to verify the simulation. The results showed that the slurry erosion of the V-shape grooved surface increased with the increasing sand concentration. There was a critical particle size between 25 μm and 75 μm, above which the slurry erosion remained stable with the particle size. In addition, no great change occurred in the flow style for all cases with different sand concentrations and particle sizes. The erosion area did not change with the increasing sand concentration but enlarged with the increasing particle size. The erosion mechanism with different sand concentrations and particle sizes was also discussed.

High-order harmonic generation in argon gaseous medium is experimentally studied, using superintense 46-fs Ti :sapphire laser pulses. The double-peak splitting in the generated harmonic spectra is clearly observed when the driving laser intensity is upgraded to far higher than the saturation intensity of the medium involved. The possible reasons for the observed splitting are discussed in this presentation. This splitting is mainly attributed to the propagation effects of harmonic fields in the rapid ionizing medium.

The optical parametric chirped pulse amplification (OPCPA) technique is promising for constructing a 100-TW/90-fs laser systern. This laser systern consists of a diode-pumped Nd : phosphate oscillator, two LBO preamplifiers and a final power KDP amplifier. A noncollinear BBO-1 optical parametric amplifier pumped by a Q-switched and frequency-doubled Nd:YAG laser has been demonstrated. The temporally-stretched chirped signal laser pulses with a bandwidth of 36nm(FWHM) are amplified without limitation in bandwidth and distortion in the spectrum. The gain bandwidth is very sensitive to the pump-signal angle. Variation of this angle of [MATH] can significantly reduce the amplified bandwidth and results in a significant distortion of the amplified spectrum.

The stability, natural characteristics and critical axial force of a supported beam are analyzed. The both ends of the beam are held by the pinned supports with rotational spring constraints. The eigenvalue problem of the beam with these boundary conditions is investigated firstly, and then, the stability of the beam is analyzed using the derived eigenfuntions. According to the analytical expression obtained, the effect of the spring constants on the critical values of the axial force is discussed.

Fluorescent microspheres are widely used as biological tracers. In this study, uniformly sized chitosan microspheres crosslinked with glutaraldehyde (CG microspheres) and formaldehyde (CF microspheres) are successfully prepared by the Shirasu Porous Glass (SPG) membrane emulsification technique. Selectively reduced CG microspheres (SRCG microspheres) are obtained by NaBH4reduction. These chitosan microspheres are found to exhibit fluorescent properties without conjugation to any fluorescent agent. The fluorescence color varies with different crosslinkers and can be modulated by further chemical reduction, whereas the fluorescence intensity can be controlled by tuning the particle size and degree of crosslinking. The autofluorescence of the microspheres is applied to study the phagocytosis of HepG2 cells using the microspheres as novel tracers. Quantitative and qualitative evaluations show that these chitosan microspheres serve as bright, inert, durable, and extremely photostable tracers.

Wavelengths and oscillator strengths for transitions among the levels of the terms belonging to the 3s2, 3s3p, 3s3d, 3s4s, 3s4p, 3s4d, 3p2, 3p3d, 3p4s, 3p4p, 3p4d, 3d4s, 3d4p, 3d4d and 3d2configurations of Mg-like Nd48+, Pm49+and Sm50+are systematically calculated using multiconfiguration-Dirac-Fock method. The predicted spectra of these three ions are, for the first time, extensively reported for n= 3-4 transitions in the 5-8 Å range and the variant trends of wavelengths and oscillator strengths along the isoelectronic sequence are discussed.

The effect of temporal synchronization between the chirped signal pulse and the pumping pulse in an optical parametric chirped pulse amplification laser system is researched theoretically and experimentally. The results show that the gain of optical parametric amplification is sensitive to the temporal synchronization. Therefore, accurate temporal synchronization between the chirped signal pulse and the pumping pulse is essential to obtain high optical parametric amplification gain and stable output from an optical parametric chirped pulse amplification laser. Based on our 16.7-TW/120-fs optical parametric chirped pulse amplification laser system with ∼1-ns pumping pulse duration and <10-ps time jitter between the signal and pumping pulse, the effect of the temporal synchronization on optical parametric chirped pulse amplification is demonstrated. The experimental results agree with the calculation. © 2004 Society of Photo-Optical Instrumentation Engineers.

Interleukin-8 (IL-8) has recently been shown to contribute to human melanoma progression by functioning as a mitogenic and angiogenic factor. In the present study, we investigated whether targeting IL-8 by a fully human anti-IL-8 antibody (ABX-IL8) could be a potential therapeutic strategy to control angiogenesis, growth, and metastasis of melanoma. The human melanoma cells A375SM (high IL-8 producer) and TXM-13 (intermediate IL-8 producer) were injected subcutaneously into nude mice, which were then treated with ABX-IL8 (1 mg/3 times weekly, i.p., for 3 weeks). Tumor growth of both melanomas in ABX-IL8-treated mice was significantly inhibited when compared with control IgG-treated animals. ABX-IL8 treatment also suppressed experimental metastasis when the melanoma cells were injected intravenously. IL-8 blockade by ABX-IL8 significantly inhibited the promoter activity and the collagenase activity of matrix metalloproteinase-2 in human melanoma cells, resulting in decreased invasion through reconstituted basement membrane in vitro. In vivo, ABX-IL8 treatment resulted in decreased expression of matrix metalloproteinase-2, and decreased vascularization (angiogenesis) of tumors concomitant with increased apoptosis of tumor cells. Moreover, in an in vitrovessel formation assay, ABX-IL8 directly interfered with the tubule formation by human umbilical vein endothelial cells. Taken together, these results point to the potential utility of ABX-IL8 as a modality to treat melanoma and other solid tumors either alone or in combination with conventional chemotherapy or other anti-tumor agents.

Leukocyte adhesion to the endothelial venules in the pancreatic islets is thought to be one of the initial steps in the development of insulin-dependent diabetes mellitus. It has been suggested that leukocyte adhesion to endothelium is a sequential multistep process involving various different homing receptors. We report here that blocking different homing receptors--namely, L-selectin and very late antigen 4 (VLA-4)--which function during different stages of the adhesion process, by specific monoclonal antibodies inhibits insulitis and prevents diabetes in mice. Moreover, leukocyte attachment to the inflamed vessels within pancreatic sections could be inhibited by anti-L-selectin and anti-VLA-4 antibodies. Interestingly, anti-L-selectin or anti-VLA-4 antibody did not appear to influence the autoimmune response to a panel of pancreatic beta-cell autoantigens. These data suggest that L-selectin and VLA-4 receptors are involved in mediating leukocyte homing to the islets and that intervention of these two adhesion pathways may provide a novel approach for treatment of autoimmune diseases such as insulin-dependent diabetes mellitus.

1. Weak excitation to rat hippocampal CA1 neurons via Schaffer collaterals at a frequency of 0.1 or 0.2 Hz accompanied by repeated brief exposures to the inhibitory transmitter gamma-amino-butyric acid (GABA) causes a long-term depression (LTD, up to 90% of the control) of the stimulated pathway. This depression can be reversed by high-frequency stimulation. 2. Although inhibition is necessary for the induction of this LTD, the depression can be produced with either the GABAA or the GABAB receptor agonists. 3. This conjunctive LTD could not be blocked by the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric acid. 4. It was, however, blocked by the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, indicating that activation of a metabotropic glutamate receptor is necessary for the LTD. Induction also appeared to require an intracellular Ca2+ increase. 5. Because GABAergic inhibition often modulates glutamatergic transmission in the brain, we propose that this form of synaptic modification is of potential importance for neural plasticity.

Murine neuroblastoma N1E-115 cells are a useful system in which to study neuronal angiotensin II (AngII) receptors. N1E-115 cells possess both type 1 (AT1) and type 2 (AT2) AngII receptor subtypes, as does mammalian brain. AT2 receptors in brain or N1E-115 cells can be solubilized in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. In the present study, heparin-Sepharose chromatography was used to partially purify solubilized N1E-115 membranes to produce an enriched population of AT2 receptors. Subsequently, an eluted peak, containing the majority of AT2 binding activity, was used as an immunogen in the development of protein-directed polyclonal antibodies. The antibodies specifically detected immunoreactive proteins of approximately 110 and 66 kDa in both solubilized N1E-115 cells, as well as the original protein material that eluted from the heparin-Sepharose column, whereas no such immunoreactivity was detected in a kidney epithelial cell line that lacks any specific 125I-labeled AngII (125I-AngII) binding activity. Moreover, the antibodies immunoreacted with affinity-purified AT2 receptors. These antibodies were also able to immunoprecipitate AT2 receptors from solubilized N1E-115 cells, as revealed by the pharmacologic profile of 125I-AngII binding to the precipitated protein. Similarly, the antibodies were able to immunoprecipitate a 66-kDa protein that had been covalently crosslinked with 125I-AngII by use of the homobifunctional crosslinker dithiobis(succinimidyl propionate). Collectively, these results demonstrate the development of a specific AT2 receptor antibody that may be used to further characterize this receptor subtype at both the cellular and molecular levels.

We report the isolation of a panel of CD4+ T helper type 1 autoreactive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cell clones express a diverse repertoire of T cell receptors, three of which recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capacity of the T cell clones correlates with their ability to produce a novel immunoregulatory activity that potently inhibits in vitro allogeneic mixed lymphocyte reaction. The partially purified activity significantly inhibited the adoptive transfer of diabetes. Our work provides evidence in support of the existence of T helper type 1, CD4+ T cells reactive to beta islet cell autoantigens that have acquired a protective instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of down-regulating immune responses, and they are likely to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance.

To elucidate the role of cell adhesion molecules in the pathogenesis of insulin-dependent diabetes mellitus and to determine the predominant lymphocytic homing pathway(s) involved in the selective lymphocytic infiltration of pancreatic islets (insulitis), nonobese diabetic mice were treated with monoclonal antibodies specific for the L-selectin and integrin alpha 4 lymphocyte adhesion molecules. Treatment of neonatal mice with either anti-L-selectin or anti-integrin alpha 4 monoclonal antibodies for the first 4 weeks of life led to a significant and long-term protection against spontaneous occurrence of insulitis and diabetes. The same treatment failed to inhibit lymphocytic infiltration of the salivary glands (sialadenitis). This tissue-specific inhibition of inflammation may be attributed to differences between the pancreas and salivary gland in their expression of endothelial ligands for L-selectin (peripheral vascular addressin) and for integrin alpha 4 (mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1). Mucosal addressin cell adhesion molecule 1 is highly expressed by vessels within the inflamed islets but was not detected in the salivary glands. In contrast, peripheral vascular addressin- and vascular cell adhesion molecule 1-expressing vessels can be found in almost every area of inflammation within the salivary glands but are seen in only 40-50% of inflamed islets. Anti-L-selectin and anti-integrin alpha 4 treatment had no demonstrable effect on anti-beta-cell autoimmunity or on the immune responses to foreign antigens. Therapeutic treatment with anti-L-selectin after the onset of insulitis from 10 to 14 weeks of age delayed the onset but failed to prevent spontaneous insulin-dependent diabetes mellitus, whereas anti-integrin alpha 4 treatment resulted in a significant and long-lasting suppression of the disease. These data strongly suggest that integrin alpha 4 plays a prominent role in the spontaneous development of insulitis and diabetes in nonobese diabetic mice.

Tumor necrosis factor (TNF) alpha is a cytokine that has potent immune regulatory functions. To assess the potential role of this cytokine in the early development of autoimmunity, we investigated the effect of TNF on the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice, a spontaneous murine model for autoimmune, insulin-dependent type I diabetes. Treatment of newborn female NOD mice with TNF every other day for 3 wk, led to an earlier onset of disease (10 versus 15 wk of age in control mice) and 100% incidence before 20 wk of age (compared to 45% at 20 wk of age in control phosphate-buffered saline treated female mice). In contrast, administration of an anti-TNF monoclonal antibody, TN3.19.12, resulted in complete prevention of IDDM. In vitro proliferation assays demonstrated that mice treated with TNF developed an increased T cell response to a panel of beta cell autoantigens, whereas anti-TNF treatment resulted in unresponsiveness to the autoantigens. In addition, autoantibody responses to the panel of beta cell antigens paralleled the T cell responses. The effects mediated by TNF appear to be highly age dependent. Treatment of animals either from birth or from 2 wk of age had a similar effect. However, if treatment was initiated at 4 wk of age, TNF delayed disease onset. These data suggest that TNF has a critical role in the early development of autoimmunity towards beta-islet cells.

Susceptibility to the human autoimmune disease insulin-dependent diabetes mellitus is strongly associated with particular haplotypes of the major histocompatibility complex (MHC). Similarly, in a spontaneous animal model of this disease, the nonobese diabetic (NOD) mouse, the genes of the MHC play an important role in the development of diabetes. We have produced transgenic NOD mice that express the class II MHC molecule I-Ad in addition to the endogenous I-Ag7 molecules in order to study the role of these molecules in the disease process. Although the inflammatory lesions within the islets of Langerhans in the pancreas appear similar in transgenic and nontransgenic animals, transgenic mice develop diabetes with greatly diminished frequency compared to their nontransgenic littermates (10% of transgenic females by 30 weeks of age compared to 45% of nontransgenic females). Furthermore, adoptive transfer experiments show that T cells present in the transgenic mice are able to interfere with the diabetogenic process caused by T cells from nontransgenic mice. Thus, the mechanism by which I-Ad molecules protect mice from diabetes includes selecting in the thymus and/or inducing in the periphery T cells capable of inhibiting diabetes development.

Long-term depression (LTD) of glutamatergic and electrotonic transmission can be induced at mixed synapses between eighth nerve fibers and the goldfish Mauthner (M) cell in vivo, by pairing weak presynaptic tetani with postsynaptic inhibition. This LTD can be reversed by stronger tetani that produce long-term potentiation (LTP). Moreover, the depression is more likely to occur and tends to last longer when the initial synaptic efficacy is high--that is, if the synaptic strength is first potentiated. In addition, when synaptic efficacy is initially elevated, a weak tetanization that usually results in a gradually developing potentiation instead produces no change in chemical transmission and even a depression of electrotonic coupling. Thus, the modifications in synaptic transmission caused by a certain tetanizing protocol depend upon the history of synaptic efficacy. This last concept provides an experimental basis for theoretical models concerned with pre- and postsynaptic contributions to the regulation of synaptic plasticity.

Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally-induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease.

Snowfall is an important component of Earth's climate system; however, long, continuous high‐resolution records of global snowfall are lacking because of the absence of suitable proxies. In this study, diatom record from the sediments of Yunlong Lake, in the southeastern Tibetan Plateau, was used to reconstruct snowfall during the Younger Dryas (YD). Variations in the abundance of low‐light‐tolerant diatoms and diatom flux indicate that the duration of lake ice cover during the YD was significantly longer than that during the colder Heinrich event 1; this suggests that heavy snowfall, rather than temperatures, was responsible for the greater duration of lake ice cover during the YD. Thus, we conclude that prolonged, heavy snowfall occurred in the southeastern Tibetan Plateau during the YD. In addition, this conclusion is supported by the results of a climate model simulation that also suggest that heavy snowfall occurred at high latitude in the Northern Hemisphere during the YD. We propose that the heavy snowfall intensified cooling in Northern Hemisphere by increasing the albedo and that it increased hydrological variability at low latitudes by increasing the duration of the southward migration of the Intertropical Convergence Zone and by delaying the onset of the Asian summer monsoon. The snowfall would have been a source of continuous freshwater that acted as a positive feedback and resulted in a prolonged weakened state of the Atlantic meridional overturning circulation, which lasted for more than 1,000 years. Overall, our results emphasize the amplification and positive feedback function of heavy snowfall in triggering abrupt climate change. We provide the first evidence for prolonged heavy snowfall during the Younger DryasProlonged heavy snowfall would have extended the duration of the southward migration of the ITCZ during the YDSnowmelt would have been a persistent source of freshwater input to the ocean which maintained a weakened AMOC during the YD

Sleep plays a significant role in human health. Along with the emergency of diseases related to sleep, sleep monitoring is becoming a hotspot. Traditionally, Polysomnography (PSG) is considered as the gold standard for sleep monitoring, but it is expensive, time-consuming, and uncomfortable, especially not ideal for long-term sleep studies. Thus, exploring alternative sleep monitoring method has drawn much attention of researchers. Currently most of the sleep monitoring methods require complicated signals and feature extraction process. However, this paper innovatively proposes a method using simple signal of heart rate and respiration rate, and integrating the prior knowledge of experts to simplify the feature extraction process, which can make the subsequent classifier distinguish wake state and sleep state easily. In this paper, we used multi-layer neural network as a classifier, getting a Cohen's kappa value of 0.739, and the overall accuracy of classifying sleep and wake state reached to 88%. Furthermore, we improved the ability of detecting wake states greatly by oversampling method, and the sensitivity and specificity reached to 91.3% and 82.3% respectively. Nowadays, the development of various bed sensors makes it easy to obtain the heart rate and respiration rate signals of human beings. Therefore, the method proposed in this paper is conducive to people's long-term sleep monitoring more conveniently and has great significance to people's health.

This experiment was conducted to evaluate the equivalency values of microbial phytase to inorganic phosphorus (Pi) in 22- to 42-d-old broilers fed a corn-soybean meal diet. Ten dietary treatments were designed in which diet 1 was the basal diet [calcium 0.90%, total phosphorus 0.35%, nonphytate phosphorus (NPP) 0.13%] and diet 4 was control (calcium 0.90%, total phosphorus 0.57%, NPP 0.35%). Diets 2 and 3 included 0.20 and 0.27% of NPP, and diets 5 to 10 contained graded levels of microbial phytase (125, 250, 500, 1,000, 2,000, and 4,000 U/kg of diet). Body weight gain, feed intake, phosphorus retained, plasma Pi concentration, tibia ash content, and tibia-breaking strength increased, but plasma calcium concentration decreased with increasing dietary NPP content (from 0.13 to 0.35%) or phytase activity. Microbial phytase caused an increase, whereas dietary NPP caused a decrease in phytate phosphorus (PP) retention. When 4,000 U of phytase was added to the basal diet with 0.13% NPP, 95% PP was released based on tibia ash content, and broiler BW gain and feed intake were equal to those of broilers fed the control diet (NPP 0.35%). Microbial phytase at 125, 250, 500, 1,000, 2,000, and 4,000 U/kg of diet was determined to be equivalent to the addition of 0.035 to 0.208% of Pi from dicalcium phosphate in 22- to 42-d-old broilers. These data suggest that high levels of microbial phytase could release almost all dietary PP and replace all supplemental Pi in growing-finishing broilers.

On p. 3153, Guang‐Hui Ma and co‐workers report on the development of autofluorescent chitosan microspheres with tunable color based on different crosslinking reagents and further chemical modification. The fluorescent intensity can also be controlled by the particle size and crosslinking degree. The autofluorescent microspheres may be useful in fluorescence assays as bright, inexpensive, and stable probes for qualitative and quantitative studies of biological interactions and drug delivery.