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In this technical note, we study a finite double-sided queue with multiple customer types, where two-sided arrivals follow independent Poisson processes. Customers arrive to one side and match with queued customers on the opposite side. A gatekeeper who has complete knowledge of the number of customers decides to accept or reject each arrival. The difference between customer types is defined by the customer's profit to the gatekeeper. Assuming no matching time between the two-sided customers, we show that the optimal admission control policy for maximizing the long-run average profit per unit time has a threshold structure. Furthermore, we also explore more selective (bias) optimal policies when the average optimal policy is not unique. Finally, using the abovementioned results, we provide an efficient iterative algorithm to produce the optimal control policy.

Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)‐modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta‐like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3‐specific NK‐92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+SCLC cell lines with DLL3‐CAR NK‐92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3‐CAR NK‐92 cells induced tumor regression in an H446‐derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3‐CAR NK‐92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor‐infiltrated DLL3‐CAR NK‐92 cells were detected in DLL3+SCLC xenografts. These findings indicate that DLL3‐CAR NK‐92 cells might be a potential strategy for the treatment of SCLC. DLL3‐CAR NK‐92 cells showed significant anti‐tumor effect on small cell lung cancer both in vitro and in vivo.

The study showed that intraocular pressure measured lower with the Proview eye pressure monitor from Bausch and Lomb than with the Goldmann Applanation Tonometer and the TonoPen. The Proview was not considered reliable.

High mobility group box-1 protein (HMGB1) is an evolutionarily ancient protein, which, as an important non-histone chromosome-binding protein in organism cells, is involved in a variety of important biological processes, including DNA repair, gene transcription, cellular inflammatory response, and autophagy. In this study, we established an eccentric exercise model to observe the effect of HMGB1 on skeletal muscle autophagy and to investigate the underlying molecular mechanisms. Forty-eight male 8-week-old SD rats were randomly divided into control group (C) and exercise group (E). Group E was subjected to a bout of eccentric exercise on a treadmill and sampled soleus at 0 h, 12 h, 24 h, 48 h, and 72 h post-exercise. The speed of the exercise protocol in this study was 16 m/min, the slope was −16°, and the time was 90 min. The ultrastructural changes of skeletal muscle were observed by transmission electron microscopy. The protein expressions of HMGB1, Beclin1, and LC3 were detected by Western Blot. The co-localizations of Beclin1/Bcl-2, Beclin1/HMGB1, and Beclin1/Vps34 were measured by immunofluorescence. The results show that eccentric exercise leads to abnormal changes in the ultrastructure of skeletal muscle, and the protein levels of Beclin1, LC3-II/LC3-I, and the content of HMGB1 in nuclear and cytoplasm were significantly increased at 24 h post-exercise (P< 0.05). The co-localization of Beclin1/Bcl-2 and Beclin1/HMGB1 were increased significantly at 0 h post-exercise and then decreased, while the co-localization of Beclin1/Vps34 showed the highest level at 24 h post-exercise. In conclusion, HMGB1 facilitates the separation of Beclin1 from Bcl-2 and promotes Beclin1 binding to Vps34, which may play an important role in eccentric exercise-induced skeletal muscle autophagy.

In this paper, Burr-X distribution with Type-II hybrid censored data is considered. The E-Bayesian estimation (the expectation of the Bayesian estimate) and the corresponding Bayesian and maximum likelihood estimation methods are studied for the distribution parameter and the reliability function. Bayesian and E-Bayesian estimates are obtained under LINEX and squared error loss functions. By applying the Markov chain Monte Carlo techniques, Bayesian and E-Bayesian estimates are obtained. Also, confidence intervals of maximum likelihood estimates, as well as credible intervals of Bayesian and E-Bayesian estimates, are constructed. Furthermore, a numerical example of a real-life dataset is provided for the purpose of illustration. Finally, a comparison among the E-Bayesian, the Bayesian and the maximum likelihood methods is presented.

In this work, a new technique of self-consumption friction plug spot welding (SFPSW) was introduced to spot welding of Ti–6Al–4V alloy sheets using a semi-consumable welding tool, and defect-free joints were successfully produced. The semi-consumable welding tool consists of a nickel-based superalloy shoulder and a titanium alloy plug. The spot welding parameters were discussed, and the effect of welding parameters on the microstructure and mechanical properties of the joints was investigated. The cross-section of the welding zone was divided into five regions: base metal (BM), heat-affected zone (HAZ), thermo-mechanically affected zone (TMAZ), stir zone (SZ), and filled zone (FZ). The final joint interface has a basket-weave structure. The maximum tensile-shear load of the joint was up to 69.5 kN and the hardness value of the welding region was lower than that of base metal. The failure mode of the tensile-shear test was a typical quasi-cleavage fracture.

•Friction stir welding of Ti-6Al-4V plates performed successfully by a newly designed tool.•The peak welding temperature exceeded the β-phase transition temperature and the final microstructure of the stir zone was lamellar (α + β) structure.•The tensile strength of the welding samples could up to 92% of that of the parent metal.•The micro-hardness of the weld cross-section has differences among layers.

The current study reported the effects of various beam offsets on macro defects, fusion ratios, chemical compositions in the weld, microstructure and mechanical performances of dissimilar joint between super duplex stainless steel (SDSS) 2507 and low carbon high strength Q235 steel using laser beam welding without filler metal. The laser beam offset was defined as the distance between the weld centerline and the position of the laser beam and the positive offsets represent the focal point of the laser beam toward the SDSS2507 side. The experimental results showed the maximum fusion ratio reached 64.7 % with the beam offset of 0.5mm which was measured by EDS indirectly. The chemical composition significantly influenced the formation of the phases in the weld. The XRD, SEM, EBSD and TEM results presented that the main phase in weld was the untempered martensite. Furthermore, the delta ferrite and retained austenite were also formed with the increasing of fusion ratio. In addition, the morphology of untempered martensite and delta ferrite transformed from columnar dendrites to cellular dendrites. The retained austenite occurred which attributed to the high fusion ratio of the SDSS2507 and distributed at the core region of untempered martensite and boundaries of lath martensite respectively. The orientation relationship between martenstie and austenite also showed a decreasing deviation from k-s relationship while the beam offset increased. A qualified welded joint was obtained, the corresponding tensile strength and hardness were 785MPa and 486HV, respectively. However, the maximum charpy impact toughness measured to be 24J showing a relatively low plasticity. Besides, the impact fracture surface suggested the mixed mode accompanying by the brittle fracture and small amount of dimples.

SYNOPTIC ABSTRACTThis article deals with Bayesian and E-Bayesian (expectation of the Bayesian estimate) estimation methods of the parameter and the reliability function of Burr-X distribution based on a generalized Type-I hybrid censoring scheme. Bayesian and E-Bayesian estimates are obtained under LINEX and squared error loss functions. By applying Markov chain Monte Carlo techniques, Bayesian and E-Bayesian estimates based on a generalized Type-I hybrid censoring scheme are derived. Also, credible intervals for Bayesian and E-Bayesian estimates are computed. Examples of generalized Type-I hybrid censored samples and real data sets are presented for the purpose of illustration. Finally, a comparison between Bayesian and E-Bayesian estimation methods is conducted.

•A CDC7 inhibitor XL413 effectively enhanced the chemotherapeutic effect of carboplatin.•Mechanistically, the CDC7 inhibitor XL413 increases the accumulation of chemotherapy-induced DNA damage by inhibiting homologous recombination repair activity and delaying the recovery of DNA double-strand breaks.•XL413 reduced relapses after treatment with carboplatin in vitro and in vivo.

The H9N2 subtype of avian influenza virus (AIV) is widely prevalent in poultry and wild birds globally, and has become the predominant subtype circulating in poultry in China. The H9N2 AIV can directly or indirectly (by serving as a “donor virus”) infect humans, posing a significant threat to public health. Currently, there is a lack of in-depth research on the prevalence of H9N2 viruses in Shanxi Province, central China. In this study, we isolated 14 H9N2 AIVs from October 2020 to April 2022 in Shanxi Province, and genetic analysis revealed that these viruses belonged to seven different genotypes. Our study on animals revealed that the H9N2 strains we identified displayed high transmission efficiency among chicken populations, and exhibited diverse replication abilities within these birds. These viruses could replicate efficiently in the lungs of mice, with one strain also demonstrating the capacity to reproduce in organs like the brain and kidneys. At the cellular level, the replication ability of different H9N2 strains was evaluated using plaque formation assays and multi-step growth curve assays, revealing significant differences in the replication and proliferation efficiency of the various H9N2 viruses at the cellular level. The antigenicity analysis suggested that these isolates could be classified into twoseparate antigenic clusters. Our research provides crucial data to help understand the prevalence and biological characteristics of H9N2 AIVs in central China. It also highlights the necessity of enhancing the surveillance of H9N2 AIVs.

To improve the degree of materials mixing in dissimilar Friction Stir Welded (FSW) joints and mechanical properties, a novel stirring tool with dual-pin structure was designed and used to perform welding AA 2024 to AA6061 aluminum alloy plates with butt configuration. The microstructure and mechanical properties of the joints fabricated by single-pin and dual-pin tools were studied using optical microscope (OM), scanning electron microscope (SEM), microshardness tester and tensile testing machine. It was found that joints produced by dual-pin tool were all free of defects throughout the selected parameters, but for the joints produced by single-pin welded joints, void defects were produced at welding speed higher than 90 mm/min. All the nugget regions of dual-pin joints were characterized by typical onion ring patterns which were absent in those obtained by dual-pin tool. The highest ultimate tensile strength (UTS) of 242 MPa was obtained with the dual-pin tool at welding speed of 150 mm/min, while for the case of single-pin the best joint was obtained at welding speed of 90 mm/min. For the defect free joints, those produced by dual-pin tool showed more uniform microhardness distribution over the cross section of joints than the ones produced by single-pin tool.

In the quest for developing a catalyst with as many desired characteristics, a facile synthetic route was designed for the preparation of mesoporous silica coated magnetic nanoparticles(MSMNP) employing a colloid mill reactor. The composite particles were characterized by the techniques, such as nitrogen adsorption-desorption isotherms, scanning electron microscopy(SEM), transmission electron microscopy(TEM), X-ray diffraction patterns (XRD), thermo-gravimetric analysis(TGA), Fourier transform infrared spectroscopy(FTIR) and vibrating sample magnetometer(VSM), etc. The analysis showed that the resulted MSMNP composites were composed of silica shell layers with open pores connecting channels and NiFe2O4with spinel structure, so the thermal treatment temperature did not show significant effect on pore textural properties, and its specific surface areas were in the range of 443–474 m2/g, while pore volume of about 0.8 cm3/g with an average pore size of around 9.5 nm. The composites with super paramagnetic nature were encapsulated entirely with amorphous silica layers contributing to optimum porosity and abundant surface hydroxyl groups.

We consider a very general interacting branching process which includes most of the important interacting branching models considered so far. After obtaining some key preliminary results, we first obtain some elegant conditions regarding regularity and uniqueness. Then the extinction vector is obtained which is very easy to be calculated. The mean extinction time and the conditional mean extinction time are revealed. The mean explosion time and the total mean life time of the processes are also investigated and resolved.

This paper is concerned with an extended Galton–Watson process in which individuals are allowed to live and reproduce for more than one unit time. We assume that each individual can live k seasons (time-units) with probability h k , and produce m offspring with probability p m at the end of each season. It can be viewed as Galton–Watson processes with countably infinitely many types in which particles of type i may only have offspring of type i + 1 and type 1. Let M be its mean progeny matrix and γ be the convergence radius of the power series ∑ k ≥ 0 r k (M k) i j . We first derive formula of calculating γ and show that γ , in supercritical case, is actually the extinction probability of a Galton–Watson process. Next, we give clear criteria for M to be γ -transient, γ -positive and γ -null recurrent from which the ergodic property of the process is discussed. The criteria for γ -recurrence of M rely on the properties of lifetime distribution which are easier to be verified than current results. Finally, we show the asymptotic behavior of the total population size of each type of individuals under certain conditions which illustrates the evolution of Galton–Watson process in which individuals have variable lifetimes. [ABSTRACT FROM AUTHOR]

This paper concentrates on discussing the regularity property of 2-type Markov branching processes with immigration. We find a curve by using a differential equation based on the related generating functions. Hence a regularity criterion which is very easy to check is obtained. [ABSTRACT FROM AUTHOR]

In this paper we consider an M/M/cqueue modified to allow both mass arrivals when the system is empty and the workload to be removed. Properties of queues which terminate when the server becomes idle are firstly developed. Recurrence properties, equilibrium distribution, and equilibrium queue-size structure are studied for the case of resurrection and no mass exodus. All of these results are then generalized to allow for the removal of the entire workload. In particular, we obtain the Laplace transformation of the transition probability for the absorptive M/M/cqueue.

In this paper, some Φ -moment martingale inequalities associated with concave functions are proved in the frame of Lorentz spaces. Our main method is to construct some new atomic decomposition theorems. [ABSTRACT FROM AUTHOR]

Magnetic TS-1 was synthesized with nanosized nickelferrite particles as nuclei via the hydrothermal synthesis and solvent vaporation method. The prepared samples were characterized with N2adsorption-desorption isotherms, FTIR spectrometry, Raman spectrometry, X-ray diffraction, Ultraviolet-visible spectroscopy and Vibrating sample magnetometry. The results show that the composite obtained was composed of TS-1 with MFI structure and NiFe2O4with spinel structure, its specific surface area was about 316 m2/g, pore volume was 0.12 cm3/g and pore size distribution was in the range of 0.5–0.7 nm. The catalytic activity of the composite was also investigated by its catalyzing the decomposition of rhodamine B oxidized by H2O2in aqueous solution. In this case Rhodamine B pollutant could be completely degraded within 150 min. Magnetic TS-1 exhibited high photocatalytic efficiency and super paramagnetic nature for cleaning polluted water with the help of magnetic separation.

Although the exact expressions for the extinction probabilities of the Interacting Branching Collision Processes (IBCP) were very recently given by Chen et al.[4], some of these expressions are very complicated; hence, useful information regarding asymptotic behaviour, for example, is harder to obtain. Also, these exact expressions take very different forms for different cases and thus seem lacking in homogeneity. In this paper, we show that the asymptotic behaviour of these extremely complicated and tangled expressions for extinction probabilities of IBCP follows an elegant and homogenous power law which takes a very simple form. In fact, we are able to show that if the extinction is not certain then the extinction probabilities {an} follow an harmonious and simple asymptotic law of an~ kn-a?cnas n? 8, where kand a are two constants, ?cis the unique positive zero of the C(s), and C(s) is the generating function of the infinitesimal collision rates. Moreover, the interesting and important quantity a takes a very simple and uniform form which could be interpreted as the ‘spectrum’, ranging from -8 to +8, of the interaction between the two components of branching and collision of the IBCP.

Abstract: We consider a kind of Collision Branching Processes with Immigration (CBIP). Some important properties of the generating functions for the CBI -matrix were first investigated in detail. Then for any given CBI -matrix, the existence and uniqueness of CBIP is proved, and sufficient and easily checked conditions for the CBIP to be recurrent are given. Moreover, the exact value of the decay parameter is obtained and expressed explicitly for the communicating class in the case that the immigration is independent of states. It is shown that this can be directly obtained from the generating functions of the corresponding -matrix. Finally, the invariant vectors and invariant measures are considered. [Copyright &y& Elsevier]

We consider decay properties including the decay parameter, invariant measures, invariant vectors, and quasistationary distributions for n-type Markov branching processes on the basis of the 1-type Markov branching processes and 2-type Markov branching processes. Investigating such behavior is crucial in realizing life period of branching models. In this paper, some important properties of the generating functions for n-type Markov branching q-matrix are firstly investigated in detail. The exact value of the decay parameter ?Cof such model is given for the communicating class C= Z+n\ 0. It is shown that this ?Ccan be directly obtained from the generating functions of the corresponding q-matrix. Moreover, the ?C-invariant measures/vectors and quasidistributions of such processes are deeply considered. ?C-invariant measures and quasi-stationary distributions for the process on Care presented.We consider decay properties including the decay parameter, invariant measures, invariant vectors, and quasistationary distributions for n-type Markov branching processes on the basis of the 1-type Markov branching processes and 2-type Markov branching processes. Investigating such behavior is crucial in realizing life period of branching models. In this paper, some important properties of the generating functions for n-type Markov branching q-matrix are firstly investigated in detail. The exact value of the decay parameter ?Cof such model is given for the communicating class C= Z+n\ 0. It is shown that this ?Ccan be directly obtained from the generating functions of the corresponding q-matrix. Moreover, the ?C-invariant measures/vectors and quasidistributions of such processes are deeply considered. ?C-invariant measures and quasi-stationary distributions for the process on Care presented.

We consider the uniqueness and extinction properties of the interacting branching collision process (IBCP), which consists of two strongly interacting components: an ordinary Markov branching process and a collision branching process. We establish that there is a unique IBCP, and derive necessary and sufficient conditions for it to be nonexplosive that are easily checked. Explicit expressions are obtained for the extinction probabilities for both regular and irregular cases. The associated expected hitting times are also considered. Examples are provided to illustrate our results.

Abstract: We consider a modified Markov branching process incorporating with both state-independent immigration-migration and resurrection. The effect of state-independent immigration-migration is firstly investigated in detail. The explicit expressions for the extinction probabilities and mean extinction times are presented. The ergodicity and stability properties of the process incorporating with resurrection structure are then investigated. The conditions for recurrence, ergodicity and exponential ergodicity are obtained. An explicit expression for the equilibrium distribution is also presented. As a preparation, the criteria for regularity and uniqueness for such structure are firstly established.

A TS-1 zeolite with a disordered network of mesopores penetrating the microporous crystalline zeolite framework was successfully synthesized by a one-pot carbon hard-templating synthesis approach. Besides conventional methods to characterize the mesoporosity, the use of variable-temperature 129Xe NMR spectroscopy was explored. At low temperature, a new resonance of 129Xe adsorbed in the mesopores could be distinguished from the signal of Xe in the micropores. The similarity of UV−vis and UV resonance Raman spectra of this mesoporous TS-1 zeolite with a conventional microporous TS-1 zeolite shows that the local coordination environment of Ti in these samples is identical. Further characterization (TEM, XRD) indicates that phase separation of titanium oxide is absent. The mesoporous TS-1 zeolite exhibits improved catalytic activity in the hydroxylation of phenol and ammoxidation of methyl ethyl ketone. The catalytic activity is substantially improved by introducing mesoporosity in TS-1, whereas the selectivity to the desired products is very similar. The improved catalytic activity of the TS-1 with the hierarchical structure is mainly attributed to the improved mass transfer of reactants and products into and out of the zeolite micropores. The generation of the hierarchical pore structure by the one-pot carbon-templating route becomes a general strategy for the synthesis of hierarchical zeolite with different compositions.

Abstract: This note provides a new probabilistic approach in discussing the weighted Markov branching process (WMBP) which is a natural generalisation of the ordinary Markov branching process. Using this approach, some important characteristics regarding the hitting times of such processes can be easily obtained. In particular, the closed forms for the mean extinction time and conditional mean extinction time are presented. The explosion behaviour of the process is investigated and the mean explosion time is derived. The mean global holding time and the mean total survival time are also obtained. The close link between these newly developed processes and the well-known compound Poisson processes is investigated. It is revealed that any weighted Markov branching process (WMBP) is a random time change of a compound Poisson process. [Copyright &y& Elsevier]

We consider decay properties including the decay parameter, invariant measures, invariant vectors, and quasistationary distributions of a Markovian bulk-arriving queue that stops immediately after hitting the zero state. Investigating such behavior is crucial in realizing the busy period and some other related properties of Markovian bulk-arriving queues. The exact value of the decay parameter ?Cis obtained and expressed explicitly. The invariant measures, invariant vectors, and quasistationary distributions are then presented. We show that there exists a family of invariant measures indexed by ? ? [0, ?C]. We then show that, under some conditions, there exists a family of quasistationary distributions, also indexed by ? ? [0, ?C]. The generating functions of these invariant measures and quasistationary distributions are presented. We further show that a stopped Markovian bulk-arriving queue is always ?C-transient and some deep properties are revealed. The clear geometric interpretation of the decay parameter is explained. A few examples are then provided to illustrate the results obtained in this paper.

We present an elegant uniqueness criterion for the weighted Markov branching process in the potentially explosive case.

Abstract: We extend the Harris regularity condition for ordinary Markov branching process to a more general case of non-linear Markov branching process. A regularity criterion which is very easy to check is obtained. In particular, we prove that a super-linear Markov branching process is regular if and only if the per capita offspring mean is less than or equal to 1 while a sub-linear Markov branching process is regular if the per capita offspring mean is finite. The Harris regularity condition then becomes a special case of our criterion. [Copyright &y& Elsevier]

We consider a branching model, which we call the collision branching process (CBP), that accounts for the effect of collisions, or interactions, between particles or individuals. We establish that there is a unique CBP, and derive necessary and sufficient conditions for it to be nonexplosive. We review results on extinction probabilities, and obtain explicit expressions for the probability of explosion and the expected hitting times. The upwardly skip-free case is studied in some detail.

We report an unusual case of acute recurrent bilateral multifocal choroidal neovascularization that was associated with histologically proven membranoproliferative glomerulonephritis type II and did not resolve with laser photocoagulation. Early development of subretinal neovascular membranes with widespread retinal pigment epithelial changes in this condition may heraid poor prognosis despite laser ablation of the neovascular tuft.

By using the highly sensitive and specific technique of enzyme-linked immunosorbent assay, we investigated the presence and amount of transforming growth factor-β2 (TGF-β2) in samples of aqueous humor obtained from 15 patients who had a clinically established diagnosis of advanced primary open-angle glaucoma (POAG), as well as from ten age-matched normal human subjects undergoing cataract surgery. The total amount of TGF-β2 in the samples of normal aqueous humor ranged from 0·41 to 2.24 ng ml^-1 (mean ± S.D.: 1·48 ± 0·68 ng ml^-1) of which 4·88 to 37·05% (11·99 ± 9·95%) was intrinsically active. Compared with normal subjects, the aqueous humor from POAG patients had a statistically significantly greater amount of total TGF-β2 (2·70 ± 0·76 ng ml^-1 P < 0·01), AS WELL AS A HIGHER LEVEL OF INTRINSICALLY ACTIVE TGF-β2 (0·45 ± 0·28 NG ML^-1

By using the techniques of reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern hybridization, we demonstrated that human Tenon's capsule fibroblasts in primary cultures, express the messenger RNA (mRNA) transcripts encoding transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF), but not those coding for aFGF and TGF-β2. Two PCR products were obtained for TGF-β1: a major fragment of 161 base pairs that corresponded to the expected size, and a minor sequence of 400 base pairs. An antisense oligonucleotide probe specific for TGF-β1 detected only the band of 161 base pair of PCR-amplified sequence. For bFGF, PDGF-A and PDGF-B, we obtained only a single PCR product with the anticipated length of 222, 225, and 217 base pairs, respectively. Southern blotting experiments revealed that these PCR-amplified fragments were specific for the respective growth factors. The negative control experiments without template did not reveal any amplification. No product for aFGF or TGF-β2 was detected. By radioimmunoassay, TGF-β1 protein was detected at the level of 24–30 pg ml−1per 2 million Tenon's fibroblasts during a 24-hour period in acid-activated conditioned medium. These results indicate that human Tenon's capsule fibroblasts in primary cultures express TGF-β1 at the translational as well as at the transcriptional levels, and they also have the capacity to synthesize bFGF and PDGF. Considering the significant effects of bFGF, TGF-β1, and PDGF in wound healing response, these growth factors are implicated in tissue repair process after glaucoma filtration surgery that contributes to the failure of the procedure.

The changes in the morphology and the amounts of selected extracellular matrix proteins in serially passaged porcine trabecular cells cultured from young animals (age range, 4–6 months) were investigated. After 4 weeks incubation, trabecular cells in primary confluent cultures had a flattened elongated profile, whereas the cells in secondary or tertiary cultures, after an additional 4 to 8 weeks incubation, respectively, were epithelioid in shape. Time-lapse micrography of the passaged cells revealed membrane ruffling at the cell periphery, but sparse cell movement. No mitotic events took place in either the secondary or tertiary cultures for 24 hr prior to harvesting the cells. No remarkable differences were observed in the total polypeptide profile of primary, secondary or tertiary cells analysed by SDS gel electrophoresis and silver staining. However, laser densitometry of immunoblots treated with antibodies against type VI collagen, thrombospondin, fibronectin, and laminin demonstrated that, compared to primary cultures of trabecular cells, the amount of type VI collagen was elevated 20.5-fold in tertiary cultures, thrombospondin 6-fold, and fibronectin 5-fold, but laminin was not detectable. Because aging trabecular cells in vitro exhibit specific biochemical characteristics that are comparable to those known to occur in the human trabecular meshwork in vivo, the present method provides a model for the investigation of age-related changes in this tissue at the cellular level under defined and controlled conditions.

By radioligand binding followed by Scatchard analysis, we characterized and quantitated the specific binding sites for bFGF on cultured trabecular meshwork cells obtained from freshly enucleated porcine eyes. We detected two binding sites: 1.67×104±5.75×103high-affinity receptors per cell with a Kdof 33.4±7.90 pM, and 1.70×106±7.57×105low-affinity binding sites per cell with a Kdof 3.84±1.41 nM. At low concentrations of125I-bFGF (<1.50 ng ml−1), binding was primarily determined by the high-affinity receptors and, at high concentrations (>2.50 ng ml−1), binding was dependent on the low-affinity binding sites. By phase-contrast time-lapse video micrography and sequential photomicrography, we demonstrated that at a concentration of 1 ng ml−1, bFGF significantly stimulated the rate of mitosis of the trabecular meshwork cells in G0-phase compared with control cultures maintained in serum-free medium alone. Treatment with higher concentrations of bFGF did not reveal more potent effects on these cells. Our findings demonstrate that trabecular meshwork cells do possess low- and high-affinity receptors for bFGF and that bFGF induces these cellsin vitroto re-enter the cell cycle.

To investigate the nature of the 140 kDa glycoprotein in the trabecular meshwork, polypeptides were extracted with either urea/sodium dodecyl sulfate (SDS)/beta-2-mercaptoethanol (BME) or guanidine hydrochloride followed by pepsin digestion. After electrophoresis and immunoblotting with anti-type-VI-collagen antibodies, a single fraction of molecular weight 140 kDa was identified in the urea/SDS/BME extracts. Pepsin solubilization revealed two immunoreactive fractions (molecular weights 75 and 85 kDa) that comigrated with purified, pepsin-solubilized type VI collagen. By using the polymerase chain reaction (PCR) and primers specific for the α2(VI) chain of type VI collagen, a single PCR product was obtained, which corresponded to the expected size of 137 base pairs, from the total RNA extracted from the trabecular meshwork ex vivo. Southern hybridization with the antisense oligonucleotide probe of the α2(VI) chain confirmed that the amplified sequence was specific. The results show that the trabecular meshwork contains a significant amount of type VI collagen and that trabecular cells express the mRNA coding for the α2(VI) chain of this glycoprotein. The presence of type VI collagen in the trabecular meshwork is implicated in cell-extracellular matrix interactions at this site, and its abnormal accumulation in glaucomatous and aging eyes probably signifies a defect in the function of the trabecular cells in these eyes. Copyright 1994, 1999 Academic Press

• Although free radical formation and lipid peroxidation have been implicated in photoreceptor degeneration following continuous light exposure, recent evidence led us to hypothesize that excessive stimulation of the photoreceptor cells in prolonged light exposure may cause intracellular calcium overload and consequent photoreceptor cell injury. To test this hypothesis, we studied the effects of flunarizine hydrochloride, a calcium overload blocker that inhibits the inositol 1,4,5-triphosphate-induced release of intracellular stores of calcium, in an established rat model of light-induced retinal degeneration. Light and electron microscopic examination of the flunarizine-treated retinas revealed remarkable preservation of the retinal pigment epithelium, rod inner and outer segments, nuclei, and synapses of the photoreceptor cells at all phases of the recovery period. This observation was further supported by morphometric evaluation of the outer nuclear layer thickness, which revealed a greater preservation of the photoreceptor nuclei in the drug-treated animals at 6 and 14 days after exposure. In addition, the rhodopsin levels in the flunarizine-treated retinas were also significantly higher than in the controls in all phases of recovery. The ability of flunarizine to ameliorate light-induced retinal degeneration in the rat supports our hypothesis that elevated intracellular calcium may indeed play a role in light-induced photoreceptor degeneration.

We investigated whether trabecular cells contain TGE-β2 mRNA and whether they synthesize this cytokine. By using a primer pair for TGF-β2 and the highly specific and sensitive techniques of reverse transcriptase-polymerase chain reaction, a single amplified sequence was obtained from cultured trabecular cells and tissue samples of trabecular meshwork, corneal epithelium, iris and ciliary body ex vivo from fresh porcine eyes. Regression analysis with standard DNA size markers indicted that the products were of the anticipated size of 310 base pairs. Southern hybridization further confirmed that all of the products were specific for TGF-β2. Enzyme-linked immunosorbent assay (ELISA) with a specific antibody against TGF-β2 revealed that this cytokine was secreted by cultured trabecular cells in the conditioned medium. The TGF-β2 produced by trabecular cells was in a latent form, and no intrinsically active protein was detected. The results suggest that TGF-β2 has an autocrine and/or paracrine action in the trabecular meshwork system, and that trabecular cells could contribute to the presence of TGF-β2 in their microenvironment as well as in aqueous humor. It is hypothesized that abnormal changes in the production of TGF-βs by trabecular cells and/or in the activation of these growth modulators contribute to the excess accumulation of extracellular matrix components in the aqueous outflow system as observed in aging and glauvomatous eyes.

The emergence of the PB2 E627K substitution is critical in the mammalian adaptation and pathogenesis of AIV. H7N9 AIVs that emerged in 2013 possess a prominent ability in gaining the PB2 E627K mutation in humans. Here, we demonstrate that the acquisition of the H7N9 PB2 E627K mutation is driven by the low polymerase activity conferred by the viral PA protein in human cells, and four PA residues are collectively involved in this process. Notably, the H7N9 PA protein leads to significant dependence of viral polymerase function on human ANP32A protein, and Anp32aknockout abolishes PB2 E627K acquisition in mice. These findings reveal that viral PA and host ANP32A are crucial for the emergence of PB2 E627K during adaptation of H7N9 AIVs to humans.

In the present work, chloropropyl-functionlized MCM-41 were prepared by a simple synthetic pathway and firstly studied as gas chromatography matrix for the separation of water–alcohol mixtures.

A simple and nonsurfactant synthesis pathway has been developed to prepare silica-based bimodal micro/mesoporous hybrids using mixed polymethylhydrosiloxane and tetraethyl orthosilicate as silica sources.

ZnS nanofibers with lamellar mesostructures were synthesized by hydrothermal reaction of Zn(Ac)2and Na2S using neutral n-alkylamines (alkyl = C8–C16) as structure-directing template and ethylenediaminetetraacetic acid as stabilizer.