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Background: The effect of two lung ventilation (TLV) with carbon dioxide artificial pneumothorax on cerebral desaturation and postoperative neurocognitive changes in elderly patients undergoing elective minimally invasive esophagectomy (MIE) is unclear. Objectives: The first aim of this study was to compare the effect of TLV and one lung ventilation (OLV) on cerebral desaturation. The second aim was to assess changes in early postoperative cognitive outcomes of two ventilation methods. Methods: This prospective, randomized, controlled trial enrolled patients 65 and older scheduled for MIE. Patients were randomly assigned (1:1) to TLV group or OLV group. The primary outcome was the incidence of cerebral desaturation events (CDE). Secondary outcomes were the cumulative area under the curve of desaturation for decreases in regional cerebral oxygen saturation (rSO2) values below 20% relative to the baseline value (AUC.20) and the incidence of delayed neurocognitive recovery. Results: Fifty-six patients were recruited between November 2019 and August 2020. TLV group had a lower incidence of CDE than OLV group [3 (10.71%) vs. 13 (48.14%),P= 0.002]. TLV group had a lower AUC.20 [0 (0–35.86) % min vs. 0 (0–0) % min, P= 0.007], and the incidence of delayed neurocognitive recovery [2 (7.4%) vs. 11 (40.7%), P= 0.009] than OLV group. Predictors of delayed neurocognitive recovery on postoperative day 7 were age (OR 1.676, 95% CI 1.122 to 2.505, P= 0.006) and AUC.20 (OR 1.059, 95% CI 1.025 to 1.094,P< 0.001). Conclusion: Compared to OLV, TLV had a lower incidence of CDE and delayed neurocognitive recovery in elderly patients undergoing MIE. The method of TLV combined with carbon dioxide artificial pneumothorax may be an option for these elderly patients.

This article presents a design automation framework for the placement and clock tree synthesis of superconducting rapid single-flux-quantum (RSFQ) logic. The framework includes a global placement method for gate-level-pipelined layout optimization, a clock tree synthesis procedure for HL-tree construction with concurrent-flow and counter-flow schemes, and a detailed placement method for congestion optimization. In the global placer, the optimization problem is reformulated to reduce the run-time cost while maintaining optimization quality; the clock tree synthesis is performed using the bottom-top iterative algorithm, combining synchronizer synthesis and clock tree construction to shrink the size of the clock tree; eventually, the detailed placer performs the algorithm based on Delaunay triangulation and Lloyd iteration, adjusting layout placement under certain constraints. Several benchmarks are used to validate the effectiveness of the proposed framework, and the results show that the framework is capable of maximizing the utilization of layout space and providing a routable layout environment for hybrid routing within a controlled run-time.

IMPORTANCE: Additional therapies for amyotrophic lateral sclerosis (ALS) are urgently needed. Immune-mediated complement activation may be involved in ALS pathogenesis as evidenced by the upregulation of terminal components; thus, complement inhibition could potentially slow progression. OBJECTIVE: To evaluate the safety and efficacy of the terminal complement C5 inhibitor ravulizumab in adults with ALS. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, parallel-group, multinational, randomized, phase 3 clinical trial was conducted from March 30, 2020, to October 17, 2021, in 81 ALS specialty centers across 17 countries. A preplanned, unmasked, nonbinding interim futility analysis was conducted when 33% of participants had completed week 26, wherein a conditional power of less than 10% would halt the trial. A total of 478 individuals were screened, and 96 were excluded. Inclusion criteria were weight of 40 kg or more, fulfillment of the El Escorial diagnostic criteria, and a minimal prestudy Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) progression score of –0.3 points per month. INTERVENTIONS: Study treatment consisted of placebo or a weight-based dose of intravenous ravulizumab every 8 weeks until week 42. Participants could continue standard-of-care treatment. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline in ALSFRS-R score at week 50 based on the Combined Assessment of Function and Survival (CAFS). RESULTS: A total of 382 participants were randomly assigned 2:1 to receive ravulizumab (n = 255; mean [SD] age, 58.6 [10.6] years; 94 female [36.9%] and 161 male [63.1%]) or placebo (n = 127; mean [SD] age, 58.0 [11.0] years; 58 female [45.7%] and 69 male [54.3%]). The interim analysis showed that the observed mean change from baseline in ALSFRS-R at week 50 was −14.67 points (SE, 0.89 points; 95% CI, −16.42 to −12.91 points) for ravulizumab and −13.33 points (SE, 1.22 points; 95% CI, −15.72 to −10.93 points) for placebo, with no significant difference between the groups (mean [SE] difference, −1.34 [1.46] points; 95% CI, −4.21 to 1.53 points). Based on these data, the trial was terminated for futility. The primary analysis at week 50 showed no significant difference in CAFS between groups (mean [SE], 5.5 [10.8] points; 95% CI, −15.7 to 26.6 points; P = .61). Overall incidence rates for treatment-emergent adverse events were similar for ravulizumab (204 participants [80.0%]) and placebo (108 participants [85.0%]). CONCLUSIONS AND RELEVANCE: This trial rapidly showed that terminal complement C5 inhibition with ravulizumab did not slow functional decline in participants with ALS and that the safety profiles of ravulizumab and placebo were similar. Highly effective, novel treatments are critically needed to slow functional decline and extend survival in patients with ALS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04248465

We have been developing a power supply analysis tool for Josephson junction-based circuits, embedded in our analog simulator JSICsim, supporting power-related analysis functions such as current distribution, invalid DC biases, and variance map analysis. The power analysis procedure involves the power mesh layout processing based on different types of models. The power mesh is converted into a netlist, which will be used to form a top-level netlist together with the core netlist. Using JSICsim for simulation and iteration, the current distribution data could be obtained, and its static and dynamic heat map could be rendered for designers. In this article, we also demonstrate several testbench circuits fabricated by using SIMIT-Nb03 technology, providing their simulation and testing results with analysis. The results show that by using this power supply analysis tool, the designers can locate the potential high-risk areas in terms of the current distribution in their design and use this information for improvement before fabrication.

This work deals with energy performance calculate results of new solid composite propellants based on Hexanitroethane (HNE) and Hydrazinium nitroformate (HNF). The energy characteristics of solid propellants with HNE and HNF are estimated using NASA Chemical Equilibrium with Applications (CEA). The effect of HNE and HNF as energetic oxidizers on the energy characteristics of composite modified double-base (CMDB) propellants, hydroxyl-terminated polybutadiene (HTPB) propellants, nitrate ester plasticized polyether (NEPE) propellants, glycidyl azide polymer (GAP) propellants has been carried out. Characteristics of ingredients and propellant formulations with HNE and HNF are presented together with the calculate results which demonstrate the increased performance compared to conventional high-performance propellants based on Ammonium Perchlorate (AP). The results show that HNE and HNF can improve the standard theoretical specific impulse of the four propellants in different degrees, and HTPB propellant has the most significant improvement, which is 12.26 s for HNE-based propellant and 14.12 s for HNF-based propellant. At the same time, both HNE and HNF reduce the infrared emission of propellant exhaust plumes when they replace AP, and reduce or even completely eliminate HCl gas in exhaust products. Therefore, it is expected that HNE-based and HNF-based propellants may provide a promising chlorine-free alternative to existing AP-based formulations.

In a proxy signature scheme, an original signer can delegate his/her signing capability to a proxy signer, so that the proxy signer can sign on behalf of the original signer. Proxy signature is an important technology in delegated authentication schemes, so it is important to design provably secure proxy signature schemes. Boldyreva et a1. (2012) gave the definition of proxy signature and formalised a model of security for proxy signature schemes. They not only formalised a model of security for proxy signature schemes, but also specified the adversary's capabilities and goals. In this paper, we propose a new provably secure proxy signature scheme under this model, which is more efficient than that of the existing ones. Furthermore, we use this signature scheme to construct a proxy blind signature scheme, and give the security analysis of the new scheme. Proxy blind signature can be applied in cloud computing.

ABSTRACTSolid tumors contain numerous regions with insufficient oxygen concentrations, a condition termed hypoxia. Tumor hypoxia is significantly associated with metastasis, refractory to conventional cancer therapies, and poor patient survival. Therefore, eradication of hypoxic tumor cells will likely have significant impact on the overall progression-free patient survival. This article reports a new discovery that Benznidazole, a bioreductive drug currently used to treat Chagas disease caused by the parasitic protozoan Trypanosoma cruzi, is activated by hypoxia and can kill clonogenic tumor cells especially those under severe hypoxic conditions (≤0.1 % O2). This type of hypoxia selectivity is important in that severely hypoxic tumor microenvironment is where tumor cells exhibit the strongest resistance to therapy. Mechanistically, activation of Benznidazole coincides with the stabilization of the Hypoxia-Inducible Factor 1α (HIF-1α), suggesting that Benznidazole is activated after tumor cells have entered into a fully hypoxic state. Under such hypoxic conditions, Benznidazole induces the formation of 53BP1 foci, a hallmark of DNA double-stranded breaks that can cause clonogenic inhibition or cell death. These results demonstrate that Benznidazole is a hypoxia-activated cytotoxin with the potential to specifically eliminate hypoxic tumor cells.

A direct as well as iterative method (called the orthogonally accumulated projection method, or the OAP for short) for solving linear system of equations with symmetric coefficient matrix is introduced in this paper. With the Lanczos process the OAP creates a sequence of mutually orthogonal vectors, on the basis of which the projections of the unknown vectors are easily obtained, and thus the approximations to the unknown vectors can be simply constructed by a combination of these projections. This method is an application of the accumulated projection technique proposed recently by the authors of this paper, and can be regarded as a match of conjugate gradient method (CG) in its nature since both the CG and the OAP can be regarded as iterative methods, too. Unlike the CG method which can be only used to solve linear systems with symmetric positive definite coefficient matrices, the OAP can be used to handle systems with indefinite symmetric matrices. Unlike classical Krylov subspace methods which usually ignore the issue of loss of orthogonality, OAP uses an effective approach to detect the loss of orthogonality and a restart strategy is used to handle the loss of orthogonality. Numerical experiments are presented to demonstrate the efficiency of the OAP.

AbstractMost current prevalent iterative methods can be classified into the socalled extended Krylov subspace methods, a class of iterative methods which do not fall into this category are also proposed in this paper. Comparing with traditional Krylov subspace methods which always depend on the matrix-vector multiplication with a fixed matrix, the newly introduced methods (the so-called (progressively) accumulated projection methods, or AP (PAP) for short) use a projection matrix which varies in every iteration to form a subspace from which an approximate solution is sought. More importantly an accelerative approach (called APAP) is introduced to improve the convergence of PAP method. Numerical experiments demonstrate some surprisingly improved convergence behavior. Comparison between benchmark extended Krylov subspace methods (Block Jacobi and GMRES) are made and one can also see remarkable advantage of APAP in some examples. APAP is also used to solve systems with extremely ill-conditioned coefficient matrix (the Hilbert matrix) and numerical experiments shows that it can bring very satisfactory results even when the size of system is up to a few thousands.

Investigation of how diatoms cope with the rapid fluctuations in iron bioavailability in marine environments may facilitate a better understanding of the mechanisms underlying their ecological success, in particular their ability to proliferate rapidly during favorable conditions. In this study, using in vivo biochemical markers and whole-cell iTRAQ-based proteomics analysis, we explored the cellular responses associated with reactive oxygen species (ROS) production and cell fate decision during the early response to Fe limitation in the centric diatom Thalassiosira pseudonana. Fe limitation caused a significant decrease in Photosystem (PS) II photosynthetic efficiency, damage to the photosynthetic electron transport chain in PS I, and blockage of the respiratory chain in complexes III and IV, which could all result in excess ROS accumulation. The increase in ROS likely triggered programmed cell death (PCD) in some of the Fe-limited cells through synthesis of a series of proteins involved in the delicate balance between pro-survival and pro-PCD factors. The results provide molecular-level insights into the major strategies that may be employed by T. pseudonanain response to Fe-limitation: the reduction of cell population density through PCD to reduce competition for available Fe, the reallocation of intracellular nitrogen and Fe to ensure survival, and an increase in expression of antioxidant and anti-PCD proteins to cope with stress.

In this paper, we consider a simplified dynamic model describing the evolution of the poloidal flux during the ramp-up phase of the tokamak discharge. We first use the Galerkin method to obtain a finite-dimensional model based on the original PDE system. Then, we apply the control parameterization method to obtain an approximate optimal parameter selection problem governed by a lumped parameter system. Computational optimization techniques are subsequently deployed to solve this approximate problem. To validate our approach, we perform numerical simulations using experimental data from the DIII-D tokamak in San Diego, California. The results show that our numerical optimization procedure can generate optimal controls that drive the current profile to within close proximity of the desired profile at the terminal time, thus demonstrating that the Galerkin and control parameterization methods are effective tools for current profile control in tokamak plasmas.

A switched system is a dynamic system that operates by switching between different subsystems or modes. Such systems exhibit both continuous and discrete characteristics—a dual nature that makes designing effective control policies a challenging task. The purpose of this paper is to review some of the latest computational techniques for generating optimal control laws for switched systems with nonlinear dynamics and continuous inequality constraints. We discuss computational strategies for optimizing both the times at which a switched system switches from one mode to another (the so-called switching times) and the sequence in which a switched system operates its various possible modes (the so-called switching sequence). These strategies involve novel combinations of the control parameterization method, the time-scaling transformation, and bilevel programming and binary relaxation techniques. We conclude the paper by discussing a number of switched system optimal control models arising in practical applications.

The single pile subsidence quantity computation and the analysis theoretically has the load to transmit the law, the cutting deflection method, the theory of elasticity law and the lamination always legitimate and so on. This article has through hierarchical total legal analysis in bored pile end grouting after pile subsidence influence factor, And in a project as a background, establishes the single pile ANSYS finite element model in civil engineering. For the pile are no grouting, grouting pile slurry bubble size, grouting pile of grouting modulus such as the change of the situation analysis. The author drew on the bored pile end after grouting pile subsidence influence factor and the main reasons as well as some useful conclusions

In this paper, we present a superconvergence result for the mixed finite element approximations of general second order elliptic eigenvalue problems. It is known that a superconvergence result has been given by Durán et al. [Math. Models Methods Appl. Sci. 9 (1999) 1165–1178] and Gardini [ESAIM: M2AN 43 (2009) 853–865] for the lowest order Raviart-Thomas approximation of Laplace eigenvalue problems. In this work, we introduce a new way to derive the superconvergence of general second order elliptic eigenvalue problems by general mixed finite element methods which have the commuting diagram property. Some numerical experiments are given to confirm the theoretical analysis.

Abstract: We introduce some ways to compute the lower and upper bounds of the Laplace eigenvalue problem. By using the special nonconforming finite elements, i.e., enriched Crouzeix-Raviart element and extended Q 1rot, we get the lower bound of the eigenvalue. Additionally, we use conforming finite elements to do the postprocessing to get the upper bound of the eigenvalue, which only needs to solve the corresponding source problems and a small eigenvalue problem if higher order postprocessing method is implemented. Thus, we can obtain the lower and upper bounds of the eigenvalues simultaneously by solving eigenvalue problem only once. Some numerical results are also presented to demonstrate our theoretical analysis.

This article take the Zhejiang some project engineering geology condition as a background, Through comparative analysis with single pile load, determine the model parameters of ANSYS finite element, The ANSYS finite element model of single pile, Respectively on the Grouting pile and Grouting for grouting of pile modulus change and Grouting in body size and changes of modulus of pile-end soils and a series of comparative analysis of the situation and analysis on bearing capacity of bored pile tip Grouting influence factors and of the main causes, draw some useful conclusions.

AbstractIn this paper, a new type of gradient recovery method based on vertex-edge-face interpolation is introduced and analyzed. This method gives a new way to recover gradient approximations and has the same simplicity, efficiency, and superconvergence properties as those of superconvergence patch recovery method and polynomial preserving recovery method. Here, we introduce the recovery technique and analyze its superconvergence properties. We also show a simple application in the a posteriori error estimates. Some numerical examples illustrate the effectiveness of this recovery method.

Solid tumors often contain regions with insufficient oxygen delivery, a condition called hypoxia. Tumor hypoxia is an independent prognostic factor significantly correlated with advanced stages of malignancy, increased resistance to conventional therapy, and reduced disease-free survival.  Hypoxic tumor cells exhibit poorly differentiated phenotypes resembling stem or progenitor cells.  Studies have shown that hypoxia can inhibit tumor cell differentiation and promote maintenance of cancer stem cells.  In addition, hypoxia also blocks the differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells.  Therefore, hypoxia may play a critical role during the evolution of the tumor stromal microenvironment and formation of the putative cancer stem cell niches.  Conceptually, hypoxia may help create a microenvironment enriched both in poorly differentiated tumor cells and in undifferentiated stromal cells.  Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells.  This review will discuss the hypoxia-regulated stem cell pathways and their roles in the maintenance of cancer stem cell functions.

Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm for a role of hypoxia in facilitating tumor progression. Hypoxia may help create a microenvironment enriched in poorly differentiated tumor cells and undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This hypothesis suggests that effectively targeting hypoxic cancer stem cells is a key to successful tumor control.

The bilinear finite element approximation for the Poisson equation has an asymptotic error expansion on the anisotropic rectangular meshes. Extrapolation can be obtained based on this expansion and the postprocessing interpolation. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2007

By means of eigenvalue error expansion and integral expansion techniques, we propose and analyze the stream function-vorticity-pressure method for the eigenvalue problem associated with the Stokes equations on the unit square. We obtain an optimal order of convergence for eigenvalues and eigenfuctions. Furthermore, for the bilinear finite element space, we derive asymptotic expansions of the eigenvalue error, an efficient extrapolation and an a posteriori error estimate for the eigenvalue. Finally, numerical experiments are reported.

Abstract An asymptotic error expansion concerning of Hood–Taylor elements for the Stokes problem is established on uniform rectangular meshes. The extrapolation based on such an expansion increases the rate of convergence by one order.

Patients afflicted with severe laminin 5-deficient junctional epidermolysis bullosa (JEB) often die in infancy with massive cutaneous blistering. Prior approaches to genetically correct this disorder have relied on stable integration of wild-type LAMB3 sequences, using retroviral vectors. To develop a nonviral approach to JEB gene therapy, we used the φC31 integrase, which mediates unidirectional genomic integration of plasmids containing a specific attB site. An attB-containing laminin 5 β3 expression plasmid was integrated into the genomes of primary keratinocytes from four unrelated, genetically characterized JEB patients. φC31 integrase supported genomic integration into epidermal progenitor cells. Regeneration of human skin on immunedeficient mice, using these cells, produced human skin tissue with restored laminin 5 expression. Furthermore, corrected JEB tissue restored hemidesmosome formation and abolished histologic evidence of subepidermal blistering. These findings provide an approach to durable nonviral correction of JEB.

Ciarlet‐Raviart's scheme is a finite element method for solving the mixed formulation of the biharmonic equation. So far, there has been no superconvergence for the vorticity from this method if a general rectangular mesh is used. In this article, we deal with the biquadratic elements under the uniform rectangular mesh and prove for the first time a superconvergence for the vorticity. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 420–427, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10010

The skin offers a tissue site accessible for delivery of gene-based therapeutics. To develop the capability for sustained systemic polypeptide delivery via cutaneous gene transfer, we generated and injected pseudotyped HIV-1 lentiviral vectors intradermally at a range of doses into human skin grafted on immune-deficient mice. Unlike Moloney murine leukemia virus (MLV)-based retrovectors, which failed to achieve detectable cutaneous gene transfer by this approach, lentivectors effectively targeted all major cell types within human skin tissue, including fibroblasts, endothelial cells, keratinocytes, and macrophages. After a single injection, lentivectors encoding human erythropoietin (EPO) produced dose-dependent increases in serum human EPO levels and hematocrit that increased rapidly within one month and remained stable subsequently. Delivered gene expression was confined locally at the injection site. Excision of engineered skin led to rapid and complete loss of human EPO in the bloodstream, confirming that systemic EPO delivery was entirely due to lentiviral targeting of cells within skin rather than via spread of the injected vector to visceral tissues. These findings indicate that the skin can sustain dosed systemic delivery of therapeutic polypeptides via direct lentivector injection and thus provide an accessible and reversible approach for gene-based delivery to the bloodstream.

Summary.: In this paper, we develop and analyze a new finite element method called the sparse finite element method for second order elliptic problems. This method involves much fewer degrees of freedom than the standard finite element method. We show nevertheless that such a sparse finite element method still possesses the superconvergence and other high accuracy properties same as those of the standard finite element method. The main technique in our analysis is the use of some integral identities.

Methods for fitting parametric disk curves to a set of disks are developed. An algorithm is presented with a numerical example

Two post-processing techniques are widely used in the literature in the context of convergence acceleration. One of them is an interpolation technique, used for partial differential equations and integral differential equations, and the other is an iteration technique used for integral equations. These two techniques, interpolation and iteration, are quite different, and the former is simpler. Can we use the interpolation technique for integral equations instead of using the second iteration technique? This report gives a positive answer.

The BP-1/6C3 antigen is a homodimeric, phosphorylated type II membrane integral glycoprotein expressed on immature B-lineage cells, bone marrow stromal cells, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. Biochemical and molecular analysis identified BP-1 as glutamyl aminopeptidase, an ectoenzyme that catalyzes the hydrolysis of acidic amino acid residues from the amino termini of regulatory peptides. We have isolated genomic clones that encode theBP-1gene (gene symbolEnpep). The gene spans more than 110 kb and contains 20 exons. Except for the first and the last exons, it is composed of small exons ranging from 56 to 171 bp that are separated by introns ranging from less than 100 bp to approximately 10 kb. The zinc binding motif HEXXH and the glutamic acid residue 19 amino acids downstream, which also binds zinc, are encoded in exons 5 and 6. Primer extension analysis revealed a common major transcriptional start site in a pre-B cell line, in a bone marrow stromal cell line, and in kidney cells. The promoter region contains a TATA-like element and potential DNA-binding motifs for lymphocyte-specific transcription factors including Ikaros, BSAP, PU.1, and octamer binding proteins, as well as DNA binding motifs for several ubiquitous transcription factors. An interferon responsive element also located in the promoter region appeared to be functional, since type I interferons (IFN-α/IFN-β) upregulated BP-1 expression in pre-B cell lines. A 2.1-kb promoter fragment, when fused to a luciferase reporter gene, was able to drive luciferase expression in pre-B cells, which normally express BP-1, and in Ag8 cells, in which BP-1 expression is extinguished. TheBP-1/Enpepgene was localized to a distal region of mouse chromosome 3 in a region homologous to human chromosome 4q25. Interestingly, while interleukin-7 (IL-7) induced both cell growth and increased BP-1 expression, IFN-α/IFN-β upregulated BP-1 expression but inhibited IL-7-induced proliferation. This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal.

Low efficiencies of gene transfer to somatic cells have frustrated therapeutic gene delivery efforts in a wide array of tissues including the skin. Production of populations of keratinocytes in which all cells contain the desired therapeutic gene may be important in future genetic therapies. This may be the case in disorders such as epidermolysis bullosa and ichthyosis, where a failure to correct the vast majority of cells within tissue could perpetuate central disease features such as skin fragility and defective barrier function. We have refined retroviral gene transfer parameters to achieve significant improvements in gene delivery efficiencies to human keratinocytes compared to those previously reported. We have also generated retroviral vectors that allow rapid pharmacologic selection of human keratinocytes without interfering with the potential of these cells to regenerate epidermis in vivo—we determined that blasticidin is superior to the commonly used neomycin. The combined capabilities for efficient retroviral gene transfer and effective pharmacologic selection allow production of entirely engineered populations of human keratinocytes for use in future efforts to achieve effective cutaneous gene delivery.

In this paper we study the finite element approximations to the Sobolev and viscoelasticity type equations and present a direct analysis for global superconvergence for these problems, without using Ritz projection or its modified forms.

In this paper we study the finite element approximations to the parabolic and hyperbolic integrodifferential equations and present an immediate analysis for global superconvergence for these problems, without using the Ritz projection or its modified forms.

In this paper, by means of Sloan's iteration technique, we present a kind of iterative correction method for Galerkin approximations of Wiener-Hopf equations, and show that this is not only a high order method but also an adaptable one.

An iteration method for roots of algebraic functions with roots of multiplicity greater than one is established using tools and techniques from interval arithmetic. The method is based on an interval iteration functions for multiple roots and it retains the convergence order of the underlying iteration method while preserving global convergence over an initial interval. A number of simple examples are provided to show that the method is feasible and that it produces reasonable results.

The general centered form for multi-variate polynomials is investigated and a computing procedure is proposed that results in a certain superset. Based on this procedure the optimal centered forms for monomials and for some special cases of polynomials are investigated.

In this paper, instead of the usual 13-point formula, a new 21-point formula for the numerical solution of the first biharmonic Dirichlet problem is presented. According to the two kinds of the fictitious mesh point interpolation, it is shown that the error is O(h3.5) and O(h4) respectively in a norm which is stronger than the maximum norm for the error function.

Durable gene delivery to human skin is necessary for lasting correction of human genetic skin disease. Current cutaneous gene-delivery strategies, however, have achieved only transient gene expression, often only within a small percentage of tissue cells. The recent inability to sustain phenotypic correction of human genetic skin disease due to loss of therapeutic gene expression in regenerated epidermal tissue has highlighted this current limitation. In an effort to surmount this problem, we have generated gene delivery vectors that produce more durable gene delivery in human skin tissue in vivo

Type I interferons α and β, naturally produced regulators of cell growth and differentiation, have been shown to inhibit IL-7–induced growth and survival of B cell precursors in vitro. After confirming an inhibitory effect on B lymphopoiesis in an ex vivo assay, we treated newborn mice with an active IFN-α2/α1 hybrid molecule to assess its potential for regulating B and T cell development in vivo. Bone marrow and splenic cellularity was greatly reduced in the IFN-α2/α1–treated mice, and B lineage cells were reduced by >80%. The bone marrow progenitor population of CD43+B220+HSA− cells was unaffected, but development of the CD19+ pro–B cells and their B lineage progeny was severely impaired. Correspondingly, IL-7–responsive cells in the bone marrow were virtually eliminated by the interferon treatment. Thymus cellularity was also reduced by >80% in the treated mice. Phenotypic analysis of the residual thymocytes indicated that the inhibitory effect was exerted during the pro–T cell stage in differentiation. In IFN-α/β receptor−/− mice, T and B cell development were unaffected by the IFN-α2/α1 treatment. The data suggest that type I interferons can reversibly inhibit early T and B cell development by opposing the essential IL-7 response.

A piecewise linear fat spline is defined. This spline is smoothed via a smoothing process involving higher-order splines. Particular attention is given to fat splines of second and third degree and some approximations to these are discussed. Conditions are developed to ensure that these splines have the same convexity properties as the original data. Two numerical examples are provided.