Enhancing conductivity of metallic carbon nanotube networks by transition metal adsorption.

The conductivity of carbon nanotube thin films is mainly determined by carbon nanotube junctions, the resistance of which can be reduced by several different methods. We investigate electronic transport through carbon nanotube junctions in a four-terminal configuration, where two metallic single-wall carbon nanotubes are linked by a group 6 transition metal atom. The transport calculations are based on the Green's function method combined with the density-functional theory. The transition metal atom is found to enhance the transport through the junction near the Fermi level. However, the size of the nanotube affects the improvement in the conductivity. The enhancement is related to the hybridization of chromium and carbon atom orbitals, which is clearly reflected in the character of eigenstates near the Fermi level. The effects of chromium atoms and precursor molecules remaining adsorbed on the nanotubes outside the junctions are also examined.

The ELPA library: scalable parallel eigenvalue solutions for electronic structure theory and computational science.

Obtaining the eigenvalues and eigenvectors of large matrices is a key problem in electronic structure theory and many other areas of computational science. The computational effort formally scales as O(N(3)) with the size of the investigated problem, N (e.g. the electron count in electronic structure theory), and thus often defines the system size limit that practical calculations cannot overcome. In many cases, more than just a small fraction of the possible eigenvalue/eigenvector pairs is needed, so that iterative solution strategies that focus only on a few eigenvalues become ineffective. Likewise, it is not always desirable or practical to circumvent the eigenvalue solution entirely. We here review some current developments regarding dense eigenvalue solvers and then focus on the Eigenvalue soLvers for Petascale Applications (ELPA) library, which facilitates the efficient algebraic solution of symmetric and Hermitian eigenvalue problems for dense matrices that have real-valued and complex-valued matrix entries, respectively, on parallel computer platforms. ELPA addresses standard as well as generalized eigenvalue problems, relying on the well documented matrix layout of the Scalable Linear Algebra PACKage (ScaLAPACK) library but replacing all actual parallel solution steps with subroutines of its own. For these steps, ELPA significantly outperforms the corresponding ScaLAPACK routines and proprietary libraries that implement the ScaLAPACK interface (e.g. Intel's MKL). The most time-critical step is the reduction of the matrix to tridiagonal form and the corresponding backtransformation of the eigenvectors. ELPA offers both a one-step tridiagonalization (successive Householder transformations) and a two-step transformation that is more efficient especially towards larger matrices and larger numbers of CPU cores. ELPA is based on the MPI standard, with an early hybrid MPI-OpenMPI implementation available as well. Scalability beyond 10,000 CPU cores for problem sizes arising in the field of electronic structure theory is demonstrated for current high-performance computer architectures such as Cray or Intel/Infiniband. For a matrix of dimension 260,000, scalability up to 295,000 CPU cores has been shown on BlueGene/P.

Robust acceleration of self consistent field calculations for density functional theory.

We show that the type 2 Broyden secant method is a robust general purpose mixer for self consistent field problems in density functional theory. The Broyden method gives reliable convergence for a large class of problems and parameter choices. We directly mix the approximation of the electronic density to provide a basis independent mixing scheme. In particular, we show that a single set of parameters can be chosen that give good results for a large range of problems. We also introduce a spin transformation to simplify treatment of spin polarized problems. The spin transformation allows us to treat these systems with the same formalism as regular fixed point iterations.

Finite-element implementation for electron transport in nanostructures.

We have modeled transport properties of nanostructures using Green's-function method within the framework of the density-functional theory. The scheme is computationally demanding, so numerical methods have to be chosen carefully. A typical solution to the numerical burden is to use a special basis-function set, which is tailored to the problem in question, for example, the atomic-orbital basis. In this paper we present our solution to the problem. We have used the finite-element method with a hierarchical high-order polynomial basis, the so-called p elements. This method allows the discretation error to be controlled in a systematic way. The p elements work so efficiently that they can be used to solve interesting nanosystems described by nonlocal pseudopotentials. We demonstrate the potential of the implementation with two different systems. As a test system a simple Na-atom chain between two leads is modeled and the results are compared with several previous calculations. Secondly, we consider a thin hafnium dioxide (HfO2) layer on a silicon surface as a model for a gate structure of the next generation of microelectronics.

Antisense RNA inhibition of cathepsin L expression reduces tumorigenicity of malignant cells.

Several tumour-forming cell lines are known to overproduce the lysosomal cysteine peptidase cathepsin L. We have used an antisense approach to investigate whether inhibition of cathepsin L overexpression in two malignant cell lines (myeloma SP cells and L cells) reduces their tumorigenic potential. Two different cDNA fragments of murine cathepsin L were inserted in the antisense direction into the pcDNA3 vector, and SP and L cells were stably transfected with these plasmid constructs. Several of the selected clones expressing the antisense transcript showed specific reduction of the mRNA level and the intracellular activity of cathepsin L, and a greatly diminished amount of secreted procathepsin L. When tested in Balb/c nu/nu mice, the cell lines with low cathepsin L activity exhibited a significantly decreased potential for tumour growth when compared with control cells expressing wild-type levels of cathepsin L activity. This observation suggests that cathepsin L is a critical factor in tumour growth.

A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis.

In a randomized, double-blind, double-placebo, multicentre study, terbinafine 250 mg daily for 12 weeks was compared with fluconazole 150 mg once weekly for 12 or 24 weeks in the treatment of onychomycosis. A total of 137 patients with culture-confirmed onychomycosis was divided into three groups: group A received terbinafine for 12 weeks, group B received fluconazole for 12 weeks, while group C received fluconazole for 24 weeks. At completion of the study (week 60), the mycological cure rate was higher in the terbinafine group than in the fluconazole groups: 89% vs. 51% and 49%, respectively (P < 0.001). The length of unaffected nail increased until week 24 in group B and until week 36 in group C, but was still increasing in group A at the final visit (week 60). Complete clinical cure of the target nail at week 60 was 67% in the terbinafine group, compared with 21% and 32% in the fluconazole groups, respectively. The incidence of adverse events was low for both study agents. We conclude that terbinafine 250 mg daily for 12 weeks is significantly more effective in the treatment of onychomycosis than fluconazole 150 mg once weekly for either 12 or 24 weeks.

Expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67 in benign, premalignant and malignant skin lesions with implicated HPV involvement.

A series of 120 biopsies from benign (verruca vulgaris and keratoacanthoma), premalignant (actinic keratosis and extragenital Bowen's disease) and malignant (squamous cell carcinoma) skin lesions were studied immunohistochemically for the expression of cell-cycle proteins p53, p21 (WAF-1), PCNA and Ki-67. The presence of human papillomavirus (HPV) DNA in these samples had been analysed previously using in situ hybridization (ISH) and PCR. Moderate to intense expression of both PCNA and Ki-67 was present in most of the lesions studied. PCNA staining was extensive in the epidermis underneath the layers where abundant HPV DNA staining was shown in HPV DNA-positive verrucas. In keratoacanthomas, p21 and PCNA expression remained low, despite intense p53 expression. In actinic keratosis, only half of the specimens showed overexpression of p53 associated with moderate or intense expression of PCNA. In extragenital Bowen's lesions, all these cell-cycle markers were overexpressed, but in squamous cell carcinomas, they were heterogeneously expressed and showed no correlation with tumour differentiation. Our results suggest a mechanism by which HPV can reactivate the host genes (leading to cell proliferation) to support its own DNA replication. Also p21 might start keratinocyte differentiation in areas where HPV DNA replication starts. Cell proliferation remained active in actinic keratosis and Bowen's lesions, emphasizing the precancer character of these lesions in contrast with the benign nature of keratoacanthoma and verruca vulgaris.

The role of low resistance blood flow pathways in the pathogenesis and healing of venous leg ulcers.

In an attempt to clarify the pathophysiology of haemodynamics in legs with venous ulcer we investigated the effect of a single intermittent pneumatic compression treatment on the peripheral resistance of leg arteries and the cutaneous laser Doppler flux in the leg. Eight patients with venous leg ulcers and 10 subjects with healthy legs were investigated. Doppler waveforms of the leg arteries and laser Doppler flux of the leg skin were recorded before and after a single intermittent pneumatic compression treatment with the subjects in a recumbent position. In the legs with venous ulcer, the peripheral resistance of the arteries was lower and the laser Doppler flux was greater, compared with healthy legs (p = 0.003 and p = 0.002, respectively). A single intermittent pneumatic compression treatment raised the peripheral resistance in the arteries of legs with ulcer and laser Doppler flux of the skin more in ulcer legs than in healthy legs (p = 0.046 and p = 0.034, respectively). These findings suggest that removal of oedema causes redistribution of skin blood flow in the legs with venous ulcer favouring the superficial capillary perfusion. This could explain why compression treatment promotes the healing of venous leg ulcers.

Continuous and intermittent itraconazole dosing schedules for the treatment of onychomycosis: a pharmacokinetic comparison.

This multicentre, double-blind, randomized study compared the pharmacokinetics of itraconazole given at 200 mg once daily for 3 months and intermittently at 200 mg twice daily for 1 week per month followed by a 3-week drug-free period for 3 months in the treatment of onychomycosis. Patients were followed for 9 months after treatment. Itraconazole and hydroxy-itraconazole plasma concentrations and itraconazole nail tip concentrations were determined at regular intervals. With intermittent therapy (n = 64), increases of consistent magnitude were seen in the mean itraconazole and hydroxy-itraconazole plasma concentrations at the end of each 1-week treatment phase; values returned towards baseline during each subsequent 3-week drug-free period. The mean concentration of itraconazole in fingernail tips increased steadily from week 4, reached a maximum value at week 24 (213 ng/g), declined sharply between weeks 24 and 36 and returned to baseline by week 48; the mean concentration profile was similar for toenail tips (maximum value 305 ng/g at week 24) but decreased at a slower rate. With continuous therapy (n = 65), steady-state mean plasma concentrations of itraconazole and hydroxy-itraconazole were obtained within 4-5 weeks of the start of treatment and remained reasonably constant between weeks 4 and 12. The mean concentration of itraconazole in fingernail tips reached a maximum value at week 12 (524 ng/g) and returned towards baseline by week 48; in contrast, the maximum mean concentration of itraconazole in toenail tips was 698 ng/g at week 36 and did not return to baseline by week 48. No clear relationship was observed between response to treatment and concentration of itraconazole or hydroxy-itraconazole in plasma or itraconazole in nails, suggesting that concentrations exceeded therapeutic levels. In conclusion, intermittent therapy resulted in higher maximum itraconazole plasma concentrations but lower total drug exposure, and hence lower itraconazole nail concentrations, than continuous therapy. However, the intermittent schedule was not associated with a lower cure rate, which indicates that itraconazole nail concentrations remained within the therapeutic range.

A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis.

In this multicentre, double-blind, parallel group study, we evaluated the efficacy and safety of continuous treatment with itraconazole, 200 mg daily for 3 months, in comparison with itraconazole pulse therapy, 400 mg daily 1 week per month for 3 months, in the treatment of toe-nail onychomycosis. The study included 129 patients with distal subungual onychomycosis of the toe-nails, confirmed by microscopy and positive for dermatophyte culture; 65 received continuous treatment and 64 received pulse therapy. Patients were followed up for 9 months after treatment. After 12 months, there were 62 evaluable patients in the continuous group and 59 evaluable patients in the pulse group. The clinical response (i.e. the size of the affected area and the progress of the infection) and mycological cure (i.e. negative results on microscopy and culture) were the main outcome measures. A clinical response was defined as a cure or a marked improvement. Clinical response rates were 69%, in the continuous group, and 81% in the pulse group at month 12; the corresponding mycological cure rates were 66 and 69%. A better improvement in signs and symptoms was noted in the pulse group. Six patients were withdrawn from treatment because of adverse events, not all of which were thought to be drug-related. There were no clinically relevant laboratory abnormalities. We conclude that both regimens are effective, safe and well tolerated. The superiority of one treatment over the other was not established, but the results tended to favour pulse therapy. Equivalence testing confirmed that pulse therapy was at least equivalent to continuous treatment.

Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients.

BACKGROUND: Onychomycosis of the toenail caused by nondermatophyte molds alone or in combination with dermatophytes is difficult to eradicate with standard antifungal therapy. OBJECTIVE: Our purpose was to determine the effectiveness of itraconazole in the treatment of toenail onychomycosis caused by molds alone or in combination with dermatophytes. METHODS: We treated 36 patients with this drug given as continuous dosing (100 or 200 mg/ day) for 6 to 20 weeks or as a 1-week pulse dosing (200 mg twice daily for 1 week per month) for two to four pulses. RESULTS: Patients with toenail onychomycosis with the following organisms were treated: Aspergillus spp. (eight patients), Fusarium spp. (four patients), Scopulariopsis brevicaulis (23 patients), and Alternaria spp. (one patient). Nineteen patients had onychomycosis with a mixed origin. At follow-up, 12 months after therapy was initiated, clinical and mycologic cure was achieved in 15 of 17 patients (88%) with onychomycosis caused by a single mold. In patients with mixed infection, a clinical cure was obtained in 16 of 19 patients (84%) and a mycologic cure in 13 of 19 patients (68%). CONCLUSION: Itraconazole appears to be effective and safe for the treatment of toenail onychomycosis caused by some nondermatophyte molds alone or in combination with dermatophytes.

The peripheral resistance in arteries of legs is inversely proportional to the severity of chronic venous insufficiency.

There are conflicting reports in the literature about the existence of arteriovenous shunting in legs with chronic venous insufficiency. Using duplex scanning, we have earlier shown that there is lowered peripheral resistance in the arteries of legs with venous ulcer together with premature venous filling in angiography. In the present study we investigated the peripheral resistance in the arteries of 16 legs with chronic venous insufficiency without present ulcer. We compared the results with those obtained from 12 healthy legs and from 18 legs with venous ulcer. There was a highly significant inverse correlation between the severity of chronic venous insufficiency and the peripheral resistance in the popliteal, the dorsal pedal and the posterior tibial arteries (p < 0.001). These results suggest that there is arteriovenous shunting in legs with chronic venous insufficiency and that this phenomenon correlates with the degree of chronic venous insufficiency.

Expression of PCNA is associated with the presence of HPV DNA in skin warts.

A series of 90 excised cutaneous warts (verrucae vulgaris) were studied for the presence of HPV (human papillomavirus) DNA using in situ hybridization (ISH) with biotinylated full genomic DNA probes of HPV types 1, 2, 3, and 4. The expression of PCNA (proliferating cell nuclear antigen) was examined using conventional immunohistochemistry. The aim was to test the hypothesis that HPV can reactivate PCNA, including in the host replication machinery. HPV DNA of the above types was detected in 60 of 90 verruca biopsies studied (66.7%): HPV 2 in 56 cases, HPV 1 in 2 cases, and HPV 3 in 2 cases. PCNA was expressed in all samples except two. The signal distribution of HPV DNA markedly differed from that of PCNA expression. ISH revealed strong HPV DNA signals in both the granular and the upper spinous cell layers, the most intense signals being detected in the upper epidermis. On the other hand, nuclear PCNA staining was present in the majority of parabasal and basal cells. Although strong PCNA signals within the wart lesions were found in the areas where HPV DNA was present, the PCNA positivity was almost invariably localized in the differentiated cells of the spinous cell layers, just below the HPV DNA-expressing cells. At the margins of the lesions, PCNA expression was still strong but disappeared abruptly towards the normal epidermis. HPV DNA-positive warts showed more intense expression of PCNA than did the HPV DNA-negative ones in this study. Our results indicate that PCNA induction is associated with the presence of HPV DNA, suggesting that HPV can reactivate PCNA, thus interfering with the host cell DNA replication machinery.

Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease of the skin.

To assess the role of human papillomavirus (HPV) in the aetiology of extragenital Bowen's disease (EBD), a series of 91 cases were analysed using in situ hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11, 12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of the 91 samples, using both the consensus primers MY09/MY11 which amplify a large number of HPV types from the L1 region and the degenerate primers CP65/CP70, which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types. All the cases were also negative in the PCR. The results suggest that EBD is not HPV-related, at least in immunocompetent patients.

Known HPV types have no association with keratoacanthomas.

Certain HPV types have been linked to the genesis and development of premalignant and malignant skin diseases. There have been several contradictory reports on the role of HPV infections in the development of keratoacanthomas (KAs). To further study the involvement of HPVs in the aetiology of KAs, we investigated paraffin-embedded specimens of 80 biopsies of KAs for the presence of HPV 1, 2, 3, 4, 5, 7, 26, 37, 38, 47 and 59 DNA by in situ hybridization (ISH) with biotinylated probes under high stringency conditions (Tm-10 degrees C). Every fourth biopsy specimens was also examined by polymerase chain reaction (PCR) with consensus primers targeting the HPV E1 and L1 regions. The positive cases were further studied by direct DNA sequencing. All specimens proved to be negative for all HPV DNAs studied by ISH. Three out of 20 cases produced in positive PCR amplifications when consensus primers targeting the L1 region were used. However, the same samples remained negative with general primers targeting the E1 region. The DNA sequence analysis of the PCR-positive products showed a 76% homology with HPV type 17. Our results suggest that the known HPV types are unlikely to have any role in the aetiology of KAs.

Expression of acid cysteine proteinase inhibitor (ACPI) in the normal human prostate, benign prostatic hyperplasia and adenocarcinoma.

Acid cysteine proteinase inhibitor (ACPI or cystatin A) is a protein (12 kDa) which inhibits the action of several cysteine proteinases, e.g. cathepsins B, H, L and S. In this study the cellular location of ACPI has been immunohistochemically investigated in the normal human prostate, in benign prostatic hyperplasia (BPH) and in adenocarcinoma. ACPI was found in the basal epithelial cells of the normal prostate. The secretory epithelial cells did not express ACPI. In the hyperplastic prostate, the expression of ACPI was decreased and it was also expressed more focally in the basal cells. Hyperplastic basal cells also expressed ACPI. In prostatic adenocarcinoma, no ACPI expression was found. The absence of ACPI expression was obvious and if the sections contained both benign and malignant cells, only the benign glandular structures always expressed ACPI. The results suggest that expression of ACPI might be related to prostatic epithelial cell proliferation and differentiation. Possibly the detection of ACPI in tissue sections might be helpful in identifying prostatic adenocarcinoma, especially in cases with small carcinomatous foci.

Acid cysteine proteinase inhibitor in cutaneous lymphocytic infiltrates.

Acid cysteine proteinase inhibitor (ACPI, cystatin A) is normally present in squamous epithelium and dendritic cells of lymphoid follicles. Its expression is altered both in proliferative and malignant squamous epithelium and in neoplastic lymphoid follicles. The expression of ACPI in the lymphoid infiltrates of cutaneous psuedolymphomas and B-cell lymphomas was studied. Eighteen pseudolymphomas from 15 patients were divided into three groups according to the proportion of B and T lymphocytes. The B-cell-type lesions with well-developed follicles and germinal centers showed a pronounced ACPI expression in dendritic cells. Varying amounts of ACPI-positive cells were present in the mixed B- and T-cell-type and also in the T-cell-type lesions. The labeled cell population was distinct from the factor XIIIa-positive dermal dendrocytes, S-100-positive histiocytes, and HAM 56-positive histiocytes. Malignant lymphomas contained a few haphazardly arranged ACPI-positive cells with short dendrites and granular cytoplasm. It was concluded that follicular dendritic cells can be reliably labeled with ACPI antiserum in cutaneous pseudolymphomas. The structure and distribution of ACPI-containing cells in malignant cutaneous B-cell lymphomas is altered when compared with pseudolymphomas.

No evidence of human papillomavirus DNA in actinic keratosis.

Human papillomaviruses (HPVs) are involved in premalignant and malignant skin diseases as well as in a variety of benign cutaneous and mucosal lesion disease. Its association with HPV infection has recently been evaluated in a few studies, but the results are contradictory. For further assessment of the role of HPVs in AK, a series of 100 paraffin-embedded biopsy specimens taken from subjects with AK were studied for the presence of HPV types 1, 2, 3, 4, 5, 7, 12, 15, 26, 36, 37 and 59 DNA using in situ hybridization (ISH) under high stringency conditions (Tm -10 degrees C). All specimens were definitely negative for all bion specimens were definitely negative for all biotinylated HPV DNA probes tested. One fifth of the specimens were studied using the polymerase chain reaction (PCR) with general primers to confirm the negative results. All cases were also in the PCR. Our results suggest that HPVs are not directly involved in the aetiology of AK.