Exchange Interactions and Intermolecular Hybridization in a Spin-1/2 Nanographene Dimer.

Phenalenyl is a radical nanographene with a triangular shape hosting an unpaired electron with spin S = 1/2. The open-shell nature of the phenalenyl is expected to be retained in covalently bonded networks. As a first step, we report synthesis of the phenalenyl dimer by combining in-solution synthesis and on-surface activation and its characterization on Au(111) and on a NaCl decoupling layer by means of inelastic electron tunneling spectroscopy (IETS). IETS shows inelastic steps that are identified as singlet-triplet excitation arising from interphenalenyl exchange. Spin excitation energies with and without the NaCl decoupling layer are 48 and 41 meV, respectively, indicating significant renormalization due to exchange with Au(111) electrons. Furthermore, third-neighbor hopping-induced interphenalenyl hybridization is fundamental to explaining the position-dependent bias asymmetry of the inelastic steps and activation of kinetic interphenalenyl exchange. Our results pave the way for bottom-up synthesis of S = 1/2 spin-lattices with large exchange interactions.

Lightwave-driven scanning tunnelling spectroscopy of atomically precise graphene nanoribbons.

Atomically precise electronics operating at optical frequencies require tools that can characterize them on their intrinsic length and time scales to guide device design. Lightwave-driven scanning tunnelling microscopy is a promising technique towards this purpose. It achieves simultaneous sub-ångström and sub-picosecond spatio-temporal resolution through ultrafast coherent control by single-cycle field transients that are coupled to the scanning probe tip from free space. Here, we utilize lightwave-driven terahertz scanning tunnelling microscopy and spectroscopy to investigate atomically precise seven-atom-wide armchair graphene nanoribbons on a gold surface at ultralow tip heights, unveiling highly localized wavefunctions that are inaccessible by conventional scanning tunnelling microscopy. Tomographic imaging of their electron densities reveals vertical decays that depend sensitively on wavefunction and lateral position. Lightwave-driven scanning tunnelling spectroscopy on the ångström scale paves the way for ultrafast measurements of wavefunction dynamics in atomically precise nanostructures and future optoelectronic devices based on locally tailored electronic properties.

Electronic characterization of silicon intercalated chevron graphene nanoribbons on Au(111).

Electronic and thermal properties of chevron-type graphene nanoribbons can be widely tuned, making them interesting candidates for electronic and thermoelectric applications. Here, we use post-growth silicon intercalation to unambiguously access nanoribbons' energy position of their electronic frontier states. These are otherwise obscured by substrate effects when investigated directly on the growth substrate. In agreement with first-principles calculations we find a band gap of 2.4 eV.

Impact of heterocirculene molecular symmetry upon two-dimensional crystallization.

Despite the development of crystal engineering, it remains a great challenge to predict the crystal structure even for the simplest molecules, and a clear link between molecular and crystal symmetry is missing in general. Here we demonstrate that the two-dimensional (2D) crystallization of heterocirculenes on a Au(111) surface is greatly affected by the molecular symmetry. By means of ultrahigh vacuum scanning tunneling microscopy, we observe a variety of 2D crystalline structures in the coverage range from submonolayer to monolayer for D(8h)-symmetric sulflower (C16S8), whereas D(4h)-symmetric selenosulflower (C16S4Se4) forms square and rectangular lattices at submonolayer and monolayer coverages, respectively. No long-range ordered structure is observed for C(1h)-symmetric selenosulflower (C16S5Se3) self-assembling at submonolayer coverage. Such different self-assembly behaviors for the heterocirculenes with reduced molecular symmetries derive from the tendency toward close packing and the molecular symmetry retention in 2D crystallization due to van der Waals interactions.

Electron scattering in intrananotube quantum dots.

Intratube quantum dots showing particle-in-a-box-like states with level spacings up to 200 meV are realized in metallic single-walled carbon nanotubes by means of low dose medium energy Ar(+) irradiation. Fourier-transform scanning tunneling spectroscopy compared to results of a Fabry-Perot electron resonator model yields clear signatures for inter- and intravalley scattering of electrons confined between consecutive irradiation-induced defects (interdefects distance

Mapping the electronic surface potential of nanostructured surfaces.

We present a method for the quantitative determination of the surface potential landscape of nanostructured surfaces based on the local analysis of the lowest field emission resonances by scanning tunneling spectroscopy. The method has a lateral resolution of approximately 1 nm and is applied to elucidate the site-specific adsorption properties of the strain relief pattern formed by two monolayers of Ag on Pt(111). For the example of C60 fullerenes, we show that the surface potential difference of up to 0.35 eV is responsible for the site-selective immobilization on the strain relief pattern.

Fabrication of a well-ordered nanohole array stable at room temperature.

We report on the fabrication of a new type of nanotemplate surface consisting of a hexagonally well-ordered array of one monolayer deep holes with a tunable size of about 4 nm (2) and a fixed spacing of 7 nm. The nanohole array fabrication is based on the strain-relief trigonal network formed in the 2 monolayer Ag on Pt(111) system. Removing about 0.1 ML of the Ag top layer of this surface structure, for example, by He- or Ar-ion sputtering, leads to the formation of nanoholes at specific domains of the trigonal network, which are stable at room temperature.

Packed-bed bioreactors for mammalian cell culture: bioprocess and biomedical applications.

This article describes the development history of packed-bed bioreactors (PBRs) used for the culture of mammalian cells. It further reviews the current applications of PBRs and discusses the steps forward in the development of these systems for bioprocess and biomedical applications. The latest generation of PBRs used in bioprocess applications achieve very high cell densities (>10(8) cells ml(-1)) leading to outstandingly high volumetric productivity. However, a major bottleneck of such PBRs is their relatively small volume. The current maximal volume appears to be in the range of 10 to 30 l. A scale-up of more than 10-fold would be necessary for these PBRs to be used in production processes. In biomedical applications, PBRs have proved themselves as compact bioartificial organs, but their metabolic activity declines frequently within 1 to 2 weeks of operation. A main challenge in this field is to develop cell lines that grow consistently to high cell density in vitro and maintain a stable phenotype for a minimum of 1 to 2 months. Achieving this will greatly enhance the usefulness of PBR technology in clinical practice.

Oxygen supply for CHO cells immobilized on a packed-bed of Fibra-Cel disks.

Packed-bed bioreactors (PBR) have proven to be efficient systems to culture mammalian cells at very high cell density in perfusion mode, thus leading to very high volumetric productivity. However, the immobilized cells must be continuously supplied with all nutrients in sufficient quantities to remain viable and productive over the full duration of the perfusion culture. Among all nutrients, oxygen is the most critical since it is present at very low concentration due to its low solubility in cell culture medium. This work presents the development of a model for oxygenation in a packed-bed bioreactor system. The experimental system used to develop the model was a packed-bed of Fibra-Cel disk carriers used to cultivate Chinese Hamster Ovary cells at high density ( approximately 6.1 x 10(7) cell/mL) in perfusion mode. With the help of this model, it was possible to identify if a PBR system is operated in optimal or sub-optimal conditions. Using the model, two options were proposed, which could improve the performance of the basal system by about twofold, that is, by increasing the density of immobilized cells per carrier volume from 6.1 x 10(7) to 1.2 x 10(8) cell/mL, or by increasing the packed-bed height from 0.2 to 0.4 m. Both strategies would be rather simple to test and implement in the packed-bed bioreactor system used for this study. As a result, it would be possible to achieve a substantial improvement of about twofold higher productivity as compared with the basal conditions.

Use of glucose consumption rate (GCR) as a tool to monitor and control animal cell production processes in packed-bed bioreactors.

For animal cell cultures growing in packed-bed bioreactors where cell number cannot be determined directly, there is a clear need to use indirect methods that are not based on cell counts in order to monitor and control the process. One option is to use the glucose consumption rate (GCR) of the culture as an indirect measure to monitor the process in bioreactors. This study was done on a packed-bed bioreactor process using recombinant CHO cells cultured on Fibra-Cel disk carriers in perfusion mode at high cell densities. A key step in the process is the switch of the process from the cell growth phase to the production phase triggered by a reduction of the temperature. In this system, we have used a GCR value of 300 g of glucose per kilogram of disks per day as a criterion for the switch. This paper will present results obtained in routine operations for the monitoring and control of an industrial process at pilot-scale. The process operated with this GCR-based strategy yielded consistent, reproducible process performance across numerous bioreactor runs performed on multiple production sites.

Potential of cell retention techniques for large-scale high-density perfusion culture of suspended mammalian cells.

This review focuses on cultivation of mammalian cells in a suspended perfusion mode. The major technological limitation in the scaling-up of these systems is the need for robust retention devices to enable perfusion of medium as needed. For this, cell retention techniques available to date are presented, namely, cross-flow filters, hollow fibers, controlled-shear filters, vortex-flow filters, spin-filters, gravity settlers, centrifuges, acoustic settlers, and hydrocyclones. These retention techniques are compared and evaluated for their respective advantages and potential for large-scale utilization in the context of industrial manufacturing processes. This analysis shows certain techniques have a limited range of perfusion rate where they can be implemented (most microfiltration techniques). On the other hand, techniques were identified that have shown high perfusion capacity (centrifuges and spin-filters), or have a good potential for scale-up (acoustic settlers and inclined settlers). The literature clearly shows that reasonable solutions exist to develop large-scale perfusion processes.

Monitoring of temperature effects on animal cell metabolism in a packed bed process.

Animal cell (Chinese Hamster Ovary) concentration was determined on-line in a packed bed process using dielectric spectroscopy. This enabled the evaluation of the effect of temperature on specific metabolic rates during 3 months of continuous culture. The effect of low cultivation temperature on cell growth and metabolism was monitored, and the data were used for process development. At 37 degrees C cells grew exponentially with a specific growth rate of 0.038 d-1 and specific glucose uptake and lactate production rates increased continually. Reduction of the temperature to 33.5 degrees C resulted in a lowering of these metabolic rates while having no effect on cell proliferation. Subsequent reduction of the temperature to 32 degrees C resulted in stabilization of the cell concentration at a high density (3.6 x 10(7) cell per mL of packed bed). In addition, the specific production rate of the protein of interest increased by a factor of 6 compared to the value at 37 degrees C. During the stationary phase at 32 degrees C, all other specific metabolic rates could be controlled to low and constant levels.

The role of vitamins and amino acids on hybridoma growth and monoclonal antibody production.

A balanced supplementation method was applied to develop a serum and protein- free medium supporting hybridoma cell batch culture. The aim was to improve systematically the initial formulation of the medium to prevent limitations due to unbalanced concentrations of vitamins and amino acids. In a first step, supplementation of the basal formulation with 13 amino acids, led to an increase of the specific IgA production rate from 0.60 to 1.07 pg cell(-1) h(-1). The specific growth rate remained unchanged, but the supplementation enabled maintenance of high cell viability during the stationary phase of batch cultures for some 70 h. Since IgA production was not growth- related, this resulted in an approximately4-fold increase in the final IgA concentration, from 26.6 to 100.2 mgl(-1). In a second step, the liposoluble vitamins E and K(3) were added to the medium formulation. Although this induced a slightly higher maximal cell concentration, it was followed by a sharp decline phase with the specific IgA production rate falling to 0.47 pg cell(-1) h(-1). However, by applying a second cycle of balanced supplementation with amino acids this decline phase could be reduced and a high cell viability maintained for over 300 h of culture. In this vitamin- and amino acid- supplemented medium, the specific IgA production rate reached a value of 1.10 pg cell(-1)h(-1) with a final IgA concentration of 129.8 mgl(-1). The latter represents an increase of approximately5-fold compared to the non- supplemented basal medium.

Hydrogen atoms cause long-range electronic effects on graphite

We report on long-range electronic effects caused by hydrogen-carbon interaction at the graphite surface. Two types of defects could be distinguished with a combined mode of scanning tunneling microscopy and atomic force microscopy: chemisorption of hydrogen on the basal plane of graphite and atomic vacancy formation. Both types show a (sqrt[3]xsqrt[3])R30 degrees superlattice in the local density of states but have a different topographic structure. The range of modifications in the electronic structure, of fundamental importance for electronic devices based on carbon nanostructures, has been found to be of the order of 20-25 lattice constants.

Takayasu arteritis and cutaneous necrotizing vasculitis.

Takayasu arteritis (TA) is an inflammatory arteriopathy involving predominantly the aorta and its main branches. The disease evolves in two phases: a first, nonspecific inflammatory stage and a late 'pulseless' stage, in which complications related to arterial stenosis and aneurysm formation predominate. In both phases, skin manifestations, such as inflammatory nodules, erythema-nodosum- and pyoderma-gangrenosum-like ulcers, have been described. We report 2 patients with TA, who had cutaneous necrotizing vasculitis as presenting manifestation of the disease. A review of the literature revealed 8 similar cases. TA does not only involve large arteries, but also small blood vessels. The observation that in TA the inflammatory process of the large arteries affects regions of the walls supplied by the vasa vasorum, the anatomy of which bears resemblance to the cutaneous vessel system, suggests that primary involvement of small vessels contributes to the development of the clinicopathological features of TA. Knowledge of the skin manifestations associated with TA remains important for its diagnosis and prompt instauration of life-saving treatment.

A new method for on-line measurement of the volumetric oxygen uptake rate in membrane aerated animal cell cultures.

Oxygen is a key substrate in animal cell metabolism and its consumption is thus a parameter of great interest for bioprocess monitoring and control. A system for measuring it based on an oxygen balance on the liquid phase was developed. The use of a gas-permeable membrane offered the possibility to provide the required quantity of oxygen into the culture, while avoiding problems of foaming or shear stress generally linked to sparging. This aeration system allowed moreover to keep a known and constant k(L)a value through cultures up to 400 h. Oxygen uptake rate (OUR) was measured on-line with a very good accuracy of +/-5%, and the specific OUR for a CHO cell line was determined during batch (growth phase) and continuous culture as, respectively, equal to 2. 85x10(-13) and 2.54x10(-13) mol O(2) cell(-1) h(-1). It was also shown that OUR continuous monitoring gives actually more information about the metabolic state of the culture than the cell concentration itself, especially during transition phases like the end of the growth phase in a batch culture.

Measurement of volumetric (OUR) and determination of specific (qO2) oxygen uptake rates in animal cell cultures.

Oxygen is a key substrate in animal cell metabolism. It has been reported that the oxygen uptake rate (OUR) is a good indicator of cellular activity, and even under some conditions, a good indicator of the number of viable cells. The measurement of OUR is difficult due to many different reasons. In particular, the very low specific consumption rate (0.2 x 10(-12) mol cell h-1), the sensitivity of the cells to variations in dissolved oxygen concentration and the difficulty to provide oxygen without damaging the cells are problems which must be taken into account for the development of OUR measurement methods. Different solutions based on an oxygen balance on either the liquid phase or around the entire reactor, and with a variable or stable concentration of dissolved oxygen have been reported. The accuracy of the OUR measurements and the required analytical devices are very different from method to method.

[Epidermolysis bullosa acquisita and metastatic cancer of the uterine cervix]. / Epidermolyse bulleuse acquise et cancer du col utérin métastatique.

INTRODUCTION: Epidermolysis bullosa acquisita may be associated to a systemic or malignant disease. Here, we report a case of epidermolysis bullosa acquisita associated with a carcinoma of the cervix. CASE REPORT: A 44-year-old woman presented inflammatory, bullous and erosive mucocutaneous lesions. Investigations lead to the diagnosis of epidermolysis bullosa acquisita and revealed pelvic metastases originating from a poorly differentiated carcinoma. The cutaneous lesions completely regressed after the treatment of the tumor but reappeared with tumoral relapse. DISCUSSION: This is the first report of an association of epidermolysis bullosa acquisita and carcinoma of the cervix. The clinical course of these two entities suggests that the EBA in this case may be paraneoplastic.

Cellulitis after hip surgery: long-term follow-up of seven cases.

Cellulitis of the buttock after hip surgery is rarely reported, but raises concern about possible infection of the implant. In view of this we have investigated the frequency of previous hip surgery in patients with cellulitis of the hip and/or buttock and assessed for any predisposing factors. A review was made of the case notes of all patients admitted to our department with infectious cellulitis of the hip and/or buttock between 1981 and 1995. Seven of nine patients previously had had implantation of a hip prosthesis. The interval between skin infection and surgery was 7-9 weeks in two patients and 55-520 weeks in five. No infection of the implant was evident. The assumed portals of entry were gluteal fold intertrigo, tinea pedis, psoriatic plaque and a carbuncle of the buttock. The infection was successfully treated by intravenous antibiotics and, after a follow-up of a mean 64 months, no recurrence of cellulitis has been observed and only one aseptic loosening has occurred. Infectious cellulitis of the hip or buttock following hip surgery can occur secondary to impaired lymphatic drainage, a few weeks up to several years after surgery, without there being any infection of the orthopaedic implant.

Long-term assessment of chronic leg ulcer treatment by autologous skin grafts.

BACKGROUND: Chronic leg ulcers (CLU) are a common and major cause of morbidity. For this reason, we systematically perform autologous skin grafting. OBJECTIVE: Long-term evaluation of this treatment. PATIENTS AND METHODS: Among the 521 out-patients or those hospitalized for CLU between 1981 and 1993, we assessed 188 (118 women, 70 men, mean age 74 years, 144 grafts, 44 non-grafted). RESULTS: For the grafted CLU, there were 46 failures (17.5%), 152 (58%) healed in a mean time of 2.2 months and 64 relapsed (24.5%). For the non-grafted CLU, 3 did not heal (3%), 20 relapsed (22.5%) and 66 healed (74.5%) in a mean time of 4.7 months. All the patients who suffered from painful CLU mentioned a regression of pain after the graft. Finally, 87.5% of patients declared that they would accept a new graft. CONCLUSIONS: We did not note any real difference in closure and recurrence rates between grafted and non-grafted ulcers. This is most likely due to an important selection bias related to the methodology of our study. The grafted ulcers were more serious: they were larger (28.9 against 7.9 cm2) and older (11.1 against 5.6 months).