Rigorous Lower Bounds for the Ground State Energy of Molecules by Employing Necessary N-Representability Conditions.

Electronic structure calculations, in particular the computation of the ground state energy, lead to challenging problems in optimization. These problems are of enormous importance in quantum chemistry for calculations of properties of solids and molecules. Minimization methods for computing the ground state energy can be developed by employing a variational approach, where the second-order reduced density matrix defines the variable. This concept leads to large-scale semidefinite programming problems that provide a lower bound for the ground state energy. Upper bounds of the ground state energy can be calculated for example with the Hartree-Fock method or numerically more exact for a given basis set by full CI. However, Nakata et al. ( J. Chem. Phys.200111482828292) observed that due to numerical errors the semidefinite solver produced erroneous results with a lower bound significantly larger than the full CI energy. For the LiH, CH-, NH-, OH, OH-, and HF molecules violations within one mhartree were observed. We applied the software VSDP which takes all numerical errors due to floating-point arithmetic operations into consideration. For two test libraries VSDP provides tight rigorous error bounds lower than full CI energies reported with an accuracy of 0.1 to 0.01 mhartree. Only little computation work must be spent in order to compute close rigorous error bounds for the ground state energy.

Decreased Th1-type inflammatory cytokine expression in the skin is associated with persisting symptoms after treatment of erythema migrans.

BACKGROUND: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e.g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. METHODS: A prospective follow-up study of 109 patients with EM was conducted at the Åland Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-γ, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. FINDINGS: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-γ in the EM biopsies (p=0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. CONCLUSION: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.

Cytotoxic mechanisms may play a role in the local immune response in the central nervous system in neuroborreliosis.

Aiming to investigate the role of cytotoxic mechanisms in neuroborreliosis (NB), the cytokines IL-2, IL-7, IL-10, IL-12p70, IL-15, GM-CSF and the Th17-cytokine IL-17 were analyzed in cerebrospinal fluid (CSF) and plasma from NB-patients. NB-patients showed increased levels in CSF compared to controls of all analyzed cytokines except IL-15 but not in plasma. Blood lymphocytes from three NB-patients showed functional cytotoxicity in response to autologous Borrelia-infected macrophages. The findings support a role for cytotoxic mechanisms in the local immune response in NB and in addition suggest an increase of IL-17.

Complement activation in Lyme neuroborreliosis--increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS.

A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.

TBE in Aland Islands 1959-2005: Kumlinge disease.

Tick-borne encephalitis, TBE, has been observed in Aland Islands (population 26,500) for more than 60 years. Because of the small population, the relative incidence is high. Antibodies to TBE virus have been found in ca. 5% of healthy blood donors, indicating that subclinical infection must be common. This study is a review of the symptoms and signs of all the 301 serologically verified cases of TBE seen in Aland during 1959-2005. It also aims at analysing any possible changes in the symptoms and signs of TBE over time. The annual number of patients has been from 1 to 26, and has increased over time. The clinical picture has not undergone any conspicuous changes during these years. A few patients have had permanent neurological damage. There were no certain deaths from TBE. Simple practical measures may be taken to diminish, but not to eliminate, the risk of tick bites. Vaccination of exposed people is recommended, and general vaccination against TBE has commenced in Aland, beginning 2006. This is expected to reduce the incidence of TBE among the population to almost nil, provided that new inhabitants are vaccinated and that booster vaccinations are carried out as required.

Characteristics of erythema migrans in Borrelia afzelii and Borrelia garinii infections.

Erythema migrans is the most common manifestation of stage I Lyme borreliosis. This study investigated the relation between the subspecies of Borrelia burgdorferi involved, the time of development and the appearance of the manifestation. The study comprised 33 cases of erythema migrans yielding B. burgdorferi sensu lato by culture of skin biopsy. The species was determined by polymerase chain reaction analysis of the cultivated spirochaetes. In 22 of the cases, B. afzelii was demonstrated, whereas 11 yielded growth of B. garinii. All 11 erythemas associated with B. garinii were homogeneous, whereas 20 of the 22 associated with B. afzelii were annular. The garinii erythemas developed more rapidly, and were generally larger than the afzelii erythemas. The observations call for comparison with other geographical areas with similar, and with different, borrelial infection spectra.

No soluble common cytokine receptor gamma chain (gamma(c)) in activated human lymphocyte cultures-comparison with soluble IL-2Ralpha.

The presence of a soluble form of the common cytokine receptor gamma chain (gamma(c)) in cell free supernatants from unstimulated and 1-6 days PHA stimulated peripheral blood lymphocyte (PBL) cultures was analyzed using a sandwich ELISA. No naturally produced soluble gamma(c) could be detected in these cell free culture supernatants, although a sensitivity in the nanogram range was achieved for recombinant baculovirus expressed human soluble gamma(c) with this assay (detection limit 0.2 ng hIL-2 sRgamma). Analysis of the very same supernatants for soluble IL-2Ralpha demonstrated increased concentrations (up to 20.4 ng/ml) of this other IL-2R member. The membrane-associated form of the common cytokine receptor gamma chain was detected in cell lysates prepared from stimulated PBL at a concentration of 3.5 ng per 0.5 x 10(6) cells. Analysis of a small panel of serum samples from patients with different disorders verified that the soluble form of hIL-2Ralpha, but not hIL-2 sRgamma, can be detected, which thereby strongly suggests that the human soluble gamma(c) seems to be a valuable marker only for a limited number of clinical disorders.