Serologic evidence of previous Campylobacter jejuni infection in patients with the Guillain-Barré syndrome

OBJECTIVE: To determine if patients with the Guillain-Barré syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms. DESIGN: A case-control study. SETTING: Several university medical centers. PATIENTS: Case patients met clinical criteria for the Guillain-Barré syndrome between 1983 and 1990 and had a serum sample collected and frozen within 3 weeks after onset of neurologic symptoms (n = 118). Disease controls were patients with other neurologic illnesses (n = 56); healthy controls were hospital employees or healthy family members of patients (n = 47). MEASUREMENTS: Serum IgA, IgG, and IgM antibodies to C. jejuni were determined by enzyme-linked immunosorbent assays. Assays were done in a blinded manner. RESULTS: Optical density ratios > or = 2 in two or more immunoglobulin classes were seen in 43 (36%) of patients with the Guillain-Barré syndrome and in 10 (10%) of controls (odds ratio, 5.3; 95% CI, 2.4 to 12.5; P < 0.001). Increasing the optical density ratio or the number of immunoglobulin classes necessary to yield a positive result increased the strength of the association. The number of patients with the Guillain-Barré syndrome who had positive serologic responses was greatest from September to November (P = 0.02). Male patients were three times more likely to have serologic evidence of C. jejuni infection (P = 0.009); the proportion of patients with the syndrome who had a positive serologic response increased with age. CONCLUSIONS: Patients with the Guillain-Barré syndrome are more likely than controls to have serologic evidence of C. jejuni infection in the weeks before onset of neurologic symptoms. Campylobacter jejuni may play a role in the initiation of the Guillain-Barré syndrome in many patients.     

Comparison of concentrations and size distributions of fungal spores in buildings with and without mould problems

Concentrations and types of airborne fungal spores and their aerodynamic sizes were studied in nine buildings with mould problems and in matched reference buildings in order to characterize the exposure in buildings with mould problems. Samples were taken with Andersen six-stage impactors in the autumn and winter. In winter, total concentrations of fungal spores in buildings with mould problems were twice those in reference buildings, even though all concentrations were quite small. In the autumn, the differences were less obvious due to the masking effect of outdoor air fungi. Also, the compositions of fungal genera differed in buildings with mould problems from that in reference buildings. The difference was most significant in the size range 2.1-4.7 μm. The size distribution of fungal spores in dwellings with mould problems skewed towards larger particles than in reference dwellings. The observed differences in size distribution indicate differences in airborne behaviour of fungal spores and, consequently, in respiratory exposure.     

Extension of the decidability of the marked PCP to instances with unique blocks

In the Post Correspondence Problem (PCP) an instance (h,g)$(h,g)$ consists of two morphisms h$h$ and g$g$, and the problem is to determine whether or not there exists a nonempty word w$w$ such that h(w)=g(w)$h\left(w\right)=g\left(w\right)$. Here we prove that the PCP is decidable for instances with unique blocks using the decidability of the marked PCP. Also, we show that it is decidable whether an instance satisfying the uniqueness condition for continuations has an infinite solution. These results establish a new and larger class of decidable instances of the PCP, including the class of marked instances.     

Design and construction of a high temperature and pressure electrodeless conductivity probe

An electrodeless conductivity probe has been designed and tested at temperatures up to 250 degrees C and pressures of 4.13 MPa (600 psi). A unique pressure seal permits temperature cycling. Design of the electronics permits accurate measurement of conductivities at various elevated temperatures in spite of the change of magnetic properties of the toroids with temperature. The design of the probe can be adapted for insertion, in-line, or bypass operation.     

Effect of Austenite Pancaking on the Microstructure,Texture, and Bendability of an Ultrahigh-Strength Strip Steel

The effect of austenite pancaking in the non-recrystallization regime on microstructure and texture evolution and thereby on bendability was investigated in an ultrahigh-strength strip steel with a martensitic-bainitic microstructure. The results indicate that an increase in rolling reduction (R _tot) below the non-recrystallization temperature, which improves the strength and toughness properties, increases the intensities of the ~{554}〈225〉 _α and ~{112}〈110〉 _α texture components along the strip centerline and of the ~{112}〈111〉 _α component at the surface region. Even with the highest R _tot of 79 pct, the bendability along the rolling direction was good, but the preferred alignment of rod-shaped MA constituents along the rolling direction led to a dramatic decrease in the bendability transverse to the rolling direction, with severe cracking occurring even at small bending angles. The early cracking is attributed to localization of the strain in narrow shear bands. It is concluded that the R_tot value has to be limited to guarantee successful bendability.     

Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody–Drug Conjugation Chemistry

Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug‐delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site‐selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate‐based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti‐EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR‐positive cancer cells.     

Consensus kNN QSAR: a versatile method for predicting the estrogenic activity of organic compounds in silico. A comparative study with five estrogen receptors and a large, diverse set of ligands

Quantitative structure-activity relationships (QSARs) have proved increasingly useful for predicting the biological activities of molecules (e.g., their binding affinities to different receptors) and can be used in environmental chemistry as a preliminary tool for screening the activities of untested molecules, producing valuable information on which compounds should be tested more thoroughly with experimental affinity assays or in animals. The predictive ability of the consensus kNN QSAR method is corroborated here using a diverse set of 245 compounds, which have been assayed for their relative binding affinities to the estrogen receptor of four species: human (ER alpha and ER beta), calf, mouse, and rat. Leave-one-out cross-validation (LOO-CV) and gamma-randomization tests were applied to the QSAR models for internal validation, and separate training and test sets were used for external validation. The internal predictive abilities of the consensus models for all five data sets were convincing, with cross-validated correlation coefficients (LOO-CV q2 values) varying from 0.69 (human ER beta data) to 0.79 (human ER alpha data). The external predictive abilities were also encouraging, as the predictive r2 scores (pr-r2 values) varied from 0.62 (human ER beta data) to 0.77 (calf and mouse data). The results indicate that consensus kNN QSAR is a feasible method for rapid screening of the estrogenic activity of organic compounds.