A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Chemically induced residual stresses in dental composites

In several European countries, dental composites are replacing mercury-containing amalgams as the most common restorative materials. One problem with dental composites is residual stresses which may lead to poor performance of the restoration. In the present study, a combined modeling and materials characterization approach is presented and predictions compare well with experimental data on residual stresses. The model takes stress relaxation into account through the complete relaxation time spectrum of the resin. The approach allows for detailed parametric studies where resin and composite composition as well as cure conditions may be tailored with respect to residual stress generation.     

Fast Parallel Reordering and Isomorphism Testing of k -Trees

In this paper two problems on the class of k -trees, a subclass of the class of chordal graphs, are considered: the fast reordering problem and the isomorphism problem. An O(log ² n) time parallel algorithm for the fast reordering problem is described that uses O(nk(n-k)/\kern -1ptlog n) processors on a CRCW PRAM proving membership in the class NC for fixed k . An O(nk(k+1)!) time sequential algorithm for the isomorphism problem is obtained representing an improvement over the O(n ² k(k+1)!) algorithm of Sekharan (the second author) [10]. A parallel version of this sequential algorithm is presented that runs in O(log ² n) time using O((nk((k+1)!+n-k))/log n) processors improving on a parallel algorithm of Sekharan for the isomorphism problem [10]. Both the sequential and parallel algorithms use a concept introduced in this paper called the kernel of a k -tree.     

GQR-based models for directional wireless channels

In this paper novel reduced complexity statistical models for the representation of directional wireless channels affected by Rayleigh fading are developed. Their derivation is based on the evaluation of Fourier integrals by means of Gaussian quadrature rules (GQRs). The proposed models represent a communication channel as a tapped-angle and -delay line with non uniform spacing between successive taps. The application of the GQR approach to three different scenarios is also illustrated. Numerical results evidence that these models can provide a simple and accurate stochastic representation of directional fading channels.     

Surgical treatment of atherosclerotic lesions of subclavian artery: carotid-subclavian bypass versus subclavian-carotid transposition

BACKGROUND: The aim of this retrospective study is to analyze the short and long term results of two different surgical treatments in patients with subclavian lesions: common carotid-subclavian artery bypass (CSB) versus transposition of subclavian artery on the common carotid artery (SCT). METHODS: From 1981 until 1995, 40 non randomized patients with symptomatic subclavian steal underwent 20 CSBs and 20 SCTs. Risk factor rates were equally balanced in the two groups. Surgery was carried out routinely under general anesthesia, with electroencephalic continuous monitoring. Patency of revascularization was assessed by physical examination, brachial blood pressure determinations, ultrasound sonography and angiography whenever recurrence of symptoms developed or when the function of repair was in doubt. Patients were examined every year. In Spring 1996 (range 9-189 mos, average 7 years) a general clinical-instrumental follow-up was performed. RESULTS: In the short term (<30 days) mortality was 5%: one death (5%) for pulmonary embolism in a patient with CSB and one for myocardial infarction in a patient with SCT. The early thrombosis rate was 5% (1 CSB and 1 common carotid artery distal to a patent SCT). During follow-up 10 patients (25%) died and 6 were lost. The six-year actuarial patency rate was 100% for SCT and 66% for CSB. Moreover there were 3 thromboses of the vertebral artery homolateral to patent CSBs. CONCLUSIONS: In conclusions SCT should be considered the surgical technical choice for the treatment of proximal subclavian artery lesions.     

From information to probability: An axiomatic approach—Inference is information processing

We define the very rich language of composed conditionals on a three‐valued logic and use this language as the communication tool between man and machine. Communication takes place for three reasons: knowledge acquisition, query, and response. Learning, thinking, and answering questions are of a pure information theoretical nature. The pivot of this knowledge processing concept is the amount of information (bit) we receive if a conditional becomes true. We follow an axiomatic approach to information theory rather than the classical probabilistic approach of Shannon; information comes first, and then comes probability. In the light of this philosophy, query and response experience new interpretations. Both, acquisition and response are realized by maximizing entropy and minimizing relative entropy, respectively. The iterative solution of these mathematical optimization problems gives new insights into the adaptation of prior knowledge to new information. Our expert system shell SPIRIT supports this kind of knowledge processing, which will be established by suitable examples. © 2003 Wiley Periodicals, Inc.     

Adaptive Radar Detection of Distributed Targets in Homogeneous and Partially Homogeneous Noise Plus Subspace Interference

This paper addresses adaptive radar detection of distributed targets in noise plus interference assumed to belong to a known or unknown subspace of the observables. At the design stage we resort to either the GLRT or the so-called two-step GLRT-based design procedure and assume that a set of noise-only data is available (the so-called secondary data). Detection algorithms have been derived modeling noise vectors, corresponding to different range cells, as independent, zero-mean, complex normal ones, sharing either the same covariance matrix (homogeneous environment) or the same covariance matrix up to possibly different (mean) power levels between primary data, i.e., range cells under test, and secondary ones (partially homogeneous environment). The performance assessment has been conducted by Monte Carlo simulation, also in comparison to previously proposed detection algorithms, and confirms the effectiveness of the newly proposed ones     

Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor: an analysis of 497 patients

BACKGROUND: There is great interpatient variability in the number of peripheral blood stem cells collected, as measured by CD34+ cell content, after the administration of chemotherapy and a growth factor. The ability to predict patients who fail to yield adequate quantities of CD34+ cells would be of value. However, very few reports include large numbers of patients treated in an identical fashion. STUDY DESIGN AND METHODS: Between 1991 and 1995, 497 consecutive patients with a variety of malignant diseases received cyclophosphamide (4 g/m2), etoposide (600 mg/m2), and granulocyte-colony-stimulating factor (6 micrograms/kg/day) for mobilization and collection of a target dose > or = 2.5 x 10(8) CD34+ cells per kg. Multivariate analyses were performed to determine the factors associated with failure to achieve this target harvest. RESULTS: A median of 14.71 x 10(6) CD34+ cells per kg (range, 0.08-137.55) was harvested with a median of 2 (range, 1-11) apheresis procedures. Ninety-one percent of patients yielded > or = 2.5 x 10(5) CD34+ cells per kg. Patients with Stage II-III breast cancer, who had pretreatment platelet counts > or = 150 x 10(9) per L and patients who underwent < or = 1 prior chemotherapy regimen had improved CD34+ cell yields. However, most patients with adverse risk factors yielded > or = 2.5 x 10(6) CD34+ cells per kg. CONCLUSION: A regimen of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor led to the successful collection of adequate numbers of CD34+ cells in most patients without excessive toxicity. These observations confirm previous reports that intense prior therapy adversely affects the quantity of CD34+ cells harvested. Pretreatment and posttreatment variables did not predict with any certainty the small fraction of patients who fail to yield > or = 2.5 x 10(6) CD34+ cells per kg via multiple apheresis procedures.