Mild and efficient copper-catalyzed N-arylation of alkylamines and N-H heterocycles using an oxime-phosphine oxide ligand

A mild and efficient copper-catalyzed system for N-arylation of alkylamines and N-H heterocycles with aryl iodides using a novel, readily prepared and highly stable oxime-functionalized phosphine oxide ligand was developed. The coupling reactions could even be performed in solvent-free conditions with moderate to good yields. (c) 2005 Elsevier Ltd. All rights reserved.

Large-Scale Neural Systems for Vision and Cognition

— Consideration of how people respond to the question What is this? has suggested new problem frontiers for pattern recognition and information fusion, as well as neural systems that embody the cognitive transformation of declarative information into relational knowledge. In contrast to traditional classification methods, which aim to find the single correct label for each exemplar (This is a car), the new approach discovers rules that embody coherent relationships among labels which would otherwise appear contradictory to a learning system (This is a car, that is a vehicle, over there is a sedan). This talk will describe how an individual who experiences exemplars in real time, with each exemplar trained on at most one category label, can autonomously discover a hierarchy of cognitive rules, thereby converting local information into global knowledge. Computational examples are based on the observation that sensors working at different times, locations, and spatial scales, and experts with different goals, languages, and situations, may produce apparently inconsistent image labels, which are reconciled by implicit underlying relationships that the network’s learning process discovers. The ARTMAP information fusion system can, moreover, integrate multiple separate knowledge hierarchies, by fusing independent domains into a unified structure. In the process, the system discovers cross-domain rules, inferring multilevel relationships among groups of output classes, without any supervised labeling of these relationships. In order to self-organize its expert system, the ARTMAP information fusion network features distributed code representations which exploit the model’s intrinsic capacity for one-to-many learning (This is a car and a vehicle and a sedan) as well as many-to-one learning (Each of those vehicles is a car). Fusion system software, testbed datasets, and articles are available from http://cns.bu.edu/techlab.

Atmospheric neutrino oscillation analysis with subleading effects in Super-Kamiokande I, II, and III

We present a search for nonzero θ13 and deviations of sin2θ23 from 0.5 in the oscillations of atmospheric neutrino data from Super-Kamiokande I, II, and III. No distortions of the neutrino flux consistent with nonzero θ13 are found and both neutrino mass hierarchy hypotheses are in agreement with the data. The data are best fit at Δm2=2.1×10-3eV2, sin2θ13=0.0, and sin2θ23=0.5. In the normal (inverted) hierarchy θ13 and Δm2 are constrained at the one-dimensional 90% C.L. to sin2θ13<0.04(0.09) and 1.9(1.7)×10 -3<Δm2<2.6(2.7)×10-3eV2. The atmospheric mixing angle is within 0.407≤sin2θ23≤0.583 at 90% C.L. © 2010 The American Physical Society.

Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886.