Maximally-localized Wannier functions for entangled energy bands

We present a method for obtaining well-localized Wannier-like functions (WFs) for energy bands that are attached to or mixed with other bands. The present scheme removes the limitation of the usual maximally-localized WFs method (N. Marzari and D. Vanderbilt, Phys. Rev. B 56, 12847 (1997)) that the bands of interest should form an isolated group, separated by gaps from higher and lower bands everywhere in the Brillouin zone. An energy window encompassing N bands of interest is specified by the user, and the algorithm then proceeds to disentangle these from the remaining bands inside the window by filtering out an optimally connected N-dimensional subspace. This is achieved by minimizing a functional that measures the subspace dispersion across the Brillouin zone. The maximally-localized WFs for the optimal subspace are then obtained via the algorithm of Marzari and Vanderbilt. The method, which functions as a postprocessing step using the output of conventional electronic-structure codes, is applied to the s and d bands of copper, and to the valence and low-lying conduction bands of silicon. For the low-lying nearly-free-electron bands of copper we find WFs which are centered at the tetrahedral interstitial sites, suggesting an alternative tight-binding parametrization.Comment: 13 pages, with 9 postscript figures embedded. Uses REVTEX and epsf macro

Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine

Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

SME 4.0: The Role of Small- and Medium-Sized Enterprises in the Digital Transformation

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The HERMES Spectrometer

The HERMES experiment is collecting data on inclusive and semi-inclusive deep inelastic scattering of polarised positrons from polarised targets of Il, D, and He-3. These data give information on the spin structure of the nucleon. This paper describes the forward angle spectrometer built for this purpose. The spectrometer includes numerous tracking chambers (micro-strip gas chambers, drift and proportional chambers) in front of and behind a 1.3 T.m magnetic field, as well as an extensive set of detectors for particle identification (a lead-glass calorimeter, a pre-shower detector, a transition radiation detector, and a threshold Cherenkov detector). Two of the main features of the spectrometer are its good acceptance and identification of both positrons and hadrons, in particular pions. These characteristics, together with the purity of the targets, are allowing HERMES to make unique contributions to the understanding of how the spins of the quarks contribute to the spin of the nucleon. (C) 1998 Elsevier Science B.V. All rights reserved

Detection of early-stage pancreatic carcinoma

4613 Background: Invasive pancreatic carcinoma is a virtually lethal disease, mostly because of the failure to detect it at a sufficiently early timepoint for successful treatment. Our laboratory has identified a unique biomarker detected by MAb PAM4 that shows high specificity for a mucin glycoprotein expressed by pancreatic carcinoma (PC). While identified in almost 90% of PC and its precursor lesions, the antigen is not detectable in normal pancreas. We are investigating this biomarker for the early detection of PC. Methods: Both immunohistochemical (IHC) and enzyme immunoassay (EIA) were employed for detection and/or quantitation of PAM4-mucin in tissue and sera, respectively. Results: We have extended our prior IHC results with precursor lesions (Clin Cancer Res 2007;13:7380–7); PAM4 gave an intense, diffuse labeling pattern in 81% of mucinous cystic neoplasms (MCN), with an additional 11% showing a focal pattern (n=27). Thus, a total of 92% of MCN showed evidence of PAM4-antigen expression. Of interest, a difference in the labeling pattern was observed in association with the grade of dysplasia, providing easy identification of MCN with high- grade dysplasia. We previously reported use of an EIA for quantitation of PAM4-antigen in sera. The assay demonstrated a sensitivity and specificity of 77% and 95%, respectively, for identification of PC (J Clin Oncol, 2006;24:252–8). We have now confirmed these results in a set of serum specimens (n= 49 PC, 13 normal) for which staging information was available. Overall specificity and sensitivity were 82% and 85%, respectively, calculated by ROC curve analysis (AUC=0.878±0.045; 95% CI=0.769–0.947). Although only a small number of specimens were from patients with stage I disease (n=12), 92% of these were above the cutoff value for positive response. A correlation was observed for average concentration of antigen in the circulation with stage of disease (R2=0.988). Conclusions: IHC and EIA results indicate that PAM4 identifies a biomarker for PC that is present at the earliest stages of neoplastic transformation, thus warranting controlled analyses of larger specimen numbers. (Supported in part by USPHS grant CA096924 from the NIH.) [Table: see text] </jats:p

Evaluation of a novel MUC1 biomarker/target antigen for pancreatic cancer

4096 Background: Pancreatic cancer provides a major challenge in terms of diagnosis and treatment. We have developed an anti-MUC1 MAb, PAM4, which identifies an epitope that is more restricted to MUC1-expressed by pancreatic cancer than MUC1 from other forms of cancer. PAM4 has been studied for in vitro and in vivo detection and therapy of pancreatic cancer. Methods: The in vitro immunoassay consists of PAM4 as the capture reagent and an IgG fraction derived from a polyclonal, anti-MUC1 antiserum as the probe. For in vivo detection and therapy, PAM4 is either directly radiolabeled or used in a 2-step pretargeting protocol. Results: The PAM4-based immunoassay provided high sensitivity (77%) and specificity (95%), with a value ≥ 10.2 units/ml indicating a high likelihood of pancreatic cancer, as compared to normal and benign disease groups and non-pancreatic cancers. A direct pairwise comparison of the PAM4 and CA19–9 immunoassays for discrimination of pancreatic cancer and pancreatitis demonstrated a superior performance of the PAM4-immunoassay (P&lt;0.003). Initial clinical studies with directly labeled 131I-PAM4 provided positive imaging in 8/10 patients, with one negative patient having only pancreatitis, and the other negative patient having a tumor that was MUC1-negative. A Phase I, dose-escalation study of 90Y-humanized PAM4 administered as a single dose to patients with advanced pancreatic cancer is in progress (Immunomedics, Inc), and has already achieved doses of 20 mCi/m2. Finally, pretargeting involving a bispecific MAb with one arm being PAM4 targeting MUC1 and the other arm capturing a hapten peptide carrying a radionuclide is under preclinical evaluation. This second generation targeting system has shown higher tumor/nontumor ratios and improved imaging (111In) as compared to directly radiolabeled PAM4. Conclusions: These results suggest that the PAM4-reactive MUC1 epitope may prove useful as a selective biomarker/target antigen for diagnosis, detection, imaging, and therapy of pancreatic cancer. (Supported in part by grants CA96924and CA98488 from the NIH). [Table: see text] </jats:p