Pallet Management System: A Study of the Implementation of UID/RFID Technology for Tracking Shipping Materials within the Department of Defense Distribution Network

Sponsored Report (for Acquisition Research Program)The purpose of this MBA project is to identify the typical pallet utilization for the Defense Distribution Depot San Joaquin (DDJC) shipments to the Defense Distribution Depot San Diego (DDDC). That information will be used as the basis for suggesting a standardized reutilization management system for wood and non-wood pallets. This project will analyze the inclusion of Radio Frequency Identification and Unique Item Identification in conjunction with bar code technology for the improvement of asset visibility within the Department of Defense''s supply network.Naval Postgraduate School Acquisition Research ProgramApproved for public release; distribution is unlimited

Methodology to demonstrate pile capacity In relaxing ground

Driven pre-stressed concrete piles have been used as a foundation system to support abutments and piers of a bridge constructed near Ballina in New South Wales, Australia. In order to achieve the required geotechnical capacity, the piles were required to be driven through soft clay and sand to moderately weathered rock. Pile Driving Analyser (PDA) testing together with CAPWAP analysis was performed to assess the integrity and geotechnical capacity of the driven piles. Pile damage was observed during driving. To prevent damage a rock shoe was retrofitted to the piles prior to installation. Reductions in pile capacity (or relaxation) were observed between end of drive (EOD) and later restrike testing (RST). A substantial amount of additional pile testing was performed at different times after driving to assess the changes in pile capacity over time. Most piles were re-driven to achieve higher capacity. Pile capacity could not be achieved in one pier and additional piles were installed to reduce the required pile test loa

Comparison of K+K^+ and e−e^- Quasielastic Scattering

We formulate $K^+$-nucleus quasielastic scattering in a manner which closely parallels standard treatments of $e^-$-nucleus quasielastic scattering. For $K^+$ scattering, new responses involving scalar contributions appear in addition to the Coulomb (or longitudinal) and transverse $(e,e')$ responses which are of vector character. We compute these responses using both nuclear matter and finite nucleus versions of the Relativistic Hartree Approximation to Quantum Hadrodynamics including RPA correlations. Overall agreement with measured $(e,e')$ responses and new $K^+$ quasielastic scattering data for $^{40}$Ca at |\qs|=500 MeV/c is good. Strong RPA quenching is essential for agreement with the Coulomb response. This quenching is notably less for the $K^+$ cross section even though the new scalar contributions are even more strongly quenched than the vector contributions. We show that this ``differential quenching'' alters sensitive cancellations in the expression for the $K^+$ cross section so that it is reduced much less than the individual responses. We emphasize the role of the purely relativistic distinction between vector and scalar contributions in obtaining an accurate and consistent description of the $(e,e')$ and $K^+$ data within the framework of our nuclear structure model.Comment: 26 pages, 5 uuencoded figures appended to end of this fil

3-Fluoro-4-hydroxyprolines:Synthesis, conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation

Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting molecular recognition of proline-containing molecules by biological systems. While hydroxyprolines and fluoroprolines are common motifs in medicinal and biological chemistry, the synthesis and molecular properties of prolines containing both modifications, i.e., fluoro-hydroxyprolines, have not been described. Here we present a practical and facile synthesis of all four diastereoisomers of 3-fluoro-4-hydroxyprolines (F-Hyps), starting from readily available 4-oxo-l-proline derivatives. Small-molecule X-ray crystallography, NMR spectroscopy, and quantum mechanical calculations are consistent with fluorination at C³ having negligible effects on the hydrogen bond donor capacity of the C⁴ hydroxyl, but inverting the natural preference of Hyp from C⁴-exo to C⁴-endo pucker. In spite of this, F-Hyps still bind to the von Hippel–Lindau (VHL) E3 ligase, which naturally recognizes C⁴-exo Hyp in a stereoselective fashion. Co-crystal structures and electrostatic potential calculations support and rationalize the observed preferential recognition for (3<i>R</i>,4<i>S</i>)-F-Hyp over the corresponding (3<i>S</i>,4<i>S</i>) epimer by VHL. We show that (3<i>R</i>,4<i>S</i>)-F-Hyp provides bioisosteric Hyp substitution in both hypoxia-inducible factor 1 alpha (HIF-1α) substrate peptides and peptidomimetic ligands that form part of PROTAC (proteolysis targeting chimera) conjugates for targeted protein degradation. Despite a weakened affinity, Hyp substitution with (3<i>S</i>,4<i>S</i>)-F-Hyp within the PROTAC MZ1 led to Brd4-selective cellular degradation at concentrations >100-fold lower than the binary <i>K</i>_d for VHL. We anticipate that the disclosed chemistry of 3-fluoro-4-hydroxyprolines and their application as VHL ligands for targeted protein degradation will be of wide interest to medicinal organic chemists, chemical biologists, and drug discoverers alike

Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic.

Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required. In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity. High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established. TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types

Universal Correlations of Coulomb Blockade Conductance Peaks and the Rotation Scaling in Quantum Dots

We show that the parametric correlations of the conductance peak amplitudes of a chaotic or weakly disordered quantum dot in the Coulomb blockade regime become universal upon an appropriate scaling of the parameter. We compute the universal forms of this correlator for both cases of conserved and broken time reversal symmetry. For a symmetric dot the correlator is independent of the details in each lead such as the number of channels and their correlation. We derive a new scaling, which we call the rotation scaling, that can be computed directly from the dot's eigenfunction rotation rate or alternatively from the conductance peak heights, and therefore does not require knowledge of the spectrum of the dot. The relation of the rotation scaling to the level velocity scaling is discussed. The exact analytic form of the conductance peak correlator is derived at short distances. We also calculate the universal distributions of the average level width velocity for various values of the scaled parameter. The universality is illustrated in an Anderson model of a disordered dot.Comment: 35 pages, RevTex, 6 Postscript figure

Restricted three body problems at the nanoscale

In this paper, we investigate some of the classical restricted three body problems at the nanoscale, such as the circular planar restricted problem for three C60 fullerenes, and a carbon atom and two C60 fullerenes. We model the van der Waals forces between the fullerenes by the Lennard-Jones potential. In particular, the pairwise potential energies between the carbon atoms on the fullerenes are approximated by the continuous approach, so that the total molecular energy between two fullerenes can be determined analytically. Since we assume that such interactions between the molecules occur at sufficiently large distance, the classical three body problems analysis is legitimate to determine the collective angular velocity of the two and three C60 fullerenes at the nanoscale. We find that the maximum angular frequency of the two and three fullerenes systems reach the terahertz range and we determine the stationary points and the points which have maximum velocity for the carbon atom for the carbon atom and the two fullerenes system

Structure Formation, Melting, and the Optical Properties of Gold/DNA Nanocomposites: Effects of Relaxation Time

We present a model for structure formation, melting, and optical properties of gold/DNA nanocomposites. These composites consist of a collection of gold nanoparticles (of radius 50 nm or less) which are bound together by links made up of DNA strands. In our structural model, the nanocomposite forms from a series of Monte Carlo steps, each involving reaction-limited cluster-cluster aggregation (RLCA) followed by dehybridization of the DNA links. These links form with a probability $p_{eff}$ which depends on temperature and particle radius $a$. The final structure depends on the number of monomers (i. e. gold nanoparticles) $N_m$, $T$, and the relaxation time. At low temperature, the model results in an RLCA cluster. But after a long enough relaxation time, the nanocomposite reduces to a compact, non-fractal cluster. We calculate the optical properties of the resulting aggregates using the Discrete Dipole Approximation. Despite the restructuring, the melting transition (as seen in the extinction coefficient at wavelength 520 nm) remains sharp, and the melting temperature $T_M$ increases with increasing $a$ as found in our previous percolation model. However, restructuring increases the corresponding link fraction at melting to a value well above the percolation threshold. Our calculated extinction cross section agrees qualitatively with experiments on gold/DNA composites. It also shows a characteristic ``rebound effect,'' resulting from incomplete relaxation, which has also been seen in some experiments. We discuss briefly how our results relate to a possible sol-gel transition in these aggregates.Comment: 12 pages, 10 figure

Effect of tensor couplings in a relativistic Hartree approach for finite nuclei

The relativistic Hartree approach describing the bound states of both nucleons and anti-nucleons in finite nuclei has been extended to include tensor couplings for the $\omega$- and $\rho$-meson. After readjusting the parameters of the model to the properties of spherical nuclei, the effect of tensor-coupling terms rises the spin-orbit force by a factor of 2, while a large effective nucleon mass $m^{*}/M_{N} \approx 0.8$ sustains. The overall nucleon spectra of shell-model states are improved evidently. The predicted anti-nucleon spectra in the vacuum are deepened about 20 -- 30 MeV.Comment: 31 pages, 4 postscript figures include