Versatile spectral imaging with an algorithm-based spectrometer using highly tuneable quantum dot infrared photodetectors

We report on the implementation of an algorithm-based spectrometer capable of reconstructing the spectral shape of materials in the mid-wave infrared (MWIR) and long-wave infrared (LWIR) wavelengths using only experimental photocurrent measurements from quantum dot infrared photodetectors (QDIPs). The theory and implementation of the algorithm will be described, followed by an investigation into this algorithmic spectrometer's performance. Compared to the QDIPs utilized in an earlier implementation, the ones used here have highly varying spectral shapes and four spectral peaks across the MWIR and LWIR wavelengths. It has been found that the spectrometer is capable of reconstructing broad spectral features of a range of bandpass infrared filters between wavelengths of 4 and 12 mu m as well as identifying absorption features as narrow as 0.3 mu m in the IR spectrum of a polyethylene sheet

Auditor Perceptions of Audit Workloads, Audit Quality, and Job Satisfaction

In this study, we use a survey instrument to obtain perspectives from over 700 auditors about present-day audit workloads and the relationship between audit workloads, audit quality, and job satisfaction. Our findings indicate that auditors are working, on average, five hours per week above the threshold at which they believe audit quality begins to deteriorate and often 20 hours above this threshold at the peak of busy season. Survey respondents perceive deadlines and staffing shortages as two of the primary reasons for high workloads and further believe that high workloads result in decreased audit quality via compromised audit procedures (including taking shortcuts), impaired audit judgment (including reduced professional skepticism), and difficulty retaining staff with appropriate knowledge and skills. We also find that auditors’ job satisfaction and their excitement about auditing as a career are negatively impacted by high audit workload, particularly when the workload exceeds a threshold that is perceived to impair audit quality. Overall, our findings provide support for the PCAOB’s recent concern that heavy workloads are continuing to threaten audit quality and suggest that the primary drivers of workload (i.e., deadlines and staffing problems) might be the actual “root cause” of workload-related audit deficiencies

S-wave/spin-triplet order in superconductors without inversion symmetry: Li2_2Pd3_3B and Li2_2Pt3_3B

We investigate the order parameter of noncentrosymmetric superconductors Li$_2$Pd$_3$B and Li$_2$Pt$_3$B via the behavior of the penetration depth $\lambda(T)$. The low-temperature penetration depth shows BCS-like behavior in Li$_2$Pd$_3$B, while in Li$_2$Pt$_3$B it follows a linear temperature dependence. We propose that broken inversion symmetry and the accompanying antisymmetric spin-orbit coupling, which admix spin-singlet and spin-triplet pairing, are responsible for this behavior. The triplet contribution is weak in Li$_2$Pd$_3$B, leading to a wholly open but anisotropic gap. The significantly larger spin-orbit coupling in Li$_2$Pt$_3$B allows the spin-triplet component to be larger in Li$_2$Pt$_3$B, producing line nodes in the energy gap as evidenced by the linear temperature dependence of $\lambda(T)$. The experimental data are in quantitative agreement with theory.Comment: Phys. Rev. Lett. (in press). More details are include

Demonstration of Bias-Controlled Algorithmic Tuning of Quantum Dots in a Well (DWELL) MidIR Detectors

The quantum-confined Stark effect in intersublevel transitions present in quantum-dots-in-a-well (DWELL) detectors gives rise to a midIR spectral response that is dependent upon the detector\u27s operational bias. The spectral responses resulting from different biases exhibit spectral shifts, albeit with significant spectral overlap. A postprocessing algorithm was developed by Sakoglu that exploited this bias-dependent spectral diversity to predict the continuous and arbitrary tunability of the DWELL detector within certain limits. This paper focuses on the experimental demonstration of the DWELL-based spectral tuning algorithm. It is shown experimentally that it is possible to reconstruct the spectral content of a target electronically without using any dispersive optical elements for tuning, thereby demonstrating a DWELL-based algorithmic spectrometer. The effects of dark current, detector temperature, and bias selection on the tuning capability are also investigated experimentally

Thermodynamic Stability of the Transcription Regulator PaaR2 from Escherichia coli O157:H7

PaaR2 is a putative transcription regulator encoded by a three-component parDE-like toxin-antitoxin module from Escherichia coli O157:H7. Although this module’s toxin, antitoxin, and toxin-antitoxin complex have been more thoroughly investigated, little remains known about its transcription regulator PaaR2. Using a wide range of biophysical techniques (circular dichroism spectroscopy, size-exclusion chromatography-multiangle laser light scattering, dynamic light scattering, small-angle x-ray scattering, and native mass spectrometry), we demonstrate that PaaR2 mainly consists of α-helices and displays a concentration-dependent octameric build-up in solution and that this octamer contains a global shape that is significantly nonspherical. Thermal unfolding of PaaR2 is reversible and displays several transitions, suggesting a complex unfolding mechanism. The unfolding data obtained from spectroscopic and calorimetric methods were combined into a unifying thermodynamic model, which suggests a five-state unfolding trajectory. Furthermore, the model allows the calculation of a stability phase diagram, which shows that, under physiological conditions, PaaR2 mainly exists as a dimer that can swiftly oligomerize into an octamer depending on local protein concentrations. These findings, based on a thorough biophysical and thermodynamic analysis of PaaR2, may provide important insights into biological function such as DNA binding and transcriptional regulation

An initial event in insect innate immune response: structural and biological studies of interactions between β-1,3-glucan and the N-terminal domain of β-1,3-glucan recognition protein

In response to invading microorganisms, insect β-1,3-glucan recognition protein (βGRP), a soluble receptor in the hemolymph, binds to the surfaces of bacteria and fungi and activates serine protease cascades that promote destruction of pathogens by means of melanization or expression of antimicrobial peptides. Here we report on the NMR solution structure of the N-terminal domain of βGRP (N-βGRP) from Indian meal moth (Plodia interpunctella), which is sufficient to activate the prophenoloxidase (proPO) pathway resulting in melanin formation. NMR and isothermal calorimetric titrations of N-βGRP with laminarihexaose, a glucose hexamer containing β-1,3 links, suggest a weak binding of the ligand. However, addition of laminarin, a glucose polysaccharide (~ 6 kDa) containing β-1,3 and β-1,6 links that activates the proPO pathway, to N-βGRP results in the loss of NMR cross-peaks from the backbone 15N-1H groups of the protein, suggesting the formation of a large complex. Analytical ultra centrifugation (AUC) studies of formation of N-βGRP:laminarin complex show that ligand-binding induces sel-fassociation of the protein:carbohydrate complex into a macro structure, likely containing six protein and three laminarin molecules (~ 102 kDa). The macro complex is quite stable, as it does not undergo dissociation upon dilution to sub-micromolar concentrations. The structural model thus derived from the present studies for N-βGRP:laminarin complex in solution differs from the one in which a single N-βGRP molecule has been proposed to bind to a triple helical form of laminarin on the basis of an X-ray crystallographic structure of N-βGRP:laminarihexaose complex [Kanagawa, M., Satoh, T., Ikeda, A., Adachi, Y., Ohno, N., and Yamaguchi, Y. (2011) J. Biol. Chem. 286, 29158-29165]. AUC studies and phenoloxidase activation measurements carried out with the designed mutants of N-βGRP indicate that electrostatic interactions involving Asp45, Arg54, and Asp68 between the ligand-bound protein molecules contribute in part to the stability of N-βGRP:laminarin macro complex and that a decreased stability is accompanied by a reduced activation of the proPO pathway. Increased β-1,6 branching in laminarin also results in destabilization of the macro complex. These novel findings suggest that ligand-induced self-association of βGRP:β-1,3-glucan complex may form a platform on a microbial surface for recruitment of downstream proteases, as a means of amplification of the initial signal of pathogen recognition for the activation of the proPO pathway

Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man

<p>Abstract</p> <p>Background</p> <p>Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a) and monocyte chemotactic factor 1(MCP-1) are detectable in peripheral blood after myocardial infarction (MI). It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium.</p> <p>Methods</p> <p>Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous) blood from patients with normal coronary arteries, stable coronary artery disease (CAD), unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI.</p> <p>Results</p> <p>Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model.</p> <p>Conclusions</p> <p>SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.</p

Total synthesis and evaluation of 22-(3-azidobenzoyloxy)methyl epothilone C for photoaffinity labeling of β-tubulin

The total synthesis of 22-(3-azidobenzoyloxy)methyl epothilone C is described as a potential photoaffinity probe to elucidate the β-tubulin binding site. A sequential Suzuki-aldol-Yamaguchi macrolactonization strategy was utilized employing a novel derivatized C1–C6 fragment. The C22-functionalized analog exhibited good activity in microtubule assembly assays, but cytotoxicity was significantly reduced. Molecular modeling simulations indicated that excessive steric bulk in the C22 position is accommodated by the large hydrophobic pocket of the binding site. Photoaffinity labeling studies were inconclusive suggesting non-specific labeling

Nanobody-aided crystallization of the transcription regulator PaaR2 from Escherichia coli O157:H7

paaR2–paaA2–parE2 is a three-component toxin–antitoxin module found in prophage CP-993P of Escherichia coli O157:H7. Transcription regulation of this module occurs via the 123-amino-acid regulator PaaR2, which forms a large oligomeric structure. Despite appearing to be well folded, PaaR2 withstands crystallization, as does its N-terminal DNA-binding domain. Native mass spectrometry was used to screen for nanobodies that form a unique complex and stabilize the octameric structure of PaaR2. One such nanobody, Nb33, allowed crystallization of the protein. The resulting crystals belong to space group F432, with unit-cell parameter a = 317 Å, diffract to 4.0 Å resolution and are likely to contain four PaaR2 monomers and four nanobody monomers in the asymmetric unit. Crystals of two truncates containing the N-terminal helix–turn–helix domain also interact with Nb33, and the corresponding co-crystals diffracted to 1.6 and 1.75 Å resolution