Electron multiplication CCD detector technology advancement for the WFIRST-AFTA coronagraph

The WFIRST-AFTA (Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset) is a NASA space observatory. It will host two major astronomical instruments: a wide-field imager (WFI) to search for dark energy and carry out wide field near infrared (NIR) surveys, and a coronagraph instrument (CGI) to image and spectrally characterize extrasolar planets. In this paper, we discuss the work that has been carried out at JPL in advancing Electron Multiplying CCD (EMCCD) technology to higher flight maturity, with the goal of reaching a NASA technology readiness level of 6 (TRL-6) by early-to-mid 2016. The EMCCD has been baselined for both the coronagraph's imager and integral field spectrograph (IFS) based on its sub-electron noise performance at extremely low flux levels - the regime where the AFTA CGI will operate. We present results from a study that fully characterizes the beginning of life performance of the EMCCD. We also discuss, and present initial results from, a recent radiation test campaign that was designed and carried out to mimic the conditions of the WFIRST-AFTA space environment in an L2 orbit, where we sought to assess the sensor's end of life performance, particularly degradation of its charge transfer efficiency, in addition to other parameters such as dark current, electron multiplication gain, clock induced charge and read noise

Technology advancement of the CCD201-20 EMCCD for the WFIRST coronagraph instrument: sensor characterization and radiation damage

The Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset (WFIRST-AFTA) mission is a 2.4-m class space telescope that will be used across a swath of astrophysical research domains. JPL will provide a high-contrast imaging coronagraph instrument—one of two major astronomical instruments. In order to achieve the low noise performance required to detect planets under extremely low flux conditions, the electron multiplying charge-coupled device (EMCCD) has been baselined for both of the coronagraph’s sensors—the imaging camera and integral field spectrograph. JPL has established an EMCCD test laboratory in order to advance EMCCD maturity to technology readiness level-6. This plan incorporates full sensor characterization, including read noise, dark current, and clock-induced charge. In addition, by considering the unique challenges of the WFIRST space environment, degradation to the sensor’s charge transfer efficiency will be assessed, as a result of damage from high-energy particles such as protons, electrons, and cosmic rays. Science-grade CCD201-20 EMCCDs have been irradiated to a proton fluence that reflects the projected WFIRST orbit. Performance degradation due to radiation displacement damage is reported, which is the first such study for a CCD201-20 that replicates the WFIRST conditions. In addition, techniques intended to identify and mitigate radiation-induced electron trapping, such as trap pumping, custom clocking, and thermal cycling, are discussed

Aniqsaaq (To Breathe): Study protocol to develop and evaluate an Alaska Native family-based financial incentive intervention for smoking cessation

Background Alaska Native and American Indian (ANAI) communities in Alaska are disproportionately affected by commercial tobacco use. Financial incentive interventions promote cigarette smoking cessation, but family-level incentives have not been evaluated. We describe the study protocol to adapt and evaluate the effectiveness and implementation of a remotely delivered, family-based financial incentive intervention for cigarette smoking among Alaskan ANAI people. Methods The study has 3 phases: 1) qualitative interviews with ANAI adults who smoke, family members, and stakeholders to inform the intervention, 2) beta-test of the intervention, and 3) randomized controlled trial (RCT) evaluating intervention reach and effectiveness on verified, prolonged smoking abstinence at 6- and 12-months post-treatment. In the RCT, adult dyads (ANAI person who smokes [index participant] and family member) recruited throughout Alaska will be randomized to a no-incentives control condition (n = 328 dyads) or a 6-month incentive intervention (n = 328 dyads). All dyads will receive cessation support and family wellness materials. Smoking status will be assessed weekly for four weeks and at three and six months. Intervention index participants will receive escalating incentives for verified smoking abstinence at each time point (maximum $750 total); the family member will receive rewards of equal value. Results A community advisory committee contributed input on the study design and methods for relevance to ANAI people, particularly emphasizing the involvement of families. Conclusion Our study aligns with the strength and value AIAN people place on family. Findings, processes, and resources will inform how Indigenous family members can support smoking cessation within incentive interventions.Ye

Thermodynamic insight into the interaction mechanism of an ESIPT drug with a serum transport protein: Slower solvent-relaxation dynamics explored through wavelength-sensitive fluorescence behavior

Recently, 3,5-diiodosalicylic acid (3,5-DISA) has garnered enormous research attention owing to its wide-spread medicinal/biological applications, use as a model to study the role of halogen bonding in drug-protein interaction and so forth. However, the arena of the study of interaction of 3,5-DISA with relevant biological targets, particularly serum transport protein still starves for meticulous exploration of a number of fundamental aspects, such as, the thermodynamics and strength of binding, effect of drug binding on the native protein conformation and functionality, rotational and solvent-relaxation dynamics within the protein scaffolds etc. The present investigation endeavors to unveil these important aspects of 3,5-DISA:HSA interaction scenario. Our spectroscopic results demonstrate a remarkable modification of the excited-state intramolecular proton transfer (ESIPT) photophysics of 3,5-DISA upon interaction with HSA. A detailed isothermal titration calorimetry (ITC) study reveals that the interaction process is governed by favorable enthalpic (∆H0 < 0) and unfavorable entropic (T∆S0 < 0) contributions. The modulation of the hydration structure at the interfaces accompanying the binding phenomenon is also delineated in this context. Circular dichroism (CD) spectroscopy has been exploited to show the slight perturbation of the native protein conformation as a result of drug binding. In complementarity, the functionality of HSA (in terms of esterase-like activity) has also been shown to decrease with added 3,5-DISA. Our cumulative exploration of the wavelength-sensitive fluorescence parameters including red-edge excitation shift (REES) points out a remarkably slower rate of solvent-relaxation dynamics of the HSA-bound 3,5-DISA in the photoexcited state. The modification of the rotational-relaxation behavior of 3,5-DISA within the protein is also addressed and rationalized on the basis of the two-step and wobbling-in-cone model

Interaction of Bile Salts with β‑Cyclodextrins Reveals Nonclassical Hydrophobic Effect and Enthalpy–Entropy Compensation

Herein, we present an endeavor toward exploring the lacuna underlying the host:guest chemistry of inclusion complex formation between bile salt(s) and β-cyclodextrin(s) (βCDs). An extensive thermodynamic investigation based on isothermal titration calorimetry (ITC) demonstrates a dominant contribution from exothermic enthalpy change (Δ<i>H</i> < 0) accompanying the phenomenon of inclusion complex formation, along with a relatively smaller contribution to total free energy change from the entropic component. However, the negative heat capacity change (Δ<i>C</i>_p < 0) displays the hallmark for a pivotal role of hydrophobic effect underlying the interaction. Contrary to the classical hydrophobic effect, such apparently paradoxical thermodynamic signature has been adequately described under the notion of “nonclassical hydrophobic effect”. On the basis of our results, the displacement of disordered water from hydrophobic binding sites has been argued to mark the enthalpic signature and the key role of such interaction forces is further corroborated from enthalpy–entropy compensation behavior showing indication for almost complete compensation. To this end, we have quantified the interaction of two bile salt molecules (namely, sodium deoxycholate and sodium glycocholate) with a series of varying chemical substituents on the host counterpart, namely, βCD, (2-hydroxypropyl)-βCD, and methyl βCD

Binding Interaction of a Prospective Chemotherapeutic Antibacterial Drug with β‑Lactoglobulin: Results and Challenges

This Article reports a detailed characterization of the binding interaction of a potential chemotherapeutic antibacterial drug, norfloxacin (NOF), with the mammalian milk protein β-lactoglobulin (βLG). The thermodynamic parameters, Δ<i>H</i>, Δ<i>S</i>, and Δ<i>G</i>, for the binding phenomenon as-evaluated on the basis of van’t Hoff relationship reveal the predominance of electrostatic/ionic interactions underlying the binding process. However, the drug-induced quenching of the intrinsic tryptophanyl fluorescence of the protein exhibits intriguing characteristics on Stern–Volmer analysis (displays an upward curvature instead of conforming to a linear regression). Thus, an extensive time-resolved fluorescence spectroscopic characterization of the quenching process has been undertaken in conjugation with temperature-dependent fluorescence quenching studies to unveil the actual quenching mechanism. The invariance of the fluorescence decay behavior of βLG as a function of the quencher (here NOF) concentration coupled with the commensurate dependence of the drug–protein binding constant (<i>K</i>) on temperature, the drug-induced fluorescence quenching of βLG is argued to proceed through static mechanism. This postulate is aided further support from absorption, fluorescence, and circular dichroism (CD) spectral studies. The present study also throws light on the important issue of drug-induced modification in the native protein conformation on the lexicon of CD, excitation–emission matrix spectroscopic techniques. Concurrently, the drug–protein interaction kinetics and the energy of activation of the process are also explored from stopped-flow fluorescence technique. The probable binding locus of NOF in βLG is investigated from AutoDock-based blind docking simulation

Interplay of Multiple Interaction Forces: Binding of Norfloxacin to Human Serum Albumin

Herein, the binding interaction of a potential chemotherapeutic antibacterial drug norfloxacin (NOF) with a serum transport protein, human serum albumin (HSA), is investigated. The prototropic transformation of the drug (NOF) is found to be remarkably modified following interaction with the protein as manifested through significant modulations of the photophysics of the drug. The predominant zwitterionic form of NOF in aqueous buffer phase undergoes transformation to the cationic form within the protein-encapsulated state. This implies the possible role of electrostatic interaction force in NOF–HSA binding. This postulate is further substantiated from the effect of ionic strength on the interaction process. To this end, the detailed study of the thermodynamics of the drug–protein interaction process from isothermal titration calorimetric (ITC) experiments is found to unfold the signature of electrostatic as well as hydrophobic interaction forces underlying the binding process. Thus, interplay of more than one interaction forces is argued to be responsible for the overall drug–protein binding. The ITC results reveal an important finding in terms of enthalpy–entropy compensation (EEC) characterizing the NOF–HSA binding. The effect of drug-binding on the native protein conformation has also been evaluated from circular dichroism (CD) spectroscopy which unveils partial rupture of the protein secondary structure. In conjunction to this, the functionality of the native protein (in terms of esterase-like activity) is found to be lowered as a result of binding with NOF. The AutoDock-based docking simulation unravels the probable binding location of NOF within the hydrophilic subdomain IA of HSA. The present program also focuses on exploring the dynamical aspects of the drug–protein interaction scenario. The rotational-relaxation dynamics of the protein-bound drug reveals the not-so-common “dip-and-rise” pattern

How Does Nanoconfinement within a Reverse Micelle Influence the Interaction of Phenazinium-Based Photosensitizers with DNA?

The major focus of the present work lies in exploring the influence of nanoconfinement within aerosol-OT (AOT) reverse micelles on the binding interaction of two phenazinium-based photosensitizers, namely, phenosafranin (PSF) and safranin-O (SO), with the DNA duplex. Circular dichroism and dynamic light-scattering studies reveal the condensation of DNA within the reverse micellar interior (transformation of the B-form of native DNA to ψ-form). Our results unveil a remarkable effect of the degree of hydration of the reverse micellar core on the stability of the stacking interaction (intercalation) of the drugs (PSF and SO) into DNA; increasing size of the water nanopool (that is, <i>w</i>₀) accompanies decreasing curvature of the DNA duplex structure with the consequent effect of increasing stabilization of the drug:DNA intercalation. The marked differences in the dynamical aspects of the interaction scenario following encapsulation within the reverse micellar core and the subsequent dependence on the size of the water nanopool are also meticulously explored. The differential degrees of steric interactions offered by the drug molecules (presence of methyl substitutions on the planar phenazinium ring in SO) are also found to affect the extent of intercalation of the drugs to DNA. In this context, it is imperative to state that the water pool of the reverse micellar core is often argued to approach bulk-like properties of water with increasing micellar size (typically <i>w</i>₀ ≥ 10), so that deviation from the bulk water properties is likely to be minimized in large reverse micelles (<i>w</i>₀ ≥ 10). On the contrary, our results (particularly quantitative elucidation of micropolarity and dynamical aspects of the interaction) explicitly demonstrate that the bulk-like behavior of the nanoconfined water is not truly achieved even in large reverse micelles

Triblock-Copolymer-Assisted Mixed-Micelle Formation Results in the Refolding of Unfolded Protein

The present work reports a new strategy for triblock-copolymer-assisted refolding of sodium dodecyl sulfate (SDS)-induced unfolded serum protein human serum albumin (HSA) by mixed-micelle formation of SDS with poly­(ethylene oxide)-poly­(propylene oxide)-poly­(ethylene oxide) triblock copolymer EO₂₀PO₆₈EO₂₀ (P123) under physiological conditions. The steady-state and time-resolve fluorescence results show that the unfolding of HSA induced by SDS occurs in a stepwise manner through three different phases of binding of SDS, which is followed by a saturation of interaction. Interestingly, the addition of polymeric surfactant P123 to the unfolded protein results in the recovery of ∼87% of its α-helical structure, which was lost during SDS-induced unfolding. This is further corroborated by the return of the steady-state and time-resolved fluorescence decay parameters of the intrinsic tryptophan (Trp214) residue of HSA to the initial nativelike condition. The isothermal titration calorimetry (ITC) data also substantiates that there is almost no interaction between P123 and the native state of the protein. However, the mixed-micelle formation, accompanied by substantial binding affinities, removes the bound SDS molecules from the scaffolds of the unfolded state of the protein. On the basis of our experiments, we conclude that the formation of mixed micelles between SDS and P123 plays a pivotal role in refolding the protein back to its nativelike state