Ordered biological nanostructures formed from chaperonin polypeptides

The following application relates to nanotemplates, nanostructures, nanoarrays and nanodevices formed from wild-type and mutated chaperonin polypeptides, methods of producing such compositions, methods of using such compositions and particular chaperonin polypeptides that can be utilized in producing such compositions

Ordered Nanostructures Made Using Chaperonin Polypeptides

A recently invented method of fabricating periodic or otherwise ordered nanostructures involves the use of chaperonin polypeptides. The method is intended to serve as a potentially superior and less expensive alternative to conventional lithographic methods for use in the patterning steps of the fabrication of diverse objects characterized by features of the order of nanometers. Typical examples of such objects include arrays of quantum dots that would serve as the functional building blocks of future advanced electronic and photonic devices. A chaperonin is a double-ring protein structure having a molecular weight of about 60 plus or minus 5 kilodaltons. In nature, chaperonins are ubiquitous, essential, subcellular structures. Each natural chaperonin molecule comprises 14, 16, or 18 protein subunits, arranged as two stacked rings approximately 16 to 18 nm tall by approximately 15 to 17 nm wide, the exact dimensions depending on the biological species in which it originates. The natural role of chaperonins is unknown, but they are believed to aid in the correct folding of other proteins, by enclosing unfolded proteins and preventing nonspecific aggregation during assembly. What makes chaperonins useful for the purpose of the present method is that under the proper conditions, chaperonin rings assemble themselves into higher-order structures. This method exploits such higher-order structures to define nanoscale devices. The higher-order structures are tailored partly by choice of chemical and physical conditions for assembly and partly by using chaperonins that have been mutated. The mutations are made by established biochemical techniques. The assembly of chaperonin polypeptides into such structures as rings, tubes, filaments, and sheets (two-dimensional crystals) can be regulated chemically. Rings, tubes, and filaments of some chaperonin polypeptides can, for example, function as nano vessels if they are able to absorb, retain, protect, and release gases or chemical reagents, including reagents of medical or pharmaceutical interest. Chemical reagents can be bound in, or released from, such structures under suitable controlled conditions. In an example of a contemplated application, a two-dimensional crystal of chaperonin polypeptides would be formed on a surface of an inorganic substrate and used to form a planar array of nanoparticles or quantum dots. Through genetic engineering of the organisms used to manufacture the chaperonins, specific sites on the chaperonin molecules and, thus, on the two-dimensional crystals can be chemically modified to react in a specific manner so as to favor the deposition of the material of the desired nanoparticles or quantum dots. A mutation that introduces a cysteine residue at the desired sites on a chaperonin of Sulfolobus shibatae was used to form planar arrays of gold nanoparticles (see figure)

A First Look at the Crypto-Mining Malware Ecosystem: A Decade of Unrestricted Wealth

Illicit crypto-mining leverages resources stolen from victims to mine cryptocurrencies on behalf of criminals. While recent works have analyzed one side of this threat, i.e.: web-browser cryptojacking, only commercial reports have partially covered binary-based crypto-mining malware. In this paper, we conduct the largest measurement of crypto-mining malware to date, analyzing approximately 4.5 million malware samples (1.2 million malicious miners), over a period of twelve years from 2007 to 2019. Our analysis pipeline applies both static and dynamic analysis to extract information from the samples, such as wallet identifiers and mining pools. Together with OSINT data, this information is used to group samples into campaigns. We then analyze publicly-available payments sent to the wallets from mining-pools as a reward for mining, and estimate profits for the different campaigns. All this together is is done in a fully automated fashion, which enables us to leverage measurement-based findings of illicit crypto-mining at scale. Our profit analysis reveals campaigns with multi-million earnings, associating over 4.4% of Monero with illicit mining. We analyze the infrastructure related with the different campaigns, showing that a high proportion of this ecosystem is supported by underground economies such as Pay-Per-Install services. We also uncover novel techniques that allow criminals to run successful campaigns.Comment: A shorter version of this paper appears in the Proceedings of 19th ACM Internet Measurement Conference (IMC 2019). This is the full versio

Versatile platform for nanotechnology based on circular permutations of chaperonin protein

The present invention provides chaperonin polypeptides which are modified to include N-terminal and C-terminal ends that are relocated from the central pore region to various different positions in the polypeptide which are located on the exterior of the folded modified chaperonin polypeptide. In the modified chaperonin polypeptide, the naturally-occurring N-terminal and C-terminal ends are joined together directly or with an intervening linker peptide sequence. The relocated N-terminal or C-terminal ends can be covalently joined to, or bound with another molecule such as a nucleic acid molecule, a lipid, a carbohydrate, a second polypeptide, or a nanoparticle. The modified chaperonin polypeptides can assemble into double-ringed chaperonin structures. Further, the chaperonin structures can organize into higher order structures such as nanofilaments or nanoarrays which can be used to produce nanodevices and nanocoatings

Towards Space-like Photometric Precision from the Ground with Beam-Shaping Diffusers

We demonstrate a path to hitherto unachievable differential photometric precisions from the ground, both in the optical and near-infrared (NIR), using custom-fabricated beam-shaping diffusers produced using specialized nanofabrication techniques. Such diffusers mold the focal plane image of a star into a broad and stable top-hat shape, minimizing photometric errors due to non-uniform pixel response, atmospheric seeing effects, imperfect guiding, and telescope-induced variable aberrations seen in defocusing. This PSF reshaping significantly increases the achievable dynamic range of our observations, increasing our observing efficiency and thus better averages over scintillation. Diffusers work in both collimated and converging beams. We present diffuser-assisted optical observations demonstrating $62^{+26}_{-16}$ppm precision in 30 minute bins on a nearby bright star 16-Cygni A (V=5.95) using the ARC 3.5m telescope---within a factor of $\sim$2 of Kepler's photometric precision on the same star. We also show a transit of WASP-85-Ab (V=11.2) and TRES-3b (V=12.4), where the residuals bin down to $180^{+66}_{-41}$ppm in 30 minute bins for WASP-85-Ab---a factor of $\sim$4 of the precision achieved by the K2 mission on this target---and to 101ppm for TRES-3b. In the NIR, where diffusers may provide even more significant improvements over the current state of the art, our preliminary tests have demonstrated $137^{+64}_{-36}$ppm precision for a $K_S =10.8$ star on the 200" Hale Telescope. These photometric precisions match or surpass the expected photometric precisions of TESS for the same magnitude range. This technology is inexpensive, scalable, easily adaptable, and can have an important and immediate impact on the observations of transits and secondary eclipses of exoplanets.Comment: Accepted for publication in ApJ. 30 pages, 20 figure

Non-trivial scaling of self-phase modulation and three-photon absorption in III-V photonic crystal waveguides

We investigate the nonlinear response of photonic crystal waveguides with suppressed two-photon absorption. A moderate decrease of the group velocity (~ c/6 to c/15, a factor of 2.5) results in a dramatic (30x) enhancement of three-photon absorption well beyond the expected scaling, proportional to 1/(vg)^3. This non-trivial scaling of the effective nonlinear coefficients results from pulse compression, which further enhances the optical field beyond that of purely slow-group velocity interactions. These observations are enabled in mm-long slow-light photonic crystal waveguides owing to the strong anomalous group-velocity dispersion and positive chirp. Our numerical physical model matches measurements remarkably.Comment: 10 pages, 4 figure

The Revised Child Anxiety and Depression Scale-Short Version: Scale reduction via exploratory bifactor modeling of the broad anxiety factor.

Using a school-based (N = 1,060) and clinic-referred (N = 303) youth sample, the authors developed a 25-item shortened version of the Revised Child Anxiety and Depression Scale (RCADS) using Schmid-Leiman exploratory bifactor analysis to reduce client burden and administration time and thus improve the transportability characteristics of this youth anxiety and depression measure. Results revealed that all anxiety items primarily reflected a single “broad anxiety” dimension, which informed the development of a reduced 15-item Anxiety Total scale. Although specific DSM-oriented anxiety subscales were not included in this version, the items comprising the Anxiety Total scale were evenly pulled from the 5 anxiety-related content domains from the original RCADS. The resultant 15-item Anxiety Total scale evidenced significant correspondence with anxiety diagnostic groups based on structured clinical interviews. The scores from the 10-item Depression Total scale (retained from the original version) were also associated with acceptable reliability in the clinic-referred and school-based samples (α = .80 and .79, respectively); this is in contrast to the alternate 5-item shortened RCADS Depression Total scale previously developed by Muris, Meesters, and Schouten (2002), which evidenced depression scores of unacceptable reliability (α = .63). The shortened RCADS developed in the present study thus balances efficiency, breadth, and scale score reliability in a way that is potentially useful for repeated measurement in clinical settings as well as wide-scale screenings that assess anxiety and depressive problems. These future applications are discussed, as are recommendations for continued use of exploratory bifactor modeling in scale development.Psycholog

Kuiper Belt Occultation Predictions

Here we present observations of seven large Kuiper Belt objects. From these observations, we extract a point source catalog with ∼0.01″ precision, and astrometry of our target Kuiper Belt objects with 0.04–0.08″ precision within that catalog. We have developed a new technique to predict the future occurrence of stellar occultations by Kuiper Belt objects. The technique makes use of a maximum likelihood approach which determines the best-fit adjustment to cataloged orbital elements of an object. Using simulations of a theoretical object, we discuss the merits and weaknesses of this technique compared to the commonly adopted ephemeris offset approach. We demonstrate that both methods suffer from separate weaknesses, and thus together provide a fair assessment of the true uncertainty in a particular prediction. We present occultation predictions made by both methods for the seven tracked objects, with dates as late as 2015. Finally, we discuss observations of three separate close passages of Quaoar to field stars, which reveal the accuracy of the element adjustment approach, and which also demonstrate the necessity of considering the uncertainty in stellar position when assessing potential occultations

Concurrent Validity of the Child Behavior Checklist DSM-Oriented Scales: Correspondence with DSM Diagnoses and Comparison to Syndrome Scales

This study used receiver operating characteristic (ROC) methodology and discriminative analyses to examine the correspondence of the Child Behavior Checklist (CBCL) rationally-derived DSM-oriented scales and empirically-derived syndrome scales with clinical diagnoses in a clinic-referred sample of children and adolescents (N = 476). Although results demonstrated that the CBCL Anxiety, Affective, Attention Deficit/Hyperactivity, Oppositional and Conduct Problems DSM-oriented scales corresponded significantly with related clinical diagnoses derived from parent-based structured interviews, these DSM-oriented scales did not evidence significantly greater correspondence with clinical diagnoses than the syndrome scales in all cases but one. The DSM-oriented Anxiety Problems scale was the only scale that evidenced significantly greater correspondence with diagnoses above its syndrome scale counterpart —the Anxious/Depressed scale. The recently developed and rationally-derived DSM-oriented scales thus generally do not add incremental clinical utility above that already afforded by the syndrome scales with respect to corresponding with diagnoses. Implications of these findings are discussed

A Psychometric Analysis of the Revised Child Anxiety and Depression Scales—Parent Version in a School Sample

The Revised Child Anxiety and Depression Scale—Parent Version (RCADS-P) is a parent-report questionnaire of youth anxiety and depression with scales corresponding to the DSM diagnoses of separation anxiety disorder, social phobia, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and major depressive disorder. The RCADS-P was recently developed and has previously demonstrated strong psychometric properties in a clinic-referred sample (Ebesutani et al., Journal of Abnormal Child Psychology 38, 249–260, 2010b). The present study examined the psychometric properties of the RCADS-P in a school-based population. As completed by parents of 967 children and adolescents, the RCADS-P demonstrated high internal consistency, test-retest reliability, and good convergent/divergent validity, supporting the RCADS-P as a measure of internalizing problems specific to depression and five anxiety disorders in school samples. Normative data are also reported to allow for the derivation of T-scores to enhance clinicians’ ability to make classification decisions using RCADS-P subscale scores