cssi/SciSciGPT-SciSciNet huggingface dataset:
Replacement of ProB28 by pipecolic acid protects insulin against fibrillation and slows hexamer dissociation

Non‐canonical amino acid mutagenesis was used to examine the biophysical consequences of changing ring size and structure at the single proline site in insulin. Addition of a methylene spacer to the prolyl ring (by replacement of proline by pipecolic acid at position B28) led to an increase in stability and a decrease in the rate of hexamer dissociation. The results of this work illustrate the power of non‐canonical amino acid mutagenesis in the engineering of macromolecular aggregation and protein therapeutics.
Major adverse limb events and major adverse cardiac events after contemporary lower extremity bypass and infrainguinal endovascular intervention in patients with claudication

Abstract Objective Major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) at 30 days provide standardized metrics for comparison and have been adopted by the Society for Vascular Surgery's objective performance goals for critical limb ischemia. However, MALEs and MACEs have not been widely adopted within the claudication population, and the comparative outcomes after lower extremity bypass (LEB) and infrainguinal endovascular intervention (IEI) remain unclear. The purpose of this study was to compare MALEs and MACEs after LEB and IEI in a contemporary national cohort and to determine predictors of MALEs and MACEs after revascularization for claudication. Methods A national data set of LEB and IEI performed for claudication was obtained using National Surgical Quality Improvement Program vascular targeted Participant Use Data Files from 2011 to 2014. Patients were stratified by LEB vs IEI and compared by appropriate univariate analysis. The primary outcomes were MALE (defined as untreated loss of patency, reintervention on the index arterial segment, or amputation of the index limb) and MACE (defined as stroke, myocardial infarction, or death). Multivariable logistic regression was used to identify predictors of MALEs and MACEs. Results A total of 3925 infrainguinal revascularization procedures (2155 LEB and 1770 IEI) were performed for claudication. There was no difference in 30-day MALEs between LEB and IEI (4.0% vs 3.2%; P = .17). On multivariable logistic regression, predictors of 30-day MALEs included tibial revascularization (odds ratio [OR], 2.2; P Conclusions In this large national cohort, LEB and IEI for claudication are associated with similar 30-day MALEs. Tibial revascularization and revascularization after prior failed bypass predict MALEs in claudicants and should therefore be undertaken with caution. LEB was associated with more 30-day MACEs but comparable 30-day mortality compared with IEI. Patients with end-stage renal disease, chronic obstructive pulmonary disease, and diabetes are at high risk for MACEs. The risk of 30-day MACEs after LEB should be weighed against the longer term outcomes of LEB vs IEI and conservative management, particularly in these higher risk patients. This analysis helps define contemporary 30-day outcomes after infrainguinal revascularization performed for claudication and serves as a baseline with which the short-term outcomes of future treatments can be compared.
Renewable Thermosets and Thermoplastics from Itaconic Acid

Renewable materials are a research necessity, with the creation of a sustainable chemical industry representing a grand challenge for the field of chemistry and materials science. On this basis, biorenewable resources are being transformed into degradable or recyclable high value polymers with a diverse array of applications. Itaconic acid (IA) is a notable biorenewable resource due to its low cost and large annual production. We report the synthesis of renewable thermosets and thermoplastics that are almost completely derived from IA. Using catalytic, solvent-free, and high yielding transformations from an itaconate source, we efficiently synthesized a saturated diol, a saturated diester, and an unsaturated diester. Subsequent binary step-growth polycondensation polymerizations between the diol and either diester generated polyesters with relatively high molar masses (>10 kg/mol). Ternary polymerizations of all three monomers in varying feed ratios produced polyesters with tunable amounts of unsaturated ...
Summary of typical parameters that affect sound transmission through general aviation aircraft structures

This paper presents results of a systematic experimental investigation of parameters which affect sound transmission through general aviation structures. Parameters studied include angle of sound incidence, panel curvature, panel stresses, and edge conditions for bare panels; pane thickness, spacing, inclination of window panes, and depressurization for dual pane windows; densities of hard foam and sound absorption materials, air gaps, and trim panel thickness for multilayered panels. Based on the study, some promising methods for reducing interior noise in general aviation airplanes are discussed.
Influence of donor brain death duration on outcomes following heart transplantation: A United Network for Organ Sharing Registry analysis.

Abstract Objectives We hypothesized that an increased duration of donor brain death may worsen survival following orthotopic heart transplantation. Methods The United Network for Organ Sharing Registry was queried for first-time, adult recipients of heart transplant from 2006 to 2018. Cox proportional hazards with penalized smooth splines was used to stratify patients based on donor brain death interval: shorter ( 42 hours). Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models. Results A total of 22,960 patients met study criteria (9.2% shorter, 55.0% reference, and 35.8% longer). Longer brain death duration recipients were more likely to have a later year of transplant and have a mechanical bridge to transplant, whereas longer duration donors were more likely to be black and die of anoxia compared with shorter duration and reference donors. Compared with reference, neither shorter (hazard ratio, 1.02; 95% confidence interval, 0.94-1.12) nor longer donor brain death interval (hazard ratio, 1.01; 95% CI, 0.94-1.08) was associated with posttransplant survival in either unadjusted or multivariable analyses (both P values >0.6). Conclusions Longer duration of brain death was not associated with worse survival following heart transplantation. Donors with prolonged interval of brain death should not necessarily be excluded based on brain death period alone.
MDL as Category

Multidistrict litigation (MDL) dominates the federal civil docket. MDL has been used to consolidate hundreds of thousands of cases, including with respect to asbestos, the BP oil spill, Johnson & Johnson baby powder, NFL concussions, opioids, and more. In recent years, MDL has attracted the attention of reformers and scholars, who have offered proposals for rules or practices that would apply to all MDLs, and to only MDLs. These proposals are premised on a fundamental error about what MDL is. Using quantitative and qualitative data, case studies, and interviews with judges, this Article demonstrates that reformers and scholars have made a categorization error with respect to MDL. MDL is not a uniform category of large civil cases demanding one-size-fits-all procedure. Recent proposals for MDL-specific rules, therefore, are misguided. Indeed, because such proposals would create incentives for parties to “procedure shop” into or out of MDL, they imperil horizontal equity and invite abuse. In this way, proposals for MDL-specific rules risk exacerbating existing problems in MDL and creating new problems that were not there before. That said, MDL is a coherent category with respect to the way MDLs are created. Every MDL is created by the Judicial Panel on Multidistrict Litigation (JPML), a group of seven judges handed picked by the Chief Justice, who have the nearly unconstrained authority to decide whether to consolidate cases and to which federal judge to assign them. Yet despite this unusual and highly consequential procedure, reformers and scholars have paid scant attention to the JPML. Having dispensed with the initial MDL categorization error, this Article examines the understudied role of the JPML and offers suggestions for JPML reform consistent with a clearer description of what MDL is.
An Extensible Software Architecture for Composing Motion and Task Planners

This paper describes a software infrastructure for developing and composing task and motion planners. The functionality of motion planners is well defined and they provide a basic primitive on top of which it is possible to develop planners for addressing higher level tasks. It is more challenging, however, to identify a common interface for task planners, given the variety of challenges that they can be used for. The proposed software platform follows a hierarchical, object-oriented structure and identifies key abstractions that help in integrating new task planners with popular sampling-based motion planners. Examples of use cases that can be implemented within this common software framework include robotics applications such as planning among dynamic obstacles, object manipulation and rearrangement, as well as decentralized motion coordination. The described platform has been used to plan for a Baxter robot rearranging similar objects in an environment in an efficient way.
Extending the research orientation and agenda for international and comparative studies in Catholic education

This article contributes to a discussion about building a research agenda for the international and comparative study of Catholic education. Globally, the Catholic Church’s work in education repres...
Solving Problem of Curved Surface Approximation by Layers with Constant and Variable Sections During Forming by Additive Methods

The paper considers the accuracy of the formation of engineering products’ surface layers using additive methods. It was determined that in case of additive forming, the accuracy characteristics of the surface layer differ significantly from the accuracy characteristics of the surface layers obtained using traditional methods. This is due to the high values of the error of forming (approximation) in additive methods. To improve the accuracy characteristics of products’ complex surfaces obtained using additive methods, it was proposed to ensure the dynamic spatial orientation of the final element of the additive equipment forming system. To control the spatial orientation of the forming system final element, it was proposed to use mechatronic 5 and 6 coordinate devices. The related area for solving the issues of improving the accuracy of additive forming methods was indicated. This area includes parallel control of the spatial orientation and section dimensions of a single layer, which, at certain values, will form the required value of approximation error at the specified performance. In this regard, the solutions of the problem of the parts’ curved surface approximation by layers with constant and variable sections were proposed. The results of geometric and computer simulation are given. A comparative assessment of the results of solving the above problems is provided. The proposed method will allow reducing the error in forming the products obtained with the help of additive methods.
Influence of in situ ceramic reinforcement towards tailoring titanium matrix composites using laser-based additive manufacturing

Increasing performance requirements of advanced components demands versatile fabrication techniques to meet application-specific needs. Composite material processing via laser-based additive manufacturing offers high processing-flexibility and limited tooling requirements to meet this need, but limited information exists on the processing-property relationships for these materials as well as how to exploit it for application-specific needs. In this study, Ti/B4C+BN composites are developed for high-temperature applications by designed-incorporation of ceramic reinforcement (5 wt% total) into commercially-pure titanium to form combined particle and in situ reinforcing phases. We combine both B4C (limited reactivity with matrix) and BN (high reactivity with matrix) reinforcements to understand the processing characteristics, in situ phase formations, and combinatorial effect of the multiphase microstructures on thermomechanical properties and high-temperature oxidation resistance. Combined reinforcement in this new composite material leads to superior yield strength and wear resistance in comparison to the other compositions and matrix, as well as comparable oxidation characteristics to commercially-developed high temperature titanium alloys, alleviating the need for multiple rare-earth alloying elements that significantly raises costs for manufacturers. Tubular structures are fabricated to demonstrate the ease of site-specific composition and dimensional tolerancing using this method. Our results indicate that tailored ceramic reinforcement in titanium via laser-based AM could lead to significantly enhanced engineering structures, particularly for developing higher temperature titanium-based materials.
Novice Debugging in Block-Based and Hybrid Environments

Debugging is an important skill for novice programmers to master, but many students struggle to learn how to debug due in part to difficulty with program syntax. Block-based environments provide an alternative to traditional textual programming that reduces syntax errors, and recently hybrid block-based/textual environments have become more common. This poster presents preliminary research to understand how novice debugging strategies differ between block- based and hybrid environments. We assigned seven participants to debug four programs within one of the two environments and conducted interviews about their debugging approaches. Thematic analysis of interview responses suggest that students adjusted their strategies based on their prior experience with textual environments. By understanding novice programmers' strategies in these environments, the field can move toward more effectively support- ing productive strategies.
Single cell characterization of CRISPR-modified transcript isoforms with nanopore sequencing

Transcript isoforms are mRNAs that arise from alternative splicing events. During RNA processing, different combinations of a gene9s exons lead to a diverse set of isoforms. Polymorphisms or mutations at splice junctions can generate alternative splicing events. Various splicing factors also impact the representation of a gene9s transcript isoforms. To assess how these two features contribute to alternative splicing, we developed a single cell approach to introduce CRISPR edits that modify mRNA transcript structure. Our method combines (1) long-read sequencing to characterize the expressed transcripts and identify the edit at single cell resolution; (2) short-read sequencing to match the single cell gene expression profiles of the cells with the altered isoform. First, we modify target exon-intron segments with CRISPR-Cas9. Second, using cDNAs with cell barcodes, we use long read sequencing to directly identify the changes in transcript isoforms from the targeted CRISPR edits. As a variation on this approach, we also determined how modifying specific splicing factors influence isoform expression and structure. Overall, we demonstrate how the integration of single cell long read analysis and CRISPR engineering can be used to directly confirm transcript isoform and target genomic edits at single cell resolution. This approach will improve our understanding of the role of alternative splicing in transcriptional regulation.
Spontaneous otoacoustic emissions are biomarkers for mice with tectorial membrane defects.

Cochlear function depends on the operation of a coupled feedback loop, incorporating outer hair cells (OHCs), and structured to assure that inner hair cells (IHCs) convey frequency specific acoustic information to the brain, even at very low sound levels. Although our knowledge of OHC function and its contribution to cochlear amplification has expanded, the importance of the tectorial membrane (TM) to the processing of mechanical inputs has not been fully elucidated. In addition, there are a surprising number of genetic mutations that affect TM structure and that produce hearing loss in humans. By synthesizing old and new results obtained on several mouse mutants, we learned that animals with abnormal TMs are prone to generate spontaneous otoacoustic emissions (SOAE), which are uncommon in most wildtype laboratory animals. Because SOAEs are not produced in TM mutants or in humans when threshold shifts exceed approximately 25 dB, some degree of cochlear amplification is required. However, amplification by itself is not sufficient because normal mice are rarely spontaneous emitters. Since SOAEs reflect active cochlear operation, TM mutants are valuable for studying the oscillatory nature of the amplification process and the structures associated with its stabilization. Inasmuch as the mouse models were selected to mirror human auditory disorders, using SOAEs as a noninvasive clinical tool may assist the classification of individuals with genetic defects that influence the active mechanisms responsible for sensitivity and frequency selectivity, the hallmarks of mammalian hearing.
The Ultramafic Belts

One petrological approach to upper mantle studies is to determine which ultramafic rocks represent mantle material. Ultramafic rocks occur in a variety of field and petrographic associations: in recent reviews, Wyllie [1967b, 1968] outlined eleven petrographic associations, some with subdivisions. In this summary, it is convenient to consider these in four larger groups: (1) layered, stratiform, and other intrusions involving gabbro or diabase, together with accumulations or concentrations of mafic minerals; (2) the alkalic rocks, including kimberlites, mica peridotites, members of ring complexes, and ultrabasic Java flows; (3) the several serpentinite-peridotite associations often classified together as alpine-type intrusions; (4) serpentinites and peridotites of the oceanic regions.
Uniting local and global controllers

A controller structure is proposed that dynamically combines predesigned local (e.g., linear) and global set-point stabilizing controllers. The local controller is only modified when the system to be controlled enters a region where the local controller loses its effectiveness. Thus, local performance and global stability are combined. Control objectives other than set-point tracking and the issue of robustness are discussed. The methodology is applied to achieve local performance and global stability for a class of fully-actuated Euler-Lagrange systems with input saturation.
Effect of adrenal steroids on testosterone and luteinizing hormone secretion in the ram.

The effects of adrenal steroids on testosterone and LH secretion and changes in serum cortisol levels in response to treatments were studied in the ram. Acute administration of synthetic ACTH (10 micrograms/kg BW) elevated (P less than 0.01) serum cortisol and transiently suppressed (P less than 0.05) serum testosterone and LH. Acute dexamethasone treatment suppressed (P less than 0.01) serum cortisol, testosterone and LH. Administration of vehicle had no effect (P greater than 0.10) on serum hormone levels. These data support the contention that adrenal steroids inhibit testicular endocrine function indirectly by acting at the hypothalamic or pituitary level because both ACTH and dexamethasone treatments suppressed serum LH. To differentiate between hypothalamic and pituitary sites of action, the pituitary and testicular responses to an LHRH challenge (100 micrograms) were examined in rams chronically treated with dexamethasone (5 mg i.m., twice daily for 5 days). This treatment regimen suppressed (P less than 0.01) serum cortisol levels. Compared with controls, basal testosterone levels were suppressed (P less than 0.05) in dexamethasone-treated rams; however, no effect (P greater than 0.10) on the magnitude of the testosterone response to LHRH or on either basal or LHRH-stimulated LH secretion was observed. Thus, although a direct testicular effect cannot be eliminated, these data suggest that, in the ram, adrenal steroids inhibit testicular endocrine function by action at the level of the hypothalamus.
E)Racing Trayvon Martin

In this essay, Cynthia Lee celebrates the 25th anniversary of Critical Race Theory (CRT) by writing about the pitfalls of the ideal of colorblindness. She starts by analyzing Devon Carbado's seminal article on CRT and the Fourth Amendment, (E)Racing the Fourth Amendment. She focuses on Carbado's critique of Justice Sandra Day O'Connor's embrace of colorblindness in Florida v. Bostick, the case in which the Supreme Court modified the test for a seizure of the person. Lee uses Carbado's article as a springboard for critiquing the embrace of colorblindness by legal decision-makers involved in George Zimmerman's 2013 murder trial. Zimmerman came under fire in 2012 for shooting and killing an unarmed Black teenager named Trayvon Martin. Zimmerman claimed he acted in self-defense. He was acquitted of murder by a mostly white 6 person jury. Lee argues that the embrace of colorblindness by the judge, the prosecution, and the defense had the effect of erasing race and the possibility that racial stereotypes influenced Zimmerman’s actions from the trial. This erasure of Martin's race had the deleterious effect of making it difficult for the prosecution to counter the implicit association most people make between young black males and violent crime. The defense was able to build a narrative based on an aggressive, violent Martin who started the affray and had the upper hand, and thus persuade the jury that Zimmerman acted reasonably in self-defense. Lee presents recent social science research on race salience that suggests calling attention to race can alleviate the effects of implicit racial bias.
Telephonic screening and brief intervention for alcohol misuse among workers contacting the employee assistance program: A feasibility study.

Introduction and Aims. Substantial empirical support exists for alcohol screening, brief intervention, and referral to treatment (SBIRT) in medical, but not non-medical settings such as the workplace. Workplace settings remain underutilised for delivering evidenced-based health services. This research aims to translate medical research into behavioural health-care practice in a telephonic call centre acting as a point of entry into an Employee Assistance Program (EAP). The goal of the study is to examine the feasibility of implementing routine telephonic alcohol SBIRT in an EAP call centre and assess whether routine SBIRT results in increased identification of workers who misuse alcohol. Design and Methods. The design was pretest–posttest, one-group, pre-experimental. An alcohol SBIRT program developed based on World Health Organization recommendations was implemented in one EAP call centre serving one large employer. Workers were offered screening using the Alcohol Use Disorder Identification Test (AUDIT) during intake, brief counselling using motivational interviewing, referral to counselling, and follow-up. Results. At 5 months, 93% of workers contacting the EAP completed the AUDIT-C: 40% prescreened positive and 52% went on to screen at moderate or high risk for an alcohol problem. Overall identification rate (18%) approached general US population estimates. Most agreed to follow-up and three-quarters set an appointment for face-to-face counselling. Discussion and Conclusions. Integration of routine alcohol SBIRT into EAP practice is feasible in telephonic delivery systems and increases identification and opportunity for brief motivational counselling. When SBIRT is seamlessly integrated workers are willing to answer questions about alcohol and participate in follow-up.[McPherson TL, Goplerud E, Derr D, Mickenberg J, Courtemanche S. Telephonic screening and brief intervention for alcohol misuse among workers contacting the employee assistance program: A feasibility study. Drug Alcohol Rev 2010;29;641–646]
Commonly Used Dietary Supplements on Coagulation Function during Surgery.

Background: Patients who undergo surgery appear to use dietary supplements significantly more frequently than the general population. Because they contain pharmacologically active compounds, dietary supplements may affect coagulation and platelet function during the perioperative period through direct effects, pharmacodynamic interactions, and pharmacokinetic interactions. However, in this regard, limited studies have been conducted that address the pharmacological interactions of dietary supplements. To avoid possible bleeding risks during surgery, information about the potential complications of dietary supplements during perioperative management is important for physicians. Methods: Through a systematic database search of all available years, articles were identified in this review if they included dietary supplements and coagulation/platelet function, while special attention was paid to studies published after 1990. Results: Safety concerns are reported in commercially available dietary supplements. Effects of the most commonly used natural products on blood coagulation and platelet function are systematically reviewed, including 11 herbal medicines (echinacea, ephedra, garlic, ginger, ginkgo, ginseng, green tea, kava, saw palmetto, St John’s wort, and valerian) and four other dietary supplements (coenzyme Q10, glucosamine and chondroitin sulfate, fish oil, and vitamins). Bleeding risks of garlic, ginkgo, ginseng, green tea, saw palmetto, St John’s wort, and fish oil are reported. Cardiovascular instability was observed with ephedra, ginseng, and kava. Pharmacodynamic and pharmacokinetic interactions between dietary supplements and drugs used in the perioperative period are discussed. Conclusions: To prevent potential problems associated with the use of dietary supplements, physicians should be familiar with the perioperative effects of commonly used dietary supplements. Since the effects of dietary supplements on coagulation and platelet function are difficult to predict, it is prudent to advise their discontinuation before surgery.
Adenine Nucleotide Levels in Neurospora, as Influenced by Conditions of Growth and by Metabolic Inhibitors

By a combination of luciferase and fluorescence methods adenine nucleotide pools in Neurospora crassa have been examined under various conditions of growth and metabolic inhibition. During sustained exponential growth (25 C, shaking liquid cultures), the intracellular adenosine 5'-triphosphate (ATP) concentration, [ATP](i), rises slowly from the conidial level near 1 mM (1 mmol/kg of cell water) to a maximum of 2.0 to 2.5 mM at 14 h, after which it slowly declines. The adenosine 5'-diphosphate and adenosine 5'-monophosphate (AMP) curves show two peaks, at 8 and 20 h, with a minimum at 16 h. The "energy charge" function varies around a mean of 0.72 throughout the period of exponential growth. Transferral of growing cells to buffer lacking a nitrogen source stabilizes the [ATP](i) near 2.5 mM, apparently independent of the cell age, and most studies of metabolic inhibitors were carried out on cells grown 14 to 16 h and then shifted to N-free buffer. Under these conditions sudden respiratory blockade (cyanide) produces exponential decay of ATP with a time constant of about 5.7 s (half-time of 3.9 s), and at a rate which implies a minimal ATP turnover of 0.44 mM/min. This figure is about one-third the rate (1.17 mM/min) which would be calculated from steady-state respiration, a discrepancy which may partly be accounted for by transphosphorylation from appreciable amounts of non-adenine nucleoside di- and triphosphates present in Neurospora. For all three adenine nucleotides, the transients associated with sudden respiratory blockade include overshoots or undershoots of several minutes duration, which are consistent with feedback regulation of glycolysis by the AMP/ATP ratio.
The influence of victim ethnicity on arrest in violent crimes

As the Hispanic population in the USA grows, studies illustrate the importance of extending dichotomous examinations of race in criminal justice research. The current study seeks to build on this growing body of scholarship. Using data from the 2008 National Incident-Based Reporting System, we examine if victim race and ethnicity affects police clearance of nonlethal violent crimes (sexual assault, robbery, aggravated assault, and simple assault). We draw on the victim-devaluing perspective as well as perceptions of police legitimacy in the Hispanic community to explain our results. Findings indicate that the race and ethnicity of the victim are related to police clearance of cases although the relationship between clearance and case solvability factors is stronger.
PROPERTIES OF PROTEINASE FROM STREPTOCOCCUS FAECALIS VAR. LIQUEFACIENS

Bleiweis, Arnold S. (The Pennsylvania State University, University Park), and Leonard N. Zimmerman. Properties of proteinase from Streptococcus faecalis var. liquefaciens. J. Bacteriol. 88:653–659. 1964.—The extracellular group D streptococcal proteinase is inactivated by chelating agents [ethylenediamine-tetraacetate (EDTA), o-phenanthroline, and 8-quinolinol] and mercaptans (cysteine, mercaptoethanol, and thioglycolate). The optimal inhibitory concentrations of EDTA (4 × 10−4m) and cysteine (2.5 × 10−2m) promote rapid loss of activity with 50% inactivation after 4 to 5 min. Enzyme inactivated by either EDTA or cysteine is reactivated about 80% by 4 × 10−4m Zn++. Such reactivation of EDTA-treated enzyme is prevented completely by iodoacetate (5 × 10−2m) and of cysteine-treated enzyme by oxidizing conditions, which suggests that the zinc binding-site may be a thiol. High levels of zinc (10−3m) do not allow reactivation in either case, and actually inhibit native proteinase. Ca++, Mg++, Co++, Fe++, Cu++, and Ni++ do not reactivate cysteine-treated enzyme, but Mn++ (10−4 to 8 × 10−4m) allows 27% reversal. N2-held, cysteine-treated enzyme can be spontaneously reactivated if the substrate is flushed with O2 during the assay; leakage of air or O2 into the samples before assay leads to loss of reactivatability. Native proteinase does not lose activity after dialysis for 43 hr against 0.07 m phosphate buffer. It is concluded that the group D proteinase obtained from Streptococcus faecalis var. liquefaciens is probably a zinc metalloenzyme that is unlike the thiol-activated, group A streptococcal proteinase, but similar to the mammalian carboxypeptidase A.
Characterization of an argon microwave plasma torch coupled to a Mattauch–Herzog geometry mass spectrometer

An atmospheric pressure argon microwave plasma torch (MPT) ionization source was coupled to a Mattauch–Herzog +mass spectrometer (MHMS) for elemental analysis. The operating conditions of the Ar MPT-MHMS were optimized for signal level, peak shape and resolution. The background spectrum was characterized, with most peaks arising from species that contain argon and nitrogen. Detection limits were in the tens to hundreds of pptr range while sensitivities are in the 106 counts s−1 ppm−1 regime for most elements. The major weakness of the Ar MPT-MHMS was isotope-ratio accuracy and precision.
Initial look at the coronagraph technology gaps for direct imaging of exo-earths

NASA's Astrophysics Division plans to initiate mission concept studies in 2016 of large candidate astrophysics missions for consideration by the 2020 Decadal Survey. The studies are expected to include two mission concepts capable of directly imaging exo-earths (HabEx and LUVOIR). Direct imaging of an exo-earth begins with starlight suppression, which is required at a depth of 10-10 in the visible for an earth-sun twin. The current results of laboratory coronagraphs are approaching the levels needed for the direct detection and characterization of an exo-earth. Other critical technologies are needed, such as ultra-low noise detectors, large format deformable mirrors, a large aperture space telescope, and sophisticated post-processing algorithms. While technologically challenging, the goal is not impossible; many of the required technologies are already at TRL 3 and beyond. After the successful on-orbit operation of WFIRST-AFTA in the next decade, some of the technologies will be at TRL 9. This paper summarizes the needed technologies that NASA's Exoplanet Exploration Program is prioritizing for maturation.
Surface-enhanced Raman spectroscopy of peptides

Surface-enhanced Raman (SER) spectroscopy has been used to probe the adsorption, surface interactions, and orientations of peptides on metal surfaces. Amino acids in homodipeptides give SER spectra with unique features that can be used to characterize the surface interactions of specific functional groups in more complicated peptides. In heterodipeptides, there is a hierarchy of functional group-surface interactions that prescribe their orientation and conformation on metal surfaces. By establishing this hierarchy, it is now possible to predict the interactions that occur between larger peptides and surfaces. Furthermore, the observed trends suggest that it should be possible to control these interactions by varying the solution pH, the charge on the surface, and other parameters of the measurement in order to adsorb species selectively from mixtures of peptides in solution. Potential biomedical applications of this technique will be described.
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins

Signaling is initiated through the T Cell Receptor (TCR) when it is engaged by antigenic peptide fragments bound by Major Histocompatibility Complex (pMHC) proteins expressed on the surface of antigen presenting cells (APCs). The TCR complex is composed of the ligand binding TCRαβ heterodimer that associates non-covalently with CD3 dimers (the eδ and eγ heterodimers and the ζζ homodimer) 1 . Upon engagement of the receptor, the CD3 ζ chains are phosphorylated by the Src family kinase, Lck. This leads to the recruitment of the Syk family kinase, Zap70, which is then phosphorylated and activated by Lck. After that, Zap70 phosphorylates the adapter proteins LAT and SLP76, initiating the formation of the proximal signaling complex containing a large number of different signaling molecules 2 .
Interconnect customization for a hardware fabric

This article describes several multiplexer-based interconnection strategies designed to improve energy consumption of stripe-based coarse-grain reconfigurable fabrics. Application requirements for the architecture as well as two dense subgraphs are extracted from a suite of signal and image processing benchmarks. These statistics are used to drive the strategy of the composition of multiplexer-based interconnect. The article compares interconnects that are fully connected between stripes, those with a cardinality of 8:1 to 4:1, and extensions that provide a 5:1 cardinality, limited 6:1 cardinality, and hybrids between 5:1 and 3:1 cardinalities. Additionally, dedicated vertical routes are considered replacing some computational units with dedicated pass-gates. Using a fabric interconnect model (FIM) written in XML, we demonstrate that fabric instances and mappers can be automatically generated using a Web-based design flow. Upon testing these instances, we found that using an 8:1 cardinality interconnect with 33p of the computational units replaced with dedicated pass-gates provided the best energy versus mappability tradeoff, resulting in a 50p energy improvement over fully connected rows and 20p energy improvement over an 8:1 cardinality interconnect without dedicated vertical routes.
Polytropic Indices of Solar Flares

The polytropic indices of solar flares are studied by means of a semiempirical model of flare thermodynamic structure that utilizes soft X-ray measurements of the Sun and two scaling laws: (1) relating the product of plasma pressure and temperature to spatial scale; and (2) relating spatial scale to flare duration. The model and the main summary results of a survey of ≈1100 flares were described in two previous papers, cited herein. The principal result of the present study is that the polytropic indices, derived from the computed macro-thermodynamic structure of individual flares, are distributed about a value of 1.66 ± 0.02 for moderate flares and trend uniquely toward the value of the ratio of specific heats of a non-relativistic ideal gas, 5/3, for the most intense flares. The main conclusion is that magnetically contained, mostly thermalized plasma manifested in soft X-rays responds quasi-adiabatically to large energy fluxes that are absorbed and released by the flare in a few tens of minutes. This finding is consistent with the hypothesis that energy deposition is exactly balanced by conductive and (mostly) radiative losses over relatively short time intervals.
Determination of reaction coordinates via locally scaled diffusion map

We present a multiscale method for the determination of collective reaction coordinates for macromolecular dynamics based on two recently developed mathematical techniques: diffusion map and the determination of local intrinsic dimensionality of large datasets. Our method accounts for the local variation of molecular configuration space, and the resulting global coordinates are correlated with the time scales of the molecular motion. To illustrate the approach, we present results for two model systems: all-atom alanine dipeptide and coarse-grained src homology 3 protein domain. We provide clear physical interpretation for the emerging coordinates and use them to calculate transition rates. The technique is general enough to be applied to any system for which a Boltzmann-sampled set of molecular configurations is available.
Induction of the Small Heat Shock Protein αB-Crystallin by Genotoxic Stress is Mediated by p53 and p73

The small heat shock protein αB-crystallin is a molecular chaperone that is induced by stress and protects cells by inhibiting protein aggregation and apoptosis. To identify novel transcriptional regulators of the αB-crystallin gene, we examined the αB-crystallin promoter for conserved transcription factor DNA-binding elements and identified a putative response element for the p53 tumor suppressor protein. Ectopic expression of wild-type p53 induced αB-crystallin mRNA and protein with delayed kinetics compared to p21. Additionally, the induction of αB-crystallin by genotoxic stress was inhibited by siRNAs targeting p53. Although the p53-dependent transactivation of an αB-crystallin promoter luciferase reporter required the putative p53RE, chromatin immunoprecipitation failed to detect p53 binding to the αB-crystallin promoter. These results suggested an indirect mechanism of transactivation involving p53 family members p63 or p73. ΔNp73 was dramatically induced by p53 in a TAp73-dependent manner, and silencing p73 suppressed the transcriptional activation of αB-crystallin by p53. Moreover, ectopic expression of ΔNp73α (but not other p73 isoforms) increased αB-crystallin mRNA levels in the absence of p53. Collectively, our results link the molecular chaperone αB-crystallin to the cellular genotoxic stress response via a novel mechanism of transcriptional regulation by p53 and p73.
Dynamics of hydrogen at the surface of supported ruthenium.

One-dimensional (1D) and two-dimensional NMR exchange measurements were performed to probe the dynamics of hydrogen adsorption on highly dispersed silica-supported ruthenium particles at pressures from ${10}^{\mathrm{\ensuremath{-}}4}$ to 600 Torr and temperatures between 292 and 400 K. We found three distinct NMR resonances, ${\mathrm{\ensuremath{\alpha}}}_{\mathit{I}}$, ${\mathrm{\ensuremath{\alpha}}}_{\mathit{M}}$, and \ensuremath{\beta}, respresenting hydrogen interacting with the metal surface. The character of motion of the three hydrogen species was inferred from 1D and 2D NMR experiments. Also, two types of exchange processes were found: (i) a slow chemical exchange occurring on a submillisecond time scale between ${\mathrm{\ensuremath{\alpha}}}_{\mathit{M}}$ and \ensuremath{\beta} and (ii) a fast exchange between weakly adsorbed hydrogen and hydrogen in the gas phase, with both hydrogen species contributing to the \ensuremath{\beta} NMR line.
Use of a slit camera for MTF measurements.

The slit camera was analyzed in order to establish its utility and limitations as an MTFmeasurement tool for characterizing radiographic imaging systems. Commercial slit cameras are attractive for MTFmeasurements because the beveled edges significantly reduce their alignment sensitivity as compared to the conventional parallel jaw slit. Radiation passing through the beveled edges increases the effective width of the slit camera so that a correction based on the nominal slit width would leave residual error in the MTFmeasurement. Experimental and Monte Carlo simulated MTFmeasurements were made on a slit camera (10 μm nominal slit width) in order to estimate its sensitivity in alignment, quantify the error in MTF due to transmission through the beveled jaws, and provide a correction factor. The alignment tolerances of the slit camera were found to be about 12 times larger than for the parallel jaw slit at small HVLs (∼1.3 mm Al) of the incident beam and 9 times larger at higher HVLs (∼7 mm Al). The magnitude of the residual error in MTF was dependent on the quality of the incident spectrum. For incident spectra with high kVp and HVL (⩾120 kVp, ⩾5 mm Al HVL), transmission through the beveled edges produced errors in MTF up to 15% at 5 cycles/mm and 30% at 10 cycles/mm. By assuming a rectangular slit profile with an effective width based on the kVp, HVL, and filtration material of the incident beam, an MTF correction factor was determined. Application of this correction factor reduced the errors to less than 4% up to 10 cycles/mm. At low beam energies and spatial frequencies, the correction is less critical. Ease of alignment and greater availability make a commercial slit camera useful for MTFmeasurements. Accurate MTFmeasurements can be made if appropriate correction factors are applied.
Molecular pathogenesis of sporadic prion diseases in man.

The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent's efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation - intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins - are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare.
Luminescence instrument for the acquisition of low-temperature fluorescence and phosphorescence spectra

An inexpensive, simple (but highly automated) instrument for acquiring high-resolution fluorescence and phosphorescence spectra of polycyclic aromatic hydrocarbons (PAHs) is described. Fluorescence and phosphorescence signals are processed by gated integration and photon counting, respectively. The instrument can be used to acquire excitation as well as emission spectra in both the frequency and time domain. In addition, a method for measuring single and double exponential phosphorescence decay times is presented. Decay times ranging from 0.3 ms to 300 ms were measured for several naphthalene derivatives, with a precision of ∼10%. The primary advantages of this instrument are high sensitivity, high selectivity, wide linear dynamic ranges, and a versatile range of applications.
Passage through the mammalian gut triggers a phenotypic switch that promotes Candida albicans commensalism.

Suzanne Noble and colleagues show that the passage of Candida albicans through the mammalian gut induces expression of the Wor1 transcription factor, triggering a developmental switch that promotes commensal fitness.
Trajectories of intrusive parenting during infancy and toddlerhood as predictors of rural, low-income African American boys' school-related outcomes.

Stability and change in maternal intrusiveness during early childhood is rarely explored, particularly within African American families. The current study examined the prediction of maternal intrusiveness during the first 3 years of life among mothers of rural, low-income African American boys and its relation to school-related outcomes. Observations of mothers (N = 230) interacting with children at 6, 24, and 36 months were coded and analyzed. Predictors of the trajectories and child outcomes were assessed using questionnaires and various tasks. On average, mothers of African American boys increased in intrusiveness across the first 3 years of life. Cumulative sociodemographic risk was associated with initial levels of intrusiveness, and child fearfulness and maternal negative regard predicted increases in intrusiveness over time. After controlling for sociodemographic risk, child temperament, and parental negativity, increases in intrusiveness over the first 3 years of life were associated with lower levels of expressive communication, inhibitory control, and intellectual functioning but not with attention focusing. Comprehensive parenting intervention efforts aimed toward improving children's outcomes must take into consideration the broader socioeconomic and affective context in which parenting behaviors occur as well as stability and change in parenting over time.