cssi/SciSciGPT-SciSciNet huggingface dataset:
High yield and semi-automated synthesis procedure of (R)-[11C]PK11195

1900 Objectives: There has been a great deal of interest recently in applying (R)-[11C]PK11195 PET for neuropathologies involving neuroinflammation and activated microglia. In our hands, radiochemical yields of (R)-[11C]PK11195 using the reported KOH/DMSO method (Camsonne et al., 1984) were inconsistent. We report here a modified radiosynthesis procedure using NaH/DMSO (Hashimoto et al., 1989) that consistently produced the desired radioligand in high radiochemical yield and purity. Methods: A solution of (R)-N-Desmethyl-PK11195 (1.0-1.2 mg) in anhydrous DMSO (250 µL) was added to 3-4 mg of NaH (60% in oil) at room temperature 10 minutes before end-of-beam (EOB). [11C]Methyl iodide was slowly introduced into the precursor solution over 2-3 minutes and then the reaction vial was closed for 1 minute. After purging for 30 sec with a flow of argon, 0.8 mL of water was added to the reaction mixture. The resulting suspension was loaded onto an on-line C-18 extraction cartridge mounted on an HPLC injector valve. The cartridge was then washed with 10 mL of water or normal saline solution. The crude product, adsorbed onto the C-18 cartridge, was purified by semi-preparative HPLC (Luna, C-18, 5 µm, 250 x 10 mm) by directing the solvent flow (65% ethanol, 3 mL/min) through the cartridge. By monitoring the eluant with a flow-through radiation detector, the major portion (149 ± 22 mCi in 2.0 mL eluant) of the (R)-[11C]PK11195 fraction was collected (tR= 11 to 13 min) in a sterile vial containing 200 µL of Tween-80 (to minimize adsorption of the radioligand on the filter and plastic components). The resulting solution was then diluted with 10 – 11 mL of normal saline and sterilized by filtration (0.2µm nylon filter). Radiochemical and chemical purities of the product were determined by HPLC (Inertsil, C-8, 5 µm, 3.2 X 250 mm) with 10 mM KH2PO4/acetonitrile, 35/65, as the eluant, employing both radioactive (NaI scintillation) and ultraviolet (300 nm) detection. With a flow rate of 1.0 mL/min, (R)-[11C]PK11195 elutes in 4.9 min. The elution time of the potential dechlorinated radiochemical impurity (Cleij et al., 2003) was 4.6 min. Results: The radiochemical yield of the formulated (R)-[11C]PK11195 (collected portion; 75 – 80% of total product produced) was 37.9 ± 4.8% (EOB, n=17). Uncorrected radiochemical yield was 12.3 ± 1.7% (based on 11CO2) with a total synthesis time of 39 minutes (EOB). Specific activity was 994 ± 131 Ci/mmol (EOS). Radiochemical and chemical purities were >98%. Conclusions: We have developed a reliable semi-automated radiosynthesis procedure which produces (R)-[11C]PK11195 in high radiochemical yield and purity.
Self-compacting concrete using recycled asphalt pavement and recycled concrete aggregate

Abstract In this study recycled concrete aggregate (RCA) and recycled asphalt pavement (RAP) are used in the production of self-consolidating concrete (SCC) with varying percentage replacements of natural coarse aggregate (NCA). A total of 16 concrete mixtures were prepared and tested. Mixtures were divided into four different groups, with constant water to cementitious (w/cm) material ratio of 0.4, based on RCARAP content: 0%, 25%, 50%, and 75% of NCA replaced by RCARAP. Portland cement was used for the control mixtures of each group, while all other mixtures were designed with partial replacement of cement by supplementary cementitious materials (70% fly-ash, 70% slag, and 25% fly-ash+25% slag). The fresh properties such as flowability, deformability; filling capacity, and resistance to segregation of concrete were investigated. The hardened properties such as compressive strength and split tensile strength were studied. The durability characteristics including the unrestrained shrinkage test, and rapid chloride permeability test (RCPT) were investigated. Partial replacement of cement using FA and S resulted in smaller 28-days-compressive strength compared to control mixtures. The replacement of NCA by RCARAP reduced the workability, and the compressive and tensile strengths of SCC mixtures.
The Fickle Crowd: Selective Differentiation in Cultural Markets

Much of previous research has made important progress in our understanding of evaluations in cultural markets. However, its predictions on the effect of past popularity on future evaluations have o...
Mixture quantification in the presence of unknown interferences

Conventional methods for multicomponent analysis such as partial least squares perform well if the constituents of the chemical mixture are known. However, these methods degrade significantly when unknown interferents are present in the mixture. We describe a sparse active-sensing approach that addresses the interference problem in chemical mixture quantification. The approach assumes that a large library is available containing hundreds (or thousands) of potential interferences. This strategy is infeasible with conventional calibration models since it leads to ill-conditioning (i.e., many solutions exist that match the measurement vector). We show that combining active sensing with a sparsity constraint allows us to recover the concentration of the target compounds, even in the presence of high concentrations of unknown backgrounds. We evaluate the performance of the method against partial least squares using simulated mixtures from a database of Fourier transform infrared (FTIR) spectra.
Co-Oriented Fluid Functional Equation for Electrostatic interactions (COFFEE)

Abstract In chemical engineering often functional groups like OH, C O, or NH x with an asymmetric charge distribution occur. Aside from polar interactions, such groups often show H-bonding interactions. The combination of both types is especially hard to describe with equations of state. This leads to the effect that including polar interactions for clearly polar pure compounds may lead to a worse description of mixtures containing this component. One possible reason for this behavior is that equations of state are usually based on perturbation theory that ignores the change in fluid structure due to interactions. This approximation is good for e.g. dispersive interactions, but is known to be bad for at least the gaseous phase of polar fluids up to moderate densities. The issue is addressed in this article by developing a perturbation theory around the target fluid rather than the reference fluid, as is usually the case. This makes it possible to include ordering effects into the equation of state and to calculate additional structural information in a fraction of the time used by typical methods like molecular simulation or integral equation theory. The perturbation theory is parameterized on the Stockmayer fluid’s structure and vapor-liquid equilibria, calculated from molecular simulation, and agrees quantitatively with them. It is verified on a second simple fluid, the shifted Stockmayer fluid, where the dipole is shifted along its axis away from the Lennard-Jones center. For this fluid also molecular simulations are performed for both structure and vapor-liquid equilibria. Both properties are predicted by the new equation of state and again agree quantitatively with simulation. The new theory is then applied to hydrogen chloride and shows improvements over models for existing theories. Namely, liquid density description is improved over a literature model for PCP-SAFT, where the dipolar nature of hydrogen chloride is considered, and vapor pressure description is improved over a literature model for PC-SAFT, where the weak H-bonding nature is considered. The number of parameters can be kept at three, as for the PCP-SAFT model, by using quantum mechanics results from literature for the dipole shift. The model shows improvements for the predicted vapor density compared to both models from literature. Aside from improving thermodynamic property description and prediction, the new theory allows the fast calculation of a fluid’s mutual orientation structure. This is useful e.g. for assessing availability of two reactant groups to each other, thereby allowing a better description of reaction kinetics. This has not been accomplished by any equation of state before.
A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy

Background M2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking. Methodology Patients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the ‘stroke belt’ were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data. Results There were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5–18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p 3 for NIHSS score ≥9 versus 30 (±34)cm 3 for NIHSS score Conclusion M2 occlusions can present with serious neurological deficits and cause significant morbidity and mortality. Patients with M2 occlusions and higher baseline deficits (NIHSS score ≥9) may benefit from endovascular therapy, thus potentially expanding the category of acute ischemic strokes amenable to intervention.
Quantities, Numbers, Number Names and the Real Number Line

This paper describes an approach to developing concepts of number using general notions of quantity and their measurement. This approach, most prominently articulated by Davydov and his colleagues, is discussed, and some arguments favouring this approach are offered. First is that it provides a coherent development of both whole numbers and fractions. Second, it makes the geometric number line continuum present from the start of the school curriculum as a useful mathematical object and concept into which real numbers can eventually take up residence. Third, in the Davydov approach, there are some significant opportunities for some early algebraic thinking. I further present an instructional context and approach to place value that simulates a hypothetical invention of a place value system of number representation.
Workplace Learning in Informal Contexts

As societies on both sides of the Atlantic are changing so rapidly, everybody needs to learn new things in order to keep abreast with the on-going developments. A great deal of learning is situational, unintended, accidental, that is, informal, and much of this occurs at work. Such workplace informal learning plays a significant role in educators’ professional growth.
Characterization of single and discretely-stepped electro-composite coatings of nickel-alumina

Electrodeposition from a sulfamate bath has been used to produce single layer and discretely stepped electro-composites consisting of a metallic nickel matrix with second phase alumina (α-Al2O3) particles. Light optical microscopy (LOM), scanning electron microscopy (SEM), quantitative image analysis (QIA), and micro-indentation techniques were used to characterize the deposits. As previously seen, an increase in bath particle loading and decrease in plating current density increased the volume percent of alumina incorporated into the coating, with a maximum of 40 vol % being attained. For samples deposited above 1 A/dm2, a direct relationship between the alumina volume percent and coating hardness was seen due in part to the related decrease in interparticle spacing (IPS) at the higher vol %. However, the strengthening mechanism of the electro-composites may be more complex with both the metallic nickel grain structure and IPS being factors, as seen for samples deposited at 0.5 A/dm2. The incorporation of alumina into the electrodeposited nickel was also observed to affect the as-plated surface structure of the coating. Due to the particles inhibiting the formation of pyramidal features found on the surface of pure nickel electrodeposits, the electro-composite surfaces were observed to be relatively flat. Also, structure within the metallic nickel matrix appeared due to rapid growth of the nickel coating around the inert particles when plated at high current densities. In addition, discretely layered functionally graded materials were produced without alterations to the original deposition procedure of the single layer deposits. It was found that the various processing stages needed to produce the stepped coatings did not affect the structure or properties of the individual layers, when compared to that of the corresponding single-layered electro-composites.
The Effect of Dispersion on Fingering in Miscible Displacements

The term “viscous fingering” generally refers to the instability associated with the displacement of a more viscous fluid by a less viscous one within a porous medium. As we will see, the mechanism of the instability is associated with the forces acting on a front as a result of a viscosity contrast near that front. However, the forces causing or mitigating the instability may also be due to density differences acting together with gravity, so perhaps the more general term, “fingering” is more appropriate.
Rotational bands in doubly odd 128Cs.

Four rotational band sequences have been established in the doubly odd {sup 128}Cs nucleus via the {sup 120}Sn({sup 11}B,3{ital n}{gamma}) reaction. One band shows the characteristic features for the {pi}{ital h}{sub 11/2}{direct product}{nu}h{sub 11/2} configuration which has systematically been observed in doubly odd nuclei throughout the {ital A}{similar to}130 mass region. Triaxial cranked shell-model calculations have been performed to assist in the assignment of quasiparticle configurations to the other bands.
Nanostructure-Driven Replication of Soft Tissue Biomechanics in a Thermoplastic Elastomer Hydrogel.

Synthesis of hydrogel networks capable of accurately replicating the biomechanical demands of musculoskeletal soft tissues continues to present a formidable materials science challenge. Current systems are hampered by combinations of limited moduli at biomechanically relevant strains, inefficiencies driven by undesirable hysteresis and permanent fatigue, and recovery dynamics too slow to accommodate rapid cycling prominent in most biomechanical loading profiles. Here, we report on a novel paradigm in hydrogel design based on prefabrication of an efficient nanoscale network architecture using the melt-state self-assembly of amphiphilic block copolymers. Rigorous characterization and mechanical testing reveal that swelling of these preformed networks produces hydrogels with physiologically relevant moduli and water compositions, negligible hysteresis, subsecond elastic recovery rates, and unprecedented resistance to fatigue over hundreds of thousands of compression cycles. Furthermore, by relying only on si...
Honor flight: Recognition of preeminent-mature tourists

Abstract The “oldest old” (aged 85+), here coined as the “preeminent-mature,” have been largely ignored by tourism scholars based on medical and access barriers. The research described herein was conducted to help close the gap in understanding this unique segment of tourists. Using participant-observation techniques, researchers joined two “Honor Flight” bus tours, comprised primarily of World War II veterans and their attendants, in order to detail the experiences of preeminent-mature tourists and highlight considerations for service provision and the creation of memorable experiences. Five themes were supported: nostalgia reenactment, relationship development/socializing, identity renegotiation, constraints removal, and comfort reassurance. The findings extend previous service excellence research by considering the distinctive needs of preeminent-mature tourists.
Advanced Spanish Language High School Students: Perceptions of Spanish Instruction, Understanding, and Cultural Appreciation

5 Chapter 1 Introduction 6 Statement of Problem 6 Purpose Statement 7 Research Question 7 Theoretical Rationale 7 Assumptions 7 Background and Need 8 Chapter 2 Review of the Literature 9 Introduction 9 Historical Context 9 Review of the Previous Literature 9 Statistical Information 13 Teaching Methodology 13 Chapter 3 Method 14 Advanced Spanish Language High School Students 4 Introduction 14 Sample and Site 14 Ethical Standards 14 Access and Permissions 14 Data Gathering Strategies 15 Data Analysis Approach 15 Chapter 4 Findings 16 Description of Site, Individuals, Data 16 Student Attitude 17 The Cultural Divide 17 Chapter 5 Discussion /Analysis 18 Summary of Major Findings 18 Comparison of Findings to Previous Research 19 Limitations/Gaps in the Study 20 Implications for Future Research 21 Overall Significance of the Study 21 About the Author 22 References 23 Advanced Spanish Language High School Students 5 Abstract The addition of foreign language study to high school core curriculum benefits learners, societyThe addition of foreign language study to high school core curriculum benefits learners, society and overlap into the success of other areas of study and critical thinking. The problem in contemporary high school curriculum is that foreign language is disappearing. High school students and educators are failing to see the benefit of foreign language and its benefit to all subjects. The purpose of this study is to identify student perceptions of the importance of foreign language study in high school. The literature review documents the disappearance of foreign language study as part of a high school curriculum. Methodology includes conversations with high school students in third year and advanced placement literature in Spanish. Information from students was collected through the use of focus group discussions. Results indicated that these high performing students all plan to pursue Spanish and additional foreign language study in higher education and future professions. While this minority group of students anticipates a multilingual future, they are aware of an ignorant majority of students that fail to recognize the seriousness, utility and opportunities through mastering Spanish fluency. Having foreign language as a part of the core curriculum needs to be examined. Language instruction can help enrich student high school experience and prepare them for a diverse world and international workforce. Advanced Spanish Language High School Students 6 Chapter
B cell superantigens in the human intestinal microbiota

IgA is prominently secreted at mucosal surfaces and coats a fraction of the commensal microbiota, a process that is critical for intestinal homeostasis. However, the mechanisms of IgA induction and the molecular targets of these antibodies remain poorly understood, particularly in humans. Here, we demonstrate that microbiota from a subset of human individuals encode two protein "superantigens" expressed on the surface of commensal bacteria of the family Lachnospiraceae such as Ruminococcus gnavus that bind IgA variable regions and stimulate potent IgA responses in mice. These superantigens stimulate B cells expressing human VH3 or murine VH5/6/7 variable regions and subsequently bind their antibodies, allowing these microbial organisms to become highly coated with IgA in vivo. These findings demonstrate a previously unappreciated role for commensal superantigens in host-microbiota interactions. Furthermore, as superantigen-expressing strains show an uneven distribution across human populations, they should be systematically considered in studies evaluating human B cell responses and microbiota during homeostasis and disease.
Lung Stereotactic Body Radiation Therapy (SBRT) dose gradient and PTV volume: a retrospective multi-center analysis.

The treatment of lung lesions with stereotactic body radiation therapy calls for highly conformal dose, which is evaluated by a number of metrics. Lung stereotactic body radiation therapy clinical trials constrain a plans gradient index. The purpose of this work is to describe the dependence of clinically achievable dose gradient on planning target volume. Three hundred seventy-four lung stereotactic body radiation therapy treatment plans were retrospectively reviewed and selected for this study. The relationship between R50% and planning target volume size was observed and compared against the RTOG 0915 and 0813 constraints noting minor and major deviations. Then a least squares regression was used to determine the coefficients for a power functional form of the dependence of gradient measure (GM) on planning target volume size. Of the 317 peripheral lung SBRT plans, 142 exhibited no deviation, 135 exhibited a minor deviation, and 40 exhibited a major deviation according to the RTOG 0915 dosimetric. conformality and dose fall-off constraints. A plot of gradient measure versus planning target volume size for peripheral lesions, excluding RTOG 0915 major deviations, is fit with an power function of GM = 0.564 V0.215. Using the PTV size and GM relationship we have characterized, treatment plans with PTV < 85 cm3 can be evaluated subjectively to our previously plans, and given a percentile GM. This relationship and evaluation is useful for volumetric modulated arc therapy lung stereotactic body radiation therapy treatment planning and quality control.
Pondering Higher-Risk Pediatric Heart Donors: Can We Use More?

Background Pediatric heart transplantation is challenged with long waiting list times and high waiting list mortality, mostly due to a continuing organ shortage and high rates of nonuse. This analysis was conducted to determine the outcomes associated with high-risk donors when recipient variability is neutralized. Methods The United Network for Organ Sharing (UNOS) thoracic organ transplant database was searched for pediatric heart transplant recipients (≤17 years old at time of listing) between January 2006 and December 2015. High-risk donors were identified using 2 previously published methods based on donor utilization (DUB) and recipient survival (RSB). Within each of the populations, which were not mutually exclusive, low- and high-risk donor cohorts were propensity matched on recipient characteristics, and outcomes (graft survival) were analyzed using Kaplan-Meier methods. Results When recipient variability was harmonized, the DUB population (n = 3048) did not have different graft survival times between the high-risk graft recipients (n = 1016) and low-risk graft recipients (n = 2032; P = .713). Likewise, the RSB population (n = 1053) also did not have different graft survival times between the high-risk graft recipients (n = 351) and low-risk graft recipients (n = 702; P = .706). Conclusions Cardiac allografts deemed high risk by use- and survival-based methods led to equivalent posttransplant survival as matched recipients with low-risk donors. This study demonstrates that traditionally high-risk donors may have been associated with worst posttransplant survival because of the recipients that used them. Therefore, accepting these “high-risk” donor grafts should be considered as a potential approach to reduce waiting list times and mortality while maintaining comparable posttransplant survival.
Research is like a bad game of ‘telephone’: mitigating the information breakdown from clinicians and researchers to the general public

In the contemporary media environment, it is impossible for researchers to control how their research is disseminated and interpreted. Researchers’ findings can become lost in translation, particularly when deemed ‘newsworthy’. This information breakdown reminds us of the children’s game, ‘telephone’. In telephone, an individual whispers a message to another individual, which is repeated to another and so on. When the final individual receives the message, it has likely changed substantially. Our model of the information breakdown within the research telephone focuses on two factors—the messenger and the receiver (figure 1). The messenger is the researcher who conducts the study, submits the manuscript for review and disseminates the findings through traditional and social media. The receivers of messaging may further propagate the findings, while making their own inferences, thereby crafting slightly revised messages. Unlike the game of telephone, the research telephone does not follow a single path; intermediate pathways can be bypassed (eg, disseminating findings prior to publication). When the scientific method is misrepresented or not comprehensively disclosed, subtle yet important misinterpretations occur, or the research message may be deliberately skewed to maximise ‘clicks’. When scientific writers fail to …
DeepDriveMD: Deep-Learning Driven Adaptive Molecular Simulations for Protein Folding

Simulations of biological macromolecules are important in understanding the physical basis of complex processes such as protein folding. However, even with increasing computational capacity and specialized architectures, the ability to simulate protein folding at atomistic scales still remains challenging. This stems from the dual aspects of high dimensionality of protein conformational landscapes, and the inability of atomistic molecular dynamics (MD) simulations to sufficiently sample these landscapes to observe folding events. Machine learning/deep learning (ML/DL) techniques, when combined with atomistic MD simulations offer the opportunity to potentially overcome these limitations by: (1) effectively reducing the dimensionality of MD simulations to automatically build latent representations that correspond to biophysically relevant reaction coordinates (RCs), and (2) driving MD simulations to automatically sample potentially novel conformational states based on these RCs. We examine how coupling DL approaches with MD simulations can lead to effective approaches to fold small proteins on supercomputers. In particular, we study the computational costs and effectiveness of scaling DL-coupled MD workflows implemented using RADICAL-Cybertools in folding two prototypical systems, namely Fs-peptide and the fast-folding variant of the villin head piece protein. We demonstrate that a DL-coupled MD workflow is able to effectively learn latent representations and drive adaptive simulations. Compared to traditional MD-based approaches, our approach achieves an effective performance gain in sampling the folded states by at least 2.3x. Together, our study provides quantitative basis to understand how coupling DL approaches to MD simulations, can lead to effective performance gains and reduced times to solution on supercomputing resources.
Differential processing and habituation in distinct spatial frequency channels in V1 of a mouse model of fragile X syndrome

Extraction of both common and unique features across different visual inputs is crucial for animal survival. Regularities in the visual input lead to learning of the general principles governing an environment, whereas unique features are important for novelty detection. Low and high spatial frequencies (SF) represent two different channels of visual perception, which may be playing different roles in the processing of global pattern and local details. Alterations in the processing of these different SF channels may lead to impaired visual perception. Excessive detail-oriented processing and reduced habituation to sensory stimuli are some of the hallmarks of altered sensory perception in autism. However, the underlying neural mechanisms of these impairments are not understood. To gain insight into the pathophysiology of these impairments, we investigated the low and high SF channels in V1 of Fmr1 KO mice, the mouse model of Fragile X syndrome (FX). We first provide behavioral evidence for reduced habituation of both pupillary baseline and surprise responses in FX mice. Using silicon probe recordings, we demonstrate excessive processing of high SF stimuli in the late stages of visual responses in V1 of FX mice. We then show a reduced adaptation during a visual oddball paradigm in neurons preferring low but not high SF. Overall, our findings suggest that altered processing in distinct SF channels might contribute to altered visual perception and learning in FX and autism.
High expectations: The landscape of clinical trials of medical marijuana in oncology.

Abstract Purpose Given the infancy and evolving complexity of medicinal marijuana, an evolving political landscape, and the growing frequency of its use in cancer care, it is important for oncologists to be actively engaged in developing and successfully implementing clinical trials focusing on medical marijuana. The purpose of this study was to analyze and evaluate trends in clinical trials focused on medical marijuana in oncology. Patients and methods Using 3 web-based registries, Clinicaltrials.gov, European Union Clinical Trials Register (EU-CTR), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), we queried for search terms related to marijuana and oncology. This search identified approximately 48 oncology clinical trials involving medical marijuana. We restricted our selection to clinical trials registered between January 2002 and May 2019. Data were summarized using descriptive statistics, and qualitative data were represented as frequency and percentage. Results A total of 474,043 trials were queried in the databases and the search strategy returned 48 trials since 2002 that met criteria for analysis in the current study: 36 from ClinicalTrials.gov, 8 from EU CTR, and 4 from ICTRP. Mean trial enrollment was 370 participants, median 53, with range of 6–10000 participants. In total, 25 % trials were phase I, 12.5 % were phase I/II, 27.1 % were phase II, 4 % were phase II/III, 18.8 % were phase III, and 12.5 % were unknown. The recruitment status were "not yet recruiting", "recruiting", "active, not recruiting", "completed", “terminated/withdrawn”, and "unknown" in 6 (12.5 %), 14 (29.2 %), 0 (0 %), 20 (41.7 %), 5 (10.4 %), and 3 (6.3 %) trials, respectively. The trial start years were “2002-2005″, 2006–2009, 2010–2013, 2014–2017, and 2018-Present in 4 (8.3 %), 5 (10.4 %), 10 (20.8 %), 15 (31.3 %), and 14 (29.2 %) of trials, respectively. Lastly, synthetic or branded compounds were investigated in 26 (54.2 %) of trials since 2002. Conclusion Our results indicate that across oncology, there is growing interest in clinical research in the use of medical marijuana.
Stimulus dependent transformations between synaptic and spiking receptive fields in auditory cortex.

Auditory cortex neurons nonlinearly integrate synaptic inputs from the thalamus and cortex, and generate spiking outputs for simple and complex sounds. Directly comparing synaptic and spiking activity can determine whether this input-output transformation is stimulus-dependent. We employ in vivo whole-cell recordings in the mouse primary auditory cortex, using pure tones and broadband dynamic moving ripple stimuli, to examine properties of functional integration in tonal (TRFs) and spectrotemporal (STRFs) receptive fields. Spectral tuning in STRFs derived from synaptic, subthreshold and spiking responses proves to be substantially more selective than for TRFs. We describe diverse spectral and temporal modulation preferences and distinct nonlinearities, and their modifications between the input and output stages of neural processing. These results characterize specific processing differences at the level of synaptic convergence, integration and spike generation resulting in stimulus-dependent transformation patterns in the primary auditory cortex. The authors compare receptive fields and nonlinearities of synaptic inputs, membrane potentials, and spiking activity in the auditory cortex for broadband stimuli revealing distinct differences, which lead to an increase in feature selectivity from neuron input to output. Frequency selectivity is distinctly higher for spectrotemporal receptive fields (STRFs) than for tonal receptive fields (TRFs).
Moving the goalposts: the evolution of voucher advocacy in framing research findings

The primary justification for school voucher programs in the United States has revolved around questions of efficacy, especially relative to student achievement outcomes. More recently, however, a ...
Lipases/esterases from extremophiles: main features and potential biotechnological applications

Abstract Organisms living in extreme conditions are called extremophiles and are characterized by their ability of adaptation to the extreme conditions. According to the living conditions extremophiles are divided into different classes in thermophiles, psychrophiles, acidophiles, alkalophiles, halophiles and barophiles. The adaptation to extreme living conditions is observed at level of membrane, showing a different composition and types of lipids present if are compared to the mesophilc counterparts, and to the proteins, in terms of amino acids compositions and structural adaptation. Extremophiles produce biocatalysts unique in their type, which are highly specialized to perform the same reactions of the non-extremophilic counterparts but in extreme conditions. This allowed evaluating with a different perspective the possibilities of enzymes in industrial applications. Enzymes that are more versatile for biotechnological applications are hydrolases able to use water molecules to break chemical bounds. The more common hydrolases are esterases, lipases, peptidases, nucleosidases, glycosidases and phosphatates. Here, we report in detail the superfamily of the esterases/lipases, which are enzymes specialized in the hydrolysis of esters/phosphoesters, and are fundamental in the metabolism of the cells. In particular we focused on enzymes from extremophiles, considering their particular structural characteristics, their specific amino acids composition, the processes in which are already used and other potential applications.
CompoundHetVIP: Compound Heterozygous Variant Identification Pipeline

Compound Heterozygous ( CH) variant identification requires distinguishing maternally from paternally derived nucleotides, a process that requires numerous computational tools. Using such tools often introduces unforeseen challenges such as installation procedures that are operating-system specific, software dependencies that must be installed, and formatting requirements for input files. To overcome these challenges, we developed Compound Heterozygous Variant Identification Pipeline (CompoundHetVIP), which uses a single Docker image to encapsulate commonly used software tools for file aggregation ( BCFtools or GATK4), VCF liftover ( Picard Tools), joint-genotyping ( GATK4), file conversion ( Plink2), phasing ( SHAPEIT2, Beagle, and/or Eagle2), variant normalization ( vt tools), annotation ( SnpEff), relational database generation ( GEMINI), and identification of CH, homozygous alternate, and de novo variants in a series of 13 steps. To begin using our tool, researchers need only install the Docker engine and download the CompoundHetVIP Docker image. The tools provided in CompoundHetVIP, subject to the limitations of the underlying software, can be applied to whole-genome, whole-exome, or targeted exome sequencing data of individual samples or trios (a child and both parents), using VCF or gVCF files as initial input. Each step of the pipeline produces an analysis-ready output file that can be further evaluated. To illustrate its use, we applied CompoundHetVIP to data from a publicly available Ashkenazim trio and identified two genes with a candidate CH variant and two genes with a candidate homozygous alternate variant after filtering based on user-set thresholds for global minor allele frequency, Combined Annotation Dependent Depletion, and Gene Damage Index. While this example uses genomic data from a healthy child, we anticipate that most researchers will use CompoundHetVIP to uncover missing heritability in human diseases and other phenotypes. CompoundHetVIP is open-source software and can be found at https://github.com/dmiller903/CompoundHetVIP; this repository also provides detailed, step-by-step examples.
Dear President Biden: We Need a Truth and Reconciliation Commission.

“Old Black Joe still picking cotton for your ribbons and bows.And everybody knows.”- Leonard Cohen, “Everybody Knows.”African-Americans and other minorities are suffering disproportionately during ...
Survival of a threatened salmon is linked to spatial variability in river conditions

Abstract Extirpation of the Central Valley spring-run Chinook Salmon ESU (Oncorhynchus tshawytscha) from the San Joaquin River is emblematic of salmonid declines across the Pacific Northwest. Habitat restoration and fish reintroduction efforts are ongoing, but recent telemetry studies have revealed low outmigration survival of juveniles to the ocean. Previous investigations have focused on modeling survival relative to river discharge and geographic regions, but have largely overlooked the effects of habitat variability. To evaluate the link between environmental conditions and survival of juvenile spring-run Chinook Salmon, we combined high spatial resolution habitat mapping approaches with acoustic telemetry along a 150 km section of the San Joaquin River during the spring of 2019. While overall outmigration survival was low (5%), our habitat-based classification scheme described variation in survival of acoustic-tagged smolts better than other candidate models based on geography or distance. There were two regional mortality sinks evident along the longitudinal profile of the river, revealing poor survival in areas that shared warmer temperatures but that diverged in chlorophyll-α, fDOM, turbidity and dissolved oxygen levels. These findings demonstrate the value of integrating river habitat classification frameworks to improve our understanding of survival dynamics of imperiled fish populations. Importantly, our data generation and modeling methods can be applied to a wide variety of fish species that transit heterogeneous and diverse habitat types.
The Rival Rationales of Vicarious Liability

Vicarious liability means holding one person responsible for the misdeeds of another just as if the wrongdoer and the defendant were the same person. There are two competing rationales for the idea. The agency rationale is based on the idea that agents act as extensions of their principals’ legal personality. According to the agency rationale, vicarious liability requires proof the wrongdoer was an agent, apparent agent, or employee of the defendant (the exact relationship depending on the type of tort) plus proof the misconduct occurred within the scope of the agency. Under an alternative approach that Dean William Prosser dubbed the “modern justification of vicarious liability,” agency does not matter. Corporate defendants must pay, regardless of fault, for enterprise related torts, even if the actual wrongdoer was an independent contractor or an employee acting outside the scope of employment. Scholars often present the modern justification as the law and ignore the agency rationale or treat it as outmoded. This Article will show that, in fact, the agency rationale is supported by powerful arguments and is generally followed by the courts (outside of California).
Accuracy of Weight Perceptions in a Nationally Representative Cohort of US 8th Grade Adolescents.

Abstract Objective To describe the accuracy of weight perceptions in a nationally representative sample of US 8th graders, its relationship with weight control intentions (WCI), and the relationship of weight misperceptions and WCI with diet and activity behaviors. Methods Data analyzed came from the 8th grade wave (2006–2007) of the Early Childhood Longitudinal Study–Kindergarten Class, a nationally representative sample. Body mass index was calculated from height and weight measurements for 7800 8th graders (mean age 14.3 years). Measured weight status was categorized into underweight, normal weight, overweight, and obese using the US Centers for Disease Control and Prevention's age- and sex-specific growth charts. Self-reported weight status was compared with measured weight status to classify adolescents into accurate perceivers, overestimators, and underestimators. Multivariate logistic and negative binomial regression models were estimated for binary and count data outcome variables, respectively. Results Overall, 42.1% of adolescents misperceived their weight status: 35.3% underestimated and 6.8% overestimated their weight status. Among overweight or obese adolescents, 68.4% misperceived their weight status; 35% of underweight adolescents overestimated their weight status. Among normal-weight adolescents, 8.5% overestimated and 18.5% underestimated their weight. Compared to accurate perception, both overestimation and underestimation of weight status were associated with greater likelihood of inappropriate WCI, but only underestimation was associated with unhealthy diet and activity behaviors. Conclusions Weight misperception was a common problem among US adolescents from all weight categories and was associated with inappropriate WCI. Future research should examine how adolescents' weight perceptions are formed and whether reducing misperceptions may improve behaviors.
A NUCLEAR POWERED AIR CUSHION FREIGHTER FOR THE 1980'S

A design for a transoceanic, dry cargo-carrying freighter is suggested; its use and operation in port are discussed. With a gross weight of 4500 metric tons (5000 tons), more than 50 percent of which is cargo, it will cruise at 50 meters per second (100 knots) in waves 2.4 meters (8 ft) high. Its peripheral jet-flexible skirt air cushion concept and air thrustors will let the freighter go over waves 8 meters high at reduced velocity. Power comes from a 1280 megawatt, helium-cooled thermal reactor. It could dock at any major port in the world, but because it needs no surface contact, it could also travel inland to land-locked ports. A modular terminal design and methods of cargo transfer are suggested. The concept of cargo containerization influences both the freighter and terminal design.
Base-Pairing Energies of Protonated Nucleoside Base Pairs of dCyd and m(5)dCyd: Implications for the Stability of DNA i-Motif Conformations.

Hypermethylation of cytosine in expanded (CCG)n•(CGG)n trinucleotide repeats results in Fragile X syndrome, the most common cause of inherited mental retardation. The (CCG)n•(CGG)n repeats adopt i-motif conformations that are preferentially stabilized by base-pairing interactions of protonated base pairs of cytosine. Here we investigate the effects of 5-methylation and the sugar moiety on the base-pairing energies (BPEs) of protonated cytosine base pairs by examining protonated nucleoside base pairs of 2′-deoxycytidine (dCyd) and 5-methyl-2′-deoxycytidine (m5dCyd) using threshold collision-induced dissociation techniques. 5-Methylation of a single or both cytosine residues leads to very small change in the BPE. However, the accumulated effect may be dramatic in diseased state trinucleotide repeats where many methylated base pairs may be present. The BPEs of the protonated nucleoside base pairs examined here significantly exceed those of Watson-Crick dGuo•dCyd and neutral dCyd•dCyd base pairs, such that these base-pairing interactions provide the major forces responsible for stabilization of DNA i-motif conformations. Compared with isolated protonated nucleobase pairs of cytosine and 1-methylcytosine, the 2′-deoxyribose sugar produces an effect similar to the 1-methyl substituent, and leads to a slight decrease in the BPE. These results suggest that the base-pairing interactions may be slightly weaker in nucleic acids, but that the extended backbone is likely to exert a relatively small effect on the total BPE. The proton affinity (PA) of m5dCyd is also determined by competitive analysis of the primary dissociation pathways that occur in parallel for the protonated (m5dCyd)H+(dCyd) nucleoside base pair and the absolute PA of dCyd previously reported.
Purification and properties of sulfite oxidase from chicken liver. Presence of molybdenum in sulfite oxidase from diverse sources.

Abstract Sulfite oxidase (EC 1.8.3.1) has been purified from chicken liver by modification of a procedure previously applied to bovine liver. The enzyme appears homogeneous as judged by its behavior in sedimentation velocity experiments and polyacrylamide disc gel electrophoresis. A new activity stain for the enzyme on acrylamide gels is described. Despite its apparent homogeneity, the enzyme consistently behaves in a heterogeneous manner in sedimentation equilibrium experiments, suggesting an associating system whose state of association depends on both enzyme concentration and anion content. The subunit molecular weight, determined by sodium dodecyl sulfate disc gel electrophoresis, is 55,000. The amino acid composition of the purified enzyme is reported. The absorption spectrum of the enzyme reveals the presence of a b5-like cytochrome, while chemical analysis and electron paramagnetic resonance (EPR) spectra indicate that molybdenum functions as a second prosthetic group. The kinetics of the reaction of the enzyme with sulfite and cytochrome c are consistent with a ping-pong mechanism. The EPR signal from the molybdenum center of the enzyme displays a pH titration behavior similar to that of the bovine enzyme. In addition, the shape of the signal is extremely sensitive to the presence of anions. The heme EPR signal is very similar to that reported for cytochrome b5. The enzyme has also been partially purified from human liver, wheat germ, and Thiobacillus thioparus; each of these preparations displays a sulfite-dependent molybdenum EPR signal.
An expression for the overall oxygen isotope fractionation between the sum of dissolved inorganic carbon and water

[1] Stable oxygen isotope fractionation factors (α's) between individual dissolved carbonate species (CO2(aq.), H2CO3, HCO3−, CO32−) and water, and their sum ( = [CO2(aq.)] + [H2CO3] + [HCO3−] + [CO32−]) and water are fundamental geochemical parameters. While values of , α, and have recently been examined, an overall mass balance for stable oxygen isotopes in the carbonate system still needs to be derived. The theoretical treatment of this mass balance is not trivial (in contrast to, e.g., stable carbon isotopes) because (1) oxygen is exchanged with H2O and (2) complications arise from the nature of the oxygen mole fractions. I use the recently reported individual α's to derive an expression for the overall oxygen isotope fractionation between and water. This allows the calculation of α(−H2O) at any given pH of the solution. The result differs from a relationship published earlier, and implications for previous studies are discussed. Numerical routines in MATLAB and Excel for the present calculation have been developed and are available as auxiliary material (Software S1). Applications of the expression include, for example, examination of biomineralization mechanisms and corrections to isotopic paleotemperature equations. The latter application can significantly alter reconstructions of Phanerozoic climate change.
Theoretical Ideas and Analysis as the Focus of Graduate Education.

An emphasis on theoretical ideas and analysis in graduate education highlights the contributions that sociologists can make to the major issues of the modern world. Such a strategy will bring sociology into a dialogue with the intellectual community and policy makers and will provide a greater degree of focus to a now disparate enterprise. Sociologists can make a distinctive contribution in addressing major social issues if they recognize the rightful relationship between theoretical ideas and research procedures.
Dual Careers: His, Mine, or Ours?

Personally Speaking provides a forum for readers to describe important issues or events in their lives and the role, if any, counseling has played. Guidelines for submitting manuscripts may be obtained from Stephen G. Weinrach, 303 Falvey Hall, Villanova University, Villanova, PA 19085–1699.