cssi/SciSciGPT-SciSciNet huggingface dataset:
Religions and Worldviews

Philosopher William Hazlitt once observed that ‘Without the aid of prejudice and custom I should not be able to find my way across the room’. 1 That simple phrase in fact says something quite profound about the human mind, and hence about human behaviour. Walking across a room was his metaphor for living through the events of everyday life. He was talking about the inner mental map each of us constructs out of our familiar surroundings and in which we live: the synthetic worldview which is a biased, shorthand reconstruction of ‘out there’. What exactly this worldview is and how each individual acquires it is the subject of Chapter 8. Here it is sufficient to reflect on Hazlitt’s words, ‘prejudice’ and ‘custom’.
Group Support Systems as Tools for HR Decision Making

Recently, many quantitative or qualitative techniques have been developed to support human resource management (HRM) activities, including Human Resource Information System (HRIS). More importantly, HRIS can include Expert System (ES), Decision Support System (DSS), and Executive Information System (EIS). As DSS and Group Support System (GSS) are able to facilitate human resources (HR) groups to gauge users’ opinions, readiness, satisfaction, etc., increase their HRM activity quality, and generate better group collaborations and decision makings with current or planned HRIS services. Consequently, GSS can help HR professionals exploit and make smart use of soft data and act intelligently in their decision making process. This paper presents an in-depth discussion on what GSS is and how it works, which may shed some enlightenments to HR professionals on what grounds GSS can be integrated as part of HRIS and support HRM.
Who Put the “A” in ATP? Generation of ATP from ADP-Ribose in the Nucleus for Hormone-Dependent Gene Regulation

In a recent issue of Science, Wright et al. (2016) describe a pathway for the synthesis of nuclear ATP, leading from NAD+ to poly(ADP-ribose) to ADP-ribose to ATP, which supports the activity of ATP-dependent chromatin remodeling enzymes during hormone-dependent transcription.
A framework for a simple and effective assessment and CQI process

This paper presents a proposed structural framework for an assessment and CQI process that is both simple and effective. The process is based on the ideas that assessment should be done where it makes sense, it should not be necessarily redundant, and it should provide useful information for improving the program. Elements of the proposed process have been piloted in two separate programs, including direct and indirect summative assessment of program outcomes and direct formative assessment. Preliminary results suggest that the process will be simple and effective.
DIVERSITY OF SUGAR PUCKER IN THE NUCLEIC ACIDS

Abstract Both the ribose and the deoxyribose sugars of polynucleotide chains exist in two major conformations. These conformations result from changes in the pucker of the sugar ring and are associated with different distances between successive phosphate groups along the chain. We consider examples of these leading to conformations in polynucleotide structures which allow them to accommodate other molecules interposed between the bases. Such structural adaptations are found in oligonucleotides as well as in the three-dimensional structure of yeast phenylalanine transfer RNA.
Interactive plant functional group and water table effects on decomposition and extracellular enzyme activity in Sphagnum peatlands

Abstract Peatland decomposition may be altered by hydrology and plant functional groups (PFGs), but exactly how the latter influences decomposition is unclear, as are potential interactions of these factors. We used a factorial mesocosm experiment with intact 1 m3 peat monoliths to explore how PFGs (sedges vs Ericaceae) and water table level individually and interactively affect decomposition processes. Decomposition was measured using litter bags at three depths filled with cellulose strips to mimic decomposition of a simple plant-derived structure, and Sphagnum tissue to simulate decomposition of the most abundant recalcitrant material in peatlands. We also analyzed the potential activity of five hydrolytic extracellular enzymes at an intermediate depth. We found lowered water table reduced activity of several enzymes and increased cellulose and Sphagnum decomposition. Presence of Ericaceae reduced decomposition of the recalcitrant Sphagnum tissue, whereas higher activity of chitinase was found in the combined presence of sedges and Ericaceae. We found no relationship between any potential enzyme activity and Sphagnum decomposition rate. Overall our results showed a dominating role of water table controlling decomposition processes, as well as support for the hypothesis that the presence of mycorrhizal Ericaceae can slow decomposition processes of complex plant tissues in peatlands.
Mitochondrial respiration and ROS emission during β-oxidation in the heart an experimental-computational study

Lipids are main fuels for cellular energy and mitochondria their major oxidation site. Yet unknown is to what extent the fuel role of lipids is influenced by their uncoupling effects, and how this affects mitochondrial energetics, redox balance and the emission of reactive oxygen species (ROS). Employing a combined experimental-computational approach, we comparatively analyze β-oxidation of palmitoyl CoA (PCoA) in isolated heart mitochondria from Sham and streptozotocin (STZ)-induced type 1 diabetic (T1DM) guinea pigs (GPs). Parallel high throughput measurements of the rates of oxygen consumption (VO2) and hydrogen peroxide (H2O2) emission as a function of PCoA concentration, in the presence of L-carnitine and malate, were performed. We found that PCoA concentration 600 nmol/mg mito prot, in both control and diabetic animals. Also, for the first time, we show that an integrated two compartment mitochondrial model of β-oxidation of long-chain fatty acids and main energy-redox processes is able to simulate the relationship between VO2 and H2O2 emission as a function of lipid concentration. Model and experimental results indicate that PCoA oxidation and its concentration-dependent uncoupling effect, together with a partial lipid-dependent decrease in the rate of superoxide generation, modulate H2O2 emission as a function of VO2. Results indicate that keeping low levels of intracellular lipid is crucial for mitochondria and cells to maintain ROS within physiological levels compatible with signaling and reliable energy supply.
DNA damage regulates direct association of TOR kinase with the RNA polymerase II-transcribed HMO1 gene

The mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient sufficiency and cellular stress. When mTORC1 is inhibited, protein synthesis is reduced in an intricate process that includes a concerted down-regulation of genes encoding rRNA and ribosomal proteins. The Saccharomyces cerevisiae high-mobility group protein Hmo1p has been implicated in coordinating this response to mTORC1 inhibition. We show here that Tor1p binds directly to the HMO1 gene (but not to genes that are not linked to ribosome biogenesis) and that the presence of Tor1p is associated with activation of gene activity. Persistent induction of DNA double-strand breaks or mTORC1 inhibition by rapamycin results in reduced levels of HMO1 mRNA, but only in the presence of Tor1p. This down-regulation is accompanied by eviction of Ifh1p and recruitment of Crf1p, followed by concerted dissociation of Hmo1p and Tor1p. These findings uncover a novel role for TOR kinase in control of gene activity by direct association with an RNA polymerase II-transcribed gene.
Idiothetic Path Integration in the Fruit Fly Drosophila melanogaster.

After discovering a small drop of food, hungry flies exhibit a peculiar behavior in which they repeatedly stray from, but then return to, the newly discovered resource. To study this behavior in more detail, we tracked hungry Drosophila as they explored a large arena, focusing on the question of how flies remain near the food. To determine whether flies use external stimuli, we individually eliminated visual, olfactory, and pheromonal cues. In all cases, flies still exhibited a centralized search behavior, suggesting that none of these cues are absolutely required for navigation back to the food. To simultaneously eliminate visual and olfactory cues associated with the position of the food, we constructed an apparatus in which the food could be rapidly translated from the center of the arena. Flies continued to search around the original location, even after the food was moved to a new position. A random search model based on measured locomotor statistics could not reproduce the centered nature of the animal’s trajectory. We conclude that this behavior is best explained by a form of path integration in which the flies use idiothetic cues to search near the location of the food. We argue that the use of path integration to perform a centered local search is not a specialization of Drosophila but rather represents an ancient behavioral mode that is homologous to the more elaborate foraging strategies of central place foragers such as ants.
Nano reversed phase versus nano hydrophilic interaction liquid chromatography on a chip in the analysis of hemopexin glycopeptides

Analysis of the glycosylation of proteins is a challenge that requires orthogonal methods to achieve separation of the diverse glycoforms. A combination of reversed phase chromatography with tandem mass spectrometry (RP-LC-MS/MS) is one of the most powerful tools for glycopeptide analysis. In this work, we developed and compared RP-LC and hydrophilic interaction liquid chromatography (HILIC) in nanoscale on a chip combined with MS/MS in order to separate glycoforms of two peptides obtained from the tryptic digest of hemopexin. We observed reduction of the retention time with decreasing polarity of glycans attached to the same peptide backbone in HILIC. The opposite effect was observed for RP-LC. The presence of sialic acids prolonged the retention of glycopeptides in both chromatographic modes. The nanoHILIC method provided higher selectivity based on the composition of glycan, compared to nanoRP-LC but a lower sensitivity. The nanoHILIC method was able to partially separate linkage isomers of fucose (core and outer arm) on bi-antennary glycoform of SWPAVGDCSSALR glycopeptide, which is beneficial in the elucidation of the structure of the fucosylated glycoforms.
The Immunocytogenetics of Human Male Meiosis

Recently, several components of the mammalian meiotic recombination pathway have been identified and new immunofluorescence approaches to the analysis of human meiosis have been developed. This has made it possible to directly examine the dynamics of chromosome behavior in meiosis I spermatocytes and address previously intractable questions, such as: How do chromosomes pair and synapse with one another? How does recombination occur? What is the relationship—if any—between abnormalities in meiosis and cases of unexplained male infertility? In this chapter, we discuss results from immunocytogenetic studies of human males, summarizing how they have contributed to our understanding of both normal and abnormal spermatogenesis.
34 – Obstructive Sleep Apnea: Why the Gender Bias?

This chapter discusses obstructive sleep apnea (OSA), the diagnostic criteria for it, studies done on prevalence of the disease between men and women, and the possible etiology of that difference. OSA is a common disorder that, for many years, was thought to be exclusively affecting men. Large scale epidemiologic studies have changed that and indicated that women are at an increased risk of OSA as well. Obesity and craniofacial morphology are significant risk factors for OSA in women, but menopausal status may contribute as well. Women tend to present with different symptoms related to OSA than men. This may be contributing to the delay in diagnosis and to women being treated for other disorders, such as depression, prior to being diagnosed with OSA. The role of male and female reproductive hormones on upper airway structure and function is still being investigated, promising some hope in unraveling the etiology of the gender difference in OSA.
Integration Site Analysis in Gene Therapy Patients: Expectations and Reality.

Integration site (IS) analysis is one of the major tools for addressing the safety of gene therapy clinical protocols based on the use of integrating vectors. Over the past years, the study of viral insertions in gene therapy–treated patients has allowed identifying insertional mutagenesis events, evaluating the safety of new viral vector platforms and tracking the in vivo clonal dynamics of genetically engineered cell products. While gene therapy is progressively expanding its impact on a broader area of clinical applications, increasingly more accessible, faster, and more reliable safety readouts are required from IS analysis. Several actors, from researchers to clinicians, from regulatory agencies to private companies, have to interface to different degrees with the results of IS analysis while developing and evaluating gene therapy products based on retroviral vectors. This review is aimed at providing a brief overview of what the current state and the future is of these studies with a particular focu...
Correlation between ulcer healing and vascular hemodynamic observed with diffuse optical spectroscopy

Patients affected by peripheral arterial disease are prone to have ulcers in their feet. The healing or worsening of these wounds are correlated with vascular hemodynamic changes observed with diffuse optical spectroscopy.
Breast Cancer Patients: Diagnostic Epigenetic Markers in Blood

Epigenetic changes are defined as changes of gene expression without changes in the DNA sequence. Both DNA methylation and histone modifications are essential in normal mammalian development. Recently, it has been shown that epigenetic alterations play an important role in tumorigenesis and represent alternative means of activation of tumor oncogenes, inactivation of tumor suppressor genes, and induction of genomic instability (Jones and Baylin, 2007). During the last 2 decades, much effort has been focused on the role of DNA methylation changes in cancer development and their utilities in cancer detection. It is now clear that histone modifications are an integral part of the epigenetic programming. DNA methylation, referring here to the addition of a methyl group to the cytosine in the cytosine-phosphate-guanine (CpG) dinucleotides, plays an important role in normal development, genomic stability, and regulation of gene expression. In normal cells, the majority of CpG dinucleotides is located in the repetitive sequences of the genome and methylated. Approximately, 50% of housekeeping genes contains a CpG rich region (called the CpG island) in their promoter region, which is not methylated regardless of whether the gene is transcribed or not. On the contrary, tumor cells are characterized by both global hypomethylation and gene-specific hypermethylation (Jones and Baylin, 2007). Hypomethylation of repetitive sequences leads to genome instability, while promoter hypermethylation leads to transcriptional silencing of many tumor suppressor genes, with similar consequence as genetic mutations. Histone modifications, referring to acetylation, methylation, phosphorylation, ubiquitination, and sumoylation of amino acids in histone tails, collectively form histone codes that link various chromatin structures to gene expression states. Accumulating evidence suggests that acetylation and methylation of different lysine and arginine residues in histones H3 and H4 are associated with either transcriptionally active or transcriptionally repressed states of gene expression. For example, acetylated histones are associated with transcribed genes, while deacetylated histones are associated with silenced genes. Methylated lysine 9 (K9) or K27 on H3 and K20 on H4 are generally associated with transcription repressed genes, whereas methylated K4, K36, and K79 are found mainly in active chromatin (Kouzarides, 11 Breast Cancer Patients: Diagnostic Epigenetic Markers in Blood
Comparison of laparoscopic and open pediatric inguinal hernia repairs at two institutions

The proposed benefits of laparoscopic inguinal hernia repair in the pediatric population include easier access to the contralateral groin and avoidance of manipulation of the spermatic cord; however, some studies also report higher recurrence rates. Due to these differences, the traditional open technique is still used by many pediatric surgeons. The objective of this study is to compare the outcomes of two institutions that employed different techniques. We retrospectively reviewed pediatric patients who had open repair of inguinal hernias at hospital A or laparoscopic repair at hospital B. Data collection included age of patients, laterality, operative time, and complications. From 2010 to 2015, 154 patients underwent open repair at hospital A and 220 patients underwent laparoscopic repair at hospital B. The mean operative time was 52 min for the open technique and 23 min for the laparoscopic technique (p 0.2). Laparoscopic hernia repairs at hospital B are associated with shorter operative times and have similar outcomes as open repairs at hospital A. A prospective study with both techniques done at the same institution is warranted.
Communication, behaviour, and decision making in crayfish: A review

Abstract Animals exhibit behavioural patterns characterized by responses to information received from internal and external stimuli. The ultimate response or decision is based on physical, chemical, or biological factors and their analysis by the nervous system, and may be influenced by previous experiences, stressors, and limitations. This review summarizes behavioural patterns connected with decision making in crayfish, and includes similarities to vertebrates and other invertebrates that may be applied to freshwater crayfish. Concurrently, purpose of this review is introduce behavioural patterns from outside and inside of crustaceans taxa, in which might crayfish have potential exhibit them. Knowledge of patterns influencing behavioural responses and decisions in organisms is necessary for understanding basic biological relationships and for extraction of information applicable to crayfish. Information on sensory and nervous systems, communication, social behaviour, reproductive behaviour, and decision making within the context of species success and adaptations to changing environments will contribute to a model design for future studies of reproductive and social behaviour and behavioural ecology of crayfish. The study of crayfish behavioural patterns can extend knowledge of habitat and reproductive requirements of native crayfish as well as investigate success and impacts of non-native species in environment.
The Hunter Became the Hunted: A Graduate Student’s Experiences with Predatory Publishing

As predatory publishing has influenced the educational research community, this study sought to understand and articulate current predatory publishing practices which may render important academic research “post-truth” or “fake news” if authors are not careful where they publish and with whom. Findings suggest predatory publishers obscure publication charges, steal identities of real scholars and position them as editors of predatory journals, mimic website aesthetics of credible journals, and gather author information to further promote predatory publishing and fake academic conferences. Future research and viability of open-access publishing are addressed, as well as a discussion of academic publishing, predatory publishing, and the pressure graduate students and junior researchers often experience during the “publish or perish” process of tenure and promotion.
Clinical measurement of portal hypertension

The development of portal hypertension and esophageal varices has been summarized. The qualitative determination of portal hypertension and esophageal varices have been discussed, and the use of quantitative technics in the evaluation has been emphasized. Five examples of the usefulness of occlusive hepatic venule catheterization coupled with more orthodox methods demonstrate the value of this direct measure of portal pressure.
A combinatorial formula for Macdonald polynomials

Abstract: We prove a combinatorial formula for the Macdonald polynomial $\tilde{H}_{\mu }(x;q,t)$ which had been conjectured by Haglund. Corollaries to our main theorem include the expansion of $\tilde{H}_{\mu }(x;q,t)$ in terms of LLT polynomials, a new proof of the charge formula of Lascoux and Schutzenberger for Hall-Littlewood polynomials, a new proof of Knop and Sahi's combinatorial formula for Jack polynomials as well as a lifting of their formula to integral form Macdonald polynomials, and a new combinatorial rule for the Kostka-Macdonald coefficients $\tilde{K}_{\lambda \mu }(q,t)$ in the case that $\mu $ is a partition with parts $\leq 2$.
Does early diagnosis and treatment of myelodysplastic syndromes make a difference

Patients diagnosed with myelodysplastic syndromes (MDS) often ask their physicians whether earlier detection of disease or more prompt initiation of treatment might have resulted in a better outcome. The concept of starting therapy at an early point in the disease process when the clonal burden of abnormal hematopoietic stem cells may be lower and somatic mutational complexity less, and therefore treatment more likely to be effective, is attractive. However, at present there is no evidence that therapy with any of the available drugs for MDS (ie, erythropoiesis stimulating agents, lenalidomide, azacitidine or decitabine) early after diagnosis is associated with better outcomes than later initiation of drug therapy. For those patients who are eligible for allogeneic hematopoietic cell transplant and have a suitable donor, early transplant of lower-risk MDS is associated with worse outcomes compared to nontransplant approach, whereas early transplant therapy of higher-risk disease improves outcomes compared to delaying transplant. Here I review available data about MDS diagnostic patterns and early versus later diagnosis and therapy initiation.
Collaborative Research: Techniques for Conducting Collaborative Research From the Science of Team Science (SciTS):

The ProblemThe field of human resource development (HRD) is a multidisciplinary field of research and practice requiring collaboration. Unfortunately, the literature on how to conduct collaborative...
Demonstrability of analytics solutions and shared knowledge of statistics and operating room management improves expected performance of small teams in correctly solving problems and making good decisions

Abstract Background There is poor understanding how much and what kind of team attributes are needed for well-functioning teams to communicate sufficiently to solve operating room (OR) management analytics-related problems. Several hundred clinicians and administrators have taken such a 3.5 day course. Teams of 2–4 participants complete multiple mathematics word problems. We surveyed prior participants. Methods Field observation was used to develop 13 items describing potential impediments of team performance. From previous communication science studies, the item expected to be judged the most important was Item A: “Knowledge of basic statistics, operations research, and operating room management concepts sufficient for everybody in the team taking part in discussions.” The content of Item A included sufficient preparation for there to be shared knowledge of statistics and OR management terms that members could demonstrate to others when they potentially had a solution. Instructions were to assign 130 points among “team attributes according to what was the most important toward completing a) the problems in the course completed as a team and b) similar tasks you have worked on since the course within small teams.” Results The N = 88 respondents were 21.7% of invitees. Physicians or nurse anesthetists were 62.5% of respondents. The respondents spent median 5.5 min [25th, 75th percentiles 3.9, 7.9 min] to complete the survey. The respondents took the course 4 years ago [2, 6 years]. These demographic variables had no associations with results. The points assigned differed among the 13 items (Kruskal–Wallis P Conclusions For team members to solve operating room management problems effectively, the team members foremost need enough shared scientific knowledge for effective discussion of the tasks.
Structural Barriers to Women's Sustained Engagement in HIV Care in Southern California.

Since the introduction of antiretroviral therapy, the number of women living with HIV (WLHIV) continues to increase. Despite the decrease in HIV diagnosis among women in California, less than half of WLHIV are retained in HIV care. Structural barriers put women at increased risk for delayed HIV diagnosis, delayed entry into HIV care, and poorer treatment outcomes. The objective of this qualitative analysis is to identify how structural barriers negatively impact women’s sustained engagement in HIV care in Southern California. WLHIV accessing local HIV support services participated in a qualitative study by completing a semi-structured interview and brief survey between January and April 2015 (n = 30). Poverty, unemployment, housing instability, and needs for transportation emerged as the dominant structural barriers for women when discussing their challenges with sustained engagement in HIV care. System-level interventions that decrease these noted barriers may help improve HIV care continuum for women living in Southern California.
Tabellion: secure legal contracts on mobile devices

A legal contract is an agreement between two or more parties as to something that is to be done in the future. Forming contracts electronically is desirable since it is convenient. However, existing electronic contract platforms have a critical shortcoming. They do not provide strong evidence that a contract has been legally and validly created. More specifically, they do not provide strong evidence that an electronic signature is authentic, that there was mutual assent, and that the parties had an opportunity to read the contract. We present Tabellion, a system for forming legal contracts on mobile devices, such as smartphones and tablets, that addresses the above shortcoming. We define four secure primitives and use them in Tabellion to introduce self-evident contracts, the validity of which can be verified by independent inspectors. We show how these primitives can be implemented securely in the Trusted Execution Environment (TEE) of mobile devices as well as a secure enclave in a centralized server, all with a small Trusted Computing Base (TCB). Moreover, we demonstrate that it is feasible to build a fully functional contract platform on top of these primitives. We develop ~15,000 lines of code (LoC) for our prototype, only ~1,000 of which need to be trusted. Through analysis, prototype measurements, and a 30-person user study, we show that Tabellion is secure, achieves acceptable performance, and provides slightly better usability than the state-of-the-art electronic contract platform, DocuSign, for viewing and signing contracts.
Whole-Room Hypochlorous Acid Atomizing Disinfection System on Healthcare Surface Contamination and Transfer

Background Surfaces play a major role in the transmission of pathogens in the healthcare environment. Manual terminal cleaning efficacy in this environment can be highly variable due to differences in training, compliance, and room layout, among other inherent complexities. Whole-room, no-touch disinfection systems have been shown to reduce microbial loads in the environment. When used in tandem with manual disinfection protocols, disinfection efficacy may be further increased. Methods Bacterial tracers were seeded onto 12 surfaces, both high- and low-touch, in a hospital room. Following seeding, 2 disinfection methods were evaluated; manual terminal cleaning alone, and manual terminal cleaning in tandem with a whole-room, hyphoclorous acid atomizing disinfection system. Surfaces were sampled pre- and post-disinfection. Each cleaning method was repeated a total of 4 times on separate days, for a total of 48 observations per method. Seeded trials were further used to determine cross-contamination potentials during cleaning practices. Labor efficiency of each method was also evaluated. Results Manual terminal cleaning alone achieved, on average, a 2.4 log (99.6%) reduction. In comparison, tandem terminal cleaning achieved a 4.9 log (99.9987) reduction on average. Cross-contamination (i.e., transfer of organisms from seeded to an uncontaminated surface during cleaning) was observed in 50% of the surfaces for manual terminal cleaning whereas in tandem 0% was observed. Tandem cleaning also resulted in a 64% decrease in the time spent manual cleaning of the rooms. Conclusions Whole-room atomized disinfection used in tandem with manual terminal cleaning protocols improved disinfection outcomes, minimized the effects of cross-contamination observed during cleaning practices, and lowered manual labor times.
Assessing the effectiveness of different sea turtle nest protection strategies against coyotes

Abstract Depredation of sea turtle nests, where a nest is either partially or completely predated by a predator, is particularly detrimental to the reproductive output of sea turtles and consequently a concern for sea turtle conservation efforts globally. To minimize depredation of sea turtle nests, several protective strategies have been trialed against different predators. However, although information on their effectiveness exists, information on the effectiveness of strategies aiming to mitigate depredation by coyotes, which is an issue at loggerhead turtle, Caretta caretta, nesting beaches in Florida and globally is inexistent. To inform future management of sea turtle nest depredation by coyotes, this study evaluated the effectiveness of three nest protection strategies (self-releasing metal cage, self-releasing plastic cage, and self-releasing metal screen). Further, to obtain insights into coyote behavior during depredation activities and inform management strategies, we used infrared camera surveillance to monitor sea turtle nests. Self-releasing plastic cages were found to be the most effective strategy at mitigating coyote depredation on loggerhead nests. Our findings provide important information for consideration when developing depredation mitigation strategies in the region and globally.
Fluorinated Small Molecule Inhibitors of Fibroblast Activation Protein-α for Imaging of Tumor Stroma

1014 Objectives: Fibroblast activation protein-alpha (FAP), also known as seprase, is a marker of cancer-associated fibroblasts, a major regulator of the tumor microenvironment [1]. FAP plays a number of biological roles in cancer and is minimally expressed in normal tissue [2], rendering it a promising target for small molecule-based imaging and/or therapy in a range of cancers. Inhibitors containing a glycyl-2-cyanopyrrolidine [3,4] or a glycylpyrrolidine-2-boronic acid [5] core structure exhibit high (&lt 1 µM) affinity and selectively for FAP when conjugated to an aromatic or heteroaromatic ring. More recently, (4-quinolynoyl)-glycyl-2-cyanopyrrolidines have been derivatized with a DOTA moiety to enable radiolabeling with 68Ga [2,6] for imaging FAP using PET. Despite promising tissue distribution and contrast to background, the use of 68Ga currently limits the volume of patients that can be imaged with these ligands. Fluorine-18 is a particularly appealing isotope for PET imaging due to its physical properties and ease of scaling production. Our aim was to design and explore structure-activity relationships (SAR) of new fluorine-containing FAP inhibitors with a view towards developing an 18F-labeled radioligand for PET imaging of tumor stroma. Methods: An initial library of five candidates based on the 2-substituted glycylpyrrolidine pharmacophore was synthesized. Either 2-cyanopyrrolidine or pyrrolidine-2-ylboronic acid was conjugated to a glycine spacer, which, in turn, was linked via an amide bond to fluorobenzoyl, fluoropyridoyl, or iodobenzoyl substituents. The iodoquinoline derivative FAPI-01 [6] was prepared as a control. The affinity of the compounds for human FAP was determined by a competition binding assay against [131I]FAPI-01 in SW872 cells. Results: The IC50 of the ligands ranged from 30 nM to greater than 100 µM. The order of affinity was FAPI-01 &gt RPS-301, RPS-300 &gt&gt RPS-303, RPS-304 &gt&gt RPS-302. Two structure-activity relationships were evident. The FAP affinity of pyrrolidinyl-2-boronic acids was more than 100-fold higher than otherwise structurally-identical 2-cyanopyrrolidines. In addition, the introduction of N-containing aromatic heterocycles in place of aromatic carbacycles led to modest-to-high improvements in FAP affinity. Conclusions: The fluoronicotinamide analogue. RPS-301, with IC50 = 139 ± 45 nM, is a high affinity inhibitor of FAP. Facile preparation of the 18F-labeled derivative by nucleophilic aromatic substitution enhances the promise of this compound as a PET ligand for FAP. Efforts are underway to evaluate [18F]RPS-301 in a preclinical cancer model, and to prepare a library of structurally-related analogues of RPS-301 with improved affinity for FAP.
Ready, Set, Flow! Automated Continuous Synthesis and Optimization

Synthetic chemistry provides access to advanced materials that facilitate innovation in key industries such as medicine, energy, and agriculture. Automation is poised to challenge the traditional process of chemical synthesis and development. Continuous flow chemistry has recently come into maturity and provides a flexible platform amenable to automation. The merger of synthesis and automation promises to democratize access to custom complex small molecules for non-experts as well as accelerate the development of new synthetic protocols by relieving expert chemists of routine tasks. In this contribution, we discuss recent case studies that present strategies towards realizing automated synthesis with a further focus on works that leverage continuous flow chemistry as an enabling technology.
Bcl-2 Inhibitors as Sensitizing Agents for Cancer Chemotherapy

Abstract This chapter reviewed B-cell lymphoma 2 (known as Bcl-2) family proteins in the cancer chemotherapy as sensitizing agents. Escaping apoptosis plays a key role in survival of the tumor. Bcl-2 family members could regulate cell apoptosis or survival through interactions between pro- and antiapoptotic proteins. Targeting Bcl-2 antiapoptotic proteins has gradually become one of the most important therapeutic strategies in cancer therapy. This chapter reviewed the discovery history of Bcl-2 molecules, the Bcl-2 family members, and their structures. The mechanisms of apoptosis regulated by Bcl-2 family and effects of Bcl-2 on the development and prognosis of cancer were also discussed. In addition, this review summarized the therapeutic agents targeting Bcl-2 in cancer chemotherapy including the mechanisms of actions, the clinical and preclinical effects, adverse effects, and future applications.
Development of an at-Home Chemistry Lab Experience for Survey of Organic Chemistry Students

Educators at Mississippi State University developed an at-home, kitchen chemistry style laboratory to accompany the Survey of Organic Chemistry lecture course. The course featured 12 lab activities; eight hands-on experiences that focused primarily on important organic concepts including acid strength, extraction techniques, chromatographic separation, recrystallization, and selected organic reactions. Four online modeling experiences used ChemSketch and three-dimensional visualization to support student understanding of stereochemistry, isomer configurations, and important reaction mechanisms. A unique component of this laboratory course was that students uploaded photo diaries of their experiments to demonstrate completion. The developed course was implemented and taught for three semesters at Mississippi State University with 119 students successfully completing the at-home, self-paced laboratory course. The authors share this at-home laboratory experience as an option for programs exploring novel, off-campus approaches to laboratory experiences.
Jesus for Zanzibar: Narratives of Pentecostal (Non-)Belonging, Islam, and Nation: by Hans Olsson, Leiden and Boston, Brill, 2019, xv + 275 pp.

Hans Olsson’s in-depth analysis of Pentecostal Christianity in contemporary Zanzibar is a broad meditation on the question of belonging, and “non-belonging” in East Africa. Belonging, as Olsson sug...
Call Me Back: Examining Provider Biases Through Callback Rates and Responsivenessψ:

We conducted a phone-based field experiment to investigate the callback rate of psychologists. Providers (N = 903) in Los Angeles, California who were selected from a health maintenance organizatio...
COVID-19 Presenting as Recurrent Pericardial Effusion

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged from Wuhan, China, in 2019, causing coronavirus disease 19 (COVID-19) and creating a global pandemic affecting millions of people worldwide. Though COVID-19 primarily affects the pulmonary structures, deleterious effects can also occur in the cardiac system. We present a case of a patient with recurrent pericardial effusions secondary to COVID-19 infection, an unusual cardiovascular manifestation of this disease. A 47-year-old man presented with altered mental status and tested positive for COVID-19. He left against medical advice and later presented two weeks later with pleuritic chest pain associated with shortness of breath. His symptoms were attributed to a moderate- to large-sized pericardial effusion, without evidence of tamponade, as confirmed by echocardiography. The fluid was removed by pericardiocentesis; analysis was negative for malignant cells, inflammatory markers, or microbiologic studies. Reaccumulation of the fluid necessitated placement of a pericardial window, resulting in the resolution of his symptoms. There are limited case reports demonstrating the association of pericardial effusion with COVID-19 infection. The effusion is likely secondary to the inflammatory response leading to capillary leakage, resulting in pericardial fluid traversing the serous pericardium. In addition to other demonstrated cardiovascular effects, COVID-19 appears to be associated with recurrent pericardial effusion. Due to the rise in COVID-19 cases, it is essential to consider pericardial effusion as a rare but potential complication of this virus. The pericardial effusion can be the primary clinical manifestation, recurrent in nature, and potentially result in tamponade physiology.
Occupational Licensure: A Perspective of Electroneurodiagnostic Technologists in the Operating Room

ABSTRACT.Intraoperative neurophysiologic monitoring is driving the changing roles and responsibilities of electroneurodiagnostic technology. The long-standing issues of technologist education, background training, range in experience, performance abilities, and credentialing are now joined by the question of appropriate practice. This is an area of emerging controversy. Public protection and occupational accountability are central to this profound problem. Without state licensing, the controls on the occupation and voluntary certification mechanisms fall short of consumer protection. This article explores the current issues surrounding state regulation of the technology.
Sophistication: A Literary and Cultural History – By Faye Hammill

If you are much taken with etymology, the connection between sophistication and sophistry might not come as a surprise. This reviewer was amazed and delighted to see Faye Hammill make the case for ...
Oil and American Security

Can oil be used to coerce, and if so, why and how? Current understandings about the coercive potential of oil are incomplete because they focus too narrowly on oil’s economic importance and neglect the crucial role oil plays for military power. A country deprived of oil has little chance of winning a war. Therefore, cutting an adversary off from its oil supply offers a possible means of coercion through a logic of military denial. Because states know this, they take preventive measures to reduce their vulnerability to cutoffs during wartime. United States foreign policy in the Middle East has historically reflected this logic. Domestic oil shortages after World War I and World War II caused policymakers to worry that the country would not be able to produce enough oil to fight another major war if one arose. Cognizant of the danger posed by oil coercion, American leaders took anticipatory measures designed to prevent it, leading to the emergence of an activist foreign policy in the Persian Gulf. Evidence suggests that the specific rationale was to reduce American military vulnerability and not simply to prevent damage to the country’s economy.
The glycerol facilitator GlpF its aquaporin family of channels, and their selectivity.

Publisher Summary The “glycerol facilitator” GlpF, a highly selective transmembrane channel that conducts glycerol and certain other small uncharged organic molecules, was the first member of the large aquaporin family (AQP family) to be identified at the genetic level and functionally characterized. Once glycerol is passaged inside the cell, it is rapidly phosphorylated by glycerol kinase to produce glycerol 3-phosphate that proceeds by dehydrogenation to dihydroxyacetone phosphate (DHAP) or to phospholipid synthesis where glycerol provides the basis for attachment of fatty acid chains and phophatidyl head groups in ∼2/3 of cellular phospholipids. The glp regulon is inducible by glycerol 3-phosphate which provides an advantage for growth of Escherichia coli on glycerol. The glpF gene is the first gene on the glp operon that also contains the gene for glycerol kinase.
Genome-wide nucleosome mapping in multiple myeloma.

Proper regulation of gene expression is essential for cellular viability, and the integrity of chromatin is a fundamental factor in maintaining proper gene regulation. In cancer cells, this precise regulation is disrupted and aberrant gene expression ensues - a hallmark of the disease. In many forms of hematological malignancy, aberrant expression, activation or deletion of a critical enzymatic regulator of chromatin modification underlies the disease. One such regulator is MMSET (multiple myeloma SET domain) protein, a histone methyltransferase, that is rearranged and joined with the immunoglobulin locus associated with t(4:14) due to aberrant class switch DNA recombination in approximately 20% of multiple myeloma cases and is associated with particularly poor prognosis. Our lab has previously shown that an increase in MMSET expression results in global histone modification changes and up-regulation of hundreds of genes. We believe that these changes are due to radical reprogramming of chromatin, including repositioning of nucleosomes in MMSET-overexpressed cells. Mechanistic insight into epigenetic changes during MMSET-mediated gene expression will provide deeper understanding of disease progression in multiple myeloma, and potentially other similar malignancies. To begin understanding the changes in chromatin structure when MMSET is overexpressed, we generated a genome wide nucleosome map in cells expressing high and low levels of MMSET. Initial analysis of this mapping reveals changes in nucleosome positioning in promoters where gene expression and histone modifications had been identified to be significantly altered in cells expressing high and low levels of MMSET. Generally, overexpression of MMSET results in an increase in H3K36 dimethylation, a histone modification associated with actively transcribed genes, and a concomitant genome-wide loss of H3K27 trimethylation, a histone modification associated with repressed genes. Indeed, in cells expressing high levels of MMSET, genes that have been identified to have an increase in expression and an increase in H3K36 dimethylation have a distinct change in nucleosome positioning compared to the cells expressing low levels of MMSET. Further, differences in nucleosome positioning can be detected in promoter regions with increased H3K27 trimethylation and decreased gene expression. We are currently examining whether these changes in nucleosome positioning are due to the presence of MMSET and require MMSET histone methyltransferase activity. Through these and related studies, our aim is to determine how MMSET behaves in multiple myeloma through a likely radical reprogramming of chromatin. We believe that mechanistic insight into MMSET-mediated gene expression changes will provide significant avenues for potential therapeutic strategies, as MMSET overexpression has been implicated in myeloma and other solid tumors. Moreover, our work will provide insight into mechanisms that may be shared amongst various diseases that are initiated through epigenetic misregulation.
Riemannian nilmanifolds and the trace formula

This paper examines the clean intersection hypothesis required for the expression of the wave invariants, computed from the asymptotic expansion of the classical wave trace by Duistermaat and Guillemin. The main result of this paper is the calculation of a necessary and sufficient condition for an arbitrary Riemannian two-step nilmanifold to satisfy the clean intersection hypothesis. This condition is stated in terms of metric Lie algebra data. We use the calculation to show that generic two-step nilmanifolds satisfy the clean intersection hypothesis. In contrast, we also show that the family of two-step nilmanifolds that fail the clean intersection hypothesis are dense in the family of two-step nilmanifolds. Finally, we give examples of nilmanifolds that fail the clean intersection hypothesis.
Symposium: Arthur Danto, The Abuse of Beauty

I am deeply indebted to Jonathan Gilmore, Gregg Horowitz, and Fred Rush, first for their initiative in organizing a symposium on my book, The Abuse of Beauty, which took place at the annual meeting...
The Effects of botulinum toxin A on muscle histology during distraction osteogenesis

Distraction osteogenesis is a highly successful method of bone formation, yet muscle fibrosis and contractures can result in significant morbidity. In the current study, we investigate the efficacy of botulinum toxin A in preventing fibrosis and potentially increasing muscle development in distracted muscles. Fifteen New Zealand White rabbits underwent tibial distraction at 1.5 mm/day until a 20% gain was achieved. Treatment groups were divided by drug (saline or botulinum toxin) and target muscle (gastrocnemius or tibialis anterior). Two additional control animals received no treatment. Bromeodeoxyuridine was delivered continuously throughout the 8-week experiment, and following muscle harvest. Tissues were stained for BrdU, Pax-7, vimentin, and haematoxylin and eosin staining. Mitotic activity increased in all distracted animals; however, in the animals receiving botulinum toxin A injections into the gastrocnemius, the antagonist tibialis anterior suffered up to 9% less fibrosis than distraction alone (p = 0.024). Use of botulinum A toxin did not appear to promote or improve neogenesis of muscle fibers, nor did it decrease fibrosis in the injected muscles. It appears from this study, and a previously published study on the effects of this toxin on muscle function, that botulinum A toxin maybe of some benefit in decreasing morbidity in the antagonist muscle but not the muscle injected with the toxin.