cssi/SciSciGPT-SciSciNet huggingface dataset:
Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins

Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10–100 µg/kg) 30 min before a l-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01–1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5–25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. Thus, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.
'Gain of function' phenotype of tumor-derived mutant p53 requires the oligomerization/nonsequence-specific nucleic acid-binding domain.

Tumor-derived p53 mutants can transcriptionally activate a number of promoters of genes involved in cellular proliferation. For this transactivation, mutant p53 does not use the wild-type p53 DNA-binding site, suggesting a mechanism of transactivation that is independent of direct DNA binding. Here we describe our analysis of the domain requirements for mutant p53 to transactivate promoters of the human epidermal growth factor receptor (EGFR), human multiple drug resistance 1 (MDR-1) and human proliferating cell nuclear antigen (PCNA) genes. We also report the identification of a structural domain required for the 'gain of function' property of mutant p53-281G. 'Gain of function' is measured as the tumorigenicity (in nude mice) of 10(3) murine cells expressing mutant p53 constitutively. We have generated internal deletion mutants of p53-281G deleting conserved domains I, II, III, IV and V, individually. We have also generated one deletion mutant eliminating amino acids 100 through 300 that removes four of the five conserved domains (II - V); another mutant, p53-281G del 393-327, deletes the oligomerization and nonsequence-specific nucleic acid-binding domains of p53. For the EGFR and MDR-1 promoters, all these mutants have significantly lower transactivation ability than intact p53-281G. These deletion mutants, however, significantly activated the pCNA promoter, suggesting that the mechanism of transactivation of the PCNA promoter is different from that of the EGFR and MDR-1 promoters. When expressed constitutively in 10(3) cells, p53-281G del 393-327 was found to be defective in inducing tumor formation in nude mice although intact p53-281G was very efficient. Thus, our results suggest that structural domains near the C-terminus are needed for 'gain of function'.
Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target

Dopaminergic (DA) neurons in the midbrain provide rich topographic innervation of the striatum and are central to learning and to generating actions. Despite the importance of this DA innervation, it remains unclear whether and how DA neurons are specialized on the basis of the location of their striatal target. Thus, we sought to compare the function of subpopulations of DA neurons that target distinct striatal subregions in the context of an instrumental reversal learning task. We identified key differences in the encoding of reward and choice in dopamine terminals in dorsal versus ventral striatum: DA terminals in ventral striatum responded more strongly to reward consumption and reward-predicting cues, whereas DA terminals in dorsomedial striatum responded more strongly to contralateral choices. In both cases the terminals encoded a reward prediction error. Our results suggest that the DA modulation of the striatum is spatially organized to support the specialized function of the targeted subregion.
Purified murine hematopoietic stem cells function longer on nonirradiated W41/Wv than on +/+ irradiated stroma

Mouse bone marrow (BM) was separated into low-density, lineage- negative, wheat germ agglutinin-positive (WGA+), Rhodamine-123 bright (Rhbright) or dim (Rhdim) cells to obtain populations that were highly enriched for committed progenitors (Rhbright cells) or for more primitive stem cells (Rhdim). When 2,500 Rhbright or Rhdim cells were seeded onto 6-week-old irradiated (20 Gy) long-term BM cultures (LTBMC), the nonadherent cell production from Rhbright cells was transient and ended after 5 weeks. Production from Rhdim cells did not begin until week 3, peaked at week 5, and ended at week 8, when the irradiated stroma seemed to fail. Termination of cell production from Rhdim cells did not occur in nonirradiated LTBMC from W41/Wv mice. During peak nonadherent cell production, 25% to 30% of the cells in the nonirradiated LTBMC from W41/Wv mice had donor cell markers. Two approaches were tested to try to enhance the proportion or number of donor cells. Addition of Origen-HGF at the time of seeding Rhdim cells caused a nonspecific increase in both host and donor cell production, but a specific increase in production of donor cells was obtained by seeding the cultures at 2 weeks rather than 6 weeks. Limiting dilution of Rhdim cells gave the same frequency of wells producing cells on both irradiated +/+ and nonirradiated W41/Wv or W/Wv cultures.
Genetic Characterization of Turkish Snake Melon ( Cucumis melo L. subsp. melo flexuosus Group) Accessions Revealed by SSR Markers

Snake melon is an important cucurbit crop especially in the Southeastern and the Mediterranean region of Turkey. It is consumed as fresh or pickled. The production is mainly done with the local landraces in the country. Turkey is one of the secondary diversification centers of melon and possesses valuable genetic resources which have different morphological characteristics in case of snake melon. Genetic diversity of snake melon genotypes collected from different regions of Turkey and reference genotypes obtained from World Melon Gene Bank in Avignon-France was examined using 13 simple sequence repeat (SSR) markers. A total of 69 alleles were detected, with an average of 5.31 alleles per locus. The polymorphism information content of SSR markers ranged from 0.19 to 0.57 (average 0.38). Based on cluster analysis, two major groups were defined. The first major group included only one accession (61), while the rest of all accessions grouped in the second major group and separated into different sub-clusters. Based on SSR markers, cluster analysis indicated that considerably high genetic variability exists among the examined accessions; however, Turkish snake melon accessions were grouped together with the reference snake melon accessions.
Clock Scheduling for Improved Reliability

The problem of determining an optimal clock skew schedule for a fully synchronous VLSI system is considered in this chapter from the perspective of improving system reliability. An original formulation of the clock skew scheduling problem by Kourtev and Friedman is introduced as a constrained quadratic programming (QP) problem [95, 96].
Examining an ambitious world history teacher׳s knowledge for planning

Abstract The goal for this study was to better understand how an ambitious teacher uses pedagogical content knowledge while planning learning environments that focus on disciplinary, inquiry-based practices in world history. We used Monte-Sano and Budano׳s (2012) framework for pedagogical content knowledge for teaching history to examine the teacher׳s planning over the course of a year. Through interviews and analysis of artifacts, we found more specific sub-categories that represent the various ways that the teacher thought about transforming, representing, framing, and attending to students’ ideas about world history. Additionally, we found a hierarchical relationship in the aspects of the teacher׳s pedagogical content knowledge that aligned with her phases of planning (skeletal, unit planning, reflective) throughout the year. These findings highlight content-specific issues in planning world history courses—particularly those focused on the earliest eras—including questions about how teachers can find appropriate resources, organize world history content for teaching, and help students understand world historical narratives. We conclude with a discussion of these issues and implications for teacher education, curriculum design, and further research.
The history of trauma in psychiatry

The accidental separation of PTSD and the dissociative disorders, based on the unfortunate fact that the PTSD and the dissociative disorder workgroups of the DSM-III never met to compare data, and the lack of knowledge within the workgroups of existing research connecting these disorders, will continue in the DSM-IV. That separation, however, is slowly being eroded by a solid body of research that shows that these conditions rarely occur independently. Thus, contemporary research is beginning to show that the original concept of "hysteria," formulated 150 years ago to capture a group of patients who have complex psychological and somatic problems and whose problems often elude intervention from the medical and psychological professions, is alive and well among patients on the verge of the twenty-first century. Although the DSM process has attempted to create cleaner diagnostic categories, 100 years of research on traumatized patients consistently shows that these patients defy easy classification, and that they seem to have symptoms that represent somatic, social, symbolic, and intrapsychic adaptations to having experienced overwhelming terror. Thus, what the DSM split when it abolished hysteria as a diagnosis, has once again been found to constitute a syndrome, a conglomeration of symptoms, first defined by Briquet and Janet more than 100 years ago, which is the result of severe and prolonged interpersonal abuse, usually starting in childhood. One hundred years of research has shown us that patients often cannot remember and, instead, re-enact their dramas. The professions ministering to these patients have had similar problems with remembering the past, and thrice in this century have forgotten the hard-earned lessons from our patients. It is not likely that these amnesias and dissociations will be a thing of the past; they are likely to continue as long as physicians and psychologists are faced, helplessly, with man's inhumanity to man.
Personality, Thoughts and Methods of a Benevolent Autocrat

Kitchener had initially been drawn to Egypt as a means of advancing his military career. That is not to say that he was unaware of the principal factor that had inspired Britain’s involvement in Egypt. He knew of French designs in the Levant and that the only sure way to avoid Britain’s threat to its vital communications system was to occupy Egypt. When he returned to Egypt the second time, the new imperial movement was at its height and through his experience and observation, he had come to share in Disraeli’s vision of the correctness of Britain’s colonial empire. He favored its expansion, not by gratuitously adding more territory but in selecting areas that were strategically located and would strengthen the country’s military power. There is no evidence, one way or the other, but the economic argument advanced then by excitable politicians and their jingoistic captains of industry may also have played a part in shaping his attraction to empire-building. The economic dominance that Britain had enjoyed in Europe for decades through the advent of the industrial revolution had narrowed considerably as the twentieth century approached. Britain was threatened with losing its wealth and security. By enlarging its empire and acquiring new markets and sources of raw materials, it was hoped that Britain again would outdistance its rivals. This proved to be an illusion, however. More recent scholarship would show that colonies in general were non-profitable and in many cases were actually a drain on the nation’s treasury.
Quotient Pipelined Very High Radix Scalable Montgomery Multipliers

This paper describes the FPGA implementation of a scalable very high radix Montgomery multiplier using quotient pipelining. It improves upon previous designs by removing critical dependencies between successive processing elements. This design can perform 1024-bit modular exponentiation in 5.1 ms using 3825 4-input lookup tables and 32 18 times 18 multipliers, a 20% speed increase over a comparable design without quotient pipelining.
Real-world visual statistics and infants' first-learned object names.

We offer a new solution to the unsolved problem of how infants break into word learning based on the visual statistics of everyday infant-perspective scenes. Images from head camera video captured ...
Abstract 2334: Disruption of TGF-β-regulated CTCF suppression of telomerase links a human stem cell disorder to tumorigenesis

Background: Beckwith-Wiedemann syndrome (BWS) is a human stem cell disorder with a prevalence of 1 in 14,000. Its clinical manifestations include an 800-fold increased risk of tumorigenesis; yet the precise mechanism of BWS-associated tumorigenesis remains elusive. In a previous study, we showed that epigenetic silencing of β2-spectrin (β2SP, gene SPTBN1), a cytoskeletal protein and a Smad adaptor for Transforming Growth Factor-beta (TGF-β) signaling, was a causal factor in BWS. To determine the mechanism for the oncogenic switch, and whether it is related to the role of β2SP in TGF-β signaling transduction or secondary to its cytoskeletal functions, we analyzed disruption of two elements of the TGF-β pathway by generating double heterozygous Sptbn1+/−/Smad3+/− mice. Materials & Methods: Tumorigenesis analysis in Sptbn1+/− /Smad3+/− mice. Whole-transcriptome sequencing and IPA analyses were performed in the BWS cells and Sptbn1+/−; Sptbn1−/−; Smad3+/−; and Sptbn1+/−/Smad3+/− MEFs. Immunohistochemical analyses were performed for determining the expression of TERT in BWS tumors and mice liver, pancreas and stomach tissue specimens. ChIP assays were performed for examining the recruitment of β2SP/Smad3/CTCF complex at the promoter of TERT. Results: (1) 80% of Sptbn1+/−/Smad3+/− mice developed multiple tumors that were phenotypically similar to those of patients with BWS. (2) Somatic mutations in SPTBN1 and SMAD3 occur in multiple human sporadic cancers. (3) Disruption of the TGF-β pathway in Sptbn1+/−/Smad3+/− mice and BWS cells. (4) β2SP Interacts with SMAD3 in a TGF-β-dependent manner. (5) β2SP and SMAD3 interact with CTCF in the cell nucleus. (6) Dysfunction of the β2SP/SMAD3/CTCF complex increases hTERT levels in BWS and in β2SP+/-/Smad3+/- mice. Conclusions: We present a novel model of the molecular pathogenesis of BWS by demonstrating a potential shift arising from disruption of TGF-β signaling leading to BWS-associated tumorigenesis and human sporadic cancer development. Citation Format: Jian Chen, Jiun-Sheng Chen, Zhixing Yao, Wilma Jogunoori, Bibhuti Mishra, Franklin H. Herlong, Yun Seong Jeong, Nipun A. Mistry, Jianping Zhang, Xiaoping Su, Asif Rashid, Marta Davila, John R. Stroehlein, Jerry W. Shay, Lopa Mishra. Disruption of TGF-β-regulated CTCF suppression of telomerase links a human stem cell disorder to tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2334. doi:10.1158/1538-7445.AM2015-2334
Assessment of copper resistance in Pseudomonas syringae pv. phaseolicola, the pathogen of halo blight on snap bean

Abstract Halo blight, caused by Pseudomonas syringae pv. phaseolicola ( Psp ), is one of major bacterial diseases on beans worldwide. The disease infects leaves and pods of beans and is most destructive in areas such as south Florida where temperatures are moderate, rainfalls are frequent, and abundant inoculum is present. Application of fixed copper is the primary method currently used by growers to reduce halo blight damage. However, the development of copper resistance in the pathogen populations has become a primary concern in managing this disease. A total of 35 strains of Psp were isolated from snap bean samples collected from commercial fields in 2009 and 2010 in Homestead, Florida. Results from this study indicate that 80% of the Psp strains (28 of 35) from commercial snap bean fields were resistant to copper, based on bacterial populations after 24-h exposure in liquid NB media. Growth of the Psp strains on CYE agar was similar to that in liquid NB, both amended with copper, suggesting that assays on CYE agar amended with copper can be used for rapid assessment of copper resistance in Psp populations. Data from greenhouse experiments indicated that addition of mancozeb improved the efficacy of copper hydroxide for management of halo blight on snap bean caused by copper-resistant Psp strains.
High Throughput Connectomics (Keynote Abstract)

Connectomics is an emerging field of neurobiology that uses cutting edge machine learning and image processing to extract brain connectivity graphs from electron microscopy images. It has long been assumed that the processing of connectomics data will require mass storage and farms of CPUs and GPUs and will take months if not years. This talk will discuss the feasibility of designing a high-throughput connectomics-on-demand system that runs on a multicore machine with less than 100 cores and extracts connectomes at the terabyte per hour pace of modern electron microscopes. Building this system required solving algorithmic and performance engineering issues related to scaling machine learning on multicore architectures, and may have important lessons for other problem spaces in the natural sciences, where until now large distributed server or GPU farms seemed to be the only way to go.
A Numerical Study of Wind-Turbine Wakes for Three Atmospheric Stability Conditions

The effects of atmospheric stability on wind-turbine wakes are studied via large-eddy simulations. Three stability conditions are considered: stable, neutral, and unstable, with the same geostrophic wind speed aloft and the same Coriolis frequency. Both a single 5-MW turbine and a wind farm of five turbines are studied. The single-turbine wake is strongly correlated with stability, in terms of velocity deficit, turbulence kinetic energy (TKE) and temperature distribution. Because of the Coriolis effect, the wake shape deviates from a Gaussian distribution. For the wind-farm simulations, the separation of the core region and outer region is clear for the stable and neutral cases, but less distinct for the unstable case. The unstable case exhibits strong horizontal variations in wind speed. Local accelerations such as related to aisle jets are also observed, whose features depend on stability. The added TKE in the wind farm increases with stability. The highest power extraction and lowest power deficit are observed for the unstable case.
Translational genomics of grain size regulation in wheat

Identifying and mapping grain size candidate genes in the wheat genome greatly empowers reverse genetics approaches to improve grain yield potential of wheat. Grain size (GS) or grain weight is believed to be a major driving force for further improvement of wheat yield. Although the large, polyploid genome of wheat poses an obstacle to identifying GS determinants using map-based cloning, a translational genomics approach using GS regulators identified in the model plants rice and Arabidopsis as candidate genes appears to be effective and supports a hypothesis that a conserved genetic network regulates GS in rice and wheat. In this review, we summarize the progress in the studies on GS in the model plants and wheat and identify 45 GS candidate loci in the wheat genome. In silico mapping of these GS loci in the diploid wheat and barley genomes showed (1) several gene families amplified in the wheat lineage, (2) a significant number of the GS genes located in the proximal regions surrounding the centromeres, and (3) more than half of candidate genes to be negative regulators, or their expression negatively related by microRNAs. Identifying and mapping the wheat GS gene homologs will not only facilitate candidate gene analysis, but also open the door to improving wheat yield using reverse genetics approaches by mining desired alleles in landraces and wild ancestors and to developing novel germplasm by TILLING and genome editing technologies.
Building a Natural and Cultural Heritage Repository for the Storage and Dissemination of Knowledge: The Algarium Veneticum and the Archivio di Studi Adriatici Case Study

ABSTRACTThe Archivio di Studi Adriatici (ASA) is a repository of the Institute of Marine Sciences (ISMAR-CNR) of Venice. The ASA repository, completely open source and open access, hosts natural collections, heritage books, documents, and maps of the Institute of Marine Sciences. It was developed following the discovery of a historical algal collection at the Biblioteca Storica di Studi Adriatici of Venice. This collection, after having been catalogued, has been digitized with a digital planetary scanner. Digitized specimens and metadata, compiled using Dublin Core and Simple Darwin Core formats, are hosted on a website, based on Fedora Repository and Islandora framework.
Stochastic travel demand estimation: Improving network identifiability using multi-day observation sets

Abstract Stochastic travel demand estimation is essential to support many resilience and reliability based transportation network analyses. The problem of estimating travel demand based on sensor data often results in an ill-posed inverse problem, where solution uniqueness cannot be ensured. To overcome this challenge, effective utilization of more information/data, preferably from reliable sources, becomes critical. Conventional demand estimation methods often sacrifice system structural information during the process of compressing sensor data into its statistics. Loss of structural information, which captures critical relation between observed and estimated parameters, inevitably causes more dependence on unrealistic assumptions and unreliable data. Our model is designed to preserve all structural information contained from different observation sets and allow it to directly contribute to the identification of population parameters of travel demand. The proposed hierarchical framework integrates two traditionally distinctive identification problems, mean demand estimation and trip table reconstruction. Through mathematical analyses and numerical experiments, we show that the proposed framework improves parameter identifiability and leads to better estimation quality compared to conventional methods. The proposed framework is also flexible to accommodate a wide variety of travel behavior assumptions and estimation principles. As an example among many possible alternatives, Wardrop equilibrium based traffic assignment and generalized least square are implemented and tested using a case study based on a moderately large network.
From “Rust Belt” to “Fresh Coast”: Remaking the City through Food Justice and Urban Agriculture

Rising levels of urban food insecurity and diet-related disease have led to many inquiries into the urban food environment and its relation to health. Community-based food activism and urban agricu...
Kv1.3 deletion induces Foxo1 expression independently of Foxp3 and biases Th cells toward an immunoregulatory phenotype (P5127)

Myelin-reactive Th cells in patients with multiple sclerosis (MS) express Kv1.3, a voltage-gated K+ channel essential for Th cell activation and function. Recently, we have demonstrated that Kv1.3 deletion prevents experimental autoimmune encephalomyelitis, a murine model of MS, by inducing a regulatory Th cell phenotype independently of Foxp3. However, the mechanism by which Th cells with regulatory properties develop in the absence of Kv1.3 remains unclear. Foxo1 has been shown to function in induction of tolerance and in Treg cell lineage commitment. Foxo1 nuclear exclusion is induced in effector Th cells by downstream T cell receptor (TCR) signaling. Herein, we demonstrate an increase in nuclear Foxo1, with concomitant reduction in T-bet, in Kv1.3 KO Th cells. Surprisingly, Kv1.3 deletion does not impair TCR-induced intracellular Ca2+ flux or the activation of the Ca2+-sensitive transcription factor NF-AT. Instead, the absence of Kv1.3 leads to p56lck relocalization from TCR to the IL-2R complex, thereby contributing to the increase in Foxo1 and the differentiation of Treg cells in the absence of changes in Foxp3 expression. Herein, we demonstrate that regulatory Th cells are generated in the absence of Kv1.3 as a consequence of disrupted TCR signaling during formation of the immunological synapse, rather than impaired Ca2+ flux, resulting in upregulation of Foxo1. These data highlight Foxo1 as a novel target for induction of Treg cells in autoimmune diseases such as MS.
Consensus relaxation on materials of interest for adaptive ATR in CT images of baggage

An adaptive automatic threat recognition system (AATR) developed at the Lawrence Livermore National Laboratory (LLNL) is described for x-ray CT images of baggage. The AATR automatically adapts to the input object requirement specification (ORS), which can change or evolve over time. These specifications characterize materials of interest (MOIs), basic physical features of interest (FOIs) (such a mass and thickness) and performance goals (detection and false alarm probability) for objects of interest (OOIs). The need and technical requirements for an AATR were developed in collaboration with DHS’s Explosives Division and Northeastern University’s Awareness and Localization of Explosives-Related Threats (ALERT) Center, a DHS Center of Excellence (http://www.northeastern.edu/alert/). Independent of the input ORS, LLNL’s AATR always uses the same algorithm and codes to process CT images. The algorithm adapts in real-time to changes in the input ORS. LLNL’s AATR is thus suitable for dynamic scenarios in which the nature of the OOIs can change rapidly. The AATR uses a spatial consensus relaxation method to determine the most likely material composition for each CT image voxel. The resulting image of most likely material compositions is segmented. An OOI classification statistic (OOI score) is computed for each voxel and each extracted image volume. OOI recognition performance is reported using various metrics on a test set of ~180 plastic bins supplied by the ALERT Center of Excellence. A method is then proposed for automatic decision threshold estimation that can adapt to the detection performance goal, the most likely material composition, and the contents of the baggage.
Bias-Dependent Chemical Enhancement and Nonclassical Stark Effect in Tip-Enhanced Raman Spectromicroscopy of CO-Terminated Ag Tips

Tip-enhanced Raman spectromicroscopy (TERS) with CO-terminated plasmonic tips can probe angstrom-scale features of molecules on surfaces. The development of this technique requires understanding of how chemical environments affect the CO vibrational frequency and TERS intensity. At the scanning tunneling microscope junction of a CO-terminated Ag tip, we show that rather than the classical vibrational Stark effect, the large bias dependence of the CO frequency shift is due to ground-state charge transfer from the Ag tip into the CO π* orbital softening the C–O bond at more positive biases. The associated increase in Raman intensity is attributed to a bias-dependent chemical enhancement effect, where a positive bias tunes a charge-transfer excited state close to resonance with the Ag plasmon. This change in Raman intensity is contrary to what would be expected based on changes in the tilt angle of the CO molecule with bias, demonstrating that the Raman intensity is dominated by electronic rather than geomet...
Cell-Based Strategies for Bone Regeneration

The cellular and molecular events of skeletal morphogenesis,remodeling,and repair have their basis in the embryonic production of bone (1, 2, 3, 4, 5, 6, 7).For this reason,detailed analysis of developing osseous tissue in experimental models can provide the framework for understanding the cellular processes that occur in skeletal tissue as an organism grows and matures.This chapter is not intended to provide a comprehensive review of all cell-based therapies directed at bone regeneration.Instead,it aims to characterize the cellular events of osteoblastic differentiation,help clarify the lineage relationships between cells at various stages of maturity,and demonstrate how this cellular information has been used to design effective therapeutic strategies for bone repair and regeneration.While the bulk of the experimental data illustrated herein is derived from the authors’ laboratory, we provide these as examples against which results from additional investigators can be compared and contrasted.
Controversy And Consensus In Disaster Mental Health Research

Controversies regarding the mental health consequences of disasters are rooted both in disciplinary orientations and in the widely varied research strategies that have been employed in disaster mental health studies. However, despite a history of dissensus, there are also key issues on which researchers agree. Disasters constitute stressful and traumatic experiences. However, vulnerability to such experiences, as well as to more chronic Stressors, is socially structured, reflecting the influence of socio-economic status and other axes of stratification, including gender, race, and ethnicity. Disaster events differ in the extent to which they generate stress for victims. A holistic perspective on disaster mental health would take into account not only disaster event characteristics, but also social-systemic sources of both acute and chronic stress, secondary and cumulative Stressors, and victims internal and external coping capacities.
On the modeling and control of coupled multi-loop thermosyphons

This paper presents a one-dimensional model for natural convection in coupled multiloop thermosyphons. The physical model is governed by a system of Navier-Stokes equations, which are reduced to coupled systems of Lorenz equations via the Galerkin method. The simulations reveal different stages of flow as the Rayleigh number increases, e.g., from heat conduction, steady convective flow, to chaotic time-dependent flow. The control objective is to either stabilize the flow in each loop at one of its equilibrium points or track a reference signal in the chaotic range of the Rayleigh number. The controller design is based on proportional and integral (PI) control principles. The design can be easily implemented because the feedback state is measurable.
Changes of fractional renal clearance of magnesium after spironolactone administration in normal subjects.

Spironolactone, 200 mg/24 hours, was administered for 4 days to 18 clinically healthy subjects and 10 hospitalised patients with normal renal function. Changes of fractional renal clearance of magnesium before and after spironolactone administration were studied in the first group. Corresponding changes of the ratio of renal clearance of potassium to renal clearance of magnesium were studied in the second group. After spironolactone administration, fractional clearance of magnesium showed a statistically significant decrease in relation to its values before spironolactone administration, while the ratio % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4bspeea0dXdd9Gqpe0dc9% vqaqpepm0xd9as0-LqLs-Jirpepeea0-is0Fb9pgea0lrP0xe9Fve9% Fve9qapdbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaSaaaeaaie% aacaWFJbGaa8hBaiaa-vgacaWFHbGaa8NCaiaa-fgacaWFUbGaa83y% aiaa-vgacaWFGaGaa83Baiaa-zgacaWFGaGaa8hCaiaa-9gacaWF0b% Gaa8xyaiaa-nhacaWFZbGaa8xAaiaa-vhacaWFTbGaa8hiaaqaaiaa% -ngacaWFSbGaa8xzaiaa-fgacaWFYbGaa8xyaiaa-5gacaWFJbGaa8% xzaiaa-bcacaWFVbGaa8Nzaiaa-bcacaWFTbGaa8xyaiaa-DgacaWF% UbGaa8xzaiaa-nhacaWFPbGaa8xDaiaa-1gaaaaaaa!5DE8! $$\frac{{clearance of potassium }}{{clearance of magnesium}}$$ showed no statistically significant change. The results suggest that spironolactone administration decreases the renal excretion of magnesium and potassium in an equivalent manner.
Investigation of recent decadal-scale cyclical fluctuations in salinity in the lower Colorado river

Beginning in the late 1970s, 10- to 15-year cyclical oscillations in salinity were observed at lower Colorado River monitoring sites, moving upstream from the international border with Mexico, above Imperial Dam, below Hoover Dam, and at Lees Ferry. The cause of these cyclical trends in salinity was unknown. These salinity cycles complicate the U.S. Bureau of Reclamation's (Reclamation) responsibility for managing salinity in the river for delivery of water to Mexico to meet treaty obligations. This study develops a conceptual model of the salinity cycles from time-series water quality, streamflow, and precipitation data in both the lower and upper Colorado River Basins in order to provide Reclamation the ability to understand, anticipate, and manage future salinity cycles in the lower river. Compared with the Lees Ferry record, both maximum and minimum salinity levels increase downstream by about 25% at Hoover Dam, by about 49% at Imperial Dam, and by about 69% at the northern international boundary with Mexico. In the upper basin, cyclical salinity trends are evident at the outflow of three major tributaries, where salinity is also noted to be inversely related to streamflow. Time series trends in precipitation within the catchments of the three upper basin tributaries indicate cyclical periods with above normal precipitation and periods with below normal precipitation. Periods of greater than normal precipitation in the contributing areas correspond with declines in salinity at the catchment monitoring sites and periods of less than normal precipitation correspond with rising salinity at the sites. Based on the conceptual model developed in this investigation, a multiple linear regression model was developed using a stepwise variable selection procedure to simulate salinity in Lake Powell inflow. Important variables in the explanation of salinity entering Lake Powell include flow from the three upper basin tributaries, seasonality, and mean precipitation in the upper basin, among others. The root mean square error of prediction for the MLR model was 31.48 mg/L (5.7%).
Exosomes and extracellular vesicles as liquid biopsy biomarkers in diffuse large B-cell lymphoma: Current state of the art and unmet clinical needs

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, constituting biologically heterogeneous entities. Standard first line therapies cure ~60% of patients, the rest being either refractory or experiencing relapse. Currently, there are no robust predictive biomarkers of therapeutic response. Heterogeneity of DLBCL is partly explained by the cell of origin (COO), i.e. germinal center B cell (GCB) or activated B cell (ABC), with the latter exhibiting worse prognosis. While gene expression profiling (GEP) is the gold standard for determining COO, surrogate immunohistochemical algorithms are used clinically, but show significant discordance with GEP. Recently, additional subgroups with different prognoses have been reported. However, the tools/expertise required for analysis prohibit widespread deployment. Liquid biopsy-based assays show promise in providing clinically actionable information, are non-invasive and facilitate serial sampling to assess mechanisms of therapy resistance. Circulating, cell free DNA analysis has shown enhanced sensitivity, however, this modality cannot provide information on signaling pathways. Exosomes are endosomally derived vesicles, are found in high abundance in body fluids, and readily isolated using a variety of methods. Tumor derived exosomes contain genetic information and can reveal details for diagnostic, prognostic and therapeutic purposes in DLBCL. At present, standardized techniques for isolating exosomes are lacking and discriminating exosomes from neoplastic or normal B cells is challenging. Refinements in isolation procedures are required to realize their full potential as precision medicine tools to provide comprehensive information on disease subtypes, identify prognostic factors, allow real time monitoring of therapy response and to delineate drug targets.
Identifying Intra-Articular Pathology With Arthroscopy Prior to Open Ankle Fracture Fixation.

Purpose To assess the prevalence of intra-articular findings with ankle arthroscopy in patients undergoing operative fixation for ankle fractures. Methods This is a retrospective review of ankle fractures that were treated with arthroscopy and open reduction and internal fixation by a single surgeon. Between August 2016 and July 2018, operative reports, office notes, and images were reviewed to identify intra-articular pathology and fracture type. An analysis was performed with regard to fracture type, presence and location of osteochondral lesions, loose-bodies, syndesmotic injury, and deltoid injury. Results Fifty-seven ankle fractures were identified that met inclusion criteria. In total, 84.2% of the fractures had intra-articular pathology, most commonly a syndesmotic injury followed by presence of intra-articular loose bodies and osteochondral defects. Conclusions In our study, use of arthroscopy before open ankle fracture fixation identified intra-articular pathology in 84.2% of subjects. The most common pathology was syndesmotic injury. The addition of an arthroscopic assessment in patients with operatively treated ankle fractures may help improve treatment provided to patients during ankle fracture surgery. Level of Evidence Level 4 Therapeutic Case Series.
Monitoring Intravenous Infusion and the Venous Circulation

Summary This is an exciting time for IV therapy. Use of the IV route of administration continues to increase as patient acuity in today’s hospitals increases. IV therapy is not without risks, however, and a fuller understanding of the physical principles employed could help clinicians to reduce the incidence and severity of injuries resulting from drug extravasation (that is, tissue infiltration) and separate this dangerous phenomenon from less serious partial vein obstruction. This article summarizes a new conceptual model that can be demonstrated and used by making simple measurements during IV therapy. The model and technique employ an infusion pump that measures pressure, allowing the user to manually calculate resistance to fluid flow. Observing a rise in resistance at the IV site is an early indicator of undesirable changes at the catheter tip (that is, drug extravasation, catheter infiltration), even before the effect of these changes is visible or palpable on inspection of the IV site. Using insights obtained from the model, we observe that a properly used pressure-monitoring pump can detect resistance and obstruction to flow and differentiate between them. Also, it appears that suboptimal location of the catheter tip can be detected, and CVP can sometimes be measured from a peripheral IV site. Requirements for “instrument-assisted IV site monitoring” are (1) a flow source (IV pump), (2) a pressure monitoring system (transducer with pressure readout), and (3) the ability to analyze the PFR. This can be done most simply by measuring pressure at two or more flow rates and calculating P0 and R, the intercept and slope of the pressure versus flow graph. PFR analysis (computing R and P0) is subject to electronic software programming and could easily be added to the software of existing pressure-monitoring infusion instruments to provide intermittent IV site evaluation. If R and P0 monitoring were performed continuously and automatically, infiltration and obstruction could be detected and diagnosed. The quality of IV infusion, protected by site monitoring, would be enhanced significantly. This development could establish a new standard for IV site care.
COVID-19: The Heart of the Matter-Pathological Changes and a Proposed Mechanism.

The SARS-CoV-2 virus has resulted in over 88 million cases worldwide of COVID-19 as of January 2021. The heart is one of the most commonly affected organs in COVID-19, but the nature and extent of ...
Nonclinical genotoxicity and carcinogenicity profile of apremilast, an oral selective inhibitor of PDE4.

Abstract Apremilast is an oral, selective small molecule inhibitor of phosphodiesterase-4 (PDE4) that has been approved for the treatment of active psoriatic arthritis, moderate to severe plaque psoriasis, and for patients with oral ulcers associated with Behcet's disease. Apremilast modulates the inflammatory cascade in cells by inhibiting PDE4, thus preventing the degradation of cyclic adenosine monophosphate, resulting in the upregulation of interleukin (IL)-10 and the downregulation of proinflammatory cytokines, including IL-23, interferon gamma (IFNγ), and tumor necrosis factor alpha (TNFα). Here, we evaluated the genotoxic and carcinogenic potential of apremilast using Good Laboratory Practice (GLP)-compliant in vitro and in vivo studies. Apremilast was not genotoxic in the genetic toxicology battery, as evaluated for mutagenicity in the Ames test up to concentrations of 5000 μg/plate, clastogenicity in cultured human peripheral blood lymphocytes up to concentrations of 700 ug/mL was in excess of the solubility limit in culture medium and not able to assess; and negative for the induction of micronuclei in the bone marrow micronucleus test in mice up to doses of 2000 mg/kg/day. Furthermore, apremilast did not increase the incidence of tumors in lifetime rat or mouse carcinogenicity studies up to the maximum tolerated dose. In summary, in non-clinical studies, apremilast is not genotoxic and is not carcinogenic.
A Four-Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotypes C and D

Human botulism can be caused by botulinum neurotoxin (BoNT) serotypes A to G. Here, we present an antibody-based antitoxin composed of four human monoclonal antibodies (mAbs) against BoNT/C, BoNT/D, and their mosaic toxins. This work built on our success in generating protective mAbs to BoNT /A, B and E serotypes. We generated mAbs from human immune single-chain Fv (scFv) yeast-display libraries and isolated scFvs with high affinity for BoNT/C, BoNT/CD, BoNT/DC and BoNT/D serotypes. We identified four mAbs that bound non-overlapping epitopes on multiple serotypes and mosaic BoNTs. Three of the mAbs underwent molecular evolution to increase affinity. A four-mAb combination provided high-affinity binding and BoNT neutralization of both serotypes and their mosaic toxins. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing and neutralizing BoNT/C and BoNT/D serotypes and their mosaic toxins. A derivative of the four-antibody combination (NTM-1634) completed a Phase 1 clinical trial (Snow et al., Antimicrobial Agents and Chemotherapy, 2019) with no drug-related serious adverse events.
Rare primary pulmonary angiosarcoma with aberrant neuroendocrine differentiation

Angiosarcomas are aggressive, malignant endothelial cell tumors derived from the vascular or lymphatic epithelium. Angiosarcomas makes up less than 1% of all soft tissue sarcomas. Primary pulmonary angiosarcoma is a rare tumor that most commonly presents as metastatic disease and carries a grim prognosis. The disease rarity and low index of suspicion make the diagnosis problematic. In this report, we present a case of primary pulmonary angiosarcoma with aberrant neuroendocrine differentiation. The diagnostic images, pathology and management strategy are discussed in this case with overall longer survival. The unique neuroendocrine pathologic subtype may contribute to the overall longer survival, however, there are only a few limited cases published. Further recognition and investigation of primary pulmonary angiosarcoma with aberrant neuroendocrine differentiation is warranted to further characterize diagnostic markers, determine more effective treatment strategies, and establish a possible link to improved survival.
WE‐D‐207‐02: Capturing Data Elements and the Role of Imaging Informatics

In the United States, Lung Cancer is responsible for more cancer deaths than the next four cancers combined. In addition, the 5 year survival rate for lung cancer patients has not improved over the past 40 to 50 years. To combat this deadly disease, in 2002 the National Cancer Institute launched a very large Randomized Control Trial called the National Lung Screening Trial (NLST). This trial would randomize subjects who had substantial risk of lung cancer (due to age and smoking history) into either a Chest X-ray arm or a low dose CT arm. In November 2010, the National Cancer Institute announced that the NLST had demonstrated 20% fewer lung cancer deaths among those who were screened with low-dose CT than with chest X-ray. In December 2013, the US Preventive Services Task Force recommended the use of Lung Cancer Screening using low dose CT and a little over a year later (Feb. 2015), CMS announced that Medicare would also cover Lung Cancer Screening using low dose CT. Thus private and public insurers are required to provide Lung Cancer Screening programs using CT to the appropriate population(s). The purpose of this Symposium is to inform medical physicists and prepare them to support the implementation of Lung Screening programs. This Symposium will focus on the clinical aspects of lung cancer screening, requirements of a screening registry for systematically capturing and tracking screening patients and results (such as required Medicare data elements) as well as the role of the medical physicist in screening programs, including the development of low dose CT screening protocols. Learning Objectives: 1. To understand the clinical basis and clinical components of a lung cancer screening program, including eligibility criteria and other requirements. 2. To understand the data collection requirements, workflow, and informatics infrastructure needed to support the tracking and reporting components of a screening program. 3. To understand the role of the medical physicist in implementing Lung Cancer Screening protocols for CT, including utilizing resources such as the AAPM Protocols and the ACR Designated Lung Screening Center program. UCLA Department of Radiology has an Institutional research agreement with Siemens Healthcare; Dr. McNitt-Gray has been a recipient of Research Support from Siemens Healthcare in the past. Dr. Aberle has been a Member of Advisory Boards for the LUNGevity Foundation (2011-present) and Siemens Medical Solutions. (2013).