cssi/SciSciGPT-SciSciNet huggingface dataset:
Improved production of cytotoxic thailanstatins A and D through metabolic engineering of Burkholderia thailandensis MSMB43 and pilot scale fermentation.

Abstract Thailanstatin A (TST-A) is a potent antiproliferative natural product discovered by our group from Burkholderia thailandensis MSMB43 through a genome-guided approach. The limited supply of TST-A, due to its low titer in bacterial fermentation, modest stability and very low recovery rate during purification, has hindered the investigations of TST-A as an anticancer drug candidate. Here we report the significant yield improvement of TST-A and its direct precursor, thailanstatin D (TST-D), through metabolic engineering of the thailanstatin biosynthetic pathway in MSMB43. Deletion of tstP , which encodes a dioxygenase involved in converting TST-A to downstream products including FR901464 (FR), resulted in 58% increase of the TST-A titer to 144.7 ± 2.3 mg/L and 132% increase of the TST-D titer to 14.6 ± 0.5 mg/L in the fermentation broth, respectively. Deletion of tstR , which encodes a cytochrome P450 involved in converting TST-D to TST-A, resulted in more than 7-fold increase of the TST-D titer to 53.2 ± 12.1 mg/L in the fermentation broth. An execution of 90 L pilot-scale fed-batch fermentation of the tstP deletion mutant in a 120-L fermentor led to the preparation of 714 mg of TST-A with greater than 98.5% purity. The half-life of TST-D in a phosphate buffer was found to be at least 202 h, significantly longer than that of TST-A or FR, suggesting superior stability. However, the IC 50 values of TST-D against representative human cancer cell lines were determined to be greater than those of TST-A, indicating weaker antiproliferative activity. This work enabled us to prepare sufficient quantities of TST-A and TST-D for our ongoing translational research.
PIV Measurements of Flow in Recirculation Cavities at the Inlet of a Centrifugal Compressor

,Because of the necessity of mass flow range as large as possible on turbocharger compressors to match different engine regimes, the surge and stall phenomena, that limit the operational range at low mass flow, need to be controlled. Numerous active and passive devices exist in order to reduce or suppress their occurrence. A method that has been proven to work and is commonly used consists of recirculation passages that extract high entropy flow from the tip of the blades to reduce blockage in the blades. The compressor used in the study features a ported shroud connected by a slot to the main passage that removes part of the flow near the inducer and mixes it upstream into the inlet. In order to understand the mechanism and assess the flow patterns in the recirculation channels, PIV measurements were carried out in the inlet region. Data was collected along a compressor speedline and allows understanding of the flow in the channels and its interaction with the incoming flow for different operating regimes of the compressor.
Measurement of visual sensitivity in migraine: Validation of two scales and correlation with visual cortex activation.

ObjectiveThe objectives of this article are to compare interictal and ictal visual sensitivity between migraine and controls using two published questionnaires, and to correlate responses with a ph...
Is our work dangerous? Should it be?

Three case histories show how work in the medical social sciences--to the extent that such work reveals the origins of health problems in social structures of wealth and power--can become dangerous enough to threaten one's livelihood and in some instances one's very life. In this presentation, I encourage critical and engaged scholarship by referring to examples of dangerous work that should receive more attention: social medicine in Latin America and the critique of managerial ideology in the United States. Although social medicine has become a widely respected field of research, teaching, and clinical practice in Latin America, its accomplishments remain little known in the English-speaking world. For centuries, indigenous cultures in Latin America have held belief systems linking social conditions to patterns of illness and death. Latin American accounts of social medicine's history emphasize its European origins, especially in the contributions of Rudolf Virchow. In the United States, with the impact of the Flexner Report (1910) and its supporters, Virchow's vision of social medicine went into decline. On the other hand, in Latin America, social medicine flourished as a focus of education and research. Since social medicine's "golden age" during the 1930s, teachers, researchers, and practitioners have produced major achievements despite the dangers of this work, which in several instances have included torture, imprisonment, or death. An ideology favoring managerial decision making in the United States has influenced crucial policy decisions, and the justifications for these decisions have manifested symbolic politics in addition to the evaluation of factual evidence. With ambiguous empirical support, managerial ideology has fostered the general growth of managed care, the implementation of Medicaid managed care by state governments, the expansion of managed care in rural areas, and the impact of "evidence-based medicine" on policy and clinical decisions. If the occupational risks of critical work in the medical social sciences are not taken, we forfeit some of the most important gifts offered by "the sociological imagination."
Barrett’s Esophagus: Radiofrequency (RF) and Other Ablation Modalities

Over the last decade, there has been a revolution in the treatment of Barrett’s esophagus (BE) with dysplasia. Up until the mid-2000s most patients who developed BE with high-grade dysplasia underwent esophagectomy because of a high risk of developing esophageal adenocarcinoma. By 2009, surgery had been replaced by endoscopic therapies. Why the change? Up to that point in time, ablative therapies for BE were cumbersome with variable results or significant complications. In 2009, endoscopic radiofrequency mucosal ablation for Barrett’s with high-grade dysplasia was proven effective, introducing the world to a well-tolerated, reproducible, and safe technology that ushered in the modern era of endoscopic treatment of dysplastic BE. This chapter briefly reviews the pathophysiology of BE and its association with esophageal adenocarcinoma, describes how to evaluate it endoscopically, and details modern techniques of esophageal mucosal ablation and their results.
Europe: The End of “Two Europes” and European Integration

Major political and cultural-intellectual trends and events of historic proportions, most of which were surprising and unpredicted, have characterized Europe during the three decades since 1980. The outcome has been a dramatic transformation of the continent. I am going to discuss those elements of this political transfiguration that were of particular historical importance. Unquestionably, the number one factor in bringing about these global changes was the collapse of communism and the Soviet superpower . The Cold War division of Europe and the world, which had determined its history since 1945, finally ended. The danger of war was eliminated. A closely related “side effect” of the end of communism was German reunification, a gigantic historical event in itself that nobody wanted to see outside Germany, but which no one was able to stop. The announced “ new world order ” became a chaotic disorder. Europe rearranged itself and realized a new European order, though not without huge dramas, including the division of states along ethnic or religious lines, sometimes attended by civil wars, armed struggles, and terrorist methods in fighting for independence. These changes accompanied another equally historic change, a milestone in European history, which was the transformation and elevation of the European Community , both in terms of its expansion and its radically “deepened” integration. It took deep roots during the Cold War. This development began the elevation of Europe as a superpower.
Red-Stained Feet: Probing the Ground on which Women Dance in Contemporary Bengal

Charged with rethinking the construct of World Histories of Dance, I wonder about the possibility of constructing histories of dancing bodies across wide terrains of time and space, histories that can only be charted through trace — stilled images in sculptures, paintings, photographs; descriptions in texts; memories; and only recently, the late nineteenth century onwards, through recordings — always, a necessarily selective project. What indeed are the possibilities for creating a ‘historical’ narrative from tracing those shifts within dancing bodies, marking changes in forums, alterations in costumes, and swings in context? For whom might these histories be important? And what inequities rise in the necessarily selective recordings of ‘world’ dance histories, as the inevitable consequence of the uneven concentration of capital and resources in particular geopolitical locations?
Comprehensive Model of Single Particle Pulverized Coal Combustion Extended to Oxy-Coal Conditions

Oxy-fired coal combustion is a promising potential carbon capture technology. Predictive CFD simulations are valuable tools in evaluating and deploying oxy-fuel and other carbon capture technologies either as retrofit technologies or for new construction. However, accurate predictive simulations require physically realistic submodels with low computational requirements. In particular, comprehensive char oxidation and gasification models have been developed that describe multiple reaction and diffusion processes. This work extends a comprehensive char conversion code (CCK), which treats surface oxidation and gasification reactions as well as processes such as film diffusion, pore diffusion, ash encapsulation, and annealing. In this work several submodels in the CCK code were updated with more realistic physics or otherwise extended to function in oxy-coal conditions. Improved submodels include the annealing model, the swelling model, the mode of burning parameter, and the kinetic model, as well as the addi...
Diabetic Nephropathy: Scope of the Problem

Diabetic nephropathy is a common complication of diabetes and the leading cause of chronic kidney disease in the developed world. Approximately 40 % of persons with type 2 diabetes develop diabetic nephropathy (albuminuria and/or decreased glomerular filtration rate). Even mild degrees of albuminuria and decrease in glomerular filtration rate are associated with significantly increased risks of cardiovascular disease, end-stage renal disease, and premature deaths. The prevalence of diabetic nephropathy in the US adult population aged 20 years and older is 3.3 % and increases with age (10.7 % among individuals aged 65 years and older). Increase in the prevalence of diabetic nephropathy is directly related to the increased prevalence of diabetes, which is largely driven by increasing obesity and metabolic syndrome. Both obesity and metabolic syndrome can directly contribute to the progression of kidney disease. These disorders likely interact with diabetes to exacerbate the kidney damage. In addition, increases in diabetic nephropathy prevalence are the largest for persons aged 65 years or older among whom diabetic nephropathy is most common. The prevention and treatment of diabetic nephropathy in older patients may require specific strategies. This chapter reviews the epidemiology of diabetic nephropathy, interrelationship between obesity, metabolic syndrome and diabetic nephropathy, and special challenges of diabetic nephropathy in the elderly.
Computational and Experimental Studies on the Effects of Monomer Planarity on Covalent Organic Framework Formation

We report the synthesis of one new boronate ester-based covalent organic framework (COF) and two new covalent organic polymers (COPs) made with fluoranthene-containing monomers and hexahydroxytriphenylene. The structure of the monomer heavily influences whether this material forms a highly ordered mesoporous material (COF) or an amorphous, microporous material (COP). The synthesis of the fluoranthene monomers was carried out using a divergent strategy that allows for systematic structural variation and the ability to conduct a careful structure-function study. We found that small structural variations in the monomers dramatically affected the crystallinity, surface area, pore structure, and luminescence properties of the polymers. While each of the monomers contains the same fluoranthene core, the resultant pore sizes range from microporous (10 A) to mesoporous (37 A), with surface areas ranging from ∼500 to 1200 m2/g. To help explain how these small structural differences can have such a large effect, we carried out a series of molecular dynamics simulations on the polymers to obtain information with atomic-scale resolution on how the monomer structure affects non-covalent COF layer stacking.
Anxiety in Children

Although the study and treatment of adult anxiety have traditionally received a great deal of theoretical and empirical attention in psychology and in psychiatry, the topic of childhood anxiety has tended to be overlooked (Wolfson, Fields, & Rose, 1987). Yet children with anxiety disorders comprise a significant portion of patients treated at mental health centers (Cytryn, McKnew, Zahn-Waxler, Radke-Yarrow, Gaensbauer, Harmon, & Lamour, 1984). The belief that anxiety in childhood is common and transient appears to have undermined interest in exploring its nature and development (Wolfson et al., 1987). Even if this were so, the distress produced when anxiety is manifest may well warrant attention (Jenkins, Bax, & Hart, 1980). Moreover, there is evidence that childhood anxiety may be predictive of pathology at later development stages of an individual’s life (Bowlby, 1973; Kellam, Branch, Agrawal, & Ensminger, 1975).
Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3′ phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2–8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome. The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.
Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations

Positional fluctuations of an atom in a protein can be described as motion in an effective local energy minimum created by the surrounding protein atoms. The dependence of atomic fluctuations on both temperature (T) and pressure (P) has been used to probe the nature of these minima, which are generally described as harmonic in experiments such as x-ray crystallography and neutron scattering. Here, a quasiharmonic analysis method is presented in which the P-T dependence of atomic fluctuations is in terms of an intrinsic isobaric thermal expansivity αP and an intrinsic isothermal compressibility κT. The method is tested on previously reported mean-square displacements from P-T molecular dynamics simulations of lysozyme, which were interpreted to have a pressure-independent dynamical transition Tg near 200 K and a change in the pressure dependence near 480 MPa. Our quasiharmonic analysis of the same data shows that the P-T dependence can be described in terms of αP and κT where below Tg, the temperature dependence is frozen at the Tg value. In addition, the purported transition at 480 MPa is reinterpreted as a consequence of the pressure dependence of Tg and the quasiharmonic frequencies. The former also indicates that barrier heights between substates are pressure dependent in these data. Furthermore, the insights gained from this quasiharmonic analysis, which was of the energy landscape near the native state of a protein, suggest that similar analyses of other simulations may be useful in understanding such phenomena as pressure-induced protein unfolding.
Public relations leadership development cycle: A cross-cultural perspective

Abstract This exploratory research study is the first known attempt to understand the process and various stages of leadership development in public relations specialists. Using purposive in-depth interviews with PR practitioners and students from five countries (Brazil, China, India, Russia and the U.S.), this study gathered qualitative data about the seven public relations leadership dimensions (Berger & Meng, 2014) to glean insights as to when these dimensions appear/are learned and how they are manifested. This study indicates that having strong technical skills (the communication knowledge and expertise dimension) is viewed as the main prerequisite to develop into a PR leader. Other personal leadership dimensions found to be learned early in life and developed more fully over time include: self-dynamics (first learned through family/peer interactions and through those of school/organizations/groups), ethical orientation (first learned from family/religious values), team collaboration (first learned through family, sports, church and school projects), relationship-building (first learned through interactions with peers, teachers, family members, coaches). Strategic decision making capabilities seem to develop later in one’s professional growth, after one has both technical skill and professional experience upon which to draw.
The Brief Perceived Cognitive Impairment Scale-Korean: A Validation Study.

BACKGROUND Practical brief measures are needed for clinicians and researchers to identify and effectively manage cognitive impairment in cancer patients. OBJECTIVE This study evaluated the reliability (ie, internal consistency reliability) and validity (ie, construct, convergent, concurrent, and known-group validity) of the Brief Perceived Cognitive Impairment Scale-Korean (BPCIS-K). METHODS From a university hospital, 249 cancer patients participated. The BPCIS-K was constructed with 6 items evaluating key aspects of cognitive impairment in cancer patients. For internal consistency reliability, Cronbach's α and item-total correlations were evaluated. For construct validity, confirmatory factor analysis was performed. For convergent validity, Pearson correlations were tested with the Functional Assessment of Cancer Therapy-Cognitive Function. For concurrent validity, Pearson correlations were tested with the Functional Assessment of Chronic Illness Therapy-Fatigue. For known-group validity, t tests were performed. RESULTS The BPCIS-K showed high internal consistency reliability (Cronbach's α = .92; item-total correlations ranged from 0.76 to 0.81). Factor analysis confirmed the scale is unidimensional. It is highly associated with another validated cognitive impairment measure (r = -0.91, P < .001) and moderately correlated with a fatigue measure (r = -0.52, P < .001). In known-group validity, female and patients undergoing treatment experienced more severe impairment than did male patients and patient awaiting treatment (P = .05, P = .08, respectively). CONCLUSION The BPCIS-K is valid and reliable for assessing cancer patients' perceived cognitive impairment, particularly in concentration, memory, and executive functions. IMPLICATION FOR PRACTICE This study introduces a practical brief measure to clinicians and researchers.
Dust Storms and Their Influence on Atmospheric Parameters over the Indo-Gangetic Plains

Dust storms are very common in the northern parts of India, and every year people living in the Indo-Gangetic plains suffer greatly. Dust storms affect day-to-day lives of people living in the Indo-Gangetic plains (IGP) and impact their health. The atmospheric and meteorological parameters are highly influenced by the dust storms and are found to affect the air quality that creates a big health threat and also affects the weather conditions. In this chapter, we discuss use of satellite remote sensing data in monitoring the dust events which occur every year during pre-monsoon season and their impacts on ocean, atmosphere, and meteorological parameters. Long-term effects of such dust storms on the climate of the northern parts of India are discussed. Such dust storms can be easily monitored using satellite data that can be used in issuing warning to the people so that they would not be exposed to such strong dust storms.
Lightly supervised acoustic model training on EPPS recordings.

Debates in the European Parliament are simultaneously translated into the official languages of the Union. These interpretations are broadcast live via satellite on separate audio channels. After several months, the parliamentary proceedings are published as final text editions (FTE). FTEs are formatted for an easy readability and can differ significantly from the original speeches and the live broadcast interpretations. We examine the impact on German word error rate (WER) when introducing supervision based on German FTEs and supervision based on German automatic translations extracted from the English and Spanish audio. We show that FTE based supervision and additional interpretation based supervision provide significant reductions in WER. We successfully apply FTE supervised acoustic model (AM) training using 143h of recordings. Combining the new AM with the mentioned supervision techniques, we achieve a significant WER reduction of 13.3% relative.
Decreased Secretion and Unfolded Protein Response Upregulation

Recombinant antibody fragments, for example, the classic monovalent single-chain antibody (scFv), are emerging as credible alternatives to monoclonal antibody (mAb) products. scFv fragments maintain a diverse range of potential applications in biotechnology and can be implemented as powerful therapeutic and diagnostic agents. As such, a variety of hosts have been used to produce antibody fragments resulting in varying degrees of success. Yeast, Saccharomyces cerevisiae, is an attractive host due to quality control mechanisms of the secretory pathway that ensure secreted proteins are properly folded. However, the expression of a recombinant protein in yeast is not trivial; neither are the quality control mechanisms the cell initiates to respond to overwhelming stress, such as an increased protein load, simplistic. The endoplasmic reticulum (ER) is a dynamic organelle, capable of sensing and adjusting its folding capacity in response to increased demand. When protein abundance or terminally misfolded proteins overwhelm the ER's capacity, the unfolded protein response (UPR) is activated. In the guidelines presented here, we discuss varying aspects of quality control, its modulation, and ways to design appropriate constructs for yeast recombinant protein expression. Furthermore, we have provided protocols and methods to monitor intracellular protein expression and trafficking as well as evaluation of the UPR, with essential controls. The latter part of this chapter will review considerations for the experimental design of microarray and quantitative polymerase chain reaction (q-PCR) techniques while suggesting appropriate means of data analysis.
Infrared Interferometry of Active Galaxies

IR interferometers operating at 2 – 20 µm. over ∼ 100 m baselines will be ideally suited to probing the interfaces between active galactic nuclei and their host galaxies. When these devices become operational, they will tell us how quasars generate infrared light and will clarify the relationships between the powerful black-hole engines at the centers of galaxies and the surrounding bursts of star formation.
Abstract 5875: Cofilin: A Novel Regulator of {beta}-arrestin Signaling

Beta adrenergic receptors ( β ARs) are important regulators of cardiac function and are desensitized in conditions of heart failure. Recent evidence suggests that actin remodeling may play a role in receptor internalization and signaling. Actin remodeling is a process regulated by many proteins including cofilin. Cofilin is a phospho-protein that is activated by dephosphor-ylation to bring about actin depolymerization. To test whether cofilin regulates β AR signaling, we generated cofilin mutants that mimic constitutively active (S3A) and inactive (S3D) proteins. Isoproterenol (ISO) stimulation of β 2 AR stable HEK 293 cells coexpressing wild type (Wt), S3A, S3D cofilin showed differential ERK activation as measured by phospho-ERK (pERK). Significant ERK activation was observed with S3D mutant that was markedly reduced in cells expressing S3A cofilin. Interestingly expression of Wt resulted in reduced ERK activation consistent with our observation that Wt cofilin undergoes marked dephosphorylation following ISO stimulation. To further test whether cofilin modulates β AR signaling via β -arrestin that mediates G-protein independent signaling, Wt and mutant cofilins were transfected into HEK cells stably expressing HA- β 2 AR and β -arrestin GFP. β -arrestin GFP translocation to plasma membrane was visualized by confocal microscopy upon agonist stimulation. Significant inhibition of β -arrestin translocation to the plasma membranes was observed with S3A cofilin mutant that was completely rescued in the presence of S3D mutant. Therefore, suggesting that loss in β -arrestin recruitment to the β AR complex in presence of active cofilin (S3A) could potentially account for the marked reduction in ERK activation. Studies in end-stage human heart failure samples showed significant ERK activation (pERK) in heart failure samples associated markedly higher levels phospho-cofilin (inactive cofilin) compared to non-failing controls. Our findings that actin remodeling play a critical role in β -arrestin mediated signaling is significant in lieu of, a) β -arrestin mediated signaling is cardioprotective and b) actin remodeling is markedly altered in heart failure. Underlying mechanism by which actin remodeling regulates β AR signaling will be presented.
Down Conversion of 351 nm Radiation for Fusion Lasers

The properties required in a laser medium to make it suitable for a fusion laser are fairly well known[1,2].
Existence of Exceptional Body Waves and Subsonic Surface Waves in Monoclinic and Orthotropic Materials

Explicit conditions are given for the existence of an exceptional body wave in monoclinic materials with the symmetry plane at x 1 = 0, x 2 = 0 or x 3 = 0 and in orthotropic materials with the symmetry planes coinciding with the coordinate planes. The non-existence of an exceptional body wave ensures the existence of a subsonic surface wave. If an exceptional body wave exists, explicit conditions are given for the existence of a subsonic surface wave in monoclinic and orthotropic materials except when tr L(\(\hat{\upsilon}\)) needs to be computed.
Omissions: The Constitution View Defended

Omissions are metaphysically puzzling: Are they something or are they nothing? This paper develops and defends the constitution view of omissions, according to which a correct analysis of a person’s omission has the form “S omitted to X by Y-ing,” where her Y-ing is what constitutes her not-X-ing. The paper explains why the constitution view should be preferred to other views of omissions and defends the view against objections.
A Calculus of Regions Respecting Both Measure and Topology

Say that space is ‘gunky’ if every part of space has a proper part. Traditional theories of gunk, dating back to the work of Whitehead in the early part of last century, modeled space in the Boolean algebra of regular closed (or regular open) subsets of Euclidean space. More recently a complaint was brought against that tradition in Arntzenius (2008) and Russell (2008): Lebesgue measure is not even finitely additive over the algebra, and there is no countably additive measure on the algebra. Arntzenius advocated modeling gunk in measure algebras instead—in particular, in the algebra of Borel subsets of Euclidean space, modulo sets of Lebesgue measure zero. But while this algebra carries a natural, countably additive measure, it has some unattractive topological features. In this paper, we show how to construct a model of gunk that has both nice rudimentary measure-theoretic and topological properties. We then show that in modeling gunk in this way we can distinguish between finite dimensions, and that nothing in lost in terms of our ability to identify points as locations in space.
Chapter 10 – Interpolation

There are many cases where one knows the value of a function at discrete points and wants to estimate the function's value between those points. That is, one wants to interpolate the function between the known values. In this chapter we review properties of polynomials and their properties of uniqueness and approximation. Then we show how a polynomial interpolating function can be constructed using the Lagrange polynomial formula. Polynomial interpolants are easy to construct but suffer from the Runge phenomenon where high-degree polynomials have unacceptable oscillations in the reconstruction. To deal with the Runge phenomenon, we present cubic splines as a way to get accurate interpolating functions in a straightforward way. We use SciPy's cubic spline functionality for this purpose.
Using national sewage sludge data for chemical ranking and prioritization

Abstract Treated sewage sludges (SSs) or biosolids are rich in organic carbon, nutrients, and, unfortunately, chemical contaminants. Accumulation of chemicals in SS is influenced by the mass of chemical produced and released into wastewater, resistance to (bio)degradation during treatment, and the chemicals' propensity to sorb to particulates. Hence, accumulation of chemicals in SS is indicative of their persistent and bioaccumulative behavior: the two characteristics that are predominantly used for chemical prioritization. Thus, it is possible for risk assessors to use existing SS survey data to identify, rank, and prioritize persistent and bioaccumulative chemicals present in the human society. In this review, we highlight unique papers that used this concept to help prioritizing chemical contaminants in SS and the environment. We additionally showcase a simple decision flowchart and scoring algorithm for prioritizing chemicals whose presence in SS warrants further investigation.
3D printing for developing patient specific cosmetic prosthetics at the point of care.

Abstract As 3D Printing methods have improved and newer advanced materials have been introduced then the ability to create a range of 3D printed prosthetic devices has developed. 3D Printing has allowed us to produce prosthetic devices that are customised to the needs of a patient. As a result, 3D printing offers a way towards the manufacture of ultraprecise patient-specific prosthetic devices to be generated at the point of care within the hospital. Because prosthetic devices can be cost effectively made to be patient specific, then they can in many circumstances improve patient recovery time (Aimar et al., 2019) [1]. We have recently used 3D printed to make a range of orthopaedic, oncology, plastics, and paediatric prosthetics.
Biologic excipients: Importance of clinical awareness of inactive ingredients

Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.
Tissue-specific Nrf2 signaling protects against methylmercury toxicity in Drosophila neuromuscular development

Methylmercury (MeHg) can elicit cognitive and motor deficits due to its developmental neuro- and myotoxic properties. While previous work has demonstrated that Nrf2 antioxidant signaling protects from MeHg toxicity, in vivo tissue-specific studies are lacking. In Drosophila, MeHg exposure shows greatest developmental toxicity in the pupal stage resulting in failed eclosion (emergence of adults) and an accompanying ‘myosphere’ phenotype in indirect flight muscles (IFMs). To delineate tissue-specific contributions to MeHg-induced motor deficits, we investigated the potential of Nrf2 signaling in either muscles or neurons to moderate MeHg toxicity. Larva were exposed to various concentrations of MeHg (0–20 µM in food) in combination with genetic modulation of the Nrf2 homolog cap-n-collar C (CncC), or its negative regulator Keap1. Eclosion behavior was evaluated in parallel with the morphology of two muscle groups, the thoracic IFMs and the abdominal dorsal internal oblique muscles (DIOMs). CncC signaling activity was reported with an antioxidant response element construct (ARE-GFP). We observed that DIOMs are distinguished by elevated endogenous ARE-GFP expression, which is only transiently seen in the IFMs. Dose-dependent MeHg reductions in eclosion behavior parallel formation of myospheres in the DIOMs and IFMs, while also increasing ARE-GFP expression in the DIOMs. Modulating CncC signaling via muscle-specific Keap1 knockdown and upregulation gives a rescue and exacerbation, respectively, of MeHg effects on eclosion and myospheres. Interestingly, muscle-specific CncC upregulation and knockdown both induce lethality. In contrast, neuron-specific upregulation of CncC, as well as Keap1 knockdown, rescued MeHg effects on eclosion and myospheres. Our findings indicate that enhanced CncC signaling localized to either muscles or neurons is sufficient to rescue muscle development and neuromuscular function from a MeHg insult. Additionally, there may be distinct roles for CncC signaling in myo-morphogenesis.
Model-based reconstructive approaches in optical coherence elastography of ocular tissues

The biomechanical characteristics of ocular tissues have a profound influence on the normal function of the human eye. We have developed noninvasive optical coherence elastography approaches to measure elastic properties of the ocular tissues. Biomechanical properties are evaluated based on developed mathematical models of the dynamic deformation of the viscoelastic medium. We have demonstrated the influence of such factors as age and intraocular pressure on the mechanical properties of the crystalline lens, cornea, and other tissues. The optical coherence elastography was demonstrated as a promising tool for noninvasive assessment of the biomechanical properties of the ocular and other tissues.
A Significant Pericardial Effusion Leading to Bronchial Compression: A Case Report:

Commonly, pericardial effusions can cause suboptimal heart contractility. Larger pericardial effusions can lead to compression of structures that surround in the heart in the mediastinum. Our patie...
Connecting the Unconnected

Der Beitrag gibt einen Uberblick uber die Wechselbeziehung zwischen Sozialarbeit und Strafverfolgung in den Vereinigten Staaten. Ausgehend von der langen Geschichte der Zusammenarbeit zwischen den beiden Professionen werden Probleme sowie die Debatten betrachtet, die in jungster Zeit im Zusammenhang mit dem landesweiten Aufstand gegen Polizeibrutalitat aufgetaucht sind. In den Blick genommen wird auch die Machbarkeit einer verstarkten interprofessionellen Zusammenarbeit, indem zeitgenossische Modelle und Fallstudien von Partnerschaften zwischen Sozialarbeit und Polizei in den USA dargestellt werden.
The Effects of User Comments on Science News Engagement

Online sources such as social media have become increasingly important for the proliferation of science news, and past research has shown that reading user-generated comments after an article (i.e. in typical online news and blog formats) can impact the way people perceive the article. However, recent studies have shown that people are likely to read the comments before the article itself, due to the affordances of platforms like Reddit which display them up-front. This leads to questions about how comments can affect people's expectations about an article, and how those expectations impact their interest in reading it at all. This paper presents two experimental studies to better understand how the presentation of comments on Reddit affects people's engagement with science news, testing potential mediators such as the expected difficulty and quality of the article. Study 1 provides experimental evidence that difficult comments can reduce people's interest in reading an associated article. Study 2 is a pre-registered follow-up that uncovers a similarity heuristic; the various qualities of a comment (difficulty, information quality, entertainment value) signal that the article will be of similar quality, ultimately affecting participants' interest in reading it. We conclude by discussing design implications for online science news communities.
Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation

ABSTRACT Graft-versus-host disease (GVHD) is a frequent complication in the first year after allogeneic stem cell transplantation (allo-HCT). Recipients of reduced-intensity (RI) or nonmyeloablative (NMA) conditioning combined with calcineurin inhibitor (CNI)–based GVHD prophylaxis frequently develop GVHD in the context of immunosuppression taper. Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity. We hypothesized that switch-maintenance GVHD prophylaxis using ixazomib would facilitate CNI taper without increased GVHD frequency and severity while maintaining graft-versus-tumor (GVT) effect and an acceptable safety profile. We conducted an open-label, prospective, single-center pilot study in patients with hematologic malignancies who received an RI or NMA conditioning and CNI-based GVHD prophylaxis that were within day 100 to 150 after HCT (n = 18). Patients were treated with ixazomib once weekly on a 28-day cycle (3 weeks on, 1 week off). Treatment was safe; most adverse events were grade 1 or 2, with cytopenia and elevation in transaminases the most common. Five patients were removed from the study because of toxicity or side effects. Only 5 of 18 patients developed GVHD during the study, and its severity was driven by acute manifestations while chronic involvement was mild. The cumulative incidence of grade II-IV acute and chronic GVHD at 1-year after HCT was 33% (95% confidence interval [CI], 13-55). No patients died during the study, and only 1 had malignant relapse. An additional patient relapsed after completion of the study but within 1 year after HCT. The probability of progression-free survival and GVHD-free/relapse-free survival (composite endpoint) at 1 year were 89% (95% CI, 75-100) and 78% (95% CI, 61-100), respectively. Immune reconstitution analysis showed a rapid and sustained recovery in T-cell subpopulations and B cell reconstitution, and vaccine response in a subset of patients demonstrated continuing or de novo positive protective antibody titers. This study demonstrated low incidence of recurrent and late acute and chronic GVHD within 1 year after HCT possible associated with switch-maintenance GVHD prophylaxis using ixazomib. This approach allowed for CNI taper while preserving GVT effect, without aggravating GVHD. Our findings support further development of this approach and provide a proof-of-concept for switch-maintenance GVHD prophylaxis.
Development of a Multiplex Fluorescence in Situ Hybridization Assay to Identify Coinfections in Young-of-the-Year Smallmouth Bass.

Histopathological assessments of young-of-the-year (age-0) Smallmouth Bass Micropterus dolomieu in the Susquehanna River drainage identified a high prevalence of the myxozoan Myxobolus inornatus. This myxozoan infects the connective tissue of the muscle below the skin but is sometimes observed in the esophagus and buccal cavity. In some instances, shallow infections cause breaks in the skin, which could increase the chance of opportunistic bacterial infections. Several microbial pathogens, including Flavobacterium columnare, Aeromonas spp., and Largemouth Bass virus, have also been cultured from clinically diseased young of year. A multiplex fluorescence in situ hybridization (FISH) assay was developed to determine potential colocalization of M. inornatus, Flavobacterium spp., and Aeromonas spp. infections. With FISH, 75% of age-0 Smallmouth Bass exhibited M. inornatus infections, 10% had Aeromonas spp. infections, and 5% had Flavobacterium spp. infections, while 3% had coinfections with both bacterial species and M. inornatus. The results of the multiplex FISH assay revealed a low occurrence of coinfections of Flavobacterium spp. and/or Aeromonas spp. with M. inornatus in randomly sampled individuals.
Interpreting the Moving Image

Forward 'Through Carroll's Looking Glass of Criticism' Tom Gunning Introduction 1. The cabinet of Dr. Kracauer 2. Entr'acte, Paris and Dada 3. The Gold Rush 4. Keaton: film acting as action 5. Buster Keaton, The General and visible intelligibility 6. For God and Country 7. Lang, Pabst and Sound 8. Notes on Dreyer's Vampyr 9. King Kong: ape and essence 10. Becky Sharp takes over 11. Interpreting Citizen Kane 12. Mind, medium and metaphor in Harry Smith's Heaven and Earth Magic 13. Welles and Kafka 14. Nothing But A Man and The Cool World 15. Identity and difference: from ritual symbolisim to condensation in Anger's Inauguration of the Pleasure Dome 16. Text of Light 17. Joan Jonas: making the image visible 18. Introduction to Journeys from Berlin/1971 19. The future of allusion: Hollywood in the seventies (and Beyond) 20. Back to basics 21. Amy Taubin's bag 22. Herzog, presence and paradox 23. Film in the age of postmodernism.
TH-CD-204-10: Probability-Driven Sorting Method for Reconstructing Variation-Independent 4D-MRI

Purpose: To develop a novel probability-driven sorting method that inherently incorporates breathing variations in the sorting process and 4D reconstruction. Methods: The probability-driven sorting method has two key steps: (a) determination of multiple principal breathing cycles that largely represent main variation patterns of the breathing signal. This will be accomplished by analyzing the breathing signal acquired during image acquisition using principal component analysis (PCA). The relative occurrence rate of each principal cycle will also be determined; (b) 4D image reconstruction based on the determined principal cycles. We will separately reconstruct a 4D-MRI for each principal cycle by optimally sorting k-space segments that best represent the principal cycle. Multi-cycle 4D reconstruction is impossible for most current 4D imaging techniques such as 4D-CT. It is however feasible for k-space reordered 4D-MRI due to the random assignment of phase/amplitude to k-space segments, as a Result of sampling scheme variations and breathing variations. To demonstrate the feasibility, we determined data completeness cures for the probability-driven sorting technique via simulation using breathing profiles from 30 cancer patients. It requires more repetitions to achieve full completeness relative to phase sorting, but is compatible to amplitude sorting. Results: We have tested the proposed method via simulation using 30 patients’ breathing profiles. We generated three PDFs per patient: one with all cycles (PDFA), one with a single cycle (PDFS), and one with the principal cycles (PDFP). We found that Dice’s similarity coefficients comparing PDFP and PDFA (0.89±0.03) are significantly (p-value < 0.001) higher than those comparing PDFS and PDFA (0.83±0.05). Conclusion: Probability-driven sorting will generate multi-cycle 4D-MRI images with embedded information regarding breathing variation. Tumor motion PDFs determined in this manner are reproducible, which is important for accurate dose delivery.
Extracellular production of singlet oxygen by stimulated macrophages quantified using 9,10-diphenylanthracene and perylene in a polystyrene film

The extracellular production of singlet oxygen (O2(1 delta g)) by stimulated macrophages was measured using a modification of our quantitative method initially developed to measure the intracellular production of O2(1 delta g) by neutrophils (Steinbeck, M. J., Khan, A. U., and Karnovsky, M. J. (1992) J. Biol. Chem. 267, 13425-13433). Glass coverslips were coated with the specific chemical trap for O2(1 delta g), 9,10-diphenylanthracene (DPA) and perylene, which is an internal standard, in a methylene chloride solution containing 0.3 mg/ml polystyrene. On evaporation, the polystyrene formed an even coating of DPA and perylene over the surface of a glass coverslip (PDP film). Unstimulated macrophages or macrophages stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (fMLP) were then added to the PDP film in a darkened room and incubated at 37 degrees C for 30 min in a humidified 5% CO2 atmosphere. Both unstimulated and stimulated cells adhered to the PDP film in approximately equivalent numbers. Only stimulated cells produced measurable amounts of O2(1 delta g) in a dose-dependent response to either PMA or fMLP. The production of O2(1 delta g) by macrophages stimulated with PMA was maximal in response to 25 ng, 17.8 +/- 1.3 nmol of O2(1 delta g)/approximately 1.00 x 10(6) cells. The maximal response for fMLP was at a concentration of 1 microM, 18.4 +/- 1.0 nmol of O2(1 delta g)/approximately 1.00 x 10(6) cells. The specific detection of O2(1 delta g) by this method was confirmed by thermally releasing O2(1 delta g) from the DPA-O2(1 delta g) reaction product, DPA-endoperoxide, regenerating the original DPA compound. Production of O2(1 delta g) by the stimulated cells was inhibited 80-89% by the addition of 60-120 micrograms of superoxide dismutase, an enzyme that converts superoxide to hydrogen peroxide and ground state molecular oxygen or 79-84% with the addition of 2 mM histidine, an avid quencher of O2(1 delta g). Neither of these additions interfered with adhesion of the cells to the PDP film. The ability of superoxide dismutase to inhibit the production of O2(1 delta g) suggested that O2(1 delta g) was produced via a superoxide-dependent route. The ability of an oxidase to produce O2(1 delta g) secondary to superoxide production was substantiated further using a xanthine oxidase-acetaldehyde system. Purified xanthine oxidase produced both superoxide and O2(1 delta g), and their production was inhibited by the addition of superoxide dismutase.(ABSTRACT TRUNCATED AT 400 WORDS)