cssi/SciSciGPT-SciSciNet huggingface dataset:
In Vivo Effect of Innate Immune Response Modulating Impurities on the Skin Milieu Using a Macaque Model: Impact on Product Immunogenicity.

Unwanted immune responses to therapeutic proteins can severely impact their safety and efficacy. Studies show that the presence of trace amounts of host cells and process-related impurities that stimulate pattern recognition receptors (PRR) can cause local inflammation and enhance product immunogenicity. Here we used purified PRR agonists as model impurities to assess the minimal level of individual innate immune response modulating impurities (IIRMIs) that could activate a local immune response. We show that levels of endotoxin as low as 10 pg (0.01 EU), 1 ng for polyinosinic:polycytidylic acid (PolyI:C), 100 ng for synthetic diacylated liopprotein, thiazoloquinolone compound, or muramyl dipeptide, 1 μg for flagellin or β-glucan, or 5 μg for CpG-oligodeoxynucleotide increased expression of genes linked to innate immune activation and inflammatory processes in the skin of rhesus macaques. Furthermore, spiking studies using rasburicase as a model therapeutic showed that the levels of PRR agonists that induced detectable gene upregulation in the skin were associated with increased immunogenicity for rasburicase. This study underscores the need for testing multiple IIRMIs in biologics, strengthening the connection between the local mRNA induction in skin, innate immune activation, and antibody development in primates, and provides an indication of the levels of IIRMI in therapeutic products that could impact product immunogenicity.
The everyday dynamics of rumination and worry: precipitant events and affective consequences

Rumination and worry are two perseverative, negatively valenced thought processes that characterise depressive and anxiety disorders. Despite significant research interest, little is known about th...
Book Review: Urquhart, J., Acott, T.G., Symes, D. and Zhao, M., editors. 2014: Social Issues in Sustainable Fisheries Management

Urquhart, J., Acott, T.G., Symes, D. and Zhao, M., editors. 2014: Social Issues in Sustainable Fisheries Management (Series Volume 9). MARE Publication Series. Netherlands: Springer. 355 pp. $129.00/€109, 99/£82.00. ISBN: 978–94-007–7910–5 (Hardcover). $99.00/€91.62/£64. ISBN: 99 978–94-007–7911–2 (eBook).
Experimental demonstration of 55-fs spin canting in photoexcited iron nanoarrays

As magnetic storage density approaches 1TB/in2, a grand challenge is looming as how to read/write such a huge amount of data within a reasonable time. The ultrafast optical manipulation of magnetization offers a solution, but little is known about the intrinsic speed limit of quantum spin switching. Here, we report that low-energy 50-fs laser pulses can induce spin canting in Fe nanoparticles within 55 fs, breaking the previous record by at least one order of magnitude. Both linearly and circularly polarized light can be used to tilt spins. In our model, the incident laser field first excites the orbital angular momentum, and through spin-orbit coupling, the spin cants out-of-plane and results in a distinctive diamond hysteresis loop. The spin canting time decreases with spin angular momentum. This spin canting is not limited to Fe nanoparticles and is also observed in Fe/Pt and Fe3O4 nanoparticles. Our results demonstrate the potential of magnetic nanostructures as a viable magnetic medium for high densi...
Parental Grief and Mourning in the Ancient Andes

Parental grief is an intense emotion shaped and mediated by cultural attitudes toward death, the strength of parent-child attachment, the age of the deceased child, and the role of children in society. Despite some assertions that high infant mortality or economic hardship may lessen parental grief, cross-cultural studies show that child death often causes emotional distress to parents, in particular mothers. Funerary treatments of children, especially infants, are often simplified, contradicting more immediate and immaterial expressions of parental grief that cannot be studied archaeologically. In this study, I examine the funerary treatment of children in ancient Andean Tiwanaku society (A.D. 500–1100). I assess the use of ritual practices and objects associated with children’s burials as indicative of children’s social identities and parental mourning. The nature of grave assemblages in regard to different ages of the children suggests that parental attitudes toward their children changed over the course of childhood. The choice of offerings seems to reflect parental attachment to and recognition of the child’s life. Modifications of ceramic vessels point to the intimate mourning gestures of grieving mothers who sought to provide their deceased children with the necessary offerings to assume their place among the community of venerated ancestors. This study draws on ethnographic, psychological, and ethnohistoric sources of parent-child bonds in the Andes and beyond to investigate children’s burials not merely as reflective of childhood and children’s role in society but as the material record of parental attachment and emotion in the past.
Socio-economic status over the life course and obesity: Systematic review and meta-analysis

Background The purpose of this review was to summarize the published literature on the association of childhood, adulthood and life course socio-economic status (SES) with obesity between January 1990 and June 2015. Methods The major medical electronic databases were searched to identify studies that examined SES over the life-course in relation to obesity. A total of 219 studies were identified through the initial search, and 35 qualified for full review. Of these, 14 publications met our inclusion criteria for the meta-analysis, all from developed or upper-middle income countries. Results There was a consistent association between lower life course SES and obesity among women (summary OR: 1.35, 95% CI: 1.04, 1.76), but not among men (summary OR: 0.92, 95% CI: 0.60, 1.40). Overall, mean BMI was higher among individuals with lower life course SES compared with those with higher life course SES (summary mean BMI difference: 0.65, 95% CI: 0.59, 0.71). Mean waist circumference (WC) was higher among women with lower life course SES compared with those with higher life course SES (summary mean WC: 4.67, 95% CI: 4.15, 5.20), but lower among men (summary mean WC difference: -0.10, 95% CI: -0.11, -0.08). Conclusion The inverse relationship between life course SES and obesity among women was consistent, based mostly on studies in developed countries. Nevertheless, critical information gaps remain in relation to the impact of childhood and life course SES on obesity in developing countries.
Bathymetric distributions of notothenioid fishes

There has been no comprehensive study of the bathymetry of notothenioid fishes. Therefore, I analyzed minimum and maximum depths and depth ranges for 128 of 142 species that collectively range from 0 to ≈3000 m. Means (and medians) for maximum depths are 176 m (75 m) for non-Antarctic, 511 m (360 m) for sub-Antarctic, and 963 m (899 m) for Antarctic species; medians are significantly different. Means (and medians) for depth ranges for the three groups are 140 (55 m), 470 (345 m), and 727 m (714 m), respectively, with significantly different medians. The mean maximum depths for the Cryonotothenioidea are: Nototheniidae—525 m, Harpagiferidae—88 m, Artedidraconidae—906 m, Bathydraconidae—1165 m, and Channichthyidae—910 m. If five species of Bathydraco, with a mean of 2098 m are excluded, the mean for the Bathydraconidae is 741 m. With the exceptions of the harpagiferids and Bathydraco, there is overlap of the 95% confidence intervals for the means of other families. Thirteen Antarctic and sub-Antarctic species with maximum depths and/or depth ranges ≥1500 m are especially deep-living: four nototheniids, four species of Bathydraco, three species of Pogonophryne, and two channichthyids. The most common depth range is 0–50 m for non-Antarctic, 200–400 m for sub-Antarctic and 600–800 m for Antarctic species. Three species have depth ranges >2000 m. Species diversity peaks at 50 m for non-Antarctic, 100 m for sub-Antarctic, and 500 m for Antarctic species. Notothenioids are not eurybathic compared with older deep-sea taxa but are eurybathic relative to marine percomorphs.
The Two Poles of Parrhēsia and Concluding Remarks

This chapter unpacks Foucault’s last two hours of lectures at the College de France in 1984 shortly before his death. He traces the way that the meaning of parrhēsia, one specific practice that is a part of the care of the self, changes over time, splitting into two different directions. Foucault calls them the “poles” of parrhēsia. In the Christian tradition, parrhēsia will become related to a renunciation of the flesh, the practice of confession—a practice that can only be mediated by ecclesiastical authorities. Foucault’s argument provides further support for my own: that disagreements about the proper way to care for the self are at the heart of differences between early Christ movements rather than doctrinal disputes per se.
The Greek Passion

Gill traces Nikos Kazantzakis’s understanding of the philosophical and theological concept of the nature of humanity in the novel The Greek Passion. This novel is about a Greek village’s reenactment of the Passion Play. Gill extrapolates how the sociopolitical dynamics and conflicts between the local village religious leaders and those who fight on the side of religiously displaced refugees. Both personal conflicts and conflicts amongst groups are played against the backdrop of the drama of the local villagers.
Control of Electromechanical Actuators: Valves Tapping in Rhythm

Electromechanical valve (EMV) actuators can replace the camshaft allowing for electronically controlled variable valve timing (VVT) on a new generation of engines. Through the use of VVT, engine operation can be optimized to allow for improvements in fuel economy, performance, and emissions. Before EMV actuators can be used in production vehicles two critical problems need to be resolved. First, impact velocities between the valve, valve seat, and the actuator itself need to be small to avoid excessive wear on the system and ensure acceptable levels of noise. Second, the opening and closing of the valve needs to be both fast and consistent to avoid collision with the piston and to reduce variability in trapped mass. An extensive control analysis of the EMV actuator and the control difficulties are presented. Finally, a linear, a nonlinear, and a cycle-to-cycle self-tuning controllers are designed and demonstrated on a benchtop experiment.
CHAPTER III – FERMENTATION AND OXIDATION OF MAJOR METABOLIC FUELS

Publisher Summary This chapter describes the fermentation and oxidation of major metabolic fuels. In the metabolism of a cell or of complicated organisms, processes of great quantitative significance occur that result in the synthesis of molecules that are necessary for the formation of biological compounds and for the performance of physiological functions. These processes are the energy-yielding reaction sequences that couple with the reactions that make the improbable structures of biology. During glycolysis in muscle each glucose molecule is converted to two molecules of lactic acid. The products of fermentation of some microorganisms include butanol, acetone, butyric acid, acetic acid, acetone, butylene glycol, propionic acid, hydrogen, and other compounds in addition to the products formed by muscle and yeast. In general, all of these products result from variations in the terminal reactions of very similar sequences. The formation of the nicotinamide mononucleotide is catalyzed by a typical kinase, using adenosine triphosphate (ATP). A specific enzyme purified from human erythrocytes has been shown to form nicotinamide mononucleotide by a second mechanism, in which phosphoribosyl pyrophosphate and nicotinamide react to form inorganic pyrophosphate and the nucleotide. This nucleotide reacts with ATP to form a dinucleotide, in which the mononucleotides of nicotinamide and adenine are joined through a pyrophosphate bond.
Launching a New Fellowship for Medical Students: The First Years of the Doris Duke Clinical Research Fellowship Program

As part of its commitment to increasing the pipeline of physicians pursuing careers in clinical research, the Doris Duke Charitable Foundation launched the Doris Duke Clinical Research Fellowship (CRF) Program for medical students in 2000. The program, which is based at 10 US medical schools, provides medical students from any US medical school with the opportunity to spend 1 year obtaining both didactic and “hands-on” mentored clinical research experience. This article describes the program and summarizes the early outcomes collected during the first 3.5 years of the program. Interest in the program among medical students has been robust and widespread, with 35% of CRF program fellows matriculated at non-CRF schools. Exit surveys of the first three classes of fellows totaling 174 fellows indicated that (1) 97% of the fellows felt that participating in the fellowship was a good decision; (2) commitment to a career in clinical research was increased among the 44% of fellows reporting that they were unsure about pursuing a clinical research career when they began their fellowship; (3) there was no difference in satisfaction level between the fellows who remained at the medical schools in which they were matriculated and those who completed their fellowship at a medical school in which they were not matriculated; and (4) the majority of fellows responded that the didactic component of their fellowship was useful.
Global Movements In Education and their Impact on Diverse Students

Policymakers, business leaders, journalists, and parents in the United States have all called upon schools to better prepare students for success in a global world. Frequently, attempts to inject global education into public schools have been framed with the idea of global competencies for students. The term ‘global education competencies’ seems to be associated with both traditional liberal (e.g. Parker 2008) and neoliberal agendas for education. On the one hand, the neoliberal notion of global education is rooted in ideas of economic advancement and global competitiveness for U.S. interests (Friedman, 2005).
The Mysterious World of Symmetry in Physics

I describe the various ways in which the concept of symmetry is used in physics today. Starting from the notion of symmetry in art, I discuss briefly its applications to physics.
The Evolution of Wound Healing

Man’s struggle to heal wounds is as old as history itself. As life forms evolved from single cell life to amphibian and finally mammal, the pristine ability to heal by regeneration was lost and thus repairs by inflammation and subsequent deposition of matrix protein (scar) evolved as the method of mammalian healing. This evolutionary change leading to scar (the deposition of collagen) seems to be the key to preventing regeneration. It is well known that when the point is reached on the ladder where regeneration on longer occurs, inflammation and collagen deposition are the difference. In fact, if one takes a form of life, which seems the first link between regeneration and scar formation and a collagen cross-linking inhibitor is fed to the animal, then regeneration will once again occur! If we could only bridge this gap, imagine how successful we could become in the management of diabetic wounds. Although uncertain regarding why this occurred in the evolutionary process, it is hypothesized that as mammals became sophisticated, they needed rapid healing to protect themselves from other predators and to eke out a physical survival in a very hostile environment. In early-recorded history, the Egyptians repaired wounds with primitive suture materials (such as insect claws) and used clean sheets on surgical fields to prevent “suppuration.”; The Greeks, led by Hippocrates, devised methods of treatment for primary wounds and chronic wounds. They used various gauze materials empirically which included wine, milk, honey, and other substances in open wounds similar to our treatment today. Today, one can assign scientific rationale to some of these ancient empirical choices. For example, the complex sugars of honey are known to suppress the growth of Gram-positive bacteria. Wine will suppress pseudomonas proliferation. Milk products may contain cytokines or serve as buffers to control wound pH. Although the ancients had no idea that pus was actually is made up of proteins and dead leukocytes, they understood that drainage of localized products of infection was a good sign (laudable pus). They understood that when signs opf inflammation could not be localized that death would inevitably follow. During the early Roman era, Celsius, unaware of the existence of bacteria, did recognize and describe the cardinal signs of clinical infection being (1) rubor—erythema, (2) tumor—swelling, (3) dolor—pain, and (4) calor—heat.
Common conditions of the aging male: erectile dysfunction, benign prostatic hyperplasia, cardiovascular disease and depression.

With increasing life expectancy, medical profession will be faced with thetask of ensuring that the large, aging population remains healthy and vitaldespite the face of increasing healthcare costs. Naturally, urology as aspecialty is concerned with important geriatric issues. This article willfocus specifically on the aging male population and the health problems thatmost frequently plague them. Four major, non-cancer, disease states havebeen identified that adversely effect males over the age of 50. Theseconditions are: erectile dysfunction (ED), benign prostatic hyperplasia(BPH), cardiovascular disease (CVD) and depression.A literature search of PubMed was conducted using the key words ED, BPH,CVD and depression as well as ADAM (Androgen Decline in the Aging Male)and quality of life (QoL). NIH and WHO conference proceedings andpublications were also referenced to insure detail and accuracy of data.Information was then organized and correlated in order to provide adetailed description of the key conditions and their interrelatedness.The spectrum of research performed thus far regarding this topic has donelittle to investigate the effects, causes and correlations between theseconditions. Research has been done linking two or three of theseconditions; however, there remains to be information discussing the fourdisease states in terms of their possible cause and effect relationships orthe effectiveness of parallel, multi-disciplinary approach to their therapy.This report calls attention to the benefits of viewing and researching theabove mentioned conditions as possibly interrelated, as opposed to thetraditional view of them as separate, unrelated and independently treatabledisease states.ED, BPH, CVD and depression are all common conditions that accompanyaging and negatively impact QoL. They almost always develop with age andprecipitate considerable morbidity and may even result in mortality.Furthermore, the presentation of one condition may correlate with thedevelopment of another. The inter-relation of these conditions, as evidentfrom their underlying similarities, cause-and-effects relationships andtherapeutic consequences, should be enough to warrant a multidisciplinaryapproach to their research. This approach, combined with careful choice oftherapy, parallel and singular, will help providers reach their goal to keeppatients healthy, and more importantly happy, late into their life, thusrealizing the concept of ``successful aging''.
US Counterpoint to Chapter 14

Proper patient selection is critical to a successful outcome for an artificial urinary sphincter (AUS). The first key issue we determine is if the urinary incontinence is the result of intrinsic sphincter deficiency. We perform a urodynamics study, as well as leak-point pressure studies to distinguish a bladder etiology from a urinary sphincter etiology. A pressure flow study and flexible cystoscopy are done to evaluate the bladder outlet for obstruction or urethral stricture disease. The presence of overactive or neurogenic bladder by urodynamics demands initial treatment with anticholinergic therapy before any consideration of AUS. Patients who receive an AUS should have good manual dexterity and enough intellectual capacity to properly work the device. This should be evaluated preoperatively.
Particle Mobilization and Piping Erosion of Granular Soil Under Various Fluid Characteristics and Flow Conditions

This paper presents the soil’s internal erosion in earthen embankments due to seepage with various physicochemical fluid characteristics and flow conditions. The paper includes two components: (1) experimental study on the relative and interactive effects of fluid’s viscosity, pH, and ionic strength on the incipient motion of a single granular particle under laminar flow condition, and (2) bench-scale piping erosion progression of sand considering the same seepage’s physicochemical characteristics under turbulent flow. An innovative experimental setup was designed and constructed that can simultaneously adjust fluid’s viscosity, pH, and ionic strength and provide repeatable test results on particle’s incipient motion and soil erosion rate index. This research showed the relative and interactive effects of three physicochemical characteristics (viscosity, pH and ionic strength) of permeating fluid on particle mobilization and on piping erosion of a sandy soil. This paper suggests in the field evaluation of piping in earthen embankments, if the subsurface seepage is known to possess different physicochemical characteristics from those of tap water or distilled water, the fluid’s properties should be considered in the laboratory tests of piping.
Optical Fiber Ultrasound Probe for Radiofrequency Ablation Temperature Monitoring: In-Vitro Results

Radiofrequency ablation (RFA) is a clinical technique which inactivates targeted biological tissues by heating to remove tumors or to cure diseases like atrial fibrillation. Temperature is a fundamental parameter for ablation dose control and treatment effect evaluation. This paper presents the design, fabrication and characterization of an all-optical fiber ultrasound temperature measurement probe. The novelty of this probe is to both generate and receive ultrasound optically through fibers. The ultrasound generation was achieved with a 425 μm multi-mode fiber based on photoacoustic (PA) principle and the receiving part applied a 125 μm single mode fiber with a Fabry-Perot (FP) interferometer on its tip. The temperature was measured through detecting the time-of-flight (TOF) of the reflected ultrasound pulses. The probe's feasibility of measuring temperature during ablation had been verified in vitro while excised bovine liver tissue was used as the ultrasound reflector.
A full-field crystal plasticity model including the effects of precipitates: Application to monotonic, load reversal, and low-cycle fatigue behavior of Inconel 718

Abstract This work advances a recently developed high-performance, full-field elasto-viscoplastic fast Fourier transform (MPI-ACC-EVPCUFFT) formulation to model large plastic deformation and low-cycle fatigue behavior of Inconel 718 (IN718). Specifically, the recently developed model of Eghtesad et al., 2020 [1] incorporating a strain rate, temperature, and strain-path sensitive hardening law based on the evolution of dislocation density and a slip system-level back-stress law influencing the resolved shear stress is advanced in several aspects. First, strengthening effects due to grain size and shape, solid solution, shearing of small precipitates, and Orowan looping around larger precipitates are incorporated into the initial slip resistance, which evolves with the hardening law including the latent hardening. Second, the resolved shear stress on the slip plane in the direction of slip is altered by accounting for the two orthogonal shear stress components and the three normal stress components, in addition to the slip system-level kinematic effects. The model is used to interpret the complex mechanical behavior and microstructural data for samples of alloy IN718 in additively manufactured (AM) forms before and after hot isostatic pressing (HIP) and in a wrought form. Voxel-based microstructural cells consistent with the characterization data are synthetically constructed to initialize the model setups for predicting simple compression, tension, load reversal, and low cycle fatigue behavior of the alloy. Variation in the microstructural features such as the distribution of grain size and shape, crystallographic texture, content of annealing twins, and precipitates among the samples facilitated reliable calibration and validation of the model parameters. Predicted anisotropy, tension/compression asymmetry, non-linear unloading upon the load reversal, the Bauschinger effect, reverse hardening, texture evolution as well as cyclic hardening/softening along with the mean stress relaxation during low-cycle fatigue are in good agreement with the corresponding experimental data for the alloy. Furthermore, the simulations based on the high-resolution microstructural cells facilitated the discussion of the mechanical fields induced by microstructure, and especially annealing twins.
Development of lysozyme loaded microneedles for dermal applications.

Abstract Microneedles are being widely explored for dermal delivery of macromolecules. They have the capability and the potential for entrapping enzymes such as lysozyme within a polymeric matrix that do not alter the protein integrity, enable a bolus or a sustained release. In this study, polymeric microneedles have been used to entrap lysozyme (14 kDa) using biodegradable and dissolving polymers such as Polyvinylpyrrolidone (PVP), Hyaluronic acid (HA), and Poly lactic co glycolic acid (PLGA). Microneedles were fabricated using mold casting technique. The structural strength was determined using texture analyzer where PLGA microneedles (16.56 ± 0.23 g) required a significantly higher puncture force as compared to PVP and HA microneedles (12.10 ± 0.04 g and 11.40 ± 0.32 g respectively). The release profile showed an instantaneous release in the case of PVP and HA with almost 50% of the drug released within the first 20 min in both cases and remaining drug was released within the next 2 h whereas Lysozyme entrapped in PLGA showed a release of 29.53 ± 0.78% of lysozyme 72 h. Lysozyme entrapped in microneedles was characterized using circular dichroism and SDS-page analysis for structural stability post microneedle fabrication. The stability studies were performed on these polymeric microneedles for understanding its delivery potential of bio-active lysozyme. At the end of 90 days lysozyme concentration entrapped was 90.35 ± 0.06% 93.76 ± 0.34% 91.74 ± 0.37% for PVP, HA and PLGA respectively. The protein integrity remained intact for three months (α + β) sheets remained intact in the three different polymeric microneedles. The enzyme assay showed that the enzyme entrapped inside microneedles is biologically active and could be used to lyse bacterial infections for dermal applications. However, a detailed analysis of protein formulations would be useful for extending microneedles applications in wounds, skin infections.
Varying the aspect ratio of toroidal ion traps: Implications for design, performance, and miniaturization

Abstract A large aspect ratio (AR) leads to higher ion capacity in miniaturized ion trap mass spectrometers. The AR of an ion trap represents the ratio between an extended trapping dimension and the characteristic trapping dimension. In contrast to linear and rectilinear traps, changing the AR of a toroidal ion trap (TorIT) results in changes to the degree of curvature and shape of the trapping potential, and hence, on performance as a mass analyzer. SIMION simulations show that higher-order terms in the trapping potential vary strongly for small and moderate AR values (below ∼10), with the effects asymptotically flattening for larger AR values. Because of the asymmetry in electrode geometry, the trapping center does not coincide with the geometric center of the trap, and this displacement also varies with AR. For instance, in the asymmetric TorIT, the saddle point in the trapping potential and the geometric trap center differ from +0.6 to −0.4 mm depending on AR. Ion secular frequencies also change with the AR. Whereas ions in the simplified TorIT have stable trajectories for any value of AR, ions in the asymmetric TorIT become unstable at large AR values. Variations in high-order terms, the trapping center, and secular frequencies with AR are a unique feature of toroidal traps, and require significant changes in trap design and operation as the AR is changed.
New Leaves of Dryopteris intermedia Develop More Slowly When the Petioles of Overwintering Leaves are Broken

Wintergreen ferns keep their leaves for an entire year before replacing them with new leaves in the spring. The overwintering leaves of Dryopteris intermedia provide carbon to the new leaves, and if these old leaves cannot become prostrate before winter via the hinge that develops at the base of the petiole, they are frost damaged and broken, which may affect the development of the new leaves in the subsequent year. I compared the vernal development of new leaves in D. intermedia between plants whose old leaves were intact and those whose petioles had been experimentally broken in the fall to determine the importance of the softening of the petiole-base in old leaves to the development of new leaves. Compared to the control, plants whose old leaves had broken petioles had a one-week delay in the development of their new leaves. This delay demonstrates that the evolutionary development of the petiole hinge may have been critical to the functional benefit associated with new leaf development in the wintergreen leaf habit in ferns.
Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein.

Immunotherapy using checkpoint blockers (antibodies) has been a major advance in recent years in the management of various types of solid cancers including lung cancer. One target of checkpoint blockers is programmed death ligand 1 (PD-L1) expressed by cancer cells, which engages programmed death 1 (PD-1) on T cells and Natural Killer (NK) cells resulting in suppression of their activation and cancer-killing function, respectively. Apart from antibodies, other clinically relevant agents that can inhibit PD-L1 are limited. PD-L1 protein stability depends on its glycosylation. Here we show that L-glutamine:D-fructose amidotransferase 1 (GFAT1) a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP) which produces uridine diphosphate-N-acetyl-β-glucosamine (UDP-GlcNAc), a precursor for glycosylation, is required for the stability of PD-L1 protein. Inhibition of GFAT1 activity markedly reduced interferon γ (IFNγ)-induced PD-L1 levels in various lung cancer cell lines. GFAT1 inhibition suppressed glycosylation of PD-L1 and accelerated its proteasomal degradation. Importantly, inhibition of GFAT1 in IFNγ-treated cancer cells enhanced the activation of T cells and the cancer-killing activity of NK cells. These findings support using GFAT1 inhibitors to manipulate PD-L1 protein level that could augment the efficacy of immunotherapy for lung cancer.
The Chemokine System and Arthritis

Rheumatoid arthritis (RA) affects 1% of the U.S. population, or 3 million people. RA is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, neovascularization, and progressive destruction of cartilage and bone. The cause(s) of RA remains poorly defined, but it is thought that both genetic and environmental factors, including molecular mimicry and host responses against cross-reactive antigens, lead to the development of autoimmune responses involving the joints. The goal of this chapter is to provide an overview of the contribution of members of the chemokine system to the immunopathogenesis of RA. This is of high clinical relevance because of the burgeoning interest in the use of chemokine and chemokine-receptor blockers in the treatment of a variety of inflammatory, autoimmune, and infectious disorders, including RA.
Classification of Initial Data for the Porous Medium Equation in N

Publisher Summary This chapter describes the classification of initial data for the porous medium equations in ℝ n . The chapter discusses the Cauchy problem for the porous medium equation with nonintegrable non-negative initial data. The chapter also discusses the implications of (s –AV D ) in relation to the solutions of (PM). It provides the meaning of a D (s) and its relation to the more intuitive quantity a B (s).
Avoiding Moral Bankruptcy

Faced with hundreds of clergy sexual misconduct cases last year, the Archdiocese of Boston hinted that it was considering filing for bankruptcy. Although it is hard to imagine an archdiocese or church filing for bankruptcy, bankruptcy has become an important forum for many social issues that cannot be easily resolved elsewhere. This Article explores the implications of a religious organization bankruptcy filing by focusing on four problems with the bankruptcy alternative: the possibility of dismissal for being filed in bad faith; the question of what church assets are subject to the process; the fact that the church might be subject to intrusive scrutiny; and the moral implications. Although these concerns suggest that a religious organization should file for bankruptcy only as a last resort, this Article concludes that, in some circumstances, a bankruptcy filing may be appropriate. Is bankruptcy always the answer? This may seem like an odd question with which to begin a discussion on clergy sexual misconduct and religious liberty. Indeed, as the number of cases involving priests in the Archdiocese of Boston mushroomed last year, the rumors that the Archdiocese was considering filing for bankruptcy took me—and I suspect most bankruptcy scholars—completely by surprise. It had never dawned on me that a religious organization would ever file for bankruptcy. But perhaps it should have. In the past two decades, bankruptcy has become the forum of choice for resolving social issues that can't easily be handled elsewhere, particularly when these issues give rise to widespread litigation. Think of asbestos liability. In 1982, when Johns Manville was facing an average of three new asbestos lawsuits every hour (and over 16,500 overall), it filed for bankruptcy in the hope of getting its litigation crisis under control.' Since then, dozens of ashes* Professor of Layv, University of Pennsylvania Law School. I am grateful to Mark Chopko, Bruce Marken, David Novak, Pat Schultz, and participants at The Impact of Clergy Sexual Misconduct Litigation on Religious Liberty Symposium on April 4, 2003 at Boston College Law School for helpful comments on earlier drafts; and to Michael Sherman for research assistance. Special thanks to Jo Ann Brighton for extensive discussions (and debates) about these issues. For discussion, see, for example, awn) A. SKEEI„ JR., DEBT'S DOMINION: A HISTORY OF BANKRUPTCY LAW IN AMERICA 217 (2001) (quoting KEVIN j..DELANEY, STRATEGIC
The climate impact of aviation aerosols

[1] A comprehensive general circulation model (GCM) is used to estimate the climate impact of aviation emissions of black carbon (BC) and sulfate (SO4) aerosols. Aviation BC is found not to exert significant radiative forcing impacts, when BC nucleating efficiencies in line with observations are used. Sulfate emissions from aircraft are found to alter liquid clouds at altitudes below emission (∼200 hPa); contributing to shortwave cloud brightening through enhanced liquid water path and drop number concentration in major flight corridors, particularly in the N. Atlantic. Global averaged sulfate direct and indirect effects on liquid clouds of 46 mWm−2are larger than the warming effect of aviation induced cloudiness of 16 mWm−2. The net result of including contrail cirrus and aerosol effects is a global averaged cooling of −21±11 mWm−2. These aerosol forcings should be considered with contrails in evaluating the total global impact of aviation on climate.
Symmetry relations of magnetic twin laws

Symmetry relationships between two simultaneously observed domain states (domain pair) are used to determine physical properties that can distinguish between the observed domains. Here the tabulation of these symmetry relationships is extended from non-magnetic cases to magnetic cases, in terms of magnetic point groups, i.e. all possible magnetic symmetry groups and magnetic twinning groups of domain pairs are determined and tabulated.
Control of thymidine kinase mRNA during the cell cycle.

Abstract To investigate the mechanism which controls the onset of DNA synthesis, we examined the regulation of thymidine kinase (TK) and its mRNA in the cell cycle. TK activity provides a useful marker for the onset of the S phase in mammalian cells. The present analysis of regulation of TK mRNA in BALB/c 3T3 cells showed that (i) the increase in TK activity depended on the availability of TK mRNA, (ii) the level of TK mRNA between G0 and S increased more than 20-fold, (iii) the rate of run-on TK transcription increased at most 2- to 4-fold between the G0 and S phases, (iv) the half-life of TK mRNA was greater than 8 to 12 h in the S and M phases and decreased as cells entered quiescence, (v) the TK mRNA increase was fully blocked by inhibition of protein synthesis by only 60%, (vi) this inhibition was completely effective for up to about 10 h following serum addition and progressively much less effective when the drugs were added later. These results suggest that the appearance of TK mRNA at the beginning of the S phase in serum-stimulated 3T3 cells is controlled not only by the rate of gene transcription but importantly also by the decreased rate of mRNA degradation. Similar mechanisms may be involved in regulation of the onset of DNA synthesis and the increase in TK mRNA since both are controlled in a manner consistent with a requirement for a labile protein.
A Critical Analysis of Cultivation Theory

This critical analysis of the "cultivation" literature reveals 3 conceptions of the term: (a) George Gerbner's macrosystem explanation of mass media processes and effects, (b) a pattern of operational practices that searches for relationships between television exposure and a wide range of cultivation indicators, and (c) a general forum of explorations of media influence where researchers break away from Gerbner's conceptualizations and boundaries. Using the criteria of heuristic value, empirical support, and precision, this essay evaluates the contribution this large cultivation literature has made to increasing our understanding of the mass media.
Community-Based Interventions in Asthma

Community and public health interventions provide potentially powerful means of decreasing morbidity, hospitalizations, emergency room visits, and mortality from asthma. This chapter thus provides an overview of community-based interventions, which have been demonstrated to be effective—and/or ineffective—in reducing the burden of disease, including development of asthma coalitions, interventions for both provider and patient education, environmental controls to reduce exposure to asthma triggers, and institutional policy and systems change. Perhaps most important is the demonstrated effect of integrated, comprehensive approaches to asthma management and control. A multidisciplinary approach spanning T1 through T4 translational research, coupled with public health activities is promising and has already demonstrated success in reducing the burden of disease.
Implementing a Notion of Modules in the Logic Programming Language Lambda-Prolog

Issues concerning the implementation of a notion of modules in the higher-order logic programming language λProlog are examined. A program in this language is a composite of type declarations and procedure definitions. The module construct that is considered permits large collections of such declarations and definitions to be decomposed into smaller units. Mechanisms are provided for controlling the interaction of these units and for restricting the visibility of names used within any unit. The typical interaction between modules has both a static and a dynamic nature. The parsing of expressions in a module might require declarations in a module that it interacts with, and this information must be available during compilation. Procedure definitions within a module might utilize procedures presented in other modules and support must be provided for making the appropriate invocation during execution. Our concern here is largely with the dynamic aspects of module interaction. We describe a method for compiling each module into an independent fragment of code. Static interactions prevent the compilation of interacting modules from being completely decoupled. However, using the idea of an interface definition presented here, a fair degree of independence can be achieved even at this level. The dynamic semantics of the module construct involve enhancing existing program contexts with the procedures defined in particular modules. A method is presented for achieving this effect through a linking process applied to the compiled code generated for each module. A direct implementation of the dynamic semantics leads to considerable redundancy in search. We present a way in which this redundancy can be controlled, prove the correctness of our approach and describe run-time structures for incorporating this idea into the overall implementation.
Random packing by matroid bases and triangles

Abstract Let M be a matroid on a finite set E ( M ). Then M is packable by bases if E ( M ) is the disjoint union of bases. A partial packing of M is a collection of disjoint bases whose union is a proper subset of E ( M ). M is a randomly packable by bases if every partial packing can be extended to a packing of M . This paper determines the structure of the matroids that are randomly packable by bases. It also gives a characterization, in terms of forbidden restrictions, of the simple matroids that are randomly packable by 3-circuits.
Modeling a low pressure steam-oxygen fluidized bed coal gasifying reactor

Abstract A comprehensive model accounting for the jetting region and homogeneous dilute phase reactions is developed for the adiabatic and continuous gasification of coal particles in a fluidized bed. The division of flows in the bed is determined by means of a modified two-phase theory which considers inlet gas jets, bubbles, free of particles, which develop at the top of the jets and grow in size as they rise, and an emulsion phase consisting of particles and the surrounding interstitial gas. The model describes the gasification of coal particles by pyrolytic devolatilization and three heterogeneous chemical reactions: oxidation by oxygen and steam, and reduction of carbon dioxide. Carbon monoxide and hydrogen produced by the heterogeneous reactions can be oxidized to carbon dioxide and steam by incoming oxygen within the dilute phase jets and bubbles. Furthermore, the water-gas shift reaction can occur in the dilute phase and interstitial gas. Simulations both with and without homogeneous reactions occurring in the jets and bubbles indicate that dilute phase homogeneous reactions have considerable influence on carbon conversion, bed temperature, and product gas composition. It has also been found that the jetting-emulsion mass and beat interchange has a substantial effect on overall bed performance and the temperature of the bed close to the inlet gas distributor. Results indicate that water-gas shift equilibrium is established rapidly and significant quantities of hydrogen and carbon monoxide and a nonuniform steam concentration are present within the combustion zone.
Understanding and harnessing the power of the cohort model in preparing educational leaders

(1997). Understanding and harnessing the power of the cohort model in preparing educational leaders. Peabody Journal of Education: Vol. 72, No. 2, pp. 66-85.
Reading epilepsy: Case report

Abstract Reading epilepsy as a new syndrome was first described in 1956 by Bickford et al., who classified their patients into two groups as primary and secondary. Symptoms of the primary group included: (a) absence of pathological signs; (b) seizures only following prolonged reading; (c) prodromal sensation of the jaw or actual “jaw clicking”; (d) generally normal resting EEG. Cases of secondary reading epilepsy were associated with more general epileptic disorder. To date, 24 cases, including the present one, have been reported. It is believed that the case herein described belongs in the category of primary reading epilepsy. The subject has had eleven seizures to date, all associated with reading and several preceded by stiffening or “quivering” of the jaw. Random 3/sec waves or 7/sec bursts have been noted on the EEG following prolonged periods of silent reading. The possible mechanisms causing seizures in association with reading are reviewed. The role of eyeball movements and/or eye strain might appear to be of some significance in the present case.
Simultaneous brightness contrast and the Pulfrich phenomenon.

If an object, moving from left to right, is viewed binocularly by an observer, and if a brightness reducing filter is placed in front of the observer’s left eye, the moving object will appear to be further away than it actually is. This demonstrates the Pulfrich phenomenon. The brightness of an object can be reduced in another way, through an intense inducing field, or glare source, placed nearby the object. This illustrates simultaneous brightness contrast. The present investigation concerns whether the Pulfrich phenomenon would occur if the brightness of the moving object were reduced (in one eye) not by a filter, but by an inducing field. Eight observers were used. When a filter was placed in front of the observer’s left eye, this produced a displacement of the moving object away from the observer. This was the Pulfrich effect. When an inducing field was presented slightly peripherally to the observer’s left eye, this produced a displacement of the moving object toward the observer, or in the opposite direction of the Pulfrich phenomenon. Displacement was directly proportional to inducing luminance. A “reverse” Pulfrich phenomenon occurred, therefore, when the brightness (to one eye) of a moving object was reduced by an inducing field rather than by a filter. From these results we can assume that the physiological mechanism for brightness reduction by an inducing field is different in whole or in part than that mechanism for brightness reduction by a filter.
Localization and characterization of binding sites for endothelin in Harder's gland in rabbits

The characterization and localization of binding sites for endothelin-1 (ET-1) labeled with iodine 125I were investigated in homogenized tissues and sections of Harder's glands of normal rabbits. The membrane of Harder's glands was harvested and incubated with 125I-ET-1 (0.25–1 nmol/L) in 20 ±4 mg of protein per 0.25 mL at 37°C for 90 min in the presence of protease inhibitors. Specific labeling was assessed by coincubating unlabeled ET-1, ET-2, ET-3 and other unrelated cytokines. The tissue labeled with 125I-ET-1 was collected by filtration and counted in a gamma counter. For an in vitro autoradiography study, 15 μm cryostat sections were incubated with 125I-ET-1 (0.1 nmol/L). They were fixed, dipped in liquid emulsion and kept for 6 days before development. Membrane counting showed that the binding of 125I-ET-1 to Harder's gland was saturable. Scatchard data analysis revealed one class of binding with a dissociation constant (Kd) of 0.33 nmol/L and a maximal density of binding (Bmax of 794 attomole/mg o...