cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel Cell Surface Targets for the Plasminogen Activating System in the Brain: Implications for Human Disease

Abstract The plasminogen (Pg) activator system plays an important role in the central nervous system (CNS), including processes of neuronal migration, neurite outgrowth, and neuronal plasticity. Pg and tissue-type plasminogen activator (t-PA) are primarily involved in fibrinolysis, however, they also play critical nonfibrinolytic functions in the CNS. Activation of Pg in the CNS is stimulated by unique cell surface protein complexes. One of such complexes involves the voltage-dependent anion channel 1 (VDAC1) in association with the Glucose Regulated Protein 78,000 (GRP78), t-PA, and Pg. VDAC1 is localized both at the mitochondrial and cell plasma membranes. In the mitochondria, VDAC1 transports ions, cholesterol, and metabolites across the outer mitochondrial and participates in the release of mitochondrial proapoptotic proteins to the cytosol. In cell plasma membranes, VDAC1 participates in the maintenance of redox homeostasis in normal cells and the promotion of anion efflux in apoptotic cells. VDAC and GRP78 are major players in the physical association between the endoplasmic reticulum (ER) and mitochondria which enables highly efficient transmission of Ca 2+ from the ER to mitochondria under both physiological and pathological conditions. GRP78 associates with VDAC1 both at the outer mitochondrial and plasma membranes. The brain is an organ devoid of fibrin, a protein essential for efficient Pg activation, however, GRP78 and VDAC mimic fibrin to enhance the activation of locally synthesized Pg and t-PA. These functions make VDAC1 and GRP78 a point of convergence for a large variety of cell survival and death signals.
Graphene coated iron oxide (GCIO) nanoparticles as efficient adsorbent for removal of chromium ions: Preparation, characterization and batch adsorption studies

Abstract Graphene coated iron oxide nanoparticles were prepared using microemulsion method for removal of Cr(VI) ions from aqueous solutions. Plausible interactions between the material and Cr(VI) ions were explored after adsorption and explained by characterizing through various analytical techniques such as Raman spectroscopy, LIBS, FTIR, TEM, EDX, SEM, particle size and zeta-potential measurements which confirmed 20% crystalline nature of GCIO, nanorange (50 nm) size of nanoparticles and great thermal stability. A simple, sensitive and highly selective direct spectrophotometric method was used for the determination of trace levels of Cr(VI) and various experimental parameters, such as the effect of time, pH, adsorbent dose, chromium concentration, temperature and composition of nanoparticles were studied on the adsorption of chromium. The equilibrium sorption data were fitted to various adsorption isotherm models and the as prepared GCIO adsorbent was found to follow the pseudo second order kinetics (R2 = 0.97) and Freundlich model isotherm (R2 = 0.97) with high adsorption capacity (352.1126 mg/g) for Cr(VI) adsorption. The nanoadsorbents were also found to be fairly reusable.
Paradoxical decrease in blood pressure after relief of cardiac tamponade: the role of sympathetic activity.

Background: In contrast to patients who develop acute cardiac tamponade after penetrating trauma, tamponade in medical patients may be accompanied by normal or even elevated systolic blood pressure. This has been attributed to heightened sympathetic nervous system activity. Case Report: We present a case of a medical patient with simultaneous hypertension and cardiac tamponade whose blood pressure fell dramatically after pericardiocentesis. We observed a decrease in normetanephrine levels in our patient concomitant with the decrease in blood pressure. Conclusions: Our case provides further support for involvement of the sympathetic nervous system in medical patients with hypertensive tamponade. To our knowledge, this is the first case documenting adrenergic status in a patient with a paradoxical decrease in blood pressure after relief of tamponade.
Clinical Significance of Sarcopenia among Patients with Advanced Oropharyngeal Cancer.

ObjectivesWe investigated the prevalence and impact of sarcopenia on disease-free survival (DFS) and overall survival (OS) in advanced oropharyngeal cancer.Study DesignRetrospective study.SettingSi...
Fundamentals of Systems Biology: From Synthetic Circuits to Whole-cell Models

For decades biology has focused on decoding cellular processes one gene at a time, but many of the most pressing biological questions, as well as diseases such as cancer and heart disease, are related to complex systems involving the interaction of hundreds, or even thousands, of gene products and other factors. How do we begin to understand this complexity? Fundamentals of Systems Biology: From Synthetic Circuits to Whole-cell Models introduces students to methods they can use to tackle complex systems head-on, carefully walking them through studies that comprise the foundation and frontier of systems biology. The first section of the book focuses on bringing students quickly up to speed with a variety of modeling methods in the context of a synthetic biological circuit. This innovative approach builds intuition about the strengths and weaknesses of each method and becomes critical in the book’s second half, where much more complicated network models are addressed—including transcriptional, signaling, metabolic, and even integrated multi-network models. The approach makes the work much more accessible to novices (undergraduates, medical students, and biologists new to mathematical modeling) while still having much to offer experienced modelers--whether their interests are microbes, organs, whole organisms, diseases, synthetic biology, or just about any field that investigates living systems.
Microfragmenting for the successful restoration of slow growing massive corals

Abstract Slow growing, massive stony corals have often been overlooked in reef-restoration activities, despite their resilience to climate change and contribution to reef framework. Techniques to effectively propagate and outplant these species have proven challenging. However, advancement in methodology may increase rates of success. In 2013, Orbicella faveolata and Montastrea cavernosa fragments were outplanted on reefs in the Florida Keys at a nearshore and offshore location, to determine whether “microfragmenting” corals, the process of creating ∼1 cm2 fragments, increased outplant survival and growth compared with larger fragments (16–64 cm2). Arrays of eight microfragments were planted near one larger fragment of similar size at each location. Six replicate pairs were haphazardly placed within each ∼700 m2 study site. Fragments at both sites were monitored for growth and survival over 31 months, spanning two bleaching events. Initial predation occurred on microfragments, but was absent in the larger fragments. Survival and growth differed between sites, but did not differ between the larger fragments and microfragment arrays. However, excluding plots with >40% predation at the nearshore site showed that O. faveolata microfragment arrays produced 10 times more tissue than traditionally used larger fragments. Results from this study suggest that if predation events are reduced, massive corals can be successfully grown and outplanted for restoration purposes.
Soil indicators of hydrologic health and resilience in cypress domes of West-Central Florida

Abstract Groundwater pumping in west-central Florida has caused water table declines that disrupt hydroperiods and negatively impact already threatened, geographically isolated freshwater wetlands in this region. Currently, aboveground biological indicators are used to determine the health status of wetlands impacted by groundwater withdrawals, however some soil properties, such as organic matter content, are partly a function of the duration of saturation and could be used as additional indicators. Therefore, this study evaluated soil organic carbon and related soil properties for comparison with the biological indicators of wetland health status. Soil samples were taken from the top 30 cm of the land surface (i.e., bulk density, soil water content, nitrogen content, and carbon and nitrogen isotopic composition) within pond cypress (Taxodium ascendens) domes previously categorized by the local water management district using wetland health classifications of “healthy”, “significantly changed”, or “severely changed”. Mean soil water content (w) was significantly higher in “healthy” wetlands as compared to “significantly changed” and “severely changed” sites, and “healthy” sites also tended to have lower bulk density and higher soil carbon and soil nitrogen content. This trend was most pronounced toward the center and lowest elevation of the wetland, presumably where soils remain saturated longest. Stable carbon isotope values (δ13C) of soil organic matter showed that “severely changed” sites exhibited more 13C-enriched values that arise from long term contributions of warm-season (C4) grasses, consistent with the observed upland grasses encroaching into the most impacted wetlands. Notably, soil characteristics may be crucial for determining the resilience of wetlands, as one sampled “healthy” site contained comparably less soil organic matter, reducing the water holding capacity and leaving it more vulnerable to water table declines. These results suggest that extensive annual saturation of soils is required to maintain the cypress dome ecological community structure and preserve wetland health and resilience. Frequent monitoring of soil water may prove a convenient proxy for soil water retention properties and ecosystem health of wetlands in similar settings.
Individual Molecular Dynamics of an Entangled Polyethylene Melt Undergoing Steady Shear Flow: Steady-State and Transient Dynamics.

The startup and steady shear flow properties of an entangled, monodisperse polyethylene liquid (C1000H2002) were investigated via virtual experimentation using nonequilibrium molecular dynamics. The simulations revealed a multifaceted dynamical response of the liquid to the imposed flow field in which entanglement loss leading to individual molecular rotation plays a dominant role in dictating the bulk rheological response at intermediate and high shear rates. Under steady shear conditions, four regimes of flow behavior were evident. In the linear viscoelastic regime ( γ ˙ τ e - 1 ), the entanglement network deteriorates such that some molecules become almost completely unraveled, and molecular tumbling becomes the dominant relaxation mechanism. The comparison of transient shear viscosity, η + , with the dynamic responses of key variables of the tube model, including the tube segmental orientation, S , and tube stretch, λ , revealed that the stress overshoot and undershoot in steady shear flow of entangled liquids are essentially originated and dynamically controlled by the S x y component of the tube orientation tensor, rather than the tube stretch, over a wide range of flow strengths.
Simulating Random Numbers from a Uniform Distribution

Because many statistical methods rely on random samples, applied statisticians often need a source of “random numbers”. Older reference books for use in statistical applications contained tables of random numbers, which were intended to be used in selecting samples or in laying out a design for an experiment. Statisticians now rarely use printed tables of random numbers, but occasionally computer-accessed versions of such tables are used. Far more often, however, the computer is used to generate “random” numbers directly.
Ancient medicinal plants of South America.

Many archaeologists suggest that shamanic practices are ancient, starting at least 30,000 y ago (1⇓–3). As an analytical concept, anthropologists define shamans as religious practitioners who interact directly with the spirit world to help their people. Shamans in each culture have their own practices and are called by different names (e.g., chayanyi , curanderos , or vegetalistas ). Shamanic practices are found in indigenous groups all over the globe, from Australia to the Arctic. The core of these practices is altered states of consciousness (ASC), during which the shaman is able to perceive and interact with the spirit world. However, the rituals used to initiate ASC greatly vary, from Australians walking into their Dreamtime to Siberian shamans drumming into trance states (4). There are many purposes for these states, but ultimately, they are the gateway to spirits and deities who help cure the sick, bring rain, find lost objects, or otherwise help people medically, physically, emotionally, and/or spiritually (4, 5). Human neurology and physiology enable people to enter trance states, which can range in intensity and duration from a sort of daydreaming-like state to having powerful hallucinations while catatonic (6). Hallucinations can be initiated using various methods, including fasting, chanting, drumming, sensory deprivation, extreme pain, and consuming psychoactive plants. Often, shamans combine these various methods and will sometimes use psychoactive plants when they are available. These psychoactive agents can be consumed in a variety of ways, including simply eating them [e.g., the Huichols of west Mexico eat fresh and dried peyote buttons (7)], inhaling them as snuff [e.g., the Yanomamo of Venezuela inhale yakoana powder (8)], using enemas [e.g., the Maya used ritual enemas laced with various psychoactive plants (9)], and brewing them (8). South American shamans brew a tea called ayahuasca, which is the focus of … [↵][1]1Email: vanpoolc{at}missouri.edu. [1]: #xref-corresp-1-1
An evaluation of United States forest Service prescribed fire regimes in East Texas

Abstract The National Forests and Grasslands in Texas (NFGT) adopted a standardized methodology to collect vegetation data in regards to both short-term and long-term effects of their prescribed fire regimes in Texas National Forests. Using this methodology, 24 research plots were installed in six unique forest cover/monitoring types in East Texas on the Sam Houston, Davy Crockett, and Angelina/Sabine National Forests. Each forest has defined objectives and target goals based on forest composition and cover type. The effectiveness of existing burn regimes and prescriptions was analyzed using data collected between 2015 and 2018 and comparing outcomes to the ecosystem-specific objectives outlined by NFGT. Ecosystem-specific objectives include parameters regarding fuel loads, litter depth, percent herbaceous cover, and understory woody stem density. Under current burn practices, the majority (85%) of objectives are not being met. Our findings suggest there is need to review or modify existing definitions and verify if current objectives are realistically achievable. Linear curve predictive models display a strong correlation between overstory density and litter weight. The models illustrate deleterious effects on herbaceous species composition from the encroachment of woody stems, as well as the benefits of frequent prescribed burns for improving herbaceous composition while reducing understory woody stem intrusion. Recommendations include altering current burn seasons and ignition patterns to be more analogous to historical standards, as well as reducing overstory tree basal area to more effectively obtain desired stand conditions and meet the defined ecosystem-specific objectives.
The voice handicap index (VHI) : Development and validation

To date, no instruments exist to quantify the psychosocial consequences of voice disorders. The aim of the present investigation was the development of a statistically robust Voice Handicap Index (...
Dissecting the Flipped Classroom: Using a Randomized Controlled Trial Experiment to Determine When Student Learning Occurs

The use of the flipped classroom approach in higher education STEM courses has rapidly increased over the past decade, and it appears this type of learning environment will play an important role i...
Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP)

The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (TH2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E2 (PGE2) in the upper airway. Blood monocyte-derived, and tissue-derived iLCs from RRP patients and controls were now studied to more fully understand innate immune dysregulation in RRP. Patients' monocytes generated fewer iLCs than controls, due to a reduced fraction of classical monocytes that generated most but not all the iLCs. Prostaglandin E2, which was elevated in RRP plasma, reduced monocyte-iLC differentiation from controls to the levels of RRP patients, but had no effect on subsequent iLC maturation. Cytokine/chemokine responses by iLCs from papillomas, foreskin, and abdominal skin differed significantly. Freshly derived tissue iLCs expressed low CCL-1 and high CCL-20 mRNAs and were unresponsive to IL-36γ stimulation. Papilloma iLCs uniquely expressed IL-36γ at baseline and expressed CCL1 when cultured overnight outside their immunosuppressive microenvironment without additional stimulation. We conclude that monocyte/iLC innate immunity is impaired in RRP, in part due to increased PGE2 exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting TH2-like/Treg HPV-specific adaptive immunity in RRP.
Systemic Treatment of Hand Eczema: Methotrexate

Methotrexate has antiproliferative, anti-inflammatory, and immunosuppressive effects. It is used for a variety of dermatoses, most notably psoriasis. Various studies have demonstrated efficacy in difficult-to-control eczema, though published data for hand eczema are limited. It should be considered an option for hand eczema that is recalcitrant to nonsystemic treatments. Adverse effects, including hepatotoxicity, pulmonary toxicity, hematologic effects, gastrointestinal effects, renal effects, and malignancy, must be discussed with patients. Careful monitoring and frequent visits with patients initially are imperative. Magnetic resonance elastography may represent a less invasive approach in monitoring hepatic fibrosis.
P.1.08 Connecting contractor safety management programs and worker perceived safety climate in commercial construction projects

Background Leading indicators are preferred to identify injuries and fatalities in construction industry. Safety climate is a leading indicator of construction injuries yet it is not known how workers’ safety climate scores relate to safety programs of different maturity levels. Methods This study examined the relationship between safety program scores based on documents and contractor reported activities and project leading indicators of contractor safety climate, safety behaviors of workers and crews, and safety attitudes of coworkers from employee surveys. Hierarchical linear regression models accounted for contractor size and number of workers, nested in contractors within projects. Separate models examined the relationships between safety program scores and 1) contractor safety climate; 2) coworker attitude scores, 3) employees’ own behavior score, and 4) crew behavior scores. Results 446 employees of 40 contractors from three commercial construction projects participated. Many contractors (n=16) had good safety programs with 15 or more safety activities (out of 17) from organizational management, worker participation, hazard identification, and training domains. Stronger safety programs had higher safety climate scores (5.15 point difference on a 100 point scale, p=0.05), better coworker safety attitudes (6.69 points, p=0.01), better crew safety behaviors (5.34 points, p=0.02) and higher self-rated behaviors (5.14 points, p=0.02) compared to safety programs with fewer safety items. Conclusions Contractors with more comprehensive safety programs were perceived to have stronger safety climate. Better safety programs were also associated with better self-reported safety performance of coworkers, crews, and individual workers. Stronger safety programs incorporated activities from all four domains Safety programs that include activities that cover safety of management and worker influence safety performance and safety climate as perceived by the workers.
Analysis of DNA methylation using pyrosequencing

Abstract Accurate site-specific quantification of DNA methylation is readily achieved via bisulfite conversion, accompanied by sequencing- or array-based technologies. Pyrosequencing has been established as the “gold standard” for DNA methylation analysis, providing an efficient, reproducible, easy, and cost effective tool for the quantification of DNA methylation at individual CpG sites on a regional scale. It can be used as a stand-alone technique to assess DNA methylation at candidate loci, or is often used as a validation tool for other higher throughput assays. In addition to its primary use as a tool for accurate quantitation of DNA methylation, it can be used to define changes in DNA hydroxymethylation, and for analysis of genetic variation, with specific applications for microbial and viral typing, and pharmacogenetics research. In the following chapter, we outline the principles of the pyrosequencing methodology, including an overview of the method and limitations of the technique, and also describe the applications of pyrosequencing, giving specific examples of how it has been used to detect altered DNA methylation in complex diseases and in response to environmental stimuli, and as a tool for understanding genetic variation.
"Are They Saying It How I'm Saying It?" A Qualitative Study of Language Barriers and Disparities in Hospice Enrollment.

Abstract Context Language barriers contribute significantly to disparities in end-of-life (EOL) care. However, the mechanisms by which these barriers impact hospice care remains underexamined. Objectives To gain a nuanced understanding of how language barriers and interpretation contribute to disparities in hospice enrollment and hospice care for patients with limited English proficiency. Methods Qualitative, individual interviews were conducted with a variety of stakeholders regarding barriers to quality EOL care in diverse patient populations. Interviews were audiorecorded and transcribed verbatim. Data were coded using NVivo 11 (QSR International Pty Ltd., Melbourne, Australia). Three researchers analyzed all data related to language barriers, first individually, then in group meetings, using a grounded theory approach, until they reached consensus regarding themes. Institutional review board approval was obtained. Results Twenty-two participants included six nurses/certified nursing assistants, five physicians, three administrators, three social workers, three patient caregivers, and two chaplains, self-identifying from a variety of racial/ethnic backgrounds. Three themes emerged regarding language barriers: 1) structural barriers inhibit access to interpreters; 2) variability in accuracy of translation of EOL concepts exacerbates language barriers; and 3) interpreters' style and manner influence communication efficacy during complex conversations about prognosis, goals of care, and hospice. Our theoretical model derived from the data suggests that Theme 1 is foundational and common to other medical settings. However, Theme 2 and particularly Theme 3 appear especially critical for hospice enrollment and care. Conclusion Language barriers present unique challenges in hospice care because of the nuance and compassion required for delicate goals of care and EOL conversations. Reducing disparities requires addressing each level of this multilayered barrier.
Exploring internal state-coding across the rodent brain

The influence of peripheral physiology on goal-directed behavior involves specialized interoceptive sensory neurons that signal internal state to the brain. Here, we review recent progress to examine the impact of these specialized cell types on neurons and circuits throughout the central nervous system. These new approaches are important for understanding how the needs of the body interact and guide goal-directed behaviors.
Target Detection in Cluttered Environments Using Infra-Red Images

The detection of targets in infra-red imagery is a challenging problem which involves locating small targets in heavily cluttered environments while maintaining a low false alarm rate. We propose a network that optimizes a “target to clutter ratio” (TCR) metric defined as the ratio of the output energies produced by the network in response to targets and clutter. We show that for target detection, it is advantageous to analytically derive the first layer of a CNN to maximize the TCR metric, and then train the rest of the network to optimize the same cost function. We evaluate the performance of the resulting network using a public domain MWIR data set released by the US Army’s Night Vision Laboratories, and compare it to the state-of-the-art detectors such as Faster RCNN and Yolo-v3. Referred to as the TCRNet, the proposed network demonstrates state of the art results with greater than 30% improvement in probability of detection while reducing the false alarm rate by more than a factor of 2 when compared to these leading methods. Ablation studies also show that the proposed approach and metric are superior to learning the entire network from scratch, or using conventional regression metrics such as the mean square error (MSE).
Work Characteristics, Body Mass Index, and Risk of Obesity: The National Quality of Work Life Survey.

Objectives To examine work characteristics in relation to body mass index (BMI) and risk of obesity. Methods We analyzed data from 1150 participants working 20+ h week-1 from the 2014 National NIOSH Quality of Work Life Survey, based on a representative sample of US workers. We used multiple linear regression for BMI and multiple logistic regression for obesity to estimate associations with 19 different work characteristics plus one set of occupational categories controlling for age, gender, race/ethnicity, education, marital status, job physical exertion, and television watching. Results We found significant positive linear associations between BMI and night shift (versus day shift) schedule (B = 2.28, P = 0.008) and blue-collar (versus management/professional) work (B = 1.75, P = 0.008). Night shift schedule [odds ratio (OR) = 2.19, P = 0.029], sales/office work (OR = 1.55, P = 0.040), and blue-collar work (OR = 2.63, P = 0.006) were associated with increased risk of obesity versus 'healthy weight'. No other statistically significant associations between work characteristics and BMI or obesity were observed. Conclusions Night shift schedule and blue-collar work were related to increased BMI and obesity risk in US workers in 2014. Identifying risk factors in blue-collar work and redesigning jobs to reduce those risk factors, and reducing night shift work, could play a role in reducing the prevalence of obesity in the USA.
Holographic confinement in inhomogeneous backgrounds

As noted by Witten, compactifying a d-dimensional holographic CFT on an S 1 gives a class of (d − 1)-dimensional confining theories with gravity duals. The proto-typical bulk solution dual to the ground state is a double Wick rotation of the AdS d+1 Schwarzschild black hole known as the AdS soliton. We generalize such examples by allowing slow variations in the size of the S 1, and thus in the confinement scale. Coefficients governing the second order response of the system are computed for 3 ≤ d ≤ 8 using a derivative expansion closely related to the fluid-gravity correspondence. The primary physical results are that i) gauge-theory flux tubes tend to align orthogonal to gradients and along the eigenvector of the Hessian with the lowest eigenvalue, ii) flux tubes aligned orthogonal to gradients are attracted to gradients for d ≤ 6 but repelled by gradients for d ≥ 7, iii) flux tubes are repelled by regions where the second derivative along the tube is large and positive but are attracted to regions where the eigenvalues of the Hessian are large and positive in directions orthogonal to the tube, and iv) for d > 3, inhomogeneities act to raise the total energy of the confining vacuum above its zeroth order value.
Nitrene Photochemistry of Manganese N-Haloamides**

Manganese complexes supported by macrocyclic tetrapyrrole ligands represent an important platform for nitrene transfer catalysis and have been applied to both C-H amination and olefin aziridination catalysis. The reactivity of the transient high-valent Mn nitrenoids that mediate these processes renders characterization of these species challenging. Here we report the synthesis and nitrene transfer photochemistry of a family of MnIII N-haloamide complexes. The S=2 N-haloamide complexes are characterized by 1 H NMR, UV-vis, IR, high-frequency and -field EPR (HFEPR) spectroscopies, and single-crystal X-ray diffraction. Photolysis of these complexes results in the formal transfer of a nitrene equivalent to both C-H bonds, such as the α-C-H bonds of tetrahydrofuran, and olefinic substrates, such as styrene, to afford aminated and aziridinated products, respectively. Low-temperature spectroscopy and analysis of kinetic isotope effects for C-H amination indicate halogen-dependent photoreactivity: Photolysis of N-chloroamides proceeds via initial cleavage of the Mn-N bond to generate MnII and amidyl radical intermediates; in contrast, photolysis of N-iodoamides proceeds via N-I cleavage to generate a MnIV nitrenoid (i.e., {MnNR}7 species). These results establish N-haloamide ligands as viable precursors in the photosynthesis of metal nitrenes and highlight the power of ligand design to provide access to reactive intermediates in group-transfer catalysis.
Parameters of Tumor Microenvironment Determine Effectiveness of Anti-PD-1/PD-L1 Therapy

Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world are trying to answer the question on how to select a target that would be effective and, in general, they are quite successful at that. The Nobel Prize-winning discovery of mechanisms for regulating activity of the immune system cells through checkpoint molecules, as well as discovery of the ability of tumor cells to use these mechanisms to suppress immune responses was an impetus for the development of modern immunotherapy, and now such inhibitors of the immune checkpoints as PD-1/PD-L1 are included in the routine chemotherapy. Use of such drugs can prolong the patient’s life, but, unfortunately, not cure the disease. This is partially due to heterogeneity of tumor cells and microenvironment, but the main reasons may be in the complex relationships between the tumor and microenvironment, which, at times, are so plastic that they can change, adjusting to newly emerging conditions. Main characteristic of the tumor microenvironment is the type of the ongoing immune-inflammatory response (IIR), and since inhibitors of the immune checkpoints act on the cells involved in IIR, it is obvious that the outcomes of cancer therapy, including outcomes of hyperprogressive disease, can be associated with this parameter. The presented review reveals the essence of interactions between the tumor and its microenvironment during therapy with PD-L1 inhibitors.
Coevolution of nonlinear trends in vegetation, soils, and topography with elevation and slope aspect: A case study in the sky islands of southern Arizona

[1] Feedbacks among vegetation dynamics, pedogenesis, and topographic development affect the “critical zone”—the living filter for Earth's hydrologic, biogeochemical, and rock/sediment cycles. Assessing the importance of such feedbacks, which may be particularly pronounced in water-limited systems, remains a fundamental interdisciplinary challenge. The sky islands of southern Arizona offer an unusually well-defined natural experiment involving such feedbacks because mean annual precipitation varies by a factor of five over distances of approximately 10 km in areas of similar rock type (granite) and tectonic history. Here we compile high-resolution, spatially distributed data for Effective Energy and Mass Transfer (EEMT: the energy available to drive bedrock weathering), above-ground biomass, soil thickness, hillslope-scale topographic relief, and drainage density in two such mountain ranges (Santa Catalina: SCM; Pinaleno: PM). Strong correlations exist among vegetation-soil-topography variables, which vary nonlinearly with elevation, such that warm, dry, low-elevation portions of these ranges are characterized by relatively low above-ground biomass, thin soils, minimal soil organic matter, steep slopes, and high drainage densities; conversely, cooler, wetter, higher elevations have systematically higher biomass, thicker organic-rich soils, gentler slopes, and lower drainage densities. To test if eco-pedo-geomorphic feedbacks drive this pattern, we developed a landscape evolution model that couples pedogenesis and topographic development over geologic time scales, with rates explicitly dependent on vegetation density. The model self-organizes into states similar to those observed in SCM and PM. Our results highlight the potential importance of eco-pedo-geomorphic feedbacks, mediated by soil thickness, in water-limited systems.
From Combat to Legacies: Novels of the Vietnam War.

any people regard America's participation in the Vietnam War as our most crucial national experience in modern times, one that continues to shape national policy and our attitudes toward others and ourselves. It is, therefore, important that we help our students understand this important event, particularly if, as historian Allen Goodman argues, we are going to help students to consider "how long the aftermath of the Vietnam War will continue to shape their lives and society" (1990, A36). One of the problems, however, in trying to teach students about the war is that they are woefully ignorant of America's recent historical and literary past. As N. Bradley Christie (1989) notes-and research (Johannessen 1992; Starr 1988) confirms-"the Vietnam War might as well be the Peloponnesian War for all [the high school students] know." Christie also points out that even though our students come to us with very little real knowledge of the war, they do have a strong desire to learn more. Unfortunately, their knowledge of the war does not go much beyond Hollywood's Rambo series or various adventure novels, such as the Saigon Commando or Night Fighters series, in which Vietnam is merely a backdrop, or the romantic novels, such as those by Ellen Elliot, Della Field, and Evelyn Hawkins (all called Vietnam Nurse) that are "little more than Harlequin romances set in Vietnam" (Puhr 1988, 174). Ironically, most of our students know more about the Civil War than
Role of humans in complexity of a system-of-systems

This paper pursues three primary objectives. First, a brief introduction to system-of-systems is presented in order to establish a foundation for exploration of the role of human system modeling in this context. Second, the sources of complexity related to human participation in a system-of-systems are described and categorized. Finally, special attention is placed upon how this complexity might be better managed by greater involvement of modeling of human behavior and decision-making. The ultimate objective of the research thrust is to better enable success in the various system-of-systems that exist in society.
The ultrastructure of the superior cervical sympathetic ganglion of the cat: II. The structure of the preganglionic end fibers and the synapses as studied by serial sections

The structure of the preganglionic end fibers and the synapses in the superior cervical ganglion of the cat has been studied by means of serial sections. The preganglionic end fibers usually have a diameter of about 0.1–0.3 μ. Along their paths they exhibit widened portions at which they establish synaptic contacts with the postganglionic neurons. The great majority of the synapses are axodendritic; a few axosomatic synapses have also been observed. The preganglionic fibers usually run parallel to or wind around the dendrites and establish synaptic contacts with the dendrites at several points. The most common organelles of the fibers are small vesicles, about 300–500 A in diameter, vesicles with a dense core about 700–1000 A in size, highly opaque granules about 0.2–0.4 μ large, and mitochondria. These structures are usually concentrated in the presynaptic widenings. The fibers also contain filamentous structures. The specialized zones of the pre- and postsynaptic membranes have a triple-layered asymmetric structure. The components of the synaptic membranes are continuous with the corresponding components of the plasma membranes. Some of the small vesicles of the preganglionic widening are always in close association with the presynaptic membrane. Highly dense material of varying thickness is associated with the cytoplasmic surface of the postsynaptic membrane. The interspace between the synaptic membranes, which is about 60–80 A wide, contains stained material showing alternating light and dense regions.
Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation

Background The relevance of focal triggers in persistent atrial fibrillation (PerAF) and long-standing persistent atrial fibrillation (LSPAF) has not been previously investigated. Objective We prospectively evaluated the prevalence and distribution of AF triggers in patients referred for catheter ablation of PerAF and LSPAF. Methods We analyzed consecutive patients undergoing first time AF ablation who underwent a standardized trigger protocol including cardioversion of induced or spontaneous AF and infusion of up to 20 μg of isoproterenol for 15–20 minutes either before or after pulmonary vein (PV) isolation accomplished. Triggers were defined as AF/sustained atrial tachyarrhythmia or repetitive atrial premature depolarizations. Results A total of 2168 patients were included (mean age 57 ± 11 years; 1636 [75%] men), with 1531 patients having paroxysmal AF (PAF) (71%), 496 having PerAF (23%), and 141 having LSPAF (7%). PV triggers were found in 1398 patients with PAF (91%), 449 patients with PerAF (91%), and 129 patients with LSPAF (91%) ( P = .856 for comparison across groups). Non-PV triggers were elicited in a total of 234 patients (11%), and the prevalence was similar across the different types of AF (PAF, 165 [11%]; PerAF, 54 [11%]; LSPAF, 15 [11%]; P = .996 for comparison across groups). Conclusion PVs are the main AF trigger site in patients with PerAF and LSPAF, with an overall prevalence similar to that found in patients with PAF. These results support the current recommendations for PV isolation as the cornerstone of catheter ablation to eliminate AF triggers in PerAF and LSPAF.
The European Family and Economy: Central Themes and Issues

This article explores ways in which recent work on the European peasant household by economic historians demographers anthropologists sociologists and womens historians fits together. The main underlying thread is the interworking of economic factors with various aspects of family structure and household strategies. It examines the effects of institutional and economic factors on family structure. It then examines the effects of family structure on inheritance strategies demographic strategies and economic strategies within the household. It traces the growth of protoindustrialization theory and evaluates its utility in a revised form. It explores the effects of the protoindustrial household on the broader economy and on family power and affective relationships such as patriarchy gender roles attitudes toward children and sibling relationships. (EXCERPT)
Ultrastructure as a diagnostic adjunct in the evaluation of lung allograft biopsies.

Humoral immunity contributes significantly to lung graft dysfunction. Recognizing a role of ultrastructural studies in the evaluation and diagnosis of chronic humoral allograft rejection in the kidney, the authors sought to explore its utility as a diagnostic adjunct in lung allograft biopsies. Ultrastructural studies were conducted on 44 biopsies from 26 lung transplant recipients. Endothelial cell activation and necrosis were seen in the setting of acute humoral allograft rejection. Septal chronic vasculopathic changes of thickening and lamellation of the basement membrane zone (BMZ) and BMZ collagen deposition were correlated with greater numbers of humoral allograft rejection episodes and with the development of chronic graft dysfunction/bronchiolitis obliterans syndrome. There was a positive correlation between the extent of septal fibrosis and certain chronic vasculopathic changes, namely collagen deposition in the BMZ and BMZ wrinkling. Patients with chronic graft dysfunction and multiple rejection...
Adsorption on graphite and catalytic reduction of O2 by the macrocyclic complex of cobalt(II) with 2,3,9,10-tetraphenyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene

Abstract The complex of Co(III) with the macrocyclic ligand ph-tim (ph-tim = 2,3,9,10-tetraphenyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene) adsorbs irreversibly on roughly polished pyrolitic graphite electrodes. The adsorbed complex exhibits two, reversible, one-electron voltammetric waves corresponding to Co(III)/Co(III) and Co(II)/Co(I) redox couples located at 0.32 V and −0.07 V, respectively. The adsorbed Co(II) complex generated at 0.32 V catalyzes the electroreduction of O 2 to H 2 O 2 in a separate voltammetric step at more negative potentials which vary with pH. Catalytic plateau currents for the reduction of O 2 at rotating pyrolytic graphite disk electrodes coated with [(ph-tim)Co] ads 3+ ar elimited by the rate of coordination of O 2 to the reduced catalyst, [(ph-tim)Co]] ads 2+ . An upper limit of 150 M −1 was placed on the equilibrium constant for the binding of O 2 to [(ph-tim)Co] ads 2+ . A catalytic mechanism compatible with the results is proposed and discussed.
How does volume status affect BNP and troponin levels as markers of cardiovascular status in peritoneal dialysis

Cardiac biomarkers such as brain natriuretic peptide, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin provide information on cardiovascular morbidity and mortality in patients with normal renal function. In a considerable number of chronic hemodialysis patients, both biomarkers—NT-proBNP and troponin—are elevated despite the absence of cardiac ischemia. The elevation of cardiac biomarkers in chronic hemodialysis patients is of prognostic value with respect to cardiovascular morbidity and mortality. Furthermore, they can serve as tools for volume assessment for optimization of the fluid management aspect of dialysis. However, the association of both these markers in peritoneal dialysis is not clear. Therefore, the authors reviewed the literature to examine the role of these markers in peritoneal dialysis patients both as prognostic indicators as well as tools for volume assessment.
Controlled-growth of single-walled carbon nanotubes using optical near-field effects

Controlled growth of self-aligned single-walled carbon nanotubes (SWNTs) was realized using optical near-field effects in a laser-assisted chemical vapor deposition (LCVD) process. Electronic devices containing ultrashort suspended SWNT channels were successfully fabricated at relatively low substrate temperatures. According to the numerical simulations using High Frequency Structure Simulator (HFSS), significant local-heating enhancement occurred at electrode tip apexes under laser irradiation, which was about ten times higher than the rest part of the electrodes. Experimental results revealed that the localized heating enhancement at the electrode tip apexes significantly stimulates the growth of SWNTs at a significantly reduced substrate temperature compared with the conventional LCVD process. The near-field enhancement dependence on metallic film thickness and laser polarization was investigated through numerical simulation using HFSS, which provided a guideline for further optimization of maximum near-field enhancement. This technique suggests a viable laser-based strategy for fabricating SWNT-based devices at relatively low substrate temperatures in a precisely controlled manner using the nanoscale optical near-field effects, which paves the way for the mass production of SWNT-based devices using expanded laser beams.
Temporal integration in global stereopsis.

Thresholds for anaglyphic dynamic random element stereograms that reversed in depth were determined using a method of adjustment. Hypercyclopean pattern type (horizontal or vertical gratings, or checkerboards in depth), spatial frequency (0.13–0.55 cpd), and interval between depth reversals (0.03 to 4.27 sec) were varied. Stereothresholds were lowest at 0.18 cpd and were elevated as hypercyclopean spatial frequency increased or decreased. Vertical gratings required approximately twice as much disparity to be detected as did horizontal gratings. Threshold disparity was minimum for depth reversal intervals exceeding 0.5 sec. For shorter intervals, disparity threshold doubled each time interval duration was halved, suggesting temporal integration by the stereoscopic mechanisms up to about 0.5 sec.
The role of GABA and serotonin in the mediation of raphe-evoked spinal cord dorsal root potentials.

Abstract The possible involvement of bulbospinal serotonergic systems in the mediation of analgesia has created a need for a better understanding of the influence this system has on neuronal mechanisms in the spinal cord. Therefore, these studies were designed to examine the effects of caudal raphe stimulation on primary afferent depolarization and to determine the role of serotonin (5-HT) and GABA in the mediation of these stimulation-produced effects. Stimulation of the raphe evoked two electronically conducted dorsal root potentials (DRP-1 and DRP-2) and two compound action potentials (VRP-1 and VRP-2) which were recorded from the dorsal and ventral roots, respectively. Length constant measurements indicated that DRP-1 was generated in group II and DRP-2 in group I primary afferent fibers. Histological determination of stimulation sites revealed that short-latency potentials (DRP-1 and VRP-1) were evoked from many sites within the caudal brain stem, while the long-latency potentials (DRP-2 and VRP-2) were evoked primarily from sites within the caudal raphe nuclei. The role of serotonin in mediating these evoked potentials was assessed by administering various antagonists of serotonin (cinanserin, methysergide and d -lysergic acid diethylamide). These agents consistently attenuated the long-latency potentials (DRP-2 and VRP-2) but increased the magnitude of DRP-1. The possibility of a GABAergic neuron in the descending systems projecting to primary afferent terminals was studied. Depletion of GABA by semicarbazide blocked DRP-1, but had only a modest effect on DRP-2. However, the putative GABA antagonist, bicuculline, inhibited both DRP-1 and DRP-2. These results suggest that a GABA interneuron is not involved in the bulbospinal serotonergic depolarization of primary afferent terminals. This system appears to contitute a presynaptic filter of afferent input, with the capacity to inhibit different fiber groups.