cssi/SciSciGPT-SciSciNet huggingface dataset:
Spinal Schwannoma and Meningioma Mimicking a Single Mass at the Craniocervical Junction Subsequent to Remote Radiation Therapy for Acne Vulgaris.

Background Schwannomas and meningiomas are relatively common tumors of the nervous system. They have been reported in the literature as existing concurrently as a single mass, but very rarely have they been shown to present at the craniocervical junction. Case Description We present a rare and interesting case of a patient previously treated with radiation therapy for acne vulgaris and who presented to us with a concurrent schwannoma and meningioma of the craniocervical junction mimicking a single mass. Conclusions These tumors can be solitary or mixed masses, and are known to be associated with certain disease processes such as long-term sequelae of radiation therapy and neurofibromatosis type 2. The precise mechanism behind the formation of these tumors is unknown; however, molecular cues in the tumor microenvironment may play a role.
P091 Comparison of four HLA next-generation sequencing typing methods

Aim HLA genotyping by next-generation sequencing has matured from a proof-of-principle concept to the development of several commercially available kits all within the space of a few years. We evaluated several kits against our own in-house developed method to determine the best-fit solution for our clinical lab. Methods Nine clinical samples were compared using kits from Omixon Holotype X2 24/7, Illumina HLA TruSight v2, Immucor MiaFora, and an in-house developed method. Directions were followed as indicated per commercial kit and all methods were performed manually. Sequencing was performed on the Illumina MiSeq and HLA assignments were made using each kit’s supplied software. The in-house method used Omixon’s Target software for analysis. Methods were evaluated for genotyping accuracy and ease of use. Results All methods gave comparable, unambiguous genotyping results (95.2–98.8%) but there were significant differences in the library construction process. Of the four methods, the Illumina HLA TruSight v2 required the fewest steps. In contrast to the other three kits, the Illumina method did not require the use of fluorometer (amplicon quantification), size-selection instrument (PippenPrep), or a real-time PCR instrument (final library quantification), which simplifies the library preparation process significantly. Both the MiaFora and the Illumina HLA TruSight use the 2 × 150 (300 cycle) MiSeq reagent kit and thus have shorter run times (20 h) in comparison to the Omixon and in-house methods that require use of the longer read length kits (2 × 250, 500 cycles) and thus have a longer run time (40 h). Conclusions All of the methods evaluated correctly genotyped a small set of samples although there were a few technical failures. The biggest difference between these methods is in the library preparation process. Depending upon the commercial method selected, additional budgeting and purchasing decisions may be required.
Pseudocharge Phonon Model

In order to identify the character and symmetry of the measured phonon events to be presented later, I employ empirical lattice dynamics calculations, based on the pseudocharge model (PCM) [1–3]. This model includes direct ion–ion interactions as well as indirect adiabatic coupling through the mediating electrons. Historically this model has been successful in reproducing surface phonon dispersion and HASS scattering amplitudes, derived from calculated surface charge deformations. Here I review some of the model’s basic characteristics and tabulate the parameters used in our realization of the model.
Accelerating splitting algorithms for power grid reliability estimation

With increasing penetration of intermittent power generation sources like wind and solar farms, overload risks in power grids due to imbalances in supply and demand of energy has become a serious concern. We model the flow of electricity through a power grid as a functional transformation of a multidimensional Ornstein-Uhlenbeck process of renewable energy injection. Previously, a rare event simulation technique called splitting, based on large deviations results has been proposed as the risk assessment method. This method requires solving a nonlinear optimization problem for every time step in every generated sample path, so significant computational challenges remain in scaling to realistic networks. We propose a new algorithmic approach to implement the large deviations splitting method that derives and exploits fundamental properties of the rate functions in order to significantly speed up the pathwise optimizations. Experimental results show a significant reduction in effort compared to a conventional numerical approach.
Catch wave power in floating nets

Zhong Lin Wang proposes a radically different way to harvest renewable energy from the ocean using nanogenerator networks.
Estimating the Mixing Density of a Mixture of Power Series Distributions

Let X 1, X 2, ..., X n be independent and identically distributed observations from a mixture of power series distributions. Based on this random sample, we consider the problem of estimating the mixing density of the mixture distribution. A mixing density kernel estimator is proposed which, under mild assumptions, has 1/log n as an upper bound for its rate of convergence to the true density under squared error loss. It is also shown that the optimal rate of convergence cannot exceed 1/n r for any constant r.
Combined stability analysis of phase-field dynamic fracture and shear band localization

Abstract Dynamic fracture of metals is a fascinating multiphysics-multiscale problem that often results in brittle and/or ductile fracture of structural components and under high strain rates may also suffer from shear banding. While fracture events are mostly driven by tensile loading, shear bands are driven by shear heating caused by inelastic deformations and associated with high temperature rise. These processes are characterized by different failure modes with distinct spatial and temporal scales. A recent unified model developed by the authors attempts to capture dynamic fracture and shear banding failure modes using implicit, mixed finite element formulations. In this model, fracture is modeled with a novel phase field formulation coupled to a set of equations that describe shear bands. While fracture is governed by a strong length-scale that propagates with a fast time scale, shear bands are dominated by a weak length-scale and propagate slower. In this work, we analyze the physical stability of both failure modes and their interaction using a linear perturbation method. The analysis provides insight into the dominant failure mode and can be used as a criterion for mesh refinement. Several numerical results with different geometries and a range of strain rate loadings demonstrate that the stability criterion predicts well the onset of failure instability in dynamic fracture applications. For the example problems considered, if a fracture instability precedes shearbanding, a brittle-like failure mode is observed, while if a shear band instability is initiated significantly before fracture, a ductile-like failure mode is expected. In any case, fracture instability is stronger than a shear band instability and if initiated will dominate the response.
Voiding Dysfunction, Incontinence, and Erectile Dysfunction Following High-Intensity Focus Ultrasound and Focal Cryotherapy in Treatment of Prostate Cancer

Prostate cancer is one of the most prevalent malignancies in males and treatment is not infrequently associated with substantial morbidity. As a result, there has been growing interest in alternative therapies for prostate cancer therapy including high-intensity focused ultrasound (HIFU) and focal cryoablation. Herein, we review the potential genitourinary sequelae of these therapies including incontinence and erectile dysfunction. Various studies have demonstrated that with improvements in delivery technique and technologies aimed at treatment of prostate cancer, the risks of urinary incontinence, urethral obstruction, and erectile dysfunction have decreased. Large studies demonstrate rates of continence in 84–100% of patients and potency in 44–77% of patients treated with HIFU. Focal cryoablation incontinence rates can be as low as 1.6% and erectile function may be preserved in 68.8% of patients. Urinary incontinence and erectile dysfunction rates are lower in patients treated with HIFU or focal cryoablation compared to patients treated with traditional therapies. However, HIFU patients may experience higher rates of urethral stricture and bladder neck obstruction compared to traditional therapies.
U.S. Army physical demands study: Prevalence and frequency of performing physically demanding tasks in deployed and non-deployed settings.

Abstract Objectives To compare percentages of on-duty time spent performing physically demanding soldier tasks in non-deployed and deployed settings, and secondarily examine the number of physically demanding tasks performed among five Army combat arms occupational specialties. Design Job task analysis. Methods Soldiers (n = 1295; over 99% serving on active duty) across five Army jobs completed one of three questionnaires developed using reviews of job and task related documents, input from subject matter experts, observation of task performance, and conduct of focus groups. Soldiers reported estimates of the total on-duty time spent performing physically demanding tasks in both deployed and non-deployed settings. One-way analyses of variance and Duncan post-hoc tests were used to compare percentage time differences by job. Two-tailed t-tests were used to evaluate differences by setting. Frequency analyses were used to present supplementary findings. Results Soldiers reported performing physically demanding job-specific tasks 17.7% of the time while non-deployed and 19.6% of the time while deployed. There were significant differences in time spent on job-specific tasks across settings (p Conclusion Soldiers spent more time performing physically demanding tasks while deployed compared to non-deployed but spent similar amounts of time performing job-specific tasks.
Canagliflozin lowers blood sugar, but does it also lower cardiovascular risk? Maybe not

For the last 25 years it has been widely accepted that diabetes mellitus is associated with a twofold or greater risk of clinical atherosclerotic disease (1). Long-standing elevated blood sugar levels, as measured by the hemoglobin A1c level, have been shown to be independent of major cardiovascular risk factors including age, body mass index, systolic blood pressure, serum cholesterol, cigarette smoking, or history of cardiovascular disease (2).
Tissue-like neural probes for understanding and modulating the brain

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we descr...
Regional-level exchange in Postclassic Central Mexico

Abstract This article uses evidence of regional-scale ceramic exchange to evaluate three proposed causal factors (Aztec imperial expansion, bottom-up demand, and elite competition) for the development of the market-based economy of Postclassic Central Mexico. The factors used to evaluate these models may be applied more widely to other cases of market development. Using previously published datasets, I compare the quantities and diversities of non-local ceramics from sites in the Basin of Mexico, Morelos, and the Toluca Valley regions of central highland Mexico across the Middle (CE 1150–1350) and Late (CE 1350–1521) Postclassic periods. The results show that the highest proportion of trade occurs under Aztec rule, and is dominated by ceramics exported out of the Basin of Mexico. However, areas outside the Basin of Mexico have higher numbers of trading partners, and these ties are well developed during the Middle Postclassic. These results provide partial support for both bottom-up demand and elite competition as causal factors for market development. This article also demonstrates the continued utility of legacy data and emphasizes the need to make basic data sets available for new analyses.
Penile neuropathy in insulin-dependent diabetes mellitus

The dorsal nerve of the penis has been linked closely to penile erection and response. We measured the nerve conduction velocity of the dorsal nerve of the penis, latency of the bulbocavernosus reflex and pudendal evoked potential in 23 normal men and 20 insulin-dependent diabetics with impotence. The conduction velocity of the dorsal nerve of the penis was significantly slower in diabetic than in normal men and passive gentle elongation of the penis by weight stretching enhanced the slowing. In contrast, the bulbocavernosus reflex and pudendal evoked potential showed no significant differences between the 2 groups. We demonstrate the potential usefulness of measurement of the conduction velocity of the dorsal nerve of the penis in the detection of penile neuropathy.
Understanding the Timing and Tempo of the Evolution of Political Centralization on the Central Andean Coastline and Beyond

One of the fundamental questions in anthropology is the origin of formal institutions of rule. A central issue in the study of the origins of centralized political organization is the timing and tempo of the emergence of pristine chiefdoms and states. Why did centralized political institutions develop rapidly at an early date in certain areas, while in other areas they emerged more slowly at a much later date? Current views of human origins propose that anatomically modern human beings had evolved by approximately 100,000 years ago, yet centralized political organizations apparently did not develop for at least another 94,000 years. Early pristine chiefdoms and states developed in only a few restricted areas between 6,000 and 3,000 years ago. Most of the world was not incorporated into state-level polities until the last 100 to 500 years during the period of colonial, nation-state expansion. Theories of the origins of centralized political organization must explain not only why centralized institutions developed, but how, when, and where. These crucial issues can be summarized in three questions: 1 How? By what process did pristine centralized polities develop? 2 Where? Why did this process occur in certain areas and not others? 3 When? Why did this process occur when it did in human prehistory?
Properties of N-methyl-N′-nitro-N-nitrosoguanidine and its action on Bacillussubtilis transforming DNA

Abstract The stability of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) was measured by a spectrophotometric assay as a function of pH, temperature, and buffer. The effect of MNNG was then tested on Bacillus subtilis transforming deoxyribonucleic acid (DNA). Conditions which lead to MNNG decomposition cause inactivation of transforming DNA. However, transforming DNA is not inactivated under conditions of MNNG stability, e.g. 0.05 M Tris-maleate buffer (pH 6).
Abstract 5147: Lactate transporters are a potential therapeutic target for LKB1-deficient lung cancers

The serine/threonine kinase LKB1 is mutated and inactivated in 20-30% of lung adenocarcinoma representing the second most commonly altered tumor suppressor in non-small cell lung cancer (NSCLC), and to date there are no effective targeting strategies for tumors bearing this mutation. Therefore, new therapeutic approaches are urgently needed for LKB1-deficient tumors. LKB1 activates AMPK, the master sensor of cellular energy and because of this, many of the best known functions of LKB1 are attributed to its ability to control metabolic alterations. Our laboratory and others have demonstrated that loss of LKB1 can promote enhanced glucose metabolism and a shift from aerobic to anaerobic respiration. A result of enhanced glycolysis is an elevated lactate production even under normoxic conditions. It has been reported that lactate-mediated extracellular acidification is a key factor mediating tumor cell invasion and metastasis. We found that LKB1-deficient NSCLC tumors significantly upregulate lactate transporters and, because these tumors exhibit an immunologically inert phenotype, we propose that inhibition of lactate transporters could represent a rational strategy to inhibit tumor growth and enhance immune responses in LKB1 mutant NSCLC. To characterize lactate transporter expression, a panel of NSCLC cell lines was stably transduced to overexpress LKB1 and with shRNA targeting LKB1. We analyzed gene expression of lactate transporters in TCGA dataset of lung adenocarcinoma (LUAD). We validated these results by qPCR and western blot analysis of expression levels of MCT1, MCT4 and MCT14 in human LKB1-intact and deficient cells and in LKB1 KO murine NSCLC cell lines that were generated using CRISPR/Cas9 in a KRASG12D mutant background. To study lactate transporter expression in tumors in vivo, we generated syngeneic NSCLC mouse models via s.c. injection of LKB1-intact and KO murine cells in immunocompetent mice and analyzed the protein expression levels of MCT4 in these tumor samples. The analysis of TCGA LUAD dataset revealed a significant upregulation of lactate transporter SLC16A14 (MCT14) gene expression levels in LKB1-deficient tumors compared with LKB1 wild-type (p Citation Format: Irene Guijarro, Alissa Poteete, Pan Tong, Jing Wang, John Heymach. Lactate transporters are a potential therapeutic target for LKB1-deficient lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5147.
Swedish Crime Fiction and Study Abroad: Literature, Politics and the Foreigner.

This paper highlights how to use Swedish crime fiction in the classroom to teach politics, especially issues related to immigration and the role of being “foreign”. Furthermore, the paper explores how Swedish crime fiction can be incorporated into a study abroad course, examining one such study abroad – known as W’International – on our campus. I argue that Swedish crime fiction novels make for a perfect venue to explore an array of political problems and challenges, and a palatable way for students unfamiliar with Sweden or crime fiction to relate to real-world issues.
Manure Application Timing Drives Energy Absorption for Snowmelt on an Agricultural Soil

Abstract Reducing agricultural runoff year-round is important, in particular during snowmelt events on landscapes that receive wintertime applications of manure. To help inform manure guidelines, process-level data are needed that link management scenarios with the complexity of snowmelt, hence runoff. Albedo and radiative energy fluxes are strong drivers of thaw, but applying these mechanistic measurements across multiple, plot-scale management treatments over time presents a logistical challenge. The objective of this study was to first develop a practical field approach to estimate winter albedo in plot-scale field research with multiple management scenarios. The second objective was to quantify the radiative drivers of snowmelt by measuring fluxes after wintertime liquid manure application. Six management treatments were tested in south-central Wisconsin during the winters of 2015–2016 and 2016–2017 with a complete factorial design: three manure application timings (early December, late January, and unmanured) and two tillage treatments (conventional tillage versus no-tillage). A multiple linear regression model was developed to estimate albedo with digital imagery and readily-obtained site characteristics. Manure timing had a significant effect on radiative energy fluxes and tillage was secondary. January applications of liquid manure produced an immediate and lasting decrease in albedo, which resulted in greater net radiation absorbed by snowpack and subsequent energy available for snowmelt. Later applications of liquid manure accelerated snowmelt, which increased runoff losses and posed a challenge for nutrient retention from the liquid manure during thaw.
The geopolitics of sport beyond soft power: event ethnography and the 2016 cycling world championships in qatar

State leaders in the Arabian Peninsula have increasingly sought to host globalized sporting events to broadcast a cosmopolitan and modern image of the region. These efforts are typically interprete...
REVEALING THE SECRETS OF IDIOPATHIC PULMONARY FIBROSIS

Modeling Idiopathic Pulmonary Fibrosis Pathogenic findings in a mouse model of idiopathic pulmonary fibrosis confirm the pivotal role played by dysfunction of the type 2 alveolar (AT2) epithelial c...
Constraints on terrestrial planet formation timescales and equilibration processes in the Grand Tack scenario from Hf-W isotopic evolution

Abstract We examine 141 N-body simulations of terrestrial planet late-stage accretion that use the Grand Tack scenario, coupling the collisional results with a hafnium-tungsten (Hf-W) isotopic evolution model. Accretion in the Grand Tack scenario results in faster planet formation than classical accretion models because of higher planetesimal surface density induced by a migrating Jupiter. Planetary embryos that grow rapidly experience radiogenic ingrowth of mantle 182W that is inconsistent with the measured terrestrial composition, unless much of the tungsten is removed by an impactor core that mixes thoroughly with the target mantle. For physically Earth-like surviving planets, we find that the fraction of equilibrating impactor core k core ≥ 0.6 is required to produce results agreeing with observed terrestrial tungsten anomalies (assuming equilibration with relatively large volumes of target mantle material; smaller equilibrating mantle volumes would require even larger k core ). This requirement of substantial core re-equilibration may be difficult to reconcile with fluid dynamical predictions and hydrocode simulations of mixing during large impacts, and hence this result does not favor the rapid planet building that results from Grand Tack accretion.
A critical review of the behavioral, neuroimaging, and electrophysiological studies of co-activation of representations during word production

Abstract A large body of behavioral, neuroimaging, and electrophysiological studies have investigated the consequences of co-activation of representations during word production. Despite such an amazing body of empirical data, it remains unclear how the production system handles co-activated items. In this paper, we review this evidence in a systematic way, and point out three common problems in the interpretations attached to these data. We then discuss alternative approaches which might be more fruitful in understanding the links between such data and the processes of spreading activation, selection, monitoring and control in language production.
Explainable AI for medical imaging: deep-learning CNN ensemble for classification of estrogen receptor status from breast MRI

Deep-learning convolutional neural networks (DCNNs) are the most commonly used approach in medical image analysis tasks at present; however, they have largely been used as black-box predictors, lacking explanation for the underlying reasons. Explainable artificial intelligence (XAI) is an emerging subfield of AI seeking to understand how models make their decisions. In this work, we applied XAI visualization to gain an insight into the features learned by a DCNN trained to classify estrogen receptor status (ER+ vs ER-) based on dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) of the breast. Our data set contained 1395 ER+ regions-of-interest (ROIs) and 729 ER- ROIs from 148 patients, each with a pre-contrast scan and a minimum of two post-contrast scans. We developed a novel transfer-trained dual-domain DCNN architecture derived from the AlexNet model trained on ImageNet data that received the spatial (across the volume) and dynamic (across the acquisition sequence) components of each DCE-MRI ROI as input. The network’s performance was evaluated with the area under the receiver operating characteristic curve (AUC) from leave-one-case-out crossvalidation. To visualize the DCNN learning, we applied XAI techniques, including the Integrated Gradients attribution method and the SmoothGrad noise reduction algorithm, to the ROIs from the training set. We observed that our DCNN learned relevant features from the spatial and dynamic domains, but there were differences in the contributing features from the two domains. We also visualized DCNN learning from irrelevant features resulting from pre-processing artifacts. These observations motivate new approaches to pre-processing our data and training our DCNN.
Statutory Interpretation—in the Classroom and in the Courtroom

This paper continues a discussion begun in an earlier paper in this journal.1 That paper dealt primarily with the implications for statutory interpretation of the interest-group theory of legislation, recently revivified by economists; it also dealt with constitutional interpretation. This paper focuses on two topics omitted in the earlier one: the need for better instruction in legislation in the law schools and the vacuity of the standard guideposts to reading statutes-the "canons of construction." The topics turn out to be related. The last part of the paper contains a positive proposal on how to interpretstatutes.
Analysis of Capacitor Charging Characteristics and Low-Frequency Ripple Mitigation by Two New Voltage-Balancing Strategies for MMC-Based Solid-State Transformers

This article investigates and compares various modulation methods and capacitor voltage-balancing algorithms of a modular multilevel converter for solid-state transformer applications. Characteristics of capacitor charging and discharging are analyzed for the existing single-step alternating voltage balancing and the conventional sorting algorithms with phase-shift (PS) modulation and nearest level control (NLC) methods. Based on the analysis, the single-step alternating algorithm leads to a low-frequency voltage ripple, while the conventional sorting algorithm introduces additional switching actions. To address these issues, two new voltage-balancing algorithms are proposed: a multistep alternating voltage-balancing algorithm, and a currentless sorting algorithm. The performance of the proposed algorithms with the PS and NLC modulation methods is comprehensively investigated and compared based on theoretical analysis and experimental results. The study results demonstrate the capability of the proposed methods to balance capacitor voltages while reducing the low-frequency voltage ripple and avoiding additional switching actions.
Orexin A induced increases in rat locus coeruleus neuronal activity are attenuated by systemic administration of OX1R and OX2R antagonists

Abstract Since the initial characterisation of the orexin/hypocretin system, the noradrenergic locus coeruleus (LC) has been a key focus due to its high expression of orexin receptors. Direct application of orexin A (OX-A) into the LC increases neural activity, and consequently arousal, attention and analgesia. We administered OX-A intracerebroventricularly to anaesthetised male CD® IGS rats and recorded spontaneous neural activity in the LC, blood pressure and heart rate. We then pre-treated with systemically administered orexin receptor 1 (OX1R) or orexin receptor 2 (OX2R) antagonists, SB-334867 and LSN2424100 respectively, and measured any changes in OX-A-induced effects. Central OX-A exposure dose dependently activated LC neurons over the period of 1 h: OX-A at 600 and 63 pmol, but not 20 pmol, increased neural activity. OX-A at 600 pmol, but not 63 or 20 pmol, altered blood pressure. OX-A did not alter heart rate at any of the doses tested. Pre-treatment with either OX1R or OX2R antagonist attenuated the OX-A-induced increase in LC firing with OX2R antagonism having a delayed onset. Neither antagonists altered LC firing on their own. We show that LC activation can be modulated by both OX1R and OX2R mechanisms, despite low OX2R expression in the LC. The LC is a key target brain nucleus in disease mechanisms that could be modulated by orexinergic pharmacology.
Responses to chronic corticosterone on brain glucocorticoid receptors, adrenal gland, and gut microbiota in mice lacking neuronal serotonin

Abstract Dysregulation of the stress-induced activation of the hypothalamic-pituitary-adrenocortical axis can result in disease. Bidirectional communication exists between the brain and the gut, and alterations in these interactions appear to be involved in stress regulation and in the pathogenesis of neuropsychiatric diseases, such as depression. Serotonin (5HT) plays a crucial role in the functions of these two major organs but its direct influence under stress conditions remains unclear. To investigate the role of neuronal 5HT on chronic stress responses and its influence on the gut microbiome, mice lacking the gene for tryptophan hydroxylase-2 were treated with the stress hormone corticosterone (CORT) for 21 days. The intake of fluid and food, as well as body weights were recorded daily. CORT levels, expression of glucocorticoid receptors (GR) in the brain and the size of the adrenal gland were evaluated. Caecum was used for 16S rRNA gene characterization of the gut microbiota. Results show that 5HT depletion produced an increase in food intake and a paradoxical reduction in body weight that were enhanced by CORT. Neuronal 5HT depletion impaired the feedback regulation of CORT levels but had no putative effect on the CORT-induced decrease in hippocampal GR expression and the reduction of the adrenal cortex size. Finally, the composition and structure of the gut microbiota were significantly impacted by the absence of neuronal 5HT, and these alterations were enhanced by chronic CORT treatment. Therefore, we conclude that neuronal 5HT influences the stress-related responses at different levels involving CORT levels regulation and the gut microbiome.
213 Use of A novel peptide ligand targeting multiple immune checkpoints: a novel approach to immunotherapy against central nervous system tumors

Background Cancer immunotherapy has revolutionized clinical management of malignancies by generating long-term, durable control of tumors, rendering more manageable diseases that previously had dismal prognoses. Unfortunately, these therapies often enhance autoimmunity, causing serious immune-related adverse events. In addition, little efficacy is noted in CNS tumors. Our research is focused on the CD200 immune checkpoint, which modulates the immune system through the inhibitory receptor (CD200R1) and activation receptors (CD200AR). We have demonstrated that targeting the CD200AR with a peptide ligand (CD200AR-L) activates the immune system, rendering it impervious to the inhibitory effects of CD200. In a clinical trial studying canine spontaneous high-grade glioma, CD200AR-L administered with tumor autologous tumor lysate resulted in a 20% two-year progression-free survival. No adverse effects were observed. We suggest this result is due to the ability of the CD200AR-L to modulate multiple immune checkpoints. During the characterization of the CD200AR-L, we discovered that signaling molecules are shared by CD200 and PD-1/PD-L1, suggesting these important immune checkpoints are interconnected. Methods CD200R1KO macrophages were used to determine the connection between the CD200 and PD-1 checkpoints. Next, we analyzed signaling molecules activated in CD11b cells pulsed with PD-L1 ± CD200AR-L, followed up with in vitro and in vivo effects of CD200AR-L on the expression of PD-1/PD-L1 and CTLA-4. Finally, we analyzed the ability of the CD200AR-L to surmount the suppressive effects of PD-L1. Results Our studies demonstrate that the inhibitory CD200R1 and PD-1 mediate immune checkpoint signaling activities through SHIP1 protein. Moreover, CD200AR-L overpowers the suppressive effects of CD200 and PD-L1, which are both shed by tumors, by downregulating the inhibitory CD200R1 and PD-1 on both antigen-presenting cells (APC) and T-cells (figure 1), In addition, CD200AR-L downregulates PD-1 on APCs and inhibits the upregulation of PD-L1 and CTLA4. Conclusions These studies led to the discovery that this novel peptide modulates the CD200, PD-1/PD-L1 and CTLA-4 pathways, providing the basis for the translatable development of a novel CD200 peptide inhibitor for clinical use against multiple tumors, including gliomas. These studies led to the FDA approval for the first in human peptide checkpoint inhibitor to initiate a phase I single center, open-label, dose-escalation clinical trial in adult patients with recurrent glioblastoma, to be followed by a clinical trial for children with recurrent malignant brain tumors.
Case 29. Indolent primary cutaneous γδ T-cell lymphoma mimicking mycosis fungoides

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is characterized by the expression of cytotoxic markers and shares clinical features with extranodal NK/T-cell lymphoma and primary cutaneous CD8+ aggressive epidermotropic T-cell lymphoma. γδ-Positive cases with panniculitis-like presentation should be called as PCGD-TCL with panniculitis-like presentation and not as subcutaneous panniculitis-like T-cell lymphoma with γδ expression. Those cases were shown to originate almost exceptionally from TCR-Vδ2 γδ T cells comprising the separate category. PCGD-TCL has a predilection for extremities and frequently ulcerates. Frequently, in clinical practice, the absence of β-F1 expression is considered to be an equivalent of γδ positivity. However, there is a small cohort of “TCR silent” cases with a lack of both markers. Therefore, TCRγ staining is still necessary. The absence of cytotoxic markers characterizes cases of MF with γδ expression. In the recent study, CCR4 expression was found to be useful in differential diagnosis of MF which are CCR4 positive from PCGD-TCL which are CCR4 negative. Clinically and prognostically, γδ-positive MF has no difference with classic counterparts. The cases with EBV+ CD56+ TCRγ+ presents a matter of active debate is that an extranodal NK/T-cell lymphoma with aberrant TCRγ expression or is that a case of EBV+ CD56+ primary cutaneous γδ T-cell lymphoma.
Our Words in a State of Emergency: Psychological-Linguistic Analysis of Utterances on the COVID-19 Situation in the Czech Republic.

The study focuses on psychological–linguistic analysis of utterances provided by N = 2522 respondents aged 18–89 years in the period of March–May 2020, for the research of JUPSYCOR (Psychological Impacts of the Coronavirus Epidemic in the Czech Republic). The utterances relate to the interpretation of the state of emergency, the COVID-19 epidemic, and its subjectively perceived impacts. Simultaneously, the study examines the relationship between the analysed texts and the results of the SEHW (Scales of Emotional Habitual Subjective Well-being) questionnaire, which determines the valence of experienced emotions. The aim of the study is to analyse the lexical and morphological layers of the utterances, especially which specific words resonated in the individual questions, what is their emotional load, and which linguistic features of the texts may refer to the respondents’ positive/negative emotional response. One of the outputs based on the results of the quantitative analyses determines that the most distinctive words are connected to negative emotions and most frequently relate to social environment, anxiety, and inhibition. Furthermore, the study proves a positive correlation between a fear scale and a higher occurrence of future tense and use of emotionally negatively loaded words, especially in women. Numerous differences among the individual age and gender cohorts were also proved. The significance of the study lies predominantly in the combination of the linguistic and psychological levels of the analysis, in the utilization of two mutually complementary utterances, and in the presentation of new insights on how people use words when they face an unexpected and emotionally disturbing situation.
Cement Stabilization of Volcanic Materials

The feasibility of using volcanic tuffs and their residual soils as aggregates for soil-cement was investigated. These lightweight materials of the Los Alamos, New Mexico, area can be used to produce stable soil-cement mixtures at low cement contents, and the addition of cement in some instances allows acceptance of lower compaction requirements. The use of Type III cement also lowers the cement requirement. The difficulties encountered in compacting volcanic tuff and soils containing pumice particles are considered, and testing procedures are outlined.
Fe16Al14B2 phase in Fe–Al alloys

Abstract The atomic structure and composition of a recently reported second phase found in Fe–Al alloys with small B and C additions have been determined using a combination of Z-contrast imaging and electron-energy-loss spectroscopy. The structure of this ordered tetragonal precipitate is found to be closely related to the B2 structure of the matrix. The derived structure and electron-energy-loss spectroscopy indicate that the phase is a new low-metalloid-content boride with B occupying specific interstitial sites.
Communicating neuronal ensembles between neuromorphic chips

The small number of input-output connections available with standard chip-packaging technology, and the small number of routing layers available in VLSI technology, place severe limitations on the degree of intra- and interchip connectivity that can be realized in multichip neuromorphic systems. Inspired by the success of time-division multiplexing in communications [16] and computer networks [19], many researchers have adopted multiplexing to solve the connectivity problem [12, 67, 17]. Multiplexing is an effective way of leveraging the 5 order-of-magnitude difference in bandwidth between a neuron (hundreds of Hz) and a digital bus (tens of megahertz), enabling us to replace dedicated point-to-point connections among thousands of neurons with a handful of high-speed connections and thousands of switches (transistors). This approach pays off in VLSI technology because transistors take up a lot less area than wires, and are becoming relatively more and more compact as the fabrication process scales down to deep submicron feature sizes.
Cytoplasmic degradation of ssrA‐tagged proteins

Degradation of ssrA-tagged proteins is a central feature of protein-quality control in all bacteria. In Escherichia coli, the ATP-dependent ClpXP and ClpAP proteases are thought to participate in this process, but their relative contributions to degradation of ssrA-tagged proteins in vivo have been uncertain because two adaptor proteins, ClpS and SspB, can modulate proteolysis of these substrates. Here, intracellular levels of these protease components and adaptors were determined during exponential growth and as cells entered early stationary phase. Levels of ClpA and ClpP increased about threefold during this transition, whereas ClpX, ClpS and SspB levels remained nearly constant. Using GFP-ssrA expressed from the chromosome as a degradation reporter, the effects of altered concentrations of different protease components or adaptor proteins were explored. Both ClpXP and ClpAP degraded GFP-ssrA in the cell, demonstrating that wild-type levels of SspB and ClpS do not inhibit ClpAP completely. Upon entry into stationary phase, increased levels of ClpAP resulted in increased degradation of ssrA-tagged substrates. As measured by maximum turnover rates, ClpXP degradation of GFP-ssrA in vivo was significantly more efficient than in vitro. Surprisingly, ClpX-dependent ClpP-independent degradation of GFP-ssrA was also observed. Thus, unfolding of this substrate by ClpX appears to enhance intracellular degradation by other proteases.
Los estudios metacognitivos y sus raíces en el tiempo

El objetivo del presente trabajo es mostrar que, aun cuando el termino"metacognicion " es de reciente aparicion, sobre todo aplicadoa los procesos de comprension y produccion de textos escritos,el tema de la relacion entre el lenguaje y la mente ha surgido una yotra vez bajo las mas diversas formulaciones y perspectivas desdela antiguedad. Estas variaciones han estado asociadas, en granmedida, a los cambios de los paradigmas epistemologicos y, conellos, la manera de concebir el conocimiento cientifico, los objetos posibles de estudio y el objetivo buscado. Sin embargo, al menos enlas ciencias del lenguaje, no se observa un avance lineal ni homogeneo:en ocasiones, temas aparentemente superados vuelven a serde interes por parte de los estudiosos y la mayor parte del tiempoconviven diversas perspectivas, en ocasiones incluso contrapuestas.Lo anterior no ha impedido, sin embargo, el avance en el conocimientoacerca del lenguaje y de la mente gracias a los aportesinterdisciplinarios cada vez mas integradores que caracterizan nuestraepoca. No obstante, queda aun un largo camino que recorrer ymuchas intenogantes que contestar.
Magnetoquasistatic position measurement above earth using the exact integral solutions

Measurements of the magnetoquasistatic coupling between a co-polarized vertical emitting and receiving coil, both located above earth, is compared to calculations using complex image theory and the exact integral solutions along a direction perpendicular to the surface normal axes of the loops. Inverting the theoretical expressions of the exact integral solution to estimate distance from measured fields resulted in an RMS error of 0.089 m for distances between 1.3–29.4 m, which corresponds to a 21.9% reduction in RMS distance error over complex image theory.
An Introductory Pharmacy Practice Experience Based on a Medication Therapy Management Service Model

Objective. To implement and evaluate an introductory pharmacy practice experience (IPPE) based on the medication therapy management (MTM) service model.Design. Patient Care 2 is an IPPE that introduces third-year pharmacy students to the MTM service model. Students interacted with older adults to identify medication-related problems and develop recommendations using core MTM elements. Course outcome evaluations were based on number of documented medication-related problems, recommendations, and student reviews.Assessment. Fifty-seven older adults participated in the course. Students identified 52 medication-related problems and 66 medical problems, and documented 233 recommendations relating to health maintenance and wellness, pharmacotherapy, referrals, and education. Students reported having adequate experience performing core MTM elements.Conclusion. Patient Care 2 may serve as an experiential learning model for pharmacy schools to teach the core elements of MTM and provide patient care services to the...
Effects of Oral Morphine on Cold Pressor Tolerance Time and Neuropsychological Performance

We investigated the analgesic effects of escalating doses (0.214, 0.286, 0.357, and 0.429 mg/kg) of oral morphine on tolerance to painful cold pressor in a double-blind, active placebo-controlled (diphenhydramine) study in 45 normal volunteers. The highest dose of morphine administered is equivalent to the starting dose recommended by the Agency for Health Care Policy and Research for the management of cancer pain and acute postoperative pain. We assessed analgesia in terms of cold pressor tolerance time and self-reported ratings of pain intensity and unpleasantness. Subjects receiving the highest dose of oral morphine showed significantly higher tolerance time than subjects receiving diphenhydramine. Neither morphine or diphenhydramine significantly reduced ratings of pain intensity and unpleasantness. Neuropsychological testing revealed that the two highest doses of morphine impaired the episodic retrieval of a word list, but the same doses did not affect motor, perceptual, or attentional tasks.
Observations on single neurons recorded in the sigmoid gyri of awake, nonparalyzed cats.

Abstract Extracellular recordings were made from 230 single neurons isolated in three regions of the sensorimotor cerebral cortex of awake, unparalyzed cats. The microdrive receptacle was affixed to the skull of each cat during aspetic surgery, and the recordings were done with the cat held in a net hammock. Cats rapidly adapted to the recording situation, often dozing or falling asleep during the recording session. Neuronal activity was evoked by forelimb manipulation. Once isolated, the size and configuration of the excitatory receptive field was determined, using various forms of natural stimulation; any spontaneous activity was also recorded. The neurons responded to discrete stimulation with a burst of spikes; a few showed sustained discharge to prolonged cutaneous stimulation. The excitatory receptive fields were continuous and were either confined to the contralateral forelimb, occupied both forelimbs and the thorax, or included the whole body surface. The behavior of some additional neurons during intravenous anesthetic injection, during electrical stimulation of limb nerves via surgically implanted electrodes, and during sleep-wake cycles was also examined. The similarities and differences between samples from anesthetized and from awake, unparalyzed cats are discussed.
Large-signal theory of a two-stage wideband gyro-TWT

A self-consistent large-signal theory is used to obtain gain and efficiency of the two-stage tapered gyro-TWT in a nonuniform external magnetic field. Calculations show that it is possible to design a device having 45 percent bandwidth at 45-dB gain and 25 percent efficiency if the axial velocity spread of the beam electrons is zero. It is found that the gain and bandwidth are very sensitive to the degree of beam velocity spread, the external magnetic field profile, and the various beam and circuit parameters. We also derive an expression for the efficiency under quasi-linear approximation in order to get a physical understanding of the device performance.
The moisture‐factor in climate

It is pointed out that in order to evaluate the moisture-factor in climate, the moisture supply or the precipitation must be compared with the water-needs or the potential evapotranspiration, The distribution of precipitation through the year never coincides with, and seldom parallels, the distribution of potential evapotranspiration. When the precipitation is in excess of the need, the surplus goes to recharge ground-water and produce runoff. When the precipitation does not equal the need, there is a deficiency which results in drought. Data on precipitation and potential evapotranspiration are presented for sixteen stations in the United States and tropical America
The Effects of Persuasive Communication On Attitudes of Smokers and Non-Smokers of Cigarettes

An experiment to determine the relationship between levels of cigarette smoking, persuasive communication, and attitude change showed outcomes quite different from those predicted by theories of co...
Coal-Fueled Diesel Cycle Simulation: The Role of Group Effects

An existing coal-water slurry fueled diesel engine cycle simulation was modified to include particle-to-particle and droplet-to-droplet interactions during the combustion and vaporization processes. Two aspects of these interactions, known as group effects, were considered. Group Effect Number 1 relates to the species concentrations and temperature profiles between particles during combustion and between droplets during vaporization. Group Effect Number 2 relates to the blockage of air entrainment to the fuel region due to the large momentum flux of volatiles and CO during combustion or water vapor during vaporization