cssi/SciSciGPT-SciSciNet huggingface dataset:
Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies. Currently, there is no standard or effective therapy for ATC. Drug repurposing for cancer treatment is an emerging approach for identifying compounds that may have antineoplastic effects. The aim of this study was to use high-throughput drug library screening to identify and subsequently validate novel therapeutic agents with anticancer effects in ATC. We performed quantitative high-throughput screening (qHTS) in ATC cell lines (SW-1736, 8505C, and C-643), using a compound library of 3282 drugs. qHTS identified 100 compounds that were active in all three ATC cell lines. Proteasome inhibitors were one of the most active drug categories according to enrichment analysis. Of the three proteasome inhibitors screened, a second-generation proteasome inhibitor, carfilzomib, was the most active. Treatment of ATC cells with carfilzomib significantly inhibited cellular proliferation and induced G2/M cell cycle arrest and caspase-dependent apoptosis. Mechanistically, carfilzomib increased expression of p27 (CDKN1B) and decreased expression of the anti-apoptotic protein ATF4. Pretreatment with carfilzomib reduced in vivo metastases (lung, bone, liver, and kidney) and disease progression, and decreased N-cadherin expression. Carfilzomib treatment of mice with established, widely metastatic disease significantly increased their survival, without significant toxicity. Our findings support the use or clinical study of carfilzomib as a therapeutic option in patients with advanced and metastatic ATC.
Studies of Prostaglandin Action on the Glomerular Microcirculation

There is a growing body of evidence to suggest that prostaglandins exert important physiological influences on the renal cortical microcirculation.1–4 We report here our findings regarding the actions of prostaglandins (PGs) E2 and I2 (prostacyclin) on the forces and flows that govern glomerular ultrafiltration in the Munich—Wistar rat.
Regulated endocytosis in a chloride secretory epithelial cell line

The colonic epithelial cell line T84 has been shown to be a good model to investigate the regulation of Cl- secretion by the adenosine 3',5'-cyclic monophosphate (cAMP)-mediated second messenger cascade. Regulated exocytic insertion and endocytic retrieval of transport proteins, or proteins that regulate transport proteins, is one mechanism proposed to regulate plasma membrane solute permeabilities. The aims of our studies were to characterize endocytic processes in T84 cells and to investigate their regulation by known activators of Cl- secretion that are mediated by the cAMP second messenger cascade. Forskolin, an activator of adenylate cyclase, caused a marked inhibition of endocytic uptake of the fluid-phase marker horseradish peroxidase (HRP) and the adsorptive marker wheat germ agglutinin conjugated to HRP. Similar inhibition was obtained with vasoactive intestinal peptide, a secretagogue whose receptor is coupled to adenylate cyclase, and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, a membrane-permeable cAMP analogue. 1,9-Dideoxy-forskolin, a forskolin analogue that fails to activate adenylate cyclase, was without effect on endocytosis. Our data show that the net rate of endocytosis, as measured by fluid-phase uptake, is decreased by a cAMP-mediated mechanism. Because the number of Cl- channels or associated regulatory proteins in the plasma membrane reflects a balance between their exocytic insertion and endocytic retrieval, we propose that the cAMP-mediated decrease in endocytosis could contribute to the concomitant increase in plasma membrane Cl- permeability.
Convex Optimization

Convex optimization problems arise frequently in many different fields. A comprehensive introduction to the subject, this book shows in detail how such problems can be solved numerically with great efficiency. The focus is on recognizing convex optimization problems and then finding the most appropriate technique for solving them. The text contains many worked examples and homework exercises and will appeal to students, researchers and practitioners in fields such as engineering, computer science, mathematics, statistics, finance, and economics.
Review: Architectural Space in Eighteenth-Century Europe: Constructing Identities and Interiors by Denise Amy Baxter, Meredith Martin

Denise Amy Baxter and Meredith Martin editors. Architectural Space in Eighteenth-Century Europe: Constructing Identities and Interiors . Farnham, Surrey, and Burlington, Vermont: Ashgate Publishing, 2010, 284 pp., 51 b/w illus. $119.95, ISBN 9780754666509 It is hard to believe that there was once a time when the decorated interior hovered at the margins of architectural history. Interiors are now the subject of such widespread and innovative scholarly attention that one can easily forget how undertheorized they used to be, and particularly how infrequently domestic interiors appeared in histories of the built environment. Recent decades have witnessed what could be called the "rise of the interior" within the study of architecture, a disciplinary shift that has significant implications for the eighteenth century. That era's architects and patrons devoted extraordinary attention to the design and outfitting of interiors, and it could be argued that the interior broadly understood became a metaphor for new cultural practices and new sensibilities. This is the implication of Denise Amy Baxter and Meredith Martin's vivid and stimulating collection of essays on eighteenth-century architectural space. The book contributes vitally to our understanding of eighteenth-century interiors, and its strength is that it conceptualizes the interior not just as pure space, but as space engaging and overlapping with other conceptions of interiority that derive from political, social, and psychic identities. It also displays how creative the study of interiors has become and the richness of the material available in that century. Baxter's introduction frames the book with a series of theoretical formulations. These derive largely from Michel de Certeau's notion of space as a "practiced place," an important concept for this collection, and Henri Lefebvre's understanding of space as a social production. The book seeks to present spaces not as static and unified, but as active entities contested by their occupants, in …
Evolving Identities among Russian-Born Buriat Mongolian Children in a Chinese Bilingual School.

This article addresses identity issues among a specific group of Indigenous youth, young Buriat Mongolian students, born in Russia, who struggled to understand their sense of cultural identity while living and studying in Chinese Inner Mongolia. This qualitative research project employed ethnographic methodology. Sociocultural theory, specifically Bakhtin, was employed to analyse findings. Results indicated that ties to the land, family practices and spiritual practices are significant identity markers for the Buriat youth involved in this study and Buriat parents and elders taught young Buriats about the moral dimensions of living upon Buriat lands.
Novel therapies of diabetic nephropathy

Diabetic nephropathy is currently the most common cause of end stage renal disease not only in the Western hemisphere but also in the developing nations. While the available therapeutic options rem...
Efficient face recognition using local derivative pattern and shifted phase-encoded fringe-adjusted joint transform correlation

An improved shifted phase-encoded fringe-adjusted joint transform correlation technique is proposed in this paper for face recognition which can accommodate the detrimental effects of noise, illumination, and other 3D distortions such as expression and rotation variations. This technique utilizes a third order local derivative pattern operator (LDP3) followed by a shifted phase-encoded fringe-adjusted joint transform correlation (SPFJTC) operation. The local derivative pattern operator ensures better facial feature extraction in a variable environment while the SPFJTC yields robust correlation output for the desired signals. The performance of the proposed method is determined by using the Yale Face Database, Yale Face Database B, and Georgia Institute of Technology Face Database. This technique has been found to yield better face recognition rate compared to alternate JTC based techniques.
Practice and Thinking of Family Doctor Service

The family doctor system is an important way to deepen community health services, change the service model in new health care reform. Family doctor system, as new thing to community health, how to meet the needs of the people, to adapt to China’s national conditions, is still in the exploration and practice. In order to establish the family doctor system with Chinese characteristics, some problems and suggestions,through the concrete practice of Songjiang District, were put forward to provide policy basis for sustainable development of family doctor.
Fluoroscopy-Guided Biopsy

For most percutaneous biopsies, fluoroscopic guidance has been replaced by cross-sectional imaging. However, fluoroscopy remains a viable imaging modality for guiding biopsies of certain lesions involving the lung or bone. Fluoroscopy is also the preferred or essential imaging modality for guiding endoluminal biopsies of bile ducts and ureters and for transjugular liver and renal biopsies. Fluoroscopy has advantages over other imaging modalities in terms of real-time imaging, wide availability, and lower cost. The addition of C-arm cone-beam computed tomography to new generation of angiography units may help overcome some of the shortcomings of fluoroscopy to guide biopsies in the future. This chapter outlines the equipment, advantages, disadvantages, applications, and techniques used in fluoroscopy-guided biopsies.
In Vivo Interrogation of the Hypoxic Transcriptome of Solid Tumors: Optimizing Hypoxic Probe Labeling with Laser Capture Microdissection for Isolation of High-Quality RNA for Deep Sequencing Analysis

Global gene expression analysis is a powerful method for identifying biological networks and regulatory mechanisms that govern cellular or tissue-level responses to physiologic stress. In the context of tumor biology, differential gene expression studies have provided information about the growth, aggressiveness, prognosis, and therapeutic response of tumors in patients. Scientists are using these valuable data to investigate pathways that can be targeted therapeutically with the goal of improving patient outcome. RNA sequencing enables nucleotide resolution of expression of whole transcriptomes, but arrives with a new set of challenges surrounding the management and analysis of large datasets. This chapter aims to review technical advancements to current methods for isolating high-quality RNA for sequencing studies directly from hypoxic tissues and introduces select widely used applications for gene expression analyses of next-generation sequencing data.
WE-H-BRA-02: Radiobiological Modeling of Tumor Control Probability (TCP) and Radiation-Induced Pneumonitis (RP) for Lung Cancer Patients Treated with Monte Carlo-Based Lung SBRT

Purpose: To present radiobiological modeling of TCP using tumor size-adjusted BED(s-BED)and PTV(D99) to lung SBRT patients treated with X-ray Voxel Monte Carlo(XVMC) algorithm, apply parameterized Lyman-NTCP model to predict grade-2 RP and subsequently, compare with clinical outcomes/observations. Methods: Dosimetric parameters and clinical follow-up for XVMC-based lung-SBRT patients were retrospectively evaluated. Patients were treated at Novalis-TX with hybrid(2 non-coplanar partial-arcs plus 3–6 static-beams)plan using HD-MLC/6MV-SRS-beam.For TCP,s-BED modelling was utilized: TCP=EXP[sBED-TCD50]/k/(1.0+EXP[sBED-TCD50]/k), where k=31Gy corresponding to TCD50=0Gy and s-BED was defined as BED10 minus 10 times the tumor diameter(in centimeters)by Ohri et al.(IJROBP,2012). For 2-yr local-control, we used more-realistic MC-computed PTVD99 as a predictive parameter, s-BED(D99).Due to relatively shorter median follow-up interval(12-months),Kaplan-Meier curves were generated to estimate 2-yr observed local-control and compared to predicted-rate by TCP modeling. For NTCP, we employed parameterized Lyman-NTCP model utilizing normal-lung DVH and α/β=3Gy fitted to predict grade-2 RP after lung-SBRT. Results: Total 108 patients (137 tumors) treated for 35–70Gy in 3–5 fractions, either primary-lung(n=74)or metastatic-lung(n=53)tumors were included.F or the given prescription dose with MC-computed MUs, 2-yr local-control rates with s-BED(D99) was 87±8%. Kaplan-Meier generated observed local-control rate at 2-yr was 87.5%,suggesting that PTV(D99) could be a potential predictor (p-value=0.38). Observed vs predicted TCP for primary-lung tumors and metastatic tumors were 97% vs 88±7% and 94% vs 86±9%.NTCP model predicted well for symptomatic-RP with predicted vs observed (3±5% vs 2%). Radiographic and clinically significant RP was observed in 13% and 2% of patients. Higher rates of radiographic change were observed in patients who received >50Gy compared to ≤50Gy(24% vs 10%). Conclusion: Utilizing MC-computed PTVD99, our TCP results were well correlated with clinical outcome. The predicted grade-2 RP rate was comparable to clinical observations. Clinical application of these radiobiological models may potentially allow for target dose escalation and/or lung-toxicity reduction. Further validation of these radiobiological models with longer follow up interval for large cohorts of lung-SBRT patients is anticipated.
Structural drivers of function in information processing networks

Structural configuration drives functionality in a range of different natural and artificial information processing systems. In this study, we use feedforward neural networks to evaluate the impact of structural variations on the ability of a network to learn and retain representations of external information. Performance is evaluated by statistically analyzing the error in the representations produced by parallel and layered networks during supervised, sequential function approximation. By varying the initial network state and the time given to learn the information, we identify tradeoffs between configurations that optimize for the best versus worst case scenarios and for the production of accurate versus retainable and generalizable representations of information. We show that these tradeoffs are maintained in larger networks and for variations in the information presented to the networks. By characterizing the curvature, depth, and participation of network connections about local error landscape minima, we find that variations in landscape structure give rise to the observed tradeoffs in performance. Consistently deep, narrow minima enable parallel networks to produce highly accurate solutions at the cost of more frequent failure in retention and generalizability. In contrast, variability in the depth and curvature of local minima enables layered networks to produce coarse but generalizable solutions at the cost of hindering consistent accuracy. Identifying structural drivers of functional performance is crucial for understanding both successes and limitations of information processing systems.
De novo, systemic, deleterious amino acid substitutions are common in large cytoskeleton‑related protein coding regions

Human mutagenesis is largely random, thus large coding regions, simply on the basis of probability, represent relatively large mutagenesis targets. Thus, we considered the possibility that large cytoskeletal-protein related coding regions (CPCRs), including extra-cellular matrix (ECM) coding regions, would have systemic nucleotide variants that are not present in common SNP databases. Presumably, such variants arose recently in development or in recent, preceding generations. Using matched breast cancer and blood-derived normal datasets from the cancer genome atlas, CPCR single nucleotide variants (SNVs) not present in the All SNPs(142) or 1000 Genomes databases were identified. Using the Protein Variation Effect Analyzer internet-based tool, it was discovered that apparent, systemic mutations (not shared among others in the analysis group) in the CPCRs, represented numerous deleterious amino acid substitutions. However, no such deleterious variants were identified among the (cancer blood-matched) variants shared by other members of the analysis group. These data indicate that private SNVs, which potentially have a medical consequence, occur de novo with significant frequency in the larger, human coding regions that collectively impact the cytoskeleton and ECM.
A comparison of suitability models to identify prehistoric agricultural fields in western New Mexico

Abstract Suitability models can help identify prime environments for a specific form of agricultural field, ak chin, that is difficult to locate with standard archaeological field methods. Using data from western New Mexico, we applied remote sensing and a geographic information system to develop suitability models based on a small training data sample. Three models, Mahalanobis Typicality, Maximum Entropy, and Multi-Criteria Evaluation Ordered Weighted Average, were used and the resulting suitability estimates were visually compared to known patterns of ak chin agriculture and quantitatively compared using receiver operating characteristic area under the curve. Although archaeological fieldwork is needed to verify these results, receiver operating characteristic validation indicates that Mahalanobis Typicality and Maximum Entropy performed well in identifying the potential location of previously undiscovered prehistoric agricultural fields.
Learner beliefs and corrective feedback in telecollaboration: A longitudinal investigation

Abstract While many studies highlight the role of telecollaboration for language learning, there is a lack of research investigating focus on form practices in synchronous, video-based exchange, let alone studies that do so longitudinally. Furthermore, none of the previous studies on telecollaboration examined beliefs as one of the individual differences that may mediate the effectiveness of corrective feedback (CF). This study examined the dynamicity of learner beliefs about error correction and its relationship with actual CF practices regarding provision and uptake of CF in a 14-week, Skype-based eTandem project between American and Japanese universities. The study collected mixed-method, longitudinal evidence from survey (N = 24), interaction (n = 6 pairs), and interview data (n = 5). The analysis of survey data revealed that by the end of the semester, the majority of participants chose recasts as the most preferred way to give and receive CF, since recasts were considered immediate, time-saving, unintrusive, and easy to provide. The interaction data revealed that successful uptake increased when CF was provided in the way learners preferred to receive it. However, no relationship was found between native speakers’ preferred method of CF provision and actual practices, suggesting a complex picture of face and identity negotiation as a friend vs. language tutor.
Opportunities to Improve Care of Hepatocellular Carcinoma in Vulnerable Patient Populations

Background Hepatocellular carcinoma (HCC) patients with Medicaid or no health insurance have inferior survival compared with privately insured patients. Safety-net hospitals that care for these patients are often criticized for their inferior outcomes. We hypothesized that HCC survival was related to appropriate surgical management. Study Design The American College of Surgeons National Cancer Database was queried for patients diagnosed with HCC (n = 111,481) from 1998 to 2010. Hospitals were stratified according to safety-net burden, defined as the percentage of patients with Medicaid or no insurance. The highest quartile, representing safety-net hospitals, was compared with lower-burden hospitals with regard to patient demographics, cancer presentation, surgical management, and survival. Results Patients at safety-net hospitals were less often white, had less income and education, but presented with similar stage HCC. Safety-net hospital patients were less likely to receive surgery (odds ratio 0.77; p Conclusions Vulnerable patients with HCC are commonly treated at safety-net hospitals, are less likely to receive curative surgery, and have worse short-term outcomes. However, safety-net patients who can endure liver surgery have a similar prognosis as patients at nonsafety-net hospitals. Providing equal access to surgery may improve survival for vulnerable populations of HCC patients.
Renal Cell Carcinoma With Pulmonary Metastasis and Metachronous Non-Small Cell Lung Cancer.

Abstract Introduction The development of a second primary malignancy in a patient with a preexisting diagnosis of metastatic cancer may be easily overlooked or misattributed to progression of disease. We report 3 patients with clear-cell renal cell carcinoma (RCC) metastatic to the lungs who were subsequently diagnosed with non–small-cell lung cancer (NSCLC). We examined the frequency of this occurrence within our institution and report on the radiographic findings that may help distinguish between metastatic RCC and primary lung cancers. Methods Patients who received systemic targeted therapy for metastatic RCC at our institution between January 2006 and October 2013 were identified, and the proportion and incidence rate for developing NSCLC with preexisting metastatic RCC were calculated. Results Two percent (3/151; 95% confidence interval [CI], 0.68%-5.68%) of patients treated for metastatic RCC with systemic targeted therapies at our institution were subsequently diagnosed with NSCLC, increasing to 3.5% (3/85; 95% CI, 1.21%-9.87%) among patients with known RCC pulmonary metastasis. The incident rate for development of NSCLC in patients with metastatic RCC was 0.87 per 100 person-years (95% CI, 0.22-2.4). Conclusion The subsequent diagnosis of a primary lung cancer in metastatic RCC patients occurred in 2% of patients at our institution and is underreported in the literature. Primary NSCLC may be underdiagnosed in patients with metastatic RCC. Both the radiographic appearance and clinical behavior of a lesion may hold clues that can help distinguish between a new primary and progression of metastatic disease.
The Rise of External Actors: Paper Tigers or Security Threats?

Intense debates have occurred among scholars and policymakers about the rise of other actors, particularly China and Russia. This chapter begins with an examination of the sources of power, analyzing hard power and economic power. The chapter shows that the US has the largest economy in the world. In addition, the US continues to outspend every country in the world on defense. This work then turns to the rise of other powers, focusing on Brazil, Russia, and China. Some scholars have argued that the rise of China will inevitably lead to struggles between the US and China. The chapter examines the rise of China, particularly in the Americas, which has traditionally been the sphere of influence of the US. This piece also highlights the rise of Russia and the debates among experts about the potential implications for US national security.
Bartonella henselae in canine cavitary effusions: prevalence, identification, and clinical associations

Background Previous reports suggest an association between Bartonella infection and effusions in dogs and human beings. Objectives The aims of this study were to determine the prevalence of Bartonella infection in canine effusions and to investigate historic and clinical parameters predictive of Bartonella in dogs with effusions. Methods Canine cavitary effusions submitted for analysis and, if available, paired EDTA blood, were screened for Bartonella infection using the Bartonella α-proteobacteria growth medium enrichment culture/PCR diagnostic platform (Bartonella enrichment PCR or ePCR) at Galaxy Diagnostics, Inc. Results Bartonella henselaeDNA was PCR-amplified and sequenced from 15% (12/80) of sampled dogs. Enrichment culture prior to PCR testing was required for Bartonella detection in 92% (11/12) of cases. Twenty percent (4/20), 13% (8/60), and 0% (0/4) of dogs with pleural, peritoneal, and pericardial effusions, respectively, tested positive. Bartonella henselae was detected most frequently in the fall, and young and middle-aged dogs appeared to be overrepresented. Golden Retrievers and Yorkshire/Silky Terriers each comprised 25% of infected dogs (odds ratio 3.4 for Golden Retrievers). There was a weak association with hemorrhagic effusions. Fifty percent of Bartonella-positive dogs had hemorrhage as a component of their effusion compared to 37% of PCR-negative dogs (odds ratio 1.7). Conclusions Viable B henselae organisms occur in pleural and peritoneal effusions of dogs; the clinical relevance of which remains unclear and may represent opportunistic infection. Associations found in this study included seasonal variation, age, breed, and site of effusion.
Effects of Cimetidine on Parathyroid Hormone in Chronic Uremia

Recent case reports suggest suppression of immunoreactive parathyroid hormone (iPTH) with cimetidine in two patients with primary hyperparathyroidism. In both patients peptic ulcer disease led to medical treatment with cimetidine. In the first patient given oral cimetidine (800 mg then 400 mg daily) for 8 months, iPTH decreased from 20 times to 6 times normal1. No changes in serum calcium and phosphorus occurred, but inhibition of gastric acid secretion and ulcer healing were demonstrated. In the second patient, a woman with a parathyoid adenoma, cimetidine treatment (1200 mg daily) was associated with a decrease in iPTH levels from a value 2.5 times normal to a normal value2,3. Concommittantly, serum calcium decreased from 11.3 mg/dl to 10.3 mg/dl and serum phosphorus increased from 2.1 mg/dl to 2.7 mg/dl. One month after discontinuation of cimetidine therapy iPTH had rebounded to values thrice normal and serum calcium and phosphorus were 10.8 and 2.3 mg/dl, respectively.
Low-weight: high-stiffness glass fiber reinforced polymer beams with embedded piezoelectric fibers

This work presents a theoretical study of the effects on stiffness and deflection of embedding piezoelectric fibers within glass fiber reinforced polymer beams. Through this study, enhancements to the beam stiffness and flexural capabilities are analyzed as a result of the piezoelectric effect of the embedded piezoelectric fibers. Fiber orientation of glass fiber reinforced polymer laminated beams is optimized based on stiffness requirements following classical lamination theory. The piezoelectric effect on the glass fiber reinforced polymer beam is analyzed for simply-supported mechanical boundary conditions. The symmetric unidirectional general stacking sequence laminates are shown to have optimal stiffness and deflection behavior. The addition of piezoelectric fibers with d333 piezoelectric actuation mode further increases stiffness and reduces deflection. This enables tuning of the mechanical properties of the laminate beam. Introducing piezoelectric fibers to the reinforcing phase further optimizes the deflection range under bending while additionally minimizing the weight of the structure. The strengthening effect of the piezoelectric fibers can reduce the required number of laminate layers while maintaining optimal behavior.
Chemical reactions at the Au/InP interface

Abstract : Chemical reactions at the Au/InP interface were investigated in the temperature range 25 510C by x-ray diffractometry, scanning electron microscopy and energy dispersive X-ray analysis. The samples were prepared by depositing gold films onto clean InP(100) single-crystal substrates under .000000001 torr vaccum. Spots appeared in SEM micrographs of the deposited film of a sample annealed at room temperature for 35 days, indicating that a solid state reaction had occurred. After the sample was heated to 330C under flowing N2 gas, dendritic islands were observed in the film. A 365C anneal turned the color of the Au film from yellow to pink, and Au, dendritic islands and Au2P3 were identified by X-ray diffractometry. In reacting with the InP substrate, dendritic islands produced silver-colored gamma and more Au2P3 at 450C. With respect to InP, gamma was relatively stable, and further reactions were minimal even when the sample was annealed at 510C for 40 min under atmospheric-pressure N2. The ternary phase diagram for the bulk Au-In-P system provides the basis for understanding the sequence of the above results and much of the information in the literature about Au/InP interfacial reactions.
Fire-climate-human interactions during the postglacial period at Sunrise Ridge, Mount Rainier National Park, Washington (USA)

Abstract With the creation of Mount Rainier National Park (MORA) in 1899 came the active management of the park's landscapes and a heavy emphasis on fire suppression. Today, managers at MORA seek to better manage current fire activity; however, this requires an improved understanding of past fire activity on the mountain. In this study high-resolution macroscopic charcoal analysis and pollen analysis of lake sediment records was used to reconstruct the postglacial fire and vegetation history for the Sunrise Ridge area of MORA. Fire activity was lowest during the Late Glacial when vegetation was sparse and climate was cool and dry. Fire activity increased during the early Holocene as the regional climate warmed and dried, and burnable biomass became more abundant. Fire activity continued to increase into the middle Holocene (until ca. 6600 cal yr BP) even as the regional climate became wetter and eventually cooler; the modern-day mesic forest and subalpine meadow landscapes of the park established at this time. Fire activity was generally highest and mean fire return intervals were lowest on Sunrise Ridge during the late Holocene, and are consistent with tree-ring based estimates of fire frequency. The similarity between the Sunrise Ridge and other paleofire records in the Pacific Northwest suggests that broad-scale climatic shifts, such as the retreat of the Cordilleran ice sheet and changes in annual insolation, as well as increased interannual climate variability (i.e., drought) particularly in the middle to late Holocene, were responsible for changes in fire activity during the postglacial period. However, abundant and increasing archaeological evidence from Sunrise Ridge during the middle to late Holocene suggests that humans may have also influenced the landscape at this time. It is likely that fires will continue to increase at MORA as drought becomes a more frequent occurrence in the Pacific Northwest.
On Producing Change in an Adversary

Public opinion polls indicate that “distrust of the Russians among the American people is about as universal as any feeling could be.” Our newspapers repeatedly refer to the “Red menace,” “Soviet intransigence,” “Communist trickery and deceit.” Leading Americans warn of the “Soviet threat to the American way of life” and castigate Communist China as an “outlaw among nations.” Many American scholars specializing in the study of Communism hold the view that the Communists are out to impose their system on the rest of the world and will succeed unless we are prepared to face up to a life-and- death competition with them.
Sef: A MEK/ERK Catcher on the Golgi

Subcellular compartmentalization is an emerging paradigm in signaling pathways including the Ras/MAPK pathway. In a recent issue of Developmental Cell, Torii et al. (2004) characterize a new MAPK scaffold, Sef, that resides on the Golgi apparatus, binds active MEK/ERK complexes, and permits signaling to cytosolic substrates but not nuclear targets.
Pyomyositis Diagnosed by Point-of-Care Ultrasound in the Emergency Department.

Abstract Background Currently, the role of ultrasound in diagnosing superficial abscesses is well validated, however, its role for deep space infections and intramuscular pathology is limited. Distinguishing between simple cellulitis and abscess is critical for emergency physicians (EP), as the treatment is very different. Management of cellulitis relies on antibiotic therapy, whereas abscess treatment requires incision and drainage. It is important that EPs can accurately distinguish between the two entities. Case Report We report a case of a 41-year-old man with a history of high blood pressure and poorly controlled diabetes who presented with right lateral thigh redness, warmth, and tenderness. A point-of-care ultrasound (POCUS) of the patient's right lateral thigh with a high-frequency linear (8 MHz) ultrasound probe showed a 2.93 × 3.38 × 6.0-cm complex fluid collection deep to the fascial plane, approximately 3.0 cm from the skin surface, that contained mixed echogenicities with posterior acoustic enhancement consistent with an intramuscular abscess of the vastus lateralis. The patient was diagnosed with pyomyositis of his vastus lateralis. He was started on vancomycin and admitted to the surgical service for antibiotic treatment and surgical drainage. Why Should Emergency Physicians Be Aware of This? This case demonstrates that the use of POCUS by EPs can facilitate the rapid recognition and treatment of a disease that is challenging to diagnose on physical examination and can be potentially life-threatening if missed. EPs can consider performing a POCUS when evaluating skin infections to ensure rapid diagnosis and appropriate medical care for a potentially severe condition.
The Effects of Discrete Work Shifts on a Nonterminating Service System

Hospital emergency departments (EDs) provide around-the-clock medical care, and as such are generally modeled as nonterminating queues. However, from the care provider's point of view, ED care is not a never-ending process, but rather occurs in discrete work shifts and may require passing unfinished work to the next care provider at the end of the shift. We use data from a large, academic medical center ED to show that the patients' rate of service completion varies over the course of the physician shift. Further, patients that have experienced a physician handoff have a higher rate of service completion than non-handed off patients. As a result, a patient's expected treatment time is impacted by when in the physician's shift treatment begins. We also show that patients that have been handed off are more likely to revisit the ED within three days, suggesting that patient handoffs lower clinical quality. Lastly, we use simulation to show that shift length and new-patient cutoff rules can be used to reduce handoffs, but at the expense of system throughput.
The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5-Year Follow-Up: The Role of Level of Response.

Author(s): Courtney, Kelly E; Infante, Maria Alejandra; Brown, Gregory G; Tapert, Susan F; Simmons, Alan N; Smith, Tom L; Schuckit, Marc A | Abstract: BackgroundAcute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5nyears later.MethodsYoung adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5nyears later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems.ResultsIn the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group.ConclusionsThis study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.
Kant on the Rationality of Morality

Kant claims that the fundamental principle of morality is given by pure reason itself. Many have interpreted Kant to derive this principle from a conception of pure practical reason (as opposed to merely prudential reasoning about the most effective means to empirically given ends). But Kant maintained that there is only one faculty of reason, although with both theoretical and practical applications. This Element shows how Kant attempted to derive the fundamental principle and goal of morality from the general principles of reason as such, defined by the principles of non-contradiction and sufficient reason and the ideal of systematicity.
Anti-inflammatory Actions of Oat Beta Glucans in an Exercise Stress Model

Beta glucans are dietary fiber but some goes intact into circulation. This could generate systemic anti-inflammatory actions. In young adult men, beta glucans (3 g/d, 4 wk) as oat bran (Oatvantage(...
The Current State of Physics Plan Review Training in Medical Physics Residency Programs in North America.

Abstract Purpose This study aimed to identify the current state of residency training in physics plan reviews. Methods and Materials A voluntary, anonymous survey was sent to all program directors of accredited therapeutic medical physics residency programs in North America. Survey questions were developed to determine whether and how residents are trained in physics plan reviews. Survey questions were developed using expert validation and cognitive pretesting. Results Using a prospectively approved study (COMIRB 18-1073), responses were collected from 70 program directors, representing a 70% response rate. All respondents (100%) designated patient safety to be the purpose of physics plan reviews. Of the respondents, 94% indicated that physicists should first receive training in physics plan reviews while in a residency program. The vast majority of respondents (99%) provide training to residents in physics plan reviews. Although 57 programs (81% of respondents) have residents perform physics plan reviews as part of clinical practice (with varying levels of independence), 13 programs (19% of respondents) do not. The majority of respondents use the following training methods: observe staff physicists (96%), perform supervised reviews on actual patients for training or clinical practice (93%), use a checklist (80%), and read reference materials (62%). Although simulation plans with embedded errors would be implemented by 71% of respondents, they are currently used in only 19% of programs. Conclusions The present study is the first to characterize chart-check teaching practices in medical physics residency programs. The vast majority of programs currently train residents in physics plan reviews. The most common teaching methods are observing and performing physics plan reviews, but there is variability in the level of resident involvement in clinical practice for physics plan reviews. There is room for the field to consider advancing current training methods, which is especially important given the critical roles that physics plan reviews have with regard to patient safety.
Refining insulin signaling in the proximal tubule at the level of the substrate.

Insulin has many varied actions in the proximal tubule. Two distinct activities include upregulation of sodium/bicarbonate reabsorption and downregulation of gluconeogenesis. The inability to perform these 2 tasks simultaneously under fed and fasted conditions can lead to hyper- or hypoglycemia, acidosis, and/or impaired extracellular fluid regulation. Nakamura and colleagues illuminate our understanding of this process, which appears to be managed in part by recruitment of different insulin receptor substrates under different physiological conditions.
Analogues of Alladi's formula

Abstract In this note, we mainly show the analogue of one of Alladi's formulas over Q with respect to the Dirichlet convolutions involving the Mobius function μ ( n ) , which is related to the natural densities of sets of primes by recent work of Dawsey, Sweeting and Woo, and Kural et al. This would give us several new analogues. In particular, we get that if ( k , l ) = 1 , then − ∑ n ⩾ 2 p ( n ) ≡ l ( mod k ) μ ( n ) φ ( n ) = 1 φ ( k ) , where p ( n ) is the smallest prime divisor of n, and φ ( n ) is Euler's totient function. This refines one of Hardy's formulas in 1921. At the end, we give some examples for the φ ( n ) replaced by functions “near n”, which include the sum-of-divisors function.
An Architectural Theory of Relations

In An Architectural Theory of Relations: Sigfried Giedion and Team X, Sarah Deyong uncovers an important aspect of the theoretical framework underpinning Team X’s work: Sigfried Giedion’s philosophical orientation and aesthetic theories in the late 1940s and early 1950s. Because Giedion is often seen as an old-guard CIAM (Congres Internationaux d’Architecture Moderne) member that Team X opposed, his contribution to Team X’s design method has been grossly underestimated. Deyong rectifies the link between Giedion and Team X to accomplish two goals. She casts new light on Giedion’s unique contribution to the reinvention of modern architecture at midcentury, and she offers a new interpretation of Team X’s legacy, constructed around missing pieces of the group’s intellectual history. Deyong’s evidence for this argument derives from two archival sources in particular: Giedion’s papers in the Archives of the Institute for the History and Theory of Architecture (gta Archives) in Zurich, and the unpublished transcripts of Team X meetings, housed in the Collection Het Nieuwe Instituut in Rotterdam.
Citizenship on the move: the deprivation and restoration of emigrants’ hukou in China

Scholars have long debated whether international migration impinges on states’ control over transborder populations. In this article, I lay bare how states consolidate control through the calculate...
Virtual Screening for Ligand Discovery at the σ1 Receptor.

The σ1 receptor is a transmembrane protein implicated in several pathophysiological conditions, including neurodegenerative disease (J. Pharmacol. Sci.2015127 (1), 1729), drug addiction (Behav. Pharmacol.201627 (2-3 Spec Issue), 10015), cancer (Handb. Exp. Pharmacol.2017244237308), and pain (Neural Regener. Res.201813 (5), 775778). However, there are no high-throughput functional assays for σ1 receptor drug discovery. Here, we assessed high-throughput structure-based computational docking for discovery of novel ligands of the σ1 receptor. We screened a library of over 6 million compounds using the Schrodinger Glide package, followed by experimental characterization of top-scoring candidates. 77% of tested candidates bound σ1 with high affinity (KD < 1 μM). These include compounds with high selectivity for the σ1 receptor compared to the genetically unrelated but pharmacologically similar σ2 receptor, as well as compounds with substantial crossreactivity between the two receptors. These results establish structure-based virtual screening as a highly effective platform for σ1 receptor ligand discovery and provide compounds to prioritize in studies of σ1 biology.
A Priority-Based Queueing Mechanism in Software-Defined Networking Environments

To support latency-sensitive applications (e.g., emergency response) in Software-Defined Networking (SDN) environments, reliable Quality of Service (QoS) mechanisms are needed to ensure the minimization of end-to-end (E2E) latency and control response time. In this research, we design a double-queue system with feedback, named QoSP, to improve data-control communication performance and impose efficient queueing control in SDN. We further study a priority-based queueing scheme to achieve differentiated QoS provisioning via maintaining multiple OpenFlow queues with different priorities at the switch ports of a data plane. The prototype of QoSP is implemented and evaluated on the NSF-sponsored GENI testbed.
The Placenta - Fast, Loose, and in Control.

Clonal Peregrinations in the Placenta A genomic analysis of 86 placentas revealed a large number of somatic variants — roughly equivalent to those found in pediatric cancer — as well as large clone...
Technical note: On the impact of the kV imaging configuration on doses from planar images during motion-synchronized treatments on Radixact®.

Kilovoltage radiographs are acquired during motion-synchronized treatments on Radixact to localize the tumor during the treatment. Several previous publications have provided estimates of patient dose from these planar radiographs. However, a recent hardware update changed several aspects of the kV imaging system, including a new X-ray tube, an extended source-to-axis distance (SAD), and a larger field size. This is denoted the extended configuration. The purpose of this work was to assess the impact of the configuration change on patient dose from these procedures. Point doses in water were measured using the TG-61 protocol for tube potentials between 100 and 140 kVp for both the standard and extended configurations under the same water tank setup. Comparisons were made for equal mAs since the same protocols (kVp, mAs) will be used for both configurations. In comparison to the standard configuration, doses per mAs from the extended configuration were found to be ~66% less and falloff less steep due to the increased SAD. However, a larger volume of tissue is irradiated due to the larger field size. Beam quality for a given tube potential was the same as determined by half-value layer measurements. Both kV configurations are available from the vendor, therefore, the values in this work can be used to compare values previously published in the literature for the standard configuration or to intercompare doses from these two system configurations.
Climatizing Human Rights: Economic and Social Rights for the Anthropocene

The climate emergency poses an existential challenge to the human rights project. If human rights are to remain relevant in the Anthropocene, budding theoretical, doctrinal, and advocacy efforts to address the climate emergency need to be deepened and expanded. The task of urgently advancing climate action through rights-based norms, frames and tactics is what I have called “climatizing” human rights. In this paper, I focus on economic and social rights (ESRs) and propose two avenues for the climatization of ESRs. The first route involves applying the existing ESR conceptual and legal tools to the climate emergency. This route entails both addressing the impacts of global warming on the enjoyment of human rights and ensuring that climate policies follow human rights norms regarding substantive and procedural equity. The second, complementary route entails adapting and updating human rights to the Anthropocene’s realities and challenges. In addition to a concern with guaranteeing at least a minimum of individual freedoms, material welfare and equity compatible with human dignity, this goal requires protecting the planetary boundaries that make life on Earth possible – and thus a concern with the limits to human economic activity. Between the minimum and the maximum there is a vast space for human activities that are productive, equitable, regenerative, and respectful of future generations and the planet.