cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1468: Antagonism of platelet-derived growth factor receptor-α as a potential therapeutic for prostate cancer bone metastases

Prostate adenocarcinoma is the second leading cause of cancer death among men, due primarily to the fact that the majority of prostate cancers will eventually spread to the skeleton. Metastatic dissemination requires a complex series of coordinated events that result in cells that escape from the primary tumor into the circulation and eventually colonize distant organs. The ability of disseminated cancer cells to evolve into metastases of clinically significant size depends strongly on their compatibility with, and ability to utilize, this new micro-environment. We previously showed that bone-metastatic prostate cancer cells exposed to human bone marrow respond by activation of cell survival pathways, such as PI3K/Akt., and that these events are mediated by the alpha-receptor for platelet-derived growth factor (PDGFRα). We also have shown that prophylactic antagonism of this receptor using IMC-3G3, a monoclonal, humanized antibody currently in phase II trials, was able to significantly reduce tumor burden in an in vivo model of skeletal metastasis. Here we show that IMC-3G3 can be used in a curative manner to reduce the growth of previously established skeletal lesions. In addition, we have successfully combined this antibody with zoledronic acid, a bisphosphonate commonly used to treat skeletal metastases, with encouraging results. Interestingly, treatment with a monoclonal antibody targeting only host PDGFRα failed to show any significant difference over saline treated mice. Lastly, we sought to dissect the mechanism by which PDGFRα may exert its role within the bone microenvironment. We provide evidence that soluble components of human bone marrow can activate PDGFRα through a mechanism that does not require the canonical binding of PDGF ligand(s) to the receptor. To establish the relevance of this phenomenon in vivo, we employed a PDGFRα mutant lacking the extracellular ligand-binding domain. Our studies show that this truncated PDGFRα was able to restore bone-metastatic potential of prostate cancer cells as effectively as the full-length form of the receptor. In addition, we have found that expression of PDGFRα, and its related signaling events, results in the regulation of a specific set of genes that we believe may aid in the survival and growth of metastatic prostate cancer cells within the bone. Studies to understand the contribution of several of these putative bone metastatic genes are currently underway in our laboratory. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1468.
Desegregation and Its Chances for Success: Northern and Southern Views

T HE mass media have kept the nation's attention focused sharply on race relations in the South since the momentous Supreme Court decision of 1954 abolishing racial segregation in public education. Little notice has been taken, however, of attitudes towards racial integration of northerners and how these attitudes compare with those of southerners. As part of a larger study of regional differences in intolerance of the Negro, attitude data concerning a number of facets of racial segregation were gathered in both the North and South. Among other measures, a 12-item, Likert-type scale of anti-Negro prejudice (the N scale) and a 10-item, Likert-type scale of authoritarianism (the F scale) were included in the interview schedule.' Six of the N scale's items bear on the subject of racial integration. In addition, direct questions concerning the discussion, viewed importance, and the possible success of school desegregation were asked. Employing public opinion polling techniques in four towns ranging in population from 4,000 to 14,000 in each region, two experienced interviewers collected data from 186 southerners and 180 northerners during the summer of 1955. The selection of white respondents from recently published town directories was done randomly. The final samples involved slightly younger, slightly less educated, and far more native born southerners than northerners-all differences that exist between the two regions taken as wholes. Random procedures were not employed in selecting the towns, however. Since all eight of them had to have new directories, they were probably somewhat more industrial and prosperous than average. Moreover, the southern communities, located in North Carolina and Georgia, were selected to have Negro densities in their populations varying from 10 percent to 45 percent. The northern towns, all located in New England, had less than 1 percent Negroes each. An introductory letter was mailed to all potential respondents within a week before the arrival of the interviewers. The letter informed the interviewee that his name had been selected by "chance" and that this poll was interested in determining the importance of mass media in shaping public opinion. The letter stressed the anonymity of the interview, and it did not refer in any way to questions concerning minority groups. The interview began with a series of questions concerning mass media reading and listening, and it seemed largely due to this guise that the blatantly phrased prejudice items of the study caused no interview break-offs. Upon arriving in each town, the interviewers first reported to the head of the local chamber of commerce and to the chief of police. Upon locating a sample member, the interviewer displayed a copy of the letter, briefly reminded him of its contents, and offered to return later if it were not convenient to be interviewed then for 20 minutes. Of the original sample 74 percent was located and of these only 8 percent refused to be interviewed.
A urea silver nitrate method for nerve fibers and nerve endings.

A silver nitrate stain for nerve fibers and endings applicable to paraffin sections on the slide utilizes the properties of urea to accelerate the procedure and improve the specificity of the stain. After removal of the paraffin the sections are run through absolute, 95% and 80% alcohol and placed for 60-90 minutes at 50-60°C. in: 1% aqueous silver nitrate, 100 ml.; urea, 20-30 g.; 1g. mercuric cyanide and 1 g. picric acid in 100 ml. of distilled water, 1-3 drops. After the silver bath they are rinsed quickly in 2 changes of distilled water and reduced for 3-5 minutes at 25-30°C. in: water, 100 ml.; sodium sulfite, anhydrous, 10g.; hydroquinone, 1-2g.; urea, 20-30g. They are then washed thoroughly in 4-5 changes of distilled water, passed through graded alcohols into 80% alcohol and examined under the microscope. If nerve fibers are not distinct, the sections are returned to the same urea-silver-nitrate bath for 10-15 minutes, rinsed, reduced, washed and dehydrated as before. This process may be repeated ...
CD4-Positive T-Cell Primary Central Nervous System Lymphoma in an HIV Positive Patient

Objectives: Primary central nervous system lymphomas (PCNSLs) in patients with human immunodeficiency virus (HIV) are predominantly B-cell lymphomas associated with Epstein-Barr virus (EBV) and rarely CD8-positive T-cell PCNSLs. Methods: Patient history, laboratory results, cerebrospinal fluid (CSF), imaging, and brain biopsy specimens were reviewed and tested for T-cell receptor clonality. Results : A 64-year-old HIV-positive woman sought treatment for lethargy and left-sided weakness. Brain imaging showed regional increased T2 signal with restricted diffusion in cerebral hemispheres. CSF flow cytometry revealed CD4-positive T lymphocytes with loss of CD3, CD5, and CD7. EBV-positive T-cell lymphoma was immunohistochemically confirmed on brain biopsy specimens. Molecular analysis detected clonal T-cell receptor gene rearrangement. The patient received intrathecal methotrexate and whole-brain radiation. She did not respond to treatment and was eventually placed in hospice care. Conclusions: To our knowledge, this is the first report of CD4-positive T-cell PCNSL in an HIV-positive patient and will help to raise clinical awareness of this previously unknown entity.
240PIL10 LOCUS AS A BIOMARKER OF MELANOMA SURVIVAL

ABSTRACT Aim: The 5-year survival rate for melanoma is higher than 90%, however there is a large degree of variability among patients. While clinicopathological variables provide a general prognostic value, there remains an urgent need for more personalized biomarkers to better predict survival outcomes. Immune related molecules, such as interleukins and cytokines, have been shown to contribute to melanoma progression via modulation of tumor immunogenicity, hence suggesting their potential as novel prognostic predictors. Methods: We have investigated germline variants tagging immunomodulatory genes for their impact on melanoma survival. This included the genotyping of 93 SNPs tagging 43 genes in a population of 1,022 patients. Using the clinical and pathological data available for these patients, we have developed a multivariate Cox model to assess the association between SNPs and recurrence-free and overall survival. Results: Multiple SNPs tagging a locus on 1q32.1 were associated with overall survival. This region contains four interleukin genes: IL10, IL19, IL20, and IL24. The strongest association was observed for rs3024493 located in a regulatory region of IL10 (P = 0.00069). In the same locus we have also replicated an association with overall survival for rs1800896, which has been suggested previously in small scale studies. In addition, using the data of 251 metastatic melanoma tumors from The Cancer Genome Atlas (TCGA) we have shown that IL10 expression strongly correlates with overall survival (P = 0.0015). Conclusions: Our findings suggest that the genetic variants in immunomodulatory genes may have a possible clinical utility as novel prognostic biomarkers. Most importantly, for IL10 our study not only validates previous associations with melanoma survival, but also identifies a novel independent SNP (rs3024493) conferring a more significant association effect with overall survival. The identification of multiple independent association signals located in regulatory regions of IL10, and the correlation of IL10 expression with clinical outcome observed in TCGA patients, suggest this locus as a putative prognostic marker of melanoma survival. Disclosure: All authors have declared no conflicts of interest.
The Need for Academia to Address Construction Site Safety through Design

Although it might seem natural for construction site safety to be addressed in the design phase, this has not evolved as a traditional task for designers. The need for change in this arena is quite apparent, as owners become more insistent on safety on their projects. From a purely ethical perspective, it is an obvious obligation for designers to address construction safety in their designs. From the professional codes of ethics, this is most clear for members of the National Society of Professional Engineers (NSPE) and less so for members of the American Institute of Architects (AIA). Despite this difference in the codes of ethics, the moral obligation is equally compelling for each group. The dilemma for designers is that they have not generally been trained to address construction safety in their designs. Designers generally learn about these techniques once they enter practice. This often occurs in an environment in which the legal advisors are very insistent that the designers not address construction safety in their designs, lest they increase their liability. While there are detractors from addressing safety in design, change is taking place and it is taking place at an accelerated rate. It therefore becomes incumbent on designers to know how to meet this task. Perhaps the best solution is for designers to enter the professional world well equipped with the needed knowledge so that designs will be safer for the construction workforce. This must be addressed aggressively in the various universities with full support of the accreditation bodies. Addressing safety in design is the right thing to do and with the necessary training this task can be performed effectively. Zero injuries should be the goal of every party in the construction process, including the designers.
Classification of sparse and irregularly sampled time series with mixtures of expected Gaussian kernels and random features

This paper presents a kernel-based framework for classification of sparse and irregularly sampled time series. The properties of such time series can result in substantial uncertainty about the values of the underlying temporal processes, while making the data difficult to deal with using standard classification methods that assume fixed-dimensional feature spaces. To address these challenges, we propose to first re-represent each time series through the Gaussian process (GP) posterior it induces under a GP regression model. We then define kernels over the space of GP posteriors and apply standard kernel-based classification. Our primary contributions are (i) the development of a kernel between GPs based on the mixture of kernels between their finite marginals, (ii) the development and analysis of extensions of random Fourier features for scaling the proposed kernel to large-scale data, and (iii) an extensive empirical analysis of both the classification performance and scalability of our proposed approach.
More than a feeling: When emotional reactions don't predict moral judgments

Many moral psychologists have proposed that the difference between people’s moral judgments about the Trolley and Footbridge dilemmas can be explained by their differing emotional responses to the dilemmas. In two experiments, we tested this explanation by presenting the dilemmas and measuring participants’ reactions using a self-report emotion measure (PANAS-X). As might be expected, participants experienced more intense emotions after reading moral dilemmas when compared to a non-moral dilemma. However, participants’ emotional reactions to the Trolley and Footbridge dilemmas did not differ. Our findings call the oft cited emotion explanation into question.
When Clergy are Threatened: Catholic and Protestant Leaders and Political Activism in Brazil

In the past three decades, observers have noted a steady rise in religious leaders’ engagement in Brazilian politics. What motivates this new activism? One prominent theory focuses on threat from religious competitors; other scholars point to church-state relations or theologically-driven political grievances. I argue that because of institutional and theological differences, Catholic and Protestant clergy are motivated into political action by different kinds of threat. I draw on two question order experiments embedded in a face-to-face survey of clergy prior to Brazil's 2014 election to examine how clergy react to threats from religious competition and from elected politicians. Threat from religious competition is associated with changes in topics of preaching among Catholics, who substitute social justice for personal morality messages. Protestant clergy instead react to ideological, policy-based threats, and secularization; these latter threats explain the much higher political engagement among Pentecostal and evangelical than Catholic clergy in 2014.
Lower bounds for rectilinear Steiner trees in bounded space

Abstract We prove that, in all dimensions, the total weight of a worst-case minimal rectilinear Steiner tree in the unit d-cube is at least n(d−1) d .
Irving’s Knickerbocker in Retrospect

Roughly a hundred miles away from the Port Folio group, the young Washington Irving convened a circle of friends in 1807 to give Manhattan its own essay serial on the British model, Salmagundi. Irving was also, like Dennie, a recalcitrant law student who barely passed the bar exam and muddled through several years of undistinguished practice before abandoning it to write full-time. The efforts of the Salmagundi circle, in fact, made an immediate impression on Dennie, who favorably noticed the serial and reprinted several essays from it in the Port Folio.1 Though Irving seems never to have had strong political commitments, Dennie saw in Salmagundi the work of ‘a well-principled Federalist’.2 In his view, the generally urbane air of Salmagundi, along with the ‘extensive knowledge of the world’ it displays, its ambition to ‘correct the manners, and improve the taste of the age’ and its drive to ‘expose the absurdity of our institutions’ allied the serial with the cultural politics that animated the Port Folio.3 Most of the qualities Dennie cites place Salmagundi firmly in the British essay tradition, but he detects a distinctively Federalist variant of this literary strain in the serial’s exposure of institutional absurdity in the Jeffersonian moment. Like the Port Folio, Salmagundi satirizes the short-sighted, anti-intellectual bent of what it sees as the new American populism.
Recombination-independent recognition of DNA homology for repeat-induced point mutation

Numerous cytogenetic observations have shown that homologous chromosomes (or individual chromosomal loci) can engage in specific pairing interactions in the apparent absence of DNA breakage and recombination, suggesting that canonical recombination-mediated mechanisms may not be the only option for sensing DNA/DNA homology. One proposed mechanism for such recombination-independent homology recognition involves direct contacts between intact double-stranded DNA molecules. The strongest in vivo evidence for the existence of such a mechanism is provided by the phenomena of homology-directed DNA modifications in fungi, known as repeat-induced point mutation (RIP, discovered in Neurospora crassa) and methylation-induced premeiotically (MIP, discovered in Ascobolus immersus). In principle, Neurospora RIP can detect the presence of gene-sized DNA duplications irrespectively of their origin, underlying nucleotide sequence, coding capacity or relative, as well as absolute positions in the genome. Once detected, both sequence copies are altered by numerous cytosine-to-thymine (C-to-T) mutations that extend specifically over the duplicated region. We have recently shown that Neurospora RIP does not require MEI-3, the only RecA/Rad51 protein in this organism, consistent with a recombination-independent mechanism. Using an ultra-sensitive assay for RIP mutation, we have defined additional features of this process. We have shown that RIP can detect short islands of homology of only three base-pairs as long as many such islands are arrayed with a periodicity of 11 or 12 base-pairs along a pair of DNA molecules. While the presence of perfect homology is advantageous, it is not required: chromosomal segments with overall sequence identity of only 35–36 % can still be recognized by RIP. Importantly, in order for this process to work efficiently, participating DNA molecules must be able to co-align along their lengths. Based on these findings, we have proposed a model, in which sequence homology is detected by direct interactions between slightly-extended double-stranded DNAs. As a next step, it will be important to determine if the uncovered principles also apply to other processes that involve recombination-independent interactions between homologous chromosomal loci in vivo as well as to protein-free DNA/DNA interactions that were recently observed under biologically relevant conditions in vitro.
Hc2 enhancement and giant Nernst effect in (TMTSF)2(PF)6

We discuss two recent discoveries in the title compound: 1) A strong enhancement in the critical field as the critical pressure for the SDW-superconductor phase boundary is approached and 2) the existence of giant resonances in the thermoelectric voltage as an applied magnetic field is rotated through the Lebed Magic Angles. 1) H c2 is highly anisotropic in this salt, but the enhancement is present for all field orientations. We suggest a model in which the near degeneracy of the superconducting and SDW states leads to a coexistence. The critical field is enhanced by the formation of thin slabs of superconductor (less than the penetration depth) parallel to the applied field and sandwiched by insulating SDW layers. As the temperature is lowered the slabs become thinner allowing a higher H c2 . 2) The thermoelectric voltage resonance indicates that the currents generated are locked-in to the interchain direction (magic angle) nearest parallel with the applied field. With the field to one side of the magic angle there is a Lorentz force up, on the other side of the magic angle the Lorentz force is down. The size of the thermoelectric voltage is 10 4 larger than might be expected from conventional transport theory.
Computer Simulations Of Three-dimensional Propagation In Ventricular Myocardium. The Effects Of Intramural Fiber Rotation And Resistive Inhomogeneity

Three-dimensional membrane-based simulations of action potential propagation in ventricular myocardium were performed. Specifically, the effects of the intramural rotation of the fiber axes and resistive inhomogeneity on the pattern of activation were examined. Two models were built, with 28,977 microscopic elements arranged in rectangular parallelpipeds in each model. Simulations used the nonlinear Ebihara and Johnson membrane equations for the fast sodium current. Constructed models had histologic features of ventricular myocardium. All simulations were performed on an IBM 3090 at the Utah Supercomputer Institute.
Radiographic evaluation in clinical practice of the types and stage of incisor tooth resorption and hypercementosis in horses.

SummaryBackground There are several reports of incisor tooth resorption and hypercementosis in horses but to date studies have been limited in case numbers and to advanced lesions. Tooth resorption in other species is a radiographic diagnosis of types of resorption that are often identified before clinical signs. Our goal was to evaluate radiographically incisor tooth resorption in a large population of horses, utilising interpretation criteria from canine and human dentistry. Objective To document and classify incisor tooth resorption and hypercementosis. Study design Retrospective descriptive case series. Methods Horses presented for routine dental care, >5 years old were included only if owners were unaware of incisor pathology. Radiographs (3 views) were obtained of the incisor teeth and incisor teeth resorption was classified according to the radiographic criteria described for humans and dogs. Hypercementosis and its location were recorded. Results Tooth resorption was detected in 149 of 169 (88.2%) horses and 951 of 1952 (48.7%) of incisor teeth. The classification system used was applicable in 926 (97.2%) of 951 affected teeth. Hypercementosis was detected in 34 (20.1%) horses and 148 (7.6%) teeth. As horses increased in age, resorption and hypercementosis was more frequent; no significant differences were found among sex or breed categories. All horses with hypercementosis had resorption, but only 23.4% of horses with resorption had hypercementosis. Advanced (stage ≥3) resorption was detected in 159 (8.1%) teeth and 54 (32.0%) horses in an otherwise clinically healthy population. Main limitations Certain horses’ anatomy precluded isolation of the mandibular third incisor teeth from the canine teeth due to superimposition. Conclusions Incisor tooth resorption, in particular external replacement resorption and external inflammatory resorption, is common in horses. Hypercementosis is consistently associated with resorption but the inverse association is inconsistent. This article is protected by copyright. All rights reserved.
Fully inorganic cesium lead halide perovskites with improved stability for tandem solar cells

A semiconductor that can be processed on a large scale with a bandgap around 1.8 eV could enable the manufacture of highly-efficient low cost double-junction solar cells. Solution-processable organic-inorganic halide perovskites have recently generated considerable excitement as absorbers in single-junction solar cells, and while it is possible to tune the bandgap of (CH 3 NH 3 )Pb(Br x I 1−x ) 3 between 2.3 and 1.6 eV by controlling the halide concentration, optical instability due to photo-induced phase segregation limits the voltage that can be extracted from compositions with appropriate bandgaps for tandem applications. Moreover, these materials have been shown to suffer from thermal degradation at temperatures within the processing and operational window. By replacing the volatile methylammonium cation with cesium, it is possible to synthesize a mixed halide absorber material with improved optical and thermal stability, a stabilized photoconversion efficiency of 6.5%, and a bandgap of 1.9 eV.
Topology management algorithms for large-scale aerial high capacity directional networks

The U.S. Department of Defense with the Joint Aerial Layer Network (JALN) concept as well as public companies like Google with their Loon project and Facebook with their solar-powered UAV concept have all invested significant funds to develop and deploy airborne high capacity backbone systems. These systems are intended to augment ground networks in support of disaster relief, to extend Internet access to infrastructure-less areas, and to support other similar missions. They can be used to replace existing satellite backbones which typically offer low capacity and high latency connections. One of the key challenges to building an airborne backbone network is large-scale topology management of directional links in a dynamic environment. In this paper, we present several topology management algorithms for large scale airborne networks and evaluate the performance of these algorithms under various scenarios. In each case, we seek to evaluate link and path availability of each algorithm.
Droplet-based non-faradaic impedance sensors for assessment of susceptibility of Escherichia coli to ampicillin in 60 min

Direct antibiotic susceptibility tests (AST) are essential for rapid detection of bacterial infection and administration of appropriate antibiotics. Conventional AST systems are usually slow as they rely on cell growth for an indirect assessment of antibiotics’ effectiveness. Therefore, a faster method is desirable, especially for emergency cases. In this work, we studied the performance of label-free, droplet-based impedance sensors for rapid characterization of the effects of ampicillin (Amp) on Escherichia coli. Ampicillin damages cell wall integrity and makes cells permeable (leaky). The leakage results in significant increase of the electrical conductance measured directly by the microfabricated sensing unit. We studied the conductance signal as a function of both antibiotic treatment time and dosage and demonstrated susceptibility testing within 60 min. These findings demonstrate the potential of droplet-based electrical chips for the realization of electrical antibiotic susceptibility testing (e-AST) for early-stage diagnostic/treatment, and consequently, preventing antibiotic misuse/overuse.
Properties of Intermediates in the Catalytic Cycle of Oxalate Oxidoreductase and Its Suicide Inactivation by Pyruvate

Oxalate:ferredoxin oxidoreductase (OOR) is an unusual member of the thiamine pyrophosphate (TPP)-dependent 2-oxoacid:ferredoxin oxidoreductase (OFOR) family in that it catalyzes the coenzyme A (CoA)-independent conversion of oxalate into 2 equivalents of carbon dioxide. This reaction is surprising because binding of CoA to the acyl-TPP intermediate of other OFORs results in formation of a CoA ester, and in the case of pyruvate:ferredoxin oxidoreductase (PFOR), CoA binding generates the central metabolic intermediate acetyl-CoA and promotes a 105-fold acceleration of the rate of electron transfer. Here we describe kinetic, spectroscopic, and computational results to show that CoA has no effect on catalysis by OOR and describe the chemical rationale for why this cofactor is unnecessary in this enzymatic transformation. Our results demonstrate that, like PFOR, OOR binds pyruvate and catalyzes decarboxylation to form the same hydroxyethylidine–TPP (HE–TPP) intermediate and one-electron transfer to generate th...
Active hot spot cooling of GaN transistors with electric field enhanced jumping droplet condensation

Mitigating heat generated by hot spots inside of power electronic devices is a formidable obstacle to further increases in power density. This paper presents the first demonstration of active cooling for hot spots via jumping droplet condensation. This newly discovered phase change cooling mechanism comprises 10 to 100 μm sized droplets leaping from a cold superhydrophobic surface onto a hot GaN transistor and efficiently transferring heat via evaporation. After discussing how electric fields can enhance this process, observations from cooling GaN transistors with this method are outlined. Experimental measurements demonstrate increased cooling rates and steerable heat transfer through the application of electric fields.
The Phe-Ile Zipper: A Specific Interaction Motif Drives Antiparallel Coiled-Coil Hexamer Formation.

Coiled coils are a robust motif for exploring amino acid interactions, generating unique supramolecular structures, and expanding the functional properties of biological materials. A recently discovered antiparallel coiled-coil hexamer (ACC-Hex, peptide 1) exhibits a unique interaction in which Phe and Ile residues from adjacent α-helices interact to form a Phe-Ile zipper within the hydrophobic core. Analysis of the X-ray crystallographic structure of ACC-Hex suggests that the stability of the six-helix bundle relies on specific interactions between the Phe and Ile residues. The Phe-Ile zipper is unprecedented and represents a powerful tool for utilizing the Phe-Ile interactions to direct supramolecular assembly. To further probe and understand the limits of the Phe-Ile zipper, we designed peptide sequences with natural and unnatural amino acids placed at the Phe and Ile residue positions. Using size exclusion chromatography and small-angle X-ray scattering, we found that the proper assembly of ACC-Hex fr...
Effects of Enflurane on the Ventilatory Response to Increased Carbon Dioxide and Metabolic Rate in Dogs

Inhaled anesthetic agents cause a dose related ventilatory depression as evidenced by an increase in arterial PCO2 (PaCO2) and blunting of the ventilatory response to hypercapnia and hypoxia (Hirschman et al., 1977). Ventilation is also closely coupled to metabolic rate, resulting in regulation of PaCO2 in spite of changes in metabolic rate (Wasserman et al., 1986). This study investigates the effects of inhalational anesthetics on this coupling.
Frequency comb linewidth of an actively mode-locked fiber laser

We have measured the linewidth of frequency comb lines from a mode-locked fiber laser. The effective linewidth is 12 kHz over 5 ms, and the intrinsic linewidth is estimated to be less than 3 kHz
Fighting Fire with Fire: Private Attorneys Using the Same Investigative Techniques as Government Attorneys: The Ethical and Legal Considerations for Attorneys Conducting Investigations

As any litigator knows, cases are won or lost on the facts. Effective factual development and investigation are crucial to the success of any case. But lawyers are often faced with legal and ethical dilemmas concerning the investigative techniques they and their investigators want to use. This is particularly true in criminal cases, where discovery is extremely limited. One of the thorniest issues is the use of deception and other surreptitious techniques to gather information. While such tactics have long been the bread and butter of investigations led by government attorneys, ethics opinions and statutes often draw a distinction between what is proper conduct for a government attorney and what a private attorney can do. This Article examines the legal and ethical considerations New York lawyers face when using the exact same techniques relied on by government lawyers, including deception, secret audio recordings, video surveillance, computer data analysis, document gathering, and witness interviews. Also considered are the significant advantages the government enjoys from numerous statutory exceptions
Error as Historiographical Challenge: The Infamous Globule Hypothesis

There is a repertoire of infamous errors that keep cropping up in standard histories of microscopy: the wheels attached to the head of rotifer, the little animals in semen, and the holes in the middle of blood corpuscles. The so-called ‘globule theory’ or ‘globule hypothesis’ of organic matter occupies a prominent place on the list. This theory concerned the basic structure of bodily tissues. According to it, muscular and nerve tissue consist of tiny globules of regular size and shape. As the standard stories go, this erroneous view of organic elements was widely advocated among microscopists in the early decades of the nineteenth century. Only in the late 1830s, the cell theory offered a more correct description of muscular and nerve tissue. The aim of my essay is twofold. First, I seek to revise the ‘standard account’ of the globule hypothesis. Secondly, I utilize the episode of globulism to consider the conditions for the use of the concept ‘error’ as an analytic tool for history and philosophy of science. What are the features of the historical record that merit the application of that concept? The episode lends itself well to this double purpose because we also have an alternative to the received view, namely, John Pickstone’s historically contextualized reconstruction of the globule theory. This reconstruction takes into account the practitioners’ theoretical assumptions that motivated their research. Remarkably – or perhaps not surprisingly? – Pickstone concludes that the globule hypothesis was not an error. I begin by reviewing the standard accounts of the episode and demonstrate how these accounts explain the source of this so-called error and the way in which it was overcome. I confront this received view with Pickstone’s narrative and show how he arrives at the conclusion that the globule hypothesis was not an error. My analysis uncovers the assumptions and implications that are tied to both accounts. I then survey various early nineteenth-century microscopical works on organic
Raven Distribution, Population Dynamics, and Ecology in Grand Teton National Park

This is a study of the distribution, population dynamics, food habits, relationships to artificial food sources and interaction with other fauna of the common raven (Corvus corax sinuatus Wagler) in Grand Teton National Park and adjacent areas. Project Number 176.
Access now, but for whom and at what cost?

Under the banner of ‘democratic access to culture,’ libraries, museums, theaters, archives, and galleries – the loci of information and cultural provision – once exclusive to elite classes or geogr...
Achieving optimal bias-variance tradeoff in online derivative estimation

The finite-difference method has been commonly used in stochastic derivative estimation when an unbiased derivative estimator is unavailable or costly. The efficiency of this method relies on the choice of a perturbation parameter, which needs to be calibrated based on the number of simulation replications. We study the setting where such an a priori planning of simulation runs is difficult, which could arise due to the variability of runtime for complex simulation models or interruptions. We show how a simple recursive weighting scheme on simulation outputs can recover, in an online fashion, the optimal asymptotic bias-variance tradeoff achieved by the conventional scheme where the replication size is known in advance.
Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing

Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage-derived EVs through an M.tb SecA2-dependent pathway and that EVs released from M.tb-infected macrophages stimulate a host RIG-I/MAVS/TBK1/IRF3 RNA sensing pathway, leading to type I interferon production in recipient cells. These EVs also promote, in a RIG-I/MAVS-dependent manner, the maturation of M.tb-containing phagosomes through a noncanonical LC3 pathway, leading to increased bacterial killing. Moreover, treatment of M.tb-infected macrophages or mice with a combination of moxifloxacin and EVs, isolated from M.tb-infected macrophages, significantly lowered bacterial burden relative to either treatment alone. We hypothesize that EVs, which are preferentially removed by macrophages in vivo, can be combined with effective antibiotics as a novel approach to treat drug-resistant TB.
Comparative analysis of commercially available single-cell RNA sequencing platforms for their performance in complex human tissues

The past five years have witnessed a tremendous growth of single-cell RNA-seq methodologies. Currently, there are three major commercial platforms for single-cell RNA-seq: Fluidigm C1, Clontech iCell8 (formerly Wafergen) and 10x Genomics Chromium. Here, we provide a systematic comparison of the throughput, sensitivity, cost and other performance statistics for these three platforms using single cells from primary human islets. The primary human islets represent a complex biological system where multiple cell types coexist, with varying cellular abundance, diverse transcriptomic profiles and differing total RNA contents. We apply standard pipelines optimized for each system to derive gene expression matrices. We further evaluate the performance of each system by benchmarking single-cell data with bulk RNA-seq data from sorted cell fractions. Our analyses can be generalized to a variety of complex biological systems and serve as a guide to newcomers to the field of single-cell RNA-seq when selecting platforms.
The mechanistic target of rapamycin pathway downregulates bone morphogenetic protein signaling to promote oligodendrocyte differentiation

Oligodendrocyte precursor cells (OPCs) differentiate and mature into oligodendrocytes, which produce myelin in the central nervous system. Prior studies have shown that the mechanistic target of rapamycin (mTOR) is necessary for proper myelination of the mouse spinal cord and that bone morphogenetic protein (BMP) signaling inhibits oligodendrocyte differentiation, in part by promoting expression of inhibitor of DNA binding 2 (Id2). Here we provide evidence that mTOR functions specifically in the transition from early stage OPC to immature oligodendrocyte by downregulating BMP signaling during postnatal spinal cord development. When mTOR is deleted from the oligodendrocyte lineage, expression of the FK506 binding protein 1A (FKBP12), a suppressor of BMP receptor activity, is reduced, downstream Smad activity is increased and Id2 expression is elevated. Additionally, mTOR inhibition with rapamycin in differentiating OPCs alters the transcriptional complex present at the Id2 promoter. Deletion of mTOR in oligodendroglia in vivo resulted in fewer late stage OPCs and fewer newly formed oligodendrocytes in the spinal cord with no effect on OPC proliferation or cell cycle exit. Finally, we demonstrate that inhibiting BMP signaling rescues the rapamycin-induced deficit in myelin protein expression. We conclude that mTOR promotes early oligodendrocyte differentiation by suppressing BMP signaling in OPCs.
Innovation in Antimicrobial Resistance: The CARB-X Perspective.

The spread of drug-resistant bacterial pathogens has been recognized as one of the largest global threats to mankind. In order to continue to benefit from the advancement of modern medicine, new tr...
Promoting socially just schools through professional learning: lessons from four US principals in rural contexts

The concept of professional learning, with the principal as lead learner working towards the institutional goal of social justice, is the focus of this descriptive qualitative study. The purpose wa...
Transformation of the Australian mining industry and future prospects

The rapid industrialization in recent decades has enormously increased demands for energy and mineral resources. At the same time, economically viable resources near the surface have been nearly de...
“I Swear”. A Précis of Hippocrates’ Oath and Asclepius’ Snake: The Birth of the Medical Profession

This is a condensed description of the contents and overarching argument found in Hippocrates’ Oath and Asclepius’ Snake: The Birth of the Medical Profession (Cavanaugh 2018). In that work, I maintain that the basic medical ethical problem concerns iatrogenic harm. I focus particularly on what I refer to as ‘role-conflation’. This most egregious form of iatrogenic harm occurs when a physician deliberately adopts the role of wounder (including when this is done at the request of the sick). A contemporary practice such as physician-assisted suicide (PAS) exemplifies a doctor’s deliberate wounding. I argue that the author of the Hippocratic Oath – aware of the chronic risk of role-conflation – responds to this threat by having the oath-taker specifically forswear signal acts that wound the sick, such as giving a deadly drug even if asked, giving an abortifacient, sexual predation, and gossiping. I argue that by means of the Oath, Hippocrates founds medicine as a profession, a practice intimately involving promising.
Diagnostic Testing of COVID-19 in Solid Organ Transplantation: Current Clinical Application and Future Strategies.

While a great deal of literature has been published recently on the viral kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and diagnostic testing performance for coronavirus disease 2019 (COVID-19) in the general population, a relative paucity of information has come to light regarding implications of COVID-19 diagnostics for solid organ transplantation. This review examines the current state of knowledge regarding the two principal diagnostic testing strategies for SARS-CoV-2 infection, polymerase chain reaction (PCR)–based testing and serology, and discusses COVID-19 diagnostic implications for solid organ transplantation. The interpretation of diagnostics for SARS-CoV-2 infection can present several challenges and raises questions regarding optimal donor and candidate screening as well as infection prevention practices in solid organ transplant recipients with SARS-CoV-2 infection. Guidance from several societies regarding donor and recipient suitability for transplantation during the COVID-19 pandemic is reviewed. Prolonged positive testing by polymerase chain reaction has been described in transplant recipients which may impact infection prevention practices. The COVID-19 pandemic has put multiple aspects of solid organ transplantation at risk, with impacts on donor and recipient suitability, and mitigation of infection and transmission after transplantation. Accumulating evidence regarding diagnostic fidelity and transmissibility of SARS-CoV-2 in immunocompromised patients will continue to inform optimal practices surrounding solid organ transplantation during the COVID-19 pandemic.
Accuracy and Completion Rate of the Fetal Anatomic Survey in the Super Obese Parturient.

OBJECTIVE To determine the completion rate of ultrasound in with a body mass index (BMI) ≥ 50 to women with BMI 18.5 to 29.9. STUDY DESIGN This study was a retrospective cohort study. Women with a singleton pregnancy, age 18 to 45 with a BMI ≥50 that delivered between 2013-2016 were compared to women with a BMI 18.5 to 29.9 during that same time period to assess the accuracy and, as a second aim, the completion rate of the fetal anatomic survey. Data were analyzed using two-sample t test, chi-square test, or logistic regression as appropriate. RESULTS Eighty-one cases with a BMI ≥50 were compared with 81 patients with a BMI 18.5 to 29.9. Maternal demographics and timing (gestational age) at the time of the ultrasound were similar between groups. In women with a BMI 18.5 to 29.9, completion of anatomy was 58% of the time with the first ultrasound, 81% with second ultrasound, and 84% with the third ultrasound. In women with BMI ≥50, completion of anatomy was 10% of the time with the first ultrasound, 33% with the second ultrasound, and 42% with the third ultrasound. Each time frame was statistically significant. Agreement level on the accuracy to detect fetal anomalies between groups were not statistically significant between the groups. CONCLUSION In women with a BMI ≥50 compared to women with BMI of 18.8 to 29.9, more ultrasounds are needed to complete the anatomic survey although overall accuracy in fetal anomaly detection is similar.
Uncertain About Uncertainty: How Qualitative Expressions of Forecaster Confidence Impact Decision-Making With Uncertainty Visualizations.

When forecasting events, multiple types of uncertainty are often inherently present in the modeling process. Various uncertainty typologies exist, and each type of uncertainty has different implications a scientist might want to convey. In this work, we focus on one type of distinction between direct quantitative uncertainty and indirect qualitative uncertainty. Direct quantitative uncertainty describes uncertainty about facts, numbers, and hypotheses that can be communicated in absolute quantitative forms such as probability distributions or confidence intervals. Indirect qualitative uncertainty describes the quality of knowledge concerning how effectively facts, numbers, or hypotheses represent reality, such as evidence confidence scales proposed by the Intergovernmental Panel on Climate Change. A large body of research demonstrates that both experts and novices have difficulty reasoning with quantitative uncertainty, and visualizations of uncertainty can help with such traditionally challenging concepts. However, the question of if, and how, people may reason with multiple types of uncertainty associated with a forecast remains largely unexplored. In this series of studies, we seek to understand if individuals can integrate indirect uncertainty about how “good” a model is (operationalized as a qualitative expression of forecaster confidence) with quantified uncertainty in a prediction (operationalized as a quantile dotplot visualization of a predicted distribution). Our first study results suggest that participants utilize both direct quantitative uncertainty and indirect qualitative uncertainty when conveyed as quantile dotplots and forecaster confidence. In manipulations where forecasters were less sure about their prediction, participants made more conservative judgments. In our second study, we varied the amount of quantified uncertainty (in the form of the standard deviation of the visualized distributions) to examine how participants’ decisions changed under different combinations of quantified uncertainty (variance) and qualitative uncertainty (low, medium, and high forecaster confidence). The second study results suggest that participants updated their judgments in the direction predicted by both qualitative confidence information (e.g., becoming more conservative when the forecaster confidence is low) and quantitative uncertainty (e.g., becoming more conservative when the variance is increased). Based on the findings from both experiments, we recommend that forecasters present qualitative expressions of model confidence whenever possible alongside quantified uncertainty.