cssi/SciSciGPT-SciSciNet huggingface dataset:
Techniques and Outcomes for the Treatment of Paravalvular Leak

Paravalvular prosthetic regurgitation is a potentially serious condition resulting from degeneration of annular tissue, affecting 6% to 15% of surgically implanted prosthetic valves and annuloplasty rings.1–3 In conditions of tissue friability from any cause, annular calcification, or infection, paravalvular defects can form and lead to varying degrees of regurgitation. Surgical factors associated with the development of paravalvular regurgitation include prostheses in the mitral position, supra-annular aortic prostheses, use of continuous sutures in the mitral position,3 and use of sutures without pledgets.4 Paravalvular defects are often crescentic and irregular in shape and may follow a serpiginous track from the downstream to upstream chamber. Chronic paravalvular mitral and aortic regurgitation can lead to left ventricular (LV), left atrial (LA) volume, and pressure overload, resulting in clinical heart failure. Because of noncompliance of the receiving chamber, the volume of regurgitation needed to induce symptoms may be relatively modest, such that standard volumetric measurements of regurgitation severity may not be applicable. In addition, conventional measures of mitral regurgitation severity such as the proximal isovelocity surface area method or pulmonary venous Doppler lack validation in this setting. Secondary elevation in pulmonary arterial pressure may result in right-sided heart failure. Paravalvular regurgitation is the most common cause of hemolytic anemia in patients with prosthetic heart valves. Increased red blood cell shear stress because of turbulent flow through the defect causes mechanical trauma and red blood cell fragmentation. Clinically significant hemolysis is more common in smaller defects with high-velocity jets, in patients with increased red blood cell fragility because of iron and folate deficiency, and in those with preexisting anemia because of the increased turbulence occurring from reduced blood viscosity and increased cardiac output. Moderate to severe paravalvular leak (PVL) after both surgical and transcatheter aortic valve replacement is associated with increased …
Learning 3D recognition models for general objects from unlabeled imagery: an experiment in intelligent brute force

In this paper we explorer the problem of training a general, 3D abject recognition system from unlabeled imagery. In particular, we attempt to identify critical issues and stumbling blocks associated with minimizing the supervision necessary to train such a system. As class learning seems to be a relatively slow and resource intensive process even for people, we consider approaches and perform experiments that entail on the order of 10/sup 1/5 basic operations, even for relatively small databases. This is the current practical limit of the computation that can be achieved. For experiments, we use a recognition system developed previously.
Modeling gene expression evolution with an extended Ornstein-Uhlenbeck process accounting for within-species variation

Much of the phenotypic variation observed between even closely related species may be driven by differences in gene expression levels. The current availability of reliable techniques like RNA-Seq, which can quantify expression levels across species, has enabled comparative studies. Ornstein-Uhlenbeck (OU) processes have been proposed to model gene expression evolution as they model both random drift and stabilizing selection and can be extended to model changes in selection regimes. The OU models provide a statistical framework that allows comparisons of specific hypotheses of selective regimes, including random drift, constrained drift, and expression level shifts. In this way, inferences may be made about the mode of selection acting on the expression level of a gene. We augment this model to include within-species expression variance, allowing for modeling of nonevolutionary expression variance that could be caused by individual genetic, environmental, or technical variation. Through simulations, we explore the reliability of parameter estimates and the extent to which different selective regimes can be distinguished using phylogenies of varying size using both the typical OU model and our extended model. We find that if individual variation is not accounted for, nonevolutionary expression variation is often mistaken for strong stabilizing selection. The methods presented in this article are increasingly relevant as comparative expression data becomes more available and researchers turn to expression as a primary evolving phenotype.
Biogeography of Neotropical Piper

The history and nature of diversification of Piper in the New World has been little investigated. The genus Piper is often among the top 10 most speciose genera in Neotropical forests (e.g., Gentry and Emmons, 1987). Superficially, however, Piper species show relatively little morphological variation. In view of the high species richness in the genus but relatively low morphological variability among species, Gentry (1989) suggested that much diversification in Neotropical Piper may have occurred relatively recently (within the last 2 million years or even more recently). The premise is that because diversification was recent, little time has been available for morphological diversification.
Effects of Land Cover Change on the Energy and Water Balance of the Mississippi River Basin

Abstract The effects of land cover change on the energy and water balance of the Mississippi River basin are analyzed using the Integrated Biosphere Simulator (IBIS) model. Results of a simulated conversion from complete forest cover to crop cover over a single model grid cell show that annual average net radiation and evapotranspiration decrease, while total runoff increases. The opposite effects are found when complete grass cover is replaced with crop cover. Basinwide energy and water balance changes are then analyzed after simulated land cover change from potential vegetation to the current cover (natural vegetation and crops). In general, net radiation decreases over crops converted from forest and increases over crops converted from grasslands. Evapotranspiration rates decrease over summer crops (corn and soybean) converted from forest and increase over summer crops converted from grassland. The largest decreases (∼0.75 mm day−1; 20%) are found in summer over former forests, and the largest increase...
¿Es suficiente el recurso humano nutricionista en el sistema hospitalario público en Chile?: Una deuda pendiente

Background: Human resource deficit is an important management problem in Chilean public hospitals Aim: To analyze the adequacy of Nutritionist (Dietician) resources in public hospitals. Material and methods: A questionnaire about Nutritionist resources was sent to head Nutritionists of all public Chilean hospitals, asking about the number of Nutritionists per service, number of hospital beds and number of daily rations served. Results were analyzed based on the Technical Guideline about Nutritional and Feeding Services of public hospitals issued by the Chilean Ministry of Health in 2005. Results: According to the guideline, there should be 1396 nutritionists working in public hospitals and the results of the survey showed that there were only 603 professionals with a 57% deficit. Conclusions: There is a huge gap between the amount of Nutritionists (Dieticians) required and those effectively working in public hospitals.
Viruses and Head and Neck Cancer

This chapter presents an overview of the viruses thought to be associated with Head & Neck cancers. Human Papillomavirus is the most common and strongly linked virus associated with this cancer. Other viruses, such as Epstein – Barr virus (EBV) and Cytomegalovirus (CMV) have controversial links to Head and Neck cancers. This controversy points to a true lack of understanding within the Head & Neck cancer field, regarding the extent of responsibility for being, or not being, causative agents. It is also perplexing as to why much of the general population is infected with one or more of these viruses, and yet, not everyone in the general population presents with cancer. Furthermore, those which do develop cancer do not always test positive for these viruses.
Abstract IA22: Developing improved diffuse intrinsic pontine glioma mouse models

Recent genomic studies have identified novel drivers in DIPG pathogenesis. These include gain of function histone mutations (K27M in H3.3 or H3.1) found in 80% of DIPGs as well as activating mutations in Activin A Receptor, Type I (ACVR1) found in 25% of DIPGs. These studies also provide support for the existence of subtypes of DIPG with H3.3K27M mutations co-occurring with PDGFRA amplifications with an older age at presentation and H3.1K27M mutations co-occurring with ACVR1 mutations with a younger age at presentation. My laboratory has been using the RCAS/tv-a system to develop genetic mouse models for these DIPG subtypes that recapitulate the genetic alterations of the human disease. Our results thus far suggest that H3.3K27M is not sufficient to drive brainstem gliomagenesis on its own or with p53 loss in the early postnatal period but cooperates with platelet-derived growth factor-B (PDGF-B) in brainstem gliomagenesis. Similarly, mutant ACVR1 (R206H or G328V) cooperates with H3.1K27M and p53 loss to induce glioma-like lesions in mice. By contrast to the PDGF-B; H3.3K27M lesions that express Olig2, the mutant ACVR1; H3.1K27M; p53 deficient lesions are Olig2 negative but express CD44 and nestin. To examine whether the cell-of-origin will influence DIPG tumor incidence or latency, we induced murine DIPGs with PDGF-B, H3.3K27M, and p53 loss in three cell populations that express the following markers in the postnatal mouse brainstem: nestin, pax3 and Olig2. We will highlight the differential expression of these markers in the postnatal brainstem and resulting differences in tumorigenesis between these murine DIPGs induced in these three putative cells-of-origin. Lastly we will demonstrate the use of these models as preclinical tools. Citation Format: Oren Josh Becher. Developing improved diffuse intrinsic pontine glioma mouse models. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA22.
Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the Course of Necrotizing Pancreatitis.

Abstract Purpose To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard. Materials and Methods Between September 2010 and August 2014, CT–guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial. Results The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P Conclusions Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective.
Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we "absorb" that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative.
Radar and phased-array breakthroughs: an update

Latest upgrades, progress, promising developments and breakthroughs are covered. Major progress has been made with regard to Monolithic Microwave Integrated Circuits (MIMC) relative to the number of transistors and components that can be placed now on a chip for microwave and mm wave circuits, the Moore's law for microwave circuits. Whole arrays are being put on a wafer. Also all the RF circuitry for mm-wave automobile radars are being put on a chip with some believing that such arrays and radars will soon be produced for just a few dollars. Major advances in printed flexible electronic circuits with diodes operating at 1.6 GHz and the potential for operation at 2.4GHz, the Wi-Fi band. A tightly coupled dipole antenna (TCDA) has been developed which provides a 1:20 bandwidth and a λ/40 thickness. Metamaterial antennas have progressed considerably in the last few years. The Army Research Laboratory in Adelphi MD has funded the development of a metamaterial 250-505 MHZ antenna with a λ/20 thickness. Kymeta had demonstrated December 2013 the transmission to satellites and back using 20 and 30 GHz antennas about the size of a laptop which use metamaterial resonators to effect the phase shifting. Lincoln Laboratory increases spurious free dynamic range of receiver plus A/D by 40 dB. The possibility of the transmission of electrical and optical signals over the same wire has been demonstrated. Also being investigated is use of IR beams in a Si chip, which is transparent to IR, for transmission of signals without ohmic loss and at the speed of light. New Symmetry Breaking Theory could allow in the future the placing of small low frequency antennas on a chip. Quantum Radar could allow us to see stealth targets and low cross section cancer cells. We live in exciting times.
Application of the Lattice-Boltzmann Method to Sub-Continuum Heat Conduction

The Lattice Boltzmann Method (LBM) is introduced in this paper as a method to simulate heat conduction across broad length scales in which continuum and sub-continuum effects exist. The paper describes the implementation of the method in both one and two dimensions. Results are presented for cases involving problems with existing solutions and show close agreement with both continuum and subcontinuum solutions of one-dimensional heat transfer through thin films. Results for a two-dimensional continuum problem agree with a known solution to within one percent. These results, combined with relative small computational effort, indicate that the LBM is a useful analysis tool for simulation of multiscale heat conduction.Copyright © 2002 by ASME
A "heat-activated" diphosphopyridine nucleotide pyrophosphatase activity of Staphylococcus aureus.

SummaryA “heat-activated” DPN pyrophosphatase activity of cells of Staphylococcus aureus and of some strains of Staphylococcus albus is described. Cell extracts exhibit no activity until they have been heated. The enzyme is quite stable to high temperatures and appears to undergo reversible heat denaturation. The enzyme shows some specificity in that it does not cleave TPN or TPNH.
Effect of number of prior reinforcements on social convergence

In a Sherif type social convergence design five groups of Ss received 0, 3, 10, 20 and 40 reinforcements in Session 1. In Session 2 S and a collaborator whose responses differed by 8 in from the Ss’ average in Session 1 responded together. The amount of response change from Session 1 to Session 2 was inversely related to number of reinforcements in Session 1.
Combined modality therapy of advanced non-Hodgkin's lymphoma: an analysis of remission duration and survival in 95 patients.

Ninety-five patients with advanced non-Hodgkin9s lymphoma were treated with four courses of cyclophosphamide, adriamycin, vincristine and prednisone, with or without procarbazine [CHOP(P)] chemotherapy; either 150 rad total body irradiation (for “extensive” disease) or 3,500 rad local radiation therapy (for “limited” disease); and a final four courses of CHOP(P) chemotherapy. Sixty-four patients had stage IV, 22 stage III, and 9 abdominal stage II disease. Histologic material was available in 80 patients for review according to the new Working Formulation: 16 had low grade, 38 intermediate grade (20 large cell, 18 diffuse small cleaved and mixed cell), and 26 high grade (12 lymphoblastic, 8 immunoblastic, 6 small noncleaved) malignancies. Complete remission was achieved in 78% of 92 evaluable patients. The remission duration curve for diffuse large cell lymphoma patients showed a plateau at 72% after 2 yr, but a pattern of continued relapse (median 3 yr) was seen in the other histologies. Multivariate analysis showed that “B” symptoms, bulky abdominal masses, and stage IV disease adversely affected survival. Overall survival by Kaplan-Meier analysis showed that 67% of diffuse small cleaved and mixed cell, 49% of large cell and immunoblastic, and 44% of lymphoblastic lymphoma patients survive 6 yr after diagnosis. When compared to reported remission duration and survival with CHOP chemotherapy alone, these data suggest a possible advantage for combined modality treatment.
Moral Development and Moral Education

Convincing people that moral education deserves a high place on the public-school agenda was once an uphill battle, but now American advocates of moral education are surrounded by an embarrassment of supportive evidence. Fresh scandals break with such numbing regularity that the list grows almost too long to remember: Watergate, international sabotage by the CIA, domestic spying by the FBI, assorted corruption in Congress, routine bribery in big business, widespread fraud in Medicare, another rash of cheating at a military academy, reports of premed students destroying each other’s lab work, and steady increases in almost every category of crime.
Educating the “Savage” and “Civilized”: Santa Clara Pueblo Indians at the 1904 St. Louis Expo

A microhistory is history on a very small scale. The unit of analysis tends to focus in on a particular event or place, a specific sliver of time, a distinct group of people, or some combination of these. Historian Edward Muir (1991) writes that by honing in on the particular, the microhistorian can create an “ethnographic history” (ix) in which s/he attempts to understand past people as they experienced the world by weaving together a contextual tapestry (Revel, 1995). Microhistories have a prismatic effect, refracting larger social phenomena through the contexts and experiences of the people studied. Microhistories can inform us of attitudes, tensions, and motivations underlying broad social, political, cultural, and economic phenomena even though microhistories are not generalizable.
Biosensors for quorum chemical signaling molecules: Implications of bacterial communication in gastrointestinal disorders

The role of bacteria in causing biofouling and a wide variety of health imbalances has been long established. Moreover, bacterial load plays a fundamental role in these processes. Bacteria regulate expression of certain specialized genes, including certain behaviors/phenotypes, as a fimction of their population density. They employ chemical language, i.e., signaling molecules for their communication and group-based coordination. This phenomenon is known as quorum sensing (QS). The signaling molecules generally are N-acylated homoserine lactones (AHLs) in Gram-negative bacteria, small peptides in Gram-positive bacteria and a furanosyl borate diester, which is common to both types of bacteria. Thus, to better elucidate the mechanism of pathogenicity in bacteria, it is important to understand bacterial communication. The first step toward that end is to be able to detect the signaling molecules in a sensitive and selective manner. We hypothesize that the levels of these quorum sensing molecules (QSMs) in individuals may correlate with their health status, thus QSMs may be significant as biomarkers of diseases. These biomarkers may serve in the monitoring of disease activity and a patient's health. In that regard, we have developed whole-cell sensing systems for the detection of AHLs. Further, we employed these sensing systems in the analysis of biological samples. Specifically, we detected AHLs in biological matrixes, such as saliva and stool, of healthy subjects as well as patients with gastrointestinal (GI) disorders. We envision that these whole-cell sensing systems will allow for the monitoring of bacterial activity in biological fluids, and, consequently, the management of a patient's health. In addition, the aforementioned QS biosensing systems could be employed in the screening of potential anti-microbial drugs that interfere with bacterial communications. Furthermore, the method is non-invasive, fast, and cost-effective and requires simple sample preparation, which makes it amenable for high throughput detection as well as for miniaturization.
Affymetrix® Mismatch (MM) Probes: Useful after All

Affymetrix® GeneChip® micro array design defines probe sets consisting of 11, 16, or 20 distinct 25 base pair (BP) probes for determining mRNA expression for a specific gene, which may be covered by one or more probe sets. Each probe has a corresponding perfect match (PM) and mismatch (MM) set. Traditional analytical techniques have either used the MM probes to determine the level of cross-hybridization or reliability of the PM probe, or have been completely ignored. Given the availability of reference genome sequences, we have reanalyzed the mapping of both PM and MM probes to reference genomes in transcript regions. Our results suggest that depending of the species of interest, 66%-93% of the PM probes can be used reliably in terms of single unique matches to the genome, while a small number of the MM probes (typically less than 1%) could be incorporated into the analysis. In addition, we have examined the mapping of PM and MM probes to five different human genome projects, resulting in approximately a 70% overlap of uniquely mapping PM probes, and a subset of 51 uniquely mapping MM probes commonly found in all five projects, 24 of which are found within annotated exonic regions. These results suggest that individual variation in transcriptome regions provides an additional complexity to micro array data analysis. Given these results, we conclude that the development of custom chip definition files (CDFs) should include MM probe sequences to provide the most effective means of transcriptome analysis of Affymetrix® GeneChip® arrays.
The 5′ UTR of the type I toxin ZorO can both inhibit and enhance translation

Many bacterial type I toxin mRNAs possess a long 5΄ untranslated region (UTR) that serves as the target site of the corresponding antitoxin sRNA. This is the case for the zorO-orzO type I system where the OrzO antitoxin base pairs to the 174-nucleotide zorO 5΄ UTR. Here, we demonstrate that the full-length 5΄ UTR of the zorO type I toxin hinders its own translation independent of the sRNA whereas a processed 5΄ UTR (zorO Δ28) promotes translation. The full-length zorO 5΄ UTR folds into an extensive secondary structure sequestering the ribosome binding site (RBS). Processing of the 5΄ UTR does not alter the RBS structure, but opens a large region (EAP region) located upstream of the RBS. Truncation of this EAP region impairs zorO translation, but this defect can be rescued upon exposing the RBS. Additionally, the region spanning +35 to +50 of the zorO mRNA is needed for optimal translation of zorO. Importantly, the positive and negative effects on translation imparted by the 5΄ UTR can be transferred onto a reporter gene, indicative that the 5΄ UTR can solely drive regulation. Moreover, we show that the OrzO sRNA can inhibit zorO translation via base pairing to the of the EAP region.
On the Definition of Marginal Ice Zone Width

AbstractSea ice features a dense inner pack ice zone surrounded by a marginal ice zone (MIZ) in which the sea ice properties are modified by interaction with the ice-free open ocean. The width of the MIZ is a fundamental length scale for polar physical and biological dynamics. Several different criteria for establishing MIZ boundaries have emerged in the literature—wave penetration, floe size, sea ice concentration, etc.—and a variety of definitions for the width between the MIZ boundaries have been published. Here, three desirable mathematical properties for defining MIZ width are proposed: invariance with respect to translation and rotation on the sphere; uniqueness at every point in the MIZ; and generality, including nonconvex shapes. The previously published streamline definition is shown to satisfy all three properties, where width is defined as the arc length of a streamline through the solution to Laplaces’s equation within the MIZ boundaries, while other published definitions each satisfy only one...
Temporal Effects on Internal Fluorescence Emissions Associated with Aflatoxin Contamination from Corn Kernel Cross-Sections Inoculated with Toxigenic and Atoxigenic Aspergillus flavus.

Non-invasive, easy to use and cost-effective technology offers a valuable alternative for rapid detection of carcinogenic fungal metabolites, namely aflatoxins, in commodities. One relatively recent development in this area is the use of spectral technology. Fluorescence hyperspectral imaging, in particular, offers a potential rapid and non-invasive method for detecting the presence of aflatoxins in maize infected with the toxigenic fungus Aspergillus flavus. Earlier studies have shown that whole maize kernels contaminated with aflatoxins exhibit different spectral signatures from uncontaminated kernels based on the external fluorescence emission of the whole kernels. Here, the effect of time on the internal fluorescence spectral emissions from cross sections of kernels infected with toxigenic and atoxigenic A. flavus, were examined in order to elucidate the interaction between the fluorescence signals emitted by some aflatoxin contaminated maize kernels and the fungal invasion resulting in the production of aflatoxins. First, the difference in internal fluorescence emissions between cross-sections of kernels incubated in toxigenic and atoxigenic inoculum was assessed. Kernels were inoculated with each strain for 5, 7, and 9 days before cross-sectioning and imaging. There were 270 kernels (540 halves) imaged, including controls. Second, in a different set of kernels (15 kernels/group; 135 total), the germ of each kernel was separated from the endosperm to determine the major areas of aflatoxin accumulation and progression over nine growth days. Kernels were inoculated with toxigenic and atoxigenic fungal strains for 5, 7, and 9 days before the endosperm and germ were separated, followed by fluorescence hyperspectral imaging and chemical aflatoxin determination. A marked difference in fluorescence intensity was shown between the toxigenic and atoxigenic strains on day nine post-inoculation, which may be a useful indicator of the location of aflatoxin contamination. This finding suggests that both, the fluorescence peak shift and intensity as well as timing, may be essential in distinguishing toxigenic and atoxigenic fungi based on spectral features. Results also reveal a possible preferential difference in the internal colonization of maize kernels between the toxigenic and atoxigenic strains of A. flavus suggesting a potential window for differentiating the strains based on fluorescence spectra at specific time points.
MICROBIOLOGICAL ANALYSIS | DNA Methods

Detection of foodborne microorganisms is an imperative component of a food safety plan for meat processors. Detection of pathogenic bacteria constitutes a tremendous challenge; therefore, traditional detection methods include a rigorous multistep process, such as enrichment, isolation, and further biochemical/serological identification. Consequently, different DNA-based molecular detection techniques have been developed in order to reduce time needed to make a decision to accept or reject product and increase sensitivity/specificity of detection. Additionally, DNA sequence-based subtyping methods have improved the discriminatory power and epidemiological concordance of characterizing bacterial foodborne pathogens involved in outbreak investigations. In this article, the most current and commonly employed DNA-based detection and subtyping methods are reviewed.
Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury

Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa-/- and Itgam-/- mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.
Genetic Studies of Age-related Macular Degeneration: Lessons, Challenges, and Opportunities for Disease Management

Background Age-related macular degeneration (AMD) is a common cause of visual impairment in individuals >55 years of age worldwide. The varying clinical phenotypes of AMD result from contributions of genetic, epigenetic, and nongenetic (environmental) factors. Genetic studies of AMD have come of age as a direct result of tremendous gains from the human genome project, genome-wide association studies, and identification of numerous susceptibility loci. These findings have implicated immune response, high-density lipoprotein cholesterol metabolism, extracellular matrix, and angiogenesis signaling pathways in disease pathophysiology. Main Outcome Measures Herein, we address how the wealth of genetic findings in AMD is expected to impact the practice of medicine, providing opportunities for improved risk assessment, molecular diagnosis, preventive, and therapeutic intervention. Conclusions We propose that the potential of using genetic variants for monitoring treatment response (pharmacogenetics) may usher in a new era of personalized medicine in the clinical management of AMD. Financial Disclosure(s) Proprietary or commercial disclosures may be found after the references.
P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a muclin-like glycoportein ligand for P- and E-selectin on myeloid cells and a subset of lymphocytes. We used flow cytometry and immunohistochemistry to examine expression of PSGL-1 on minor leukocyte populations, differentiating hematopoletic cells, and nonhematopoietic tissues using two monoclonal antibodies to distinct protein epitopes on PSGL-1. In the bone marrow, PSGL-1 was expressed on myeloid cells from the myeloblast stage to the segmented neutrophil, but was not detected on erythroblasts or megakaryocytes. All types of circulating myeloid cells expressed PSGL-1, and PSGL-1 was retained after extravasation of myetoid cells into tissues. PSGL-1 was also expressed on circulating dendritic cells, monocyte-derived dendritic cells, dendritic cells in lymphoid tissues and epidermis, and follicular dendritic cells. All types of lymphoid cells examined expressed PSGK-1, including immature and mature thymocytes, naive and memory T cells, gamma/delta T cells, netural killer cells, B cells and CD34+ progenitor cells. However, PSGL-1 levels were substantially lower on tonsillar lymphocytes than on circulating lymphocytes, suggesting that PSGL-1 expression is down regulated during or after entry of lymphocytes into secondary lymphoid tissue. Although PSGL-1 antigen was detected primarily on hamatopoietic cells, it was also present on time epithelium of the fallopian tube. Furthermore, PSGL-1 antigen gen was detected sporadically on microvascular endothelium in some pathologic tissues. This suggests that PSGL-1 may have functions other than mediating leukocyte adhersion.
Defending Attacks Against Transhumanism

This chapter is one that is particularly rich in philosophical arguments and has as its main focus the critical evaluation of the arguments against transhumanism that have been raised by a number of prominent philosophers and other individuals. Based on the critiques of transhumanism offered by critics such as Leon Kass, Francis Fukuyama, and Michael Sandel, the chapter critically assesses five commonly raised arguments why human enhancement by artificial means should not be undertaken: fairness, human dignity issues, “slippery slope” arguments, the “repugnance” argument, and safety issues. The weakness of “slippery slope” arguments and “repugnance” arguments are given special attention. In the end it is concluded that safety issues are the most realistic concerns that the pursuit of transhumanism raises.
Proliferation and cytolytic function of anti-CD3 + interleukin-2 stimulated peripheral blood mononuclear cells following bone marrow transplantation

We evaluated the proliferation, cytolytic function, and phenotypic characteristics of anti-CD3 plus interleukin-2 (IL-2) stimulated peripheral blood mononuclear cells (PBMCs) from 44 patients with leukemia or non-Hodgkin's lymphoma (NHL) treated with multiagent chemotherapy or following bone marrow transplantation (BMT). BMT patients had decreased cell growth with only a 1.35 +/- 0.25 (autologous BMT for acute lymphoblastic leukemia [ALL]), 1.24 +/- 0.25 (autologous BMT for NHL), and 0.8 +/- 0.1 (allogeneic BMT for leukemia) mean fold increase by day 5 of culture compared with controls (4.0 +/- 0.4), P less than .001. Anti-CD3 + IL-2 activated cells from patients with ALL and NHL who had received autologous BMT and cells from patients with leukemia who underwent allogeneic BMT were more effective in lysing the natural killer (NK) sensitive target, K562, and the NK-resistant target, Daudi, compared with controls. In contrast, cytolysis of K562 and Daudi by cultured PBMCs from patients with ALL and NHL receiving multi-agent chemotherapy was similar to that of controls. Cultures from BMT recipients had a significant increase in CD16+ (autologous ALL 5.7 +/- 1.5%, P less than .01; autologous NHL 12.4 +/- 3.5%, P less than .001; allogeneic 14.3 +/- 2.9%, P less than .001) and CD56+ cells (autologous ALL 27.6 +/- 12.0%, P less than .01; autologous NHL 39.3 +/- 9.5%, P less than .001; allogeneic 42.7 +/- 7.4%, P less than .001) compared with controls (CD16+ 2.5 +/- 0.4%; CD56+ 6.9 +/- 0.9%). Stimulation of PBMCs with anti-CD3 + IL-2 is effective in generating cells with high cytolytic function post-BMT.
A vexing vulvitis: a case report and review of plasma cell vulvitis.

Plasma cell vulvitis (PCV), also referred to as Zoon’s vulvitis and vulvitis plasmacellularis circumscripta, is an idiopathic, benign, chronic inflammatory condition in females. Women with PCV have...
Anterior-posterior patterning of Drosophila wing discs I: A baseline mathematical model.

Abstract The wing imaginal disc of Drosophila is one of the commonly used model systems for the studies of patterning, growth, and scaling. Development of the wing disc involves many interacting components as well as a variety of compound processes whose underlying mechanisms are still under investigation. For instance, it remains unclear about how to form compound experimentally-measured patterns of Decapentaplegic (Dpp) type-I receptor Thickveins (Tkv), as well as phosphorylated Mothers Against Dpp (pMad, the latter of which is the indicator of Dpp signaling activities. In this work, we proposed a baseline mathematical model that integrates established experimental facts to investigate the formation of pMad and Tkv gradients. Our model is validated by the accurate reproduction of complex asymmetric profiles of Tkv and pMad in both anterior and posterior compartments of the wing disc. Moreover, using our model as a numerical platform, we examined specific roles played by Engrailed (En), Hedgehog (Hh) and Dpp in the establishment of Tkv and pMad profiles. It turns out that En, Hh, Dpp all play an essential role in the formation of pMad and Tkv patterns. In particular, our proposed model supports the crucial part of the downregulation of Tkv by Dpp. Further, dual negative regulations of Tkv by both Hh and Dpp simultaneously prevent the Dpp signaling from interfering the Hh signaling and expand the effective range of Dpp gradients. Finally, parameter sensitivity was carried out to ensure that our results and conclusions are robust against specific choices of parameter values.
Operator Size at Finite Temperature and Planckian Bounds on Quantum Dynamics

It has long been believed that dissipative timescales τ obey a "Planckian" bound τ≳(ℏ/k_{B}T) in strongly coupled quantum systems. Despite much circumstantial evidence, however, there is no known τ for which this bound is universal. Here we define operator size at a finite temperature, and conjecture such a τ: the timescale over which small operators become large. All known many-body theories are consistent with this conjecture. This proposed bound explains why previously conjectured Planckian bounds do not always apply to weakly coupled theories, and how Planckian timescales can be relevant to both transport and chaos.
The Rich Get Richer: Osseous Chimeric Versatility to the Anterolateral Thigh Flap.

Background The lateral femoral circumflex artery (LFCA) system, which supplies the anterolateral thigh (ALT) flap territory, offers a plethora of tissue types for composite, functional reconstruction. However, the ability to include a reliable and flexible osseous component is limited. Based on cadaveric dissections, we describe an isolated LFCA branch to the femur separate from the vastus intermedius that can be included in ALT flap harvest in cases requiring bony reconstruction. Methods Cadaveric dissection was undertaken to define the LFCA vascular system with specific dissection of the proximal branches of the descending branch of the LFCA (db-LFCA) to define any muscular, periosteal, and/or osseous branches to the femur. Results Six thighs in four cadavers were dissected. Consistent in all specimens, there was an isolated branch extending distally, medially, and posteriorly from the proximal LFCA and entering the periosteum of the femur. In five specimens, the identified branch to the femur was located approximately 1-cm distal to the rectus femoris branch of the LFCA and approximately 1-cm proximal to a separate branch entering and supplying the vastus intermedius. In one specimen, there was a common trunk. The length of this branch from the origin at the LFCA to insertion into the femoral periosteum was approximately 6 to 8 cm. Conclusion There appears to be a consistent and reliable branch to the femur based on the proximal LFCA that may be included in ALT flap harvest, adding even more versatility, as another option in complex cases requiring composite reconstruction, including bone.
A Qualitative Metasynthesis of the Experience of Fatigue Across Five Chronic Conditions.

Abstract Context Fatigue is a symptom reported by patients with a variety of chronic conditions. However, it is unclear whether fatigue is similar across conditions. Better understanding its nature could provide important clues regarding the mechanisms underlying fatigue and aid in developing more effective therapeutic interventions to decrease fatigue and improve quality of life. Objectives To better understand the nature of fatigue, we performed a qualitative metasynthesis exploring patients' experiences of fatigue across five chronic noninfectious conditions: heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease. Methods We identified 34 qualitative studies written in the last 10 years describing fatigue in patients with one of the aforementioned conditions using three databases (Embase, PubMed, and CINAHL). Studies with patient quotes describing fatigue were synthesized, integrated, and interpreted. Results Across conditions, patients consistently described fatigue as persistent overwhelming tiredness, severe lack of energy, and physical weakness that worsened over time. Four common themes emerged: running out of batteries, a bad life, associated symptoms (e.g., sleep disturbance, impaired cognition, and depression), and feeling misunderstood by others, with a fear of not being believed or being perceived negatively. Conclusion In adults with heart failure, multiple sclerosis, rheumatoid arthritis, chronic kidney disease, and chronic obstructive pulmonary disease, we found that fatigue was characterized by severe energy depletion, which had negative impacts on patients' lives and caused associated symptoms that exacerbated fatigue. Yet, fatigue is commonly misunderstood and inadequately acknowledged.
Combined Vascular Brachytherapy and Stenting for the Treatment of In-Stent Restenosis.

In-stent restenosis (ISR) remains a therapeutic challenge in the current drug-eluting stent (DES) era. Vascular brachytherapy (VBT) is a therapeutic option for ISR, but data about the outcomes of combination therapy with VBT and stenting for ISR lesions are sparse. We retrospectively analyzed patients who presented with ISR at our institution from 2003 through 2017. Three treatment arms were compared: VBT alone, VBT plus bare-metal stent (BMS), and VBT plus DES. Clinical, procedural, and 1-year outcome data were collected. Follow-up was obtained by phone calls and clinic visits. The patient cohort included 461 patients (764 ISR lesions). Of these, 333 patients (533 lesions) were treated with VBT alone, 89 patients (158 lesions) with VBT plus BMS, and 39 patients (73 lesions) with VBT plus DES. There were no significant differences in baseline characteristics among the 3 groups except for more patients with a remote smoking history in the VBT plus BMS (43.8%) and VBT plus DES groups (56.4%), and more patients with history of peripheral vascular disease (39.5%) and congestive heart failure (27%) in the VBT plus DES group. The most common clinical presentation was unstable angina (64.6%). In the VBT plus DES group, 10.3% of patients presented with MI, versus 5.5% in the VBT alone group and 2.2% in the VBT plus BMS group. At 1-year follow-up, the VBT plus DES group had higher rates of target vessel revascularization-major adverse cardiovascular events (38.5%) than the VBT plus BMS (21.3%) and VBT alone (15.6%) groups (p = 0.002). In conclusion, in patients with ISR, combination therapy with VBT and stenting at the same setup is associated with worse outcomes at 12 months and, if possible, should be avoided.
25.5 A Self-Calibrated 1.2-to-3.8GHz 0.0052mm2 Synthesized Fractional-N MDLL Using a 2b Time-Period Comparator in 22nm FinFET CMOS

Increasing speed and complexity of modern SoCs demand low-jitter clock generators, which conventionally use LC resonators. But, low power operation at sub-6GHz frequencies requires large L, increasing the form factor. Digital multiplying delay-locked loops (MDLL) [1], [2] or injection-locked phased-locked loops (IL-PLL) [3] based on ring oscillators (ROSCs) are preferred due to their smaller form factor and superior jitter performance than that of basic PLLs. Using a ROSC as a digitally controlled oscillator (DCO) enables a fully synthesizable design solution, which has the benefit of easy portability to scaled technologies while greatly reducing the design effort and complexity associated with manual placements of layout cells and design rule checks [3]–[6]. However, a synthesizable design needs to be insensitive to layout parasitics and mismatches, which makes the design of an MDLL or IL-PLL challenging. The performance is much worse in fractional-N architectures due to the stringent gain and linearity requirement of the digital-to-time converter (DTC) [2], [3] or time-to-digital converter (TDC) [4], [6]. [3] uses digital standard cells to implement blocks with analog functionality. That makes the design synthesizable but sensitive to process-voltage-temperature (PVT) variations, requiring careful device sizing. A dual-reference TDC in [4] reduces the PVT sensitivity but uses same TDC for each DCO phase, adding significant power and area overhead. This paper presents a synthesizable fractional-N MDLL using a 2b time-period comparator (TPC). The TPC comprises a tunable reference delay $(\uparrow_{\mathrm{p}})$ and a 2b phase detector (PD). It adjusts the DCO period $(\mathrm{T}_{\mathrm{DCD}})$ and $\mathrm{T}_{\mathrm{P}}$ using two independent feedback loops operating simultaneously. A TPC based bang-bang PD was implemented in [1], but 1b output to control both $\mathrm{T}_{\mathrm{DCD}}$ and $\mathrm{T}_{\mathrm{P}}$ requires an initial calibration to reduce the PLL lock time and avoid lock failure as $\mathrm{T}_{\mathrm{DCD}}$ continuously updates in alternate cycles. In this work, the 2b output in the proposed TPC provides automatic tuning of $\mathrm{T}_{\mathrm{DCO}}$ and $\mathrm{T}_{\mathrm{P}}$ without additional calibration. Faster locking can be achieved over a wide range of resolutions, hence making it synthesizable. Furthermore, the MDLL uses a replica of the DCO to implement the DTC for fractional-N generation, which self-calibrates its gain to suppress the fractional spurs.
Fully-Integrated Mechanoluminescent Devices with Nanometer-Thick Perovskite Film as Self-Powered Flexible Sensor for Dynamic Pressure Sensing

Flexible pressure sensors have numerous future applications in artificial electronic skins, foot ulcer detection, structural health monitoring, soft robotics, and wearable technology. We, herein, r...