cssi/SciSciGPT-SciSciNet huggingface dataset:
Extrahematopoietic Manifestations of Telomere Syndromes

Abnormally short telomeres give rise to a group of premature aging, cancer-prone disorders known as the telomere syndromes. They are caused by germline mutations in telomerase and telomere genes. Although bone marrow failure was one of the first complications to be described in dyskeratosis congenita, there is increasing appreciation that this classic presentation is rare. Extra-hematopoietic telomere-mediated disease is frequently the first and predominant presentation in adults and leads to significant morbidity and mortality in patients with bone marrow failure (BMF), especially after bone marrow transplantation. It shows stereotypic manifestations that are age-dependent. Enterocolitis can precede the onset of BMF in infants with Hoyeraal-Hreidarsson syndrome, and it represents an intestinal epithelial defect that progresses in the setting of immunodeficiency. In adults with familial lung disease, idiopathic pulmonary fibrosis and emphysema are the predominant manifestations. These patients show variable degrees of BMF and are at risk for clonal abnormalities. In the lung transplant setting, adult telomere syndrome patients have an increased risk of complications due to immunosuppressive medications which challenge their reserves in the bone marrow, intestinal tract and elsewhere. Liver disease, often manifesting as hepatopulmonary syndrome, causes organ failure in approximately 10% of cases. The molecular mechanisms underlying telomere-mediated disease outside the bone marrow likely involve stem cell failure. For example, in the lung, alveolar stem cell senescence is sufficient to drive remodeling, inflammation, and susceptibility to injury, which are hallmark features of pulmonary fibrosis and emphysema. The stem cell failure mechanism has implications for approaching treatment in these lung disorders which have heretofore been considered mediated by inflammation. This session will present evolving scientific evidence that sheds light on the mechanisms and natural history of telomere syndromes. Considerations in the diagnostic work-up of suspected cases and the implications for patient care will be reviewed. Disclosures No relevant conflicts of interest to declare.
Brain natriuretic peptide stimulates K and Cl secretion across porcine distal colon epithelium

Porcine distal colon epithelium was mounted in Ussing chambers and bathed with porcine Ringer solution. The serosal addition of brain natriuretic peptide (BNP; 50 nM) or atriopeptin III (AP-III; 500 nM) produced significant increases (50-75 microA/cm2) in short-circuit current (Isc). These increases in Isc were not inhibited by pretreatment with tetrodotoxin (TTX) or 5,8,11,14-eicosatetraynoic acid (ETYA). Analysis of concentration-response relationships revealed that BNP was 5.8-fold more potent than AP-III in stimulating the Isc. BNP and AP-III significantly increased the serosal-to-mucosal (S----M) Cl flux and reduced net Cl absorption by 38 and 41%, respectively. The BNP-stimulated S----M Cl flux was abolished when HCO3 was removed. In contrast, the vasoactive intestinal peptide (VIP)-stimulated S----M Cl flux was not affected by HCO3 replacement. In addition to their effects on Cl transport, BNP and AP-III increased net Rb secretion by 79 and 58%, respectively. BNP-stimulated Rb secretion was reduced by 76% after HCO3 replacement. These results indicate that natriuretic peptides stimulate K- and HCO3-dependent Cl secretion which is not present under basal conditions or after VIP stimulation. The difference in potency between BNP and AP-III suggests that ANP-B receptors may mediate their effects on ion transport in the porcine colon.
The Scientific and Industrial Revolutions

Few events have transformed the modern world as much as Europe’s Scientific81 and Industrial Revolutions.
Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don't Change a Thing

Currently, 380 000-400 000 occupational exposures to blood-borne pathogens occur annually in the United States. The management for occupational HIV or hepatitis B virus exposures includes postexposure prophylaxis (PEP) when necessary; however, PEP is not recommended for hepatitis C virus (HCV) exposures. Recent approval of HCV direct-acting antivirals (DAAs) has renewed discussions as to whether these therapies could be used to prevent infection after exposure. There are no published studies addressing this question, but the prescribing of DAAs for PEP has been reported. We will discuss the differences in transmission of the 3 most common blood-borne pathogens, the natural history of early HCV infection, and the scientific rationale for PEP. In particular, we will discuss how the low feasibility of conducting an adequately powered clinical trial of DAA use for PEP and the low cost-effectiveness of such an intervention is not supportive of targeting limited resources for such use.
Cardioversion and Defibrillation

Cardioversion and defibrillation are both techniques of terminating cardiac arrhythmias. Direct current (DC) cardioversion uses the discharge of electrical energy through the myocardium to terminate certain arrhythmias. In DC cardioversion shock delivery is synchronized with the QRS complex to avoid provoking ventricular fibrillation (VF). If a shock is given during the vulnerable refractory period of ventricular repolarization, VF may result [1]. In comparison defibrillation uses no synchronization and the shock is given randomly in the cardiac cycle. Monophasic and biphasic waveforms have been shown to be effective in cardioversion and defibrillation. In the use of biphasic waveforms current polarity becomes reversed which more consistently terminates arrhythmias with less energy delivered.
Application of a pore-scale reactive transport model to a natural analog for reaction-induced pore alterations

Abstract Dissolved CO2 in the subsurface resulting from geological CO2 storage may react with minerals in fractured rocks, confined aquifers, or faults, resulting in mineral precipitation and dissolution. The overall rate of reaction can be affected by coupled processes including hydrodynamics, transport, and reactions at the (sub) pore-scale. In this work pore-scale modeling of coupled fluid flow, reactive transport, and heterogeneous reactions at the mineral surface is applied to account for permeability alterations caused by precipitation-induced pore-blocking. This work is motivated by observations of CO2 seeps from a natural CO2 sequestration analog, Crystal Geyser, Utah. Observations along the surface exposure of the Little Grand Wash fault indicate the lateral migration of CO2 seep sites (i.e., alteration zones) of 10–50 m width with spacing on the order of ~100 m over time. Sandstone permeability in alteration zones is reduced by 3–4 orders of magnitude by carbonate cementation compared to unaltered zones. One granular porous medium and one fracture network systems are used to conceptually represent permeable porous media and locations of conduits controlled by fault-segment intersections and/or topography, respectively. Simulation cases accounted for a range of reaction regimes characterized by the Damkohler (Da) and Peclet (Pe) numbers. Pore-scale simulation results demonstrate that combinations of transport (Pe), geochemical conditions (Da), solution chemistry, and pore and fracture configurations contributed to match key patterns observed in the field of how calcite precipitation alters flow paths by pore plugging. This comparison of simulation results with field observations reveals mechanistic explanations of the lateral migration and enhances our understanding of subsurface processes associated with the CO2 injection. In addition, permeability and porosity relations are constructed from pore-scale simulations which account for a range of reaction regimes characterized by the Da and Pe numbers. The functional relationships obtained from pore-scale simulations can be used in a continuum scale model that may account for large-scale phenomena mimicking lateral migration of surface CO2 seeps.
(Re)defining "Good Teaching": Teacher Performance Assessments and Critical Race Theory in Early Childhood Teacher Education.

Using three tenents of Critical Race Theory, this study examines the influence of edTPAs on diverse early childhood pre-service teachers in a graduate program. Findings suggest that (1) Color-blind admissions policy and practice were at odds with edTPA’s perceived academic language demands; (2) A tension emerged between financial demands of edTPA and the constraints of immigrant and linguistically diverse students; and (3) edTPA rubrics and requirements required students of color to write and rewrite their teaching selves to match the external standard.
Learn While You Wait: An Experience of a Novel, Interactive VHA e-Notebook Education Program for Multiple Myeloma

Abstract 4743 We evaluated a novel e-notebook -based education program for patients with multiple myeloma. The program was developed by the Myeloma Initiative in the Veteran9s Administration (MIVA) consortium to educate patients while they wait for clinic appointments or procedures. The goals of this study were to assess feasibility of the program in a busy clinic setting, patients’ gain in knowledge from the program, patients’ acceptance of the e-notebook format, and potential use of program in other populations and in different formats. Study subjects were patients with multiple myeloma being treated at the Central Arkansas Veterans Healthcare System McClellan Hospital. Eligibility criteria were diagnosis of multiple myeloma, ability to follow instructions in the program and complete a paper questionnaire. Study subjects underwent the program while awaiting their oncology visit and then completed a survey consisting of ten multiple-choice questions designed to measure the goals of the study. The scope of the questions were: patients’ perceived benefit of the education program in improving their understanding of their disease (three questions), patients’ primary source of medical education, patients’ preferences in regard to educational formats (three questions), and multiple myeloma knowledge (three questions). Program use did not adversely affect patient flow in our busy oncology clinic, and was well accepted by the patients. Eight patients were enrolled in the study. All patients considered their oncologist to be their primary source of information about their disease. All patients stated that the education program helped them better understand the information provided by their oncologists and better understand multiple myeloma treatment options. Five patients (63%) answered that the program motivated them to learn more about myeloma. Seven patients (88%) recommended that this program be expanded to spouses or family members, and seven patients (88%) advocated creating a video format of the program for repeat viewing. Five patients (63%) stated they plan to view the content again at a later time. Of all multiple myeloma knowledge questions, 71% were answered correctly and 50% of the patients attributed their correct answers to information they learned in the education program. We conclude that this e-notebook -based multiple myeloma education program is well accepted, can be adopted in a busy clinic and has the potential for further applications. It is an effective and motivating tool for patient education in adjunct with physician efforts. It can be a productive utilization of waiting room time. Disclosures: No relevant conflicts of interest to declare.
Population effect model identifies gene expression predictors of survival outcomes in lung adenocarcinoma for both Caucasian and Asian patients.

Background We analyzed and integrated transcriptome data from two large studies of lung adenocarcinomas on distinct populations. Our goal was to investigate the variable gene expression alterations between paired tumor-normal tissues and prospectively identify those alterations that can reliably predict lung disease related outcomes across populations. Methods We developed a mixed model that combined the paired tumor-normal RNA-seq from two populations. Alterations in gene expression common to both populations were detected and validated in two independent DNA microarray datasets. A 10-gene prognosis signature was developed through a l1 penalized regression approach and its prognostic value was evaluated in a third independent microarray cohort. Results Deregulation of apoptosis pathways and increased expression of cell cycle pathways were identified in tumors of both Caucasian and Asian lung adenocarcinoma patients. We demonstrate that a 10-gene biomarker panel can predict prognosis of lung adenocarcinoma in both Caucasians and Asians. Compared to low risk groups, high risk groups showed significantly shorter overall survival time (Caucasian patients data: HR = 3.63, p-value = 0.007; Asian patients data: HR = 3.25, p-value = 0.001). Conclusions This study uses a statistical framework to detect DEGs between paired tumor and normal tissues that considers variances among patients and ethnicities, which will aid in understanding the common genes and signalling pathways with the largest effect sizes in ethnically diverse cohorts. We propose multifunctional markers for distinguishing tumor from normal tissue and prognosis for both populations studied.
Synergistic effects of plasma–catalyst interactions for CH4 activation

The elucidation of catalyst surface–plasma interactions is a challenging endeavor and therefore requires thorough and rigorous assessment of the reaction dynamics on the catalyst in the plasma environment. The first step in quantifying and defining catalyst–plasma interactions is a detailed kinetic study that can be used to verify appropriate reaction conditions for comparison and to discover any unexpected behavior of plasma-assisted reactions that might prevent direct comparison. In this paper, we provide a kinetic evaluation of CH4 activation in a dielectric barrier discharge plasma in order to quantify plasma–catalyst interactions via kinetic parameters. The dry reforming of CH4 with CO2 was studied as a model reaction using Ni supported on γ-Al2O3 at temperatures of 790–890 K under atmospheric pressure, where the partial pressures of CH4 (or CO2) were varied over a range of ≤25.3 kPa. Reaction performance was monitored by varying gas hourly space velocity, plasma power, bulk gas temperature, and reactant concentration. After correcting for gas-phase plasma reactions, a linear relationship was observed in the log of the measured rate constant with respect to reciprocal power (1/power). Although thermal catalysis displays typical Arrhenius behavior for this reaction, plasma-assisted catalysis occurs from a complex mixture of sources and shows non-Arrhenius behavior. However, an energy barrier was obtained from the relationship between the reaction rate constant and input power to exhibit ≤∼20 kJ mol−1 (compared to ∼70 kJ mol−1 for thermal catalysis). Of additional importance, the energy barriers measured during plasma-assisted catalysis were relatively consistent with respect to variations in total flow rates, types of diluent, or bulk reaction temperature. These experimental results suggest that plasma-generated vibrationally-excited CH4 favorably interacts with Ni sites at elevated temperatures, which helps reduce the energy barrier required to activate CH4 and enhance CH4 reforming rates.
Simulation of micro-scale shear bands using peridynamics with an adaptive dynamic relaxation method

Abstract A peridynamic (PD) implementation of crystal plasticity with an adaptive dynamic relaxation method is presented. Non-ordinary state-based peridynamics and the Newmark’s dynamic method with artificial damping are employed to capture strain localizations in polycrystalline microstructures based on a rate-independent crystal plasticity model. Numerical simulations for planar polycrystals are conducted under plane strain pure shear and compression, respectively. The computational efficiency of the explicit PD model is demonstrated to be superior to an implicit PD model for modeling crystal plasticity. The stress field distribution, texture formation, and homogenized stress-strain response predicted by the finite element method and the new dynamic PD model are compared. Finer localization bands are observed in the latter model. The origin and evolution of these shear bands are studied by PD simulations during deformation of three polycrystals with different orientation distributions. Emphasis is placed on the accuracy and efficiency of the adaptive dynamic relaxation method working with crystal plasticity PD models.
Penalized MLAA with spatially-encoded anatomic prior in TOF PET/MR

PET/MR scanner has been developed for both molecular and morphological assessment with great potentials. In the PET/MR scan, the attenuation correction is still a problem. One method is the MR-based attenuation correction that generates the synthetic CT images from MR images. However, the lack of bone signal and the bias from the synthetic CT image can degrade the PET image quality. Another method is a maximum likelihood reconstruction of activity and attenuation (MLAA) using the time-of-flight (TOF) PET emission data, however, the noise component is considerably high from TOF PET data. To address this issue, we propose a penalized MLAA using a spatially-encoded anatomic MR prior, which jointly use a patch-based spatially-encoded similarity weight of MR image to improve the attenuation image quality. In addition, we propose a non-divergence criteria using a consistency condition in the iterative process. We exploit an alternating direction method of multipliers (ADMM) algorithm to optimize the cost function. In computer simulations, we demonstrate that the proposed method outperform the conventional MLAA.
Wnt in Hematopoietic and Leukemic Stem Cells

When first discovered, it was clear that Wnts and their downstream targets played a pivotal role in the evolution of cancer in mice. However, recent research has underscored the importance of the Wnt pathway in essential regenerative and repair processes, particularly in the maintenance of self-renewing, blood-forming stem cells. Seminal studies involving a multiplicity of human cancers revealed epigenetic and genetic changes that activated the Wnt pathway, primarily through deregulation of the destruction complex, rendering it a vital potential therapeutic target in cancer. Wnt pathway deregulation is particularly prominent in leukemia, which has provided an important paradigm for dissecting the molecular mechanisms involved in Wnt pathway deregulation in a cell type and context-specific manner. Perhaps most importantly, the discovery of leukemia stem cells provided the impetus for investigating the role of the Wnt pathway in fueling their characteristically unbridled self-renewal capacity. In this review, we examine the contribution of the Wnt pathway to normal hematopoietic stem cell (HSC) versus leukemic stem cell (LSC) propagation in order to establish whether a therapeutic index is likely to exist that will warrant the development of Wnt inhibitor clinical trials in cancer.
Ricoeur’s “Allegory” and Jakobson’s Metaphoric/Metonymic Principles

Paul Ricoeur denies symbolic effect to expressions where the original sense of an expression is destroyed in the process of interpretation, calling such discourse “allegory”, the mere “rhetorical” and “didactic” procedure in which the literal meaning is “eliminated once it has done its job”. Such language is a vehicle, or a ladder: “Having ascended the ladder”, says Ricoeur, “we can then descend it” (Ricoeur 1976: 55).1 Ricoeur thus employs two categories, and if we are to have two categories — one in which the initial sense is destroyed (Ricoeur’s “allegory”), and the other in which the original meaning is retained and added to the second meaning (Ricoeur’s “symbol”) — I believe it is more helpful to subject symbolism to Roman Jakobson’s paradigm, establishing two forms of symbolism, each signaled by contextual cues: the metaphoric symbol, in which the literal expression is discarded, and the metonymic symbol in which no such discarding occurs.2
E-business solutions in the cable TV industry

This paper aims at developing implementable e-business solutions for the cable TV industry to accelerate the information technology and information system adoptions; and thereby, increase value for the operations in the industry. Specifically, an electronic value chain is developed to show how to improve value by using information technology and information system. Then, a set of implementable solution items are developed based on this electronic value chain model. Finally, recommendations are provided on how to implement these solution items.
Wu Wei (Non-doing) and the Negativity of Depression

The anxiety of being drives us to the quest for security and certainty. The question emerges, “what is the Way?” In an attempt to find the Way through cognitive process, we are further removed from It. This parallel process takes place when depressed individuals struggle with the negativity of depression. Wu wei is an invitation to return to the Way and to the self. The self that embraces negativity is able to rest in itself.
Jazz and the African-American Experience: The Expressiveness of African-American Music

While Paul never published articles in the area of Ethics, he nonetheless read a great deal of ethical theory. He concluded that there were too many mush-heads doing ethics. When asked which ethicists he thought worth reading, he suggested Bentham, Prichard, Hegel’s Philosophy of Right, Bradley’s essays, and the ethical writings of Amartya Sen. That he suggested these writers did not mean he endorsed their positions. Over the years, we discussed his approach to philosophy and why he attacked what was often thought to be “sacred doctrines.” In the end, his work has always had as one of its goal to stop mush headed thinking.
Intramolecular Dynamics: Regular and Stochastic Vibrational States of Molecules

The nature of molecular vibrational states at low and high energies has been studied both classically and quantum mechanically. At low energies the classical vibrational motion is highly “regular” (quasiperiodic) in the usual harmonic normal mode regime. Interestingly enough, it can still remain so when the motion is anharmonic. However, at high enough vibrational energies numerical calculations indicate that the classical mechanical motion usually becomes chaotic (frequently termed “stochastic”) although still deterministic, of course. The corresponding quantum mechanical behavior is discussed using semiclassical ideas, and a method of calculating eigenvalues in the quasiperiodic regime is described.
Right Leg Pain, Swelling, and Erythema for Two Days

A 40-year-old male with diabetes mellitus and hepatitis C-related cirrhosis presents to the emergency department with a two-day history of right leg pain, redness, and swelling. He states that he thinks he may have been bitten in the leg by some kind of bug while sleeping. On physical examination, his temperature is 100.5 °F, heart rate is 110/min, blood pressure is 90/60 mmHg, and respiratory rate is 18/min. His right leg is markedly swollen as compared to the left. The skin overlying the calf region is erythematous, with one 3 cm bullae that in the center has violaceous skin. There is no palpable crepitus. Plain X-ray of the leg demonstrates gas bubbles within the soft tissue in the calf. The foot itself is pink and warm, with normal pulses. Laboratory values are significant for a BUN of 40 mg/dL (normal 7–20 mg/dL), serum glucose of 200 mg/dL (70–100 mg/dL), creatinine of 1.6 mg/dL (0.8–1.4 mg/dL), WBC of 24 × 103/μL (4.1–10.9 × 103/μL), hemoglobin of 9.5 g/dL (13.8–17.2 g/dL), and a serum sodium of 128 mEq/L (136–144 mEq/L).
Addressing Mandatory Lane Change Problem with Game Theoretic Model Predictive Control and Fuzzy Markov Chain

We develop a game theoretic model predictive controller (GTMPC) to deal with the mandatory lane change (MLC) problem for a subject vehicle (SV) in presence of multiple surrounding vehicles (SRV). The GTMPC uses game theory as a high-level controller, which regards at most three SRVs as the game theoretic candidate vehicles (GCV), with each playing a game with SV. The payoff of GCV is defined as the acceleration utility plus a convex combination of the space utility and safety utility, whose weights are associated with GCV's aggressiveness. Model predictive control (MPC) is utilized as a metric for SV's payoff in the game as well as a low-level controller that is responsible for both SV's longitudinal positioning and lane decision. GTMPC uses fuzzy Markov chain to generate the prediction of GCV's future motion, which is utilized in both defining GCV's payoffs over the prediction horizon in the game and as the reference of the MPC. Simulation showed the GTMPC was able to intelligently drive SV into the selected gap and accomplish the MLC in a dynamic situation without knowing the exact model of SRVs.
From Crystal Skulls to the Caste War: Intersections of Tourism, Archaeology and Heritage in the Yucatán Peninsula of Mexico

Archaeological sites in the Yucatan Peninsula are among the leading attractions for a thriving tourism industry and have helped to significantly boost the local economy since the 1970s. While the s...
Advancement of flow velocity measurements in excised canine larynx model

In the classic source-filter model of speech production, flow modulation is the source of sound. Modulation of the flow refers to the fact that the volume flow, Q, is changing as the glottis opens and closes. Furthermore, studies have shown that the maximum flow declination rate (MFDR), which occurs during the latter part of the closing phase, is highly correlated with acoustic intensity (loudness) and acoustic energy in the higher harmonics. Therefore, measurements of the glottal airflow can provide important insights into voice mechanisms, dysfunction and efficiency. In recent years, particle image velocimetry (PIV) have become the method of choice for measuring Q because the technique can quantify, non-intrusively, the spatial and temporal information of the flow. The discussion includes progress of PIV measurements, from 2D to tomographic measurements, in the excised canine larynx model. Key findings related to intraglottal flow and glottal geometry, and their extension to modeling of voice mechanisms, are described.In the classic source-filter model of speech production, flow modulation is the source of sound. Modulation of the flow refers to the fact that the volume flow, Q, is changing as the glottis opens and closes. Furthermore, studies have shown that the maximum flow declination rate (MFDR), which occurs during the latter part of the closing phase, is highly correlated with acoustic intensity (loudness) and acoustic energy in the higher harmonics. Therefore, measurements of the glottal airflow can provide important insights into voice mechanisms, dysfunction and efficiency. In recent years, particle image velocimetry (PIV) have become the method of choice for measuring Q because the technique can quantify, non-intrusively, the spatial and temporal information of the flow. The discussion includes progress of PIV measurements, from 2D to tomographic measurements, in the excised canine larynx model. Key findings related to intraglottal flow and glottal geometry, and their extension to modeling of voice mechanisms...
Robotic Inguinal Hernia: The Why and the Hows

Robotic inguinal hernia is a controversial topic. The use of a robotic platform to perform a minimally invasive, preperitoneal hernia repair builds on the 20-year debate between traditional open versus laparoscopic inguinal hernia. In 2018, 80% of all inguinal hernia are repaired using an open technique, despite two decades of training and experience with laparoscopic inguinal hernia surgery. The robotic technique is based on the well-delineated transabdominal preperitoneal (TAPP) laparoscopic inguinal hernia repair. The lack of adoption of minimally invasive (MIS) techniques in inguinal hernia runs counter to trends of MIS increased adoption for procedures such as appendectomy, colectomy, cholecystectomy, and even ventral hernia. One would expect that adding more potential cost to the high cost of a laparoscopic inguinal repair would decrease the perceived value of the robotic inguinal hernia. This does not appear to be the case, as early trends are showing migration of both open and laparoscopic surgeons to the robotic platform. The central questions this chapter will address are how can the cost of robotic inguinal hernia surgery be minimized and in which patient population does the value proposition become positive.
What’s in a Name? How “Deep Brain Stimulation” May Influence Patients’ Perceptions

While the study by Lawrence and colleagues (Lawrence, Kaufmann, DeSilva, and Appelbaum 2019) offers several important insights into the ethical issues related to the use of DBS for depression, a no...
Microbial nutrient factories in insects on extreme diets

Insects are renowned for their capacity to specialize on a wide diversity of diets, many of which are nutrient-poor or nutritionally unbalanced. For example, various insects feed through the life cycle on wood, vertebrate blood, plant sap and other extreme diets that are variously deficient in vitamins, sterols and essential amino acids . These insects circumvent the fundamental “rules” of animal nutrition because they possess symbiotic microorganisms that overproduce the limiting dietary nutrients. Many associations between insects and microorganisms are evolutionarily ancient and involve the exquisite coevolution of metabolic function in the insect and microbial partners, including the restructuring of microbial metabolism as nutrient factories for the host ( Fig. 1 ). These insects include major pests and vectors of animal, human and crop disease agents. Their dependence on specific microorganisms offers novel routes for the control of these globally important insect pests .
Current status of histone deacetylase inhibitors in cutaneous T-cell lymphoma.

Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin's lymphoma with a heterogenous presentation and highly variable disease course. The most common subtypes of CTCL are mycosis fungoides (MF) and Sezary Syndrome (SS). Treatment varies based on the stage of the disease with skin directed therapies typically utilized for early stage disease, and systemic therapies employed for more advanced disease. There are few highly effective treatments available, and systemic therapies have limited response rates. Histone deacetylase inhibitors have emerged as mainstream treatments for MF/SS over the past several years. Here, we discuss the mechanism of action of histone deacetylase inhibitors in relation to the pathogenesis of MF/SS, evaluate the clinical trials that led to Food and Drug Administration approval of two of the histone deacetylase inhibitors for MF/SS and describe the results for those still under investigation. Additionally, we discuss the potential for combination therapies in order to optimize outcomes of treatment with histone deacetylase inhibitors.
Determining the Sediment Distribution of Methanogenic Bacteria by Direct Fluorescent Antibody Methodology

A direct fluorescent antibody (FA) methodology was devised to accurately quantitate a select number of known methanogenic bacteria in the sediments of Lake Erie. The specificity of the respective fluorescent antibodies was evaluated against a limited number of hetero- and methylotrophic bacteria. The fluorescent antibodies for each of the surveyed methanogens were specific in that no cross reactions with the other methanogenic species could be shown. The autofluorescence of the methane bacteria and nonspecific absorption were masked by rhodamine isothiocyanate conjugated bovine serum albumin (RhoITC-BSA) The FA methodology devised permitted the detection of the specific methanogens in numbers as low as 10 6 cells per gram of lake sediment. The FA method worked equally well when applied to fine silt, sand-silt, or sand sediments. The presence of large numbers of other microorganisms did not interfere with the staining process. To increase the sensitivity of this sediment analysis, organic and inorganic enrichments were.pursued. These procedures permitted the selective enrichments of specific methanogens to population sizes (10 6 /ml or greater) large enough for direct FA observation. Thus, this direct FA staining methodology can specifically and accurately quantitate the known methanogenic bacteria in lake sediments. This procedure can be combined with concentration techniques to increase the sensitivity of the FA procedure. Also, this staining procedure could be adapted to other methanogenic bacteria, either known pure cultures or natural isolates, which could be obtained from lake sediments. The greatest advantage this enumeration has over other methods of enumerating methanogens [most probable number (MPN), substrate limitations, or general cellular morphology] is that it is a direct count that is species specific.
A Money Multiplier Approach to How Open Market Operations Stimulate Securities Markets and the Real Economy

This chapter presents a model of crowd out and loanable funds effects in money multiplier methodology model showing the effects of changes in crowd out or loanable funds on Mishkin’s sophisticated money multiplier.
Topical Review: Gene Therapy for Neurologic Disease: Benchtop Discoveries to Bedside Applications. 2. The Bedside

Important advances in basic research have made it possible to examine the safety, toxicity, and efficacy of gene therapy in humans for over 5 years. The development of sophisticated gene delivery systems has resulted in approval by the Recombinant DNA Advisory Committee (RAC) of 125 gene therapy or gene marking studies. One of the primary applications of current retroviral-mediated gene insertion technology has been for malignant brain tumors. Studies are therefore underway to examine the efficacy of "suicide" gene therapy in children with recurrent brain tumors and adults with newly diagnosed or recurrent gliomas. Since a high proportion of genetic disorders produce neurologic dysfunction, gene therapy is likely to impact the management of neurologic disease in the foreseeable future. Patients with human immunodeficiency virus (HIV), Gaucher's disease, and Hunter syndrome are now enrolled in gene therapy trials. It will be challenging for the child neurologist to stay abreast of rapid developments in the...
Bilevel stochastic methods for optimization and machine learning: Bilevel stochastic descent and DARTS.

Two-level stochastic optimization formulations have become instrumental in a number of machine learning contexts such as neural architecture search, continual learning, adversarial learning, and hyperparameter tuning. Practical stochastic bilevel optimization problems become challenging in optimization or learning scenarios where the number of variables is high or there are constraints. The goal of this paper is twofold. First, we aim at promoting the use of bilevel optimization in large-scale learning and we introduce a practical bilevel stochastic gradient method (BSG-1) that requires neither lower level second-order derivatives nor system solves (and dismisses any matrix-vector products). Our BSG-1 method is close to first-order principles, which allows it to achieve a performance better than those that are not, such as DARTS. Second, we develop bilevel stochastic gradient descent for bilevel problems with lower level constraints, and we introduce a convergence theory that covers the unconstrained and constrained cases and abstracts as much as possible from the specifics of the bilevel gradient calculation.
Development, Verification and Use of Gust Modeling in the NASA Computational Fluid Dynamics Code Fun3d

This paper presents the implementation of gust modeling capability in the CFD code FUN3D. The gust capability is verified by computing the response of an airfoil to a sharp edged gust. This result is compared with the theoretical result. The present simulations will be compared with other CFD gust simulations. This paper also serves as a users manual for FUN3D gust analyses using a variety of gust profiles. Finally, the development of an Auto-Regressive Moving-Average (ARMA) reduced order gust model using a gust with a Gaussian profile in the FUN3D code is presented. ARMA simulated results of a sequence of one-minus-cosine gusts is shown to compare well with the same gust profile computed with FUN3D. Proper Orthogonal Decomposition (POD) is combined with the ARMA modeling technique to predict the time varying pressure coefficient increment distribution due to a novel gust profile. The aeroelastic response of a pitch/plunge airfoil to a gust environment is computed with a reduced order model, and compared with a direct simulation of the system in the FUN3D code. The two results are found to agree very well.
Histone Acetylation and Deacetylation

Gene expression in eukaryotic organisms can be influenced by a host of internal and external stimuli. The magnitude and duration of the response can often determine the effect of a diverse array of biological functions, many of which can be driven by gene expression. The catalog of possibilities encoded within an organism's primary DNA sequence is heritable and, by design, is immutable in response to these temporally defined internal and external factors and events. It has become increasingly evident that the primary sequence alone is not the only determinant of phenotype and function. Rather, epigenetic mechanisms can influence gene expression without directly affecting the primary DNA sequence. These epigenetic mechanisms can affect gene expression directly via the modification of DNA, or indirectly via the modification of chromatin (storage state of DNA). The acetylation and deacetylation of the N-terminal tails of histones (the core protein component of chromatin) represents an important epigenetic mechanism which affects chromatin structure and, ultimately genomic response, via gene expression. The regulation of histone acetylation status is tightly balanced by the opposing function of two families of enzymes: the HATs (histone acetyltransferases) and the HDACs (histone deacetylases). The function and regulation of these enzymes, which is highly conserved in evolution, can have a profound effect on a multitude of biological processes including transcription, DNA repair and replication, and cellular differentiation. Keywords: Chromatin; Euchromatin; Heterochromatin; Nucleosome; Histones; Acetylation; Deacetylation; HDACs (histone deacetylases); HATs (histone acetyltranferases); Sirtuins
MPEG video traffic models: sequentially modulated self-similar processes

New traffic models are called for to facilitate the design of effective admission and flow control algorithms, and network performance evaluation in accommodating video traffic. We propose a new approach, sequentially modulated self-similar processes (SMSSPs), to model MPEG coded video traffic. SMSSPs are shown to be able to capture both short range dependency (SRD) and long range dependency (LRD) of the video traffic accurately. Traffic data are decomposed according to the MPEG data structure, into several parts, each modeled as a self-similar process. These processes are then modulated sequentially in a manner similar to how the frames are grouped into the GOP (Group of Pictures) pattern.
Introduction to Elasticity Theory for Crystal Defects

1. Introduction 2. Basic linear elasticity 3. Methods 4. Green's functions for unit point force 5. Interactions between defects and stress 6. Inclusions in infinite homogeneous regions 7. Interactions between inclusions and imposed stresses 8. Inclusions in finite homogeneous regions - image stresses 9. Inhomogeneities 10. Point defects in infinite homogeneous regions 11. Interactions between point defects and stresses 12. Dislocations in infinite homogeneous regions 13. Interactions between dislocations and stresses 14. Interfaces 15. Interactions between interfaces and stresses 16. Interactions between defects Appendices Index.
5′-Deoxy-5′-methylthioadenosine phosphorylase—III: Role of the enzyme in the metabolism and action of 5′-halogenated adenosine analogs

Abstract 5′-Deoxy-5′-halogenated adenosines are alternative substrates for 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAPase), an enzyme responsible for the metabolism of 5′-deoxy-5′-methylthioadenosine (MTA), a by-product of polyamine biosynthesis. The relative reactivity of these nucleosides with MTAPase from HL-60 human promyelocytic leukemia cells is MTA > 5′-deoxy-5′-fluoroadenosine (5′-FlAdo) > 5′-chloro-5′-deoxyadenosine (5′-ClAdo) > 5′-bromo-5′-deoxyadenosine (5′-BrAdo) > 5′-deoxy-5′-iodoadenosine (5′-IAdo). In MTAPase-containing cells, the adenine released from the 5′-halogenated adenosine was incorporated into adenine nucleotide pools; cleavage by (MTAPase appeared to be the rate-limiting step in this process. 5′-BrAdo and 5′-IAdo were growth inhibitors (Spec 50 values 65 μM) against MTAPase-deficient cell lines (the CCRF-CEM human T cell leukemia and the L1210 murine leukemia). The full cytotoxidty of these compounds, therefore, appeared to be related to their phosphorolysis by MTAPase. Indirect evidence suggests that 5-halogenated ribose-1 -phosphate derivatives of 5′-BrAdo or 5′-IAdo produced by the MTAPase reaction were the active metabolites of these 5′-halogenated adenosines.
GANGLION-a fast hardware implementation of a connectionist classifier

The authors describe the implementation of GANGLION, a fully interconnected, digital, feedforward connectionist classifier with one hidden layer capable of 4.48 billion interconnections per second. The single card classifier, built using only off-the-shelf components, relies heavily on field-programmable gate arrays. The high speed of the classifier makes it especially suited for applications in machine vision, and in particular in industrial inspection tasks, where sensor speeds beyond the speed of ordinary TV cameras are common. >
Lymphocyte and polymorphonuclear enzymes in stress: V. Changes associated with a viral infection: Herpes simplex

Abstract Rabbits were infected with herpes simplex virus by instillation of the suspension into the conjunctival sac. The disease was studied at three levels of severity. Protein, LDH, MDH, ALD, CPK concentrations of differentially separated peripheral leukocytes were determined at regular intervals after exposure. Decreases in leukocyte protein and enzyme concentrations were noted in the most acute disease that contrasted with the increases observed, especially in C2 lymphocytes, in the more moderate disease. The increases in C2 protein and LDH in an acute herpes simplex infection are in contrast to the effects of infection with Diplococcus pneumoniae in which C1 protein was elevated. A further contrast is the elevation of C5 LDH or MDH in the viral infection not observed in the pneumococcal infection. Increases in protein and LDH in the mildest, completely localized disease were under 200%. The consistency or lack of change in leukocyte enzyme levels over a 3 wk period, when the stress is minimal, is noteworthy, and resembles the changes observed in rabbits subjected only to the stress of repeated bleedings.
Does change in acetylcholine receptor antibody level correlate with clinical change in myasthenia gravis

Introduction: The objective of this study is to determine if change in acetylcholine receptor antibody (AChR-ab) levels reflects change in clinical severity in patients with myasthenia gravis (MG). Methods: We reviewed results from a prospective trial in MG and from all 85 patients in an MG Clinic who had AChR-ab determinations performed at least twice by the same commercial laboratory. Results: Change in AChR-ab levels correlated only weakly with change in clinical severity. AChR-ab levels fell in 92% of patients who improved and in 63% who did not. A fall in AChR-ab level had a positive predictive value for clinical improvement of 83% and a negative predictive value of only 59%. Conclusions: AChR-ab levels fell in almost all patients who improved, but also in most patients who did not. Thus, we do not recommend commercially available AChR-ab levels as a biomarker of improvement in MG. However, antibody levels might be useful as a marker for inadequate immunotherapy. Muscle Nerve 49:483–486, 2014
Percutaneous coronary intervention in pediatric and adolescent patients.

Objective Percutaneous coronary intervention (PCI) is commonly used in adult patients with coronary artery disease, but data on PCI in children and adolescents remain limited. Herein, we describe our experience with the use of PCI in pediatric and adolescent patients. Design This is a retrospective review. Setting The study was conducted at Mayo Clinic, Rochester, MN. Patients All patients ≤18 years old who underwent PCI from 2004 to 2012 were included. Interventions Intravascular ultrasound and balloon angioplasty were performed in all patients, with subsequent stent placement in 6/7 (86%) procedures. Outcome Measures Residual postintervention stenosis, early procedural morbidity and mortality were the outcome measures. Results Overall, seven unique PCI procedures were performed in five patients (four males, mean age 13.2 ± 3.8 years, range 8–18 years). Mean follow-up interval was 2 (0.6–5.5) years. Indications for the procedures included transplant coronary vasculopathy (n = 1), coronary dissection (n = 1), and acute coronary thrombosis/myocardial infarction (n = 1). Additionally, there were two patients (n = 2) who experienced coronary compression as a sequelae of prior heart surgery. Intravascular ultrasound and balloon angioplasty were performed in all patients, with subsequent stent placement in 6/7 (86%) procedures. A total of eight stents were placed (average stent diameter 3 ± 0.5 mm), including six (75%) drug-eluting stents. The targeted coronary artery lesions were successfully treated in all seven procedures. There was no early procedural morbidity or mortality. Two patients were noted to have angiographic evidence of in-stent restenosis at 3 and 15 months postdeployment, respectively, despite treatment with aspirin and clopidogrel. Conclusion PCI in children and adolescents can be utilized to improve coronary blood flow in a variety of clinical situations. It may be particularly effective in cases of postsurgical coronary compression. Close angiographic follow-up is critical as these patients are at risk for in-stent restenosis.
Coevolution of bed surface patchiness and channel morphology: 1. Mechanisms of forced patch formation

Riverbeds frequently display a spatial structure where the sediment mixture composing the channel bed has been sorted into discrete patches of similar grain size. Even though patches are a fundamental feature in gravel bed rivers, we have little understanding of how patches form, evolve, and interact. Here we present a two-dimensional morphodynamic model that is used to examine in greater detail the mechanisms responsible for the development of forced bed surface patches and the coevolution of bed morphology and bed surface patchiness. The model computes the depth-averaged channel hydrodynamics, mixed-grain-size sediment transport, and bed evolution by coupling the river morphodynamic model Flow and Sediment Transport with Morphological Evolution of Channels (FaSTMECH) with a transport relation for gravel mixtures and the mixed-grain-size Exner equation using the active layer assumption. To test the model, we use it to simulate a flume experiment in which the bed developed a sequence of alternate bars and temporally and spatially persistent forced patches with a general pattern of coarse bar tops and fine pools. Cross-stream sediment flux causes sediment to be exported off of bars and imported into pools at a rate that balances downstream gradients in the streamwise sediment transport rate, allowing quasi-steady bar-pool topography to persist. The relative importance of lateral gravitational forces on the cross-stream component of sediment transport is a primary control on the amplitude of the bars. Because boundary shear stress declines as flow shoals over the bars, the lateral sediment transport is increasingly size selective and leads to the development of coarse bar tops and fine pools.