cssi/SciSciGPT-SciSciNet huggingface dataset:
Localized Adenovirus‐Mediated Gene Transfer Into Vascular Smooth Muscle in the Hamster Cheek Pouch

Objective:Our purpose was to develop a method for adenovirus delivery to the hamster cheek pouch to experimentally target gene transfer in tissue used for microvascular studies. Methods:Separate constructs were tested with transgenes for lacZ or green fluorescent protein (GFP) driven by three promoters: RSV, CMV, and SM22. With university approval, adenovirus was delivered in anesthetized (pentobarbital, 70 mg/kg) hamsters (n = 28) by using either a vascular systemic injection or tissue infiltration (interstitial space behind the pouch). During 3 days, animals receiving infiltration gained the expected weight, whereas those receiving vascular injection lost weight; no other behavior changes were noted. Results:On day 3 postadenoviral delivery (infiltration), expression of lacZ (histology, β-galactosidase) or GFP (fluorescence microscopy) was confirmed across the tissue (CMV and RSV promoters) and exclusively in vascular smooth muscle cells (specific SM22 promoter), without evidence of tissue inflammation....
Towards schema-based, constructivist robot learning: Validating an evolutionary search algorithm for schema chunking

In this paper, we lay the groundwork for extending our previously developed ASyMTRe architecture to enable constructivist learning for multi-robot team tasks. The ASyMTRe architecture automatically configures schemas within, and across, robots to form the highest utility solution that achieves a given multi-robot team task. We believe that the schema- based approach used in ASyMTRe is a useful abstraction not only for forming heterogeneous coalitions, but also for enabling constructivist learning, in which chunks of schemas that solve intermediate subproblems are learned and then made available for future task solutions. However, the existing ASyMTRe search algorithm for finding configurations of schemas that completely solve given tasks (Centralized ASyMTRe - CA) is not well-suited for identifying useful chunks of schemas that could solve intermediate subtasks that may be useful in the future. Thus, in this current work, we explore an Evolutionary Learning (EL) technique for the offline learning of schema chunks that could be saved and used later in an online search (using the regular CA algorithm) for coalition configurations. However, we do not want to sacrifice solution quality in making use of the evolutionary search technique. Thus, we compare the solutions discovered by the EL algorithm with those that are found using CA, as well as with a third algorithm that randomizes the CA algorithm, called RA. Four different applications in simulation are used to evaluate the EL, CA, and RA techniques. Our results show that the EL approach indeed finds solutions of comparable quality to the CA technique, while also providing the added benefit of learning highly fit partial solutions, or schema chunks, that may be beneficial for future tasks via constructivist learning. We conclude by arguing that the combination of the online CA search for solving current multi-robot tasks can be combined with the offline EL approach that can identify intermediate solutions (or schema chunks) that may be useful for future team tasks. This combination should lead to an overall efficiency improvement for identifying coalition formations, as well as for continual learning.
Time-Resolved Reflectivity Studies of Electric Field Effects in III-Nitride Semiconductors

Comparison of room temperature, frequency degenerate and nondegenerate femtosecond pump-probe reflectivity measurements reveal an additional component in the transient reflectivity (ΔR) decays for near bandgap probe in GaN that is attributed to a reduction of bandedge broadening due to screening of internal electric fields by photogenerated carriers. Pump-probe measurements with pulses spectrally centered at 363 nm show a ΔR component with a nanosecond decay time that is essentially absent from data obtained from nondegenerate experiments performed under identical pumping conditions, but with a probe at 385 nm far enough from the bandedges to minimize the electric field contribution and monitor primarily the carrier lifetime in the band states. The observation of significantly shorter decay times for 385 nm probe suggests that the carriers leave the band states on a picosecond time scale, but the slow decay of the field screening observed with 363 nm probe implies that they recombine from trap states at longer times. In addition, this field screening provides a mechanism for generation and detection of strain pulses in strained GaN and AlGaN epilayers that is used to measure the longitudinal sound velocity in bulk GaN and AlGaN with up to 0.4 Al content.
Neutral Evolution, Population Genetic Tests of

Tests of neutrality assess whether patterns of genetic variation are compatible with neutral evolutionary models. They have been successfully used for genome-wide selection scans, yielding important candidate genes for recent adaptation in humans and other species. Here, we present a short overview of commonly used tests of neutrality and the patterns of genetic variation on which they are based. Understanding the performance of particular neutrality tests under various demographic histories and types of selection is crucial for their correct interpretation. Therefore, we place particular emphasis on the specific assumptions of each test.
A Systematic Review of Opioid and Benzodiazepine Misuse in Older Adults

Objective The authors assessed the prevalence of opioid and benzodiazepine prescription drug misuse in older adults, the risk factors associated with misuse, and age-appropriate interventions. Methods Following PRISMA guidelines, a literature search of PubMed, PsycINFO, and EMBASE for peer-reviewed journal articles in English through April 2014 with updates through November 2015 was conducted for reports on misuse of prescription benzodiazepines and opioids in older adults. Relevant publications were reviewed that included participants age ≥65 years. Reference lists were manually searched for key identified articles and geriatric journals through April 2016. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. Results Of 4,932 reviewed reports, 15 were included in this systematic review. Thirteen studies assessed the prevalence of prescription drug misuse and included studies related to opioid shopping behavior, assessment of morbidity and mortality associated with opioid and/or benzodiazepine use, frequency and characteristics of opioid prescribing, frequency of substance use disorders and nonprescription use of pain relievers, and health conditions and experiences of long-term benzodiazepine users. One study identified risk factors for misuse, and one study described the effects of provider education and an electronic support tool as an intervention. Conclusion There is a dearth of high quality research on prescription drug misuse in older adults. Existing studies are heterogeneous, making it difficult to draw broad conclusions. The need for further research specific to prescription drug misuse among older adults is discussed.
Multi-decadal variability of soil moisture-temperature coupling over the contiguous United States modulated by Pacific and Atlantic sea surface temperatures.

Regions of strong land–atmosphere coupling are often depicted as static in time. However, the mechanisms through which the land surface impacts atmospheric conditions vary on sub-daily to multi-decadal timescales. Therefore, characterizing the long-term variability of land–atmosphere interactions may provide a means of predicting when surface-induced extreme temperature events will be more or less likely to occur. We evaluate the coupling strength between soil moisture, as represented by in situ observations and 1-month Standardized Precipitation Index (SPI), and subsequent monthly maximum temperature (TMAX) over the contiguous United States. We find that the utility of SPI as a proxy for soil moisture anomalies is limited to the summer, as the correlations between SPI and TMAX are not significantly related in the other seasons. We examine the variability in summer SPI–TMAX coupling in four regions of the United States. In general, we find the strongest relationships between SPI and TMAX in the Southern Great Plains. However, our results demonstrate that the coupling strength varies considerably over time in most regions of the United States. The long-term variability in SPI–TMAX coupling strength is strongly related to the Pacific Decadal Oscillation in the northwest and midwest United States, and the Atlantic Multidecadal Oscillation in the southeast United States The results of this study suggest that land–atmosphere coupling in the contiguous United States is modulated by multi-decadal oscillations in Pacific and Atlantic sea surface temperatures.
Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells

Intestinal iron absorption is highly regulated since no mechanism for iron excretion exists. We previously demonstrated that expression of an intestinal copper transporter (Atp7a) increases in parallel with genes encoding iron transporters in the rat duodenal epithelium during iron deprivation (Am. J. Physiol.: Gastrointest. Liver Physiol., 2005, 288, G964–G971). This led us to postulate that Atp7a may influence intestinal iron flux. Therefore, to test the hypothesis that Atp7a is required for optimal iron transport, we silenced Atp7a in rat IEC-6 and human Caco-2 cells. Iron transport was subsequently quantified in fully-differentiated cells plated on collagen-coated, transwell inserts. Interestingly, 59Fe uptake and efflux were impaired in both cell lines by Atp7a silencing. Concurrent changes in the expression of key iron transport-related genes were also noted in IEC-6 cells. Expression of Dmt1 (the iron importer), Dcytb (an apical membrane ferrireductase) and Fpn1 (the iron exporter) was decreased in Atp7a knockdown (KD) cells. Paradoxically, cell-surface ferrireductase activity increased (>5-fold) in Atp7a KD cells despite decreased Dcytb mRNA expression. Moreover, increased expression (>10-fold) of hephaestin (an iron oxidase involved in iron efflux) was associated with increased ferroxidase activity in KD cells. Increases in ferrireductase and ferroxidase activity may be compensatory responses to increase iron flux. In summary, in these reductionist models of the mammalian intestinal epithelium, Atp7a KD altered expression of iron transporters and impaired iron flux. Since Atp7a is a copper transporter, it is a logical supposition that perturbations in intracellular copper homeostasis underlie the noted biologic changes in these cell lines.
Eye-Gaze Analysis of Facial Emotion Recognition and Expression in Adolescents with ASD

Impaired emotion recognition and expression in individuals with autism spectrum disorder (ASD) may contribute to observed social impairment. The aim of this study was to examine the role of visual attention directed toward nonsocial aspects of a scene as a possible mechanism underlying recognition and expressive ability deficiency in ASD. One recognition and two expression tasks were administered. Recognition was assessed in force-choice paradigm, and expression was assessed during scripted and free-choice response (in response to emotional stimuli) tasks in youth with ASD (n = 20) and an age-matched sample of typically developing youth (n = 20). During stimulus presentation prior to response in each task, participants’ eye gaze was tracked. Youth with ASD were less accurate at identifying disgust and sadness in the recognition task. They fixated less to the eye region of stimuli showing surprise. A group difference was found during the free-choice response task, such that those with ASD expressed emotion...
OCoM-SOCoM: Combinatorial Mutagenesis Library Design Optimally Combining Sequence and Structure Information

High-throughput screening of combinatorial mutagenesis libraries has enabled and accelerated the development of beneficial protein variants. However, since even the most massive library contains only a miniscule fraction of the possible variants of a target protein, it is advantageous to use computational methods to design a library for enrichment in beneficial variants. Here we develop a general-purpose method, OCoM-SOCoM, that designs large combinatorial libraries simultaneously for both the sequence properties (OCoM) and the structural properties (SOCoM) of their constituent variants. Our algorithm optimizes library designs along the continuum of optimal trade-offs (the Pareto frontier) between library-based scores efficiently assessing expected structure-based energy (via Cluster Expansion analysis) vs. sequence-based evolutionary acceptability (via statistical analysis of homologs). Significantly, while the combinatorics of library design are even worse than individual protein design, in practice OCoM-SOCoM requires only hours even to optimize 109-member libraries (for 30 sites) within even larger library design spaces. Case study applications to green fluorescent protein and β-lactamase provide insights into how sequence-structure relationships drive differences in library composition, and demonstrate that OCoM-SOCoM libraries incorporate mutations previously experimentally found to be valuable while also providing novel and diverse mutational combinations.
Infrared problem in quantum acoustodynamics

Quantum electrodynamics (QED) provides a highly accurate description of phenomena involving the interaction of atoms with light. We argue that the quantum theory describing the interaction of cold atoms with a vibrating membrane---quantum acoustodynamics (QAD)---shares many issues and features with QED. Specifically, the adsorption of an atom on a vibrating membrane can be viewed as the counterpart to QED radiative electron capture. A calculation of the adsorption rate to lowest order in the atom-phonon coupling is finite; however, higher-order contributions suffer from an infrared problem mimicking the case of radiative capture in QED. Terms in the perturbation series for the adsorption rate diverge as a result of massless particles in the model (flexural phonons of the membrane in QAD and photons in QED). We treat this infrared problem in QAD explicitly to obtain finite results by regularizing with a low-frequency cutoff that corresponds to the inverse size of the membrane. Using a coherent-state basis for the soft-phonon final state, we then sum the dominant contributions to derive a new formula for the multiphonon adsorption rate of atoms on the membrane that gives results that are finite, nonperturbative in the atom-phonon coupling, and consistent with the Kinoshita-Lee-Nauenberg theorem. For micromembranes, we predict a reduction with increasing membrane size for the low-energy adsorption rate. We discuss the relevance of this to the adsorption of a cold gas of atomic hydrogen on suspended graphene.
Robotic Assisted Laparoscopic Augmentation Ileocystoplasty.

ABSTRACT Introduction: Augmentation ileocystoplasty is a common treatment in adults with low capacity bladders due to neurogenic bladder dysfunction. We describe here our technique for robotic assisted laparoscopic augmentation ileocystoplasty in an adult with a low capacity bladder due to neurogenic bladder dysfunction. Materials and Methods: The patient is a 35 years-old man with neurogenic bladder due to a C6 spinal cord injury in 2004. Cystometrogram shows a maximum capacity of 96cc and Pdet at maximum capacity of 97cmH2O. He manages his bladder with intermittent catheterization and experiences multiple episodes of incontinence between catheterizations. He experiences severe autonomic dysreflexia symptoms with indwelling urethral catheter. He has previously failed non operative management options of his bladder dysfunction. Our surgical technique utilizes 6 trocars, of note a 12mm assistant trocar is placed 1cm superior to the pubic symphysis, and this trocar is solely used to pass a laparoscopic stapler to facilitate the excision of the ileal segment and the enteric anastomosis. Surgical steps include: development of the space of Retzius/dropping the bladder; opening the bladder from the anterior to posterior bladder neck; excision of a segment of ileum; enteric anastomosis; detubularizing the ileal segment; suturing the ileal segment to the incised bladder edge. Results: The surgery had no intraoperative complications. Operative time was 286 minutes (4.8 hours). Estimated blood loss was 50cc. Length of hospital stay was 8 days. He did experience a postoperative complication on hospital day 3 of hematemesis, which did not require blood transfusion. Cystometrogram at 22 days post operatively showed a maximum bladder capacity of 165cc with a Pdet at maximum capacity of 10cmH2O. Conclusions: As surgeon comfort and experience with robotic assisted surgery grows, robotic surgery can successfully be applied to less frequently performed procedures. In this case we successfully performed a robotic assisted laparoscopic augmentation ileocystoplasty displaying improvement in measurable functional outcomes.
LBP features for hand-held ground penetrating radar

Ground penetrating radar (GPR) has the ability to detect buried targets with little or no metal content. Achieving superior detection performance with a hand-held GPR can be very challenging due to the quality of the data, inconsistency of target signatures, variety of target types, and effects of a human operator. In this paper, we investigate the use of a local binary patterns (LBP) feature vector for target versus non-target discrimination from hand-held GPR data. First, a prescreener algorithm is applied to the GPR data. Then, a GPR B-scan is gathered at each prescreener alarm location and separated into several spatial and depth regions. LBP processing is applied to each spatial and depth cell individually and the LBP features from each cell are group together to form a feature vector. The resulting LBP features are invariant to amplitude scaling and represent the texture in the data. Using this feature vector, a classifier is trained to perform target versus non-target discrimination at each prescreener declaration. Experimental results illustrate the ability of the LBP features to improve detection of buried targets, especially low-metal and non-metal anti-tank and anti-personnel targets.
Powering a CO2 Reduction Catalyst with Visible Light through Multiple Sub-picosecond Electron Transfers from a Quantum Dot.

Photosensitization of molecular catalysts to reduce CO2 to CO is a sustainable route to storable solar fuels. Crucial to the sensitization process is highly efficient transfer of redox equivalents from sensitizer to catalyst; in systems with molecular sensitizers, this transfer is often slow because it is gated by diffusion-limited collisions between sensitizer and catalyst. This article describes the photosensitization of a meso-tetraphenylporphyrin iron(III) chloride (FeTPP) catalyst by colloidal, heavy metal-free CuInS2/ZnS quantum dots (QDs) to reduce CO2 to CO using 450 nm light. The sensitization efficiency (turnover number per absorbed unit of photon energy) of the QD system is a factor of 18 greater than that of an analogous system with a fac-tris(2-phenylpyridine)iridium sensitizer. This high efficiency originates in ultrafast electron transfer between the QD and FeTPP, enabled by formation of QD/FeTPP complexes. Optical spectroscopy reveals that the electron-transfer processes primarily responsi...
Local recurrence in the conservatively treated breast cancer patient: a correlation with age and family history.

BACKGROUND The purpose of this study was to evaluate the relationships among young age at diagnosis, family history status, and local recurrence in breast cancer patients treated with lumpectomy and radiation therapy. METHODS Between January 1970 and December 1990, 984 early-stage breast cancer patients were treated with conservative surgery and radiation therapy at Yale-New Haven Hospital. All patient data, including demographics, staging information, treatment, and outcome variables were entered into a computerized database. The current study focused on the relationships between young age, family history, and local relapse. A group of 52 patients who experienced a local recurrence in the conservatively treated breast and 52 matched control patients who had not experienced a local recurrence were asked to participate in a study to determine whether local recurrence was associated with family history. Detailed family history interviews were conducted, and pedigrees were analyzed by a genetic counselor who was blind to the clinical history of the patients. RESULTS As of September 1997, with a median follow-up of 12.3 years for the 984 patients in the database, the overall actuarial 10-year survival is 73%, and the 10-year distant metastasis-free survival is 78%. Of the 984 patients, 112 have experienced a local relapse in the conservatively treated breast, resulting in a 10-year actuarial breast relapse rate of 15%. The 10-year survival after breast relapse is 69%. Patient age tested as a continuous variable correlated strongly with ipsilateral breast tumor relapse. Using age 40 as a cutpoint, patients aged 40 years or less had a significantly higher local relapse rate than patients older than 40 years (P < 0.001). Although the relationship between local relapse and young age was strong, no association was found between family history and local relapse in the detailed family history study. CONCLUSIONS Young age at diagnosis was a significant prognostic factor for local relapse. In a detailed family history study using a case-control design, no significant differences in family history status were found between patients who had experienced a local relapse and patients who had not.
Aspirin, Prostaglandins and Platelet Function: Pharmacology and Thrombosis Prevention

Since the early 1970’s, there has been significant progress made in de fining the mechanism of action and pharmacology of aspirin, one of the most significant anti-thrombotic agents known. Today, a wealth of studies, extending over the past three decades and ranging from molecular biology to clinical epidemiology, all point to the conclusion that aspirin exerts it’s anti-thrombotic effect via a single specific reaction with cyclooxygenase, an enzyme found in platelets (1–3). The purpose of this chapter is to elucidate mechanisms of platelet function by outlining how aspirin acts on platelets to inhibit its prothrombotic properties; this physiologic information will then be integrated with information from randomized clinical trials that address aspirin’s important role in the prevention of thromboembolic disease.
Successful Treatment of Recalcitrant Palmoplantar Pustulosis with Ixekizumab

Palmoplantar pustulosis (PPP) is a chronic dermatosis that is often viewed as difficult to treat and manage. Many treatment modalities exist for PPP, starting with topical agents and moving to syst...
Natural and Synthetic Growth Regulators and Their Use in Horticultural and Agronomic Crops

Plant growth regulators have been an important component in agricultural production even prior to the identification of plant hormones. As early as the turn of the century, fires were lit adjacent to fields in order to synchronize flowering in mango and pineapple (50). Gas powered generators were used as the source for the post-harvest heat treatment of lemons that stimulated ripening and degreening (12). The ethylene generated as a result of incomplete combustion, rather than higher temperatures, stimulated flowering and ripening in both cases, although this fact was unknown at the time. Plant growth regulators are now used on over one million hectares worldwide on a diversity of crops each year (61). Most of these applications are, however, confined to high-value horticultural crops rather than field crops, although there are several significant exceptions. Chlormequat chloride (2-chloroethyltrimethylammonium chloride) is used to reduce lodging in wheat. This application is generally limited to Europe, where under conditions of high fertility, lodging in small grains contributes significantly to yield reduction. Glyphosine (N,N,bis(phosphonomethyl)glycine) is used in sugarcane to increase the sucrose content of the cane. This compound acts by diverting carbohydrate into sucrose storage rather than fiber production.
The Commodification of Classroom Discourse

Marx (1867/1978) presents “the commodity” as the organizing principle of capitalist society. This review describes research on classroom discourse which shows that — although classroom language use seems removed from the marketplace — verbal practice in schools is often commodified. A clearer understanding of Marx’ concept can help us better understand language use in contemporary schools, and how schools fit into the social system.
An analysis of full-disk observations of facular contrast in the blue and red

Full-disk images from the Cartesian Full-Disk Telescope no. 2 (CFDT2) were used to study the center-to-limb (CLV) variation of facular contrast in two colors. The CFDT2 images, which have 2.5 arc sec pixels, were obtained during the summer months of 1993, 1994 and 1995. In order to minimize the bias in finding faint facular features in continuum images, we have used coaligned images obtained in the Ca K-line to identify faculae. Faculae were sorted into 20 annular bins of equal width. To reduce the effects of seeing, faculae were not identified closer to the limb than μ=0.2. The facular pixel contrasts were fitted to various trial functions. The contrast in the blue filter (470.6 nm) rose from 0.122% at disk center to 12.2% at μ=0.2. The contrast in the red filter (672.3 nm) rose from 0.13% at disk center to 8.16% at μ=0.2. We have also analyzed the facular contrasts multiplied by their μ-value to obtain an estimate of facular flux tube contrasts. These flux tube contrasts increased roughly linearly from μ=0.95 to 0.25. The blue flux tube contrast reached a maximum of 2.48% near μ=0.25. The red flux tube contrast reached a maximum of 1.59% at μ=0.2. These contrast values are not corrected for the filling factor. The blue curve leveled off slightly betwen μ=0.25 and 0.2 while the red curve showed no deviation from its linear trend. These results may provide some support for the hot wall model of facular flux tubes.
Comparison of Machine Learning Algorithms for Predictive Modeling of Beef Attributes Using Rapid Evaporative Ionization Mass Spectrometry (REIMS) Data.

Ambient mass spectrometry is an analytical approach that enables ionization of molecules under open-air conditions with no sample preparation and very fast sampling times. Rapid evaporative ionization mass spectrometry (REIMS) is a relatively new type of ambient mass spectrometry that has demonstrated applications in both human health and food science. Here, we present an evaluation of REIMS as a tool to generate molecular scale information as an objective measure for the assessment of beef quality attributes. Eight different machine learning algorithms were compared to generate predictive models using REIMS data to classify beef quality attributes based on the United States Department of Agriculture (USDA) quality grade, production background, breed type and muscle tenderness. The results revealed that the optimal machine learning algorithm, as assessed by predictive accuracy, was different depending on the classification problem, suggesting that a “one size fits all” approach to developing predictive models from REIMS data is not appropriate. The highest performing models for each classification achieved prediction accuracies between 81.5–99%, indicating the potential of the approach to complement current methods for classifying quality attributes in beef.
Look, Listen, and Learn More: Design Choices for Deep Audio Embeddings

A considerable challenge in applying deep learning to audio classification is the scarcity of labeled data. An increasingly popular solution is to learn deep audio embeddings from large audio collections and use them to train shallow classifiers using small labeled datasets. Look, Listen, and Learn (L3-Net) is an embedding trained through self-supervised learning of audio-visual correspondence in videos as opposed to other embeddings requiring labeled data. This framework has the potential to produce powerful out-of-the-box embeddings for downstream audio classification tasks, but has a number of unexplained design choices that may impact the embeddings’ behavior. In this paper we investigate how L3-Net design choices impact the performance of downstream audio classifiers trained with these embeddings. We show that audio-informed choices of input representation are important, and that using sufficient data for training the embedding is key. Surprisingly, we find that matching the content for training the embedding to the downstream task is not beneficial. Finally, we show that our best variant of the L3-Net embedding outperforms both the VGGish and SoundNet embeddings, while having fewer parameters and being trained on less data. Our implementation of the L3-Net embedding model as well as pre-trained models are made freely available online.
Diet Diversity and the Declining Importance of Staple Grains

Changing diets poses critical demand-side challenges for food systems. Increase in income, urban growth, processes of globalization and demographic changes have led to a reduction in the relative importance of cereals, while consumption of animal-based protein, processed and purchased foods have increased. We argue that such dietary transitions should move food security debates away from access to calories towards access and affordability of diverse and quality diets. Diet diversification should become a focus for food and agricultural policy. At the same time, food and nutrition policy should also concern itself with the rising instances of obesity and other non-communicable diseases, resulting from changing diets. Finally, given that 65.5 million Indians live in urban slums, urban food security concerns should also be a part of the broader policy discussions.
The gut microbiota perspective for interventions in MS.

Abstract The heritable genetic variation that explains phenotypic differences in a population fluctuates for different autoimmune disorders. Particularly in multiple sclerosis (MS) etiology, modest genetic and major environmental effects emerge. Increasingly recognized as a major environmentally shaped contributor to disease and treatment outcomes are gut microbiota. As discussed here, the observed impact of gut microbiome on MS pathophysiology, involves both quantitative and functional changes in composition, metabolism, gut permeability, homeostasis and modulation of the immune system. Although the first supplementary therapeutic interventions have been approached in general autoimmune disorders they are relatively cruder and a translation of knowledge from other pathologies is valuable but still required. Consequently initial therapeutic interventions with microbiota for autoimmune disorders could be correspondingly improved.
Rightful Machines and Dilemmas

Tn this paper I set out a new Kantian approach to resolving conflicts and dilemmas of obligation for semi-autonomous machine agents such as self-driving cars. First, I argue that efforts to build explicitly moral machine agents should focus on what Kant refers to as duties of right, or justice, rather than on duties of virtue, or ethics. In a society where everyone is morally equal, no one individual or group has the normative authority to unilaterally decide how moral conflicts should be resolved for everyone. Only public institutions to which everyone could consent have the authority to define, enforce, and adjudicate our rights and obligations with respect to one other. Then, I show how the shift from ethics to a standard of justice resolves the conflict of obligations in what is known as the "trolley problem" for rightful machine agents. Finally, I consider how a deontic logic suitable for governing explicitly rightful machines might meet the normative requirements of justice.
Block Adjustment of Bundles

The characteristic features of programs for the block adjustment of bundles are described in the context of their historical development, and the approach used in the program developed by the autho...
Wolff-Parkinson-White: Who’s Afraid of the Big Bad Wolff?

Wolff-Parkinson-White (WPW) is a described accessory pathway between the atria and the ventricles. This pathway allows for conduction of impulses between the atria and ventricle to occur in addition to the normal conduction through the atrioventricular (AV) node. The classic WPW electrocardiogram (EKG/ECG) demonstrates a shortened PR interval and a delta wave. Up to 35% of cases may not show the classic delta wave and these are called concealed accessory pathways. Most patients with WPW are asymptomatic while some develop supraventricular tachycardia or atrial fibrillation. These patients can develop sudden cardiac death. Treatment during an arrhythmia can include adenosine, procainamide, or electrical cardioversion, depending on the patient’s symptoms and the specific pattern of arrhythmia.
Carbonating the household diet: a Pakistani tale.

Objective Carbonated beverage consumption is associated with various adverse health conditions such as obesity, type 2 diabetes and CVD. Pakistan has a high burden of these health conditions. At the same time, the carbonated beverage industry is rapidly growing in Pakistan. In this context, we analyse the trends and socioeconomic factors associated with carbonated beverage consumption in Pakistan. Design We use six waves of the cross-sectional household surveys from 2005-2006 to 2015-2016 to analyse carbonated beverage consumption. We examine the trends in carbonated beverage consumption-prevalence for different economic groups categorised by per capita household consumption quintiles. We estimate the expenditure elasticity of carbonated beverages for these groups using a two-stage budgeting system framework. We also construct concentration curves of carbonated beverage expenditure share to analyse the burden of expenditure across households of different economic status. Setting Pakistan. Participants Nationally representative sample of households in respective survey waves. Results We find that the wealthier the household, the higher is the prevalence of carbonated beverage consumption, and the prevalence has increased for all household groups over time. From the expenditure elasticity analysis, we observe that carbonated beverages are becoming an essential part of food consumption particularly for wealthier households. And, lastly, poorer households are bearing a larger share of carbonated beverage expenditure in 2014-2016 than that in 2006-2008. Conclusion Carbonated beverages are becoming an increasingly essential part of household food consumption in Pakistan. Concerns about added sugar intake can prompt consideration of public health approaches to reduce dietary causes of the disease burden in Pakistan.
Abstract B36: Therapy-induced YAP hyperactivation is a mechanism driving the evolution of residual disease and resistance to targeted cancer therapy

Initial profound responses of precision medicines against cancer are limited in duration in part due to residual disease states that are therapy refractory and serve as a prelude to acquired drug resistance and tumor relapse. A prominent clinical example is in the collection of BRAF mutant cancers, including lung cancer and melanoma, which often respond initially, but incompletely and temporarily, to targeted RAF and MEK inhibition. The Hippo pathway transcriptional coactivator, Yes-associated protein (YAP), is a chief mediator of RAF and MEK inhibitor response in BRAF mutant cancers. However, the underlying mechanism for YAP-driven resistance is not fully understood. Here, we modeled the kinetics of patient-derived and isogenic BRAF mutant (V600E) cell lines in response to BRAF inhibitor and MEK inhibitor treatment. Our analysis indicated that in response to drug treatment the cells evolve through a “persister,” residual disease state that is distinct from therapy-naive cells or cells with acquired resistance. We observed that drug treatment induced early nuclear translocalization of YAP and this response peaked at the “persister” cell state before returning towards baseline upon acquired resistance. Additionally, our functional analysis of the proteomic and transcriptional landscape of the “persister” cells demonstrated drug-dependent reversible and concomitant activation of AKT, YAP target gene expression, and an epithelial mesenchymal transition (EMT). These programs underlay acquired vulnerabilities, as pharmacologic perturbation of AKT and genetic ablation of YAP was lethal specifically in the “persister” cells. Remarkably, AKT was required and sufficient for drug-induced nuclear localization of YAP, indicating that therapy-mediated hyperactivation of AKT is required for YAP induction and YAP-mediated residual disease. Current studies are focused on characterizing the molecular events causing AKT-mediated hyperactivation of YAP in response to MAPK pathway inhibition. Overall, this work aims to deconvolute a novel molecular mechanism of YAP activation in cancer cells and establish the functional implications of YAP signaling on “persister” cell biology and the evolution of targeted cancer therapy resistance. Citation Format: Aubhishek Zaman, Trever Bivona. Therapy-induced YAP hyperactivation is a mechanism driving the evolution of residual disease and resistance to targeted cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B36.
Financial Crowding Out

Using a novel dataset of accounting and market information that spans most publicly traded firms over the last century, we show that government deficit financing crowds out nonfinancial corporate debt financing and investment. Specifically, an increase in the supply of treasury debt is associated with a significant reduction in corporate leverage, debt issuances, and investment, but no significant change in corporate equity issuances. Further, this crowding out effect is present across industries and is more pronounced for larger, less risky firms whose debt is a closer substitute for treasuries. The channel through which this effect appears to operate is financial intermediaries, whose balance sheets reveal a substitution between lending to the federal government and lending to the corporate sector.
ARF4-mediated Retrograde Trafficking Drives Chemoresistance in Glioblastoma

Glioblastoma (GBM) is the most common type of adult malignant brain tumor, with a median survival of only 21 months. This is partly due to the high rate of resistance to conventional therapy, including temozolomide (TMZ), leading to recurrence rates close to 100%. It still remains unknown what drives the development of this resistance. To identify the unknown genes driving the development of this resistance, we performed a genome-wide CRISPR knockout screen comparing a DMSO-treated population with a TMZ-treated population over 14 days. We identified 4 previously unstudied genes – ARF4, PLAA, SPTLC1, and PIGK – that showed significant elevations in expression in recurrent tumors in patient datasets, along with significant survival benefits corresponding to low gene expression. Further investigation of ARF4, known to be involved in retrograde trafficking, allowed us to identify a mechanism of resistance that is mediated by increased retrograde transport of EGFR into the nucleus. Ultimately, our CRISPR-Cas9 screen has identified a promising therapeutic target, ARF4, which may drive GBM9s high resistance to chemotherapy.
The Problem of (un)Belonging: Memory, Land Conflict, and Environmental Degradation in Mt. Elgon, Kenya

In the face of the present harsh realities of global climate change, many state-mediated initiatives to protect the environment have supposedly aimed at safeguarding the livelihoods of communities living in critical ecosystems. Paradoxically, however, such ventures have often exacerbated environmental degradation by causing conflict with the communities that claim indigeneity on lands targeted for conservation. In many places in Africa, protracted land alienation since colonialism, a lack of clear land ownership structures, corrupt land deals, and claims of autochthony have bred bloody ethnic battles and contributed to further environmental destruction. This article explores the intersection between autochthony claims, ideas of (un)belonging, ethnopolitical violence, and environmental degradation from the vantage point of memory. I argue that the land-related conflicts in Mt. Elgon, Kenya, are not just a problem of flawed environmental conservation programs but also a failure to address people’s memories of “home.”
Narrative Braids: Performing Racial Literacy (Interviewed by Gene Grant)

The performance that is the basis for this joint publication was performed at the Harriet Tubman Theatre at the National Underground Railroad Justice Center in Cincinnati, Ohio. The two of us, Christine Zuni Cruz, a Pueblo woman from the Rio Grande Pueblos of Oke Owingeh and lsleta in New Mexico, and Margaret Montoya, a mestiza/Chicana from northern New Mexico, using both our personal voices and our professional voices as legal scholars, enacted the theatrical performance, a conversation between two women of color from different communities with different identities.This performance experiments with both method and content. The method is a set of stories told at times to the audience and at times to each other; the stories use family and personal photographs, contemporary Pueblo music and Mexican mariachis,judicial opinions, cultural myths, and family stories. The performance is a conversation about ancestry, motherhood, personal identity, and race, as well as inter- and intra-racial conflict, co-existence and collaborations. Our stories are about memory colliding with history and the professional squeezing the personal. The law and different forms of in/justice are one strand in this narrative braid.
Children’s Competence to Consent

The question of children’s competence to give or refuse consent1 is of largely recent origin (see Chapter 9). Until the mid-sixties it was not clear that children were “persons” within the meaning of the Fourteenth Amendment, which makes the Bill of Rights applicable to the states. Although there were several early-twentieth-century “children’s rights” cases decided by the United States Supreme Court,2 each of these could be construed as a vindication of parents’ liberty interest in childrearing as they saw fit (Melton, 1982). In none of the early cases was there a clear indication of minors’ possessing constitutionally protected fundamental liberties independent of their parents. Children were perceived as properly dependent upon their parents who possessed a “right of control” over them.3 Even though parents’ rights in this regard are limited by the fact that they are not “free … to make martyrs of their children,’4 this restriction emanated from the state’s interest in the socialization of children.5 Indeed, the Supreme Court had held that it “would hardly seem open to question” that the state could impinge on basic freedoms of minors (e.g., freedom of religion) in ways that would be clearly unconstitutional if the same restrictions were placed on adults.6 Given clear indications that both parents and the state as parens patriae 7 could exercise control over minors (see Chapter 9 for additional discussion), the question of the limits of children’s actual competence to make personal decisions was moot.
Mutants of Escherichia coli Variably Resistant to Bacteriophage T1

Carta, Guy R. (Rutgers, The State University, New Brunswick, N.J.), and Vernon Bryson. Mutants of Escherichia coli variably resistant to bacteriophage T1. J. Bacteriol. 92: 1055–1061. 1966.—Mutants resistant to bacteriophage T1 were isolated from ultraviolet (UV)-irradiated cultures of Escherichia coli B/r, a UV-resistant variant. Bacterial populations derived from some of these mutants were partially but not completely resistant to the bacteriophage. Such mutants, designated variably resistant (B/r/1v), could not be obtained from E. coli B. Phage-free mutant populations taken from different stages in growth consisted of significantly different proportions of T1-resistant and T1-sensitive cells. The growth stage-dependent range of variation exceeded 1,000-fold. In broth cultures, the highest proportion of resistant cells consistently appeared at mid-log phase, and the highest proportion of sensitive cells at lag and stationary phases. Comparable evidence for environmentally dependent changes in host-cell phenotype was obtained by efficiency of plating and cloning efficiency analysis tests. Micromanipulation showed that, in clones growing in the presence of phage T1, sensitive bacteria appeared with high frequency and underwent lysis. Images
Termination Proofs and Complexity Certification

We show that simple structural conditions on proofs of convergence of equational programs, in the intrinsic-theories verification framework of [16], correspond to resource bounds on program execution. These conditions may be construed as reflecting finitistic-predicative reasoning. The results provide a user-transparent method for certifying the computational complexity of functional programs. In particular, we define natural notions of data-positive formulas and of data-predicative derivations, and show that restricting induction to data-positive formulas captures precisely the primitive recursive functions, data-predicative derivations characterize the Kalmar-elementary functions, and the combination of both yields the poly-time functions.
High frequency dielectrophoretic response of microalgae over time

The high frequency dielectrophoresis (>20 MHz) response of microalgae cells with different lipid content was monitored over time. Chlamydomonas reinhardtii was cultured in regular medium and under nitrogen-depleted conditions in order to produce populations of cells with low and high lipid content, respectively. The electrical conductivity (EC) of the culture media was also monitored over the same time. The upper crossover frequency (UCOF) decreased for high-lipid cells over time. The single-shell model predicts that the upper crossover frequency is dictated primarily by the dielectric properties of the cytoplasm. The high frequency DEP response of the high-lipid cells’ cytoplasm was changed by lipid accumulation. DEP response of the low-lipid cells also varied with the conductivity of the culture media due to nutrient consumption. Relative lipid content was estimated with BODIPY 505/515 dye by calculating the area-weighted intensity average of fluorescent images. Finally, microalgae cells were successfully separated based on lipid content at 41 MHz and DEP media conductivity 106 ± 1 µS/cm.