cssi/SciSciGPT-SciSciNet huggingface dataset:
Androgenesis and Homozygous Gynogenesis in Muskellunge (Esox masquinongy): Evaluation Using Flow Cytometry

The purpose of this work was to study the effects of ultraviolet (UV) irradiation on denucleation of eggs and investigate the heat-shock conditions for diploidization for induction of androgenesis in muskellunge, Esox masquinongy. Several egg incubation media, including saline, Ringer's solution, and Ringer's solution supplemented with bovine serum albumin (BSA), were found suitable to maintain the egg fertility as high as in muskellunge ovarian fluid. The optimal doses of UV radiation were 660-1320 J/m2, at which 100% haploid larvae were produced at a hatching rate of 22.5 +/- 2.8%. UV irradiation at low doses (165-330 J/m2) generated abnormal larvae, which were morphologically identical to haploids. Using a flow cytometry method, it was found that cellular DNA content of these larvae was close to that of diploids but significantly lower in value and had a wider distribution (expressed as coefficient of variation) than that of control fish. This suggested that a low dose of UV irradiation might cause gene mutations, alteration of chromosomal conformation and fragmentation, but did not prevent maternal DNA from participating in mitotic division. Interference of maternal DNA residues could be another reason for the poor viability of androgenetic fish. A high dose of UV radiation (1980 J/m2) caused development of severely deformed embryos, indicating that UV radiation also damaged molecules in the eggs other than the denucleation. Our results suggest that classic color and allozyme markers might not be sufficient to prove a complete androgenesis. In order to optimize time and duration of shock for induced diploidization, we investigated the heat-shock conditions for inhibiting the first mitotic cleavage through induction of homozygous gynogenesis. We found that heat-shock treatment at 31 degrees C for 9 min starting at 1.4 tau 0 (a dimensionless factor describing progress in embryo development) after fertilization produced the highest percentage of diploids at hatching.
Membranous nephropathy transplanted in the donor kidney: observations of resolving glomerulopathy in serial allograft biopsies

We report a case of idiopathic, PLA2R-negative membranous nephropathy (MN) transplanted via a deceased donor kidney. Changes in glomerular immune deposits were followed in serial biopsies. The allograft recipient had end-stage disease without significant proteinuria from ischemic nephropathy due to chronic heart failure, hypertension, atherosclerosis and presumed diabetic nephropathy. Combined cardiac and renal transplants were performed. Maintenance immunosuppression consisted of prednisone, a calcineurin inhibitor and mycophenolate mofetil. MN was identified in the pre-implantation biopsy of the donor kidney. The recipient never developed significant proteinuria and there was no identifiable impact on graft function. Serial biopsies performed at Days 0, 18, 150, 234 and 812 revealed mild effacement of podocyte foot processes, progressive change from Ehrenreich-Churg Stage III-IV lesions of MN to segmental resolution by electron microscopy, and progressive decrease of IgG staining by immunofluorescence. The findings provide a novel observation of the protracted process of glomerular immune deposit resolution in healing MN transplanted in a neutral host environment.
The double femoral sound.

Abstract A double femoral sound is described in patients with congestive heart failure of varied etiology. The factor common to all patients was a powerful atrial contraction secondary to increased right ventricular diastolic pressure or increased resistance to right ventricular filling. The first sound is produced by atrial systole transmitted by the venae cavae to the femoral veins; the second sound by left ventricular systole transmitted by the aorta to the femoral arteries.
Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

Background The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?
Epitope-Specific CD8+ T Lymphocytes Cross-Recognize Mutant Simian Immunodeficiency Virus (SIV) Sequences but Fail To Contain Very Early Evolution and Eventual Fixation of Epitope Escape Mutations during SIV Infection

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) evade containment by CD8(+) T lymphocytes through focused epitope mutations. However, because of limitations in the numbers of viral sequences that can be sampled, traditional sequencing technologies have not provided a true representation of the plasticity of these viruses or the intensity of CD8(+) T lymphocyte-mediated selection pressure. Moreover, the strategy by which CD8(+) T lymphocytes contain evolving viral quasispecies has not been characterized fully. In the present study we have employed ultradeep 454 pyrosequencing of virus and simultaneous staining of CD8(+) T lymphocytes with multiple tetramers in the SIV/rhesus monkey model to explore the coevolution of virus and the cellular immune response during primary infection. We demonstrated that cytotoxic T lymphocyte (CTL)-mediated selection pressure on the infecting virus was manifested by epitope mutations as early as 21 days following infection. We also showed that CD8(+) T lymphocytes cross-recognized wild-type and mutant epitopes and that these cross-reactive cell populations were present at a time when mutant forms of virus were present at frequencies of as low as 1 in 22,000 sequenced clones. Surprisingly, these cross-reactive cells became enriched in the epitope-specific CD8(+) T lymphocyte population as viruses with mutant epitope sequences largely replaced those with epitope sequences of the transmitted virus. These studies demonstrate that mutant epitope-specific CD8(+) T lymphocytes that are present at a time when viral mutant epitope sequences are detected at extremely low frequencies fail to contain the later accumulation and fixation of the mutant epitope sequences in the viral quasispecies.
A Non-Equilibrium Thermodynamical Analysis of the Origin of Life

This presentation will attempt to bring together the basic concepts of non-equilibrium thermodynamics and biochemical energetics, in order to sharply define the problem of the origin of life. Having defined the problem, an assessment of its current state of solution will be presented. In addition, a number of new experiments will be suggested.
Freedom of Information and Privacy

Again, we have a topic that could fill an entire volume by itself. In keeping with the spirit of this book, however, this chapter will contain brief overviews of areas related to information access and privacy, and the interested reader may consult the references for more detail. As we will see later in this chapter, the area of privacy contains rules affecting who may obtain data gathered by a researcher and rules for how scientists may obtain data gathered by the government.
Abstract 1943: miR-148a overexpression reduces TRAIL resistance and tumorigenesis in NSCLC.

Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer throughout the world. Although some advances have been made in lung cancer therapy, patient survival is still poor. Tumor-necrosis factor related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL. MicroRNAs (miRNAs) are small non-coding RNAs of ∼24 nt that can block mRNA translation and/or negatively regulate its stability. miRNAs are often aberrantly expressed in cancer and their function is linked to the regulation of oncogenes and/or tumor suppressor genes involved in cell signaling pathways. Several miRNAs have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins. In order to identify the miRNAs involved in TRAIL resistance in NSCLC, we evaluated the differential expression of miRNAs in H460 sensitive cells compared with H460R cells that have acquired TRAIL-resistance. MiR-148a was the most downregulated miR in the acquired resistant cells compared to the sensitive cells. Treatment of NSCLC cells with TRAIL after miR-148a overexpression decreased cell viability and increased apoptosis. Furthermore, miR-148a overexpression induced downregulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1) by targeting their 3’ untranslated regions as analysed by Western blot and luciferase reporter assay. Previous studies have shown that MMP15 acts as an anti-apoptotic factor involved in TRAIL resistance in cancer cells. Both, MMP15 and ROCK1 have been reported to be activators of tumor invasion and migration. Our preliminary functional studies using small interference RNA (siRNA) knockdowns of these genes in NSCLC cells support these data. A better understanding of the tumor-supressive role of miR-148a could be the key to developing an effective prognostic and therapeutic tool for treating NSCLC. Citation Format: Pooja Joshi, Michela Garofalo, Carlo M. Croce. miR-148a overexpression reduces TRAIL resistance and tumorigenesis in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1943. doi:10.1158/1538-7445.AM2013-1943
Trajectory Planning for Sensing Effectiveness with High Angle-of-Attack Flight Capability

High angle-of-attack flight at which the aircraft operates beyond aerodynamic stall is utilized scarcely in unmanned aircraft. There are likely great advantages to this flight capability, particularly in close-proximity sensing missions in cluttered environments. However, there are also drawbacks to high angle-of-attack flight such as reduced flight speed and uncommanded wing rock. Despite these disadvantages, it is shown that including high angle-of-attack flight capability can improve several phases of a close-proximity sensing mission. The reduced turning radius afforded by the reduced speed of high angle-of-attack flight permits more direct trajectories to be planned through cluttered environments. The reduction in path length outweighs the required reduction in flight speed to result in an improvement to total path duration. Additionally, the sensing effectiveness is shown to be improved in many situations by utilizing the extreme attitude and reduced speed of high angle-of-attack flight.
A child with a painful swollen ear

A previously healthy 2-year-old boy presented to the emergency department with a 1-day history of pain, swelling and redness of his left auricle, which spared his earlobe (figure 1). There was no reported preceding trauma, fever or otorrhea, and no history of otitis media or change in hearing. On examination, there was erythema, oedema and warmth with tenderness on moving the auricle but no fluctuance …
Character of Hot Extrusion Gasification Briquette and Its Gasification Result

the fundamental principle and typical process of hot extrusion process technology were introduced briefly. Character and quality of hot extrusion gasification briquette are analyzed. It is shown that it can be used as raw material in fuel gas gasifier instead of lump coal through industrial gasification test.
A Fatal Cause of Sexual inadequacy in Men: Adrenoleukodystrophy

AbstractDiminished libido, impotence and infertility have been detected in 5 of 6 men with adreno leukodystrophy, a universally fatal disease. The importance of the clinical recognition of these patients and their separation from others with relatively innocuous causes of testicular dysfunction are discussed.
Introduction: Technology and Ethics

Technology shapes every aspect of human experience. It is the primary driver of social and ecological change. It is a source of power, vulnerability, and inequality. It influences our perspectives and mediates our relationships. Given this, it is surprising that we spend so little time studying, analyzing, and evaluating new technologies. Occasionally, an issue grabs public attention — for example, the use of human embryonic stem cells in medical research or privacy in social networking. However, these are the exceptions. For the most part, we seem to suffer from technological somnambulism (to borrow a term from Langdon Winner [Ch. 4]) — we incorporate new technologies into our lives with little critical reflection on what the impacts will be.
Positive Medication Changes Resulting from Comprehensive and Noncomprehensive Medication Reviews in a Medicare Part D Population

BACKGROUND: Health care organizations face the challenge of reducing costs while improving health outcomes. Currently, more than 39 million seniors are enrolled in a Medicare Part D prescription benefit plan, many of whom also qualify for medication therapy management (MTM) services. MTM programs provide valuable services designed to prevent or resolve medication-related problems (MRPs). Two core components of all MTM programs include comprehensive medication reviews (CMRs) with followup interventions and focused non-CMR interventions. Currently, there is limited research comparing the rate of MRPs resolved by CMR and non-CMR interventions. OBJECTIVE: To determine whether CMRs versus non-CMR interventions resulted in more pharmacist-initiated intervention recommendations and positive medication changes. METHODS: This retrospective, cross-sectional quality improvement project evaluated outcomes for individuals who received interventions following a CMR compared with those who received non-CMR interventions...
21-year-old with exertional dyspnoea

A 21-year-old, previously healthy, woman presents to the emergency department with 2 months of dyspnoea on exertion. She is short of breath walking up a flight of stairs. She has a history of intravenous drug use and takes no medications. Family history is negative for cardiac disease. Heart rate is 110 bpm and blood pressure is 125/55 mmHg. She has an elevated jugular venous pressure, bibasilar rales, a soft S1 and a systolic in addition to a diastolic murmur. Shortly after initial presentation in the emergency department, she is intubated for respiratory failure. A transthoracic echocardiogram is obtained (figure 1). Figure 1 ( A ) M-mode recording of …
Predation on reproducing wolf spiders: access to information has differential effects on male and female survival

Predation has widespread influences on animal behaviour, and reproductive activities can be particularly dangerous. Males and females differ in their reactions to sensory stimuli from predators and potential mates, which affects the risk experienced by each sex. Thus, the information available can cause differential survival and have profound implications for mating opportunities and population structure. The wolf spider, Pardosa milvina, detects and responds in a risk-sensitive manner to chemotactile information from a larger predator, the wolf spider Tigrosa helluo. Male P. milvina use similar chemotactile cues to find females whereas female P. milvina focus on the visual, and perhaps vibratory, aspects of the male display. Our aim was to document the risk posed by T. helluo predators on P. milvina during reproduction and to determine whether augmenting chemotactile information would affect that outcome. In the laboratory, we explored the effects of adding predator and/or female cues on the predatory success of T. helluo on P. milvina males or observing females. Additional cues from prospective mates or from predators enhanced male survival. The addition of female cues increased predation on females whereas predator cues augmented female survival. In field enclosures, we documented the impact of T. helluo, with and without additional predator cues, on the sex ratio of survivors and the reproductive success of females. Additional predator cues shifted the sex ratio towards males, however, 90% of the remaining females in that treatment produced eggsacs whereas less than 60% reproduced in female-biased populations. Thus, augmenting the available predator information shifted the risk from males to females, presumably due to differences in their sensory priorities. By altering the availability of potential mates, this shift appears to have influenced the intensity of sexual selection for this spider.
Abstract LB-098: Sequential azacitidine and histone deacetylase inhibition induces a potent antitumor response in Kras G12D mouse model of NSCLC

Combination epigenetic treatment as a therapeutic approach holds much promise. However, to unlock the true potential of these combinatorial paradigms, further optimization is required. We have elucidated in our current study, a treatment schedule combining Azacitidine with Histone Deacetylase Inhibition (HDACi) which considers both schedule and isoform specificity. We have deployed a sequential schedule with HDACi administered post Azacitidine in a chronic low dose manner. This schedule takes advantage of two key parameters altered by Azacitidine: dsRNA induced immune signature and MYC depletion. In our system, HDACis amplify an existing immune signature and the MYC depleted environment acts as a potent sensitizer. HDACi induced augmentation of immune gene transcription seems driven predominantly through the inhibition of HDAC1/2 and HDAC6 isoforms, with broad spectrum HDACi inhibitors demonstrating the greatest potency. While the combination treatment induced perturbation of proliferation is driven by inhibition of HDAC1/2/3 isoforms. Applying this concept to a genetically engineered mouse model of NSCLC we observe a potent anti-tumor response as evidenced by a reduction in tumor burden, progression and proliferation. These phenotypic parameters are correlated with modification of both immune and proliferative gene signatures as well as alteration of key immune populations in the tumor microenvironment. We propose that this combinatorial alteration of both immune and proliferative parameters holds the promise to be a more robust treatment for NSCLC. Note: This abstract was not presented at the meeting. Citation Format: Michael Topper, Michelle Vaz, Katherine Chiappinelli, Christina DeStefano Shields, Alyssa Wenzel, Cynthia Zahnow, Pam Strissel, Reiner Strick, Stephen Baylin. Sequential azacitidine and histone deacetylase inhibition induces a potent antitumor response in Kras G12D mouse model of NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-098. doi:10.1158/1538-7445.AM2017-LB-098
Edge Detection of Cryptic Lamellipodia Assisted by Deep Learning

Cell protrusion plays important roles in cell migration by pushing plasma membrane forward. Cryptic lamellipodia induce the protrusion of submarginal cells in collective cell migration where cells are attached and move together. Although computational image analysis of cell protrusion has been done extensively, the study on protrusion activities of cryptic lamellipodia is limited due to difficulties in image segmentation. This study seeks to aid in the computational analysis of submarginal cell protrusion in collective cell migration by using deep learning to detect the cryptic lamellipodial edges from fluorescence time-lapse movies. Due to the noisy features within overlapping cells, the conventional image analysis algorithms such as Canny edge detector and intensity thresholding are limited. By combining Canny edge detector, Convolutional Neural Networks (CNNs), and local intensity thresholding, we were able to detect cryptic lamellipodial edges of submarginal cells with high accuracy from the fluorescence time-lapse movies of PtK1 cells stained with a plasma membrane marker. We used relatively small effort to prepare the training set to train the CNN to detect the cryptical lamellipodial edges in fluorescence time-lapse movies. This work demonstrates that deep learning can be combined with the conventional image analysis algorithms to facilitate the computational analysis of highly complex time-lapse movies of collective cell migration.
Intimate economies of immigration detention: critical perspectives

In the forward to Intimate Economies of Immigration Detention, feminist geographer Alison Mountz warns the reader to ‘prepare yourself to experience sadness and anger, revelation and frustration’ (...
Light-Activatable Theranostic Agents for Image-Monitored Controlled Drug Delivery

A novel drug delivery vehicle using nanodroplets activated by light irradiation for drug release in a controlled manner has been developed. The drug encapsulated in the nanodroplets was released upon phase transition from a liquid droplet to microbubbles (vaporization) by plasmonic photothermal heat from gold nanorods adsorbed on the surface of the nanodroplets. The nanodroplets were stable against aggregation and dissolution at 4 °C over 3 months to date. The phase transition was quantitatively analyzed by ultrasound imaging to examine the amount of drug release noninvasively. In vitro studies showed that cell death occurred only when light irradiation was performed on the drug-encapsulated nanodroplets. Ex vivo studies demonstrated a potential application of the nanodroplets for treating posterior eye diseases. Thus, it has been demonstrated that our gold-nanorod-coated light-activatable nanodroplets can be a candidate for a controlled release and a dosage-monitored drug delivery system.
Music in the Academy: Process, Product, and the Cultivation of Humanity

In the academy, as in contemporary society, music’s role extends beyond recreation and entertainment. The act of creating, whether by composer or performer, moves inner knowledge outward and proffers a communicative transaction which can be the start of community. While tensions exist between educational models of liberal and professional study, music provides a potential model for integration, balancing action and reflection, the abstract and the concrete. Drawing on Nussbaum’s vision of liberal learning in the post-modern age (Cultivating Humanity, 1997), music is considered as a distinctive expressive form capable of mediation between the spiritual and the material; between the cultivated and the vernacular; and between the self and the other.
“See the Revolution of the Times”: Ivo van Hove’s Materialist Shakespeare Cycles

ABSTRACTThis review essay examines Flemish theatre director Ivo van Hove’s history cycles, Roman Tragedies (Coriolanus, Julius Caesar and Antony and Cleopatra) and Kings of War (Henry V, Henry VI Parts 1, 2 and 3 and Richard III), as examples of ways contemporary directors can utilise Shakespeare to present a cultural materialist vision of today’s late capitalist society. The essay provides an overview of van Hove’s theatrical work, a brief trajectory of Shakespeare history cycles, and argues that van Hove’s performative conflation of theatrical audiences with the broader public masses highlights the ways in which apparent public participation in the state is often illusory. Through productions such as these, van Hove reveals himself as an heir to Bertolt Brecht and Jan Kott, who read Shakespeare’s history plays as meditations on the cyclical nature of authoritarian power structures.
A Fish Out of Water? Armenia(ns) and the Mediterranean

La Porta challenges ways in which Armenia and Armenians have been either included or excluded from the Mediterranean discourse. He explores how the Armenian experience can expand the conversation of Mediterranean Studies and argues that essentialized notions of Armenian identity, pre-supposed both by Armenologists and scholars of the Mediterranean, should be deconstructed in order to engage in a discussion of Armenians “of” the Mediterranean, rather than just “in” it. La Porta further suggests the contested notion of Armenia as a Mediterranean analogue, and posits that Mediterranean Studies can provide Armenian specialists with methodological tools for conceptualizing the intricacies of Armenian history.
Rapid-Eye-Movement Sleep Behavior Disorder

Foreword -- Part I. Introduction -- RBD: Historical Perspective -- The Human Dimension of RBD -- The Foundation of the International RBD Study Group -- Part II. RBD: Clinical Aspects -- Clinical Spectrum -- Idiopathic (cryptogenic) RBD -- Idiopathic RBD -- Secondary RBD -- RBD Associated With Parkinson's Disease and Multiple System Atrophy -- RBD and Dementia with Lewy Bodies -- RBD and Non-Synuclein Neurodegenerative Disorders: A Critical Appraisal -- RBD Associated With CNS Autoimmune Diseases and Paraneoplastic Disorders -- Lesional RBD -- RBD, Antidepressant Medications and Psychiatric Disorders -- RBD in Narcolepsy-Cataplexy -- Acute RBD -- Physiological Substrates of RBD Subtypes -- RBD: Age and Gender Implications -- RBD in Childhood and Adolescence -- RBD in Adults Under 50 Years Old -- RBD: Gender implications -- Dreams and RBD -- RBD: A Window Into the Dreaming Process -- Diagnosis -- Diagnosis of RBD -- Instruments for Screening, Diagnosis and Assessment of RBD Severity and Monitoring Treatment Outcome -- PSG findings in RBD -- Video Analysis of Behaviors and Movements -- Clinical Vignettes -- Illustrative, Unusual, and Challenging RBD cases -- Therapy -- Management of a Patient with RBD -- Melatonin therapy of RBD -- Clonazepam and Other Therapies of RBD -- Differential Diagnosis and Related Disorders -- RBD Mimics -- Parasomnia Overlap Disorder: RBD and NREM Parasomnias -- Status Dissociatus and Its Relation to RBD -- Clinical Research in RBD -- Imaging -- Activation of the Visual and Motor Systems During REM sleep and Implications for RBD -- Brain Imaging of RBD -- Neurophysiology -- The Electromyographic Diagnosis of REM Sleep Without Atonia and RBD -- Autonomic Function -- RBD and the Autonomic Nervous System -- Cardiac Scintigraphy in RBD -- Neuropsychological Aspects -- Cognition in RBD -- Impulse Control Disorders and Other Neuropsychiatric Features in RBD -- Contemporary Clinical Issues -- Biomarkers of Neurodegenerative Disease in Idiopathic RBD -- RBD, Gastric Peptides, and Gastric Motility -- Gait and Postural Disorders in RBD -- H1N1 Influenza Infection and H1N1 Vaccination -- Vaccination: Implications for Narcolepsy-RBD -- Part III. RBD: Basic Science -- REM Sleep Physiology -- REM Sleep Physiology and Implications for RBD -- Pathology -- Neuropathology of RBD -- Genetics -- Genetics of RBD -- Animal Models of RBD -- Animal Models of RBD -- Breakdown in REM Sleep Circuitry Underlies RBD -- Part IV. Neuroprotection and Disease Modification -- Clinical Trial Design in RBD – Challenges and Opportunities -- Part V. RBD: Future Directions in Clinical Care and Research. .
Patient Safety: Building a Triangle of Importance

years, and the expectations of healthcare providers, management, and administrators, not to mention patients, keep growing. While we appreciate the increasing levels of consumer consciousness, the numbers of medical malpractice-based litigations have reached staggering heights, with sometimes unreasonable, jury awards. Perhaps for this reason, and also because of the leaps made in the technology of medicine and care, the cost of healthcare has sky rocketed. But this has marginalized a good segment of the population from even seeking the basic levels of standard and quality care. One might wonder why we should even bother to address this problem when the big governments are themselves unable to handle it. Unless this problem is addressed in every forum, and unless everyone in the healthcare industry, most notably engineers and technologists, also becomes involved in bringing healthy solutions, it will continue to elude us. Looking at this scenario, the three areas that one can immediately attend to include the safety of patients in healthcare systems, the cost control and affordability of medical care, and conformity to bioethical standards. This triangle of importance is certainly a demanding imposition on the healthcare facilities and the care givers. Obviously it is a lifelong, inter-generational, multidisciplinary team effort, and the engineers and technologists have a lot to offer in this game. For instance, care givers’ errors in judgment or medications, inappropriate practices, lack of effective communication with patients and their relatives, and failure to seek expert opinions will continue to generate litigation and increases in healthcare costs, and superficially it may appear that engineering and technology staff can do so little to help in these areas. But in the lines of the old adage, “an ounce of prevention is worth a pound of cure,” engineers and technologists have enormous responsibilities in terms of appropriate design, development, and 45 Patient Safety: Building a Triangle of Importance
Abstract 1764: Neurovascular-targeting antibodies discovered using yeast biopanning enhance drug delivery and improve survival for glioblastoma

INTRODUCTION: Median survival for newly diagnosed glioblastoma (GBM) patients remains less than two years despite aggressive clinical interventions. Antibody-based GBM-targeting could improve brain delivery and accumulation of therapies, but it has been challenging to identify universal tumor cell antigens due to intra-tumor and inter-patient GBM heterogeneity. We hypothesized that antigens of the neurovascular extracellular matrix (nvECM) within GBM-disrupted blood-brain barrier (BBB) may localize and enhance efficacy of therapeutic agents. METHODS: Yeast surface display biopanning and high throughput screening identified Variable Lymphocyte Receptors (VLR, i.e. jawless vertebrate lamprey antibodies) that preferentially accumulate at nvECM. Lead VLR candidates were tested for tumor targeting via combination with chemotherapeutic doxorubicin (DOX) liposomes and assessed for anti-GBM effects in vitro and against orthotopic mouse xenografts in vivo. RESULTS: VLR clones were enriched for binding to mouse brain endothelial cell (bEnd.3 line) ECM with two rounds of biopanning, then screened for preferential binding to brain-derived ECM. Lead VLR clone P1C10 was chosen for further testing for nvECM specificity vs. fibroblast (3T3 line) ECM in a high throughput screen, high affinity (Kd=48±6.1 nM), and immunolabeling of normal mouse and human brain, and GBM samples. Clone P1C10 demonstrated tumor-specific targeting in orthotopic U87 GBM xenografts, with 50% more DOX fluorescence detected at GBM after intravenous injection of P1C10-DOX liposomes compared to control, non-specific VLR-DOX. Finally, administration of P1C10-DOX liposomes (15 mg/kg, i.p., 1/week) significantly improved survival of mice bearing U87 xenografts, compared to non-targeted VLR-DOX (Kaplan-Meier, p CONCLUSIONS: We report combining yeast surface display biopanning and screening to identify VLRs that preferentially accumulate at disrupted nvECM of GBM-disrupted BBB, and demonstrate GBM-targeting specificity in vitro and in vivo with significant survival benefit. These results support the nvECM immune-targeting strategy to improve anti-GBM therapeutic efficacy, potentially improving survival and quality-of-life in brain cancer patients. Citation Format: Paul A. Clark, Benjamin J. Umlauf, Eric V. Shusta, John S. Kuo. Neurovascular-targeting antibodies discovered using yeast biopanning enhance drug delivery and improve survival for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1764.
Police vehicles as symbols of legitimacy

To experimentally evaluate the effects of police vehicle types and esthetics on participants’ perceptions of police officers. Using participant data (N = 307) from the Police Officer Perception Project (Simpson 2017), I experimentally assess the effects of police vehicles on perceptions of police officers. Specifically, I evaluate the impact of presenting officers in marked police vehicles (black and white versus white and blue), unmarked police vehicles, and unrelated (or civilian) police vehicles on perceptions of them as aggressive, approachable, friendly, respectful, and accountable. Police officers are perceived differently when occupying different types and colors of police vehicles. For example, officers are generally perceived more favorably when occupying marked police vehicles than when occupying non-marked police vehicles. When occupying marked police vehicles, officers are generally perceived more favorably when such vehicles have a black and white color scheme than a white and blue color scheme. Police vehicle types and esthetics impact perceptions of police officers in significant and meaningful ways. Like uniforms, police vehicles can be important symbols of legitimacy which exude presence and nonverbally communicate philosophies and intentions to the public. Police departments may tailor the perceived intentions of their motorized patrols by strategically manipulating the appearance of their vehicles.
Effect of hormone modulations on donor-derived spermatogenesis or colonization after syngeneic and xenotransplantation in mice.

Background Cytotoxic cancer treatments, such as irradiation, can cause permanent sterility in male mammals owing to the loss of spermatogonial stem cells. In animal models, spermatogenesis could be restored from transplanted spermatogonial stem cells. Previously, we showed that transient suppression of FSH, LH, and testosterone in the recipient with a gonadotropin-releasing hormone antagonist (GnRH-ant), given immediately after irradiation, enhanced spermatogenesis from transplanted spermatogonial stem cells in mice and monkeys. Objectives To explore improvements in the preparation of the recipient for efficient and reliable spermatogenic recovery from spermatogonial stem cell transplantation, so that it can be used effectively in clinical practice. Materials and methods In mouse recipients, we evaluated the effects of hormone suppression given after germ cell depletion was complete, which is a more clinically relevant model, and also the importance of total androgen ablation and maintenance of FSH levels. Three regimens, GnRH-ant, GnRH-ant plus flutamide (androgen receptor antagonist), and GnRH-ant plus FSH, were administered prior to and around the time of transplantation of testis cells from immature mice or from prepubertal monkeys. Results Treatment with GnRH-ant resulted in a fourfold increase in spermatogenic recovery from GFP-marked transplanted mouse cells. Total androgen ablation with the addition of flutamide, started two weeks before transplantation, did not further enhance recovery. Surprisingly, FSH supplementation, started around the time of transplantation, actually reduced spermatogenic recovery from transplanted spermatogonial stem cells in GnRH-ant-treated mice. When prepubertal monkey testicular cells were transplanted into nude mice that were given the same hormone treatments, the numbers of donor-derived colonies were independent of hormone treatment. Discussion and conclusion The enhancements in spermatogenic recovery may only occur when syngeneic or closely related donor-recipient pairs are used. These results are useful in further investigations in choosing a hormone suppression regimen in combination with spermatogonial transplantation as a treatment to restore fertility in primates after cytotoxic therapy.
Impact of rapid weight loss on risk reduction of developing arterial hypertension in severely obese patients undergoing bariatric surgery. A single-institution experience using the Framingham Hypertension Risk Score

Abstract Background Morbid obesity is strongly associated with hypertension. Objective The objective of this study is to compare the risk of developing hypertension before and after bariatric surgery. Setting U.S. university hospital. Methods We retrospectively reviewed all patients who underwent bariatric surgery from 2010 to 2015 at our institution. Nonhypertensive white individuals without diabetes at baseline were included in our study. The Framingham Hypertension Risk Score was used to predict the near-term incidence of the disease. This calculator predicts 1-, 2-, and 4-year incidence of hypertension. Results A total of 475 patients met the criteria for the hypertension risk score calculation. Females composed 72% (n = 342) of our population with a mean age of 42.6 ± 11.6 years. Laparoscopic sleeve gastrectomy was the most prevalent procedure at 81.89% (n = 389). At 12- month follow-up, the 1-year absolute risk reduction (ARR) and the relative risk reduction (RRR) were 6.2% and 69.2% (P Conclusions Sleeve gastrectomy and Roux-en-Y gastric bypass significantly diminish the risk of developing hypertension in morbidly obese patients. Prospective studies are needed to better comprehend these findings.
Development of a Transdermal Delivery System for Tenofovir Alafenamide, a Prodrug of Tenofovir with Potent Antiviral Activity Against HIV and HBV

Tenofovir alafenamide (TAF) is an effective nucleotide reverse transcriptase inhibitor that is used in the treatment of HIV-1 and HBV. Currently, it is being investigated for HIV prophylaxis. Oral TAF regimens require daily intake, which hampers adherence and increases the possibility of viral resistance. Long-acting formulations would significantly reduce this problem. Therefore, the aim of this study was to develop a transdermal patch containing TAF and investigate its performance in vitro through human epidermis. Two types of TAF patches were manufactured. Transparent patches were prepared using acrylate adhesive (DURO-TAK 87-2516), and suspension patches were prepared using silicone (BIO-PSA 7-4301) and polyisobutylene (DURO-TAK 87-6908) adhesives. In vitro permeation studies were performed while using vertical Franz diffusion cells for seven days. An optimized silicone-based patch was characterized for its adhesive properties and tested for skin irritation. The acrylate-based patches, comprising 2% w/w TAF and a combination of chemical enhancers, showed a maximum flux of 0.60 ± 0.09 µg/cm2/h. However, the silicone-based patch comprising of 15% w/w TAF showed the highest permeation (7.24 ± 0.47 μg/cm2/h). This study demonstrates the feasibility of developing silicone-based transdermal patches that can deliver a therapeutically relevant dose of TAF for the control of HIV and HBV infections.
Hyperprogressive disease in patients with recurrent high grade gliomas treated with immune checkpoint inhibitors or other therapies.

e13575Background: Hyperprogressive disease (HPD) has been described in solid tumor patients treated with immune checkpoint inhibitors (ICI). HPD is defined as a ≥2-fold increase in tumor growth rat...
Halogen versus Hydrogen Bonding in Binary Cocrystals: Novel Conformation a Coformer with [2+2] Photoreactivity of Criss-Crossed C=C Bonds.

A series of cocrystals involving the hydrogen- and halogen-bond donor coformers catechol (cat) and 1,2-diiodotetrafluorobenzene (1,2-di-I-tFb), respectively, is reported. Each coformer forms a cocrystal with each of the three symmetric bipyridines trans-1,2-bis(n-pyridyl)ethylene (n,n'-bpe, where: n=n'=2, 3, 4). Four novel cocrystals (cat) ⋅ (3,3'-bpe), 2(1,2-di-I-tFb) ⋅ (2,2'-bpe), 2(1,2-di-I-tFb) ⋅ (3,3'-bpe), and (1,2-di-I-tFb) ⋅ (4,4'-bpe) comprise components that assemble by either O-H⋅⋅⋅N hydrogen bonds (cat) or N⋅⋅⋅I halogen bonds (1,2-di-I-tFb). In (cat) ⋅ (3,3'-bpe), cat acts as a template to support an intermolecular [2+2] photocycloaddition of 3,3'-bpe. The reactivity occurs via a one-dimensional (1D) hydrogen-bonded tape with stacked and criss-crossed olefins that react stereoselectively and quantitatively to form rctt-tetrakis(3-pyridyl)cyclobutane (3,3'-tpcb). The reactivity of the criss-crossed olefins is facilitated by a hitherto not reported cis-gauche conformation adopted by cat. The stereochemistry of 3,3'-tpcb is confirmed in the cocrystal 2(cat) ⋅ (3,3'-tpcb).
Sport consumers motivation for live attendance and mediated sports consumption: a qualitative analysis

Live spectatorship and mediated sports consumption are two distinct, although intertwined, types of consumption practices. Based on this premise, this study examined the similarities and difference...
A survey of decision making and optimization under uncertainty

Recent advances in decision making have incorporated both risk and ambiguity in decision theory and optimization methods. These methods implement a variety of uncertainty representations from probabilistic and non-probabilistic foundations, including traditional probability theory, sets of probability measures, uncertainty sets, ambiguity sets, possibility theory, evidence theory, fuzzy measures, and imprecise probability. The choice of uncertainty representation impacts the expressiveness and tractability of the decision models. We survey recent approaches for representing uncertainty in both decision making and optimization to clarify the trade-offs among the alternative representations. Robust and distributionally robust optimization are surveyed, with particular attention to standard form ambiguity sets. Applications of uncertainty and decision models are also reviewed, with a focus on recent optimization applications. These applications highlight common practices and potential research gaps. The intersection of behavioral decision making and robust optimization is a promising area for future research and there is also opportunity for further advances in distributionally robust optimization in sequential and multi-agent settings.
The German Art Market

This paper discusses various aspects of the German art market, including a brief history of German art throughout the twentieth century and the great influence of World Wars I and II. Different styles and movements, such as Expressionism (e.g. Die Brucke, Der Blaue Reiter), Neue Sachlichkeit (New Objectivity) including Dada and Bauhaus and the classification of Entartete Kunst (Degenerate Art) during the Nazi regime, will be discussed. It also elaborates on German art after World War II, including East Germany's Socialist Realism and West Germany's international influences, the influence of Conceptual Art on contemporary German art and the more recent emergence of German photography and figurative paintings of the Neue Leipziger Schule (New Leipzig School). This paper analyzes the specific characteristics of collecting and dealing as it takes place in Germany. It therefore provides a more detailed account of galleries, auction houses and art fairs, as well as a short overview of museums and exhibitions. Finally, it discusses the position of the German art market in the international market and analyses transactions and sales turnover data. It also evaluates the recent market performance of different styles and individual artists. Finally, this chapter closes with a discussion of whether art might serve as an alternative asset class, with a special focus on the first German art fund.
Niche Cells and Signals that Regulate Lung Alveolar Stem Cells In Vivo

The distal lung is a honeycomb-like collection of delicate gas exchange sacs called alveoli lined by two interspersed epithelial cell types: the cuboidal, surfactant-producing alveolar type II (AT2) and the flat, gas-exchanging alveolar type I (AT1) cell. During aging, a subset of AT2 cells expressing the canonical Wnt target gene, Axin2, function as stem cells, renewing themselves while generating new AT1 and AT2 cells. Wnt activity endows AT2 cells with proliferative competency, enabling them to respond to activating cues, and simultaneously blocks AT2 to AT1 cell transdifferentiation. Acute alveolar injury rapidly expands the AT2 stem cell pool by transiently inducing Wnt signaling activity in "bulk" AT2 cells, facilitating rapid epithelial repair. AT2 cell "stemness" is thus tightly regulated by access to Wnts, supplied by a specialized single-cell fibroblast niche during maintenance and by AT2 cells themselves during injury repair. Two non-AT2 "reserve" cell populations residing in the distal airways also contribute to alveolar repair, but only after widespread epithelial injury, when they rapidly proliferate, migrate, and differentiate into airway and alveolar lineages. Here, we review alveolar renewal and repair with a focus on the niches, rather than the stem cells, highlighting what is known about the cellular and molecular mechanisms by which they control stem cell activity in vivo.
Effects of mobile oxygen ions in top-gated synthetic antiferromagnet structure

In this work, we study the effects of mobile oxygen ions in a synthetic antiferromagnet structure gated by a sputtered SiO2 dielectric layer for memory and logic applications. Our devices utilize electrochemical reactions between dielectric reactive species and magnetic elements to create irreversible changes in magnetization. We analyzed the dependence of ion velocity on the gate dielectric properties such as the lattice parameter, oxygen migration energy barrier, and electric field (E-field). Hall bar devices were patterned and tested to determine the interlayer exchange coupling between the CoFeB and [Co/Pd]n layers. The anomalous Hall effect (AHE) of the CoFeB layer at different gate voltages (Vg) was measured to determine the Vg dependence. A sharp change in the behavior of the CoFeB layer with respect to negative Vg results in a non-reciprocal decrease in the coercivity and magnetization and an increase in exchange bias. The observed change in exchange bias field and magnetization allows us to measure the change in the effective thickness of the CoFeB layer. This led us to conclude that the source of such behavior is the negatively charged mobile oxygen ions from the SiO2 gate.
Das Maß aller Dinge

Im ersten Viertel des zwanzigsten Jahrhunderts erschutterten zwei bedeutende Theorien die Welt. Sie zerstorten die Relikte der Physik, die vorher da war, und veranderten unser Verstandnis der Realitat auf ewig. Eine dieser Theorien, die Relativitatstheorie, wurde in wahrer Science-Fiction-Manier durch ein einsames Genie entwickelt, das vollkommen fur sich allein gearbeitet hat. Es hatte die Hochschule nur verlassen, um in einem blendenden Triumphzug mit tiefgreifenden Wahrheiten in seinen Handen zuruckzukehren – das war naturlich Albert Einstein.
Pericardiocentesis induced right ventricular changes in patients with and without pulmonary hypertension.

BACKGROUND Pericardial effusion drainage in patients with significant pulmonary hypertension (PH) has been questioned because of hemodynamic collapse concern, mainly because of right ventricular (RV) function challenging assessment. We aimed to assess RV function changes related to pericardiocentesis in patients with and without PH. METHODS Consecutive patients with symptomatic moderate-to-large pericardial effusion who had either echocardiographic or clinical signs of cardiac tamponade and who underwent pericardiocentesis from 2013 to 2018 were included. RV speckle-tracking echocardiography analysis was performed before and after pericardiocentesis. Patients were stratified by significant PH (pulmonary artery systolic pressure [PASP] ≥50 mm Hg). RESULTS The study cohort consisted of 76 patients, 23 (30%) with PH. In patients with PH, both end-diastolic and end-systolic areas (EDA, ESA) increased significantly after pericardiocentesis (22.6 ± 8.0 cm2 -26.4 ± 8.4 cm2 , P = .01) and (15.9 ± 6.3 cm2 -18.7 ± 6.5 cm2 , P = .02), respectively. However, RV function indices including fractional area change (FAC: 30.6 ± 13.7%-29.1 ± 8.8%, P = .61) and free-wall longitudinal strain (FWLS: -16.7 ± 6.7 to -15.9 ± 5.0, P = .50) remained unchanged postpericardiocentesis. In contrast, in the non-PH group, after pericardiocentesis, EDA increased significantly (20.4 ± 6.2-22.4 ± 5.9 cm2 , P = .006) but ESA did not (14.9 ± 5.7 vs 15.0 ± 4.6 cm2 , P = .89), and RV function indices improved (FAC 27.9 ± 11.7%-33.1 ± 8.5%, P = .003; FWLS -13.6 ± 5.4 to -17.2 ± 3.9%, P < .001). CONCLUSION Quantification of RV size and function can improve understanding of echocardiographic and hemodynamic changes postpericardiocentesis, which has the potential to guide management of PH patients with large pericardial effusion.