cssi/SciSciGPT-SciSciNet huggingface dataset:
Learning Probabilistic Models for Contour Completion in Natural Images

Using a large set of human segmented natural images, we study the statistics of region boundaries. We observe several power law distributions which likely arise from both multi-scale structure within individual objects and from arbitrary viewing distance. Accordingly, we develop a scale-invariant representation of images from the bottom up, using a piecewise linear approximation of contours and constrained Delaunay triangulation to complete gaps. We model curvilinear grouping on top of this graphical/geometric structure using a conditional random field to capture the statistics of continuity and different junction types. Quantitative evaluations on several large datasets show that our contour grouping algorithm consistently dominates and significantly improves on local edge detection.
Bronchial artery embolization for malignant hemoptysis: a single institutional experience

Objective: To assess the effectiveness of bronchial artery embolization (BAE) in patients with malignant hemoptysis. Methods: An IRB-approved retrospective study at our academic institution was conducted on all patients treated by BAE for hemoptysis from lung malignancy. Outcome and safety measures were documented according to Society of Interventional Radiology (SIR) practice guidelines. Results: A total of 26 patients (13 male, 13 female) with lung malignancy underwent BAE for hemoptysis from 2003-2013. Histologic analysis revealed 80% (21/26) of cases were from primary lung malignancies, while the remaining 20% (4/26) represented metastatic disease. Sixty-five percent (17/26) of patients underwent bronchoscopy prior to BAE. Follow-up ranged from 2 to 1,909 days, with average of 155 days. Technical success was achieved in 77% of patients (20/26). Clinical success rate was 75% (15/20). Eighty-five percent of embolized patients (17/20) were treated with particles, 15% (3/20) with gelfoam, and 20% (4/20) with coils. Single-vessel embolization was performed in 70% (14/20), two-vessel in 20% (4/20), and multiple vessels in 10% (2/20). No complications were reported. Six-month all-cause mortality of treated cases was 55% (11/20) with an in-hospital mortality of 25% (5/20). Ten percent (2/20) had remote re-bleeding events beyond 6 months. Statistically significant predictors of mortality were intubation status, hemoglobin/ hematocrit at presentation, and thrombocytopenia. Conclusions: BAE is a safe and useful treatment for clinically significant hemoptysis in patients with primary or metastatic lung masses despite high overall mortality. Intubation status, low hemoglobin/ hematocrit, and thrombocytopenia may represent clinical predictors of short term mortality following BAE. Advances in knowledge: Most patients undergoing BAE for malignant hemoptysis achieve high clinical success despite suffering a high mortality from underlying disease.
Learning by Solving Problems: Cognitive Load Theory and the Re-Design of an Introductory GIS Course

This article presents a teaching model to support learning by solving problems with geographic information technology. Using the case study of a re-designed introductory course in geographic information systems, I present research from studies of expertise and Cognitive Load Theory that identify learning objectives and methods for problem-based instruction. I illustrate a general template for learning geographic technology by solving a problem based on a process of understanding the problem, developing a plan, and implementing the plan. This template also reinforces learning during practice and exam problems. The article aims to encourage future research on problem-based instruction of geographic information technologies that integrate cognitive studies of learning, spatial thinking, and problem solving.
Fusion Folk: A Comment on Law and Music

This article is, in its most general sense, a critique of the idea of autonomy which is common to the understanding of both law and music. The idea of the autonomy of law, as an enterprise with its own rules and its own conventions, is parallel to a view of the composer working alone, uninfluenced by what has gone before, creating masterpieces free of cultural contexts. The stress here is on the point that both build on previous material, official and unofficial, and that in both there are latitudes and boundaries, ways in which the legal interpreter is free and ways in which the composer is constrained. The article is in two parts. Part I reviews some general questions about law and music and considers a number of "forms of music" that have been found to be useful metaphors in other fields. Part II of the article treats the folk element in high culture, arguing that both law and music contain illustrations of fusion folk.
Clinical activity of ceritinib in ROS1-rearranged non-small cell lung cancer: Bench to bedside report

We read with great interest the article by Davare et al. (1) on structural insight of ROS1 tyrosine kinase inhibitors. Non-small cell lung cancer (NSCLC) is no longer a single disease but a collection of genetically heterogeneous tumors with different therapeutic options [e.g., aberrations in EGFR, BRAF, HER2/Neu, RET, anaplastic lymphoma kinase (ALK), and ROS1 -rearranged tumors]. Each of these options has different clinical characteristics and therapeutic options with agents that have varying degrees of systemic activity. ROS1 gene rearrangements define a distinct molecular subgroup of NSCLC. ROS1 rearrangement leads to constitutive ROS1 activation and activity of crizotinib against ROS1-rearranged NSCLC was noted and crizotinib received regulatory approval for the treatment of ROS1 rearranged NSCLC (2). However, patients develop resistance and newer agents are needed. As shown by Davare et al. (1), molecular docking … [↵][1]1To whom correspondence should be addressed. Email: vsubbiah{at}mdanderson.org. [1]: #xref-corresp-1-1
Prediction of imminent, severe deterioration of children with parallel circulations using real-time processing of physiologic data

Abstract Objectives Sudden death is common in patients with hypoplastic left heart syndrome and comparable lesions with parallel systemic and pulmonary circulation from a common ventricular chamber. It is hypothesized that unforeseen acute deterioration is preceded by subtle changes in physiologic dynamics before overt clinical extremis. Our objective was to develop a computer algorithm to automatically recognize precursors to deterioration in real-time, providing an early warning to care staff. Methods Continuous high-resolution physiologic recordings were obtained from 25 children with parallel systemic and pulmonary circulation who were admitted to the cardiovascular intensive care unit of Texas Children's Hospital between their early neonatal palliation and stage 2 surgical palliation. Instances of cardiorespiratory deterioration (defined as the need for cardiopulmonary resuscitation or endotracheal intubation) were found via a chart review. A classification algorithm was applied to both primary and derived parameters that were significantly associated with deterioration. The algorithm was optimized to discriminate predeterioration physiology from stable physiology. Results Twenty cardiorespiratory deterioration events were identified in 13 of the 25 infants. The resulting algorithm was both sensitive and specific for detecting impending events, 1 to 2 hours in advance of overt extremis (receiver operating characteristic area = 0.91, 95% confidence interval = 0.88-0.94). Conclusions Automated, intelligent analysis of standard physiologic data in real-time can detect signs of clinical deterioration too subtle for the clinician to observe without the aid of a computer. This metric may serve as an early warning indicator of critical deterioration in patients with parallel systemic and pulmonary circulation.
Late-phase response to food in atopic dermatitis.

Atopic dermatitis may be initiated by contact between ingested antigens and cutaneous mast cells. The IgE-mediated reaction is sustained into a late phase by a number of biochemical events including Chemotaxis of eosinophils and their release of cytolytic major basic protein, and possibly the secretion of histamine-releasing factor, a nonantigenic activator of basophils and mast cells.
In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection.

Summary HIV-1 infection is enhanced by adhesive structures that form between infected and uninfected T cells called virological synapses (VSs). This mode of transmission results in the frequent co-transmission of multiple copies of HIV-1 across the VS, which can reduce sensitivity to antiretroviral drugs. Studying HIV-1 infection of humanized mice, we measured the frequency of co-transmission and the spatiotemporal organization of infected cells as indicators of cell-to-cell transmission in vivo. When inoculating mice with cells co-infected with two viral genotypes, we observed high levels of co-transmission to target cells. Additionally, micro-anatomical clustering of viral genotypes within lymphoid tissue indicates that viral spread is driven by local processes and not a diffuse viral cloud. Intravital splenic imaging reveals that anchored HIV-infected cells induce arrest of interacting, uninfected CD4 + T cells to form Env-dependent cell-cell conjugates. These findings suggest that HIV-1 spread between immune cells can be anatomically localized into infectious clusters.
Antidotal effectiveness of N-acetylcysteine in reversing acetaminophen-induced hepatotoxicity: Enhancement of the proteolysis of arylated proteins☆☆☆

Abstract The post-arylative mechanisms by which N-acetylcysteine (NAC) reduces the severity of the hepatotoxicity induced by acetaminophen (APAP) were investigated in primary cultures of mouse hepatocytes. When administered at selected times immediately following removal of medium containing 10 mM APAP, 2.0mM NAC was shown to restore glutathione levels through 16 hr of APAP pretreatment and to minimize the leakage of glutamate-oxaloacetate transaminase resulting from the first 8 hr of drug exposure. This temporal difference denned a critical period in which cells were responsive to NAC and permitted the investigation of potential post-arylative mechanisms of the antidote. In the absence of NAC during the recovery period, the cellular loss of covalently-bound APAP could be accounted for by the appearance of arylated proteins in the medium without any apparent degradation of APAP-bound proteins. By contrast, when NAC was present during the recovery period, there was a decrease in intracellular protein-bound APAP which could not be accounted for by that detected in the medium. Since during the recovery period the low residual intracellular concentration of APAP could not contribute significantly to any additional covalent binding in this system, NAC could not merely be acting as a nucleophilic trap for the reactive electrophile. Furthermore, NAC is not likely to dissociate covalently bound APAP from proteins. Hence, the overall decrease in covalent binding observed in cultures previously exposed to APAP for up to 8hr must have arisen from an NAC-dependent enhancement of the degradation of the arylated proteins. However, after a more prolonged exposure to APAP, the ineffectiveness of NAC may have resulted from APAP-induced irreparable damage to the intracellular proteolytic system. These data suggest that the post-arylative efficacy of NAC may reside in the ability of the antidote to restore the functional capacity of the proteolytic system to rid the cells of arylated proteins.
Physical activity, mental health, and weight gain in a longitudinal observational cohort of nonobese young adults.

Objective To investigate the relationship among moderate-to-vigorous physical activity (MVPA), mental health symptoms, and weight gain in young adults. Methods Fifty-nine healthy men and women (age 26.8 ± 4.7 years, body mass index [BMI] 22.4 ± 2.3 kg/m2) were assessed at baseline and year 2. Weight, BMI, fat mass by dual-energy X-ray absorptiometry, anxiety and depression by the SCL-90, and MVPA by accelerometry were assessed. Sex-stratified linear regression models were used to examine associations between baseline anxiety/depression and body composition change, then repeated controlling for baseline MVPA. Results Overall, weight, BMI, fat mass, and subcutaneous adiposity significantly increased at year 2 (P < 0.05). For women, a higher depression and anxiety score predicted increased weight, BMI, fat mass, and subcutaneous adiposity (P < 0.05). Controlling for MVPA attenuated these associations to nonsignificance. For men, MVPA did not alter the associations between anxiety and increased weight, BMI, fat mass, and subcutaneous adiposity (P < 0.05) or the associations between depression and decreased weight, BMI, fat mass, and subcutaneous adiposity (P < 0.05). Conclusions Anxiety and depression were related to body composition change for young adults. In women, MVPA attenuated these associations to nonsignificance. MVPA may buffer the adverse effects of depression and anxiety symptoms on young women's weight gain.
Analysis of Cheating on Academic Assignments

Instances of cheating on study guide assignments were observed for 245 college students. Mean cheating rate was 50.8% (i.e., the typical student cheated on about half the study guide questions). Cheating on assignments tended to increase across the semester and was associated with lower grades on exams. The typical student’s tendency to cheat varied considerably across the semester, suggesting that transient setting factors were major determinants of cheating on assignments. Admission of cheating was increased by reinforcement, but this increase in admissions did not result in a corresponding change in rates of cheating. A positive correlation was found between cheating and admission of cheating, except when penalties were instated for admissions. Neither an honor pledge nor values counseling (involving confrontation about actual rates of cheating) diminished cheating. In fact high-rate cheaters generally did not even bother to attend the scheduled counseling sessions.
Neurodevelopmental Outcome in Children after Fetal Cardiac Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Objective To characterize neurodevelopmental outcomes after fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome and determine the risk factors for adverse neurodevelopment. Study design Questionnaires were mailed to families of children who underwent fetal aortic valvuloplasty from 2000 to 2012, and medical records were reviewed retrospectively. The primary outcome was the General Adaptive Composite score of the Adaptive Behavior Assessment System Questionnaire-Second Edition. Other questionnaires included the Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, and Pediatric Quality of Life Inventory. Results Among 69 eligible subjects, 52 (75%) completed questionnaires at median age of 5.5 (range 1.3-12) years; 30 (58%) had biventricular status circulation. The General Adaptive Composite mean score (92 ± 17) was lower than population norms ( P P = .10). On multivariable analysis, independent predictors of a lower General Adaptive Composite score were total hospital duration of stay in the first year of life ( P = .001) and, when forced into the model, biventricular status ( P = .02). For all other neurodevelopmental questionnaires (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, Ages and Stages, Pediatric Quality of Life Inventory), most subscale scores for patients with biventricular and single ventricular status were similar. Conclusion Children who underwent fetal aortic valvuloplasty have neurodevelopmental delay, similar to patients with hypoplastic left heart syndrome without fetal intervention. Achievement of biventricular circulation was not associated with better outcomes. We infer that innate patient factors and morbidity during infancy have the greatest effect on neurodevelopmental outcomes.
TIPS: a system for automated image-based phenotyping of maize tassels

The maize male inflorescence (tassel) produces pollen necessary for reproduction and commercial grain production of maize. The size of the tassel has been linked to factors affecting grain yield, so understanding the genetic control of tassel architecture is an important goal. Tassels are fragile and deform easily after removal from the plant, necessitating rapid measurement of any shape characteristics that cannot be retained during storage. Some morphological characteristics of tassels such as curvature and compactness are difficult to quantify using traditional methods, but can be quantified by image-based phenotyping tools. These constraints necessitate the development of an efficient method for capturing natural-state tassel morphology and complementary automated analytical methods that can quickly and reproducibly quantify traits of interest such as height, spread, and branch number. This paper presents the Tassel Image-based Phenotyping System (TIPS), which provides a platform for imaging tassels in the field immediately following removal from the plant. TIPS consists of custom methods that can quantify morphological traits from profile images of freshly harvested tassels acquired with a standard digital camera in a field-deployable light shelter. Correlations between manually measured traits (tassel weight, tassel length, spike length, and branch number) and image-based measurements ranged from 0.66 to 0.89. Additional tassel characteristics quantified by image analysis included some that cannot be quantified manually, such as curvature, compactness, fractal dimension, skeleton length, and perimeter. TIPS was used to measure tassel phenotypes of 3530 individual tassels from 749 diverse inbred lines that represent the diversity of tassel morphology found in modern breeding and academic research programs. Repeatability ranged from 0.85 to 0.92 for manually measured phenotypes, from 0.77 to 0.83 for the same traits measured by image-based methods, and from 0.49 to 0.81 for traits that can only be measured by image analysis. TIPS allows morphological features of maize tassels to be quantified automatically, with minimal disturbance, at a scale that supports population-level studies. TIPS is expected to accelerate the discovery of associations between genetic loci and tassel morphology characteristics, and can be applied to maize breeding programs to increase productivity with lower resource commitment.
3-Arm spiral antennas for direction finding applications

This paper presents a study of 3-arm Archimedean spiral antennas for direction finding (DF) systems. First, we discuss the DF performance of the antenna using an amplitude and phase comparison method, where Mode 1 and Mode 2 radiation patterns of the spiral are used to determine the direction-of-arrival of a source signal with known polarization. Next, the antenna's DF capability is assessed using the Cramer Rao bound, which determines the lowest possible RMS error for angular estimation. Results show that a 3-arm spiral provides a low-cost, feasible alternative for multi-channel, digital reception.
Low-level orientation information for social evaluation in face images

Observers make a range of social evaluations based on facial appearance, including judgments of trustworthiness, warmth, competence, and other aspects of personality. What visual information do people use to make these judgments? While links have been made between perceived social characteristics and other high-level properties of facial appearance (e.g., attractiveness, masculinity), there has been comparatively little effort to link social evaluations to low-level visual features, like spatial frequency and orientation sub-bands, known to be critically important for face processing. We explored the extent to which different social evaluations depended critically on horizontal orientation energy vs. vertical orientation energy, as is the case for face identification and emotion recognition. We found that while trustworthiness judgments exhibited this bias for horizontal orientations, competence and dominance did not, suggesting that social evaluations may depend on a multi-channel representation of facial appearance at early stages of visual processing.
ZnO and Cu-based adsorbents for biogas desulfurization at room temperature

Synthesis and structural characterization of ZnO and Cu based materials were done in order to compare chemical, morphological and microstructural effects in sorbent materials for gas-phase desulfurization reaction at room temperatures as a potential application in biogas cleaning. The materials were synthesized through two wet chemical routes, firstly using zinc nitrate, hexamethylenetetramine and NaOH reagents at 70 and 90 °C for ZnO flower-like and rod-like structures, respectively; and secondly a typical calcination of metallic copper to obtain CuO. Powder X-ray diffraction, X-ray fluorescent spectroscopy analysis were realized. Results showed a unique zincite phase for ZnO and three phases in copper samples: Cu0, Cu2O and CuO (76.3, 18.3 and 5.4 wt%). The size of crystal domains varied from 180 to 1600 nm, while the particle size varied from 660 to 1020 nm. These materials were tested in desulfurization reactions at room temperature using a fixed-bed glass reactor. In order to avoid poisoning and asphyxiation risks a non-desulfurized biogas influent was simulated by a gas mixture of N2 and H2S (100 ppm). The reactor was fed with the gas mixture at rate of 450 ml/min (GHSV 9120 h−1). The composition of effluent gas was determined using a biogas detector, coupled with an electrochemical H2S sensor. Results show that CuO and ZnO could be feasible adsorbents for the removal of hydrogen sulfide; however, they became saturated after 300 s while high surface area materials, evidenced by SEM, showed higher saturation capacity. Characterization of wasted adsorbents using electron microscopy techniques and fluorescence X-ray spectroscopy evidenced the presence of metallic sulfides at amounts less than 0.05 wt%, although no crystalline phases were detected in further analysis.
Sporadic Late-Onset Nemaline Myopathy (S31.005)

Objective: To define the clinical spectrum and treatment outcomes of sporadic late-onset nemaline myopathy (SLONM). Background: SLONM is a rare disorder characterized by accumulation of nemaline rods in atrophic muscle fibers. SLONM can be associated with a monoclonal gammopathy of undetermined significance (MGUS) or HIV infection. The diagnosis remains challenging and little is known regarding treatment outcomes, especially in the absence of HIV infection. Design/Methods: We collected clinical and laboratory data of SLONM patients seen at our institution between 2000 and 2017. We assessed response to treatment as adjudged by improvement of: muscle strength, pulmonary or cardiac function, gait and daily living activity. Hematologic response was also evaluated. Results: We identified 28 patients with SLONM: 18 with MGUS and 10 without. No patient was HIV-positive. Median age at presentation was 61.5 years (range 41–82); 36% of patients were women. Symptoms at onset included proximal limb weakness (57% of patients; 14% unilaterally), axial weakness (39%), dysphagia (11%), dyspnea (4%) and ptosis (4%). 36% of patients reported severe neck/back pain preceding the onset of weakness. At the time of clinical evaluation, median duration of symptoms was 28.5 months (range 2–120). On examination, patients demonstrated various combinations of limb, axial (head drop, camptocormia, scapula winging, core weakness) and bulbar weakness. The MGUS was always of IgG-type. Thirteen patients had evidence of neuromuscular respiratory insufficiency. EMG showed fibrillation potentials in 81% of patients, short duration motor unit potentials in all patients, mixed with long duration motor unit potentials in 48% of patients. Fourteen patients received treatment (11 with IVIG, 5 with autologous stem cell transplant, 5 with corticosteroids, 5 with a steroid-sparing immunosuppressant drug and 1 with lenalidomide). Neurological and hematological treatment outcomes and survival data will be presented. Conclusions: SLONM is a rare, potentially fatal, yet treatable condition. Establishing the diagnosis remains crucial for timely treatment. Disclosure: Dr. Naddaf has nothing to disclose. Dr. Milone has nothing to disclose. Dr. Kansagra has nothing to disclose. Dr. Buadi has nothing to disclose. Dr. Kourelis has nothing to disclose.
Introduction: The Ethics of Killing

In this Introduction, I have two goals. First, I try to contextualize the reasons most people believe both that, all else being equal, killing animals is wrong, and that some justification is needed, at least implicitly, to perform these killings. In the course of this discussion, I briefly discuss the comparative badness of killing human and nonhuman animals. Second, I provide short summaries of all of the papers in this section of the Handbook.
How to Conceptualize a Research Project

The research process has three phases: the conceptual phase, the empirical phase, and the interpretative phase. In this chapter, we focus on the first phase: the conceptual phase—the part of the research process that determines which questions are to be addressed by the research and how research procedures are to be used as tools in finding the answers to these questions. Here we describe the various components of the conceptualization phase that need to be carefully considered before moving on to the empirical and interpretative phases of the research. Conceptualization involves simultaneously bringing together several considerations to identify a good research idea, i.e., an answerable research question that is worth answering. Components of this process include conducting a thorough search of the peer-reviewed literature, finding a research mentor and other collaborators, considering methodology and study design, and assessing feasibility. It should be noted that although we describe these various components in a linear fashion in the text, in reality, the conceptualization phase is not a linear process and will require consideration of these components to varying degrees at various stages depending upon evolving circumstances and the reader’s unique strengths and weaknesses. Even though careful attention to all these components will require considerable time and effort on the part of the physician scientist, we consider this to be time well spent as it will lay the ground for a successful research endeavor.
A Note on Spectral Triples on the Quantum Disk

By modifying the ideas from our previous paper [SIGMA 13 (2017), 075, 26 pages, arXiv:1705.04005], we construct spectral triples from implementations of covariant derivations on the quantum disk.
Corrigendum to “Effectiveness of lead-hazard control interventions on dust lead loadings: Findings from the evaluation of the HUD Lead-Based Paint Hazard Control Grant Program”: [Environ. Res. 98 (2005) 303–314]

Corrigendum to ‘‘Effectiveness of lead-hazard control interventions on dust lead loadings: Findings from the evaluation of the HUD Lead-Based Paint Hazard Control Grant Program’’ [Environ. Res. 98 (2005) 303–314] Sherry L. Dixon, Jonathan W. Wilson , C. Scott Clark, Warren A. Galke, Paul A. Succop, Mei Chen National Center for Healthy Housing, 10320 Little Patuxent Pkwy, Suite 500, Columbia, MD 21044, USA Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA
Management of the Aortic Arch in the Modern Era

There are two main treatment strategies for advanced aortic arch pathology: traditional surgical replacement and hybrid repair. Regardless of the treatment strategy, cerebral protection is of paramount importance to minimize morbidity and mortality. As result, numerous cerebral protection strategies have been utilized including hypothermia and cerebral perfusion which have rendered aortic arch interventions safe. Traditional open arch replacement represents the gold standard by which all other aortic arch interventions should be measured as it has been shown to be safe and effective. Recently, hybrid arch procedures have been developed which incorporate both open surgical replacement and thoracic aortic endograft repair. While effective with specific anatomy and patient populations, hybrid arch repair in its current state has not supplanted open surgical repair in the general population.
Implementation of an Acknowledgment and Signature Based Intrusion Detection System for MANETS

Mobile Ad Hoc Networks (MANETS) are highly vulnerable to security attacks than wired network. In this paper, we propose an acknowledgment and signature based intrusion detection system for securing data packets from malicious nodes during packet transmission over MANETS. The system is named as Malicious Node Detection System (MaDS). We implemented and evaluated MaDS in NS2 and compare the result against 2ACK and EAACK in terms of packet delivery ratio.
Application of the Dötz Reaction to Construction of a Major Portion of the Ansa Macrocycle (−)-Kendomycin

A Dotz reaction employing a terminal alkyne and a Fischer-type alkenylchromium carbenoid led to a pentasubstituted benzene from which a major portion of the Streptomyces metabolite (−)-kendomycin was synthesized.
Nongenetic Techniques for Isolating Fusion Products between Different Cell Types

Until recently, virtually all investigations into the behavior of cell hybrids have employed genetic selection techniques, such as the hypoxanthine-aminopterin-thymidine (HAT) system (Littlefield, 1964), to isolate the cell fusion products. In this approach, one starts with two cell lines, one of which lacks enzyme A and the other of which lacks enzyme B. After fusing the two cell types together, they are placed in a specially designed culture medium in which only cells that have both enzymes are able to grow. Under these conditions, neither parental cell line is able to divide. However, since the cell line that lacks enzyme A has enzyme B and vice versa, fusion products between the two do contain both enzymes and the cell hybrids are able to multiply. Although systems based on this approach have been extremely useful, there are a variety of practical and theoretical problems associated with their use. Obviously, only special cell lines that lack the necessary enzymes can be used. Although in some cases this problem can be surmounted by mutagenizing and isolating cells carrying the required defect, this can only be done with immortal cell lines. The cultured life span of normal diploid cells (Hayflick, 1965) is limited, so that by the time mutant clones are isolated they are essentially senescent.
Assessment of Response to Neoadjuvant Therapy Using CT Texture Analysis in Patients With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma

OBJECTIVE. The goal of this study was to assess the correlation between CT-derived texture features of pancreatic ductal adenocarcinoma (PDAC) and histologic and biochemical markers of response to neoadjuvant treatment as well as disease-free survival in patients with potentially resectable PDAC. SUBJECTS AND METHODS. Thirty-nine patients completed this prospective study protocol between November 2013 and December 2016. All patients received neoadjuvant chemotherapy, underwent surgical resection, and had histologic grading of tumor response. Similar CT protocol was used for all patients. Pancreatic (late arterial) phase of pre- and posttreatment CT scans were evaluated. Histogram analysis and spatial-band-pass filtration were used to extract textural features. Correlation between textural parameters, histologic response, biochemical response, and genetic mutations was assessed using Mann-Whitney test, chi-square analysis, and multivariate logistic regression. Association with disease-free survival was assessed using Kaplan-Meier method and Cox model. RESULTS. Pretreatment mean positive pixel (MPP) at fine- and medium-level filtration, pretreatment kurtosis at medium-level filtration, changes in kurtosis, and pretreatment tumor SD were statistically different between patients with no or poor histologic response and favorable histologic response (p < 0.05). Changes in skewness and kurtosis at medium-level filtration significantly correlated with biochemical response (p < 0.01). On the basis of multivariate analysis, patients with higher MPP at pretreatment CT were more likely to have favorable histologic response (odds ratio, 1.06; 95% CI, 1.002-1.12). The Cox model for association between textural features and disease-free survival was statistically significant (p = 0.001). CONCLUSION. Textural features extracted from baseline pancreatic phase CT imaging of patients with potentially resectable PDAC and longitudinal changes in tumor heterogeneity can be used as biomarkers for predicting histologic response to neoadjuvant chemotherapy and disease-free survival.
Maternal vitamin D deficiency induces transcriptomic changes in newborn rat lungs

Abstract Vitamin D deficiency (VDD) during pregnancy is common and related to several maternal and fetal morbidities. Vitamin D (VD) plays a role in normal lung development and VDD causes abnormal airway, alveolar, and vascular growth in newborn rats. Here we use an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from VDD dams. The lungs of newborn offspring from VD replete and VDD dams were removed and RNA from these samples were analyzed using Affymetrix microarrays. Data were RMA normalized, differential gene expression was determined using Significance Analysis of Microarrays (5 % FDR) and pathway enrichment analysis was assessed. There were 2233 differentially expressed transcripts between the VDD and control lungs (1889 up, 344 down). Consistent with the suppression of lung growth in the VDD group, there were significant suppression of signal transduction pathways related to vascular biology and anabolic signaling pathways, e.g. the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), cell cycle control. A major, enriched functional category was upregulation of pathways related to the innate immune system, including pathways for granulocyte and macrophage development, chemotaxis, and activation of cytokine signaling through Jak/Stat (e.g. resulting in higher IL1 α and β ). We conclude that VDD during fetal development alters multiple pathways beyond the predicted angiogeneic alterations. These changes either contribute to, or reflect, the abnormal airway, alveolar, and vascular growth seen in the neonatal lung resulting from maternal VDD. The pattern also suggests abnormal lung development caused by maternal VDD creates a proinflammatory milieu that could contribute to the suppression of lung growth and development.
6.05 – Degenerative and Regenerative Events in the Central and Peripheral Nervous System☆

The ability of xenobiotics and numerous disease conditions to produce cell death in the nervous system is well established with examples involving all cell types. In contrast to the varied nature of primary initiating events responsible for cell death, there is a smaller group of prevalent secondary processes including excitotoxicity, oxidative stress, energy deprivation, and dysregulation of Ca2 + homeostasis that commonly interact to bring about a cell’s demise and determine which death pathway is followed. For both neurons and glial cells, necrosis and a group of closely related programmed cell death (PCD) mechanisms including apoptosis, autophagy, and necroptosis are well-recognized pathways leading to cell death. Individual cells within a given population may follow different pathways as a result of temporal effects and the nature of the insult. Moreover, the PCD pathways utilize some of the same mechanisms to carry out the process of cell death and thus, some cells exhibit characteristics inherent to more than one pathway. While there are sufficiently established biochemical and morphological characteristics to distinguish the prevailing mechanisms of necrosis from PCD, distinguishing the PCD pathway activated in a particular cell or tissue is not always readily accomplished. Necrosis is most typically a pathological event associated with a more severe and acute insult involving an entire population of localized cells and PCD is associated with more moderate stress or injury commonly exhibited by individual cells within an otherwise unaffected population of cells. Neural networks also can be disrupted and functional deficits incurred in the absence of neuronal loss through axonal degeneration. Whether or not normal function of the nervous system is maintained or regained following pathological loss of cells is dependent on the capacity of the nervous system to compensate. This compensation may be achieved either through regenerative processes that replace lost cells and axons or through compensatory plasticity by remaining components that adapt and assume the function of the lost cells or structures. The peripheral nervous system is considerably more efficient at repair than the central nervous system. Relatively recent studies on neurogenesis have provided a credible challenge to the previously held dogma that in the fully developed nervous system there is a cumulative loss of neurons throughout life and that in the absence of an ability to replace lost neurons leads to an inevitable decline of function with age. Although there are considerable challenges, these discoveries have generated interest in neurogenesis and transplantation of neural stem cells as potential therapeutic approaches for neurological injury. The first part of this article will discuss the most prevalent secondary processes and final pathways that execute degenerative events within the nervous system and the second part will describe and contrast regenerative processes within the central and peripheral nervous system.
The discovery of dystrophin, the protein product of the Duchenne muscular dystrophy gene

Duchenne muscular dystrophy was a well-established medical and genetic enigma by the 1970s. Why was the new mutation rate so high in all world populations? Why were affected boys doing well in early childhood, but then showed relentless progression of muscle wasting? What was wrong with the muscle? The identification of the first fragments of DMD gene cDNA in 1986, prediction of the entire 3685 amino acid protein sequence, and production of antibodies to dystrophin, both in 1987, provided key tools to understand DMD genetics and molecular pathology. The identification of dystrophin nucleated extensive research on myofiber membrane cytoskeleton, membrane repair, muscle regeneration, and failure of regeneration. This in turn led to molecular therapeutics based on understanding of dystrophin structure and function. This historical perspective describes the events surrounding the initial identification of the dystrophin protein.
Endoscopic endonasal resection of orbital schwannoma assisted with small-incision medial orbitotomy: case series and surgical technique

To describe a surgical approach for the resection of schwannomas occurring in the medial aspect of the orbit and to review a series of patients who underwent this novel technique. This retrospectiv...
Insulated Switches: Dual-Function Protein RalGEFRGL-1 Promotes Developmental Fidelity

The C. elegans vulva is an excellent model for the study of developmental biology and cell–cell signaling. The developmental induction of vulval precursor cells (VPCs) to assume the 3°-3°-2°-1°-2°-3° patterning of cell fates occurs with 99.8% accuracy. During C. elegans vulval development, an EGF signal from the anchor cell initiates the activation of RasLET-60 > RafLIN-45 > MEKMEK-2 > ERKMPK-1 signaling cascade to induce the 1° cell. The presumptive 1° cell signals its two neighboring cells via NotchLIN-12 to develop 2° cells. In addition, RasLET-60 switches effectors to RalGEFRGL-1 > RalRAL-1 to promote 2° fate. Shin et al. (2019) showed that RalGEFRGL-1 is a dual-function protein in VPCs fate patterning. RalGEFRGL-1 functions as a scaffold for PDKPDK-1 > AktAKT-1/2 modulatory signaling to promote 1° fate in addition to propagating the RasLET-60 modulatory signal through RalRAL-1 to promote 2° fate. The deletion of RalGEFRGL-1 increases the frequency of VPC patterning errors 15-fold compared to the wild-type control. We speculate that RalGEFRGL-1 represents an “insulated switch”, whereby the promotion of one signaling activity curtails the promotion of the opposing activity. This property might increase the impact of the switch on fidelity more than two separately encoded proteins could. Understanding how developmental fidelity is controlled will help us to better understand the origins of cancer and birth defects, which occur in part due to the misspecification of cell fates.
Light-matter interactions in perovskites (Conference Presentation)

The ability to probe and control light-matter interaction at the nanometer scale not only advances frontiers of fundamental science, but also is a critical prerequisite to device applications in electronics, sensing, catalysis, energy harvesting, and more. Exploiting and enhancing the originally weak light-matter interactions via nanofabricated photonic structures; we will be able to sense chemical species at single molecule levels, to devise better imaging and manufacturing tools, to transfer data more efficiently at higher speed. In this invited talk, I will present recent progress in Prof. Xiang Zhang's group on the subject of light-matter interaction in perovskites.
Vascularized Bone Marrow Cellular Depletion or Discontinuity Abrogates Protection of Vascularized Composite Allografts in Nonhuman Primates.

Background Vascularized composite allografts (VCA) have demonstrated good clinical outcomes dependent on chronic immunosuppression. Previous work by our group and others supports that cotransplanted vascularized bone marrow (VBM) as a component of VCA offers immunologic protection to prolong graft survival. We aimed to characterize the requirements and potential mechanisms of VBM-mediated protection of VCA by modifying grafts through various strategies. Methods Experimental groups of mismatched cynomolgus macaque recipients received VCA transplants modified by the following approaches: heterotopic separation of the VCA and VBM components; T-cell depletion of either donor or recipient; irradiation of donor VCA; and infusion of donor bone marrow. All groups received standard immunosuppression with tacrolimus and mycophenolate mofetil. Results Experimental modifications to donor, recipient, or graft all demonstrated short-graft survivals (31 d). Chimerism levels without bone marrow infusion were transient and minimal when detected and were not associated with prolonged survival. Donor bone marrow infusion increased levels of chimerism but resulted in alloantibody production and did not improve graft survival. Conclusions VCA graft survival is significantly reduced compared with previously reported VCA with VBM transplants (348 d; P = 0.01) when the hematopoietic niche is removed, altered, or destroyed via irradiation, depletion, or topographical rearrangement. These experimental manipulations resulted in similar outcomes to VCA grafts without cotransplanted VBM (25 d). These data support the presence of a radiosensitive, T-cell population within the VBM compartment not reconstituted by reinfusion of bone marrow cells.
Introduction to Ecoregional Green Roofs

This chapter introduces ecoregional green roofs by discussing the development of native plant communities, the history of modern green roofs, and some observations about ecoregional green roofs. It examines the development of the natural vegetation in the western U.S. and Canada and the kinds of plant communities that make up ecoregions appropriate for different forms of green roofs. The history of green roof origins and the development of ecoregional green roofs provide insight into the growth of the modern green roof industry in Europe and North America. Original intentions for green roofs can be misguided, as design decisions or maintenance practices can be out of line with the vegetation selected, or the microclimate of the roof. Several early examples of built ecoregional green roofs highlight successes and lessons learned. Although the conceptual framework laid out in Chap. 1 (and Chap. 2) can be applied anywhere, the climate characteristics for green roofs growing west of the 100th meridian provide background and rationale for the targeted regions of this book. Our knowledge and research literature is only beginning to include the analysis of ecoregional green roofs located in cities where plants experience prolonged exposure to heat and drought, or both.
Multinational Investment Policy: Why Do Multinational Enterprises Invest Less?

A small number of U.S. multinational enterprises (MNEs) are dominant producers in the economy, yet they invest considerably less and exhibit lower Tobin's q than domestic firms. Contrary to standard model predictions, investment and q fall sharply as firms multinationalize despite the preceding productivity increase. This paper rationalizes these findings extending a standard model with a multinationalization option. More productive domestic firms endogenously multinationalize inside the model and their optimal investment and q fall despite increasing productivity. The average multinationalization option is worth as much as 40% of assets among public firms at the time of multinationalization. Investment regressions that ignore multinational status may mistakenly suggest a secular underinvestment for the most productive group of firms, while our model suggests that investment reduction is a natural consequence of multinationalization.
Human Papillomaviruses Target the DNA Damage Repair and Innate Immune Response Pathways to Allow for Persistent Infection

Persistent infection with high-risk human papillomaviruses (HPVs) is the major risk factor associated with development of anogenital and oropharyngeal cancers. Initial infection by HPVs occurs into basal epithelial cells where viral genomes are established as nuclear episomes and persist until cleared by the immune response. Productive replication or amplification occurs upon differentiation and is dependent upon activation of the ataxia-telangiectasia mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) DNA damage repair (DDR) pathways. In addition to activating DDR pathways, HPVs must escape innate immune surveillance mechanisms by antagonizing sensors, adaptors, interferons and antiviral gene expression. Both DDR and innate immune pathways are key host mechanisms that crosstalk with each other to maintain homeostasis of cells persistently infected with HPVs. Interestingly, it is still not fully understood why some HPV infections get cleared while others do not. Targeting of these two processes with antiviral therapies may provide opportunities for treatment of cancers caused by high-risk HPVs.