cssi/SciSciGPT-SciSciNet huggingface dataset:
Demonstration of H‐2 antigens on preimplantation mouse embryos using conventional antisera and monoclonal antibody

Mouse embryos at the 2-cell, 8-cell, and blastocyst stages of development were examined for the presence of H-2 antigens by immunoperoxidase labeling and transmission electron microscopy. Conventional antisera made in congenic mouse strains were used to study embryos of four different haplotypes: b, a, k, and d. Blastocysts showed uniform heavy labeling of all cells of the trophectoderm, 8-cell embryos showed lighter labeling of only some of the cells, and 2-cell embryos showed no labeling. Similar results were found for all four haplotypes studied. In addition, monoclonal antibody 11-4.1 (anti-Kk) was reacted with homologous (H-2k) and heterologous (H-2b) blastocysts. Positive results with the monoclonal antibody corroborates the concept that H-2 antigens are expressed on early mouse embryos.
Engineered and Natural Processing: Neurocomputing and Neuromorphological Processing Platforms

This paper applies and integrates digital design, complexity and communication to further advance an enabling paradigm of neuromorphological processing in three-dimensional (3D) space. Those developments promise one to achieve superhigh-performance processing (computing) as well as devise advanced processing platforms (PPs). We apply a neurocomputing paradigm to engineered processing systems. Our theoretical findings are predominantly focused on engineered (humandevised) natural-centric processing. We coherently integrate sound premises and utilize massive vector processing in 3D space. Our neurocomputing paradigm implies application of basic fundamentals of computer engineering and science, as well as emerging technological developments. To ensure high performance computing, both synthesis (design) and technology centric realization (microelectronics and fluidic/solid molecular synthesis) must be accomplished. The proposed developments and advancements in the fundamental areas of theoretical computer science and applied engineering are inspired by natural processing and emerging molecular engineering.
Preparation and in-vitro/in-vivo evaluation of surface-modified poly (lactide-co-glycolide) fluorescent nanoparticles.

Objective The aim was to develop biodegradable nanoparticles suitable for cellular delivery of chemotherapeutic drugs. Methods Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared using a modified solvent evaporation method. Chitosan and calcium chloride were tested as surface modifiers. Coumarin-6 was incorporated into some formulations as a fluorescent marker. Key findings The median size of the particles was between 400 nm and 7 μm, and scanning electron microscope pictures showed that the particles were smooth and spherical. The zeta potentials of the particles with and without surface modifier ranged between -25.7 mV and -7.0 mV, respectively. Fluorescence microscopy and flow cytometry (FACS) analysis showed that smaller surface-modified particles were efficiently internalised by neoplastic 4T1 cells. Image analysis of frozen tissue sections from Balb/c mice given nanoparticles via the tail vein showed that the particles were distributed preferentially into the lungs, followed by the liver, spleen, kidney and heart. Conclusions Chitosan-modified PLGA nanoparticles showed significant uptake by neoplastic 4T1 cells, and were distributed to several major organs frequently seen as sites of cancer metastasis in mice.
The predictive value of initial cytostatic response in primary unresectable rhabdomyosarcoma in children.

The relation between the initial tumour regression produced by chemotherapy and the later event-free survival was studied in a prospective multicentre study on soft-tissue sarcomas in children. The event-free survival rate in patients with complete remission after seven weeks of chemotherapy was 95%; in patients with incomplete tumour reduction of >2/3, 61%; and in patients with tumour reduction of 1/3, 31 %. Patients with partial remission at week 7, who achieved complete remission by week 16 after additional chemotherapy had an event-free survival rate of 64%. A multivariate analysis suggested that the response per unit of time was an important prognostic factor.
Fe-based bulk metallic glasses with diameter thickness larger than one centimeter

Fe–Cr–Mo–(Y,Ln)–C–B bulk metallic glasses (Ln are lanthanides) with maximum diameter thicknesses reaching 12 mm have been obtained by casting. The high glass formability is attained despite a low reduced glass transition temperature of 0.58. The inclusion of Y/Ln is motivated by the idea that elements with large atomic sizes can destabilize the competing crystalline phase, enabling the amorphous phase to be formed. It is found that the role of Y/Ln as a fluxing agent is relatively small in terms of glass formability enhancement. The obtained bulk metallic glasses are non-ferromagnetic and exhibit high elastic moduli of approximately 180–200 GPa and microhardness of approximately 13 GPa.
Equity and Access to Fishing Rights: Exploring the Community Quota Program in the Gulf of Alaska

The right to fish has been privatized for most commercial fisheries in Alaska. Policies that limit and commodify fishing rights have had disproportionately negative effects on certain communities and certain groups of participants. For a complex set of reasons, small, remote, primarily indigenous fishing communities in Alaska tend to be disadvantaged by the switch to privatized fishing rights. The Community Quota Program implemented in the Gulf of Alaska in 2005 was designed to provide a mechanism to redistribute wealth in two privatized-access fisheries. In this article, I explore the political history of this program and the concept of equity implicit in its formation. Drawing on ethnographic fieldwork conducted in the Kodiak Archipelago, I examine the participation possibilities and challenges experienced in three eligible fishing villages. I conclude with a discussion of the repoliticization of fisheries privatization and emerging social movements that are opening up more fertile spaces for creating n...
An Empirical Test of the Mg II λ1240 Doublet Branching Ratio and Oscillator Strength

We empirically confirm the theoretical branching ratio and oscillator strength for the weak Mg II 3s-4p doublet at 1240 A as determined by Theodosiou & Federman. We use the independent methods of apparent optical depth analysis for the sight lines toward μ Col, γ Ara, and ρ Leo and profile component fitting for the sight line toward μ Col in order to determine the branching ratio. We find f1239/f1240 = 1.74 ± 0.06, in agreement with the theoretical value of 1.78 ± 0.03. Profile fitting for the line of sight toward μ Col gives an f-value for the doublet of 9.71 ± 0.32 × 10-4, which agrees with both the theoretical value of Theodosiou & Federman and the empirical value of Fitzpatrick.
Upper Respiratory Tract Infections in Young Children: Duration of and Frequency of Complications

This study was performed to determine the usual duration of community-acquired viral upper respiratory tract infections and the incidence of complications (otitis media/sinusitis) of these respiratory tract infections in infancy and early childhood. Children in various forms of child-care arrangements (home care, group care, and day care) were enrolled at birth and observed for 3 years. Families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval. Only children remaining in their original child-care group for the entire study period were compared. The mean duration of an upper respiratory tract infection varied between 6.6 days (for 1- to 2-year-old children in home care) and 8.9 days (for children younger than 1 year in day care). The percentage of apparently simple upper respiratory tract infections that lasted more than 15 days ranged from 6.5% (for 1- to 3-year-old children in home care) to 13.1% (for 2- to 3-year-old children in day care). Children in day care were more likely than children in home care to have protracted respiratory symptoms. Of 2741 respiratory tract infections recorded for the 3-year period, 801 (29.2%) were complicated by otitis media. During the first 2 years of life, children in any type of day care were more likely than children in home care to have otitis media as a complication of upper respiratory tract infection. In year 3, the risk of otitis media was similar in all types of child care.
The Behavior of a Stratified Sea

As discussed at some length in Chapter 1, an important factor in the pressure distribution within a shallow sea is the stratification of the water column. Whether over continental shelves or in enclosed basins, the temperature and salinity distribution gives rise to density differences of the order of 1‰. The lighter water generally overlies heavier layers, but the surfaces of constant density are only approximately horizontal. Figure 3.1 shows an observed distribution of temperature in a cross section of Lake Michigan, which in a freshwater lake is also a direct indication of density, with the vertical scale exaggerated by a factor of about 3000. The density of the top layers compared to those at the bottom (18 °C versus 4 °C in freshwater) was about 1.4‰ on this occasion. Most of the density change is seen to take place in a relatively thin layer, the thermocline, between about the 5° and 15 °C isotherms.
Changing Philosophies of Fisheries Management as Illustrated by the History of Fishing Regulations in Wyoming

Inland fisheries management began in the United States in the 1800s with a focus on fish as food and the use of stocking to create new fisheries and replenish depleted stocks. In the early 20th century, recreational fishing came to the forefront and regulations limiting the number and size of fish that could be harvested were enacted. Major trends in the regulation of recreational fisheries included a reduction in creel limits, more complexity in the application of regulations, increasingly restrictive use of baitfish, and limitations on competitive fishing tournaments. In the latter part of the 20th century, fisheries managers embraced a broader perspective that included conservation of native species and control of invasive species. These changes in regulations reflect the evolution of fisheries management philosophy along pathways emphasizing fishing for sustenance, fishing for recreation, and, most recently, biodiversity management. This evolution is illustrated by the history of angling regulations i...
The Effect of Thermal History on the Structure of Chemically and Vapor Deposited Silver Films on Glass

The observation1 of silver agglomeration in second surface mirrors used for solar applications has emphasized consideration of the effect of thermal history on the optical properties of mirrors. Thermal history effects may arise from the processing of mirrors, the application of protective coatings, or from outdoor exposure. Mirrors may be subject to elevated temperatures (T≤400°C) for short periods of time, or to low temperatures (T≤60°C) for long (≤30 years) periods of time. Although a significant amount of work has been done on thermally driven agglomeration of silver films,2–7 most of these studies have been restricted to vapor deposited films on vitreous silica. Large area reflectors, such as those used in heliostats, will almost certainly be deposited by commercial chemical methods on substrates of soda-lime-silicate or other glasses which differ considerably from vitreous silica in composition and properties. The present study addresses the effect of this change in deposition technique and substrate on silver agglomeration. These problems were studied by optical and scanning electron microscopy, refleetometry, and x-ray diffraction. The results indicate that both the method used to deposit the silver and the type of glass affect the agglomeration process and the character of the reflective film.
An oncology nurses' guide to new targeted agents for metastatic colorectal cancer.

Background Colorectal cancer (CRC) that has metastasized before being discovered, or reoccurs following surgery, remains a major treatment challenge. Trials have established the usefulness of antiangiogenic agents and new regimens in prolonging survival in patients with advanced disease. In the United States, the antiangiogenic agents approved for treating metastatic CRC often are combined with traditional chemotherapeutic agents and include bevacizumab (Avastin®), ziv-aflibercept (Zaltrap®), and regorafenib (Stivarga®). Objectives This article reviews factors that guide the development of a nursing plan for monitoring and managing patients who are receiving antiangiogenic therapies. Methods Regorafenib and ziv-aflibercept, two newer agents that nurses and other healthcare professionals may have had less experience with, were reviewed. Findings The key to maximizing the potential benefit of these agents is understanding where these new therapies fit in the overall scheme of treatment options and how to help patients tolerate treatment.
"Don't get burned": The role of nuclear medicine in the burn unit

1243 Learning Objectives We discuss the role of nuclear medicine and three phase bone scan in the evaluation of the patient admitted to the hospital burn unit. In a pictorial poster review, we will demonstrate the nuclear medicine evaluation of various burn injuries which include thermal injuries, electrical burns and frostbite. We will also discuss the nuclear medicine evaluation of other injuries admitted to the burn unit which includes the evaluation of purpura fulminans. Due to the widespread number of burns, health care professionals must appreciate the physiologic and pathologic effects as it applies to burn care, and the role of nuclear medicine in the evaluation of these patients. Burns may be associated with greater degrees of deep tissue injury than is appreciated and it may be difficult to identify the extent of deep tissue damage for debridement. Clinical examination alone can underestimate the extent of tissue damage. In a pictorial poster review, we demonstrate the role of the 3 phase bone scan in assisting the surgeon in the evaluation of muscle necrosis and viability, and its role in the treatment decision making process.
Revisiting Preadolescent Cardiomyocyte Proliferation in Mice.

No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice Alkass et al Cell . 2015;163:1026–1036. Understanding cardiomyocyte cell cycle regulation after birth is key to optimizing regenerative strategies for the heart post injury, yet poses multiple technical challenges, as evidenced by recent studies that have arrived at divergent conclusions. In a recent publication in Cell , Alkass et al undertook multiple approaches to examine cardiomyocyte cell cycle regulation in the first 3 weeks after birth. Here, we summarize results of Alkass et al and 3 other groups in examining preadolescent cardiomyocyte cell cycle regulation, highlighting the distinct approaches and incumbent caveats . Understanding cardiomyocyte cell cycle activity during the perinatal and preadolescent period is extremely challenging and is a subject of intense debate. From a classical viewpoint, throughout embryonic development, cardiomyocytes progressively lose their ability to divide and proliferate. After the period between postnatal day 5 (P5) and 10 (P10), the second and final wave of nonreplicative DNA synthesis ends with binucleation of existing cardiomyocytes.1 Recently, Naqvi et al proposed that cardiomyocytes undergo an additional burst of synchronized proliferation on postnatal day 15 (P15) that results in a 40% increase in the number of cardiomyocytes.2 However, in a recent study, Alkass et al observed that an increase in cardiomyocyte number after birth is largely restricted to the first postnatal week, with no significant increase in number after postnatal day 11.3 Consistent with Alkass et al, 2 other groups were not able to substantiate a proliferative burst of cardiomyocytes during preadolescence between the second and third postnatal weeks.4,5 Interestingly, Alkass et al observed a peak of polyploidization of binucleated cardiomyocytes between the second and third postnatal weeks, introducing further complexity to the model of cardiomyocyte cell …
Symposium on “the Life Cycle in Insects”

In a discussion of the life cycles of insects it is logical to begin with Apterygota because their type of life cycle is the simplest, as it involves no metamorphosis. Though Thysanura and Collembola undergo no changes that are sufficiently striking to constitute a metamorphosis, they nevertheless exhibit in their postembryonic development various minor changes of structure and coloration.
Contributions of Plant Pest Control Programs The Need For Pest Detection Followups

An effective domestic insect detection program should step up the discovery incidence of the insect pests new to this country. Thereafter, those who are responsible must be alert to properly identify them and evaluate their economic importance. All entomologists must be mindful of the continuing threat of new insect introductions and cooperatively assume some of the responsibility in order to cope with the problems that may arise in the 60's.
Characterization of filter performance under low-pressure operation

ABSTRACTParticulate gas filters are a critical element in the purification systems used to ensure defect-free manufacturing in semiconductor industry. In atomic layer deposition (ALD) processes, these filters are typically operated under sub-atmospheric pressure conditions, but their filtration characteristics are, often, only known at atmospheric pressure. In this study, performance of a metal filter that is typically used in low-pressure ALD precursor delivery systems is studied experimentally and theoretically down to 4.5 kPa. The experimental procedure was designed to minimize the presence of multiply charged particles in the test aerosol for different operating pressures and flowrates. The experimental results suggest that most penetrating particle size only slightly varies with pressure, but the shape of the penetration curve and the maximum value of the penetration changes significantly with pressure. The experimental data are used to test predictions of filter performance at low pressures made usi...
This “Ethical Trap” Is for Roboticists, Not Robots: On the Issue of Artificial Agent Ethical Decision-Making

In this paper we address the question of when a researcher is justified in describing his or her artificial agent as demonstrating ethical decision-making. The paper is motivated by the amount of research being done that attempts to imbue artificial agents with expertise in ethical decision-making. It seems clear that computing systems make decisions, in that they make choices between different options; and there is scholarship in philosophy that addresses the distinction between ethical decision-making and general decision-making. Essentially, the qualitative difference between ethical decisions and general decisions is that ethical decisions must be part of the process of developing ethical expertise within an agent. We use this distinction in examining publicity surrounding a particular experiment in which a simulated robot attempted to safeguard simulated humans from falling into a hole. We conclude that any suggestions that this simulated robot was making ethical decisions were misleading.
Multi-stream Recognition of Noisy Speech with Performance Monitoring

A prototype multi-stream system with a performance monitor for stream selection is proposed to recognize speech in unknown noise. The speech signal is decomposed into seven band-limited streams. Posterior probabilities of phonemes are estimated by a multi-layer perceptron (MLP) in each of these band-limited streams. Estimated posterior vectors of all 127 combinations (processing streams) of the seven band-limited streams form inputs to a second-stage MLP that estimates posterior probabilities of phonemes in each processing stream. A performance monitor is designed to predict the reliability of individual processing streams based on the outputs from these streams. The top N streams that are least affected by noise are selected and their outputs are averaged to yield the final posterior probability vector used in Viterbi search for the best phoneme sequence. Experimental results show that the proposed technique is effective in dealing with noise.
An Answer in Search of a Problem: Genetically-Modified Crops in an Era of Climate Change

This chapter will address two specific narratives about genetically modified organisms in an era of changing climate—the putative role for genetically-engineered crops in adaptation to climate change, and the putative role for genetic engineering as a mitigation strategy to reduce the climate change trajectory. After a brief introduction to the technology itself, this chapter will take up each set of claims in turn, and will examine how genetically-engineered crops might, or might not, be part of a climate change solution.
Correction of esophageal atresia with distal tracheoesophageal fistula

Correction of the full spectrum of esophageal atresia with tracheoesophageal fistula (TEF) remains controversial. Circular myotomy and other lengthening procedures have shown promise to reduce tension when a relatively wide gap exists between esophageal segments; nevertheless a relatively high complication rate persists. We believe anastomotic tension is commonly found with repair of this anomaly. Therefore, the construction of the anastomosis will be a primary determinant of success. Twenty-four infants with TEF were admitted, 12 (50%) weighing 2.5 kg, nine (37%) 1.8 to 2.5 kg, and three (13%) 1.8 kg. All underwent gastrostomy and end-to-end single-layer anastomosis. Gaps of up to 4.5 cm were encountered, and in one case a cervical incision was necessary for mobilization of the upper pouch. For eight patients (33%) the gap was at least 2.5 cm and significant anastomotic tension was generated. For the series, there were no anastomotic leaks (all confirmed by barium swallow), reoperations, or surgical complications (there were two late, unrelated deaths). Prophylactic dilation was routinely performed 6 weeks and 3 months postoperatively. Subsequently, seven of the 24 (29%) required additional (one to five) dilatations but are now asymptomatic at least 2 years later. Follow-up for the entire series is 5 months to 5 years. Three infants (13%) required fundoplication for reflux without stricture and two infants (8%) an aortopexy. For successful esophageal anastomosis we consider the following technical points important: (1) no-touch technique to minimize tissue damage, (2) generous (5 to 7 mm) full-thickness suture depth, (3) fine (6/0) monofilament suture to reduce tissue reactivity, and (4) in cases of significant tension, the sutures are preplaced and used to provide traction to eliminate tension during tying. Tension is often unavoidable in TEF, yet a carefully constructed anastomosis will withstand this stress. This approach provides results at least as satisfactory as the reported experience with a variety of techniques.
Phytoplankton Photosynthesis in the Atlantic Ocean as Measured from a Submersible Pump and Probe Fluorometer in Situ

Photosynthesis by phytoplankton in the sea accounts for 40 to 50% of the total global primary productivity. The assessment of photochemical activity from variable fluorescence has conceptually increased the potential for the measurement of photosynthesis under natural conditions. Pulsed light fluorometers (1,2) or pump and probe fluorometers (3,4) can measure photochemical and non-photochemical quenching under ambient light. We report here on measurements of variable fluorescence yields made in real-time, in situ, under ambient irradiance in the northwest Atlantic Ocean. Using a submersible pump and probe fluorometer, we measured the relative absorption cross sections of PS II, the kinetics of electron transport, and components which contribute to changes in variable fluorescence in natural phytoplankton communities. From these measurements we calculated ongoing photosynthetic rates and compared the results with concurrently measured photosynthetic rates based on radiocarbon labeling.
Safety of L-tryptophan for pigs.

Epidemic eosinophilia-myalgia syndrome (EMS) associated with excess L-tryptophan (Trp) consumption in humans has been declared a major public health problem. The EMS problem has not been observed in pigs, nor has comprehensive pathology associated with EMS in humans been described. Experiments were therefore conducted to evaluate the pathology and effects of excess dietary L-Trp for finishing (79 to 119 kg) pigs and to determine an LD50 of Trp for pigs. In Exp. 1, addition of .1 or 1% Trp to corn-soybean meal diets had no effect on growth performance or leukocyte and relative eosinophil counts or on plasma aspartate transferase, creatine phosphokinase, and lactate dehydrogenase activities. Likewise, untoward pathological effects of Trp feeding were not observed in the animals under study. In Exp. 2, supplementing the basal diet with 0, 2, and 4% Trp caused linear (P less than .05) decreases in weight gain, feed intake, and gain:feed ratio. Mortality could not be produced by acute oral dosing in the LD50 study (Exp. 3), wherein Trp doses between 2.00 and 5.71 g/kg of BW were administered by stomach tube. Vomiting occurred at oral doses greater than 5.71 g/kg of BW. These results suggest that oral ingestion of Trp in pigs is safe and that pigs can tolerate considerable excesses of Trp.
MIMO capacity calculation and fading estimation for indoor/outdoor wireless communication environments

This paper reports on simulation results for the MIMO capacity and fading characteristics for indoor/outdoor propagation environments. The finite-difference time-domain (FDTD) method is used for the calculation of the reflection and transmission characteristics through windows and metal-framed structures and the obtained diffraction-type effects were then represented by an equivalent ray-tracing model. An integrated ray tracing code that accounts for these effects is then used to calculate MIMO capacity and Rician K-factor. The obtained results are then compared with those based on available data for Gaussian channels. In related preliminary results, it is shown that for an indoor environment with realistic walls of complex structures, the MIMO capacity and the K values are very different from those calculated based on simplified wall structures.
330. Genetic Modification To Achieve Targeting of Adenoviral Vectors To Malignant Cells of Lymphocyte Origin

Hematologic malignancies comprise tumors that affect three related cellular compartments; blood, bone marrow and lymphatics Gene therapy is an outstanding approach to treat hematological malignancies as the molecular basis of these disorders is increasingly understood. Therapeutic genes are available and alternative therapies are often lacking efficiency however, the, systemic nature of hematologic malignancies requires selective tumor targeting. Recombinant Adenoviral (Ad) vectors derived from human serotype 2 and 5, are currently, the most common vehicle for efficient in vivo transgene delivery and account for 23.8% of nearly 1700 clinical trials that were conducted by using both viral and non-viral vectors. Initial binding of virus fiber knob to the cell surface coxsackie-adenovirus receptor (CAR) followed by secondary binding with avb3/5 integrins on the cell surface are the prerequisites for successful viral internalization to the target cell. However, several studies have shown that cells of lymphocyte origin (B cell, T cell, NK cells etc.) are poorly infected by adenovirus due to the paucity of both CAR and integrins. Hence, retargeted adenovirus must be developed that will bypass both CAR and integrin requirements. Our goal is to explore mechanisms to target lymphocytes at the level of transduction (or infection). Transductional targeting provides improved gene transfer into cancerous cell and spares normal cells. This is typically accomplished through surface modification of the gene delivery vehicle to enhance specific interactions with cancer cell membrane proteins. We hypothesize that, transductional targeting of adenovirus by utilizing anti-Interleukin-2-receptor (IL-2R) antibody to target cell surface Il-2R will allow us to conduct CAR and integrin independent cell specific targeting of adenovirus to malignant lymphocytes. To accomplish this goal, the sequences of canine, human and murine IL-2 and IL-2R were compared to each other. This data shows that human and canine IL-2 and IL-2R may cross react whereas murine IL-2 has diverged significantly. Based on these results, canine IL-2 and IL-2R were cloned, followed by sub-cloning these constructs, along with the ectodomain of IL-2R (Ecto-IL-2R), into eukaryotic expression vectors. Antibody constructs will be generated by immunizing with Ecto-IL-2R. The DNA encoding these antibodies will be cloned and inserted into the adenoviral fiber gene to allow knob-scIL-2RAb fusion proteins to be produced.
167. Genome Editing to Generate the First Mouse Model of Alpha-One Antitrypsin Deficiency, the Leading Cause of Genetic COPD

Alpha-one antitrypsin (AAT) deficiency is a common autosomal co-dominant genetic disorder. This condition affects 1:2500 individuals of European ancestry, leading to the development of lung and liver disease. Within North American and Northern European populations, an estimated 4% of individuals are carriers of mutant alleles. AAT deficiency presents with an emphysema phenotype in the lungs of older subjects. AAT deficient subjects can also suffer from liver disease of varying severity; however, lung disease is the principle cause of death. AAT is a protease inhibitor predominantly synthesized in the liver that belongs to the serine protease inhibitor (serpin) family. Upon secretion into the blood stream, AAT enters the lungs where it inactivates excess neutrophil elastase, thereby preventing damage to the alveoli. Mutations of the Serpina1 gene can lead to reduced serum levels of AAT and decreased protein functionality, allowing for unrestricted elastin breakdown, pulmonary inflammation and eventual emphysema. Currently, an animal model simulating the lung condition does not exist, which severely limits the development of therapeutics. This is due to the higher genomic complexity of mice compared to humans. Indeed due to amplification events, C57BL/6 mice have five genes that are homologous to human SERPINA1. To address this we generated a quintuple gene knockout using CRISPR/Cas9 system via zygote microinjection. We generated three founding lines in which all 5 copies of the gene were disrupted. Mice from all three lines demonstrate absence of hepatic and circulatory AAT protein as well as a reduced capability to inactivate neutrophil elastase. We also characterized the lung phenotype in response to a lipopolysaccharide challenge, where the model recapitulated many characteristics of the human lung disease including decreased elastance and increased compliance, and lung morphometry was also affected. Genomic and transcriptomic characterization will be presented. Future work will include challenges with cigarette smoke, a well-known disease accelerator in patients. Further, the ongoing generation of a new transgenic model carrying both the quintuple disruption of the murine Serpina1 genes and a single copy of the Z variant of human SERPINA1 will bring to the field the ultimate disease model that will finally allow researchers to evaluate the effects of liver-directed gene augmentation in the presence of Z-AAT polymers.
Cav1.2 channels mediate persistent chronic stress-induced behavioral deficits that are associated with prefrontal cortex activation of the p25/Cdk5-glucocorticoid receptor pathway

Chronic stress is known to precipitate and exacerbate neuropsychiatric symptoms, and exposure to stress is particularly pathological in individuals with certain genetic predispositions. Recent genome wide association studies have identified single nucleotide polymorphisms (SNPs) in the gene CACNA1C, which codes for the Cav1.2 subunit of the L-type calcium channel (LTCC), as a common risk variant for multiple neuropsychiatric conditions. Cav1.2 channels mediate experience-dependent changes in gene expression and long-term synaptic plasticity through activation of downstream calcium signaling pathways. Previous studies have found an association between stress and altered Cav1.2 expression in the brain, however the contribution of Cav1.2 channels to chronic stress-induced behaviors, and the precise Cav1.2 signaling mechanisms activated are currently unknown. Here we report that chronic stress leads to a delayed increase in Cav1.2 expression selectively within the prefrontal cortex (PFC), but not in other stress-sensitive brain regions such as the hippocampus or amygdala. Further, we demonstrate that while Cav1.2 heterozygous (Cav1.2+/-) mice show chronic stress-induced depressive-like behavior, anxiety-like behavior, and deficits in working memory 1-2 days following stress, they are resilient to the effects of chronic stress when tested 5-7 days later. Lastly, molecular studies find a delayed upregulation of the p25/Cdk5-glucocorticoid receptor (GR) pathway in the PFC when examined 8 days post-stress that is absent in Cav1.2+/- mice. Our findings reveal a novel Cav1.2-mediated molecular mechanism associated with the persistent behavioral effects of chronic stress and provide new insight into potential Cav1.2 channel mechanisms that may contribute to CACNA1C-linked neuropsychiatric phenotypes.
The Novel Modafinil Analog, JJC8-016, as a Potential Cocaine Abuse Pharmacotherapeutic.

(±)Modafinil ((±)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (±)MOD analogs, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD were evaluated for binding across ~70 receptors, transporters, and enzymes. Although at a concentration of 10 μM, there were many hits for JJC8-016, binding affinities in the range of its DAT affinity were only observed at the serotonin transporter (SERT), dopamine D2-like, and sigma1 receptors. R-MOD was more selective, but had much lower affinity at the DAT (Ki=3 μM) than JJC8-016 (Ki=116 nM). In rats, systemic administration of R-MOD alone (10–30 mg/kg i.p.) dose-dependently increased locomotor activity and electrical brain-stimulation reward, whereas JJC8-016 (10–30 mg/kg i.p.) did not produce these effects. Strikingly, pretreatment with JJC8-016 dose-dependently inhibited cocaine-enhanced locomotion, cocaine self-administration, and cocaine-induced reinstatement of drug-seeking behavior, whereas R-MOD inhibited cocaine-induced reinstatement only at the high dose of 100 mg/kg. Notably, JJC8-016 alone neither altered extracellular dopamine in the nucleus accumbens nor maintained self-administration. It also failed to induce reinstatement of drug-seeking behavior. These findings suggest that JJC8-016 is a unique DAT inhibitor that has no cocaine-like abuse potential by itself. Moreover, pretreatment with JJC8-016 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by interfering with cocaine binding to DAT. In addition, off-target actions may also contribute to its potential therapeutic utility in the treatment of cocaine abuse.
Cooperating Context Method: A Contextual Approach to Story Generation and Telling

Oral story telling has become a lost art because social media and technology have come to dominate personal interactions. The concept of creating a computational system capable of creating, modifying and telling a story, all in real time, could be a compelling way to revive this lost art of oral storytelling. It could serve as a source of alternative entertainment for children. The stories could be decomposed into a series of end-to-end contexts faced by the characters in the story as they seek to attain their sometimes conflicting goals. Thus, contextualization of the story, and of the storytelling process, could become advantageous. With that in mind, this paper presents and evaluates a contextual approach called the Cooperating Context Method (CCM) that helps create and convey dynamic stories in real time. These stories can be easily customized by the listener, also in real time, even while the story is already being told. CCM was designed to overcome the limitations found in other contextual approaches during story generation, while still meeting the design criteria selected through an analysis of human storytellers. CCM begins by examining the current situation to create list of tasks. Through a series of algorithms, the list of tasks is narrowed down into two lists of high priority and low priority contexts while removing the irrelevant contexts. The set of context best suited to manage the tasks are selected and the contextual knowledge is utilized to solve the tasks defined. Testing of CCM revealed that it performs as it was intended.
The partially closed Griffith crack

A solution is presented for a Griffith crack subjected to an arbitrary polynomial loading function which causes one end of the crack to remain closed. Closed form expressions are presented for the crack opening length and for the stress and displacements in the plane of the crack. The special case of pure bending is presented as an example and for this case the stress intensity factor is computed.
Influence of various factors on farrowing rate on farms using early weaning

A database containing 12,110 farrowing records from 16 commercial farms was abstracted from the PigCHAMP production information system. The farms were selected based on the willingness of producers to keep records and average weaning age. The ADFI records of 10,846 of these lactating sows were also obtained. Sows weaned at 28 d after farrowing were excluded. Farrowing rate excluding sows culled for nonreproductive reasons after mating from the denominator was 85.5%. Parity, farrowing season, and the lactation length x ADFI interaction were associated with farrowing rate (P or = 6 (P or = 5.7 kg) group, no differences in farrowing rate were observed between lactation length groups. In the low ( or = 5.7 kg) alleviates the negative effects of lactation length on farrowing rate.
The Role of Hand Carried Ultrasound in Guiding Management of Challenging Heart Failure Patients

Purpose Accurate assessment of volume status and estimation of central venous pressure is critical in directing management of acute heart failure (HF) patients . We evaluated the impact of hand carried ultrasound (US) in guiding therapy for HF patients with uncertain volume status on physical examination (PE) or with worsening serum creatinine (Cr). Methods We prospectively included patients admitted to the hospital with acute HF exacerbation and had uncertain volume status or worsening Cr to undergo US-guided management between January 2017 to October 2018. HF team provided initial management plan based on standard of care (PE, symptoms and lab results), then they were provided with US estimation of intravascular volume (by assessing inferior vena cava size and respiratory variation, right and left jugular veins size, respiratory variation and compressibility). Primary outcome was percent change of initial plan after providing US results. Logistic regression was used to compare the percent change in plan by HF type. Results A total of 151 (Age 64±15,46% females, 78% white) patients were included during study duration. 47(31%) patients had HF with preserved ejection fraction (HFpEF), and 104 (69%) patients had HF with reduced ejection fraction (HFrEF). A change in plan was observed in 77.5% of the patients after using ultrasound. No difference in percent change of plan between HFrEF (81%) and HFpEF patients (70%), (OR 1.7, 95% CI: 0.73, 3.9, p= 0.2). Conclusion Ultrasound management of patients with HF and uncertain volume status or worsening Cr may significantly impact management decisions regardless of HF type, Further studies are needed to explore whether these changes improve outcomes of this population.
Novel percutaneous dual-lumen cannula-based right ventricular assist device provides effective support for refractory right ventricular failure after left ventricular assist device implantation.

Objectives Right heart failure after left ventricular assist device (LVAD) implantation is associated with significant morbidity and mortality. A new generation of percutaneous right ventricular assist devices (RVADs) may mitigate the need for invasive surgical RVAD implantation. The purpose of this study was to evaluate the safety and efficacy of the Protek Duo (TandemLife, Pittsburgh, PA, USA) RVAD in patients who developed severe acute right heart failure in the intensive care unit after LVAD implantation. Methods This was a retrospective cohort study of 27 patients who received a Protek Duo after LVAD implantation from January 2016 to March 2019 at our centre. The primary outcome of interest was survival to hospital discharge. Secondary outcomes included procedural success, device-related complications and conversion to a surgical RVAD. Results The median age of patients was 63 years (interquartile range 58-71), 78% were men and 78% were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2. Patients were on a median of 2 inotropes and 2 pressors prior to Protek Duo insertion. The device successfully implanted on the first attempt in all patients a median of 1 day (interquartile range 1-2) after LVAD implantation and the median duration of support was 11 days (interquartile range 7-16). Device weaning occurred in 86% of patients, with 15% in-hospital mortality. Major complications related to the device included new moderate-to-severe tricuspid regurgitation (36%), haemolysis (14%) and cannula migration (7%). Three patients (11%) required conversion to surgical RVAD. Overall survival to 1 year was 81%. Conclusions The use of the Protek Duo as a percutaneous RVAD is a safe and feasible treatment for patients who develop acute right heart failure after LVAD implantation.
Equilibria in Doodle polls under three tie-breaking rules

Abstract Doodle polls allow people to schedule meetings or events based on time preferences of participants. Each participant indicates on a web-based poll form which time slots they find acceptable and a time slot with the most votes is chosen. This is a social choice mechanism known as approval voting, in which a standard assumption is that all voters vote sincerely—no one votes “no” on a time slot they prefer to a time slot they have voted “yes” on. We take a game-theoretic approach to understanding what happens in approval voting assuming participants vote sincerely. While our instances are framed in the context of the Doodle poll application, the results apply more broadly to approval voting. First we characterize Doodle poll instances where sincere pure Nash Equilibria (NE) exist, under lexicographic tie-breaking, random candidate, and random voter tie-breaking. We then study the quality of such NE voting profiles in Doodle polls, showing the price of anarchy and price of stability are both unbounded, even when a time slot that many participants vote yes for is selected. Finally, we find some reasonable conditions under which the quality of the NE (and strong NE) is good.
A serious gaming framework for decision support on hydrological hazards

With increasing population and human intervention on the natural environment, hazards are a growing threat, coming in many forms, including floods, droughts, soil erosion, and water pollution. A key approach to mitigate hydrological disaster risk at the community level is informed planning with decision support systems. The literature shows emerging efforts on multi-hazard decision support systems for hydrological disasters and demonstrates the need for an engaging, accessible, and collaborative serious game environment facilitating the relationship between the environment and communities. In this study, a web-based decision support tool (DST) was developed for hydrological multi-hazard analysis while employing gamification techniques to introduce a competitive element. The serious gaming environment provides functionalities for intuitive management, visualization, and analysis of geospatial, hydrological, and economic data to help stakeholders in the decision-making process regarding hydrological hazard preparedness and response. Major contributions of the presented DST include involving the community in environmental decision making by reducing the technical complexity required for analysis, increasing community awareness for the environmental and socio-economic consequences of hydrological hazards, and allowing stakeholders to discover and discuss potential trade-offs to hazardous scenarios considering the limitations in budget, regulations, and technicality. The paper describes the software design approaches and system architecture applied for a modular, secure, and scalable software as well as the framework's intuitive web-based user interfaces for real-time and collaborative data analysis and damage assessment. Finally, a case study was conducted to demonstrate the usability of DST in a formal setting and to measure user satisfaction with surveys.
Do Children and Adults Take Social Relationship Into Account When Evaluating People's Actions?

Two studies examined whether children (5- and 6-year-olds; 8- and 9-year-olds, n = 214) and adults (n = 72) consider social relationship when evaluating unhelpful or helpful actions. Participants learned about a person-in-need who was (or was not) helped by someone they knew (a friend) and someone they did not know (a stranger). Older children and adults judged an unhelpful friend as meaner than an unhelpful stranger, and judged a helpful stranger as nicer than a helpful friend. Younger children did not judge an unhelpful friend as any meaner than an unhelpful stranger, and they judged a helpful friend as nicer than a helpful stranger. These findings suggest that a mature appreciation of how social relationship matters for evaluation emerges relatively late in development.
Transscleral Cyclophotocoagulation for Glaucoma in the Setting of Uveal Melanoma.

Abstract This case series describes 4 eyes with refractory glaucoma in the setting of uveal melanoma. Transscleral cyclophotocoagulation led to intraocular pressure lowering and there was no evidence of tumor disturbance or extravasation from the eye.
Human-in-the-Loop AI for Analysis of Free Response Facial Expression Label Sets

Facial expressions (FEs) communicate a rich variety of social, grammatical, and affective signals. However, the most generally accepted set of recognizable FEs remains limited to seven basic displays of emotion: happiness, sadness, fear, anger, disgust, surprise and contempt. To develop intelligent virtual agents capable of interpreting and synthesizing nuanced facial behavior, we need a more complete lexicon. One roadblock has been the limiting nature of forced-choice study designs, the most common paradigm for investigating observer judgements of FEs. However, there has been no consensus on an objective way to evaluate alternative free response designs. We present a human-in-the-loop artificial intelligence pipeline for analyzing sets of freely chosen natural language labels. The pipeline, FreeRes-NLP, makes it possible to automatically identify whether there is consensus on the signal value of an FE and which label best classifies it. FreeRes-NLP scales to process very large datasets. We validate our approach in two stages: 1) comparison between label synonymy scores from ten computer algorithms and human raters across three synonym datasets, and 2) examples of pipeline results compared with manual data processing results from emotion and FE recognition studies. The pipeline can potentially improve automated facial expression recognition and procedural modeling of virtual humans.