cssi/SciSciGPT-SciSciNet huggingface dataset:
Activity of Rituximab and Ofatumumab Against Mantle Cell Lymphoma (MCL) in Vitro in MCL Cell Lines and Ex Vivo in Tumor Cells Derived From Patient Tumor Samples

Abstract Abstract 4972 Mantle cell lymphoma (MCL) is an aggressive form of non-Hodgkin lymphoma (NHL) that frequently presents with advanced stage disease. The addition of rituximab, a monoclonal anti-CD20 antibody, to high dose chemotherapy regimens often followed by stem cell transplant has improved outcomes, but survival still remains low at 3–5 years. Novel agents are needed to improve outcomes in MCL. Ofatumumab is a fully human anti-CD20 monoclonal antibody directed against a novel epitope on the CD20 antigen. Ofatumumab has been shown to be more potent than rituximab against B-NHL cells in pre-clinical investigations. Ofatumumab is FDA approved for the treatment of CLL that is fludarabine and alemtuzumab refractory or with bulky disease resistant to fludarabine and is being investigated in clinical trials in NHL. In order to characterize the activity of ofatumumab against MCL, we performed pre-clinical investigations into the activity of ofatumumab against MCL cell lines and primary MCL tumor cells derived from patient tumor samples (n=2). Antibody-dependant cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) assays were performed in the MCL cell lines Mino, Jeko, Rec-1 and Z-138 to demonstrate sensitivity to rituximab and ofatumumab. Lymphoma cells were labeled with 51Cr prior to incubation with rituximab or ofatumumab at 10ug/mL plus human serum or effector cells (efector:target ratio of 20:1). 51Cr-release was measured and the percentage of lysis was calculated. Patient tumor cells were isolated from tumor biopsy samples by MACS sorting (negative selection). Patient tumor cells were incubated with ofatumumab or rituximab at 10ug/mL in the presence of human serum as a complement source. Cell viability was determined at 48 hours by CellTiterGlo assay. Means were compared using a t-test. Expression of CD20 and the complement inhibitory proteins (CIPs) CD55 and CD59 in MCL cell lines were determined by flow cytometry and compared to the rituximab-sensitive cell line Raji and the rituximab-resistant cell line Raji 4RH. Surface density of CD20, CD55 and CD59 were determined by Imagestream analysis. Western blot was performed to measure total CD20 protein expression. Ofatumumab induced significantly higher levels of cell lysis compared to rituximab in CDC assays of all MCL cell lines tested (Mino: 65.9% vs 0.5%; JeKo 43.9% vs 13.3%; REC-1 25.4% vs 4.7%; Z-138: 56.4% vs 0.65%; all p-values Disclosures: Czuczman: Genmab: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding. Hernandez-Ilizaliturri: Genmab: Research Funding.
Effects of Specific Foods and Dietary Components on Drug Metabolism

Describe the major dietary components known to alter drug metabolism. Indicate the magnitude of changes in drug metabolism that can be induced by drugs. Understand why diet–drug interactions are difficult to recognize in patients and have been studied mostly in healthy subjects and laboratory animals.
Epidemiology of tsetse flies and trypanosomes with a case study in Ethiopia

The aim of this study was to quantify the abundance of tsetse ies using traditional traps and using anti-tsetse saliva ELISA test and the trypanosome infection prevalence in the tsetse ies and cattle. An area-wide tsetse fly and cattle trypanosomosis survey was conducted in Ethiopia. Groups of mice and pigs were experimentally exposed to G. m. morsitans bite to develop total saliva and rTsal ELISA tests that are capable to detect and monitor the induced anti-saliva antibodies of tsetse following host exposure to tsetse bite. A meta-analysis was conducted on prevalence of trypanosome infection in tsetse flies in the field or in laboratory-controlled conditions. Published information available since 1950s was reviewed. The findings indicated that tsetse ies and trypanosome infections of cattle are widely distributed in Ethiopia and their abundance is affected by spatial factors such as altitude, river drainage system, local factors at PA level (presence of game reserves and land use/encroachment). There was no significant association between tsetse density and prevalence of trypanosomes in cattle. Total tsetse saliva and recombinant Tsal1 protein coated indirect ELISA are sensitive immunological probes to detect contact with tsetse flies. The new serological test at hand is a sensitive indicator that can differentiate regimens of tsetse y bites (various degree of exposure of animals) and that can also detect tsetse fly bite after a prolonged period without exposure. The overall prevalence of trypanosome infection in tsetse fly populations was 10.3% and 31.0% for the eld survey data and laboratory experiment data, respectively. Both spatial (country) and temporal (year of pub- lication) variation are noticed in trypanosome infection prevalence of eld collected tsetse flies. The lack of association between tsetse density and prevalence of trypanosomes in cattle needs further investigation on the role of Tabanus and Stomoxys for mechanical trypanosome transmission. Due to the ongoing interventions, the vector could decline to a low level beyond the fly catching capacity by traps. The current serological ELISA test could be an important surveil- lance tool with sensitive diagnostic value. Key words: cattle trypanosomosis, tsetse fly abundance, tsetse infections, tsetse monitoring tools
Ethanol confers differential protection against generalist and specialist parasitoids of Drosophila melanogaster

As parasites coevolve with their hosts, they can evolve counter-defenses that render host immune responses ineffective. These counter-defenses are more likely to evolve in specialist parasites than generalist parasites; the latter face variable selection pressures between the different hosts they infect. Natural populations of the fruit fly Drosophila melanogaster are commonly threatened by endoparasitoid wasps in the genus Leptopilina, including the specialist L. boulardi and the generalist L. heterotoma, and both wasp species can incapacitate the cellular immune response of D. melanogaster larvae. Given that ethanol tolerance is high in D. melanogaster and stronger in the specialist wasp than the generalist, we tested whether fly larvae could use ethanol as an anti-parasite defense and whether its effectiveness would differ against the two wasp species. We found that fly larvae benefited from eating ethanol-containing food during exposure to L. heterotoma; we observed a two-fold decrease in parasitization intensity and a 24-fold increase in fly survival to adulthood. Although host ethanol consumption did not affect L. boulardi parasitization rates or intensities, it led to a modest increase in fly survival. Thus, ethanol conferred stronger protection against the generalist wasp than the specialist. We tested whether fly larvae can self-medicate by seeking ethanol-containing food after being attacked by wasps, but found no support for this hypothesis. We also allowed female flies to choose between control and ethanol-containing oviposition sites in the presence vs. absence of wasps and generally found significant preferences for ethanol regardless of wasp presence. Overall, our results suggest that D. melanogaster larvae obtain protection from certain parasitoid wasp species through their mothers’ innate oviposition preferences for ethanol-containing food sources.
Orthotic Device Research

Orthoses are assistive devices that support joints through alignment, stabilization, or assisting weakened musculature. The cost associated with orthotic treatment is substantial, and the demand is outpacing the supply. Patient comfort and performance are influenced by orthosis fit (size or shape) as well as function (mechanical aspects). To achieve optimal performance outcomes, an orthosis must be customized to the individual patient. However, traditional fabrication methods do not readily support the objective prescription and manufacture of orthosis mechanical aspects. There is a need for processes that promote better patient outcomes. Here, we seek to identify promising approaches, contemporary methods, and existing gaps that may provide enhanced benefit and value to the orthotic user. This chapter examines the current state of patient care practices as well as cutting-edge research and technologies primarily associated with ankle-foot orthoses.
PyDREAM: high-dimensional parameter inference for biological models in python.

Author(s): Shockley, Erin M; Vrugt, Jasper A; Lopez, Carlos F | Abstract: Summary:Biological models contain many parameters whose values are difficult to measure directly via experimentation and therefore require calibration against experimental data. Markov chain Monte Carlo (MCMC) methods are suitable to estimate multivariate posterior model parameter distributions, but these methods may exhibit slow or premature convergence in high-dimensional search spaces. Here, we present PyDREAM, a Python implementation of the (Multiple-Try) Differential Evolution Adaptive Metropolis [DREAM(ZS)] algorithm developed by Vrugt and ter Braak (2008) and Laloy and Vrugt (2012). PyDREAM achieves excellent performance for complex, parameter-rich models and takes full advantage of distributed computing resources, facilitating parameter inference and uncertainty estimation of CPU-intensive biological models. Availability and implementation:PyDREAM is freely available under the GNU GPLv3 license from the Lopez lab GitHub repository at http://github.com/LoLab-VU/PyDREAM. Contact:c.lopez@vanderbilt.edu. Supplementary information:Supplementary data are available at Bioinformatics online.
Are consumers willing to go the extra mile for fair trade products made in a developing country? A comparison with made in USA products at different prices

Abstract We investigated whether fair trade messages (fair labor/environment-friendly production) can counterbalance the negative country of origin effect on brand evaluations and increase willingness to pay premium prices. Our findings suggest that fair trade messages led consumers to evaluate a product made in a developing country as favorably as a product made in the U.S. While brand attitude and brand trust were higher for a fair trade product made in a developing country, consumers hesitated to buy a product with a fair trade message when the premium price was 15% higher than the base price product with no fair trade message. We discussed implications of these findings.
Identification of drought-induced genes in giant leucaena ( Leucaena leucocephala subsp. glabrata )

A number of drought-induced genes have been identified from giant leucaena. Leucaena leucocephala subspecies glabrata (leucaena), which is also known as ‘giant leucaena’, is a multipurpose tree legume that can be grown and maintained as a woody tree for wood and paper pulp production, or as a shrubby legume through repeated harvest of foliage for use as a fodder. Leucaena is naturally resistant to most biotic and abiotic stresses including drought. The objective of this research was to identify drought-responsive genes in leucaena seedlings through microarray and qRT-PCR analyses. Ten thousand cDNA sequences selected from a leucaena transcriptome were screened for higher expression in a 4 × 180 k microarray using RNA isolated from drought-treated and untreated leucaena seedlings. Microarray analysis identified 73 and 39 drought-responsive genes sequences that were upregulated in the root and shoot, respectively. qRT-PCR analyses confirmed the root- and shoot-specific upregulation of some of the most highly expressed gene sequences identified in the microarray analysis. The proteins encoded by these genes could be grouped into four classes: (1) receptors that sense osmotic and oxidative stresses, (2) transcription factors, (3) degradation pathway enzymes, and (4) biosynthetic enzymes and structural proteins. The functions of these four classes of proteins can be used to explain the drought response in leucaena. The NB-LRR class of disease-resistance proteins may serve as receptors for detecting osmotic and oxidative stresses induced by drought, leading to induction of transcription factors such as zinc finger CCCH domain-containing protein and TCP14. As result, the genes for some degradative pathway enzymes, such as GDSL esterase/lipase, lipid acyl hydrolase patatin, and serine carboxypeptidase, were induced. Similarly, the expression of certain biosynthetic enzymes and structural proteins such as flavonoid 3-O-galactosyl transferase, caffeoyl-CoA O-methyltransferase, 9-cis-epoxy carotenoid dioxygenase, β-amyrin synthase, pentatricopeptide-containing protein, GPI-anchored protein COBRA, and peroxin, were also induced. High expression of some of these drought-inducible genes in leucaena seedlings may be used as a selection criterion in future breeding programs for drought resistance in leucaena and other legumes.
Gore, Al. (1992). Earth in the Balance: Ecology and the Human Spirit

(1993). Gore, Al. (1992). Earth in the Balance: Ecology and the Human Spirit. Journal of Leisure Research: Vol. 25, No. 2, pp. 218-220.
Opioid Use following Outpatient Breast Surgery: Are Physicians Part of the Problem?

Background The increasing rate of opioid abuse warrants standardization of postoperative pain management. The purpose of this study was to analyze the use of opioids in pain control and patient satisfaction following ambulatory breast surgery. Methods This was a prospective study of a consecutive series of patients undergoing secondary breast reconstruction (n = 60) or breast reduction (n = 35). All patients were given a pain questionnaire preoperatively. Postoperatively, women received 30 tablets of oxycodone 5.0 mg/acetaminophen 325 mg. Patients were contacted three times: postoperative days 3 to 5, 8 to 10, and 30 or higher. All patients were queried on narcotic use, pain level (0 to 10), and satisfaction with pain control. Patients with allergies or taking narcotics preoperatively were excluded. Results Most in the secondary breast reconstruction group (61.5 percent) had stopped taking opioids by postoperative day 5. Patients consumed a mean of 11.4 tablets following secondary breast reconstruction and a mean of 17.5 tablets after breast reduction. A majority reported feeling satisfied with their pain management. At postoperative day greater than 30, most experienced very mild pain, with an improvement of 3.74 points following breast reduction. There were 18.6 and 12.5 tablets per patient left over for secondary breast reconstruction and breast reduction, respectively. A total of 1551 unused tablets were left over for the entire cohort at postoperative day greater than 30. There was no significant difference in average pain scores or interference with enjoyment or activity between those who did or did not take pain medication. Conclusions This commonly prescribed pain regimen provides adequate pain relief and satisfaction for breast surgery, with a substantial number of leftover tablets. Physicians as prescribers should be aware of discrepancies. Prescription of 30 opioid tablets after outpatient breast surgery appears unnecessary and excessive. Clinical question/level of evidence Therapeutic, IV.
Decompositions of Solvent Response Functions in Ionic Liquids: A Direct Comparison of Equilibrium and Nonequilibrium Methodologies.

Time-dependent Stokes shift (TDSS) measurements provide crucial insights into the dynamics of liquids. The interpretation of TDSS measurements is often aided by molecular dynamics simulations, where solvent response functions are computed either with an equilibrium or nonequilibrium approach. In the nonequilibrium approach, the solvent is at equilibrium with the ground electronic state of the solute and its charge distribution is instantaneously changed to that of the first excited state. The solvation response function is then calculated as a nonequilibrium average of the subsequent evolution of the solvent influence on the electronic energy gap. In the equilibrium approach, the normalized time correlation function of the fluctuations of the solvent-perturbed electronic energy gap is calculated. If the linear response approximation is valid, then the nonequilibrium solvation response function is identical to the equilibrium time correlation function. The nonequilibrium methodology conceptually mimics the...
A Neo-Piagetian Approach to Object Relations

Terry is fifteen years old. She is admitted to the psychiatric ward of a general hospital by her mother, who can no longer deal with her. She is a chronic truant, will obey none of her mother’s rules, steals money. According to Terry her mother is “stern”, “stubborn”, “nagging”, “unwilling to compromise”, and “headstrong”. Terry experiences her mother, and a lot of other people, as “trying to invade my life”. Terry worries that she is “going to have to submerge my personality”. She feels that she is “no longer whole”. “I feel like others are being woven into me.”
Chapter 13 – Victor Frankl

Viktor Frankl’s name is clearly associated with the will to meaning. He believed that, within people’s unconscious, there is a noӧlogical dimension of transcendence. It is the responsibility of every person to discover their personal ultimate meaning of life. Frankl highlights that the Greek root of the term logotherapy connotes not only the will or search for meaning, but also suffering. It is through the times of suffering people may discover or enhance their religiosity/spirituality. Frankl’s writings on his imprisonment in Nazi concentration camps during the Holocaust have been a source of inspiration for many to find their own personal convictions. The research on meaning as a mediator variable between religion/spirituality and wellbeing is scant; however, there does appear to be some evidence that religious/spiritual people do find solace in the meanings provided by their faiths.
Life beyond eradication: veterinary viruses in basic science.

To some, the focus of research in virology entails the search for solutions of practical problems. By definition then, attention is limited to those viruses that cause disease or to exploitation of some aspect of virology to a practical end (e.g., antiviral drugs or vaccines). Once a disease is cured, or the agent eradicated, it is time to move on to something else. To others, virology offers the opportunity to study fundamental problems in biology. Work on these problems may offer no obvious practical justification; it is an affliction of the terminally curious, perhaps with the outside hope that something “useful” will come of it. To do this so-called “basic science”, one must find the most tractable system to solve the problem, not the system that has “relevance” to disease. I have found that veterinary viruses offer a variety of opportunities to study relevant problems at the fundamental level. To illustrate this point, I describe some recent experiments in my laboratory using pseudorabies virus (PRV), a swine herpesvirus.
Bayesian Designs for Approximate Normality

In many experimental design problems, the primary interest is in estimating functions of the parameters and a design is selected according to some optimality criterion. The assumption that parameter estimates are approximately normally distributed is often used to find optimal designs, as well as simplify data analysis. How well this approximation holds for small to moderate sample sizes depends on the intrinsic and parameter-effects curvatures. These measures depend on both the parameterization used as well as the experimental design. For a particular parameterization of interest, these curvatures can be reduced by the choice of the experimental design. A Bayesian approach is taken to find designs that optimize the primary design criterion subject to satisfying constraints based on these curvature measures, with the goal of improving normal approximations. The constrained designs depend on the sample size, but as the sample size increases the constraints are satisfied. A nonlinear regression example is used to illustrate the approach.
Zoledronic acid-induced orbital inflammation in a patient with multiple myeloma.

Multiple myeloma is a cancer of malignant plasma cells which stimulates osteoclasts and is associated with increased bone turnover and osteolysis. Bisphosphonates including zolendronic acid are use...
Persistence and Drivers of High-Cost Status Among Dual-Eligible Medicare and Medicaid Beneficiaries: An Observational Study

Background Little is known about the persistence of high-cost status among dual-eligible Medicare and Medicaid beneficiaries, who account for a substantial proportion of expenditures in both programs. Objective To determine what proportion of this population has persistently high costs. Design Observational study. Setting Medicare-Medicaid Linked Enrollee Analytic Data Source data for 2008 to 2010. Participants 1 928 340 dual-eligible Medicare and Medicaid beneficiaries who were alive all 3 years. Measurements Medicare and Medicaid payments for these beneficiaries were calculated for each year. Beneficiaries were categorized as high-cost for a given year if their spending was in the top 10% for that year. Differences in spending were then examined for those who were persistently high-cost (all 3 years) versus those who were transiently high-cost (2008 but not 2009 or 2010) and those who were non-high-cost in all 3 years. Results In the first year, 192 835 patients were high-cost. More than half (54.8%) remained high-cost across all 3 years. These patients were younger than transiently high-cost patients, with fewer medical comorbidities and greater intellectual impairment. Persistently high-cost patients spent $161 224 per year compared with $86 333 per year for transiently high-cost patients and $22 352 per year for non-high-cost patients. Most of the spending among persistently high-cost patients (68.8%) was related to long-term care, and very little (<1%) was related to potentially preventable hospitalizations for ambulatory care-sensitive conditions. Limitation Potential misclassification of preventable spending and lack of detailed clinical data in administrative claims. Conclusion A substantial majority of high-cost dual-eligible beneficiaries had persistently high costs over 3 years, with most of the cost related to long-term care and very little related to potentially preventable hospitalizations. Primary Funding Source Peterson Center on Healthcare.
Concurrent Zinc-Blende and Wurtzite Film Formation by Selection of Confined Growth Planes.

Recent research on nanowires (NWs) demonstrated the ability of III–V semiconductors to adopt a different crystallographic phase when they are grown as nanostructures, giving rise to a novel class o...
Demonstration of self-healing barrier films for vacuum insulation panels

Abstract This article presents the demonstration of a rapid self-healing system for barrier films of vacuum insulation panels (VIPs). The proposed self-healing films can improve the durability of VIPs by in-situ remediation of film defects. The self-healing concept has seen limited applications in buildings, and the current work is the first proposed application to VIPs. VIPs can achieve an order-of-magnitude lower thermal conductivity than traditional foam and fibrous building insulations. The key to the ultra-low thermal conductivity of VIPs is an evacuated core that is fully-encapsulated within impermeable barrier films. Evacuation of the core eliminates the gas conductivity, which is the dominant contributor to heat transfer in traditional insulation materials. Thus, the integrity of the VIP barrier films is critical. The proposed self-healing system can seal accidental cuts and punctures to the barrier films to maintain their impermeability and, hence, the low conductivity of VIPs. Here, the proof-of-principle of a two-part chemical reaction-based self-healing system is presented, including the evaluations of reaction kinetics using chemical-structure analysis and time-dependent viscosity change, and demonstration of self-healing performance via puncture tests in a vacuum pump apparatus. Multiple chemical combinations of epoxies and curing agents were investigated with respect to reaction kinetics and chemical stability. Epon 8111 as an epoxy and poly(ethyelenimine) (PEI) as a curing agent were identified as the optimum chemicals with a curing time of 22 s as evaluated by an agitating stirrer experiment. 1H nuclear magnetic resonance (NMR) spectra analysis identified the curing reaction occurring mainly via the Michael amine-acrylate addition. The measured time-dependent viscosity change of diluted Epon 8111 and PEI solutions agreed well with a gelation model of typical epoxy curing kinetics, which predicted a very fast reaction rate for the undiluted chemicals. Finally, puncture tests of small-scale film specimens containing Epon 8111 and PEI in a vacuum pump system demonstrated that the self-healing reaction happens very rapidly and the healed films maintain the system vacuum.
Monte Carlo Simulations of Framework Defects in Layered Two-Dimensional Nanomaterial Desalination Membranes: Implications for Permeability and Selectivity

Two-dimensional nanomaterial (2-D NM) frameworks, especially those comprising graphene oxide, have received extensive research interest for membrane-based separation processes and desalination. How...
Refusing the king’s portion: A reexamination of Daniel’s dietary reaction in Daniel 1:

In Dan. 1, scholarship has proposed a range of plausible answers to the question, why did Daniel and his friends refuse the king’s provision of food and drink? Given that such a refusal was not abs...
A multi-criteria decision support tool for biorefinery siting: Using economic, environmental, and social metrics for a refined siting analysis

Abstract Facility siting has traditionally been performed using economic metrics alone to determine suitable locations for a new facility. In this era of climate change concerns and political discord, a more holistic approach to biorefinery siting may yield alternative locations that meet stakeholder goals for community acceptance and reduced environmental impacts. A multi-criteria decision support tool (DST) that incorporates economic, environmental, and social metrics concurrently is introduced to assess the repurpose potential of existing facilities as a wood-based biorefinery. Economic siting criteria are represented by biorefinery operational cost components that vary geospatially. The environmental criterion is the Global Warming Potential of the supply chain, as measured through greenhouse gases emitted from the feedstock procurement, preprocessing, and transport equipment. Social criteria are represented by 1) the number of regional jobs created through the installation of a biofuel supply chain, and 2) county-level social assets that may influence biorefinery project success. Weights and scale values are derived for each set of metrics. An overall facility score is produced by summing the three metric scores. Additionally, overall user-defined metric weights are used to adjust the importance of the three metrics, thus altering the overall facility scores. The DST is applied to a case study in Western Oregon and Western Washington to refine a list of candidate pulp mills down to a select few for further investigation. It was found that the mills scored differently when overall metric weights were adjusted. Therefore, different stakeholder preferences may yield a different priority list of facilities.
Prealbumin Is Associated With In-Hospital Mortality in Critically Ill Patients

Background Prealbumin (PAB) has been shown to be a useful index of nutrition status in clinically stable patients. In the setting of critical illness, however, PAB is a negative acute phase reactant and may also reflect severity of illness. The purpose of this study was to evaluate the relationship between PAB and clinical outcomes in critically ill patients. Methods This was a single-center, retrospective, nonrandomized cohort study of adult intensive care unit (ICU) patients. Baseline PAB and change in PAB were analyzed. The primary outcome was in-hospital mortality, and the secondary outcome was hospital length of stay (LOS). Data collected included PAB levels, Charlson Comorbidity Index, LOS, in-hospital mortality, and nutrition intake. Linear and logistic regressions were used to characterize the association between PAB levels and clinical outcomes. Results Our study included 926 patients. Patients expiring in hospital experienced a greater decrease in PAB over time, -1.3 vs -0.7 mg/dL (odds ratio 0.94 [0.9-0.98] in multivariable regression, P = .002). Baseline PAB was not associated with in-hospital mortality or LOS. Exploratory analyses demonstrated a weak correlation between nutrition and change in PAB. Conclusion Our data demonstrate that change in PAB is associated with hospital mortality. Nutrition intake weakly correlated with change in PAB. PAB does not appear to be a robust marker of nutrition therapy but may have value as a prognostic indicator in the ICU setting.
Update on Clinical Practice Guidelines for Human Immunodeficiency Virus.

It has been more than 38 years since the first reported case of human immunodeficiency virus (HIV). Over this period of time, there has been an evolution in the care, management, and survival of those living with HIV and acquired immunodeficiency syndrome (AIDS). Current efforts to stabilize HIV incidence have targeted pharmacologic management with antiretroviral therapy (ART) coupled with programs that focus on individual characteristics, social norms, and structural barriers. It is important that clinicians are knowledgeable of prevention efforts and up-to-date clinical practice guidelines in order to best provide care for people living with HIV.
Unmanned air-traffic management (UTM): Formalization, a prototype implementation, and performance evaluation.

Unmanned Aircraft Systems (UAS) are being increasingly used in delivery, infrastructure surveillance, fire-fighting, and agriculture. According to the Federal Aviation Administration (FAA), the number of active small commercial unmanned aircraft is going to grow from 385K in 2019 to 828K by 2024. UAS traffic management (UTM) system for low-altitude airspace is therefore immediately necessary for its safe and high-density use. In this paper, we propose the first formalization of FAA's Concept of Operations for UTM for building and analyzing traffic management protocols and systems. We formalize FAA's notion of operation volumes (OVs) that express aircraft intent in terms of 4D blocks of airspace and associated real-time deadlines. We present a prototype coordination protocol using OVs, involving participating aircraft and an airspace manager. We formally analyze the safe separation and liveness properties of the protocol. Our analyses showcase how the de-conflicting and liveness of the system can be proven assuming each aircraft conforms to the deadlines specified by OVs. Through extensive simulations, we evaluate the performance of the protocol in terms of workload and response delays. Our experiments show that the workload on the airspace manager and the response time of each aircraft grow linearly with respect to the number of aircraft. The experiments also delineate the trade-off between performance, workload, and violation rate across different strategies for generating OVs. Lastly, we implement a UTM violation detection and resolution mechanism on top of our protocol. We include a simple fault injection technique that introduces failures with different probabilities. We demonstrate how to use it to empirically evaluate the impact of aircraft failure on the safety of surrounding aircraft, and how the performance of the airspace manager changes under different failure probabilities.
Effects of Cryopreservation on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Assessing Drug Safety Response Profiles.

Burgeoning applications of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in disease modeling, regenerative medicine, and drug screening have broadened the usage of hiPSC-CMs and entailed their long-term storage. Cryopreservation is the most common approach to store hiPSC-CMs. However, the effects of cryopreservation and recovery on hiPSC-CMs remain poorly understood. Here, we characterized the transcriptome, electro-mechanical function, and drug response of fresh hiPSC-CMs without cryopreservation and recovered hiPSC-CMs from cryopreservation. We found that recovered hiPSC-CMs showed upregulation of cell cycle genes, similar or reduced contractility, Ca2+ transients, and field potential duration. When subjected to treatment of drugs that affect electrophysiological properties, recovered hiPSC-CMs showed an altered drug response and enhanced propensity for drug-induced cardiac arrhythmic events. In conclusion, fresh and recovered hiPSC-CMs do not always show comparable molecular and physiological properties. When cryopreserved hiPSC-CMs are used for assessing drug-induced cardiac liabilities, the altered drug sensitivity needs to be considered.
Aggressive Therapy for Acute Pulmonary Embolism: Systemic Thrombolysis and Catheter-Directed Approaches

Venous thromboembolism (VTE) is the third most common cause of cardiovascular disease after myocardial infarction and stroke. Population-based studies estimate that up to 94,000 new cases of pulmonary embolism (PE) occur in the United States annually with an increasing incidence with age. Mortality from PE is the greatest in the first 24 hours, with a decreased survival extending out 3 months. Thus, acute PE is a potentially fatal illness if not recognized and treated in a timely manner. Contemporary management includes systemic anticoagulation, thrombolysis, catheter-based procedures, and surgical embolectomy. This article reviews current clinical evidence and societal guidelines for the use of systemic and catheter-directed thrombolysis for treatment of acute PE.
High Power Optically Pumped Submillimeter Laser Systems

The production of high power submillimeter radiation by 200 MW level CO 2 laser pumping of various gases such as CH 3 F and D 2 O has been studied. A number of cavity and amplifier configurations were used to produce narrow linewidth radiation. A 384.6 μm D 2 O oscillator amplifier system was used to produce a 12.7 millijoule, 195 kW, 70 MHz wide single mode beam in 60-70 nsec pulses.
Cannabis Banking: What Marijuana Can Learn from Hemp

Marijuana-related businesses have banking problems. Many banks explain that because marijuana is illegal under federal law, they will not serve the industry. Even when marijuana-related businesses can open bank accounts, they still have trouble accepting credit cards and getting loans. Some hope to fix marijuana’s banking problems with changes to federal law. Proposals range from broad reforms removing marijuana from the list of controlled substances to narrower legislation prohibiting banking regulators from punishing banks that serve the marijuana industry. But would these proposals solve marijuana’s banking problems? In 2018, Congress legalized another variant of the Cannabis plant species—hemp. Prior to legalization, hemp-related businesses, like marijuana-related businesses, struggled with banking. Some hoped legalization would solve hemp’s banking problems. It did not. By analyzing the hemp banking experience, this Article provides three insights. First, legalization does not necessarily lead to inexpensive, widespread banking services. Second, regulatory uncertainty hampers access to banking services. When banks were unsure what state and federal law required of hemp businesses and were unclear about bank regulators’ compliance expectations for hemp-related accounts, they were less likely to serve the hemp industry. Regulatory structures that allow banks to easily identify who can operate cannabis businesses and verify whether the business is compliant with the law are more conducive to banking. Finally, even with clear law and favorable regulatory structures, the emerging cannabis industry still presents credit, market, and other risks that make some banks hesitant to lend.
Raspberry Increases Expression of Antioxidant Enzymes in the Kidney of Angiotensin II-Treated Rats

Objectives To examine whether dietary supplementation with raspberries attenuates angiotensin (Ang) II-induced oxidative stress in the kidneys of rats.
FXa cleaves the SARS-CoV-2 spike protein and blocks cell entry to protect against infection with inferior effects in B.1.1.7 variant

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human natural defense mechanisms against SARS-CoV-2 are largely unknown. Serine proteases (SPs) including furin and TMPRSS2 cleave SARS-CoV-2 spike protein, facilitating viral entry. Here, we show that FXa, a SP for blood coagulation, is upregulated in COVID-19 patients compared to non-COVID-19 donors and exerts anti-viral activity. Mechanistically, FXa cleaves the SARS-CoV-2 spike protein, which prevents its binding to ACE2, and thus blocks viral entry. Furthermore, the variant B.1.1.7 with several mutations is dramatically resistant to the anti-viral effect of FXa compared to wild-type SARA-CoV-2 in vivo and in vitro. The anti-coagulant rivaroxaban directly inhibits FXa and facilitates viral entry, whereas the indirect inhibitor fondaparinux does not. In a lethal humanized hACE2 mouse model of SARS-CoV-2, FXa prolonged survival while combination with rivaroxaban but not fondaparinux abrogated this protection. These preclinical results identify a previously unknown SP function and associated anti-viral host defense mechanism and suggest caution in considering direct inhibitors for prevention or treatment of thrombotic complications in COVID-19 patients.
Enhancing the Accessibility of Unified Modeling Systems: GFDL SHiELD v2021b in a Container

Abstract. Container technology provides a pathway to facilitate easy access to unified modeling systems and opens opportunities for collaborative model development and interactive learning. In this paper, we present the implementation of software containers for the System for High‐resolution prediction on Earth‐to‐Local Domains (SHiELD), a unified atmospheric model for weather-to-seasonal prediction. The containerized SHiELD is cross-platform and easy to install. Flexibility of the containerized SHiELD is demonstrated as it can be configured as a global, a global-nest, and a regional model. Bitwise reproducibility is achieved on various x86 systems tested in this study. Performance and scalability of the containerized SHiELD are evaluated and discussed.
On quasistatic and dynamic fracture

The interaction of inertia effects with fracture is explored by comparing the analytical results for four cases of crack propagation under antiplane loading. The four cases are: (1) quasistatic loading and quasistatic fracture; (2) quasistatic loading and dynamic fracture; (3) dynamic loading and dynamic fracture; (4) dynamic loading and quasistatic fracture. The balance of rates of energies is employed as a criterion to determine the conditions for fracture. For dynamic fracture the balance of rates of energies also produces an equation for the computation of the rate of crack propagation. Stress intensity functions and rates of energy flux are displayed as functions of the rate of crack propagation.
Monaural and binaural contributions to interaural-level-difference sensitivity in human auditory cortex.

Abstract Whole-brain functional magnetic resonance imaging was used to measure blood-oxygenation-level-dependent (BOLD) responses in human auditory cortex (AC) to sounds with intensity varying independently in the left and right ears. Echoplanar images were acquired at 3 Tesla with sparse image acquisition once per 12-second block of sound stimulation. Combinations of binaural intensity and stimulus presentation rate were varied between blocks, and selected to allow measurement of response-intensity functions in three configurations: monaural 55–85 dB SPL, binaural 55–85 dB SPL with intensity equal in both ears, and binaural with average binaural level of 70 dB SPL and interaural level differences (ILD) ranging ± 30 dB (i.e., favoring the left or right ear). Comparison of response functions equated for contralateral intensity revealed that BOLD-response magnitudes (1) generally increased with contralateral intensity, consistent with positive drive of the BOLD response by the contralateral ear, (2) were larger for contralateral monaural stimulation than for binaural stimulation, consistent with negative effects (e.g., inhibition) of ipsilateral input, which were strongest in the left hemisphere, and (3) also increased with ipsilateral intensity when contralateral input was weak, consistent with additional, positive, effects of ipsilateral stimulation. Hemispheric asymmetries in the spatial extent and overall magnitude of BOLD responses were generally consistent with previous studies demonstrating greater bilaterality of responses in the right hemisphere and stricter contralaterality in the left hemisphere. Finally, comparison of responses to fast (40/s) and slow (5/s) stimulus presentation rates revealed significant rate-dependent adaptation of the BOLD response that varied across ILD values.
Properties of metK Mutants of Escherichia coli K-12

Abstract Some of the properties of three metK mutants of Escherichia coli K-12 have been examined. All three strains have lower than normal levels of SAM (S-adenosyl-l-methionine) synthetase and elevated levels of cystathionine synthetase and cystathionase. One strain (RG73) appears to have an unstable SAM synthetase, suggesting that it carries a structural gene mutation. The two strains (RG62 and RG109) which have the lowest levels of SAM synthetase when grown on minimal medium have appreciably higher levels of enzyme when grown on complete medium. Growth on defined media supplemented with leucine or methionine causes a several-fold increase in the specific activity of SAM synthetase with associated decreases in cystathionine synthetase and cystathionase, but the changes are not as large as those seen in cells grown on LB broth. The SAM pools of strains RG62 and RG109 are markedly lower than normal while that of strain RG73 is slightly below normal. The methionine pools of all three strains are elevated several-fold. The metK strains are able to synthesize cyclopropane fatty acids, but the rate of their formation is slowed. Modification and restriction of phage 21 appears to be normal, suggesting that these strains are able to methylate DNA.
Managing Conflicts between Rulings of WTO and RTA Tribunals: Reflections on the Brazil-Tyres Case

The proliferation of international tribunals has given rise to much concern about potential conflicts between judicial decisions and possible ‘fragmentation’ of international law. Most of the discussions have focused on conflicts of jurisdictions and conflicts of norms that may result from competing or overlapping jurisdictions. The worst type of conflicts however is the conflict of obligations where a State cannot comply with the decisions of two tribunals at once because their separate decisions require the State to act in opposite directions. Unfortunately, such a direct conflict of obligations has occurred as a result of the decision of the WTO Appellate Body in the case of Brazil - Tyres (DS332). The Appellate Body held that, by following the ruling of an arbitral tribunal of Mercosur - the regional trade agreement (RTA) between several South American countries - Brazil acted inconsistently with WTO rules. Furthermore, in the subsequent compliance proceedings a WTO arbitrator refused to allow Brazil time to negotiate a solution with other Mercosur countries. Consequently, Brazil found itself in a legal bind: it could not comply with WTO obligations without breaching its Mercosur obligations. Significantly, this conflict of obligations did not stem from competing or overlapping jurisdictions or conflicting treaty norms. Instead, it occurred entirely as a result of the Appellate Body’s interpretation of a WTO provision. This paper submits that the conflict in this case could have been avoided because alternative interpretations, arguably legally sounder ones, do exist, and should have been avoided because there are international rules requiring a presumption against conflicts in treaty interpretation. The paper suggests that in rendering its decision the Appellate Body showed little concern regarding conflicts with the RTA, and that such lack of concern reflected an outdated mindset of WTO centrality or superiority. In light of international legal principles and the realities of the multi-polar global trading environment, the WTO judiciary is urged to adopt a clear policy on the avoidance of conflicts with RTA decisions.
Antibiotic Resistance Plasmids in Bacteria

Antibiotic resistance plasmids are bacterial extrachromosomal elements that carry genes conferring resistance to one or more antibiotics. They are notorious for their ability to transfer by conjugation between bacterial species and are significantly involved in the emergence and dissemination of multiple drug resistance associated with bacterial infections in humans. The information provided here includes some of the history and nature of antibiotic resistance as well as how plasmids have become significantly involved as intercellular carriers via the phenomenon of bacterial conjugation. The manner by which resistance determinants are able to move onto plasmids via their initial association with transposons and integrons is discussed. The existence of elements with both transpositional and conjugative properties, such as the conjugative transposons and integrative conjugative elements, is also noted. Key Concepts: Multiple antibiotic resistance represents a serious and growing clinical problem with regard to bacterial infections in humans. Resistance genes are commonly found on plasmids, which are small extrachromosomal elements commonly found in bacteria. Plasmids can vary widely with regard to their size and copy number in the cell. Plasmids are commonly able to move from one bacterial cell to another by a mechanism known as conjugation, which involves cell-to-cell contact followed by transfer of a copy of plasmid DNA from a donor to a recipient. Genes conferring antibiotic resistance are commonly found on elements known as integrons and transposons, which facilitate movement between different replicons such as between the bacterial chromosome and a plasmid. Some transposable elements, known as conjugative transposons, also carry resistance traits; and, although unable to replicate autonomously, they can move from one bacterial cell to another by a plasmid-like mechanism. Excessive use of antibiotics in the treatment of human infections has, over time, contributed to the emergence and selection of resistant bacteria in the gut, a phenomenon that includes passage of resistance traits between nonpathogens and pathogens. Keywords: conjugative transposon; horizontal transfer; insertion sequence; integron; plasmid; transposon
Medication-Related Osteonecrosis of the Jaw: Basic and Translational Science Updates

In the late 1990s and the early 2000s, bisphosphonates had become the clinical pillar of excellence for treating metabolic bone disease, and thus their connection with osteonecrosis of the jaw (ONJ) caused significant concern. Over the past decade, progress has been made in understanding what is now referred to as medication-related ONJ (MRONJ), because of its connections to agents other than bisphosphonates, although in many respects the progress has been slow. This review highlights the key basic science and translational (animal) studies in the area of MRONJ and suggests areas of focus as the field moves into the next decade.