cssi/SciSciGPT-SciSciNet huggingface dataset:
Probing the RNA Binding Surface of the HIV‑1 Nucleocapsid Protein by Site-Directed Mutagenesis

The highly conserved nucleocapsid protein domain in HIV-1 recognizes and binds SL3 in genomic RNA. In this work, we used the structure of the NCp7-SL3 RNA complex to guide the construction of 16 NCp7 mutants to probe the RNA binding surface of the protein [De Guzman, R. N., et al. (1998) Science 279, 384-388]. Thirteen residues with functional or structural significance were mutated individually to Ala (Asn(5), Phe(6), Val(13), Phe(16), Asn(17), Gly(19), Glu(21), Ile(24), Gln(45), Met(46), Gly(22), Pro(31), and Gly(40)), and three salt bridge switch mutants exchanged Lys and Glu (Lys(14)-Glu(21), Lys(33)-Glu(42), and Lys(38)-Glu(51)). Dissociation constants (Kd) determined by fluorescence titration and isothermal titration calorimetry were used to compare affinities of SL3 for the variant proteins to that for the wild type. The F16A (Phe(16) to Ala) variant showed a 25-fold reduction in affinity, consistent with a loss of organized structure in f1, the protein's first zinc finger. I24A, Q45A, and M46A reduced affinity by 2-5-fold; these residues occupy nearly equivalent positions in f1 and f2. E21A increased affinity by 3-fold, perhaps because of the mutant's increased net positive charge. Among the salt bridge switch mutants, only K14E/E21K in f1 caused a substantial change in affinity (5-fold reduction), binding SL3 with a biphasic binding isotherm. Aside from these six variants, most of the mutations studied have relatively minor effects on the stability of the complex. We conclude that many side chain interactions in the wild-type complex contribute little to stability or can be compensated by new contacts in the mutants.
Estimation of transcription factor profiles from fluorescent protein reporter systems

This work presents a generally-applicable technique for reconstructing transcription factor profiles from fluorescence microscopy images of GFP reporter systems. The approach integrates dynamic optimization and a Tikhonov regularization to avoid over-fitting caused by the highly ill-conditioned structure of this inverse problem. The advantage that the presented approach has over existing methods is that no assumptions are made about the transcription factor profile, the linearity, or lack thereof, of the dynamic model used, and the sampling time of the measurements. Moreover, the method allows to use discretization times for the model different from the measurement sampling times and can also deal with state constraints. The technique has been applied to experimental data in a case study where the presented technique exhibits excellent performance for estimating the profile of the transcription factor STAT3.
Fermat’s Equation

Of all Diophantine equations, by far the most famous is Fermat’s equation $${x^n} + {y^n} = {z^n}$$ .
Japan and Extended Nuclear Deterrence: Security and Non-proliferation

ABSTRACTTo an observer, Japan’s approach to nuclear weapons can appear confused and contradictory. The only country to have been attacked with nuclear weapons is variously described as a pacifist and non-nuclear nation and as a proliferation threat. These widely varied and conflicting conclusions are understandable given that conflicting messages are sent by senior figures. However Japan’s stance is in fact a coherent, if not uncomplicated, response both to its security needs and to domestic public opinion. However, the security provided by US extended nuclear deterrence underlines and enables this approach. The key policies and decisions were taken in both Washington and Tokyo between China’s first nuclear test (1964) and Japan’s ratification of the Nuclear Non-Proliferation Treaty (1976). How the United States came to offer this additional security guarantee to Japan and how Japan came to rely upon it underscore this complex stance and are crucial to understanding a longstanding and ongoing security arr...
Capillary red cell residence as a measure of tissue oxygen delivery.

Experimental measurements of changes in the fluorescence intensity of endogenous and exogenous indicators of tissue oxygen tension must be corrected for changes in red cell mass in the observed volume of tissue. In our presentation last year (Longmuir et al. 1984) we assumed that localized increased oxygen consumption in the sensory cortex on peripheral stimulation would result in increases only in red cell mass. Thus any observed increases in fluorescence of pyrenebutyric acid would be equal to or less than the actual change in fluorescence quenching by oxygen: that there was a real fall in local tissue oxygen tension. However, subsequent studies have shown that following sensory stimulation, some areas of the cortex show reduced red cell mass. These reductions in microregional blood flow do not appear to be a direct consequence of sensory stimulation, but are part of the normal pattern of fluctuations in the distribution of red cells which occur continuously in the brain, giving rise to the oscillations in local PO2 described by Manil et al. (1984). When large areas of cortex are studied, these fluctuations average out and the problem of correction is simplified.
Villous Adenocarcinoma of the Male Urethra

AbstractWe report on 2 men with multifocal papillary adenocarcinoma arising in the bulbous urethra proximal to a urethral stricture. Histologically, the tumors appeared similar to villous adenocarcinomas of the colon and rectum. Both patients were treated with segmental urethrectomy. Villous adenocarcinoma of the male urethra is a distinctive clinicopathologic entity. Although uncommon it should be added to squamous cell carcinoma and transitional cell carcinoma on the list of tumor types causing cancer of the male urethra.
Brand Compromises: An Examination of Cultural Influences on Consumer Complicity with Counterfeit Brands

International trade in counterfeit goods has been showing a steady increase in the new millennium, totaling an estimated $250 billion, or nearly two percent of world trade, in 2007 (OECD, 2009). This increase in buying and selling of pirated and fake goods continues to gain ground despite global efforts to respect intellectual property rights through transnational organizations like the WTO, and a commitment to do so by member countries (WTO, 2012). Academics have examined the problem of counterfeiting from a “supply side” perspective, examining sources of counterfeit goods and factors such as political, legal, and economic infrastructure that may facilitate the practice (Berrell and Wrathall, 2007; Lambkin and Tyndall, 2009).
The regulation of mitotic nuclear envelope breakdown: A role for multiple lamin kinases

The chapter reviews the structure and function of the nuclear envelope and describes its dynamic structural changes during cell cycle. Particular emphasis is placed on the regulation of mitotic nuclear envelope breakdown (NEBD), the process by which the physical barrier between cytoplasm and nucleus is dissolved to allow for cell division. The literature suggesting the involvement of multiple protein kinases in NEBD is reviewed and evidence is presented that multiple mitotic lamin kinases, including p34cdc2/cyclin B kinase and protein kinase C, play key roles in mitotic nuclear lamina disassembly. Finally, a model for regulation of mitotic nuclear lamina disassembly by multi-site phosphorylation is described.
Predicting overlap between drift gillnet fishing and leatherback turtle habitat in the California Current Ecosystem

Concern over bycatch of protected species has become a key factor in shaping fisheries management decisions. In 2001, the National Marine Fisheries Service established an annual closure of a large mesh drift gillnet fishery targeting swordfish from central Oregon to central California between August 15 and November 15 because of concerns of bycatch of endangered leatherback turtles (the Pacific Leatherback Conservation Area, PLCA). The spatio‐temporal constraints of the PLCA were developed to encompass nearly all previously observed leatherback turtle bycatch events in the fishery. The PLCA has been effective at reducing bycatch of leatherback turtles but has reduced fishing opportunities. In this study, we examined whether the timing of the current PLCA closure is optimal for leatherback turtle conservation, by developing statistical models of leatherback turtle presence inside the PLCA based on environmental variables. We also examined finer‐scale spatiotemporal patterns of potential overlap between the fishery and leatherback turtle foraging habitat using Maxent and Random Forests applied to logbook data and leatherback turtle telemetry data. Our results suggest that the temporal extent of the current static closure period is the shortest and most effective for protecting the turtles while allowing fishing during low bycatch‐risk periods. We also found that it is possible to predict foraging habitat of leatherback turtles and fishing effort using environmental variables. Identification of spatial and temporal hotspots of potential overlap between fishing effort and leatherback turtle distribution can form a basis for dynamic management approaches.
Fast and easy parallel processing on GPUs using C++ AMP

This paper shows how one can easily incorporate parallel processing into a research project or classroom lesson using C++ AMP (Accelerated Massive Parallelism). AMP is a set of C++ language extensions that makes it easy to execute some algorithms in parallel on a graphics card's processor (GPU). With a powerful GPU, minor code modifications can make a program run in parallel on a GPU hundreds of times faster than a serial version on the CPU. This is demonstrated by using a simple brute-force algorithm to calculate a discrete Voronoi diagram and to solve a facility location problem based on it.
Enforced E47 Expression Has Differential Effects on Lmo2-Induced T-Cell Leukemia

Abstract Abstract 4637 Lmo2 is one of the most commonly deregulated oncogenes in human T-cell acute lymphoblastic leukemia (T-ALL). In mouse models, Lmo2 overexpression causes a differentiation block before the onset of T-ALL at a developmental stage that is similar to the block seen in E47 knockout mice. Furthermore, Lmo2 and E47 are part of an oligomeric protein complex in hematopoietic stem and progenitor cells. Since E47 knockout mice also develop T-ALL, it has been hypothesized that Lmo2 may induce T-ALL by redirecting E47 activity away from its normal target genes. We noted downregulation of many E2A targets in Lmo2-induced T-ALL. To directly test whether E47 is required in Lmo2-induced T-ALLs, we transduced four stable T-ALL lines established from Lmo2 transgenic mice with retrovirus expressing E47 fused with estrogen receptor. All 4 lines tolerated stable high- level protein expression of E47-ER with no change in from their baseline growth rates. The E47-ER fusion protein allowed forced dimerization upon treatment with 4-hydroxytamoxifen. Tamoxifen treatment increased expression CD4 and other described E2A targets in all 4 T-ALL lines; but two lines underwent G0/G1 cell cycle arrest. Our data suggest that E47 deficiency is not a universal feature of Lmo2- induced T-ALL and E47 forced expression has differential effects on T-ALL. Disclosures: No relevant conflicts of interest to declare.
Pulmonary Foreign Body Embolism and Granulomatosis in Intravenous Substance Abuse

Prescription drug abuse has increased in the United States in part because of the relative ease of acquisition. Some drug abusers resort to the injection of crushed tablets for rapid onset and incr...
Against Brute Fundamentalism

In metaphysics, the fundamental is standardly equated with that which has no explana- tion – with that which is, in other words, ‘brute’. But this doctrine of brutalism is in tension with physicists’ ambitions to not only describe but also explain why the fundamental is as it is. The tension would ease were science taken to be incapable of furnishing the sort of explanations that brutalism is concerned with, given that these are understood to be dis- tinctively ‘metaphysical’ in character. But to assume this is to assume a sharp demarcation between physics and metaphysics that surely cannot be taken for granted. This paper sets out to examine the standing of brutalism from the perspective of contem- porary fundamental physics, together with theories of explanation drawn from philosophy of science and metaphysics. Focusing on what fundamental kinds the world instantiates and how physicists go about determining them, I argue that a partial explanation, in Hempel’s sense, may be given of this fundamental feature. Moreover, since this partial explanation issues, at least in part, from stipulations as to the essential nature of the kinds involved, I claim that it has as much right to be regarded as a metaphysical explanation as do grounding explanations. As such, my conclusion will be that the doctrine of brutalism can no longer be regarded as tenable: at least modulo certain plausible essentialist assumptions, it is no longer the case that no explanation can be given of the fundamental.
Signer-independent classification of American sign language word signs using surface EMG

The field of Sign Language Recognition (SLR) has become an increasingly popular research topic. The goal of this study is an SLR system that will be capable of identifying a subset of 50 of the most common American Sign Language (ASL) word signs using surface electromyography and accelerometer data for multiple signers. All data was collected from deaf, fluent ASL users. A windowing approach is used with different time domain features for feature extraction. The samples are divided into one and two-handed signs, each of which are used to train a Support Vector Machine classifier. Samples from all but one subject are used to train the classifiers. The classifiers are then tested on both data held out from the subjects used for training and the subject that was left out. The resulting system had an average accuracy of 59.96% for trained subjects and 33.66% for the subject left out. To compare this approach to others, 40-word and 7-word sign sets are trained and tested using this method. The proposed system performed comparably with literature for the 40-word set, and better for the 7-word set.
Rome and the Making of a World State, 150 BCE - 20 CE

In the century following 150 BCE, the Romans developed a coherent vision of empire and a more systematic provincial administration. The city of Rome itself became a cultural and intellectual center that eclipsed other Mediterranean cities, while ideas and practices of citizenship underwent radical change. In this book, Josiah Osgood offers a new survey of this most vivid period of Roman history, the Late Republic. While many discussions focus on politics in the city of Rome itself, his account examines developments throughout the Mediterranean and ties political events more firmly to the growth of overseas empire. The volume includes a broad overview of economic and cultural developments. By extending the story well beyond the conventional stopping date of Julius Caesar's assassination in 44 BCE, Osgood ultimately moves away from the old paradigm of the fall of the Republic. The Romans of the Late Republic emerge less as the disreputable gangsters of popular imagination and more as inspired innovators.
A Theoretical Study of Na Overlayers on the GaAs (110) Surface

Although many efforts have been focused on gaining a microscopic understanding of the metal-semiconductor interfaces, many properties, such as the pinning of the Fermi-level, and the formation of the Schottky barrier, are still controversial. [1,2] Experimental results were affected by the interface morphology, and surface relaxation, while theoretical results suffer from proper models and a well defined reference energy.
Ion Channeling and Blocking Investigations of the Structure of Ideal and Reconstructed Metal Surfaces

The last few years has seen a rapidly increased use of medium energy ion scattering (MEIS) with channeling and blocking, a technique originally developed at the FOM institute in Amsterdam [1]. Ion scattering is a quantitative and very direct probe of local surface structure. The interaction law is simple and well understood (essentially only elementary Rutherford scattering theory is needed for the analysis) and the outcome of the experiments can be modeled accurately using Monte Carlo simulations.
Oral anticoagulants: Pharmacologic issues for use in the elderly

There has been a marked expansion of the indications for oral anticoagulant therapy, particularly among the elderly. Despite the documented benefits, the use of warfarin remains strikingly low among patients 80 years of age and older. Elderly patients often exhibit an enhanced dose response to warfarin. On average, steady-state warfarin doses decrease by 11% per decade of age. Pharmacokinetic changes in the elderly are negligible. Pharmacodynamic differences have not been well characterized. Initiating warfarin dosing in the elderly should be done cautiously, with doses of 5 mg or less. Doses should be adjusted downward in the presence of congestive heart failure, advanced obstructive lung disease, liver disease, malignancy, protracted diarrhea, enteral feedings, or concurrent potentiating medications. Numerous medications interfere with the anticoagulant response of warfarin. The most powerful potentiating drugs are those that interfere with the metabolism of (S)-warfarin. Examples include amiodarone, trimethoprim-sulfamethoxazole, and metronidazole. These drugs should be prescribed with caution in the elderly and mandate frequent INR monitoring during the induction period. An extensive assessment of patient-specific factors that might increase the hazards related to warfarin therapy needs to be conducted and documented before initiating oral anticoagulant therapy. Patients and their caregivers need to understand the risks and benefits, and to recognize signs of abnormal bleeding and the need for frequent monitoring. Patients should be encouraged to maintain consistency in their vitamin K intake and should strive to meet the recommended dietary allowance for vitamin K. To improve anticoagulation control, physicians and other health care providers need to be aware of the many warfarin drug interactions and be cognizant of the increased dose response of warfarin seen in the elderly. Concurrent prescription of multiple drugs known to affect warfarin's anticoagulant response should be minimized and use of nonselective nonsteroidal anti-inflammatory drugs should be limited given their deleterious effects on the gastric mucosa. Transitions from inpatient care to subacute care and back to outpatient care are particularly vulnerable periods for patients' anticoagulation control. Enhanced provider communication and more seamless transitions help to ensure optimal INR follow-up and timely warfarin dose adjustment if indicated.
Pacing mode and long-term survival in elderly patients with congestive heart failure: 1980-1985.

Dual-chamber pacing may improve short-term hemodynamics and functional class in some patients with congestive heart failure, even in the absence of conventional indications for pacemaker implantation. However, the impact of different pacing modes on survival of patients with congestive heart failure is controversial. In this retrospective study we analyzed survival data from 546 elderly patients, aged 70 years and older, who underwent implantation of a permanent dual-chamber (DDD, n = 62, DVI, n = 102) or single-chamber (VVI) pacemaker (n = 382) between 1980 and 1985. Survival was further analyzed according to the presence or absence of congestive heart failure, and pacemaker mode (DDD vs. DVI vs. VVI). Overall, dual-chamber pacing (DDD and DVI) was associated with a more favorable long-term outcome when compared with single-chamber ventricular pacing, although differences were only significant for DDD pacing (P = 0.002). When patients with and without preexisting congestive heart failure were analyzed separately, survival following dual-chamber pacing (DDD and DVI) was significantly better than survival following single-chamber pacing in patients without congestive heart failure (P = 0.03), but not in patients with preexisting heart failure (P = 0.139). When patients were analyzed according to the electrophysiological indication for pacemaker implantation, overall survival of patients with AV block (P = 0.0025) but not sinus node dysfunction (P = 0.346) was improved with dual-chamber pacing. This survival advantage in patients with AV block following dual-chamber pacing was lost in the presence of heart failure P = 0.11). These findings suggest that dual-chamber pacing, in particular DDD pacing, improves the survival in elderly patients without preexisting congestive heart failure. In contrast to the short-term hemodynamic improvement observed in selected patients with congestive heart failure, dual-chamber pacing in elderly patients with congestive heart failure, paced for conventional indications, is not associated with improved survival when compared with single-chamber ventricular pacing.
Integrating Leisure, Human Flourishing, and the Capabilities Approach: Implications for Therapeutic Recreation

The value-laden nature of therapeutic recreation (TR) entails therapeutic recreation specialists (TRSs) acting as moral agents who help people with disabilities live well. To be effective agents, TRSs seek guidance from moral visions or conceptualizations of what it means to live well. A challenge for TRSs is that people they serve pursue a plurality of secular and religious moral visions. Thus, the profession and professionals need an overarching, guiding framework compatible with diverse views of the good life. This article describes such a theoretical framework, the Capabilities Approach authored by Nussbaum (2006, 2013), illustrates the theory’s compatibility with a moral vision recently presented in the TR literature and explores how adopting the approach leads to TRSs taking on the concomitant role of social justice agent.Subscribe to TRJ
Strong Magneto-Optical Response Enabled by Quantum Two-Level Systems

The magneto-optical effect breaks time-reversal symmetry, a unique property that makes it indispensable in nonreciprocal optics and topological photonics. Unfortunately, all natural materials have a rather weak magneto-optical response in the optical frequency range, posing a significant challenge to the practical application of many emerging device concepts. Here we theoretically propose a composite material system that exhibits an intrinsic magneto-optical response orders of magnitude stronger than most magneto-optical materials used today. This is achieved by tailoring the resonant interplay between the quantum electrodynamics of electronic transitions in two-level systems and the classical electromagnetic response of local plasmon resonance in metallic nanostructures. © 2019 The Author(s)
Spatiotemporal Patterns of Granule Cell Activity Revealed by a Large-Scale, Biologically Realistic Model of the Hippocampal Dentate Gyrus

Interest in the hippocampus has generated vast amounts of experimental data describing hippocampal properties, including anatomical, morphological, biophysical, and synaptic transmission levels of analysis. However, this wealth of structural and functional detail has not guaranteed insight into higher levels of system operation.
Blood Utilization and Transfusion Reactions in Pediatric Patients Transfused with Conventional or Pathogen Reduced Platelets

Objectives To assess the safety and efficacy of a Food and Drug Administration-approved pathogen-reduced platelet (PLT) product in children, as ongoing questions regarding their use in this population remain. Study design We report findings from a quality assurance review of PLT utilization, associated red blood cell transfusion trends, and short-term safety of conventional vs pathogen-reduced PLTs over a 21-month period while transitioning from conventional to pathogen-reduced PLTs at a large, tertiary care hospital. We assessed utilization in neonatal intensive care unit (NICU) patients, infants 0-1 year not in the NICU, and children age 1-18 years (PED). Results In the 48 hours after an index conventional or pathogen-reduced platelet transfusion, respectively, NICU patients received 1.0 ± 1.4 (n = 91 transfusions) compared with 1.2 ± 1.3 (n = 145) additional platelet doses (P = .29); infants 0-1 year not in the NICU received 2.8 ± 3.0 (n = 125) vs 2.6 ± 2.6 (n = 254) additional platelet doses (P = .57); and PEDs received 0.9 ± 1.6 (n = 644) vs 1.4 ± 2.2 (n = 673) additional doses (P .05). The number and type of transfusion reactions did not significantly vary based on PLT type and no rashes were reported in NICU patients receiving phototherapy and pathogen-reduced PLTs. Conclusions Conventional and pathogen-reduced PLTs had similar utilization patterns in our pediatric populations. A small, but statistically significant, increase in transfusions was noted following pathogen-reduced PLT transfusion in PED patients, but not in other groups. Red cell utilization and transfusion reactions were similar for both products in all age groups.
Preclinical characterization of PF-03732010: A human IgG1 mAb against P-cadherin, reveals antitumor and antimetastatic activity in xenografts

2575 P-cadherin is one member of the classical cadherin family and plays a critical role in tumor cell-cell and cell-stroma adhesions. Up-regulation of P-cadherin has been frequently reported in major tumors such as colon, lung, breast, pancreatic and bladder cancers. Here we report the in vivo antitumor activity of PF-03732010, a human IgG1 mAb that binds to both human and mouse P-cadherin with high affinity and selectivity. Antitumor acitivity of PF-03732010 was assessed in orthotopic or ectopic xenografts models including 1) PC-3M-luc-P-Cad 2) MDA-MB-435-luc-P-Cad subrenal capsule model (SRC) and 3) MDA-MB-435-luc-P-Cad experimental metastasis model. Surgically implanted tumor models are inaccessible to traditional caliper measurements; therefore, bioluminescence imaging (BLI) was applied to evaluate the antitumor activity of PF-03732010. PC3M-luc-PCad and MDA-MB-435-HAL-luc-PCad cells were stably transfected to constitutively express luciferase and overexpress P-Cadherin. PF-03732010 (5 and 20 mg/kg) displayed significant tumor growth inhibition (TGI) of 57% and 73% respectively in the PC3M-luc-PCad model. In addition, BLI revealed PF-03732010 at 5 and 20 mg/kg inhibited lymph node metastases. In MDA-MB-435-HAL-luc-PCad SRC model, distant metastasis in the lungs can be visualized the 4 th week after the tumor implant. PF-03732010 (10, 20 & 40 mg/kg) showed significant antitumor activity in MDA-MB-435-HAL-luc-PCad SRC model with TGI of 51.8%, 66.5% and 68.0% respectively against the primary tumor; and antimetastatic activity of 54.2%, 72.8% and 82.2% respectively against the tumor burden in the lungs. Kaplan-Meier survival plot showed that PF-03732010 significantly improved mouse medium survival time compared to the vehicle treated group. IHC examination of MDA-MB-435-HAL-luc-PCad SRC tumors showed a dose-dependent decrease in β-actin and Ki67, suggesting antitumor activity is a result of cytoskeletal disruption and reduced proliferation due to PF-03732010 blockade of P-cadherin signaling. We further evaluated the antimetastatic activity of PF-03732010 in an experimental model of metastasis, IV delivery of MDA-MB-435-HAL-luc-PCad cells to mice. When mice were treated with PF-03732010 either twenty-four hours before or 14 days after injection of tumor cells, PF-03732010 (20 mg/kg) significantly inhibited metastases and tumor burden increase in lungs (TGI 93% and 87% respectively) with a concomitant increase in median survival of 39 and 19 days respectively. Overall, PF-03732010 consistently demonstrated significant antitumor activity, reduction in metastatic burden and improvement in survival. PF-03732010 is expected to possess antitumor activity against tumors that over-express P-cadherin and is a promising new antibody for the treatment of certain cancers.
Fundamentals of Drug Metabolism and Pharmacogenomics Within a Learning Healthcare System Workflow Perspective

This chapter introduces fundamental concepts of pharmacogenomics, including drug metabolism, and provides an informatics workflow-based perspective inspired by a learning healthcare system framework. Our intent is that the reader sees pharmacogenomics as a foundation of precision medicine, which is reliant upon informatics to deliver actionable patient-tailored knowledge at the point of care. Further, pharmacogenomics knowledge is poised to be further developed so as to be amenable to multi-drug comorbid disease treatment necessitated by precision medicine practice. Upon reviewing this chapter, we hope the reader understands how informatics is uniquely suited to i) enhance clinic-based precision medicine practice through appropriate dissemination of patient-tailored actionable pharmacogenomics knowledge, and ii) to advance the knowledge base underpinning pharmacogenomics by gleaning insights from real world outcomes of these same clinic-based populations. The methodologic considerations highlighted within this workflow-base perspective encompass end-to-end forward and reverse translational informatics activities, designed to both appropriately deploy existing pharmacogenomics knowledge, as well as contribute to its advancement by harnessing insights from real-world data.
In vitro, primarily microfluidic models for atherosclerosis

Abstract Atherosclerosis develops over many years, so in vivo and in vitro models are necessary to understand each step in the progression of the disease and to test interventions meant to prevent, halt, or reverse it. While animal models are immensely useful, they do not fully recapitulate the biochemistry or pathology of human disease. Therefore, in vitro models fill an important role, and sophisticated systems for incorporating fluid flow to mimic arterial hemodynamics have developed over the last 40 years. The earliest designs gradually became more complex to include more cell types, stenosis geometry, and disturbed flow regimes. These custom, in vitro flow devices culminated in microfluidic designs in the 2000s once investigators could mold arbitrary geometry at the microscale to finely control cellular exposure to flow. This chapter explores the evolution of in vitro models of atherosclerosis and the variety of hypotheses and results that have emerged from these efforts.
Practical experience and lessons learnt on public health interventions to prevent and control novel coronavirus pneumonia (COVID-19) in Huangpu District, Shanghai

The novel coronavirus pneumonia (COVID-19) quickly spread from Wuhan, Hubei Province to the all other provinces in China, and globally since December 2019. Huangpu District of Shanghai is one of the communities where COVID-19 occurred earlier. By summarizing and reviewing experience and lessons learnt in Huangpu District, Shanghai, the article characterized the innovative public health interventions to prevent and control COVID-19 that may be of relevance to urban communities in other provinces and cities of similar size. Key words: novel coronavirus pneumonia; working mode; practice; thought
Innovative Strategies to Finance and Deliver Long-Term Care

Policymakers have long tried and failed to solve the vexing problem of long-term care insurance. The federal Community Living Assistance Services and Supports (CLASS) Act, a voluntary, publicly administered long-term care (LTC) insurance program, was repealed in 2013, and the problem has gone from bad to worse. The number of private insurers offering LTC insurance has plummeted from over 100 in 2002, to about a dozen today. While some of this is due to consolidation, the larger force driving the exit is lack of profitability. This paper explores issues surrounding the LTC market including pricing, modeling, and alternative payment models, to better understand the reasons for market failure. We provide a review of innovative approaches used successfully in other industries, which may serve as a model for new ways to finance and deliver long-term care. Based on interviews with thought leaders across multiple disciplines and industries, we identify three of the most promising solutions: public and private long-term care insurance solutions, Medicare expansion solutions, and technology solutions.
On large norm periodic solutions of some differential equations

This paper is concerned with the existence of periodic solutions of large norm for a class of general Hamiltonian systems as well as a related family of second order Hamiltonian systems. The nature of the results presented here is if the nonlinear terms in the system satisfy appropriate conditions for large values of their arguments, then the systems possess arbitrarily large periodic solutions of arbitrary period.
Model Predictive Control for a Five-Phase PMSM Drive Using Four-Leg Five-Phase Inverter

In this paper, a cost-effective four-leg five-phase inverter is proposed for controlling permanent magnet synchronous motors (PMSM). In this topology, one of the phases of the five-phase PMSM is connected to the midpoint of DC voltage sources. The mathematical model of four-leg five-phase drive is derived. In addition, the discrete model of the five-phase PMSM is developed. The model predictive control for this motor is developed to regulate the motor speed. Simulation results are presented to validate the effectiveness of the proposed drive and control method.
Targeting therapy-resistant prostate cancer via a direct inhibitor of the human heat shock transcription factor 1.

Heat shock factor 1 (HSF1) is a cellular stress-protective transcription factor exploited by a wide range of cancers to drive proliferation, survival, invasion, and metastasis. Nuclear HSF1 abundance is a prognostic indicator for cancer severity, therapy resistance, and shortened patient survival. The HSF1 gene was amplified, and nuclear HSF1 abundance was markedly increased in prostate cancers and particularly in neuroendocrine prostate cancer (NEPC), for which there are no available treatment options. Despite genetic validation of HSF1 as a therapeutic target in a range of cancers, a direct and selective small-molecule HSF1 inhibitor has not been validated or developed for use in the clinic. We described the identification of a direct HSF1 inhibitor, Direct Targeted HSF1 InhiBitor (DTHIB), which physically engages HSF1 and selectively stimulates degradation of nuclear HSF1. DTHIB robustly inhibited the HSF1 cancer gene signature and prostate cancer cell proliferation. In addition, it potently attenuated tumor progression in four therapy-resistant prostate cancer animal models, including an NEPC model, where it caused profound tumor regression. This study reports the identification and validation of a direct HSF1 inhibitor and provides a path for the development of a small-molecule HSF1-targeted therapy for prostate cancers and other therapy-resistant cancers.
Cerebral and Brainstem Diseases of Cattle

Cerebral and brainstem diseases cause a change in the mental status of the affected animal. Clinical signs suggestive of cerebral or brainstem diseases are commonly seen in cattle.1 There are more than 120 diseases that are reported to affect cerebral and/or brainstem function resulting in either coma, severe depression or seizure.2 The scope of this paper is not to review all the causes of cerebral-brainstem disease in cattle. The intent is to provide information on how the clinical exam can be used to localize dysfunction to these areas and to review recent (since 1990) information regarding some of the diseases of cattle which affect the cerebral cortex or brainstem. The methodology for collecting cerebrospinal fluid (CSF) from cattle and the diagnostic implications that can be derived from the CSF analysis will be presented. Most diseases of the brain in cattle are caused by infectious, toxic or metabolic causes and have been so divided in the following review.
Abstract 59: Post-stroke Delivery of Microrna-363 to Middle-aged Female Rats is Internalized by Neurons and Suppresses the Cell Death Effector Pathway

Background: MicroRNAs serve as translational inhibitors and offer a unique therapeutic target for acute diseases such as stroke. Profiling of circulating miRNA after stroke identified mir363, whose...
Social Policy Reform and Local Agency in China

This introductory chapter presents the central claims of this book and its salience. It begins with an assessment of social policy reform in China and the “new welfare politics” with subnational variations. What does the new social policy mean for the “new urban poor”? Why are there persistent subnational variations despite increasing top-down pressure? To answer the key research questions, the chapter turns to the book’s two key frames, authoritarian political institutions and local growth strategies, and how they together have shaped the varying trajectories of local agency. The chapter then clarifies the salience of the policy domains and cases selected and previews the chapter to come.
Modified Broström With and Without Suture Tape Augmentation: A Systematic Review.

Abstract The Modified Brostrom has become the gold standard for operative management of chronic lateral ankle instability. Despite overall good clinical outcomes with this procedure, recent biomechanical data has called into question the strength and durability of this technique. Accordingly, the addition of suture tape to the Modified Brostrom construct has been described in an attempt to more closely recreate the natural biomechanical properties of the ankle lateral ligament complex. We performed a systematic review of the literature was using PubMed, Embase, and CINAHL to identify English-language articles from 2009 - present discussing outcomes with the augmented Modified Brostrom technique. A total of 4 studies (2 retrospective cohort studies, 2 case series) involving 156 patients with Modified Brostrom with augmentation met inclusion criteria. Average follow-up time was 13.8 months. Of the 3 studies reporting patient-reported outcome measures both pre-and post-operatively, there was a significant improvement in all measures (p 0.05) between the two procedures across studies. There were no significant differences in complications between techniques. Modified Brostrom with suture tape augmentation for chronic lateral ankle instability can produce good short-term clinical outcomes with few complications, comparable to the Modified Brostrom alone.
Systematic review of pediatric mandibular arteriovenous malformations.

Abstract Objectives The management of arteriovenous malformations (AVMs) can be challenging in the pediatric population. It is of utmost importance to keep in mind various management options as these lesions can have disastrous outcomes. This is a systematic review of the treatment AVMs describing the current practices so that practitioners can be aware of what is currently reported in the literature. The challenges of AVM management can be mitigated when approaching these patients through a multidisciplinary team-based approach. Methods A systematic review of the literature was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to gain insight into pediatric mandibular AVMs. Demographics, arterial involvement, clinical symptoms, imaging, treatment, complications, follow-up, and outcomes were reviewed. Results 63 articles were included in the systematic review with 106 distinct cases. The age range was from 3 to 17 years with a mean of 12 years. 51% of the patients were female. The most common clinical presentation was emergency hemorrhage (37.4%), swelling or edema (33.0%), and persistent bleeding (31.9%). The most common CT findings were osteolytic changes and radiolucencies (60.8%). With regards to treatment, 56.6% of patients had embolization alone and 34.9% were treated with embolization in combination with other surgical treatments. Of the patients who had surgical resection of the lesion, 50% had resection followed by reconstruction, 23.7% had curettage of the lesion, and 13.2% had resection/curettage then immediate reimplantation of the mandible segment. The most common complications after intervention included bleeding in 17.9% of patients and infection in 8.3% of patients. 89.5% of patients were clinically cured without recurrence at follow-up. Conclusion Diagnosing AVMs can be difficult as they have variable clinical and radiographical presentations. Although rare, because of risk of massive hemorrhage, it is important for healthcare professionals to be aware of this pathology. Many surgical techniques, routes of embolization, embolic material, and other experimental therapies have been described and this review shows that the most cases had embolization as a part of the treatment. The role of therapies targeted at the molecular level still needs to be further explored.
The Delegation of Decision Rights: An Experimental Investigation

Abstract Purpose Despite the benefits of delegation, anecdotal and survey-based evidence suggests that firms do not optimally delegate decision-making authority. However, to date, no quantifiable evidence supports this claim. Methodology/approach We design an experiment to explore the superior’s choice between delegation and information elicitation. We also examine the effect of the superiors’ choice on the amount of effort provided by subordinates to gather decision-facilitating information. Findings We find that, compared to economic predictions, superiors delegate less often than they should. Subordinates exert lower effort when superiors elicit information than when superiors delegate the decision to them. As a result, superiors earn lower profit when they elicit information than when they delegate decision-making authority. Research implications Our empirical evidence supports two main tenets espoused in the literature on the allocation of decision rights. First, the evidence of under delegation contributes to the literature which maintains that superiors’ tendency to under-delegate leads firms to become overly centralized. Originality/value By designing a novel experimental, we identify systematic ways in which behavior deviates from economic theory and contribute to the discussion on how firms utilize information. In particular, under delegation prevents firms from exploiting economies that arise from local capabilities and task specialization, and results in forgone profits.
A New Model for the Living Cell: A Summary of the Theory and Recent Experimental Evidence in Its Support

Publisher Summary This chapter focuses on a new model for the living cell. It is generally acknowledged that living organisms, although vastly complex, can eventually be understood in terms of basic principles derived from studies of the simple inanimate world. The primary function of a biologist is thus not so much to deduce basic principles-that belongs to physics-but to understand how these principles apply in a unique complex system. The most logical time to begin fundamental biological research, therefore, would be when men have achieved complete understanding of the physical world. Then one could be certain that the foundations of his reasoning would be sound. Since this has not been the case-investigations of living matter are as old as the study of the inanimate world-the student of biology must be doubly cautious in accepting assumptions presented as facts. The chapter begins with such a reevaluation of the basic assumptions of an old and venerable concept, the membrane theory. After discussing some of the difficulties in this concept, it goes on to summarize both theoretical aspects and experimental evidence for an alternative model of the living cell.
America's Main Street Hotels: Transiency and Community in the Early Auto Age

Review of: "America's Main Street Hotels: Transiency and Community in the Early Auto Age," by John A. Jakle and Keith A. Sculle.
From lab bench to innovation: Critical challenges to nascent academic entrepreneurs

University research laboratories are important sources of the inventions and discoveries that become significant innovations with broad economic and societal impact. Invention alone is not innovation; innovation is the long, hard work of taking new technologies and bringing them to commercialization. There are many pathways for the dissemination of new knowledge that arises from basic research at universities, ranging from traditional methods such as publication and training students to licensing technology to established firms or new ventures. One way to transform new knowledge into valuable innovations is for university researchers to undertake the creation of new firms based on their discoveries through academic entrepreneurship. The problem is that university scientists and inventors with a discovery made at a laboratory bench face challenges beyond those experienced by traditional high-technology venture founders: they must finish creating the technology before they can begin using it (Jensen and Thursby, 2001; Pisano, 2006). Academics typically start with inventions so immature that their commercial success cannot be predicted (Jensen and Thursby, 2001). Academic entrepreneurship is an emerging and developing phenomenon, and there is a growing body of literature about new ventures based on university academic. However, limited research has been directed toward nascent academic entrepreneurs (NAEs) to understand the key challenges of bringing innovations to market. The majority of this work has focused on the institutional experience rather than the academic entrepreneurs and their individual experiences (Rothaermel et al., 2007). Within the broader fields of entrepreneurship and innovation, it has been argued that high-potential startups such as academic ventures should receive particular attention from scholars (Davidsson and Gordon, 2011). The following research addressed this gap. Nascent academic entrepreneurship involves more than transforming an invention into a commercialized innovation. It is about the genesis of ideas and the emergence of opportunities, the birth of new organizations, their evolution into new companies, and the transformation of scientists into leaders. It also is about providing the foundation for future innovation by others. Though nascent academic entrepreneurship is increasing in frequency, it is not well understood. The dissertation examines this important topic.
The State of CD4+ T Cell Activation Is a Major Factor for Determining the Kinetics and Location of T Cell Responses to Oral Antigen

Current models suggest that inductive immune responses to enteric Ag are initiated in Peyer’s patches (PP) and mesenteric lymph nodes (MLN) followed by migration of activated, memory-like CD4 + T cells to extralymphoid sites in the intestinal lamina propria (LP). The resultant immune system contains both naive and activated T cells. To examine the differential responses of naive and memory-like T cells to oral Ag, bone marrow chimeras (BMC) were generated. Irradiated BALB/c hosts were reconstituted with a mix of DO11.10 × RAG-1 −/− and BALB/c bone marrow. In unprimed DO11.10 and BMC models, LP and PP DO11.10 T cells responded to oral Ag with similar kinetics. Responses of activated, memory-like T cells to oral Ag were examined in thymectomized BMC 60 days after i.p. immunization with OVA peptide in Freund’s adjuvant (OVA 323–339 /CFA). Results indicate that i.p. OVA 323–339 /CFA generated a high proportion of memory-like CD45RB low DO11.10 T cells in peripheral lymphoid (40%) and intestinal LP (70%) tissue. Previously activated DO11.10 T cells in the LP responded to oral Ag earlier and at 50% higher levels compared with memory CD4 + T cells localized to PP tissue. These data indicate that responses to oral Ag in antigenically naive animals are initiated in PP whereas in Ag-experienced animals LP T cells respond earlier and more vigorously than cells in PP. Taken together, these data suggest that previous activation alters the hierarchy of T cell responses to oral Ag by enhancing the efficiency of LP T cell activation.