cssi/SciSciGPT-SciSciNet huggingface dataset:
Calcium antagonist receptors.

It is clear that the regulation of calcium movement plays a pivotal role in the control of a multitude of cellular activities. A discussion of the function of intracellular calcium, and of the many processes that are believed to control the level of cytoplasmic calcium ions, is beyond the scope of this chapter, and the reader is referred to one of the many excellent reviews available on this topic (Rahamimoff et al., 1976; Bolton, 1979; Kretsinger, 1979; Sulakhe and St. Louis, 1980; Siesjo, 1981; Campbell, 1983; Berridge, 1984; Schulman, 1984; Carafoli, 1985). Instead, we intend to focus on the mechanism by which calcium enters excitable cells following electrical stimulation, and, more specifically, the ways in which drugs modify this process. Electrically excitable cells possess one or more classes of transmembrane proteins that have been termed ion channels, based on their ability to conduct normally impermeant cations or anions into or out of these cells. Such channels open in response to changes in membrane potential, and the subsequent passage of ions may influence cell excitability, as in the case of sodium or potassium channels, or may alter the activity of a variety of intracellular enzymes, as in the case of calcium channels.
Collaborative study of a spectrofluorometric assay for Rauwolfia serpentina tablets and powdered root.

Reserpine-rescinnamine group alkaloids are extracted from Rauwolfia serpentina preparations into a dimethylsulfoxide (DMSO)-methanol mixture and diluted with 0.5N H2SO4. The chloroform extract of this solution is passed through a 0.1N NaOH-Celite column and then through a silica gel column. The weakly basic alkaloids trapped on the latter column are eluted with a methanol mixture; a portion of the eluate is treated with nitrous acid and the reserpine-rescinnamine content is determined by measuring the intensity of fluorescence of the oxidation product. The following means and standard deviations (11 collaborators) were obtained for the determination of reserpine-rescinnamine group alkaloids in 4 samples of Rauwolfia serpentina (NF reference powder, 100 mg and 50 mg commercial tablets, and a 45 mg synthetic tablet formulation) : 0.174% +/- 0.0112, 0.131% +/- 0.0047, 0.160% +/- 0.0100, and 0.153% +/- 0.0083, respectively.
Family expenditures supporting children across income and urbanicity strata

Abstract Recent decades have seen growth in the level, geographic distribution, and repercussions of income inequality, with unequal access to enriching resources hypothesized to support the intergenerational transmission of inequality. Yet little evidence delineates economic or contextual variation in resources directed at children. Using data from the Consumer Expenditure Survey on 31,842 families, this study assessed how family expenditures vary across income and urbanicity strata. Results found that high income families spent proportionally more of their total budget on child resources and proportionately less on basic needs compared to lower income families. These patterns buttress arguments that access to enriching resources may be an important mechanism through which economic advantage is passed on to the next generation. Results further found that income disparities in expenditures were heightened in large urban areas and tempered in rural areas. Together results highlight both income and urbanicity disparities in families' expenditures on child-promotive resources.
Updated Results from a Phase II Study of Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory, Follicular NHL.

Abstract Galiximab is a PRIMATIZED®, anti-CD80, monoclonal antibody with human IgG1 constant regions and macaque variable regions. CD80 is an immune costimulatory molecule that is constitutively expressed on the surface of follicular lymphomas. Modest single-agent clinical activity was demonstrated in a Phase I study in relapsed or refractory, follicular NHL (ORR=11%). Preclinical data show that galiximab + rituximab may be more effective than either antibody alone. Here we report updated results from the Phase II part of a multicenter study (Study 114–21) evaluating galiximab + rituximab for relapsed or refractory, follicular NHL. Patients (pts) were administered galiximab (500 mg/m2 qwk x 4) concurrently with a standard course of rituximab (375 mg/m2 qwk x 4). Rituximab-refractory pts (no response or a response with TTP
MARRIAGE AND DISSOLUTION AMONG WOMEN'S COHABITATIONS: VARIATIONS BY STEPFAMILY STATUS AND SHARED CHILDBEARING.

Cohabiting unions increasingly involve children, either born during the union and/or from prior relationships (i.e., stepchildren). Drawing from arguments about the institutionalization of cohabita...
The Effects of Increasing Temperature on Solenopsis invicta (Hymenoptera:Formicidae)

This experiment focuses on the Solenopsis invicta’s ability to withstand increasing temperatures in a dry, arid environment and determining the highest temperature that it would be possible for them to survive without the protection of an underground mound. Forty organisms were collected and separated in half, one being the control group and the other being the test group. The test organisms were then placed into a commercial food dehydrator and temperature was gradually increased. The behaviors of the organisms were noted as each increase in temperature took place. The lowest temperature that a change was observed was at 115°F and the highest temperature found that a fire ant could withstand was 125°F. The majority of change occurred at 120°F. At this temperature, 90% of the test ants became motionless and died. These results demonstrate the importance of the complex nests that fire ants build underground in order to regulate their temperatures.
Can we avoid reductionism in risk reduction

Risk assessment and risk reduction have become increasingly central to criminal justice policy and practice in the last 25 years. Yet there remains a lack of consensus both on the theoretical and methodological foundations of risk and on its social and practical implications. Some proponents see risk assessment and reduction as solutions to the inefficiencies and injustices of contemporary mass incarceration. Some critics see actuarial risk as being partially responsible for mass incarceration, and warn that recent iterations will only reinscribe existing inequalities under a new guise of objectivity. Both perspectives contain elements of truth, but each falls short because neither adequately specifies the different dimensions of risk that condition its effects. Using two prominent frameworks as foils, this article excavates the contested terrain of risk assessment and exposes a set of distinctions that can inform the use—and prevent the abuse—of risk knowledge in criminal justice policy.
Abstract TP276: Mild Short-term Hypertension Exacerbates Amyloid Pathology and Microhemorrhages in Mouse Model of Amyloidosis

Introduction: Multiple epidemiological studies link vasculature-affecting disorders, such as hypertension, diabetes mellitus, kidney failure and stroke, with dementia and Alzheimer’s disease (AD). ...
Characterizing the allopolyploid species among the wild relatives of soybean: Utility of reduced representation genotyping methodologies

Allopolyploidy is a common feature in many angiosperm genera. The perennial wild relatives of soybean in the genus Glycine include at least nine recently formed (within the last million years) allopolyploid taxa. This study examined three allopolyploid and four diploid progenitor taxa using genome-wide single nucleotide polymorphisms (SNPs) and network analysis. Genotyping by sequencing (GBS) was used to generate SNPs and results were compared with previous analyses from transcriptome data. Three lanes of Illumina sequencing produced genotypes for 70 accessions and an alignment of 22,806 SNPs across eight taxa with no missing data. The alignment combined with network analysis confirmed results from previous studies. In addition, the extended sampling made possible by GBS identified accessions that have either been misclassified or samples that came from mixed seed stocks. The most intriguing results are the discovery of previously unrecognized substructure within diploid taxa, and the likelihood that allopolyploids were derived from particular subgroups. Separation of allopolyploid SNPs into SNPs derived from homoeologous progenitor species indicate that allopolyploids no longer share genotypes with their diploid progenitors but have evolved separately long enough for signals from direct progenitor genotypes to be obscured.
Abstract 514: Jak2 Tyrosine Kinase Mediates Angiotensin II Renal Pathogenesis via its Pressor Dependent Actions

We previously found that Jak2 kinase, expressed within vascular smooth muscle cells (VSMC), plays a critical role in angiotensin II (Ang II)-mediated hypertension. Given that Jak2 mediates both pressor-dependent and pressor-independent events, we sought to determine the role of blood pressure (BP), per se, on the deleterious effects of Jak2 within the kidney. To investigate this, three groups of mice were examined; i) wild type mice (Controls) that received Ang II infusion, ii) mice lacking Jak2 expression within the VSMC (VSMC Jak2 Null) that also received Ang II, and iii) Control mice that received Ang II plus an anti-hypertensive triple therapy (3Rx). After baseline BP recordings, Ang II was infused (1000 ng/kg/min, SC) to all groups and the 3Rx regimen (80 mg/L hydralazine, 5 mg/L reserpine, 30 mg/L hydrochlorothiazide in the drinking water) was initiated two days later to the 3Rx group, in order to maintain BP at similar levels to the VSMC Jak2 Null group. After 28 days of Ang II, mice were euthanized and the kidneys were assessed via histological, molecular, and functional approaches. Chronic Ang II infusion significantly increased the levels of intrarenal Ang II in all three groups; Control = 1,262±283 fmol/g, VSMC Jak2 Null = 1,655±666 fmol/g, and 3Rx = 2,174±588. While Ang II infusion significantly increased the mean BP in the Control group (152 ± 2 mm Hg), it was significantly, and similarly, lower in both the VSMC Jak2 Null and 3Rx groups (125 ± 5 mm Hg and 131 ± 5 mm Hg, respectively). Glomerular sclerosis was absent and interstitial fibrosis ranged from absent- mild- moderate, and was similar in all groups. The increases in i) perivascular infiltration of CD3+ lymphocytes, ii) CTGF gene expression, iii) tubule casts and iv) albuminuria that were observed in the Control mice, were significantly reduced in both the VSMC Jak2 Null and 3Rx groups. [CTGF mRNA Levels: Control = 100%±17, VSMC Jak2 Null = 70%±12*, 3Rx= 56%±17*. Urine Albumin (ng/day): Control = 414 ± 262, VSMC Jak2 Null = 138 ± 172*, 3Rx= 101 ± 89* (*, p
Induction of human cytochrome P450 3A4 by the irreversible myeloperoxidase inactivator PF-06282999 is mediated by the pregnane X receptor

1. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide (PF-06282999) is a member of the thiouracil class of irreversible inactivators of human myeloperoxidase enzyme and a candidate for the treatment of cardiovascular disease. PF-06282999 is an inducer of CYP3A4 mRNA and midazolam-1'-hydroxylase activity in human hepatocytes, which is consistent with PF-06282999-dose dependent decreases in mean maximal plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of midazolam in humans following 14-day treatment with PF-06282999. 2. In the present study, the biochemical mechanism(s) of CYP3A4 induction by PF-06282999 was studied. Incubations in reporter cells indicated that PF-06282999 selectively activated human pregnane X receptor (PXR). Treatment of human HepaRG cells with PF-06282999 led to ∼14-fold induction in CYP3A4 mRNA and 5-fold increase in midazolam-1'-hydroxylase activity, which was nullified in PXR-knock out HepaRG cells. TaqMan® gene expression analysis of human hepatocytes treated with PF-06282999 and the prototypical PXR agonist rifampin demonstrated increases in mRNA for CYP3A4 and related CYPs that are regulated by PXR. 3. Docking studies using a published human PXR crystal structure provided insights into the molecular basis for PXR activation by PF-06282999. Implementation of PXR transactivation assays in a follow-on discovery campaign should aid in the identification of back-up compounds devoid of PXR activation and CYP3A4 induction liability.
Advancing open science with version control and blockchains

The scientific community is facing a crisis of reproducibility: confidence in scientific results is damaged by concerns regarding the integrity of experimental data and the analyses applied to that data. Experimental integrity can be compromised inadvertently when researchers overlook some important component of their experimental procedure, or intentionally by researchers or malicious third-parties who are biased towards ensuring a specific outcome of an experiment. The scientific community has pushed for "open science" to add transparency to the experimental process, asking researchers to publicly register their data sets and experimental procedures. We argue that the software engineering community can leverage its expertise in tracking traceability and provenance of source code and its related artifacts to simplify data management for scientists. Moreover, by leveraging smart contract and blockchain technologies, we believe that it is possible for such a system to guarantee end-to-end integrity of scientific data and results while supporting collaborative research.
HIV Viral Suppression, 37 States and the District of Columbia, 2014

Achieving viral suppression among HIV-positive persons is a critical component of HIV treatment and prevention, because it leads to improved health outcomes for the individual and reduced risk of HIV transmission. There is wide variation in viral suppression across jurisdictions, races/ethnicities, age groups, and transmission risk groups. This analysis uses HIV surveillance data to examine rates of viral suppression among people living with diagnosed HIV (PLWDH) in 38 jurisdictions with complete lab reporting. Among people who received a diagnosis in 2014, the percentage with viral suppression within 12 months of diagnosis and the average time to viral suppression was assessed. Overall, among PLWDH in 2014, 57.9% were virally suppressed, and, among people with HIV diagnosed in 2014, 68.2% were suppressed within 12 months of diagnosis with an average time to suppression of 6.9 months. All outcomes varied by jurisdiction, but most had similar patterns of disparities with a few exceptions. These data highlight the need for tailored interventions at the local level. In addition, jurisdictions with relatively low viral suppression among particular groups could adapt effective interventions from jurisdictions who have higher rates of suppression.
Military Veterans and Neighborhood Racial Integration: VA Mortgage Lending Across Three Eras

The military has long been seen as an avenue for increasing racial equality for minorities, especially black Americans. In this article, we examine to what extent military veterans also experience residential integration by looking at neighborhood residential outcomes for black and white men utilizing the popular Veterans Affairs (VA) loan program to purchase a home. We draw on data from the Home Mortgage Disclosure Act (HMDA) to examine residential integration among white and black veteran homebuyers compared to homebuyers utilizing conventional loans over three major lending eras: 1990s, 2000–2007, and 2008–2015. By 2015, a quarter of all home purchase mortgages loans to black men were VA loans even though veterans made up only a tenth of the adult black male population. In our multivariate analyses, we uncover a sizeable combined swing toward neighborhood minority-white integration, 14.4% points, among black and white veterans who use VA loans. Compared to those with conventional loans, black veterans live in neighborhoods with 10% points fewer minorities and, white veterans, 4.4% points fewer whites. Our results illustrate how racial integration in the US military has the potential to foster lasting housing integration among veterans.
Kinship Classification through Latent Adaptive Subspace

We tackle the challenging kinship classification problem. Different from kinship verification, which tells two persons have certain kinship relation or not, kinship classification aims to identify the family that a person belongs to. Beyond age and appearance gap across parents and children, the difficulties of kinship classification lie in that any data of the children to be classified are unavailable in advance to help training. To handle this challenge, an auxiliary database with complete parents and children modalities is employed to uncover the parent-children latent knowledge. Specifically, we propose a Latent Adaptive Subspace learning (LAS) to uncover the shared knowledge between two modalities so that the unseen test children are implicitly modeled as latent factors for kinship classification. Moreover, person-wise and family-wise constraints are designed to enhance the individual similarity and couple the parents and children within families for discriminative features. Comprehensive experiments on two large kinship datasets show that the proposed algorithm can effectively inherit knowledge from different databases and modalities and achieve the state-of-the-art performance.
Emerging Class III Antiarrhythmic Agents:Mechanism of Action and Proarrhythmic Potential

The goal of developing an antiarrhythmic agent effective against malignant ventricular arrhythmias while maintaining a low side-effect profile remains elusive. The class III drugs amiodarone and sotalol are the best available agents. However, both drugs possess properties outside the realm of a pure class III effect, and their use is limited by a variety of dose-related side effects. There are several drugs with more selective class III properties currently in development. This review provides an overview of the optimal characteristics of an effective theoretical class III drug and a summary of the properties of a number of class III drugs under active investigation. An ideal class III antiarrhythmic agent for a reentrant arrhythmia should provide use-dependent prolongation of the action potential duration with slow onset and rapid offset kinetics. This drug would prolong the effective refractory period of cardiac tissue selectively at the rapid heart rates achieved during ventricular tachycardia or fibrillation with a delayed onset of action, and a rapid resolution of its effects on resumption of physiologic heart rates. With little effect on the refractory period at normal or slow heart rates, the ability to induce torsade de pointes would be lessened. In contrast to these ideal properties, most currently available and investigational agents have a reverse use-dependent effect on the action potential duration, producing more effects on the refractory period at slower heart rates. This property results in part from preferential block of the rapidly activating component of the delayed rectifier potassium channel (I_Kr), with little or no effect on the slowly activating component (I_Ks). The development of a drug with favorable blocking kinetics that selectively blocks I_Ks may result in lower proarrhythmic events while still maintaining effective antiarrhythmic properties.
Theory of Association and Substitution Reactions

We have interpreted the assigned title a bit liberally and selected some theoretical aspects of charge transfer reactions in solution as our topic.
Current Techniques for the Repair of Complex Orbital Fractures: Miniplate Fixation and Cranial Bone Grafts

Background: Computerized imaging of complex fractures of the orbit and facial skeleton have brought about demands for methods of anatomic restoration. In this article, the author outlines techniques for metallic rigid anatomic fixation of facial fractures and the cranial bone graft method of augmentation. Methods: Clinical results of fracture repair using various types of metallic plates and replacement of missing bone with cranial bone grafts are presented and techniques are described. Conclusion: Rigid three-dimensional fixation of the facial skeleton with metallic plate fixation and augmentation with cranial bone grafts has produced more predictable correction of severe fractures of the orbit and facial skeleton.
Glaucoma secondary to intraocular tumors: mechanisms and management.

Purpose of review Glaucoma secondary to intraocular tumors is important to consider in eyes with a known tumor and those with unilateral or refractory glaucoma. The purpose of this review is to discuss the mechanisms and management of intraocular tumors with related secondary glaucoma. Recent findings Several intraocular tumors can lead to glaucoma, including iris melanoma, iris metastasis, iris lymphoma, trabecular meshwork melanoma, choroidal melanoma, choroidal metastasis, retinoblastoma, and medulloepithelioma. The mechanisms for glaucoma include solid tumor invasion into the angle, tumor seeding into the angle, angle closure, and iris neovascularization. Management of the tumor can lead to resolution of glaucoma. Management of the secondary glaucoma may involve medical therapy, transscleral cyclophotocoagulation, laser trabeculoplasty, and potentially antivascular endothelial growth factor therapy. Minimally invasive glaucoma surgery (MIGS) can be considered for eyes with treated, regressed posterior segment malignancies if there is no iris or ciliary body involvement. Importantly, avoidance of MIGS, filtering, or shunting surgery in eyes with active malignancies is emphasized. Summary Intraocular tumors can produce secondary glaucoma. Treatment of the primary tumor can sometimes resolve the glaucoma. Topical, oral, or laser therapies can be considered. Avoidance of MIGS, filtering, or shunting surgery is advised until the malignancy is completely regressed.
Preliminary investigation of honey-doped electrospun scaffolds to delay wound closure.

Manuka honey is an ancient remedy to improve wound healing; however, an effective delivery system is needed to facilitate extended release of honey into wounds. We developed an electrospun dermal regeneration template consisting of a poly (e-caprolactone) (PCL) scaffold embedded with 1%, 5%, 10%, or 20% manuka honey. In vitro studies demonstrated that honey PCL scaffolds were not toxic to macrophages, and they allowed for macrophage infiltration into the scaffolds. Vascular endothelial growth factor (VEGF), a marker of angiogenesis, was released by macrophages cultured with scaffolds and macrophage/scaffold conditioned media promoted endothelial cell tube formation in an angiogenesis assay. In a full thickness murine wound model, the scaffolds prevented rapid wound contraction. In vivo, cells infiltrated the scaffolds by post-wounding day 7, but the honey scaffolds did not affect collagen deposition at that time. In summary, preliminary studies investigating the effect of honey on tissue repair show that scaffolds prevent rapid wound contraction, allow for cell infiltration, and promote angiogenesis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2620-2628, 2019.
Direct Comparison Between Multi-Dimensional Terahertz Vibrational Spectroscopies

Multidimensional terahertz (THz) spectroscopy is a powerful tool for understanding nonlinear excitation, coherent energy flow, and coupling between collective degrees of freedom on ultrafast time scales. With extreme vibrational excitation using high-field THz light, 2D THz spectroscopy can reveal how anharmonic mode coupling results in coherent energy transfer and ascertain the excitation pathways behind nonlinear sample responses. We directly compare 2D THz-THz transmission measurements to 2D THz-THz-Raman measurements and explore evidence of anharmonic coupling between phonon modes in β-barium borate.
You're (Probably) Not Bad at Your Job: Impostor Syndrome and IT Work

What is it about working in IT that can make us feel like everyone will ‘figure out’ we have no idea what we're doing? ‘Impostor syndrome’ refers to the belief that you are under-qualified or inadequate, even in the face of overwhelming evidence to the contrary. In only seven minutes we'll examine the various ways impostor syndrome manifests itself and why is it so common in IT work. This will hopefully alleviate any feelings you may have of being a complete and total fraud. We're pretty sure we know what we're talking about...mostly.
Changing Results-Engage and Activate to Enhance Wellness: A Randomized Clinical Trial to Improve Cardiovascular Risk Management.

Background Despite the success of current cardiovascular disease (CVD) management programs, many patients do not achieve optimal control of CVD‐related risk factors. New strategies are needed to be...
Preemption and Priority

Our discussion up to this point has been focused on normal operation where system users are regular drivers/vehicles and the objective is to provide equitable service to all. In this chapter, we consider special operations that give preferential treatment to some special vehicles such as public transit, emergency vehicles, and vehicles that might be endangered by a passing train. Depending on the nature of the problem, the preferential treatment may be arranged as priority control or preemption control, topics of which will be discussed in this chapter.
Performance evaluation of soil moisture profile estimation through entropy-based and exponential filter models

In this study we analyzed two models commonly used in remote sensing-based root-zone soil moisture (SM) estimations: one utilizing the exponential decaying function and the other derived from the p...
REDESCOBRINDO OS MÉTODOS AUTOCOMPOSITIVOS DE SOLUÇÃO DE CONFLITOS EM TEMPOS DE COVID-19

The paper aims to reflect on best ways to deal with juridical effects of COVID-19 pandemic in Brazil. It proposes to encourage the use of consensual forms of conflict resolution, alternative or complementary to the Judicial Branch. Dialogue, understanding and self-compositional methods such as negotiation, mediation and conciliation, more than the conflicts judicialization, can provide adequate solutions to minimize some impacts of the pandemic in the field of obligations, to deal with breached contracts. The research is based on bibliographic research and experiences report.
Aarohi: Making Real-Time Node Failure Prediction Feasible

Large-scale production systems are well known to encounter node failures, which affect compute capacity and energy. Both in HPC systems and enterprise data centers, combating failures is becoming challenging with increasing hardware and software complexity. Several data mining solutions of logs have been investigated in the context of anomaly detection in such systems. However, with subsequent proactive failure mitigation, the existing log mining solutions are not sufficiently fast for real-time anomaly detection. Machine learning (ML)-based training can produce high accuracy but the inference scheme needs to be enhanced with rapid parsers to assess anomalies in real-time. This work tackles online anomaly prediction in computing systems by exploiting context free grammar-based rapid event analysis.We present our framework Aarohi1, which describes an effective way to predict failures online. Aarohi is designed to be generic and scalable making it suitable as a real-time predictor. Aarohi obtains more than 3 minutes lead times to node failures with an average of 0.31 msecs prediction time for a chain length of 18. The overall improvement obtained w.r.t. the existing state-of-the-art is over a factor of 27.4×. Our compiler-based approach provides new research directions for lead time optimization with a significant prediction speedup required for the deployment of proactive fault tolerant solutions in practice.
NME/NM23/NDPK and Histidine Phosphorylation

The NME (Non-metastatic) family members, also known as NDPKs (nucleoside diphosphate kinases), were originally identified and studied for their nucleoside diphosphate kinase activities. This family of kinases is extremely well conserved through evolution, being found in prokaryotes and eukaryotes, but also diverges enough to create a range of complexity, with homologous members having distinct functions in cells. In addition to nucleoside diphosphate kinase activity, some family members are reported to possess protein-histidine kinase activity, which, because of the lability of phosphohistidine, has been difficult to study due to the experimental challenges and lack of molecular tools. However, over the past few years, new methods to investigate this unstable modification and histidine kinase activity have been reported and scientific interest in this area is growing rapidly. This review presents a global overview of our current knowledge of the NME family and histidine phosphorylation, highlighting the underappreciated protein-histidine kinase activity of NME family members, specifically in human cells. In parallel, information about the structural and functional aspects of the NME family, and the knowns and unknowns of histidine kinase involvement in cell signaling are summarized.
ENERGETICS OF GROWTH IN CATTLE

Fifty-nine energy-balance measurements were made on eight Hereford heifers during the fattening period in order to estimate the maintenance requirement at body weights between 220 and 430 kg. Analysis of covariance indicated that partial efficiency of metabolizable energy (ME) use for tissue deposition was not affected by diet, but maintenance requirement on the same diet decreased by 54–75 kJ/W 0.75 for each 100 kg increase in body weight.
A closed-loop self-righting controller for seated balance in the coronal and diagonal planes following spinal cord injury.

Abstract Spinal cord injury (SCI) often results in loss of the ability to keep the trunk erect and stable while seated. Functional neuromuscular stimulation (FNS) can cause muscles paralyzed by SCI to contract and assist with trunk stability. We have extended the results of a previously reported threshold-based controller for restoring upright posture using FNS in the sagittal plane to more challenging displacements of the trunk in the coronal plane. The system was applied to five individuals with mid-thoracic or higher SCI, and in all cases the control system successfully restored upright sitting. The potential of the control system to maintain posture in forward-sideways (diagonal) directions was also tested in three of the subjects. In all cases, the controller successfully restored posture to erect. Clinically, these results imply that a simple, threshold based control scheme can restore upright sitting from forward, lateral or diagonal leaning without a chest strap; and that removal of barriers to upper extremity interaction with the surrounding environment could potentially allow objects to be more readily retrieved from around the wheelchair. Technical performance of the system was assessed in terms of three variables: response time, recovery time and percent maximum deviation from erect. Overall response and recovery times varied widely among subjects in the coronal plane (415±213 ms and 1381±883 ms, respectively) and in the diagonal planes (530±230 ms and 1800±820 ms, respectively). Average response time was significantly lower (p
The Covariant Stone-von Neumann Theorem for Actions of Abelian Groups on C ∗ -Algebras of Compact Operators

In this paper, we formulate and prove a version of the Stone–von Neumann Theorem for every $$ C^{*} $$ -dynamical system of the form $$ \left( G,{\mathbb {K}} \left( {\mathcal {H}} \right) ,\alpha \right) $$ , where G is a locally compact Hausdorff abelian group and $$ {\mathcal {H}}$$ is a Hilbert space. The novelty of our work stems from our representation of the Weyl Commutation Relation on Hilbert $$ {\mathbb {K}} \left( {\mathcal {H}} \right) $$ -modules, instead of just Hilbert spaces, and our introduction of two additional commutation relations, which are necessary to obtain a uniqueness theorem. Along the way, we apply one of our basic results on Hilbert $$ C^{*} $$ -modules to significantly shorten the length of Iain Raeburn’s well-known proof of Takai–Takesaki Duality.
Chance-constrained optimization-based solar microgrid design and dispatch for radial distribution networks

We consider a solar microgrid design and dispatch problem using an adaptive stochastic optimization framework. First, we propose a two-stage mixed-integer model for optimal placement and planning of distributed generation (DG) units and energy storage system units. We incorporate time series modeling into stochastic optimization approach to characterize the solar irradiance uncertainty. In the first stage, design decisions (e.g., location and sizing of DGs) are made and in the second stage, dispatch decisions (e.g., how much to generate, how much to store) are made such that electricity demand is met in a reliable and cost effective way. Chance constraints are employed to control the real load shedding within a predefined probability level. Then, we propose a combined sample average approximation (SAA) and linearization technique to solve this problem more efficiently. The advantage of this approach is that no additional binary variables are introduced while reformulating the chance constraints. Computational time, quality of solution, and load shedding percentage are compared with the traditional SAA. Moreover, we carry out a comprehensive out-of-sample simulation on a real-world case study in the state of Arizona assessing the effectiveness of our approach. Numerical experiments demonstrate that the chance constraints are effective tools for control of load shedding in distributed generation and the proposed approach outperforms traditional methods both in terms of true load shedding percentage and computational time.
Turning Practicing Surgeons Into Health Technology Innovators: Outcomes From the Stanford Biodesign Faculty Fellowship.

Background. The Stanford Biodesign Faculty Fellows program was established in 2014 to train Stanford Medical and Engineering faculty in a repeatable innovation process for health technology transla...
αSMA+ fibroblasts suppress Lgr5+ cancer stem cells and restrain colorectal cancer progression

The development and progression of solid tumors is dependent on cancer cell autonomous drivers and the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) in the TME possess both tumor-promoting and tumor-restraining functions. In the current study, we interrogated the role of αSMA+ CAFs in a genetic mouse model of metastatic colorectal cancer (CRC). Selective depletion of αSMA+ CAFs resulted in increased tumor invasiveness, lymph node metastasis, and reduced overall survival. Depletion of αSMA+ CAFs reduced BMP4 and increased TGFβ1 secretion from stromal cells, and was associated with increased Lgr5+ cancer stem-like cells (CSCs) and the generation of an immunosuppressive TME with increased frequency of Foxp3+ regulatory T cells and suppression of CD8+ T cells. This study demonstrates that αSMA+ CAFs in CRC exert tumor-restraining functions via BMP4/TGFβ1 paracrine signaling that serves to suppress Lgr5+ CSCs and promote anti-tumor immunity, ultimately limiting CRC progression.
Abstract LB174: Discovery and preclinical characterization of INCA00186, a humanized monoclonal antibody antagonist of CD73, as a cancer immunotherapy

In the tumor microenvironment, dying cells release ATP which gets converted to AMP by CD39. AMP is subsequently converted to immunosuppressive adenosine by the extracellular 59-nucleotidase CD73. CD73 is linked to the cell surface by a GPI-anchor and can be released into the plasma as soluble CD73. In order to lower extracellular levels and reverse the immunosuppressive activity of adenosine in the tumor microenvironment, an antibody was researched and discovered that antagonizes CD73 function. INCA00186 is a humanized monoclonal antibody that binds and inhibits CD73 function. INCA00186 binds human and cynomolgus CD73 with sub-nanomolar affinity, and inhibits CD73 enzymatic activity in a manner that is non-competitive for AMP binding. In functional studies, INCA00186 restored effector T cell proliferation in the presence of high concentrations of AMP. In the human A375 melanoma tumor model in CD34+ humanized NSG mice, INCA00186 decreased levels of cell surface CD73, displayed high receptor occupancy on tumor cells, and decreased CD73 activity in ex vivo assays of tumor homogenates. In the human MDA-MB-231 breast tumor model in CD34+ humanized NSG mice, INCA00186 decreased intratumoral adenosine concentrations. In combination with the novel A2A/A2B adenosine receptor antagonist INCB106385, INCA00186 synergistically restored effector T cell activity as measured by interferon gamma (IFNγ) production in the presence of high concentrations of AMP. In the human MDA-MB-231 breast tumor model in CD34+ humanized NSG mice, combination treatment with INCA00186 and INCB106385 controlled tumor growth significantly better than monotherapies. In summary, the data presented in this study demonstrates that INCA00186 is a potent CD73 antagonist and effectively attenuates adenosine induced immunosuppression in the tumor microenvironment. INCA00186 demonstrated anti-tumor immunity alone and, to a greater extent, in combination with the A2A/A2B adenosine receptor antagonist INCB106385. Citation Format: Shaun Stewart, Rebecca Buonpane, Jing Zhou, Michael Hansbury, Michael Smith, Hui Wang, Lu, Bin Su, Rahel Awdew, Cheng-Yen Huang, Ashwini Kulkarni, Shane Harvey, Arpita Mondal, Steve Wang, Christina Stevens, Michael Pratta, Elham Behshad, Alexandra Fanuka, Xiaodi Ren, Holly Koblish, Horacio Nastri, Patrick Mayes. Discovery and preclinical characterization of INCA00186, a humanized monoclonal antibody antagonist of CD73, as a cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB174.
Continuously Reinforced Concrete Pavement Cracking Patterns and Properties with Internal Curing and Active Cracking

Transverse cracking in continuously reinforced concrete pavement (CRCP) develops over time and may exhibit irregular patterns such as cluster cracks, Y-shaped cracks, and divided cracks. These unde...
Synergy between NAFLD and AFLD and potential biomarkers

Summary Fatty liver (hepatosteatosis) is the earliest abnormality in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) due either to metabolic risk factors associated with insulin resistance and/or metabolic syndrome in the absence of alcohol consumption or to chronic alcohol abuse. When unchecked, both NAFLD and AFLD lead to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and eventual death. A number of common mechanisms contribute to the above various stages of hepatocyte injury, including lipotoxicity, endotoxin release, oxidative and ER stress leading to increased pro-inflammatory cytokines that stimulate hepatic fibrogenesis and cirrhosis by activating the quiescent hepatic stellate cells (HSC) into myofibroblasts. Significantly, patients with either NAFLD or AFLD respond favorably to early treatment modalities to reduce hepatic fat accumulation and consequent increased inflammatory signalling and activation of hepatic stellate cells. Although the pathogenic pathways associated with NAFLD and AFLD are seemingly similar, differentiation of the molecular mechanism/s of the pathogenesis of these liver diseases is critical in identifying the unique molecular signatures, especially in the early diagnosis of NAFLD and AFLD. Current clinical practice requires the invasive biopsy procedure for the conclusive diagnosis of NAFLD and AFLD. Micro RNAs (miRNAs) are ∼22 nucleotide non-coding sequences that bind to the 3′-untranslated region of target transcripts and regulate gene expression by degradation of target mRNAs or inhibition of translation. Emerging studies may prove to establish miRNAs as excellent non-invasive tools for the early diagnosis of various stages of liver diseases.
Conflict as a heuristic in the development of an interaction mechanics

The prevailing belief that the replacement of conflict with cooperation among artificial or human agents improves performance was supported in the field for the solution of well-defined problems (wdp’s), but ironically, only when the underlying hypothesis that logic concepts and reality correspond is no longer true. In contrast, our theory, based on the bistable information derived from action-observation complementarity, predicts that resolving conflict between autonomous agents reduces the available information, I, into skills which solve wdp’s, but that conflict or social tension increases the I available to discover optimal paths for the solution of ill-defined problems (idp’s). Earlier we confirmed both predictions; first, in an experiment with USAF combat pilots in simulated air-combat, we found that observations in extreme environments produce I that converges to form knowledge independent of reality, R; second, convergence underdetermines R, promoting multiple, independent worldviews of R and a tension between them which we enhanced at a DOE military nuclear facility to significantly improve its environmental remediation decisions. We extend our theory to model the transition from social statics to dynamics by combining action-observation complementarity with a model of feedback resonance. It indicates that cooperation to solve wdp’s in social systems enhances acculturation and stasis, but that competition to solve idp’s at the level of macroeconomics powers the evolution of new social structures to manage human interaction.
Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and ...
A Poorly Differentiated Germ Cell Tumor (Seminoma) in a Long Evans Rat

A large neoplasm that replaced 1 testis of a Long Evans Rat was noted at the final necropsy of a dietary 2-yr study. By light microscopy. the morphological features were consistent with a poorly differentiated seminoma. Ultrastructurally. the cells were po- lygonal, had a round nucleus, had straight cellular boundaries, and bore no resemblance to Sertoli cells. Although there was little evidence of spermatocytic differentiation, the presence of proacrosomal granules and vesicles, prominent Golgi apparatus, tight inter- cellular junctions. and a few centriolar pairs without axoneme development, in conjunction with the absence of lipid droplets or abundant smooth endoplasmic reticulum, supported the diagnosis of seminoma rather than Leydig cell tumor. The cells were S-100- and vimentin-positive, although cytokeratin- and a-fetoprotein-negative. Seminomas are extremely rare neoplasms in rats: this is the first report in this strain and the first extensive analysis of a rat seminoma without spermatocytic differentiation. Keyivords. Testis: immunohistochemistry; electron microscopy; virnentin: S-100; neoplasm
Expert Systems: Implications for Educators:

This paper discusses the relevance of expert systems to hospitality educators. A brief overview of expert systems is provided followed by current applications in the hospitality industry as well as other business applications. Three major implications for educators are then presented. Educators should include the concept of expert systems in their curriculum. Expert systems can be used to design teaching tools. Finally, expert systems provide the opportunity for educators to lead industry by becoming the knowledge engineers of their field.
Normal spirometric values in healthy Hispanic Americans.

FVC, FEV 1 , FEV 1 /FVC, and FEF25-75% were measured in 259 (116 men and 143 women) healthy nonsmoking Hispanic American volunteers from Utah and California. Linear regression equations were created for women ≥ age 20 years and men ≥ age 25 years using height, age, and weight as independent variables and the spirometric indices as dependent variables. Weight was a significant predictor only for female FEV 1 . The raw data from this study were compared with data from our previous studies in North American Indians and Salt Lake City whites with Middle European ethnic backgrounds. No differences were found for any of the age and height coefficients. The only differences found were in the comparisons of the equation intercepts (bias) for male FVC and FEV 1 between data for the Salt Lake City white subjects and both Hispanic American and North American Indian men. These small biases could be explained by technical or sampling biases or they may represent small ethnic differences. Although the differences from our Salt Lake City study are small, we recommend that ethnic-specific equations be used where they are available.
Bone Marrow-Derived Cells in the Pathogenesis of Lung Fibrosis

Progressive pulmonary fibrosis is characterized by failed alveolar reepithelialization and fibroblast/myofibroblast accumulation, with deposition of extracellular matrix. This results in loss of lung elasticity, alveolar collapse and fibrosis, impaired gas exchange and progressive decline in pulmonary function. Myofibroblasts represent an activated, contractile cellular phenotype that are potent producers of collagen and other extracellular matrix proteins. It is generally thought that myofibroblasts derive from local tissue fibroblasts. However, recent evidence suggests a portion of the progenitors for these cells may arise from the bone marrow. Fibrocytes, which share both leukocyte and mesenchymal markers, are found in increased numbers in bone marrow and lung of injured mice. Fibrocytes circulate in blood and are recruited to injured sites via chemotactic signals. Studies with bone marrow chimeric and parabiotic mice suggest that fibroblasts (and in some cases myofibroblasts) arise from circulating bone marrow precursors. Chemokine and chemokine receptor interactions are critical for the recruitment of bone marrow-derived progenitors. Once fibrocytes arrive in injured tissues, local factors induce their differentiation into fibroblasts/myofibroblasts. This review will summarize the experimental findings, supporting a role for the participation of bone marrow-derived cells in animal models of lung fibrosis, and potential implications for the pathogenesis of fibrotic lung diseases.
Climate Change and Pesticide Loss in Watershed Systems: A Simulation Modeling Study

This paper aims at examining the impacts of climate change on pesticide loss to surface water through a modeling study. An integrated modeling system which combined a distributed pesticide loss model with geographic information system (GIS), database, and climate change scenarios was proposed. It can predict pesticide loss through runoff under climatic change conditions. A case study was used to calibrate and verify the proposed system. The atrazine loss in 2050 and 2100 was predicted under different climate change scenarios. With the global warming, the annual streamflow would augment by 3 to 5% and the total atrazine losses would also gradually increase by 1.4 to 1.7%. The maximum concentrations of atrazine in river would be raised by 2.5 to 23%. It was also found that the wet season would always take the biggest share of pesticide-loss contribution to the river. A sensitive analysis disclosed that both of streamflow and pesticide concentration are more sensitive to temperature increase than decrease. This study is the first one to quantify the relationship between pesticide loss and climate change through a mathematic modeling system. The results can help people more effectively assess climate-change impacts, manage pesticide practices, and control water pollution.