cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract SY27-02: Targeting leukemia stem cells with small molecule inhibitors of PRC1

Bmi1 is a stem cell gene, which determines the proliferative capacity and self-renewal potential of normal and leukemic stem cells. Multiple studies identified Bmi1 to be able to induce oncogenic transformation and promote tumor growth in a variety of in vitro and in vivo animal models. Bmi1 is a central component of the Polycomb Repressive Complex 1 (PRC1) and interacts with Ring1B protein to form an active E3 ligase, which ubiquitinates histone H2A on lysine K119. This epigenetic modification of H2A is required to maintain transcriptionally repressive state of many genes. Small molecule inhibitors of the Ring1B-Bmi1 E3 ligase activity have not been reported to date, but are highly desired as potential therapeutic agents targeting cancer stem cells. Employing fragment screening approach we identified small molecule inhibitors of Ring1B-Bmi1. Using medicinal chemistry, we developed potent compounds that bind to Ring1B-Bmi1 and inhibit its E3 ubiquitin ligase activity with low micromolar affinities. In cells, Ring1B-Bmi1 inhibitors revealed robust downregulation of H2A K119 ubiquitination. Treatment of model cell lines enriched in leukemia initiating cells show that the Ring1B-Bmi1 inhibitor blocks the self-renewal capacity and induces cellular differentiation. Our approach validates that RING ligases represent novel class of ‘druggable’ epigenetic targets. Citation Format: Tomasz Cierpicki. Targeting leukemia stem cells with small molecule inhibitors of PRC1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY27-02.
Postoperative temporal hollowing: Is there a surgical approach that prevents this complication? A systematic review and anatomic illustration

Summary Background Temporal hollowing is a common complication following surgical dissection in the temporal region. Our objectives were to: (1) review and clarify the temporal soft tissue relationships – supplemented by cadaveric dissection – to better understand surgical approach variations and elucidate potential etiologies of postoperative hollowing; (2) identify if there is any evidence to support a surgical approach that prevents hollowing through a systematic review. Methods Cadaveric dissection was performed on six hemi-heads. A systematic review of the literature was undertaken to identify surgical approaches with a decreased risk of postoperative hollowing. Results A total of 1212 articles were reviewed; 19 of these met final inclusion criteria. Level I and II evidence supports against the use of a dissection plane beneath the superficial layer of the deep temporal fascia or through the intermediate temporal fat pad. Level II evidence supports preservation of the temporalis muscle origin – no evidence is available to support other temporalis resuspension techniques. For intracranial exposure, refraining from temporal fat pad dissection (Level I Evidence) and use of decreased access approaches such as the minipterional craniotomy (Level I Evidence) appear to minimize temporal soft tissue atrophy. Conclusions This study highlights the significance of preservation of the temporal soft tissue components to prevent hollowing. Preserving the temporalis origin and avoiding dissection between the leaflets of the deep temporal fascia or through the intermediate temporal fat pad appear to minimize this complication.
Medical management of claudication

Peripheral artery disease (PAD) is common and associated with significant morbidity and mortality. Optimal medical management of PAD is required for each patient, irrespective of the decision regarding lower extremity revascularization. The goals include reducing cardiovascular morbidity and mortality and improving quality of life. The approach should consist of aggressive and individualized risk factor modification including smoking cessation, antiplatelet therapy, a statin, and an angiotensin-converting enzyme inhibitor. Exercise is critical for cardiovascular health and highly effective for improving claudication symptoms. Cilostazol may be considered for symptomatic treatment in certain patients.
A CLINICAL ECONOMY OF SPECULATION: Financial Trading and Gambling Disorder in Spain

This article concerns itself with financial traders in Spain who have been diagnosed with gambling disorder. It analyzes what I call the clinical economy of speculation, in which the category of problem gambler is repurposed to draw new lines around proper financial trading. In exploring the expansion of post–financial crisis regulatory mechanisms for credit and debt, as well as widening inequalities across the field of investment, I depict how both traders and clinicians become invested in medicalizing trading as gambling disorder. My theorizing interrogates whether and why common speculative practices are seen as sick and unsafe when everyday people, instead of banks and other financial institutions, perform them. I argue that the pathologized trader is an attempt to regulate, at the individual level, the increasing use of borrowed capital to make financial profits. The commodification of debt, however, is not a gender-neutral development. Female traders pay a greater price for venturing into the heights of finance. This focus on gender brings into view the redefinition of credit and debt within the domain of trading, and shows the role of debt-fueled financial speculation in the expansion of financial markets. These ethnographic findings are particularly relevant in a country like Spain, where the Great Recession has bred more new millionaires than ever before, even as the smaller fish of the economy are being medicalized and sometimes even incarcerated.
A tri-state 4-switch bi-directional converter for interfacing supercapacitors to DC micro-grids

Supercapacitors are energy storage devices that can contribute with a fast varying current for the regulation of DC grids. However, its power electronics interface should present fast dynamic response what is not exactly the case for the conventional 2-switch buck-boost bi-directional DC-DC converter. The alternative considered in this paper is a 4-switch bi-directional DC-DC converter with an intermediate inductor, which allows the implementation of a tri-state logic that eliminates the RHP zero of the transfer function V o /D. This paper presents a dynamic model for the 4-switch tri-state converter connected to a droop-controlled DC micro-grid, discusses the benefits of implementing the tri-state logic with different sequences, and provides simulation results showing an improved performance when compared to the conventional scheme.
Investigating illocutionary monism

Suppose I make an utterance, intending it to be a command. You don’t take it to be one. Must one of us be wrong? In other words, must each utterance have, at most, one illocutionary force? Current debates over the constitutive norm of assertion and over illocutionary silencing, tend to assume that the answer is yes—that each utterance must be either an assertion, or a command, or a question, but not more than one of these. While I think that this assumption is intuitive, I will argue in this paper that it is not sustainable. I’ll argue that this assumption makes it hard to explain what determines illocutionary force in a consistent and non-ad hoc way. I will demonstrate this is not fatal for the notion of illocutionary force writ large by offering some alternatives.
Microstructure deformation and white etching matter formation along cracks

Abstract Rolling elements made of 52100 steel were subjected to high austenitizing temperatures to embrittle the steel. The embrittled rolling elements were intentionally given a rougher surface finish and were subjected to bearing tests under rolling-sliding conditions. Post-test material investigations revealed cracks in the raceways and rollers. Detailed electron microscopy investigations showed highly deformed microstructure in the vicinity of the cracks and white etching matter (WEM) along the cracks in the subsurface regions. Intergranularly oriented cracks and associated WEM were observed in the lower subsurface areas of the rollers. In contrast to the cracks formed closer to the surface, the martensitic microstructure in the vicinity of the intergranular cracks did not exhibit the microstructure deformation. The highly deformed microstructure and associated cracking are result of the high surface roughness of the rollers combined with the sliding conditions. The formation of the white etching matter, which was composed of a nanograin structure, is attributed to the crack faces rubbing. These results advance the understanding of damage mechanisms in bearings and the associated microstructural changes in the steel.
Seasonal variation in hospitalization outcomes in patients admitted for heart failure in the United States.

Background There is lack of evidence of the impact of varying season on heart failure (HF) hospitalization outcomes in the U.S. Hypothesis HF hospitalization outcomes exhibit significant seasonal variation in the U.S. Methods Using data from the National Inpatient Sample (2011-2013), seasonal variation was classified based on meteorological classification of Northern Hemisphere–Spring, Summer, Fall, & Winter–and analysis was conducted via multivariable-adjusted mixed-effect model. Results An estimated 2.8 million adults were hospitalized for HF in the U.S. from 2011 to 2013. Of all hospitalizations, admissions were highest in Winter (27%), followed by Spring (26%), Fall (24%), and Summer (23%). The overall mortality rate was 3.1%. Compared with Spring, there was significantly lower mortality in Summer (odds ratio [OR]: 0.95, 95% CI: 0.91-0.99) and Fall (OR: 0.94, 95% CI: 0.89-0.98), but the highest mortality was in Winter (OR: 1.06, 95% CI: 1.02-1.11). In addition, mean length of stay and median cost of hospitalization were highest in Winter (5.3 days, USD7459, respectively) and lowest in Summer (5.1 days, USD7181, respectively). However, age and sex differences existed (e.g. seasonal variation in inpatient mortality was only significant for patients age ≥65 years, and, compared with the Spring season, males had higher risk of inpatient mortality in Winter (OR: 1.10, 95% CI: 1.04-1.17) and females had lower risk of inpatient mortality in Summer (OR: 0.94, 95% CI: 0.88-1.00) and Fall (OR: 0.92, 95% CI: 0.87-0.98). Conclusions Among HF patients in the U.S., hospitalization outcomes were worse in Winter but better in Summer.
Pulmonary arterial hypertension related to connective tissue disease: a review

PAH associated with connective tissue diseases is associated with significant functional impairment and morbidity, and carries with it a poor prognosis. The mortality is as high as 10% to 15% in the first year after diagnosis; making it a devastating disease. The availability of ever-increasing numbers of treatment options in the recent era have improved survival in this patient population and have made early and accurate diagnosis a more important goal. According to the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL), 1-year, 3-year, 5-year, and 7-year survival rates from time of diagnostic right-sided heart catheterization in patients with PAH were found to be 85%, 68%, 57%, and 49%, respectively, which is a considerable improvement since the National Institutes of Health registry 2 decades previously. In a study by Condliffe and colleagues, survival rates in patients with SSC-associated PAH have improved to 78%at 1 year and 47% at 3 years. Patients with SLE-related PAH have a much higher survival rate of up to 75% at 3 years. Proper screening, early diagnosis, and early treatment can have a significant impact in reducing morbidity and mortality. A small study to assess outcomes in patients with asymptomatic CTD found to have exercise induced PAH suggest that bosentan may be safe and effective in improving the hemodynamics and outcomes in these patients. This study included only 10 patients, and additional randomized trials with larger numbers of subjects are needed to affirm this hypothesis. Studies are under way to find additional therapeutic modalities in the form of PDGF receptor blockers, VEGF blockers, tyrosine kinase inhibitors, endothelial dysfunction inhibitors, multikinase inhibitor of Raf-1, serotonin receptor antagonists,and rho kinase inhibitors. Despite these, clinical suspicion, early diagnosis, early
Basic Morse Theory

The main goal of this chapter is to show how to construct a CW-complex that is homotopy equivalent to a given smooth manifold M using some special functions on M called “Morse” functions (Theorem 3.28). The CW-homology of the resulting CW-complex is isomorphic to the singular homology of M by Theorem 2.15, and hence it is independent of the choice of the Morse func­tion used to build the CW-complex. As a consequence we derive the Morse inequalities. The last section of this chapter is an introduction to Morse-Bott functions.
Laminar Organization of the Visual Cortex

The cerebral cortex is the seat of the highest forms of biological intelligence in all sensory and cognitive modalities. The neocortex has an intricate design which exhibits a characteristic organization into six distinct cortical layers (Brodmann, 1909; Martin, 1989). Differences in the thickness of these layers and the sizes and shapes of neurons led the German anatomist Korbinian Brodmann to identify more than fifty divisions, or areas, of neocortex. This classification has been invaluable as a basis for classifying distinct functions of different parts of neocortex. The functional utility of such a laminar organization in the control of behavior has, however, remained a mystery until recently.
Effects of progestins on the progesterone receptor in guinea pig uterus.

To understand how steroid hormones exert their effects on target tissues it is necessary to know how the concentration of hormone receptors is regulated. Receptor regulation may be divided, somewhat arbitrarily, into long and short term regulation. Both are influenced by hormones.
Impact of metformin on survival and mTOR pathway in head and neck cancer patients: An updated analysis.

e17500Background: Metformin is hypothesized to suppress tumor cell growth by mTOR pathway inhibition, which mediates the phosphoinositide 3-kinase/Akt signaling pathway (frequently deregulated in h...
Decision-Making Tools and Strategic Planning in Project Environments: The Overlap Of The Two Concepts

Decision-making is at the core of business strategy. This paper studies that role of economic decision-making in strategic planning. It discusses methods such as foresight and roadmapping, and the contributions they make to the strategic vision. The literature gathered provides information on the methods used to implement foresight in policy making, as well as the business organization environment. We begin by providing a background of decision-making and strategic planning. The importance of making quality decisions is explained in the literature review with the intent of creating a setting for the need of decision-making tools. The literature selected for this study discusses tools such as trend analysis, change driver identification, and the overall of assessment capacity levels. The finding of this paper validates the assumption that decision-making tools are used to identify areas of improvement, as well as business opportunities. Information on the use of specific analytical tools is provided, as well as a comparison of tools used public administrator and company managers. The results of the study demonstrate the intention of managers and decision-makers to make decisions that are in alignment with the company's strategic vision. Some of the barrier and implications of the study are discussed, as well as areas for future study.
Predicting Antimicrobial Resistance and Associated Genomic Features from Whole-Genome Sequencing.

ABSTRACT Thanks to the genomics revolution, thousands of strain-specific whole-genome sequences are now accessible for a wide range of pathogenic bacteria. This availability enables big data informatics approaches to be used to study the spread and acquisition of antimicrobial resistance (AMR). In this issue of the Journal of Clinical Microbiology, Nguyen et al. (M. Nguyen, S. W. Long, P. F. McDermott, R. J. Olsen, R. Olson, R. L. Stevens, G. H. Tyson, S. Zhao, and J. J. Davis, J Clin Microbiol 57:e01260-18, 2019, https://doi.org/10.1128/JCM.01260-18) report the results obtained with their machine learning models based on whole-genome sequencing data to predict the MICs of antibiotics for 5,728 nontyphoidal Salmonella genomes collected over 15 years in the United States. Their major finding demonstrates that MICs can be predicted with an average accuracy of 95% within ±1 2-fold dilution step (confidence interval, 95% to 95%), an average very major error rate of 2.7%, and an average major error rate of 0.1%. Importantly, these models predict MICs with no a priori information about the underlying gene content or resistance phenotypes of the strains, enabling the possibility to identify AMR determinants and rapidly diagnose and prioritize antibiotic use directly from the organism sequence. Employing such tools to diagnose and limit the spread of resistance-conferring mechanisms could help ameliorate the looming antibiotic resistance crisis.
Deep-learning enables cross-modality super-resolution in fluorescence microscopy (Conference Presentation)

We present a deep learning-based framework for super-resolution image transformations across multiple fluorescence microscopy modalities. By training a neural network using a generative adversarial network (GAN), a single low-resolution image is transformed into a high-resolution image that surpasses the diffraction limit. The deep network’s output also demonstrates improved signal-to-noise ratio and extended depth-of-field. This framework is solely data-driven which means that it does not rely on any physical models of the imaging formation process, and instead learns a statistical transformation from the training image datasets. The inference process is non-iterative and does not require sweeping over parameters to achieve optimal results, in contrast to state-of-the-art deconvolution methods. The success of this framework is demonstrated by super-resolving wide-field images captured with low-numerical aperture objective-lenses to match the resolution of images captured with high-numerical aperture objectives. In another example, we demonstrate the transformation of confocal microscopy images into images that match the performance of stimulated emission depletion (STED) microscopy, by super-resolving the distributions of Histone 3 sites within cell nuclei. We also applied this framework to total-internal-reflection fluorescence (TIRF) microscopy and super-resolved TIRF images to match the resolution of TIRF-based structured illumination microscopy (TIRF-SIM). Our super-resolved TIRF images/movies reveal endocytic protein dynamics in SUM159 cells and amnioserosa tissues of a Drosophila embryo, providing a very good match to TIRF-SIM images/movies of the same samples. Our experimental results demonstrate that the presented data-driven super resolution approach generalizes to new types of images and super-resolves objects that were not present in the training stage.
Beyond Cages : Animal Law and Criminal Punishment

For all the diversity of views within the animal protection movement, there is a surprising consensus about the need for more severe criminal justice interventions against animal abusers. More prosecutions and longer sentences, it is argued, will advance the status of animals in law and society. Breaking from this mold, Professor Justin Marceau demonstrates that a focus on 'carceral animal law' puts the animal rights movement at odds with other social justice movements, and may be bad for humans and animals alike. Animal protection efforts need to move beyond cages and towards systemic solutions if the movement hopes to be true to its own defining ethos of increased empathy and resistance to social oppression. Providing new insights into how the lessons of criminal justice reform should be imported into the animal abuse context, Beyond Cages is a valuable contribution to the literature on animal welfare and animal rights law.
How Partisanship and Perceived Political Bias Affect Wikipedia Entries of News Sources

Increased polarization and partisanship have become a consistent state of politics, media, and society, especially in the United States. As many news publishers are perceived as “biased” and some others have come under attack as being “fake news”, efforts to make such labels stick have increased too. In some cases (e.g., InfoWars), the use of such labels is legitimate, because some online publishers deliberately spread conspiracy theories and false stories. Other news publishers are perceived as partisan and biased, in ways that damages their reporting credibility. Whether political bias affects journalism standards appears to be a debated topic with no clear consensus. Meanwhile, labels such as “far-left” or “alt-right” are highly contested and may become cause for prolonged edit wars on the Wikipedia pages of some news sources. In this paper, we try to shine a light into this phenomenon and its extent, in order to start a conversation within the Wikipedia community about transparent processes for assigning political orientation and journalistic reliability labels to news sources, especially to unfamiliar ones, which users would be more likely to verify by looking them up. As more of Wikipedia’s content is used outside Wikipedia’s “container” (e.g., in search results or by voice personal assistants), the issue of where certain statements appear in the Wikipedia page and their verifiability becomes an urgent one to consider not only by Wikipedia editors, but by third-party information providers too.
High Resolution Imaging of Chaotic Bistatic Radar

High resolution imaging using chaos-based frequency modulation (CBFM) in a bistatic radar system is evaluated in terms of the cross-ambiguity function. A 3-D Lorenz system is used to generate and transmit a wideband CBFM waveform. The bistatic radar's receiver is synchronized with its transmitter utilizing a direct synchronization scheme. The cross-correlation between the reconstructed and transmitted waveforms is of high quality and, consequently, down-range resolution is achievable. However, cross-range resolution is more elusive as the shape of the cross-ambiguityg function between the reconstructed waveform and scattered echo depends on the geometric configuration of the bistatic radar. For the cosite region and nonnegative look angles of the receiver-centered region, the ambiguity function has a near thumbtack shape. For negative look angles of the receiver-centered region, cross-range resolution is gradually lost. To assess high-resolution capability, the signature analysis of a complex point target is modeled. Results demonstrate that the synchronized chaotic FM bistatic radar provides a high range and cross range resolution with negligible sidelobes. Using an entropy analysis, it is determined that when only the echo is corrupted with additive noise, high resolution imaging is feasible for low SNR. In contrast, if both the target echo and the waveform received from the transmitter are corrupted with noise, imaging is adversely affected for relatively high noise levels.
Detecting Deep Brain Stimulation Currents with High Resolution Transcranial Acoustoelectric Imaging

The efficacy of deep brain stimulation (DBS) for relieving motor symptoms from Parkinson’s disease or essential tremor is highly dependent on accurate placement of the electrode. New current-steering electrodes can reduce the burden of placement by directing the stimulating currents toward the target locations. However, no imaging modality exists in the clinic or operating room to provide feedback of the currents as they are delivered/steered from the contacts. In this study we investigate the prospects of high resolution, transcranial acoustoelectric imaging (AEI) as a method for non-invasively imaging DBS currents. A DBS electrode was inserted into a brain gel phantom inside a human skull and monopoles were generated at individual contacts. A linear array ultrasound (US) transducer was coupled to the temporal window and focused toward the DBS electrode to induce AE signals proportional to the time-varying current densities. The AE signals using an injected current of 11 mA and focal pressures of 2.04 MPa were detected with SNRs between 716 dB, mean accuracy along the length of the electrode of 0.35 mm, radial separation of segmented contacts in a ring-triplet of 1.21 mm, mean monopole FWHMs of 3.54 mm, and a sensitivity of 0.283 pVfmA/MPa. Our results advocate AEI as a promising tool for providing non-invasive, high resolution feedback of the spread of current from a directional DBS electrode with potential roles in enhancing placement of the electrode and chronically monitoring the integrity of the stimulation.
Ethnographic research in healthcare - patients and service users as participants.

This discussion paper provides an introduction and overview of Ethnography as a qualitative research methodology and outlines its usefulness in understanding the experiences of patients and service...
The ups and downs of mentoring relationship formation: What to expect

Abstract The current study examines the development of formal youth mentoring relationships over time in a sample of female mentors. While benefits of youth mentoring have been shown across a variety of domains, research suggests that qualities of the mentoring relationship, including duration and satisfaction, are instrumental in determining mentee outcomes. Despite the central role of the relationship in mentoring, there is a paucity of research examining how mentoring relationships develop over time. Mentors were participants in a school-based mentoring program that is curriculum driven and includes both a group and a one-on-one component. Weekly reports of relationship satisfaction were collected from mentors. Multilevel modelling was used to analyze relationship quality over time. Relationship development was best modeled by a random-effects, random-slopes model. Satisfaction generally started high and grew slightly over the academic year. The intercept, slope and their interaction was not associated with mentee outcomes (e.g., mentee relationship satisfaction or peer self-esteem). This study is a first step towards understanding the developmental pattern of mentoring relationships as measured by mentor reports of relationship strength. Results from this study provide important information to aid in mentor training and to advance the mentoring field. Limitations of the research design include inability to make causal claims, small sample size, and lack of generalizability.
Rescission, Restitution and the Principle of Fair Redress: A Response to Professors Brooks and Stremitzer

Brooks and Stremitzer write that a limited rescission model is “excessive” and based on a “misunderstanding” of the economic effects of these remedies.Their key premise is that legal authorities have exaggerated the threat to contract stability and other normative values posed by liberal access to rescission. Therefore, the authors posit that rational parties from an ex ante perspective would often bargain for broad rights of rescission even if damages for breach “were fully compensatory and costless to enforce."In contrast, I will perform an intensive case law and statutory analysis showing that the law appropriately follows a principle of “fair redress,” which follows a liberal rescission/fair restitution approach. Indeed, the authors’ opposition to reliance and disgorgement is particularly counterproductive because their stance undermines the core policy of rescission and restitution, which is to afford the injured party an equitable remedy.
A field trial comparing four oral nonsteroidal anti-inflammatory drugs on controlling cautery dehorning pain and stress in calves

The purpose of this study was to compare the analgesic effect of four nonsteroidal anti-inflammatory drugs (NSAIDs) administered as a single, standardized, oral dose in dairy calves at the time of cautery dehorning. The NSAIDs investigated have pharmacokinetic properties in cattle that produce persistent plasma concentrations that may provide prolonged analgesia with the added practicality of a simple administration regimen. One hundred and eighty-five Holstein calves aged approximately 50 d old were either sham dehorned (n = 31) or cautery dehorned following oral administration of carprofen (n = 31), firocoxib (n = 31), flunixin meglumine (n = 30), meloxicam (n = 31) or placebo (n = 31) in a randomized, controlled trial. A standard dose of 2.0 mg/kg was administered to all calves receiving an oral NSAID. All calves received local anesthesia prior to actual or sham dehorning. Cortisol concentrations, heart rate, mechanical nociception thresholds, ocular and dehorning area temperatures, and average daily gains were evaluated. A linear mixed-effects model with repeated measures was used for statistical analysis. Administration of oral meloxicam, flunixin meglumine, and firocoxib at 2.0 mg/kg resulted in decreased cortisol concentrations compared to placebo-treated controls for the first 24 h postdehorning (AUEC0-24) (P = 0.03). Moreover, firocoxib, flunixin meglumine, and meloxicam attenuated the maximum cortisol concentrations compared to placebo-treated calves (P = 0.04, P= 0.02). In calves treated with flunixin meglumine, cortisol concentrations was reduced at 4 h (P = 0.04) and 8 h (P = 0.02). In addition, analgesic administration was associated with changes in ocular and dehorning area temperature differences (P = 0.09). Carprofen and meloxicam reduced heart rates during the entire study period (P = 0.003). Although a treatment effect (P < 0.0001) was observed in the determination of mechanical nociception threshold among all treatment groups, meloxicam expressed marginally significant effects (P = 0.09) among NSAID treated groups dehorned. A single dose of oral meloxicam, flunixin meglumine, or firocoxib administered at 2.0 mg/kg reduced the acute stress response associated with cautery dehorning. However, carprofen administration was associated with increased cortisol concentrations and dehorning area temperatures for the initial 24 h. Given the changes in pain and stress outcome variables assessed in this study, NSAIDs should be administered at the time of dehorning.
The Law of Attraction: Affinity-Aware Placement Optimization using Graph Neural Networks

Placement is one of the most crucial problems in modern Electronic Design Automation (EDA) flows, where the solution quality is mainly dominated by on-chip interconnects. To achieve target closures, designers often perform multiple placement iterations to optimize key metrics such as wirelength and timing, which is highly time-consuming and computationally inefficient. To overcome this issue, in this paper, we present a graph learning-based framework named PL-GNN that provides placement guidance for commercial placers by generating cell clusters based on logical affinity and manually defined attributes of design instances. With the clustering information as a soft placement constraint, commercial tools will strive to place design instances in a common group together during global and detailed placements. Experimental results on commercial multi-core CPU designs demonstrate that our framework improves the default placement flow of Synopsys IC Compiler II (ICC2) by 3.9% in wirelength, 2.8% in power, and 85.7% in performance.
Inhibition of the PI3K/mTOR Pathway in Breast Cancer to Enhance Response to Immune Checkpoint Inhibitors in Breast Cancer.

Objectives: Inhibition of the PI3K/mTOR pathway suppresses breast cancer (BC) growth, enhances anti-tumor immune responses, and works synergistically with immune checkpoint inhibitors (ICI). The objective here was to identify a subclass of PI3K inhibitors that, when combined with paclitaxel, is effective in enhancing response to ICI. Methods: C57BL/6 mice were orthotopically implanted with syngeneic luminal/triple-negative-like PyMT cells exhibiting high endogenous PI3K activity. Tumor growth in response to treatment with anti-PD-1 + anti-CTLA-4 (ICI), paclitaxel (PTX), and either the PI3Kα-specific inhibitor alpelisib, the pan-PI3K inhibitor copanlisib, or the broad spectrum PI3K/mTOR inhibitor gedatolisib was evaluated in reference to monotherapy or combinations of these therapies. Effects of these therapeutics on intratumoral immune populations were determined by multicolor FACS. Results: Treatment with alpelisib + PTX inhibited PyMT tumor growth and increased tumor-infiltrating granulocytes but did not significantly affect the number of tumor-infiltrating CD8+ T cells and did not synergize with ICI. Copanlisib + PTX + ICI significantly inhibited PyMT growth and increased activation of intratumoral CD8+ T cells as compared to ICI alone, yet did not inhibit tumor growth more than ICI alone. In contrast, gedatolisib + ICI resulted in significantly greater inhibition of tumor growth compared to ICI alone and induced durable dendritic-cell, CD8+ T-cell, and NK-cell responses. Adding PTX to this regimen yielded complete regression in 60% of tumors. Conclusion: PI3K/mTOR inhibition plus PTX heightens response to ICI and may provide a viable therapeutic approach for treatment of metastatic BC.
Comparison of Mycoplasma pneumoniae IgM and IgE Antibody Levels in Asthmatic and Non-Asthmatic Adults.

Objective Mycoplasma pneumoniae (M. pneumoniae), an extracellular pathogen lacking a cell wall, causes respiratory infection in adults and children and has been implicated in asthma exacerbation; immunoglobulin (Ig) E may be involved in these exacerbations. Specific IgM and IgG immune response to M. pneumoniae has been reported, but less is known about IgE M. pneumoniae antibody (Ab) responses in asthma. Previous studies in our laboratory demonstrated that asthmatic children have increased IgM M. pneumoniae levels, but not IgE. Thus, we sought to investigate whether past M. pneumoniae infection triggers production of M. pneumoniae-specific IgE Abs in adult subjects with/without asthma. Methods M. pneumoniae- IgE and -IgM Ab responses were studied in adult asthmatic (N=22) and non-asthmatic (N=22) subjects (ELISA). Data are reported as antibody index. Threshold detection levels: IgE, IgM: 0.2, 0.9, respectively. Results M. pneumoniae-IgE Ab levels were low and below the threshold of detection in both asthmatic and non-asthmatics (0.002±0.008 vs. 0.02±0.03; P=0.021). However, specific-IgM levels were slightly higher in non-asthmatics compared with asthmatics (0.96±0.37 vs. 0.79±0.31; P=0.054). M. pneumoniae-IgM Ab positivity was similar in both groups (P=1.0). Conclusion IgM M. pneumoniae Abs may play an important role in non-asthma and persist for months after acute infection. IgE M. pneumoniae Abs may play a less important role in both groups.
Multifactor Asset Pricing Analysis of International Value Investment Strategies

Using a large international equity market database that has not been previously used for such a purpose, this paper documents that value (i.e., high book-to-market ) stocks outperform growth (i.e., low book-to-market ) stocks, on average, in most countries during the January 1975 - December 1995 period, both absolutely and after adjusting for risk. The international evidence confirms the findings of previous work reported for the U.S.. For 1975-1995, the annual difference between the average returns on portfolios of high and low book-to-market stocks is 12.94% in North America, 10.42% in Europe, 17.26% in Pacific-Rim per year, and value stocks outperform growth stocks in 17 out of 18 national capital markets. Our analysis also shows that a three-factor model explains most of the cross-sectional variation in average returns on industry portfolios across countries and that the superior performance of the value investing strategy, documented in this study, is a manifestation of size and book-to-market effects. These results are consistent with those reported by Fama and French (1994, 1996) that show that the value-growth pattern in stock returns is largely explained by a three-factor asset pricing model. Our results suggest that the Fama and French (1996) three-factor asset pricing model is not limited to the U.S. stock market.
Electron spin resonance of metallocarbonic anhydrases.

Abstract Electron spin resonance (ESR) spectra of Cu(II) and Co(II) derivatives of human, monkey, and bovine carbonic anhydrases and their anion complexes are reported. The ESR signals of most of the Cu(II) derivatives indicate a coordination geometry with axial symmetry. Copper carbonic anhydrase complexes appear to have one coordination site filled by a monodentate ligand from solution. This ligand causes increasing electron delocalization from the copper ion in the order CH3COO- l OCN- l ethoxzolamide l HCO3- l azosulfamide l H2O l N3- l SH- l CN- as indicated by decreasing values of g||. The presence of highly resolved nitrogen superhyperfine structure in the spectra of the cyanide complexes of Cu(II) human carbonic anhydrases B and C identifies at least 2 equivalent nitrogen atoms as ligands to the metal ion. Carboxymethylation of the human B enzyme modifies the coordination site, but appears to leave the metal ligands unchanged. A new 2:1 cyanide complex of Co(II) carbonic anhydrase is described with an intense ESR signal typical of low spin Co(II) in an axially symmetrical environment. This is in contrast to the broad, weak absorption of the cobalt enzyme and its 1:1 anion complexes which we have examined and which appear to be high spin Co(II). While the ESR spectra of the Cu(II) and Co(II) carbonic anhydrase complexes which show intense signals are best explained by a square planar or five-coordinate square pyramidal geometry, the geometry of these inactive derivatives probably deviates from that of the catalytically active complex. These studies suggest that there is some flexibility of the ligands at the active site and that certain metal ions or anions may force deviation from the active highly distorted four-coordinate geometry.
Catalyst Modeling – Biological

The catalytic power of enzymes reflects billions of years of refinement by evolution. Thus, understanding enzyme action should be very instructive as a guide for general principles of catalysis. This review describes the emerging use of computer modeling as a key toll in correlating enzyme structures and catalysis. The review starts by describing general computer simulation approaches for calculations of free energies and related properties. It then moves to methods that allow one to evaluate the free energy of enzymatic reactions. This includes hybrid quantum mechanical/molecular mechanics (QM/MM) molecular orbitals methods, the empirical valence bond (EVB) method, and other approaches. Emphasis is placed on specifying the requirement from reliable simulation approaches, including the need for accurate potential surfaces and a proper configurational sampling. The ability of different approaches to satisfy these serious requirements is critically examined. Next, we examine what has been learned from simulations of enzymatic reactions about the origin of enzyme catalysis. It is pointed out that consistent simulation studies concluded that electrostatic effects are the key catalytic factor and that the corresponding catalytic energy is stored in preorganized polar active sites. Studies that examined the magnitude of other catalytic contributions and the validity of the corresponding catalytic proposals are also considered. These include studies of various ground state destabilization effects (e.g. entropic, strain, and desolvation contributions), studies of dynamical effects, and studies of the low barrier hydrogen bond proposal. It is concluded that these contributions do not play a major role in enzyme catalysis. Finally, the future of computer simulations as a critical tool in studies of enzymatic reaction is briefly considered. Keywords: enzyme catalysis; electrostatics; QM/MM; EVB; enzyme dynamics; steric strain; entropy in catalysis; FEP
Exactly solvable one-dimensional transport. I - Prism bounded by partially absorptive walls

The steady-state transport in a prism bounded by partially absorbing walls of emissivitye at temperaturesT1 andT2 and containing fixed scattering centers is obtained exactly in the limit of sufficiently low temperature that onlyS-wave scattering is important and Boltzmann statistics are valid. The integro-differential equations are solved and boundary conditions satisfied by using the techniques of singular integral equations. The properties of the thermodynamic quantities are discussed.
Semantic Rules on Drug Discovery Data

Aggregating and presenting a wide variety of information pertinent to the biological and pharmacological effects of chemical compounds will be a critical part of 21st century drug discovery. However there is currently a lack of tools for effectively integrating and aggregating information about chemical compound. In this paper we tackle this problem using Semantic Web Technologies, particularly OWL ontologies,compound-centric RDF networks, and RDF inference to detect relationships between compounds and biological affects, genes,and diseases, and to present information to a user clustered by disease area.
Worrisome histologic alterations following fine-needle aspiration of benign parotid lesions.

Abstract Objective.—To describe the histologic changes associated with preoperative fine-needle aspiration biopsies of benign parotid lesions and the features that distinguish these changes from malignant neoplasms. Materials and Methods.—Ten benign parotid lesions with a recent history of preoperative fine-needle aspiration were selected, including pleomorphic adenoma (4 cases), oncocytic adenoma (3 cases), myoepithelioma (1 case), Warthin tumor (1 case), and lymphoepithelial cyst (1 case). Results.—A spectrum of histologic alterations were observed. Alterations included squamous cell metaplasia (8 cases), infarction and necrosis (4 cases), subepithelial stromal hyalinization (3 cases), acute and chronic hemorrhage and inflammation with multinucleated giant cells (all cases), granulation tissue with subsequent fibrosis (all cases), cholesterol cleft formation (1 case), pseudoxanthomatous reaction (1 case), pseudocapsular invasion (1 case), and microcystic degeneration (2 cases). In cases with exuberant s...
Design, implementation and measurement of a collision avoidance multiple broadcast tree network

The design and implementation of a local area network architecture based on collision avoidance, called the collision avoidance multiple broadcast (CAMB) tree network, are described. The implementation follows the protocol layering architecture of the IEEE 802 local area networks and includes CAMB tree switches, station/network interface boards, and support of transport protocols. The performance measurements of the experimental CAMB tree network are presented. >
Nanoscale Surface Patterns from 103 Single Molecule Helices of Biodegradable Poly(l-lactic acid)

Atomic force microscopy, reflection absorption infrared spectroscopy, and X-ray reflectivity studies reveal that poly(L-lactic acid) molecules in Langmuir-Blodgett (LB) films exist as 10(3) helices over nearly the entire length of the polymer chain. This feature gives rise to LB films with highly ordered nanoscale smectic liquid crystalline-like surface patterns with low surface roughness and lamellar spacings that scale with molar mass. These studies provide a new approach for controlling surface morphology with a biodegradable polymer commonly used for drug delivery and tissue engineering.
Image Segmentation with a Unified Graphical Model

We propose a unified graphical model that can represent both the causal and noncausal relationships among random variables and apply it to the image segmentation problem. Specifically, we first propose to employ Conditional Random Field (CRF) to model the spatial relationships among image superpixel regions and their measurements. We then introduce a multilayer Bayesian Network (BN) to model the causal dependencies that naturally exist among different image entities, including image regions, edges, and vertices. The CRF model and the BN model are then systematically and seamlessly combined through the theories of Factor Graph to form a unified probabilistic graphical model that captures the complex relationships among different image entities. Using the unified graphical model, image segmentation can be performed through a principled probabilistic inference. Experimental results on the Weizmann horse data set, on the VOC2006 cow data set, and on the MSRC2 multiclass data set demonstrate that our approach achieves favorable results compared to state-of-the-art approaches as well as those that use either the BN model or CRF model alone.
What has happened in the cores of globular clusters

It is found that some aspects of the observed data for globular cluster cores cannot be easily explained in terms of the existing theory of dynamical evolution. It is noted that globular clusters span only a factor of 40 in core mass, while ranging over a factor of 10 to the 6th in central density, an observation that cannot be explained as a selection effect. A strong correlation is found between the central density and the distance of a cluster from the galactic center. In addition, when cluster cores are evolved backward in time in their initial conditions, using the available theory of dynamical evolution, evidence emerges that many clusters have already undergone core collapse, for which no evolutionary theory exists. It is concluded that these results indicate the incompleteness of the theory of dynamical evolution.
Ultralow-temperature magnifying glass: how Bose-Einstein condensation makes quantum mechanics visible

Experiments in Bose-Einstein condensation provide an unusually direct view of the working quantum wave mechanics. We make use of two internal states of Rb-87 to engineer desired wavefunction patterns, and with the use of simple optical imaging, we characterize the results of these efforts.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
QR‐SCMEH‐MO calculations on the complex [Pt (SnCl3)5]3−: Electronic structure, UV–visible spectrum, magnetic properties, and bond energy

A molecular orbital study via the QR-SCMEH-MO (quasi-relativistic self consistent modified extended Hűckel molecular orbital) method has been carried out on the unusual Pt 5- coordinated complex Pt (SnCl3). The computed UV–Visible spectral data and NMR parameters are found to be in good agreement with the reported experimental values. In addition, the magnetic susceptibility and PtSn bond energy have been calculated, although there are no reported experimental data with which to compare these results. PtSn bond energies of other Pt-SnX3 (X = Cl, Br) systems and are compared with proposed bond energy trends based on NMR and observed bond distances. © 2012 Wiley Periodicals, Inc.