cssi/SciSciGPT-SciSciNet huggingface dataset:
Transformation by Mutant IDH and (R)-2HG Is Reversible.

Abstract 2413 Somatic mutations in IDH1 and IDH2 are common in normal karyotype AML as well as in other clonal myeloid disorders and several solid tumors. Mutant IDH overproduces the R -enantiomer of 2-hydroxyglutarate, ( R )-2HG (Dang, et al Nature 462: 739, 2009), which is hypothesized to alter the epigenetic landscape of cancer cells by inhibiting the activity of α-ketoglutarate-dependent enzymes, including the TET family of 5-methylcytosine hydroxylases and the jumonji-domain-containing family of histone demethylases. There is considerable interest in developing inhibitors of mutant IDH in the hope that, by decreasing ( R )-2HG production in cancer cells, their epigenetic regulation can be restored. However, there is, to date, no evidence that transformation by mutant IDH is reversible or that inhibiting production of ( R )-2HG has any effect on cancers harboring IDH mutations. Herein we report that in two different myeloid transformation assays, transformation by ( R )-2HG and mutant IDH1 is reversible by removal of ( R )-2HG. We previously reported that stable expression of a tumor-derived mutant IDH1 (IDH1R132H) induces growth factor independence and blocks EPO-induced differentiation in the human TF-1 erythroleukemia cell line, and that treatment of TF-1 cells with a cell-permeable form of ( R )-2HG, TFMB-( R )-2HG, is sufficient to recapitulate this phenotype (Late Breaking Abstract #LBA-4, ASH 2011). We have extended these studies and found that transformation by TFMB-( R )-2HG is reversible and that this reversibility is influenced by the duration and intensity (dose) of ( R )-2HG exposure. We developed a second myeloid transformation assay using a murine myeloid leukemia cell line that is transformed by expression of a HoxB8-ER fusion protein when cultured in the presence of estrogen. Upon estrogen withdrawal, the cells undergo monocytic differentiation and apoptosis. We expressed wild-type IDH1 or IDH1R132H in the cells and found that cells expressing wild-type IDH1 differentiate normally, but cells expressing IDH1R132H do not upregulate monocytic markers CD11b/Mac1 and Gr1 upon estrogen withdrawal. Furthermore, treatment of the IDH1R132H-expressing cells with an inhibitor of mutant IDH1 restores their ability to undergo monocytic differentiation upon estrogen withdrawal. Our findings suggest that continued exposure to ( R )-2HG is required to maintain the cellular changes induced by mutant IDH, and further suggest that targeting ( R )-2HG production may have therapeutic efficacy in the treatment of cancers harboring IDH mutations. Disclosures: No relevant conflicts of interest to declare.
Differentiation Therapy for Poor Risk Myeloid Malignancies: Results of a Dose Finding Study of Bryostatin-1 (BRYO) + GM-CSF.

Clinically effective differentiating therapy has been limited to the use of all-trans-retinoic acid in patients (pts) with acute promyelocytic leukemia. We recently demonstrated that the in vitro activity of many pharmacologic differentiating agents, including the protein kinase C agonist bryo, was dependent on their ability to block cell cycle and maximized by the addition of growth factors. We studied the safety and efficacy of continuous infusion bryo in combination with GM-CSF (125 ug/m 2 /day SC) in patients (pts) with refractory and poor risk myeloid malignancies. Bryo was dose escalated using the Continual Reassessment Method from 6ug/m 2 /day to 20ug/m 2 /day for 14 days monthly and followed by 16ug/m 2 /day to 20ug/m 2 /day over 21 days each month. The treatment plan called for 2 cycles of combination therapy prior to response evaluation. A total of 32 patients with refractory or poor risk myeloid malignancies (9 relapsed or refractory AML, 1 therapy-related AML, 2 poor risk AML age >70, 19 poor risk MDS, 1 progressive PNH) were treated. The median age of subjects was 65 (range 23–75) yrs and a total of 73 (58 full + 15 partial) cycles were administered. The dose-limiting toxicity of the combination mirrored results from previous trials of bryo; grade 3–4 myalgias and arthralgias were observed in 12 of 14 pts at the highest dose levels (18 and 20ug/m 2 /day x 14 days, 16ug/m 2 /day x 21 days). Three pts discontinued therapy within a week of cycle 1 and were not considered evaluable for response. Eighteen (62%) pts responded (2 CRs and 16 PRs), 6 (21%) had stable disease, and 5 (17%) progressed. The PRs included 15 lineage responses and 1 bone marrow response ( 2 /day x 14 days followed by a 2 nd cycle @ 18ug/m 2 /day x 14 days (dose-reduced due to toxicity) who achieved a CR and continues to show improving cytogenetics at 11 mos and a 74 year old with newly diagnosed primitive leukemia (>50% marrow blasts) who received a single cycle @ 16ug/m 2 /day x 21 days and remains in CR at 5 mos. Both pts refused further courses due to myalgias and arthralgias, and interestingly, the CRs were not achieved until 4–6 weeks after completion of therapy. Our newly developed assay (sensitivity 50 pg/ml) detected measurable bryo only at the highest doses which supported the correlative in vitro assays that detected in vivo differentiation at the same doses. Bryo + GM-CSF has remarkable clinical activity in refractory myeloid malignancies, but is intolerable at biologically active doses. These results do suggest that strategies utilizing differentiating agents in conjunction with growth factors warrant further investigation.
The Associate Dean for Faculty Research Position: Encouraging and Promoting Scholarship

This Article recounts the experience at the University of Cincinnati College of Law with the Associate Dean for Faculty Research and Development position in the hope that it may be of interest to those schools that either have a similar position or are contemplating establishing such a position. Along the way, we offer our thoughts on the respective roles of the Dean, Associate Dean, and Faculty in improving the quality, productivity, and visibility of a law school faculty and their scholarship. The Associate Dean position was established at Cincinnati two years ago to (1) promote excellence in scholarship and teaching, (2) facilitate and coordinate scholarly activities, and (3) publicize the scholarly activities of the faculty. Responding to the first two charges, the Associate Dean has worked to provide greater institutional support for faculty research at each stage of the production process in the form of various initiatives such as a Work-in-Progress Group, Summer Scholarship Series, Faculty Workshop Series, Scholar Exchange Program, and Law School Working Paper Series. In response to the third charge, the Associate Dean has ramped up our publicity efforts, using both old and new technologies in increasing faculty participation in our alumni magazine, monthly web-based faculty news, and periodic e-mail and print publicity. The Dean has revamped our system of scholarly incentives and rewards, combining elements of both the all-for-one-and-one-for-all approach and the eat-what-you-kill approach. In the end, all of these efforts are aimed at strengthening a scholarly community in which the whole is greater than its parts. The guiding ethos should be that a rising scholarly tide lifts all boats, and that when we row together we not only get to our common destination quicker and easier, it also makes for a more enjoyable and satisfying journey. Like the man who sets out to slay a whale armed only with a row boat and a faith that leads him to bring along a jar of tarter sauce, we come to this task armed only with the ideas described in this Article and a faith in our colleagues that allows us to experiment with different ways to build this scholarly community.
SIGCHI Lifetime Research Award Talk -- RUBY: Reminiscing about User interfaces by Brad over the Years

Brad Myers has been doing research in the area of human-computer interaction for the last 40 years. Along the way, he and his students created over 60 software systems, whose names are often acronyms for gemstones. This talk's acronym, Ruby, is fittingly the gemstone associated with a 40th anniversary. Myers's MIT Master's thesis, Incense, was one of the earliest data visualization systems. While working for PERQ Systems Corporation, Brad created one of the first commercial window managers, called Sapphire, with a number of features that later became widespread. His PhD dissertation featured an interactive tool called Peridot, a programming-by-demonstration system that specified the look and behaviors of widgets without conventional programming. At Carnegie Mellon University, he created the Garnet and Amulet toolkits that incorporated novel designs for objects, constraints, output handling, input handling, command objects, and interactive tools. Many of the innovations in these projects have been adopted by later research and commercial systems. Brad was one of the early researchers on innovative uses for handheld devices, in a large-scale project called Pebbles. Another focus has been on using HCI techniques to improve programming for novice, expert, and end-user programmers.
Feedback Error Learning Neural Network for Above-Knee Prosthesis

Abstract The purpose of this paper is to show how Feedback Error Learning can be applied to control hip and knee joints in an active Above-Knee Prosthesis. Feedback Error Learning is a control scheme based on neural networks and has its origin in physiological studies. A total energy method is used, thus eliminating the need for a known mathematical model of the prosthesis. The system's total energy is extracted from kinematic analysis, and used as an equivalent mathematical model. The findings conclusively show Feedback Error Learning is a suitable control strategy for an active above-knee prosthesis.
Identification of O-Glycosylation Sites with a Gas Phase Sequencer

Publisher Summary Glycoproteins generally contain carbohydrate structures attached via either of two linkages. They may be N-linked to the amide nitrogen of asparagine or they may be O-linked glycosidically to the hydroxyl groups of threonine or serine residues. O-linked oligosaccharides are characteristically found on mucins or cell surface mucin-like molecules, which are often heavily glycosylated, containing up to 65–85% carbohydrate by weight. A number of problems are frequently encountered in structural studies of heavily glycosylated glycoproteins. Although it is desirable to analyze intact glycopeptides, such glycoproteins are frequently resistant to proteolytic cleavage and high yield purification of glycopeptides may be hampered by microheterogeneity of the extent of glycosylation at each serine or threonine residue. Sequencing methods using standard gas phase reagents and polybrene carrier for peptide immobilization are generally unsatisfactory for glycopeptides. Sequencer cycle blanks are usually observed at the attachment site of the large relinked carbohydrate units; however, the interpretation of HPLC chromatograms of O-glycosylated amino acid phenylthiohydantoin derivatives may be much more deceptive. This chapter describes a methodology for sequencing glycopeptides and identifying O-glycosylated threonine residues.
Manitoba Oculo-tricho-anal Syndrome: Complex Surgical Correction of an Extensive Upper Lid Coloboma with Congenital Symblepharon

Manitoba Oculo-tricho-anal Syndrome (MOTA) is a rare autosomal recessive disorder characterized by eyelid coloboma, cryptophthalmos, anophthalmia or microphthalmia, abnormal hair growth from scalp to eyebrow, bifid or broad nasal tip, and gastrointestinal anomalies including omphalocele and anorectal malformations.[1, 2] We describe a multi-stage surgical approach to repair a right upper lid coloboma with an extensive congenital superomedial symblepharon obscuring the pupil in the context of MOTA. Surgical steps included reconstitution of the eyelid’s anatomical landmarks with dissection of the symblepharon invading the opacified cornea, freeing the pupillary axis, creation of a superior fornix, advancement of myocutaneous/periosteal flaps, and insertion of an implant to recreate the absent eyelid. This resulted in significant improvement of ocular surface protection, quality of life, and allowed for amblyopia treatment.
Augmented virtuality for model-based teleoperation

Ground-based teleoperation of robots in space is subject to time delays of several seconds or more. This leads to the use of model-based approaches, where the operator interacts with a model (simulation) of the remote environment and the remote robot attempts to reproduce the results of that interaction. But, it is also desirable for the operator to view (delayed) images from the remote scene. These images, however, are often from one or more monocular cameras mounted on the robot end-effector, which leads to several other problems: unintuitive teleoperation due to the eye-in-hand configuration, limited field of view, and lack of stereo visualization. We present an augmented virtuality interface for teleoperation, which can solve these problems by projecting the real camera images onto a registered 3D model of the environment and allowing the operator to select any desired viewpoint. This approach is suitable when there is at least a partial model of the environment, as is the case for satellite servicing. The proposed method begins with a video survey to register the 3D model to the physical environment, followed by a user interface that presents a stereo visualization of the model, augmented by projections of real camera images onto the model. We quantitatively and qualitatively compare the augmented virtuality images to real camera images taken from the same viewpoint and perform experiments to evaluate the efficacy of the augmented virtuality paradigm for teleoperation. The results suggest that this approach can improve operator situation awareness, potentially leading to better performance, especially when the camera views are unintuitive or limited.
Points to Consider for Design and Control of Continuous Bioprocessing

Abstract The primary objective for implementing continuous processing is cost reduction of operations in the production of biopharmaceuticals, motivated by high production costs and the promise of significant productivity gains from continuous operations. However, changing the currently prevailing production technology from batch operation to continuous operation will have broad implications on manufacturing and quality systems. The realization of integrated continuous operations in large scale biopharmaceutical manufacturing needs to take existing constraints into account. Regulatory expectation and quality procedures and their impact on the design of operations have to be respected. Operational challenges like supply flexibility, process scale turndown, equipment complexity, fault recovery, and aseptic sampling have to be addressed. Utilization of “single use” equipment, equipment utilization, and the application of process analytical technologies have impact of process and facility design.
Child and Adolescent Sleep Disorders

Disorders and disturbances in sleep are common problems in children and adolescents. These problems frequently occur concurrently with psychiatric symptomatology, and there appears to be a complex interrelationship between the regulation of sleep and emotional or behavioral problems. This article focuses on appropriate use of medications in the treatment of these common disorders through a comprehensive approach of careful evaluation, diagnosis, and the use of behavioral and other nonpharmacologic treatments.
HIC: An interactive and ubiquitous home controller system for the smart home

This paper presents the Home Interactive Interface (HIC), a ubiquitous projected GUI providing the dwellers of a Smart Home with an instrument for controlling appliances, comfort metrics and systems. This paper describes the architecture of the HIC and its underlying system, focusing on its appearance, modules and functions. The services provided by HIC are contextualized in two different use cases taking place inside a domestic environment. The first use case illustrates HIC's services and functionalities dedicated to support the dwellers during meal preparations; the use case describes how HIC is able to provide step-by-step tailored instructions and to monitor the whole process. In the second use case, HIC's features for easy comfort metrics management are depicted. The main advantages deriving from the adoption of this home controller system are summarized in the last section, together with the future directions of this work and the usability tests considered to validate the home controller.
Analysis of Probabilistic News Recommender Systems

The focus of this research is the N “most popular” (Top-N) news recommender systems (NRS), widely used by media sites (e.g. New York Times, BBC, Wall Street Journal all prominently use this). This common recommendation process is known to have major limitations in terms of creating artificial amplification in the counts of recommended articles and that it is easily susceptible to manipulation. To address these issues, probabilistic NRS has been introduced. One drawback of the probabilistic recommendations is that it potentially chooses articles to recommend that might not be in the current “best” list. However, the probabilistic selection of news articles is highly robust towards common manipulation strategies. This paper compares the two variants of NRS (Top-N and probabilistic) based on (1) accuracy loss (2) distortion in counts of articles due to NRS and (3) comparison of probabilistic NRS with an adapted influence limiter heuristic.
Impacts of Heat and Ozone on Mortality Risk in the New York City Metropolitan Region Under a Changing Climate

Climate change may lead to both increased heat and ozone (O3) levels in urban areas over the coming century. To assess potential human health impacts of these changes, models are needed for projecting regional-scale temperature and O3 changes under climate change, and for characterizing the independent and joint health effects of heat and O3. To meet these needs, mortality transfer functions for summer heat and O3 were developed and applied in a regional health risk assessment for the New York City metropolitan region. The objective was to analyze and project the relative impacts of climate-related changes in mean daily temperature and 1-hour maximum O3 concentrations on acute non-accidental mortality from all internal causes of death. Exposure-response relationships were developed using a 10-year record of daily summer observations for the region (1990–1999). This was done using a time series Poisson regression model that jointly estimated O3 and temperature effects on mortality, controlling for time trends and day of week effects. To project impacts into future decades, we developed a integrated modeling system that took global scale climate projections for the 2020s, 2050s, and 2080s, using the Intergovernmental Panel on Climate Change (IPCC) A2 and B2 emission scenario assumptions, and down-scaled these to a 36 km grid using regional models for climate and air quality. Regional downscaling was carried out using the GISS-MM5 linked global-regional model system for climate and the Community Multiscale Air Quality (CMAQ) model for air quality. Mortality risks were projected using the transfer functions estimated from the 1990s data. Results showed that both O3 and heat stress had measurable impacts on mortality risk, but that the relative impacts changed over time. This modeling strategy could be applied in other metropolitan areas and for other health outcomes to assess health impacts of heat and O3 under a changing climate.
Tuning glucose decomposition in hot-compressed gamma-valerolactone/water mixtures: From isomerization to dehydration reactions

Abstract This study reports the reaction mechanism and kinetics of glucose hydrothermal decomposition in hot-compressed gamma-valerolactone(GVL)/water (HCGW) at 175–225 °C and various GVL concentrations (0–75 vol%) for the production of biofuels and value-added biochemicals. Increasing GVL addition tunes glucose decomposition from isomerization into fructose and mannose to dehydration into 5-hydroxymethylfurfural (5-HMF) and levoglucosan (LGA). Particularly, direct dehydration of glucose to 5-HMF is found to be a primary reaction during glucose decomposition in HCGW. With the GVL concentration increasing from 1 to 75%, the selectivities of dehydration reactions to 5-HMF and LGA at 175 °C increase from 22 and 12% to 30 and 33%, respectively, while the selectivity of isomerization reaction to fructose at 175 °C decreases from 46 to 20%. Kinetic analysis indicates that glucose decomposition in HCGW follows first-order reaction kinetics. Further analysis shows that the reaction rate constants of dehydration reactions almost increase linearly with the GVL concentration, while those of isomerization reactions almost decrease linearly with the GVL concentration. The activation energy of glucose decomposition in HCGW also reduces slightly from 117 kJ/mol in water to 96 kJ/mol in 75% GVL. This study demonstrates that GVL/water co-solvent is effective to tune the glucose decomposition reaction for the production of biofuels and value-added biochemicals.
RNA interference screen identifies NAA10 as a regulator of PXR transcription.

Abstract The pregnane X receptor (PXR) is a principal xenobiotic receptor crucial in the detection, detoxification, and clearance of toxic substances from the body. PXR plays a vital role in the metabolism and disposition of drugs, and elevated PXR levels contribute to cancer drug resistance. Therefore, to modulate PXR activity and mitigate drug resistance, it is imperative to fully understand its regulation. To this end, we screened a transcription factor siRNA library in pancreatic cancer cells that express high levels of PXR. Through a comprehensive deconvolution process, we identified N-alpha-acetyltransferase 10 (NAA10) as a factor in the transcriptional machinery regulating PXR transcription. Because no one single factor has 100% operational control of PXR transcriptional regulation, our results together with other previous findings suggest that the transcriptional regulation of PXR is complex and that multiple factors contribute to the process including NAA10.
The Omega-3 Index in National Collegiate Athletic Association Division I Collegiate Football Athletes.

Context The essential omega-3 fatty acids (ω-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit vital biological roles and are critical for cardiovascular and neurologic heal...
AFFIX: Automatic Acceleration Framework for FPGA Implementation of OpenVX Vision Algorithms

Computer vision algorithms are computationally expensive and difficult to implement efficiently. Field Programmable Gate Arrays (FPGA)s offer a promising direction to reduce the computation cost by exploiting hardware parallelism. However, it is difficult to translate vision algorithms to FPGA bitstream efficiently. OpenVX is an industry standard for graph-based representation of vision algorithms. It defines a set of widely used vision kernels and data structures that can be used to form a Directed Acyclic Graph (DAG) to represent a vision algorithm. This paper proposes a framework for automatic FPGA acceleration of computer vision algorithms based on OpenVX specification, called AFFIX. AFFIX receives a vision algorithm formed using the OpenVX and generates a heterogeneous CPU-FPGA implementation. AFFIX incorporates several high level and low-level optimization methods to improve the efficiency of the FPGA implementation. It provides a configurable and extensible framework that enables vision algorithm developers to quickly develop, verify and test FPGA implementations of vision algorithms. We demonstrate the effectiveness of the proposed framework via development and evaluations of multiple vision algorithms.
Efficient pathways to reduce carbon emissions in the electric sector

Abstract The study develops a 2-dimensional map of the feasible design space for an electric generation system. Cost and CO2 emissions contours are plotted across the map. The principles of constrained optimization are used to identify the efficient pathways eliminating emissions and the technology drivers that determine them. The CO2 intensity of the baseload is shown to be the primary driver. Further, the need for large, seasonal storage depends strongly on the level of baseload deployed.
Cooperative Light Emission in the Presence of Strong Inhomogeneous Broadening.

We study photon emission by an ensemble of two-level systems, with strong inhomogeneous broadening and coupled to a cavity mode whose frequency has linear time dependence. The analysis shows that, regardless of the distribution of energy level splittings, a sharp phase transition occurs between the weak and strong cooperative emission phases near a critical photonic frequency sweeping rate. The associated scaling exponent is determined. We suggest that this phase transition can be observed in an ensemble of negatively charged ${\mathrm{NV}}^{\ensuremath{-}}$ centers in diamond interacting with a microwave half-wavelength cavity mode even in the regime of weak coupling and at strong disorder of two-level splittings.
Spatial scale affects novel and disappeared climate change projections in Alaska

The formation of novel and disappeared climates between the last glacial maximum (LGM) and the present is important to consider to understand the expansion and contraction of species niches and distributions, as well as the formation and loss of communities and ecological interactions over time. Our choice in climate data resolution has the potential to complicate predictions of the ecological impacts of climate change, since climate varies from local to global scales and this spatial variation is reflected in climate data. To address this issue, we downscaled LGM and modern (1975-2005) 30-year averaged climate data to 60-m resolution for the entire state of Alaska for 10 different climate variables, and then upsampled each variable to coarser resolutions (60 m to 12 km). We modeled the distributions of novel and disappeared climates to evaluate the locations and fractional area of novel and disappeared climates for each of our climate variables and resolutions. Generally, novel and disappeared climates were located in southern Alaska, although there were cases where some disappeared climates existed within coastal and interior Alaska. Climate resolution affected the fractional area of novel and disappeared climates in three patterns: As the spatial resolution of climate became coarser, the fractional area of novel and disappeared climates (a) increased, (b) decreased, or (c) had no explainable relationship. Overall, we found the use of coarser climate data increased the fractional area of novel and disappeared climates due to decreased environmental variability and removal of climate extremes. Our results reinforce the importance of downscaling coarse climate data and suggest that studies analyzing the effects of climate change on ecosystems may overestimate or underestimate their conclusions when utilizing coarse climate data.
“A History We Can Neither Accept nor Deny: Feeding and Purging the Spirits in Maya Angelou’s All God’s Children Need Traveling Shoes ”

This essay examines Maya Angelou’s 1980 memoir All God’s Children Need Traveling Shoes. From 1962 to 1965, Angelou was part of a community of African American writers, artists, intellectuals, and activists who settled in Ghana as its first president, Kwame Nkrumah, seemed poised to usher in a new era of pan-African unity. Hoping to situate her identity within this dream of global pan-Africanism, Angelou narrates her relationship to Africa through the trope of diaspora-as-family. Her use of this metaphor, however, is complicated by her growing awareness of the involvement of Africans in the trans-Atlantic slave trade, as both victims and participants. While other scholarship on All God’s Children focuses on Angelou’s supposed inability to achieve a diasporan identity, I argue that Angelou is successfully able to come to terms with the trauma of the middle passage by listening to the “voices” of her enslaved ancestors (as they emerge within her own consciousness), and participating in an indigenous Ewe mourning ritual that she inadvertently precipitates. As a result of these experiences, Angelou comes to realize that while narration is important to the formation of both identity and community, African-descended people living in the Americas must first grapple with a historical trauma that exceeds the limits of narration. It is only when Angelou realizes this that she allows herself to be receptive to the spectral voices of her enslaved ancestors and the power of mourning to forge community across divides of time and place.
Prevalence and Prognostic Significance of Mitral Regurgitation in Acute Decompensated Heart Failure: The ARIC Study.

Abstract Objectives This study investigates the prevalence and prognostic significance of mitral regurgitation (MR) in acute decompensated heart failure (ADHF) patients. Background Few studies characterize the burden of MR in heart failure. Methods The ARIC (Atherosclerosis Risk In Communities) study surveilled ADHF hospitalizations for residents ≥55 years of age in 4 U.S. communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF): Results From 2005 to 2014, there were 17,931 weighted ADHF hospitalizations of which 49.2% had an LVEF Conclusions Patients with ADHF have a significant MR burden that varies with sex and race. In ADHF patients with an LVEF
Status Gains versus Status Losses: Loss Aversion and Deviance

The relationship between associating with (non)deviant peers and one’s own delinquent tendencies is often attributed to the motivation for positive reinforcement and status attainment. Guided by pr...
RTL-to-GDS design tools for monolithic 3D ICs

In this paper, we propose RTL-to-GDS design flow for monolithic 3D ICs (M3D) built with carbon nanotube field-effect transistors and resistive memory. Our tool flow is based on commercial 2D tools and smart ways to extend them to conduct M3D design and simulation. We provide a post-route optimization flow, which exploits the full potential of the underlying M3D process design kit (PDK) for power, performance and area (PPA) optimization. We also conduct IR-drop and thermal analysis on M3D designs to improve the reliability. To enhance the testability of our M3D designs, we develop design-for-test (DFT) methodologies and integrate a low-overhead built-in self-test module into our design for testing inter-layer vias (ILVs) as well as logic circuitries in the individual tiers. Our benchmark design is RISC-V Rocketcore, which is an open source processor. Our experiments show 8.1% of power, 19.6% of wirelength and 55.7% of area savings with M3D designs at iso-performance compared to its 2D counterpart. In addition, our IR-drop and thermal analyses indicate acceptable power and thermal integrity in our M3D design.
Evaluation of Solvency Standards for State Unemployment Insurance Trust Funds1

As a result of relatively large state unemployment insurance trust fund (UITF) balances and the perceived low risk of recessionary economic conditions, business leaders and policy makers across the U.S. are appealing for a moratorium or a reduction of unemployment insurance (UI) taxes. This article examines the advisability of this action in relation to adequacy standards endorsed by industry advisory groups. Using multivariate techniques, this article evaluates the relevance of the most widely used standard and determines how the maintenance of this standard affects the estimated length of time until insolvency after the onset of a recession. Assuming an economic downturn of the severity of the 1970s recession, we find that the standard is overly conservative with an associated probability of failure of less than 1 percent and with an ability to withstand a recession 100 months in length.
Laser and Light-Based Device Education in a Plastic Surgery Residency Program: A Continuing Medical Education Overview

The increasing prevalence of laser use, particularly in plastic surgery, demands the need for education of both practitioners and trainees to ensure patient safety and efficacy. The purpose of this continuing medical education module is to provide the learner with a detailed outline for laser training education for plastic surgery trainees. In this overview, a discussion of the characteristics of light, an introduction to fundamental laser principles, a comparison between lasers and pulsed light systems, and examples of several therapeutic applications for light-based devices in the clinical setting will be presented. Additionally, the five parameters necessary for operation of light-based devices, as well as the importance of laser safety education will be reviewed. It is the authors' hope that this CME will provide both practicing plastic surgeons and trainees the proper education on the lasers and pulsed light devices that they will use in their clinical practices.
The Case for Adopting Outside Reverse Veil Piercing in New Mexico

While the common law doctrine of veil piercing is well established in New Mexico, New Mexico courts have not explicitly considered whether to adopt and apply outside reverse veil piercing. In a traditional veil piercing case, courts disregard the corporate form to reach the assets of a corporate shareholder to satisfy the corporation’s debt. In an outside reverse veil piercing case, courts disregard the corporate form to reach the assets of a corporation to satisfy the debt of a corporate shareholder. The number of states to consider and adopt outside reverse veil piercing has grown rapidly in recent decades, and it is only a matter of time before New Mexico courts will be asked to explicitly consider its applicability in the state. In anticipation of such development, this article surveys New Mexico veil piercing jurisprudence and other states’ reverse piercing jurisprudence, observing that the similarities between traditional and outside reverse veil piercing doctrines make it difficult to articulate cogent reasons for adopting one and excluding the other. More, outside reverse veil piercing is consistent with both New Mexico law and public policy. The article concludes by suggesting a likely approach to outside reverse veil piercing for New Mexico courts.
Senotherapeutics: Experimental therapy of cellular senescence

Abstract Our global population is aging, and this changing demographic portends unprecedented levels of chronic diseases and healthcare burden. In response, new efforts to extend human healthspan are underway, informed by the “geroscience hypothesis,” which holds that incidence of aging-related chronic disease can be prevented, delayed, or attenuated by therapeutically targeting fundamental biology shared by the aging process and common chronic diseases. The promise of geroscience is that interventions will be found that target biological aging processes, thereby delaying the onset of multiple chronic diseases simultaneously. A major geroscience accomplishment has been to frame a set of tightly interrelated cellular biologic processes that are altered with aging that could be targeted to extend lifespan and healthspan: macromolecular damage, metabolism, proteostasis, inflammation, adaptation to stress, epigenetics, cell senescence, stem cells/regeneration, and pleiotropic processes. One of these biologic processes, cellular senescence and its related senescence-associated secretory phenotype, is an underlying contributor to age-related loss of physiologic integrity and function. Thus, interventions that mitigate senescent cell burden, termed “senotherapeutics,” would be expected to improve function, chronic diseases, and geriatric syndromes. This chapter is intended as an in-depth summary of research evaluating the clinical potential of senotherapeutics, with a focus on current testing of preclinical and clinical drugs, and practical considerations on translation of experimental therapy of cellular senescence to humans.
The history of orthopaedic surgery in India: from antiquity to present.

Indian orthopedists have a legacy dating back more than 4000 years. Starting with the Harappan civilization, ancient orthopaedic surgeons reduced fractures and conducted therapeutic trepanations. Since then, Indian physicians have pioneered many of the orthopaedic techniques still used today — including the use of prosthetics, fracture tables, and rehabilitative physical therapy. Today, orthopaedic surgeons coexist with traditional Indian bonesetters. Although bonesetting practices can have complication rates as high as 40%, bonesetters still handle a majority of fractures in India and are often culturally preferred. Importantly though, bonesetters are often the only expedient option available in both rural and urban settings.
Thermalization of orbital angular momentum in highly multimoded nonlinear optical fibers

We demonstrate that, due to nonlinear interactions, the orbital angular momentum in a multimode optical fiber can reach a thermal equilibrium state that is characterized by a temperature and a generalized Rayleigh-Jeans distribution.
3D MRI Models of the Musculoskeletal System.

Computed tomography (CT) is most commonly used to produce three-dimensional (3D) models for evaluating bone and joint morphology in clinical practice. However, 3D models created from magnetic resonance imaging (MRI) data can be equally effective for comprehensive and accurate assessment of osseous and soft tissue structure morphology and pathology. The quality of 3D MRI models has steadily increased over time, with growing potential to replace 3D CT models in various musculoskeletal (MSK) applications. In practice, a single MRI examination for two-dimensional and 3D assessments can increase the value of MRI and simplify the pre- and postoperative imaging work-up. Multiple studies have shown excellent performance of 3D MRI models in shoulder injuries, in the hip in the setting of femoroacetabular impingement, and in the knee for the creation of bone surface models. Therefore, the utility of 3D MRI postprocessed models is expected to continue to rise and broaden in applications. Computer-based and artificial intelligence–assisted postprocessing techniques have tremendous potential to improve the efficiency of 3D model creation, opening many research avenues to validate the applicability of 3D MRI and establish 3D-specific quantitative assessment criteria. We provide a practice-focused overview of 3D MRI acquisition strategies, postprocessing techniques for 3D model creation, MSK applications of 3D MRI models, and an illustration of cases from our daily clinical practice.
Eco-CMB: A Hardware-Accelerated Band-Power Feature Extractor for Tactile Embedded Systems

Real-time and energy efficient signal feature extraction has become increasingly important for machine-learning-enabled smart sensor systems in mobile and Edge applications. As considerable scientific and technological efforts have been devoted to developing tactile sensing with prospective applications in many fields, such as smart prosthetics, remote palpation, and robotic surgery with the sense of touch; in this paper, we develop a parallel hardware-software signal feature extraction method and apply it to a dataset of tactile texture classification. Being easily parallelizable, a set of passband-power feature extraction blocks compute signal power in various passbands and can be clock gated for accuracy-energy trade-offs controlled by a proposed feature summarization algorithm. Our experimental results on the tactile dataset have shown that the proposed method works at high levels of parallelization and realtimeness, performs with lower computational complexity, and achieves accuracy levels comparable to those of convolutional neural networks.
Substrate Binding to the Acetylcholinesterase Peripheral Site Promotes Substrate Hydrolysis but also Gives Rise to Substrate Inhibition

Many ligands that bind to the peripheral site of acetylcholinesterase (AChE) inhibit substrate hydrolysis at the acylation site, though the interpretation of this inhibition has been unclear. Since previous explanations based upon equilibrium ligand binding cannot be justified for AChE, we introduced an alternative nonequilibrium analysis. This analysis incorporates a steric blockade mechanism which assumes that the only effects of a small bound peripheral ligand are to slow down the rates of substrate association and dissociation at the acylation site and concomitantly reduce the product dissociation rate. Experimental data using propidium and gallamine as peripheral site ligands and acetylthiocholine, phenyl acetate, huperzine A and m-((N, N, N -trimethylammonio)-trifluoroacetophenone as acylation site ligands agreed well with our theory. The nonequilibrium model has been extended to account for substrate inhibition based upon acetylthiocholine affinity for the peripheral site. This affinity was determined by measuring acetylthiocholine inhibition of the association rate k on for the slowly equilibrating peripheral site ligand fasciculin 2. The measured K s of about 1–2 mM was considerably lower than the K ss estimate of about 20 mM determined by application of the Haldane equation to the steady-state substrate inhibition curve. A better understanding of the interaction between peripheral site ligands and acetylcholinesterase may help to understand the physiological role of the peripheral site and to design new ligands that inhibit organophosphorylation.
Retirement Security and Defined Contribution Pension Plans: The Role of Company Stock in 401(k) Plans

Proposals have been suggested recently that would attempt to transfer part or all of the investment risk inherent in defined contribution plans from the employee to another entity. Although the party initially exposed to said risk varies among the proposals, the likely targets would be the employer, a government agency (perhaps the Pension Benefit Guaranty Corporation) and/or a private insurance company. While the cost of the guarantees and/or financial uncertainty inherent in such an arrangement may be borne by the employer at least initially, it is unlikely that, in the long-term, such a shift in risk-bearing would not somehow alter the provisions of the existing defined contribution plans. It is obviously impossible to model the financial consequences of such proposals until additional detail is provided; however, a highly stylized example of one method of achieving this objective can be readily simulated.
Sites on the Landscape: The Early Mesolithic

The Early Mesolithic, or Beuronien, lasted for approximately 2500 years, from 10,300 to 7800 b.p. The hallmark of this period is the abundance of microliths, which have been classified by Taute (1972/73) and used to establish a stylistic chronology. Three primary stages have been recognized in this scheme, derived from stratigraphic sequences in cave sites and supported by radiocarbon determinations: Beuronien A, characterized by isosceles triangles with obtuse angles, narrow, irregular trapezes, and lanceolate points with convex, dorsoventrally retouched bases; Beuronien B, with isosceles triangles with acute angles and lanceolate points with concave, dorso-ventrally retouched bases; and Beuronien C, typified by backed bladelets, very small and narrow scalene triangles, bilaterally backed micropoints, and lanceolate points with concave, dorsally retouched bases. Since this sequence was developed, a poorly defined fourth stage, the “Earliest Mesolithic,” has been recognized underlying the Beuronien A at a few sites.
Acyl coenzyme A:1-acylglycerophosphorylglycerol acyltransferase from rat liver.

Abstract Rat liver microsomes are capable of catalyzing the acylation of 1-palmitoyl-sn-glycero-3-phosphoryl-rac-glycerol for phosphatidylglycerol formation. The requirements for the reaction appear to be the same as the analogous reaction for lecithin synthesis. In contrast, however, to oleoyl-CoA:1-palmitoyl-sn-glycero-3-phosphorylcholine acyltransferase, which has a pH optimum of 7.0, oleoyl-CoA:1-palmitoyl-sn-glycero-3-phosphoryl-rac-glycerol acyltransferase functions optimally at pH 9.0. The latter is also distinguishable by being more stable at the alkaline pH than the former. The data indicate that in addition to positional specificity and acyl group preferability, acyl-CoA:acyl glycerophospholipid acyltransferases also possess phosphorylalcohol group specificity.
Reassociation of eukaryotic ribosomal subunits. Kinetics of reassociation; role of deacylated transfer ribonucleic acid; effect of cycloheximide.

The reassociation of ribosomal subunits to from 80 S monomers is catalyzed by a rat liver cytosol fraction (G-25) and by the initiation factor M1 (formerly called 40 S binding factor). Reassociation requires a template (we have generally used poly(U)) and either aminoacyl-tRNA or deacylated tRNA. Initiation factor-catalyzed formation of 40 S-60 S couples can occur in two ways. The first pathway of reassociation has faster kinetics, requires aminoacyl-tRNA, is insensitive to cycloheximide, and leads to the formation of 80 S ribosomes active in the synthesis of protein. The second pathway has slower kinetics, uses deacylated-tRNA, is sensitive to inhibition by cycloheximide, and the 80 S ribosomes formed do not synthesize protein. Although cycloheximide inhibits reassociation by the second pathway it does not interfere with the binding of deacylated tRNA to 40 S subunits (or of aminoacyl-tRNA, for that matter). That reassociation which occurs in the absence of initiation factors probably proceeds by the second pathway since it has slow kinetics and is inhibited by cycloheximide. Reassociation of ribosomal subunits catalyzed by purified M1 is also inhibited by cycloheximide, which suggests that a second factor is normally required.
Transcriptional silencing of fetal hemoglobin by BCL11A

The beta-thalassemia syndromes are a major global health problem. Increased levels of fetal hemoglobin (HbF) ameliorate the clinical symptoms seen in this disease. By taking advantage of the natural variation in the level of HbF in various populations, we and others identified several common genetic variants in three major loci that regulate HbF levels. One of these variants resides in the gene BCL11A. We have studied the role of this gene product and established that BCL11A maintains silencing of gamma-globin expression in adult erythroid cells and functions as a direct transcriptional regulator of the fetal to adult hemoglobin switch in humans. Moreover, we found that BCL11A plays a central role in the evolutionarily divergent globin gene switches of mammals. As a factor critical for gamma-globin gene silencing, BCL11A should be considered as a therapeutic target to increase HbF in a directed manner in beta-thalassemia patients.
Dietary Glycemia Reversibly Contributes to Age-related Macular Degeneration and Metabolic Disease in Aged C57Bl/6J Mice

Dietary Glycemia Contributes Reversibly to Age-related Macular Degeneration and Metabolic Disease in Aged C57Bl/6J Mice Objective: Consuming high glycemia diets is a risk factor for Age-related Mac...
1,2‐Dibromo‐1,1,2,2‐tetrafluoroethane

[124-73-2] C2Br2F4 (MW 259.82) InChI = 1S/C2Br2F4/c3-1(5,6)2(4,7)8 InChIKey = KVBKAPANDHPRDG-UHFFFAOYSA-N (reagent used as a brominating reagent, an alkylating reagent, and as a solvent; can function as a precursor for the introduction of Br, CF2CF2Br into organic compounds) Physical Data: bp 46–48 °C; d 2.149 g cm−3.1 Solubility: soluble in ether, acetone, alcohol, and most organic solvents. Form Supplied in: colorless liquid. Preparative Methods: can be prepared by the reaction of CF2CF2 with Br2 in HSO3F or HSO3F/SbF5,1 or by the reaction of CF2CF2 with Br2 and SO3.2 Handling, Storage, and Precautions: use in a fume hood. [Note: C2Br2F4 is known as the flame retardant Halon 2402 and has been classified as an ozone-depleting material, category 6, by the EPA (http://www.epa.gov/ozone/ods.html).]