cssi/SciSciGPT-SciSciNet huggingface dataset:
Circuits, Signals, and Systems

These twenty lectures have been developed and refined by Professor Siebert during the more than two decades he has been teaching introductory Signals and Systems courses at MIT. The lectures are designed to pursue a variety of goals in parallel: to familiarize students with the properties of a fundamental set of analytical tools; to show how these tools can be applied to help understand many important concepts and devices in modern communication and control engineering practice; to explore some of the mathematical issues behind the powers and limitations of these tools; and to begin the development of the vocabulary and grammar, common images and metaphors, of a general language of signal and system theory.Although broadly organized as a series of lectures, many more topics and examples (as well as a large set of unusual problems and laboratory exercises) are included in the book than would be presented orally. Extensive use is made throughout of knowledge acquired in early courses in elementary electrical and electronic circuits and differential equations.Contents: Review of the "classical" formulation and solution of dynamic equations for simple electrical circuits; The unilateral Laplace transform and its applications; System functions; Poles and zeros; Interconnected systems and feedback; The dynamics of feedback systems; Discrete-time signals and linear difference equations; The unilateral Z-transform and its applications; The unit-sample response and discrete-time convolution; Convolutional representations of continuous-time systems; Impulses and the superposition integral; Frequency-domain methods for general LTI systems; Fourier series; Fourier transforms and Fourier's theorem; Sampling in time and frequency; Filters, real and ideal; Duration, rise-time and bandwidth relationships: The uncertainty principle; Bandpass operations and analog communication systems; Fourier transforms in discrete-time systems; Random Signals; Modern communication systems."Circuits, Signals, and Systems" is included in The MIT Press Series in Electrical Engineering and Computer Science, copublished with McGraw-Hill.
Brainstem Melanocortin 3/4 Receptor Stimulation Increases Uncoupling Protein Gene Expression in Brown Fat

Central administration of melanocortin 3 and 4 receptor (MC3/ 4-R) agonists increases energy expenditure, with the hypothalamus commonly held as the primary site of action. It is also clear, however, that MC4-R are expressed in caudal brainstem structures of relevance to the control of energy expenditure. Three experiments investigated whether hindbrain MC-R contribute to the energy expenditure effects of central MC3/4-R agonist treatments; in each, we examined the effect of fourth intracerebroventricular (icv) administration of a MC3/4-R agonist, MTII (three injections, each separated by 12 h), on uncoupling protein 1 (UCP-1) gene expression in brown adipose tissue (BAT). First, we compared the effects of fourth and third icv administration of MTII and found that the hindbrain and forebrain treatments were equally effective at elevating UCP-1 mRNA expression in BAT compared with the respective vehicletreated group results. A second experiment demonstrated that the fourth icv MTII-induced rise in UCP-1 expression was mediated by sympathetic outflow to BAT by showing that this response was abolished by surgical denervation of BAT. In the third experiment, we showed that chronic decerebrate rats, like their neurologically intact controls, elevated UCP-1 mRNA expression in response to fourth icv MTII administration. Taken together, the results indicate that: 1) there is an independent caudal brainstem MC3/4-R trigger for a sympathetically stimulated elevation in BAT UCP-1 gene expression, and 2) the MTIIinduced rise in UCP-1 expression can be mediated by circuitry intrinsic to the caudal brainstem and spinal cord. (Endocrinology 144: 4692–4697, 2003)
Mitochondrial hyperfusion induced by loss of the fission protein Drp1 causes ATM-dependent G2/M arrest and aneuploidy through DNA replication stress

Mitochondrial fission and fusion cycles are integrated with cell cycle progression. In this paper, we demonstrate that the inhibition of mitochondrial fission protein Drp1 causes an unexpected delay in G2/M cell cycle progression and aneuploidy. In investigating the underlying molecular mechanism, we revealed that inhibiting Drp1 triggers replication stress, which is mediated by a hyperfused mitochondrial structure and unscheduled expression of cyclin E in the G2 phase. This persistent replication stress then induces an ATM-dependent activation of the G2 to M transition cell cycle checkpoint. Knockdown of ATR, an essential kinase in preventing replication stress, significantly enhanced DNA damage and cell death of Drp1-deficienct cells. Persistent mitochondrial hyperfusion also induces centrosomal overamplification and chromosomal instability, which are causes of aneuploidy. Analysis using cells depleted of mitochondrial DNA revealed that these events are not mediated by the defects in mitochondrial ATP production and reactive oxygen species (ROS) generation. Thus dysfunctional mitochondrial fission directly induces genome instability by replication stress, which then initiates the DNA damage response. Our findings provide a novel mechanism that contributes to the cellular dysfunction and diseases associated with altered mitochondrial dynamics.
Molecular modeling-based analysis of interactions in the RFC-dependent clamp-loading process.

Replication and related processes in eukaryotic cells require replication factor C (RFC) to load a molecular clamp for DNA polymerase in an ATP-driven process, involving multiple molecular interactions. The detailed understanding of this mechanism is hindered by the lack of data regarding structure, mutual arrangement, and dynamics of the players involved. In this study, we analyzed interactions that take place during loading onto DNA of either the PCNA clamp or the Rad9-Rad1-Hus1 checkpoint complex, using computationally derived molecular models. Combining the modeled structures for each RFC subunit with known structural, biochemical, and genetic data, we propose detailed models of how two of the RFC subunits, RFC1 and RFC3, interact with the C-terminal regions of PCNA. RFC1 is predicted to bind PCNA similarly to the p21-PCNA interaction, while the RFC3-PCNA binding is proposed to be similar to the E. coli δ-β interaction. Additional sequence and structure analysis, supported by experimental data, suggests that RFC5 might be the third clamp loader subunit to bind the equivalent PCNA region. We discuss functional implications stemming from the proposed model of the RFC1-PCNA interaction and compare putative clamp-interacting regions in RFC1 and its paralogs, Rad17 and Ctf18. Based on the individual intermolecular interactions, we propose RFC and PCNA arrangement that places three RFC subunits in association with each of the three C-terminal regions in PCNA. The two other RFC subunits are positioned at the two PCNA interfaces, with the third PCNA interface left unobstructed. In addition, we map interactions at the level of individual subunits between the alternative clamp loader/clamp system, Rad17-RFC2–5/Rad9-Rad1-Hus1. The proposed models of interaction between two clamp/clamp loader pairs provide both structural framework for interpretation of existing experimental data and a number of specific findings that can be subjected to direct experimental testing.
Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F–DP

The E2F and DP protein families form heterodimeric transcription factors that play a central role in the expression of cell cycle-regulated genes. The crystal structure of an E2F4–DP2–DNA complex shows that the DNA-binding domains of the E2F and DP proteins both have a fold related to the winged-helix DNA-binding motif. Recognition of the central c/gGCGCg/c sequence of the consensus DNA-binding site is symmetric, and amino acids that contact these bases are conserved among all known E2F and DP proteins. The asymmetry in the extended binding site TTTc/gGCGCc/g is associated with an amino-terminal extension of E2F4, in which an arginine binds in the minor groove near the TTT stretch. This arginine is invariant among E2Fs but not present in DPs. E2F4 and DP2 interact through an extensive protein–protein interface, and structural features of this interface suggest it contributes to the preference for heterodimers over homodimers in DNA binding.
Molecular Mechanisms of Insulin-like Growth Factor I Receptor Function: Implications for Normal Physiology and Pathological States

The sections in this article are: 1 Structural Aspects of Insulin-Like Growth Factor Receptors 1.1 Structure of the Insulin-Like Growth Factor I Receptor 1.2 Structure of the Insulin-Like Growth Factor I Receptor Gene and mRNA 1.3 The Regulatory Region of the Insulin-Like Growth Factor I Receptor Gene 2 Regulation of the Insulin-Like Growth Factor I Receptor Gene 2.1 Transcriptional Regulation 2.2 Regulation by Growth Factors 2.3 Repression of the Insulin-Like Growth Factor I Receptor by Tumor Suppressors 2.4 Developmental Regulation of the Insulin-Like Growth Factor I Receptor 3 Heterogeneity of the Insulin-Like Growth Factor I Receptor 3.1 Differences in Primary Structure 3.2 Additional Structural Heterogeneity 3.3 Hybrid Receptors 4 Function of the Insulin-Like Growth Factor I Receptor 4.1 The Receptor and Signaling 4.2 The Insulin-Like Growth Factor I Receptor and the Cell Cycle 4.3 The Insulin-Like Growth Factor I Receptor and Apoptosis 4.4 Function as Assessed by Loss of the Insulin-Like Growth Factor I Receptor: Studies of “Knock-out” Mice 4.5 Human Genetic Short Stature 5 The Role of Insulin-Like Growth Factor I Receptors in various Systems and Pathological States 5.1 Nervous System 5.2 Muscle 5.3 Reproductive System 5.4 Kidney 5.5 Immune System 5.6 Cancer 5.7 Effects of Insulin-Like Growth Factor I on Gene Expression 6 Conclusion
Ultrafast Carrier Dynamics in Nanostructures for Solar Fuels

Sunlight can be used to drive chemical reactions to produce fuels that store energy in chemical bonds. These fuels, such as hydrogen from splitting water, have much larger energy density than do electrical storage devices. The efficient conversion of clean, sustainable solar energy using photoelectrochemical and photocatalytic systems requires precise control over the thermodynamics, kinetics, and structural aspects of materials and molecules. Generation, thermalization, trapping, interfacial transfer, and recombination of photoexcited charge carriers often occur on femtosecond to picosecond timescales. These short timescales limit the transport of photoexcited carriers to nanometer-scale distances, but nanostructures with high surface-to-volume ratios can enable both significant light absorption and high quantum efficiency. This review highlights the importance of understanding ultrafast carrier dynamics for the generation of solar fuels, including case studies on colloidal nanostructures, nanostructured photoelectrodes, and photoelectrodes sensitized with molecular chromophores and catalysts.
Energy and Network Aware Workload Management for Sustainable Data Centers with Thermal Storage

Reducing the carbon footprint of data centers is becoming a primary goal of large IT companies. Unlike traditional energy sources, renewable energy sources are usually intermittent and unpredictable. How to better utilize the green energy from these renewable sources in data centers is a challenging problem. In this paper, we exploit the opportunities offered by geographical load balancing, opportunistic scheduling of delay-tolerant workloads, and thermal storage management in data centers to facilitate green energy integration and reduce the cost of brown energy usage. Moreover, bandwidth cost variations between users and data centers are considered. Specifically, this problem is first formulated as a stochastic program, and then, an online control algorithm based on the Lyapunov optimization technique, called Stochastic Cost Minimization Algorithm (SCMA), is proposed to solve it. The algorithm can enable an explicit trade-off between cost saving and workload delay. Numerical results based on real-world traces illustrate the effectiveness of SCMA in practice.
From Polychronicity to Multitasking: The Warping of Time Across Disciplinary Boundaries

Anthropologist Edward T. Hall's contrast between polychronic and monochronic orientations toward time has stimulated research in the business and management sciences. While Hall's approach to time is ethnographic, the business and management sciences measure polychronicity with a survey instrument, the Inventory of Polychronic Values (IPV). An examination of the IPV and the results it has yielded, however, indicate that it is not measuring polychronicity in the ethnographic sense. The IPV remains firmly within monochronic time and thus fails to seriously engage cultural difference. The transformation of the ethnographic meaning of polychronic to a conceptual one raises methodological and analytical questions of general relevance to the cross-cultural study of work.
An ECG dataset representing real-world signal characteristics for wearable computers

We present an ECG dataset collected in real-world scenarios for wearable devices that includes over 260 recordings of 90–210 seconds that provide guidance for designers to evaluate signal acquisition circuit and system solutions. Several variations on the signal acquisition path are demonstrated, including various sources of interference (baseline wander, motion artifacts, and power line interference), signal path variations (electrode type, coupling method, and common-mode rejection method), and electrode placements (wrist and chest). Based on detailed analysis of signal characteristics under different scenarios, analog front-end (AFE) design recommendations are proposed.
Letter by Bishu Regarding Article, “Effect of Pulmonary Hypertension Hemodynamic Presentation on Clinical Outcomes in Patients With Severe Symptomatic Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: Insights From the New Proposed Pulmonary Hypertension Classification”

I read with interest the study entitled “Effect of Pulmonary Hypertension Hemodynamic Presentation on Clinical Outcomes in Patients With Severe Symptomatic Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: Insights From the New Proposed Pulmonary Hypertension Classification.”1 The authors are to be congratulated on an admirably executed study. Multiple studies have shown that severe pulmonary hypertension (PH) is associated with worse outcomes after transcatheter aortic valve replacement (TAVR) for aortic stenosis.2,3 O’Sullivan et al1 classified patients with severe aortic stenosis undergoing TAVR according to the PH hemodynamics into those with …
A novel method of imaging dopamine release in awake animals with positron emission tomography (PET)

718 Objectives: Determine if the neurochemical affects of a behavioral paradigm or various drug challenges could be measured without the confounding influences of anesthesia associated with the imaging of animals using positron emission tomography. Methods: Control animals(n=8), S.D. Rat, were permitted to move freely for 30 min following intravenous(IV) 11C-raclopride(RAC) admin. Animals were then anesthetized and scanned for 25 min. Separate groups of animals received pharmacological challenges of: unlabeled rac(5mg/kgIV) co-administered with RAC(n=4), methamphetamine(METH,5mg/kg IP,n=5) and S-GVG(150mg/kgIP) followed by METH(n=6) 10 min prior to RAC. Another group(n=5) underwent hand restraint and lifting during the 30 min uptake period of RAC. All challenged groups were anesthetized and scanned for 25 min. following 30min of RAC uptake. Traditional 60 min scans of RAC were performed in animals(n=4) anesthetized for the 30min uptake period. Striatal to cerebellar ratios were calculated for all groups during the last 25 min of scanning. Results: There was no significant difference between awake freely moving animals vs anesthetized animals. Unlabeled rac produced a ~93% occupancy of D2 receptors in both awake and anesthetized animals. METH administration decreased RAC binding by 35%. S-GVG blocked METH induced increases of dopamine. Animal restraint produced a 39% decrease in RAC binding. Conclusions: These studies support a novel molecular imaging methodology in which animals receive the imaging agent without anesthesia. During this uptake period animals can be subjected to various behavioral paradigms or pharmacological challenges and then scanned within the tomograph. This provides researchers with increased flexibility in measuring specific molecular events associated with more complex behaviors. Research Support: NIH DA15041 and DA22346
Absence of Residues in Milk After Dimethoate and Malathion Were Applied with Backrubbers to Dairy Cattle

Several backrubber-applied insecticides are effective against insect pests on dairy cattle; however, very few have been recommended because of the possibilty of milk contamination. At the piesent time only one insecticide, Ciodrin® ( alpha -methylbenzyl 3-hydroxycrotonate dimethyl phosphate), is registered for backrubber application to dairy cattle (Entomology Research Division 1964). A test was conducted at the Clemson University Dairy Science Barn to determine if detectable residues were excreted in the milk of dairy cattle that were treated with either dimethoate or malathion applied by backrubbers.
Allogeneic bone marrow chimerism in germ-free mice. II. Prevention of reticulum cell sarcomas in SJL-J mice.

SummaryGerm-free and conventional SJL/J mice develop reticulum cell sarcomas spontaneously, whereas C3H mice do not. Chimerism was established in lethally irradiated SJL/J mice by transplanted bone marrow cells from C3H mice. Conventional chimeric mice died of graft-versus-host disease, but germ-free chimeric mice survived indefinitely. At age 12 months, 95% of the germ-free SJL/J mice had reticulum cell sarcomas, while up to the age of 15 months, germ-free chimeric SJL/J mice had none.
Experimental Study on Magnetized Combustion Technology of Fuel Oil

On the basis of a South Korean GE200 small home use fuel oil boiler,a small fuel oil magnetization burning test system has been established.A great number of experiments have been conducted on the boiler's combustion efficiency,the exhaust smoke temperature and the harmful gas emission when the fuel oil was magnetized.The effect of different magnetism intensities and its regularity are discussed.The result shows that a magnetic field installed on the fuel oil pipe can improve the fuel oil's burning effect,saving energy,forming low-oxygen working condition and lessen the environmental pollution effectively.
Fire All the Boomers: How Generational Labeling Legitimizes Age Discrimination

Costanza and Finkelstein (2015) make a number of important observations in their exploration of how generation-based differences are understood by academics and practitioners. The absence of a unifying theory, the lack of a clear pattern of findings, and the conceptual ambiguity about generational membership have all limited the utility of generational membership to researchers, while the practice of describing large groups of individuals in generational terms has become enormously popular outside of academia. Certainly, there are several topics that are popular among the public and widely used by businesses despite being viewed negatively by academics; however, there is some danger in the widespread perception that group differences between individuals of different ages can be explained by generational membership. Although it might be tempting to consider these generational stereotypes as simply innocuous misperceptions supervisors may hold, they may, in fact, be quite harmful. The purpose of this article is to further expand on the potential for these stereotypes to be harmful for older and younger employees.
Detection and Quantitative Characterization of Macromolecular Heteroassociations via Composition Gradient Sedimentation Equilibrium

A novel approach to the detection and characterization of macromolecular heteroassociations is described, based upon a combination of short-column sedimentation equilibrium measurements and the utilization of a composition gradient spanning the entire range of mole fractions of interacting components. Simulations are presented to demonstrate that the method described provides a high degree of discrimination between alternative models for heteroassociation equilibria. Comparison with experimental protocols utilized previously shows that the new approach provides equivalent information with less sample and a considerably shorter duration of centrifugation.
Gradual correction of knee flexion contracture using external fixation

Introduction: Knee flexion contracture (KFC) is a debilitating condition that may affect patients with neurogenic conditions, congenital deformities, posttraumatic deformities, and after total knee replacement. The recurrence rate of the deformity following either operative or nonoperative treatment remains high. The aim of the present study is to assess clinical outcomes of patients with KFCs and associated ankle equinus using gradual correction with a circular external fixator (CEF). Methods: Twenty-one patients with knee flexion contraction were treated using a CEF. Seven patients were also simultaneously treated for ankle equinus. All but two patients underwent a combination of open or arthroscopic knee arthrolysis, distal hamstrings lengthening, and gastrocsoleus release. The CEF was applied to match the residual deformity, following the minimal incision soft-tissue release. Results: Mean follow-up was 13 months. The mean range of motion (ROM) at final follow-up was −10° extension, 64° flexion, 9° ankle dorsiflexion, and 29° ankle plantar flexion. The difference between preoperative and postoperative ROMs was statistically significant (P Discussion: The present study suggests that gradual distraction using a CEF is a safe and effective technique in the management of KFC and concurrent ankle equinus. It is crucial to maintain the postoperative correction with braces for at least 1-3 months, depending on the severity of the condition.
Nuclear Data Measurements, Analysis and Evaluation at the Oak Ridge National Laboratory in Support of Nuclear Criticality Safety

This paper describes the activities in nuclear data measurement, nuclear data evaluation, and nuclear data testing at the Oak Ridge National Laboratory in support of the US Department of Energy Nuclear Criticality Safety Program. Data measurement’s activities are performed at the Oak Ridge Electron Linear Accelerator (ORELA); data evaluations are done with the computer code SAMMY; and cross section processing is performed by the AMPX and/or NJOY code systems.
Characterization of Iron Phthalocyanine as the Cathode Active Material for Lithium-Ion Batteries

The developed thermodynamic functions for the determination of Gibbs free energy, enthalpy, and entropy of formation of solid lithium-iron phthalocyanine (LixFePc) from solid lithium and iron phthalocyanine as a function of x, defined as g-moles of the intercalated lithium per g-mole of iron phthalocyanine, at a fixed set of temperature and pressure conditions are presented. In addition, a proposed expression for the evaluation of lithium diffusion coefficient in solid iron phthalocyanine as a function of both x and temperature, and the experimental results from the ongoing research/development work on the lithium/iron phthalocyanine cells are included
Colposcopic imaging using visible-light optical coherence tomography

High-resolution colposcopic optical coherence tomography (OCT) provides key anatomical measures, such as thickness and minor traumatic injury of vaginal epithelium, of the female reproductive tract noninvasively. This information can be helpful in both fundamental investigations in animal models and disease screenings in humans. We present a fiber-based visible-light OCT and two probe designs for colposcopic application. One probe conducts circular scanning using a DC motor, and the other probe is capable of three-dimensional imaging over a 4.6 × 4.6 - mm 2 area using a pair of galvo scanners. Using this colposcopic vis-OCT with both probes, we acquired high-resolution images from whole isolated macaque vaginal samples and identified biopsy lesions.
Gigging “classical” in Iran

ABSTRACTThe term “classical” is often applied to the genre of Iranian music known as musiqi-e sonnati (traditional music), normally identified by a form of music making involving extensive extemporization based on a structural framework called the radif, historically performed at length in intimate settings among initiated individuals. Today, classically trained musicians working the public concert circuit in Iran face a somewhat different picture of musical practice. Concert halls are typically much larger, audiences much wider, and performances much shorter. Many musicians tend to categorize themselves as classical, though they do not always perform according to the traditional parameters of the sonnati genre. This raises questions about new developments in classical music that fall just outside radif-based performance, and about the perceived conceptual relationship between sonnati and new-classical performance as the genre evolves. This article explores some of these dynamics through reflections among...
Ditio: Trustworthy Auditing of Sensor Activities in Mobile & IoT Devices

Mobile and Internet-of-Things (IoT) devices, such as smartphones, tablets, wearables, smart home assistants (e.g., Google Home and Amazon Echo), and wall-mounted cameras, come equipped with various sensors, notably camera and microphone. These sensors can capture extremely sensitive and private information. There are several important scenarios where, for privacy reasons, a user might require assurance about the use (or non-use) of these sensors. For example, the owner of a home assistant might require assurance that the microphone on the device is not used during a given time of the day. Similarly, during a confidential meeting, the host needs assurance that attendees do not record any audio or video. Currently, there are no means to attain such assurance in modern mobile and IoT devices. To this end, this paper presents Ditio, a system approach for auditing sensor activities. Ditio records sensor activity logs that can be later inspected by an auditor and checked for compliance with a given policy. It is based on a hybrid security monitor architecture that leverages both ARM's virtualization hardware and TrustZone. Ditio includes an authentication protocol for establishing a logging session with a trusted server and a formally verified companion tool for log analysis. Ditio prototypes on ARM Juno development board and Nexus 5 smartphone show that it introduces negligible performance overhead for both the camera and microphone. However, it incurs up to 17% additional power consumption under heavy use for the Nexus 5 camera.
How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition

Background Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Methods Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Results Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. Conclusions These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments.
Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

OBJECTIVE. FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head wa...
Estimating cancer risk from 99mTc pyrophosphate imaging for transthyretin cardiac amyloidosis.

Increasing recognition that transthyretin cardiac amyloidosis (ATTR-CA) is much more common than previously appreciated and the emergence of novel disease-modifying therapeutic agents have led to a paradigm shift in which ATTR-CA screening is considered in high-risk populations, such as patients with heart failure with preserved ejection fraction (HFpEF) or aortic stenosis. Radiation risk from 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, a test with very high sensitivity and specificity for ATTR-CA, has not been previously determined. Radiation doses to individual organs from 99mTc-PYP were estimated using models developed by the Medical Internal Radiation Dose Committee and the International Commission on Radiological Protection. Excess future cancer risks were estimated from organ doses, using risk projection models developed by the National Academies and extended by the National Cancer Institute. Excess future risks were estimated for men and women aged 40-80 and compared to total (excess plus baseline) future risks. All-organ excess cancer risks (90% uncertainty intervals) ranged from 5.88 (2.45,11.4) to 12.2 (4.11,26.0) cases per 100,000 patients undergoing 99mTc-PYP testing, were similar for men and women, and decreased with increasing age at testing. Cancer risks were highest to the urinary bladder, and bladder risk varied nearly twofold depending on which model was used. Excess 99mTc-PYP-related cancers constituted < 1% of total future cancers to the critical organs. Very low cancer risks associated with 99mTc-PYP testing suggest a favorable benefit-risk profile for 99mTc-PYP as a screening test for ATTR-CA in high-risk populations, such as such as patients with HFpEF or aortic stenosis.
Quasigeostrophic Modelling of Eddy-Resolved Ocean Circulation

A discussion is given of the development and application of quasigeostrophic models of ocean circulation. Several applications are shown, including simple basin models, North Atlantic models, and several limited area models that illustrate the flexibility and power of QG eddy-resolving models for understanding ocean dynamics.
Estrogen Regulation of Growth and Specific Protein Synthesis in Human Breast Cancer Cells in Tissue Culture

Successful endocrine therapy in breast cancer has been theorized to be dependent upon retention by the tumor of at least part of the cell’s differentiated endocrine functions (1). Estrogen receptors (ER) therefore have been measured extensively in breast tumor biopsies in numerous laboratories as a potential marker of a functional endocrine system. Accordingly, tumors containing ER are much more likely to respond to endocrine therapies than tumors without ER (2). ER alone however is not a totally reliable marker of tumor sensitivity to hormones since certain tumors containing ER do not respond to endocrine manipulations. This is not surprising however, considering that binding of the hormone to the estrogen receptor is only the first step in a complex biochemical pathway leading to the physiological effect of estrogens (3). Any number of points in the pathway may conceivably be missing or defective. For this reason, we hypothesized that an end product of estrogen stimulation would improve the reliability of ER as a marker of hormone-responsive tumor growth (4). Progesterone receptor (PgR) is a likely candidate since it has been shown to be regulated by estrogens in animal mammary tumor models (5, 6) and in human breast cancer cells in tissue culture (7). Simultaneous measurement of PgR and ER in fact does improve the reliability of ER measurement alone in predicting patient response to endocrine therapies (8).
Selenium Content and Oxidation States in Fly Ashes from Western U.S. Coals

A selective extraction scheme was developed for the determination of the oxidation states of Se species in coal ashes. As compared to HF dissolution, extractions with 70% HClO4 mobilized 90 to 100% of all compound and redox forms of Se from four of the five fly ashes. Extractions with 16M HNO3 did not mobilize all forms of Se as effectively as perchloric acid. Both oxidized forms of Se (IV and VI) were completely mobilized by 12M HCl extraction. Deionized-distilled water was not an effective extractant for mobilizing all compound forms of Se(IV) from fly ashes. Extraction data (70% HClO4, 16M HNO3, 12M HCI, DI water) indicated that the solid:solution ratio is a critical factor in Se extractability from fly ashes. Maximum extractions in all cases were obtained only with very high (1:500) solid:solution ratios. Extraction times from 1.5 to 25 hours did not significantly change Se extractability with any of the extractants except with 12M HCI, which required a minimum reaction time of 48 hours to attain maximum Se extractability. Reaction times shorter than the critical time and low solid:solution ratios significantly affected Se extractability from these fly ashes. Measurements of Se content and redox state in particle size and density fractions five western United States coal ashes indicated that typically, the Se content increased with decreasing particle size.. However, no consistent trend in Se concentration between the light and heavy density fractions of <2.7-µm size fraction was observed. Selenium redox state data indicated that only Se(0) and Se(IV) forms were present in these five coal ashes. The presence of Se(IV) is significant since it is much more easily mobilized than the elemental form. Examination of fly ashes by the proposed scheme to determine Se redox species could permit better estimation of the Se content of plants grown on fly ash amended soils.
Association of gene expression with outcomes with everolimus as post-VEGF inhibitor therapy for renal cell carcinoma (RCC).

e16554Background: The use of everolimus (E) monotherapy to treat RCC has diminished due to the approvals of new agents. We hypothesized that gene expression associated with benefit may provide the ...
Developments of the Jülich-Bonn Dynamical Coupled-Channel Analysis

A new analysis of $$K\varLambda $$ photoproduction is presented, including the latest data measured at Jefferson Lab and other facilities. Evidence for two states has been found, the $$N(1900)3/2^+$$ and $$N(2060)5/2^-$$ resonances that have been seen in other analysis. Future extensions are discussed like the use of model selection techniques to achieve a minimal resonance content of the amplitude. Also, conceptual aspects like three-body unitarity are highlighted that can help to provide a connection between phenomenology and ab-initio lattice QCD calculations.
On Single Versus Multiple Imputation for a Class of Stochastic Algorithms Estimating Maximum Likelihood

We discuss a special class of stochastic versions of the EM algorithms. The advantage of the single imputation procedure in non-exponential family applications is highlighted. We prove that ergodic properties of the stochastic algorithms are dependent not on the multiplicity of the imputation scheme but rather on the stability of the deterministic component of an underlying stochastic difference equation.
High-throughput optical coherence tomography (HT-OCT) imaging of tumor spheroids for drug screening (Conference Presentation)

The feasibility of using optical coherence tomography, a label-free, non-invasive technique, to monitor three-dimensional (3D) morphology and pathology of tumor spheroids has been previously demonstrated. Growth kinetics of each spheroid, with its size and volume measured, could be accurately characterized. However, the previous system was not fully optimized for the collection of spheroid data from the whole plate. Here, in a follow-up study, we demonstrated a high-throughput optical coherence tomography (HT-OCT) platform capable of performing automatic 3D imaging and analyses for all tumor spheroids in a multi-well plate. The total screening time for a 96-well plate was ~23 min, including the OCT acquisition time of ~3.2min. Employing HT-OCT system, we successfully characterized a plate of tumor spheroids modeling cell invasions, with 3 different drug treatments. The HT-OCT system can be a powerful tool for fast, robust 3D morphological characterization of simple and complex spheroids for different cancer models. Further, they can also be utilized to analyze other models like organoids and artificial skins.
Reliability and practical clinical application of an accelerometer-based dual-task gait balance control assessment.

Abstract Background Gait balance control assessment using whole body center of mass (COM) kinematic measures in concussed individuals reveals persistent balance deficits up to two months post-injury. A reliable and clinically practical gait balance control assessment leveraging similar kinematic measures is necessary to improve concussion assessment and management. Research question Can peak accelerations collected during a dual-task (DT) gait assessment from a single low back placed accelerometer be measured reliably on different days, by different raters, in different environments, and be practically applied in a Division One (D1) athletics program? Methods A single accelerometer placed on the low back over the L5 vertebra was utilized with a DT gait analysis protocol. Twenty (10 F) healthy participants performed the assessment in a laboratory and non-laboratory environment, on two separate days, and with two different raters. Eight gait event specific peak accelerations along three orthogonal axes were collected. In addition, data were collected from a cohort of 14 D1 female soccer players during a single assessment to explore the practical clinical application. Results Cronbach’s α values for the eight metrics ranged from 0.881 to 0.980 and ICC values from 0.868 to 0.987. Average assessment time for the 14 D1 female athletes was 8.50 ± 0.58 min, and significant differences between walking conditions were identified for Vert Accel 1 (p Significance High Cronbach’s α and ICC values coupled with a short assessment time and sensitivity to differences in gait balance control indicate our testing apparatus and protocol are both reliable and clinically practical. Additionally, gait event specific peak accelerations from a single accelerometer can detect subtle changes in gait balance control and may facilitate improvements in sport-related concussion diagnosis and return to activity decision making.
Implementation of a Portable Medical Summary for Adolescents and Young Adults With Medical Complexity in Transition to Adult Health Care

Abstract Background Adolescents and young adults (AYA) with special health care needs are living into adulthood, as improvements in care increase the likelihood of survival. Fewer than half have the resources needed to transition to adult care (McPheeters et al., 2014). A portable medical summary is a concise document summarizing current medical information about a patient that can be used across healthcare systems as AYA transition to adult care. Though a consensus statement recommending the use of such a summary has existed for over a decade (American Academy of Pediatrics (AAP), American Academy of Family Physicians (AAFP), American College of Physicians-American Society of Internal Medicine (ACP-ASIM), 2002), little progress had been made in the development of a portable medical summary. Methods The Institute for Healthcare Improvement (IHI) Model was used to implement a process to provide a portable medical summary to AYAs with medically complex conditions ( Institute for Healthcare Improvement, 2017 ). Interventions The tool was developed using the electronic health record and shared with families. Feedback from care providers and families led to modifications to improve its usefulness and feasibility. Implementation of the process was tested for four months. Results The number of AYA, ages 16–24, who were being seen for well care or chronic care management visits, and had a portable medical summary initiated, had increased from 0% to 100%. Conclusions The use of a PMS that summarizes medical care received in the pediatric system, is one tool that may be used to bridge the gap between pediatric and adult care.
M 2 factor of a vector Schell-model beam

Extending existing scalar Schell-model source work, we derive the M2 factor for a general electromagnetic or vector Schell-model source to assess beam quality. In particular, we compute the M2 factors for two vector Schell-model sources found in the literature. We then describe how to synthesize vector Schell-model beams in terms of specified, desired M2 and present Monte Carlo simulation results to validate our analysis.
Fast cycle time and the role of information technology: A framework for analysis

Achieving fast cycle time is increasingly becoming an overriding objective for organiza­ tions wanting to succeed in the global business environment. In such an increasingly competi­ tive and global environment of declining margins, information technology is both driving and enabling business. The focus of these organizations is the adoption of a fast cycle time (FCT) strategy that achieves increased customer satisfaction and/or cost reduction. This paper examines the organizational processes in the context of interdependence, and indentifies areas where information technology can play a pivotal role in bringing about an effective and responsive transformation. It also, with the help of a framework, addresses the issue of cycle time reduction and information technology leverage and provides a methodology for implementing a fast cycle time strategy successfully in organizations.
Approaches to support continued iCCM implementation during a flooding emergency in rural Bangladesh

Background More evidence is needed on how integrated community case management (iCCM) service delivery is affected and on how to maintain service availability during crises. This study documented the implementation of iCCM through two cadres of community health workers (community health care providers [CHCPs] and village doctors [VDs]) in communities that were affected by a 2015 flooding emergency in Bangladesh. Methods We conducted a retrospective case study to assess iCCM services provided by CHCPs and VDs during a flooding emergency that occurred from June to August 2015. We purposively selected nine unions within four sub-districts in Bhola District. In this mixed methods study, we analyzed trends in quantitative service delivery indicators over the time period from January 2015 to February 2016. Qualitative data were obtained through 28 in-depth interviews and 13 focus group discussions with policy makers, implementers, supervisors, CHCPs, VDs, community leaders, and caregivers of under-five children. Results All stakeholders reported disruptions in iCCM service delivery and in access to CHCPs and VDs for community members. The quantitative data showed a 30% reduction in average number of children who received treatment from both CHCPs and VDs during flooding months compared to pre-flood months (from 2273/month to 1593/month). There was also an increase in the number of children referred by CHCPs and VDs, reduced supervision, and increased stock-outs of commodities during the flooding months. CHCPs and VDs, in collaboration with community members, came up with several locally adapted initiatives to maintain iCCM services, including changing clinic hours according to the tide, organizing temporary clinics at alternative sites that were located on higher ground, use of community boats to visit clients in their homes, and use of mobile phones for communication with supervisors and community members. Conclusion Our study results demonstrate that iCCM services can continue during a natural disaster, albeit with significant disruptions. Ad hoc adaptations to services by local implementers and community members were key in maintaining availability of services during the emergency. In future emergencies, service delivery could be significantly strengthened by enacting key preparedness activities prior to a natural disaster such as severe flooding.
Chapter 10 – Target- and System-Based Strategies for Drug Discovery

Publisher Summary This chapter illustrates the different strategies for drug discovery. There is evidence to suggest that, while more drugs are being discovered, there is no commensurate increase in the number of novel treatments for disease. A major approach to discovery is target-based, whereby a single biological target is identified (and validated) as a primary cause of disease. Ligands that produce a defined action at the target are therefore expected to alleviate the disease in the therapeutic situation. Recombinant systems are the main tools of target-based approaches. Biological targets may consist of single entity proteins, complexes of receptors, or receptors plus accessory proteins. Mixtures of gene products can produce unique phenotypic biological targets. An alternative approach involves testing of new drug entities on whole cell systems and measuring effects on integrated cellular pathways. Favorable phenotypic responses are identified with this approach, which may better produce alteration of multicomponent disease processes. An added complexity, but one that may better predict therapeutic activity, is the testing of drugs in assays with different contexts. Testing in vivo can further produce therapeutic model systems. Certain multicomponent disease conditions can be adequately modeled only in vivo. The ultimate model is the human in the clinical situation. Translational medicine with noninvasive imaging techniques and biomarkers now are able to furnish valuable information that can be used in the initial discovery process to produce better-defined drugs. In addition to complex biological targets, complex chemical targets can be used to produce therapeutically useful phenotypic responses.