cssi/SciSciGPT-SciSciNet huggingface dataset:
Less Pulsatile Levodopa Therapy (6 Doses Daily) Is Associated with a Reduced Incidence of Dyskinesia

OBJECTIVE To evaluate whether less pulsatile levodopa therapy (LPT) can reduce the development of levodopa-induced dyskinesia (LID). METHODS This is a retrospective cohort study of patients with Parkinson's disease at the movement disorders clinic of Medstar Washington Hospital Center. The study was not blinded or randomized. Patients were seen between August 2002 and August 2018. During these years, we treated patients with less pulsatile (6 doses daily) levodopa treatment to reduce LID. Occurrence of LID was recorded. RESULTS Ninety-five patients with Parkinson's disease taking levodopa were divided into two groups: 1) patients who were initially managed on LPT or who switched from traditional therapy (TT) (n = 61) (mean disease duration: 7.7 ± 4.8 years, mean levodopa duration: 5.6 ± 4.5 years and mean observation time: 4.3 ± 3.4 years), and 2) patients on TT throughout the observation period or until they developed dyskinesia (n = 34) (mean disease duration: 8.3 ± 3.8 years, mean levodopa duration: 6.2 ± 4.2 years and mean observation time: 4.1 ± 3.4 years). Three of the 61 LPT patients developed dyskinesia during the observation period. One of the patients developed dyskinesia after being switched to pulsatile doses by another doctor. In the other two, dyskinesia was minimal. In contrast to this 4.9% cumulative incidence, dyskinesia occurred in 50% (17/34) of TT patients, an incidence similar to that in published data (p < 0.001). CONCLUSION Less pulsatile levodopa with 6 daily doses was associated with a low incidence of LID. Further study of this method of treatment is warranted.
Colonial Wig Pancreaticojejunostomy.

Postoperative pancreatic fistula (POPF) is one of the most problematic complications after pancreaticoduodenectomy (PD). We describe a series of 48 pancreatic-head resections from our institution, in which we compare a new technique to create the pancreaticojejunostomy (PJ) reconstruction with standard techniques. The goal is to achieve a lower rate of POPF. This new PJ is termed the "Colonial Wig" (CW) PJ due to the novel appearance of the jejunum wrapping around the pancreas, resembling a Colonial wig wrapping around the head of a Colonial Whig (e.g., George Washington). In our consecutive series, 22 cases were performed using the new CW technique to perform the PJ and were compared to 26 traditional PDs with traditional reconstruction. There was an incidence of clinically relevant POPF of 0% in the CW group, compared to 15% in 26 conventional PJs. Our proposed CW PJ reconstruction is associated with a lower the incidence of POPF following PD, and hence may be a way to improve outcomes after PD.
ANIMATING RELATIONS: Digitally Mediated Intimacies between the Living and the Dead

Recent theorizations of animation offer intriguing possibilities for recognizing and attending to the sociality of a range of entities, including the dead. Today, diverse digital media are being used to maintain and even deepen intimate relationships with deceased loved ones. These media bring the dead to presence through forms of animation, understood not only in the narrow technical sense as a media genre but more broadly as a mode of mediation that vivifies in particular ways. This mode of mediation is iterative, bringing forth the multiplicity of the dead. Their materializations are partial and fragmentary, cohering around a database of elements rather than a cohesive, narrative identity. They are sparsely outlined, evoked rather than depicted. When the dead are animated by digital media, they invite their loved ones to fill them, expanding into many versions to which shifting attachments can form. Those who answer their call extend their ambivalent hospitality, maintaining mutually constitutive relationships through which both the living and the dead are carried forth.
Boosting Soft Actor-Critic: Emphasizing Recent Experience without Forgetting the Past.

Soft Actor-Critic (SAC) is an off-policy actor-critic deep reinforcement learning (DRL) algorithm based on maximum entropy reinforcement learning. By combining off-policy updates with an actor-critic formulation, SAC achieves state-of-the-art performance on a range of continuous-action benchmark tasks, outperforming prior on-policy and off-policy methods. The off-policy method employed by SAC samples data uniformly from past experience when performing parameter updates. We propose Emphasizing Recent Experience (ERE), a simple but powerful off-policy sampling technique, which emphasizes recently observed data while not forgetting the past. The ERE algorithm samples more aggressively from recent experience, and also orders the updates to ensure that updates from old data do not overwrite updates from new data. We compare vanilla SAC and SAC+ERE, and show that ERE is more sample efficient than vanilla SAC for continuous-action Mujoco tasks. We also consider combining SAC with Priority Experience Replay (PER), a scheme originally proposed for deep Q-learning which prioritizes the data based on temporal-difference (TD) error. We show that SAC+PER can marginally improve the sample efficiency performance of SAC, but much less so than SAC+ERE. Finally, we propose an algorithm which integrates ERE and PER and show that this hybrid algorithm can give the best results for some of the Mujoco tasks.
Orbitofrontal cortex volume prospectively predicts cannabis and other substance use onset in adolescents.

Background:Identifying neural characteristics that predict cannabis initiation is important for prevention efforts. The orbitofrontal cortex is critical for reward response and may be vulnerable to...
Multiplicative Stieltjes Functions and Associated Pairs of Reproducing Kernel Hilbert Spaces

Pairs of reproducing kernel Hilbert spaces associated with multiplicative Stieltjes functions are characterized in terms of shift invariance and structural identities.
Topology Error Detection and Robust State Estimation Using Nonlinear Least Absolute Value

This paper proposes a new technique for robust state estimation in the presence of a small number of topological errors for power systems modeled by AC power flow equations. The developed method leverages the availability of a large volume of SCADA measurements and minimizes the $\ell_{1}$ norm of nonconvex residuals augmented by a nonlinear, but convex, regularizer. Noting that a power network can be represented by a graph, we first study the properties of the solution obtained by the proposed estimator and argue that, under mild conditions, this solution identifies (small) subgraphs of the network that contain the topological errors in the model used for the state estimation problem. Then, we propose a method that can efficiently detect the topological errors by searching over the identified subgraphs. Furthermore, we develop a theoretical upper bound on the state estimation error to guarantee the accuracy of the proposed state estimation technique. The efficacy of the developed framework is demonstrated through numerical simulations on an IEEE benchmark system.
The Obesity Parenting Intervention Scale: Factorial Validity and Invariance Among Head Start Parents.

Introduction Obesity affects 15.7% of U.S. preschoolers, with higher rates among low-income and Spanish-speaking populations. Food, physical activity, and sleep parenting practices, referred to collectively as obesity-related parenting practices, are linked with children's risk of obesity and are a common target in family-based obesity interventions. Yet, there is no brief, validated measure of obesity-related parenting practices that is appropriate for use in intervention studies and for diverse audiences. This study tests the factorial validity of a brief measure of obesity-related parenting and measurement invariance of the English and Spanish versions of the scale, as well as among mothers and fathers. Methods Parents of children enrolled in Head Start (n=578; 500 mothers and 78 fathers) completed a brief survey of food (7 items), physical activity (5 items), and sleep parenting (3 items) in fall of 2017 and 2018. Scale items were drawn from existing measures and the evidence base, initially drafted in English, and then translated to Spanish. One parent per family completed the scale independently in English (n=448) or Spanish (n=130). A confirmatory factor analysis framework was adopted to test a 3-factor model for the total sample. Multi-group structural equation modeling was used to assess measurement invariance of the scale by the language of administration (English or Spanish) and among mothers and fathers separately. Results Results supported a 3-factor model of obesity parenting with a single factor each for food, physical activity, and sleep parenting. There was statistically significant measurement invariance across all groups (p Conclusions This brief obesity-parenting scale demonstrates adequate factorial validity in English and Spanish and among mothers and fathers. This measure has been integrated into an intervention, and future work will test sensitivity to change.
AAAPT Diagnostic Criteria for Acute Abdominal and Peritoneal Pain After Surgery

Abstract Abdominal and peritoneal pain after surgery is common and burdensome, yet the lack of standardized diagnostic criteria for this type of acute pain impedes basic, translational, and clinical investigations. The collaborative effort among the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks, American Pain Society, and American Academy of Pain Medicine Pain Taxonomy (AAAPT) provides a systematic framework to classify acute painful conditions. Using this framework, a multidisciplinary working group reviewed the literature and developed core diagnostic criteria for acute abdominal and peritoneal pain after surgery. In this report, we apply the proposed AAAPT framework to 4 prototypical surgical procedures resulting in abdominal and peritoneal pain as examples: cesarean delivery, cholecystectomy, colorectal surgical procedures, and pancreas resection. These diagnostic criteria address the 3 most common surgical procedures performed in the United States, capture diverse surgical approaches, and may also be applied to other surgical procedures resulting in abdominal and peritoneal pain. Additional investigation regarding the validity and reliability of this framework will facilitate its adoption in research that advances our comprehension of mechanisms, deliver better treatments, and help prevent the transition of acute to chronic pain after surgery in the abdominal and peritoneal region. Perspective Using AAAPT, we present key diagnostic criteria for acute abdominal and peritoneal pain after surgery. We provide a systematic classification using 5 dimensions for abdominal and peritoneal pain that occurs after surgery, in addition to 4 specific surgical procedures: cesarean delivery, cholecystectomy, colorectal surgical procedures, and pancreas resection.
Mountain, Water, Rock, God: Understanding Kedarnath in the Twenty-First Century: Luke Whitmore. 2018. Oakland: University of California Press. 258 pp., ISBN 978-0-520-29802-6.

Luke Whitmore has produced a wonderful book that will be of great interest to readers of this journal. He presents the central Himalaya of India as a sacred space identified as the Land of the Gods...
Electrically controlled phased array OAM radar

Control of orbital angular momentum (OAM) offers the potential for increases in control, sensitivity, and security for high-performance microwave systems. OAM is characterized by an integer OAM mode where zero represents the case of a plane wave. Microwaves with a nonzero OAM mode propagate with a helical wavefront. Orthogonal OAM modes can be used to carry distinct information at the same frequency and polarization, increasing the data rate. The OAM waveform may also increase radar detection capability for certain shaped objects. OAM can be induced by broadcasting a plane wave through a spatial phase plate (SPP) dielectric which introduces an azimuthally dependent phase delay. However, SPPs are frequency-specific, which presents an obstacle for harnessing OAM in frequency-modulated communication systems and wide-bandwidth radar. In this study, we develop a circular phased array to synthesize the desired vortex-shaped wavefront. This approach offers a critical advantage: the phases of all antenna elements are easily programmable under different frequencies. As a result, transmission and reception of the OAM beam can be controlled with great flexibility, making it operable over a wide frequency spectrum, which leverages OAM radar functionality and performance. In this paper, we will investigate a wide-bandwidth radar with OAM mode-control and signal processing.
Normoxic re-oxygenation ameliorates end-organ injury after cardiopulmonary bypass.

In a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney. After 60 min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120 min. Left ventricular systolic contractility (LV + dP/dt) and diastolic relaxation (LV –dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis. Following aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV + dP/dt: 70 ± 14% of pre-CPB vs. 36 ± 21%, p = 0.018; LV -dP/dt: 72 ± 36% of pre-CPB vs. 33 ± 20%, p = 0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0 ± 0.5 vs. 7.1 ± 0.8 mg/dL, p = 0.004; S100B: 4.0 ± 0.8 vs. 6.7 ± 1.0 ng/mL, p = 0.047; NSE: 57.7 ± 6.8 vs. 101.3 ± 16.1 pg/mL, p = 0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions. Normoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.
A Study of Large Scale Power Extraction and Insertion on Turbofan Performance and Stability

This paper describes the effects of turbofan power extraction and insertion (augmentation) on engine performance and stability. The purpose of this paper is to present how power augmentation affects a dual spool gas turbine engine cycle where the engine will also be required to provide thrust. The goals for the paper are to describe effective limits of power augmentation and offer strategies, utilizing spool choice and variable geometries, to maximize augmentation effect. While Analysis is general, two potential uses are explored: Power extraction for electrified aircraft propulsion and power insertion for thrust assist. Results of the paper show it is possible to extract over 20% (at 85% max thrust) and gain roughly 12% of maximum thrust through power insertion.
Influence of fish meal and supplemental fat on performance of finishing steers exposed to moderate or high ambient temperatures.

Ninety-six Hereford x Angus steers (mean initial BW = 295 kg) were used in two growth experiments conducted at moderate and high ambient temperatures (AT), 48 steers per AT. Within each AT, calves were assigned to six dietary treatments consisting of a basal diet (approximately 60% corn and 20% grass hay) supplemented with either 0, 2.5, or 5% fat and with either soybean meal (SBM) or Menhaden fish meal (FM) included at levels such that a ratio of 16.3 kcal of NEm per kilogram of CP was maintained. Blood and ruminal fluid were collected 40 d before slaughter. During the final 28 d of the moderate AT experiment, apparent digestibility of dietary components was measured in four individually fed steers from each dietary treatment. Steer ADG was not affected by fat, and DMI and efficiency of gain were not affected (P > .10) by treatment. Average daily gain was lower for steers fed FM than for those fed SBM at moderate AT but higher at high AT (CP source x AT interaction; P < .05). Ruminal ratio of acetate to propionate declined linearly with increasing fat at moderate AT but was not affected by fat at high AT (fat x AT interaction trend; P = .08). Plasma urea N concentration increased linearly (P < .05) with increasing fat and was higher (P < .05) in steers kept at high than in those kept at moderate AT. Although apparent digestibility was not altered in steers fed FM, DM and NDF (P < .05) and ADF (P = .07) digestibility decreased with increasing fat in steers fed SBM (CP source x fat interaction).(ABSTRACT TRUNCATED AT 250 WORDS)
Smart Mechanical Circulatory Support Devices: Requirements and Perspectives

Although current mechanical circulatory support devices are smaller and more reliable than those of a decade before, the current devices are still responsible or associated with a variety of significant adverse events that need to be reduced or eliminated before there will be wider usage of the devices to support the failing heart.
Machine perfusion of donor organs for transplantation.

The ever-widening gap between organ supply and demand has resulted in an organ shortage crisis that affects patients all over the world. For decades, static cold storage (SCS) was the gold standard preservation strategy because of its simplicity and cost-effectiveness, but the rising unmet demand for donor organ transplants has prompted investigation into preservation strategies that can expand the available donor pool. Through ex vivo functional assessment of the organ prior to transplant, newer methods to preserve organs such as perfusion-based therapy can potentially expand the available organ pool. This review will explain the physiologic rationale for SCS before exploring the advantages and disadvantages associated with the two broad classes of preservation strategies that have emerged to address the crisis: hypothermic and normothermic machine perfusion. A detailed analysis of how each preservation strategy works will be provided before investigating the current status of clinical data for each preservation strategy for the kidney, liver, pancreas, heart, and lung. For some organs there is robust data to support the use of machine perfusion technologies over SCS, and in others the data are less clear. Nonetheless, machine perfusion technologies represent an exciting frontier in organ preservation research and will remain a crucial component of closing the gap between organ supply and recipient demand.
A 44-Year-Old Woman With a 10-Year History of Dyspnea and Pulmonary Nodules.

Case Presentation A 44-year-old woman was referred for evaluation of dyspnea on exertion and multiple nodular opacities on a chest CT scan. She had a medical history of autoimmune encephalitis, diabetes mellitus, hypertension, migraines, and allergic rhinitis. Ten years earlier, the patient was admitted to an outside institution with symptoms of shortness of breath. She was found to have multiple pulmonary nodules and was diagnosed empirically with and treated for sarcoidosis. She was told that her pulmonary nodules had improved on follow up. However, she continued to have symptoms of dyspnea. Due to progressive symptoms of shortness of breath, she was referred to pulmonology. She reported a weight gain of 80 pounds over the last year. She denied fever, chills, hemoptysis, night sweats, joint swelling, or skin rash. She is a former cigarette smoker with a 15 pack-year smoking history, quit smoking in 2005. She denied alcohol or drug use. She resided in Arkansas and Texas over the past decade. She previously worked as a teacher and is currently unemployed. She had no other relevant exposures. She denied a family history of autoimmune diseases or malignancies.
Vowel Quality and Direction of Stress Shift in a Predictive Model Explaining the Varying Impact of Misplaced Word Stress: Evidence From English

The use of suprasegmental cues to word stress occurs in many languages. Nevertheless, L1 English listeners’ pay little attention to suprasegmental word stress cues and evidence shows that segmental cues are more important to L1 English listeners in how words are identified in speech (Cutler, 2015; Levis, 2018; Zhang & Francis, 2010). L1 English listeners assume strong syllables with full vowels mark the beginning of a new word, attempting alternative resegmentations only when this heuristic fails to identify a viable word string (Cutler & Butterfield, 1992; Cutler & Carter, 1987). English word stress errors have been shown to severely disrupt processing for both L1 and L2 listeners (Benrabah, 1997; Cutler, Dahan & van Donselaar, 1997; Field, 2005), but not all word stress errors are equally damaging (Cutler, 1986; Slowiaczek, 1990). Vowel quality (Bond & Small, 1983; Cutler, 2015) and direction of stress shift (Cutler & Clifton, 1984; Field, 2005) are thought to be predictors of the intelligibility of nonstandard stress pronunciations—but most research so far on this topic has been limited to two-syllable words (e.g., Yu & Andruski, 2010). The current study uses auditory lexical decision and delayed word identification tasks to test a hypothesized English Word Stress Error Gravity Hierarchy for words of two to five syllables. Results indicate that English word stress errors affect intelligibility most when they introduce concomitant vowel errors, an effect that is somewhat mediated by the direction of stress shift. As a consequence, the relative intelligibility impact of any particular lexical stress error can be predicted by the Hierarchy for both L1 and L2 English listeners. These findings have implications for L1 and L2 English pronunciation research and teaching. For research, our results demonstrate that varied findings about loss of intelligibility are connected to vowel quality changes of word stress errors and that these factors must be accounted for in intelligibility research. For teaching, the results indicate that not all word stress errors are equally important, and that only word stress errors that affect vowel quality should be prioritized.
Verizon’s “Certification Process” and Why the FCC Needs To Take a Stand

Jeff Jarvis is quite upset with Verizon Wireless, and he has a right to be.1 In September 2013, Google released its newest tablet, dubbed the Nexus 7. Mr. Jarvis was one of the first consumers to get the tablet, and he quickly took it to a Verizon Wireless store to obtain a SIM card to activate the tablet on Verizon’s 4G Long Term Evolution (LTE) Network.2 Much to Mr. Jarvis’s dismay, the Verizon store employees notified him that the tablet could not be activated on the Verizon Network “because the IMEI numbers weren’t added to Verizon’s system”3—for reference, an IMEI number is a “15 or 17 digit unique number to identify mobile devices.”4 Following his frustrating visit to the Verizon store, Mr. Jarvis voiced his irritation by publicly calling out the wireless company on Twitter, writing, “Knock, knock, @VZWSupport, is anybody there? I’m trying to give you money. You’re making it hard. No, impossible.” He also provided a link to a more in-depth rant on his personal Google Plus page.5 Verizon Wireless responded through its company Twitter page a day later, tweeting, “I’m excited you got your Nexus 7 but not all LTE tablets are created equal. It’s not part of our lineup & can’t be activated.”6 The problem, however, was that the Nexus 7 could be activated on Verizon’s network.7 Jarvis
Comparison of the Deuterium Dilution and Test-Weighing Techniques for the Determination of Human Milk Intake

The deuterium dilution and test-weighing techniques to determine human milk intake were compared in 5 exclusively breast-fed infants, mean age 93 days, and in 4 supplemented infants, mean age 112 days. Deuterium oxide was administered orally to the mothers at 100 mg/kg body weight. The monoexponential decay curve of 2H from the mother’s milk was defined from milk sampled on days 1, 2, 6, 10, 13, 14 of the experiment. Milk samples were defatted by centrifugation and the milk water was reduced to hydrogen gas for hydrogen isotope ratio measurements by gas-isotope ratio mass spectrometry (GIRMS). Total body water (TBW) of the infants was determined by dilution after the administration of 60 mg 18O/kg body weight. Infant urine was sampled on days 1, 2, 4, 6, 8, 10, 12, 14 of the experiment and analyzed for 2H and 18O enrichment by GIRMS. The SAAM27 computer program for compartmental analysis was used to estimate fractional rate constants and predict the average human milk intake over the 14 days of the experiment. The test-weighing procedure was conducted for 5 consecutive days. All supplemental formula and solid foods consumed during the 14 days were measured.
PENAL INSTITUTIONS Pardons and Paroles: Require Further Education as Condition of Parole; Require Alcohol and Drug Use Risk Reduction Program as Condition of Parole

The Act mandates further education as a condition of parole for those inmates who do not have a high school diploma or a general educational development equivalency diploma (GED). The requirement may be fulfilled by obtaining a GED or by attending a trade or business school. The Act also requires inmates whose criminal offense or history suggests an alcohol or drug problem to participate in an Alcohol or Drug Use Risk Reduction Program before becoming eligible for parole.
Fat and Water

In this chapter, we will consider some of the important ways that fat and water interact in the MR image. Specifically, we will discuss chemical shift artifacts as well as methods to suppress water and fat. We will find that all but one of the phenomena to be covered are based on one fundamental notion: because of the molecular differences between fat and water, the hydrogen MDM vectors in fat precess 220 cycles per second faster than the hydrogen MDM vectors in water. Hence for a 1.5T magnet, the water MDM’s precess at 64,000,000 Hz* , and the fat MDM’s precess at 64,000,220 Hz. We will see that this simple difference in precession frequency lies at the root of much of what follows in this chapter.
Tversky, Amos (1937–96)

Amos Tversky was a cognitive and mathematical psychologist, whose research examined the foundations of human judgment and decision making. Much of it concerned the strengths and weaknesses of intuitive inferences, as people cope with life's diverse, complex, and subtle choices. These processes were typically characterized in terms of a formal model and by comparison with a normative performance standard. Doing so required fundamental research into the mathematics of models and the interpretation of standards, as well as extensive experimentation and observation. Together with Daniel Kahneman, Tversky created the heuristics-and-biases approach to judgment under uncertainty and Prospect Theory for choices involving risk. The former assumes that people base their judgments on general rules of thumb; although often useful, these heuristics can produce predictable biases (e.g., overestimating the probability of risks that the news media disproportionately report, making them unduly ‘available’ in memory). The latter proposes an alternative to utility theory, integrating well-established psychological principles. With other collaborators, from diverse disciplines, he developed theories of multiattribute choice, similarity judgments, and the evaluation of evidence (support theory). His applied work considered such diverse topics as conflict resolution, medical decision-making, law, and basketball. He co-authored the three-volume Foundations of Measurement.
Abstract 15783: Lineage Reprogramming of Mouse Fibroblasts to Proliferative and Multipotent Induced Cardiac Progenitor Cells by Defined Factors

Several studies have reported reprogramming of fibroblasts to induced cardiomyocytes (CMs). However, reprogramming to cardiac progenitor cells (CPCs), which may be more favorable for cell therapy because of their proliferative properties and multipotency, remains to be accomplished. We cloned a library of 22 genes, including cardiac-related transcription factors and chromatin remodeling agents, into a doxycycline inducible lentivirus vector. Fibroblasts used for reprogramming were derived from an Nkx 2.5-EYFP cardiac progenitor reporter mouse model, which when uninfected yielded no EYFP+ cells. However, adult cardiac fibroblasts infected with all 22 factors yielded some EYFP expressing cells only after doxycycline treatment. The factor pool was subsequently reduced to 11, and eventually to 5 factors. After infection with cardiac factors, EYFP+ cells were first observed 4-6 days after doxycycline treatment. By day 20, EYFP+ cells developed into highly proliferative EYFP+ colonies of cells that, upon passaging, exhibited a high nuclear-to-cytoplasmic ratio. Transcriptome analysis and immunocytochemistry of EYFP+ cells revealed up-regulation of CPC markers including Mesp1, Mef2c, Irx4, Gata6, Tbx5, Tbx 20 accompanied by downregulation of fibroblast-specific genes such as Fsp1 and Thy1. Based on lineage specific marker expression, the EYFP+ cells could be differentiated into various cardiac lineages, including cardiomyocytes (α-MHC), smooth muscle (SM-MHC) and endothelium (CD31). Even after doxycycline withdrawal cells remained EYFP+, expressed CPC markers, and retained multipotency for over 30 passages, all indicative of stable reprogramming to an induced CPC (iCPC) state. iCPCs co-cultured with mESC-derived CMs formed intercellular gap junctions and showed synchronous beating accompanied by spontaneous calcium transients. When injected into the cardiac crescent of E8.5 mouse embryos, iCPCs migrated to the developing heart tube and differentiated into MLC2v and cardiac actin expressing CMs. Similar iCPC reprogramming was achieved using adult lung- and tail tip-derived fibroblasts. These results demonstrate the ability of inducible defined factors to reprogram mouse fibroblasts into proliferative and multipotent iCPCs.
Towards a Biorobotic Electrosensory System

Weakly electric fish hunt and navigate without visual cues by sensing perturbations of a self-generated electric field. The ability to detect, characterize and localize objects using electric fields is called electrolocation. This capability could be beneficial for underwater robots sent to explore dark aquatic environments, from those on Earth to those that might exist on other planets and moons such as Europa. Here we describe initial progress on the development of an artificial sensor array that could provide electrosensory capabilities to a submarine robotic explorer. The design of the sensor array and the associated signal processing algorithms are inspired by ongoing empirical and theoretical studies of signal detection, estimation, and active sensor positioning in weakly electric fish as they hunt for small prey. Here we describe a simple test setup consisting of a small electrosensory array and a robotic platform for controlling the movement of an electrolocation target. This system allows us to acquire and analyze electrosensory signals similar to those obtained a weakly electric fish.
Prevalence of complement-fixing antibodies to cytomegalovirus in a semirural southern county

Abstract Alachua County is a semirural county with a per capita income of less than $3,000.00 per year. Over a one-year period, 395 clinic patients were selected by a predetermined collection system for the study of presence or absence of complement-fixing antibodies against the AD 169 strain of cytomegalovirus. These data were contrasted with that obtained from a white private patient population obtained by the same collection system during the same study period. A statistically significant difference with respect to the prevalence of antibodies to the cytomegaloviruses was observed between the two populations. The data suggest an inverse correlation between socioeconomic status and prior antigenic experience with cytomegalovirus.
Regulatory Substances Produced by Lymphocytes

A factor which suppresses DNA synthesis in rat lymph-node cells stimulated with phytohemagglutinin (PHA) and in mouse fibroblasts (L cells) was obtained from the culture supernatant of rat lymph-node cells stimulated with ovalbumin in vivo and rechallenged with the same antigen in vitro. The factor is protein in nature, as evidenced by its sensitivity to trypsin. It is relatively heat stable and its activity is lost after periodate treatment, suggesting that it is glycoprotein. On Sephadex gel filtration, it gives 2 peaks with estimated molecular weights of 80,000 and 160,000–200,000 daltons. Their isoelectric points were estimated as 2.7 and 3.0 by isoelectric focusing analysis. The factor had almost no effect on the synthesis of RNA and protein, but inhibited DNA synthesis completely. This inhibition followed multihit kinetics with a multiplicity estimated as 20–40. The suppressive effect of the factor was reversible when it was removed within 14 h after addition of PHA to cultures of rat lymph-node cells, but became completely irreversible by 30 h. Between 14 and 30 h the effect was partially reversible. These results suggest that the factor acts by inhibiting a process or processes occurring shortly before the initiation of DNA synthesis. They also imply that the factor may play a role as a short-range regulator of immune responses.
A personal computer based VLSI design curriculum

We have developed a VLSI curriculum based on personal computers that can be used at teaching institutions and corporations alike. The curriculum consists of three courses: a capstone VLSI course, an analog design course, and an advanced digital design synthesis course. No workstations are necessary, laboratories may be given without teaching assistants, and the entire system be used with minimal required infrastructure support. Emphasis of the teaching curriculum is on design methodology and practicable applications.
Differential Expression of Epigenetic Modulators During Human Embryonic Stem Cell Differentiation

Although the progression of aging and the diseases associated with it are extensively studied, little is known about the initiation of the aging process. Telomerase is down-regulated early in embryonic differentiation, thereby contributing to telomeric attrition and aging. The mechanisms underlying this inhibition remain elusive, but epigenetic studies in differentiating human embryonic stem (hES) cells could give clues about how and when DNA methylation and histone deacetylation work together to contribute to the inactivation of hTERT, the catalytic subunit of telomerase, at the onset of the aging process. We have confirmed the differentiation status of cultured hES colonies with morphological assessment and immunohistochemical stainings for pluripotent stem cells. In hES cells with varying degrees of differentiation, we have shown a stronger association between hES differentiation and expression of the epigenetic regulators DNMT3A and DNMT3B than between genetic modulators of differentiation such as c-MYC. We also propose a new model system for analyses of stem cell regions, which are differentially down-regulating the expression of hTERT and the actions of epigenetic modulators such as the DNMTs and histone methyltransferases.
Towards Quantum Engineering

Control of material composition at the nanometer and atomic scale dramatically increases electronic device design space due, in part, to quantum effects. New engineering tools are needed to explore this space and ensure that the best, technologically significant device designs are discovered in a most efficient manner. Using a few prototype examples, this paper describes how a methodology for synthesis might be implemented to advance quantum engineering for electronics.
Some properties of myofibrillar proteins from thawed muscles.

Abstract 1. 1. Ammonium sulphate salting-out curves of myofibrillar proteins prepared from muscles in contracture after thawing show that most of Dubuisson 's γ-myosin corresponds to a component which precipitates at 12–18% of saturation. The same results have been obtained in muscles in rigor mortis. 2. 2. The presence of increased amounts of γ-myosin in the myofibrillar-protein solutions causes a decrease of ATPase activity and a lower viscosity. 3. 3. The extractability of the myofibrillar proteins is strongly decreased in contracture after thawing; nevertheless, the increase of γ-myosin seems to be only relative.
The Volume of Prostate Cancer in the Biopsy Specimen Cannot Reliably Predict the Quantity of Cancer in the Radical Prostatectomy Specimen on an Individual Basis

AbstractPrevious studies suggest that prostate cancer with a volume of 0.5 ml. or less and a Gleason score of less than 7 may be clinically insignificant and may be managed with watchful waiting. A proposed method of determining the volume of cancer in the prostate gland has been the grade and volume of cancer present in the transrectal needle biopsy specimen. Volume of cancer in the biopsy specimen as a predictor of volume of cancer in the prostate gland was studied in 130 men who underwent radical retropubic prostatectomy for adenocarcinoma. Of the men 46 (35 percent) had clinical stage T1c (nonpalpable) disease, while 84 (65 percent) had clinical stage T2 (palpable) disease. Each radical prostatectomy specimen was whole-mounted and step-sectioned for accurate cancer volume determination. Three parameters for measuring volume of cancer in the biopsy specimen (percentage of biopsy cores involved, millimeters of cancer per biopsy core and percentage of cancer in the biopsy specimen) were determined and co...
Involvement of the cytoskeleton in the movement of cortical granules during oocyte maturation, and cortical granule anchoring in mouse eggs.

Exocytosis of cortical granules in mouse eggs is required to produce the zona pellucida block to polyspermy. In this study, we examined the role of microfilaments and microtubules in the regulation of cortical granule movement toward the cortex during oocyte maturation and anchoring of cortical granules in the cortex. Fluorescently labeled cortical granules, microfilaments, and microtubules were visualized using laser-scanning confocal microscopy. It was observed that cortical granules migrate to the periphery of the oocyte during oocyte maturation. This movement is blocked by the treatment of oocytes with cytochalasin D, an inhibitor of microfilament polymerization, but not with nocodazole or colchicine, inhibitors of microtubule polymerization. Cortical granules, once anchored at the cortex, remained in the cortex following treatment of metaphase II-arrested eggs with each of these inhibitors; i.e., there was neither inward movement nor precocious exocytosis. Finally, the single cortical granule-free domain that normally becomes localized over the metaphase II spindle was not observed when the chromosomes become scattered following microtubule disruption with nocodazole or colchicine. In these instances a cortical granule-free domain was observed over each individual chromosome, suggesting that the chromosome or chromosome-associated material, and not the spindle, dictates the localization of the cortical granule-free domain.
How emotions inform judgment and regulate thought

Being happy or sad influences the content and style of thought. One explanation is that affect serves as information about the value of whatever comes to mind. Thus, when a person makes evaluative judgments or engages in a task, positive affect can enhance evaluations and empower potential responses. Rather than affect itself, the information conveyed by affect is crucial. Tests of the hypothesis find that affective influences can be made to disappear by changing the source to which the affect is attributed. In tasks, positive affect validates and negative affect invalidates accessible cognitions, leading to relational processing and item-specific processing, respectively. Positive affect is found to promote, and negative affect to inhibit, many textbook phenomena from cognitive psychology.
Copper and cadmium: responses in Pseudomonas putida KT2440.

Aims: To compare responses of a soil bacterium to Cu and Cd. Methods and Results: In minimal medium, Cd caused a dose-dependent growth stasis of logarithmic phase cells of Pseudomonas putida, strain KT2440, whereas Cu did not compromise growth up to 10 mg l−1. Proteomics showed changes in accumulation of both membrane and soluble proteins by 6 h of treatment; increased Krebs cycle enzymes were apparent. Transcript analysis showed Cd- and Cu-induced different genes. Cd-induced genes encoding the transcriptional regulator CzrR2; an outer membrane protein associated with lipopolysaccharide stability, H1; two oxidative stress protective proteins and the P-type ATPase, CadA2, associated with Cd2+ efflux. The genes most responsive to Cu encoded the regulator CopR1 and the outer membrane resistance protein regulated by CopR1, CopB1; a putative porin, PorD and the Cu-binding protein, PacZ or CopZ, and CopA2. Conclusions: These findings support that a soil pseudomonad restricts internalization of the metals by using different sets of binding proteins and efflux pumps. Activation of mechanisms to protect against oxidative stress also was evident especially with Cd exposure. Significance and Impact of the Study: The differential cellular responses to Cd and Cu suggest that risk assessment for Cd and Cu should be different.
FSM decomposition for pipelined data

Abstract This paper describes a new FSM decomposition algorithm which extracts a data register from a given FSM. This algorithm is useful for creating an efficient implementation of a pipelined state transition graph generated by high-level synthesis. The algorithm is a generalization of the standard minimization algorithm—it selects output values which, when stored in a separate data register, will make additional states in the control machine equivalent. This algorithm is useful in high-level synthesis: pipelining can introduce data into a controller's state transition graph; decomposing the controller into a data register and smaller FSM improves the system's implementation. Experimental results show that the algorithm is fast and effective.
Cheirolumbar Dysostosis: A Phenotype of Pseudohypoparathyroidism*

Cheirolumbar dysostosis is a skeletal dysplasia characterized by brachydactyly and stenosis of the lumbar vertebral canal. Our recent experience with a patient having these clinical features indicates that this condition may be a phenotype of pseudohypoparathyroidism, rather than a distinct entity.
Formal Theory of Nonlinear Response

This paper presents the derivation of formal, exact expressions for "generalized response coefficients," quantities which characterize the response of a system to conservative forces of arbitrary strength and time dependence. The development avoids all expansions of the response in powers of the driving forces. The generalized response coefficients thus provide the basis for calculations of nonlinear effects in those situations for which expansions in powers of the forces are not suitable. It is shown how the linear and higher-order response functions obtained first by Kubo can be obtained in a relatively more compact way. The expressions corresponding to static forces are considered in some detail. Generalized response coefficients are also derived for systems in equilibrium; the lowest order of these is just the isothermal susceptibility as usually defined.
Pyrimidine nucleoside, pseudouridine, and modified nucleoside excretion by growing and resting fibroblasts.

We are examining the relationship of RNA metabolism and de novo pyrimidine synthesis as parameters of malignant transformation. These initial experiments on normal hamster embryo fibroblasts have shown that excreted nucleosides are markers for intracellular RNA metabolism. We employed affinity chromatography to concentrate the nucleosides in the medium and sensitive column chromatographic procedures to quantitatively measure them. The excretion of pyrimidine nucleoside from hamster embryo fibroblasts in culture was found to be dependent on the growth stage of the cells, with the greatest accumulation occurring during cell quiescence. The major nucleosidee excretion products, uridine and cytidine, were both normal end products of RNA metabolism and the major nucleoside excretion products from cultured cells. The modified nucleosides N-1-methylguanosine, N-2-methylguanosine, N-2-dimethylguanosine, N-4-acetylcytidine, N-1-methylinosine, pseudouridine, N-1-methyladenosine, N-3-methylcytidine, and 5-methylcytidine were found, as were several unidentified nucleosides.
Walking the ethical highwire: Genetic screening and hereditary tyrosinemia

Background: Hereditary tyrosinemia type I is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The disorder clusters in the Saguenay-Lac-St.-Jean area of Quebec. In this region, 1 of 1846 newborns is affected and 1 of every 22 persons is thought to be a carrier. Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I. Methods: We used allele-specific-oligonucleotide hybridization to examine the frequency of these three candidate mutations in patients with tyrosinemia type I and in the population of Quebec. Results: The splice mutation was found in 100 percent of patients from the Saguenay-Lac-St.-Jean area and in 28 percent of patients from other regions of the world. Of 25 patients from the Saguenay-Lac-St.-Jean region, 20 (80 percent) were homozygous for this mutation, a guanine-to-adenine change in the splice-donor sequence in intron 12 of the gene, indicating that it causes most cases of tyrosinemia type I in the region. The frequency of carrier status, based on screening of blood spots from newborns, was about 1 per 25 in the Saguenay-Lac-St.-Jean population and about 1 per 66 overall in Quebec. Conclusions: This study identified the most prevalent mutation causing hereditary tyrosinemia in French Canada; it also showed the feasibility of DNA-based testing for carriers in the population at risk. (N Engl J Med 1994;331:353–7.)