cssi/SciSciGPT-SciSciNet huggingface dataset:
Extraction efficiency and implications for absolute quantitation of propranolol in mouse brain, liver and kidney tissue sections using droplet-based liquid microjunction surface sampling high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

Rationale Currently, the absolute quantitation aspects of droplet-based surface sampling for tissue analysis using a fully automated autosampler/high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) system have not been fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from tissue sections. Methods Adjacent tissue sections of propranolol-dosed mouse brain (10-μm-thick), kidney (10-μm-thick) and liver (8-, 10-, 16- and 24-μm-thick) were obtained. The absolute concentration of propranolol was determined in tissue punches from serial sections using standard bulk tissue extraction protocols and subsequent HPLC separations and MS/MS analysis. These values were used to determine propranolol extraction efficiency from the tissues with the droplet-based surface sampling approach. Results Extraction efficiency of propranolol using 10-μm-thick brain, kidney and liver tissues using droplet-based surface sampling varied between ~45 and 63%. The extraction efficiency decreased from ~65% to ~36% with liver thickness increasing from 8 μm to 24 μm. Selecting half of the samples as standards, the precision and accuracy of propranolol concentrations were determined for the other half of the samples that were employed as a quality control data set. The resulting precision (±15%) and accuracy (±3%) were within acceptable limits. Conclusions Quantitation of adjacent mouse tissue sections of different organs and of various thicknesses by droplet-based surface sampling in comparison with bulk extraction of tissue punches showed that extraction efficiency was incomplete using the former method, and that it depended on the organ and tissue thickness. However, once extraction efficiency was determined and applied, the droplet-based approach provided satisfactory quantitation accuracy and precision for assay validations. Thus, once the extraction efficiency was calibrated for a given tissue type, tissue thickness and drug, the droplet-based approach provides a non-labour-intensive and high-throughput means to acquire spatially resolved quantitative analysis of multiple samples of the same type. Published in 2016. This article is a U.S. Government work and is in the public domain in the USA.
Optimization of a turbocharger and supercharger compound boosting system for a Miller cycle engine

This paper describes the design optimization of a compound boosting system consisting of a turbocharger and a supercharger for a 2.0 l four-cylinder Miller cycle engine which has a high expansion r...
Outcome of palbociclib based therapy in hormone receptor positive metastatic breast cancer patients after treatment with everolimus.

1054Background: Resistance mechanisms to CDK 4/6 inhibition are not well defined. Outcome data on hormone receptor positive (HR+) metastatic breast cancer patients (MBCP) treated with palbociclib (PA) after treatment with everolimus (EV) are lacking. The PALOMA 3 trial (P3) showing benefit of PA plus fulvestrant (FU) compared to FU in HR+ MBCP after progression on endocrine therapy excluded women previously treated with EV. The aim of our study was to investigate the outcomes of HR+ MBCP with prior EV treatment on PA based therapy. Methods: This is a retrospective, single institute review of HR+, HER 2 nonamplified MBCP from Jan 2014 - Nov 2016 treated with PA after treatment with EV. Women who received EV for < 1 month or PA < 14 days were excluded. Progression free survival (PFS) was defined as the time from the initiation of PA to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available rad...
Large deformation solutions to post-buckled beams confined by movable and flexible constraints: A static and dynamic analysis

Abstract This paper develops a static and dynamic large deformation model to investigate the post-buckling response of slender beams constrained by movable and flexible bilateral confinements. A novel discretization algorithm is proposed to convert the irregular constraints into gap vectors. Governing equations are formulated based on the Euler-Bernoulli beam theory. An energy method is presented to solve the equations using a modified Nelder–Mead algorithm. A constrained minimization of the total energy is carried out with respect to the gap vectors. The theoretical results of the proposed model, i.e., the deformed beam shape configuration and force-displacement relationship, are compared with existing studies and experiments. The regularly and movably constrained, static model is compared with the existing small and large deformation models, respectively. The regularly and flexibly confined, dynamic model is compared with experiments. Satisfactory agreements are observed. Parametric studies are conducted to investigate the post-buckling response in terms of loading and constraints conditions. In particular, the loading condition is first examined by changing the loading frequency. The highest achievable buckling mode is then studied with respect to the Young's moduli ratios of movable constraints-to-beam and flexible constraints-to-beam, respectively, and the ratio of walls gap-to-beam length. The proposed theoretical models are effective in understanding and predicting the static and dynamic post-buckling response of beams constrained by movable and flexible confinements.
Recent encounters with rattlesnakes enhance ground squirrel responsiveness to predator cues

A diverse range of prey taxa exhibit stereotyped antipredator behaviors when confronting live predators. Predator cues also elicit antipredator responses, and previous research indicates that prey possess mechanisms to discriminate between the relative risk posed by particular predator cues, which mediates their investment in antipredator behaviors (i.e., “threat-sensitive” behavior). However, the salience of such predator cues may change according to perceived predation risk, which can vary temporally or spatially. We hypothesized that prey modify responses to predatory cues according to their recent experience with predators, which would prime prey to attend to predator-related cues. In the present study, we found that recent encounters with live tethered rattlesnakes increased perceived predation risk in free-ranging California ground squirrels (Otospermophilus beecheyi), leading to concomitant increases in the intensity of antipredator behaviors displayed toward a predator model. The increase in antipredator behavior following snake encounters was higher toward the predator model than a novel object, suggesting that squirrels exhibit threat-sensitive responses toward objects resembling predators. However, squirrels did not treat either of these objects with caution, nor did they differ in antipredator behavior, when presented with the model or novel object when no live snake was encountered. This suggests that increased vigilance following predator encounters modulates responses to predator cues. Such increases in antipredator behavior could assist in detecting nearby predators quickly but could also have indirect effects on prey. Underresponding to predators could lead to death, while overresponding could reduce time spent on other fitness-related activities. Prey balance these costs by using environmental cues to modify antipredator responses. Detecting a live predator in the environment could indicate that the chance of predation is high, which may enhance preys’ antipredator responses. We show that ground squirrels significantly enhance antipredator behaviors toward snake models and novel objects after encountering a live tethered rattlesnake predator. However, the predator model elicited greater antipredator behavior than the novel object following snake encounters, suggesting that squirrels are primed to attend to predator-related cues in this context. Both objects were treated similarly, and with less caution, when no snake was detected. Vigilance following predator interactions therefore mediates threat-sensitive responses to subsequent predator cues.
Priority Setting in the Administration of the Danish Act on Contaminated Sites

Danish legislators have introduced a clear administrative distinction between contaminated sites of old and new origin respectively. By the Parliament’s adoption of the Act on Environmental Protection it was made illegal to dump, bury or spill oil waste or chemicals after 1972/1974, which implies that in case of pollution the polluter shall pay. It was realized that as regards most of the sites contaminated before 1972/74 the polluter could no longer be reached in many cases. Consequently the Act on Contaminated Sites, which only covers contaminati-on from before 1972/74 and includes a special State financed funding system, was adopted.
An app-titude for learning

The second in a series exploring practical activities for introducing concepts that will help children in the Understanding the world area of learning – this month, we look at the use of iPads and tablets.
An Aggressive Approach to HIV Antiretroviral Therapy

The introduction of highly active antiretroviral therapy offers the first real hope of durable control of HIV infection and prevention of clinical sequelae. But success hinges on early and complete suppression of viral replication. That demands near-perfect adherence to a complex regimen involving three or more drugs, each with its own dosage and dietary requirements.
A System for Cyber Attack Detection Using Contextual Semantics

In this paper, we present a layered cyber-attack detection system with semantics and context capabilities. The described approach has been implemented in a prototype system which uses semantic information about related attacks to infer all possible suspicious network activities from connections between hosts. The relevant attacks generated by semantic techniques are forwarded to context filters that use attack context profiles and host contexts to filter out irrelevant attacks. The prototype system is evaluated on the KDD 1999 intrusion detection dataset, where the experimental results have shown competitive precision and recall values of the system compared with previous approaches.
Removal of ocular artifacts from EEG using learned templates

Electroencephalogram (EEG) data can provide information on cognitive states and processes with high temporal resolution, but to take full advantage of this temporal resolution, common transients such as blinks and eye movements must be accounted for without censoring data. This can require additional hardware, large amounts of data, or manual inspection. In this paper we introduce a greedy, template-based method for modeling and removing transient activity. The method iteratively models an input and updates a template; a process which quickly converges to a unique and efficient approximation of the input. When combined with standard source separation techniques such as Independent Component Analysis (ICA) or Principal Component Analysis (PCA), the method shows promise for the automatic and data driven removal of ocular artifacts from EEG data. In this paper we outline our method, provide evidence for its effectiveness using synthetic EEG data, and demonstrate its effect on real EEG data recorded as part of a minimally constrained cognitive task.
Exploring the development of information literacy concepts among community college students

The purpose of this qualitative study was to explore the experiences of community college students and their development of the concept of information literacy. The participants’ individual definition of information literacy was explored as well as the people, places, and events that helped shape their concept of information literacy. Data were gathered applying narrative inquiry using a combination of interviews and document analysis. It was anticipated that reflection on their prior experiences would illuminate the meaning students make of information literacy, and could help inform instruction for future students. Information literacy had different meanings to each of the participants. There was no one clear description of the term or the concept. Themes that emerged were centered on types of resources, documentation systems, and fears of plagiarism. Information literacy did not emerge as a process learned over time by these students. This study was conducted using a small sample of students (7 students) from one institution and should not be generalized to other populations. A larger study conducted nationwide is needed to gain a national perspective of information literacy development in students. Further research should be conducted to assess the experience instructors in the K12 systems as well as in community colleges systems have with learning and teaching information literacy skills. In order to affect change and proceed with the recommendation that instructors are also trained to teach these skills, there must be an understanding of the level at which instructors operate as well as standards that currently exist which support a shift to embedding information literacy into the curriculum.
Colorectal Cancer Screening and Surveillance

Colorectal cancer (CRC) is the second most common cause of cancer death among American men and women. In 2005, it accounted for more than 145,000 new cancer cases, and resulted in more than 56,000 deaths. Currently available screening tests are effective in detecting early-stage CRC and its premalignant precursor lesion, the adenomatous polyp. Detection of early-stage disease at the time of cancer diagnosis is associated with significantly improved survival, with a 5-yr survival rate of 90% in those with localized disease. Removal of adenomatous polyps by colonoscopic polypectomy has been demonstrated to significantly reduce the incidence of developing CRC. Routine screening of asymptomatic average-risk individuals will result in a reduction in CRC incidence and mortality. Screening and surveillance recommendations should be based on the individual.s CRC risk assessment. High-risk groups with hereditary cancer syndromes such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer should be referred for genetic counseling and offered appropriate genetic testing and specialized screening recommendations.
Prevalence of Emergency Department Patients Presenting with Heroin or Prescription Opioid Abuse Residing in Urban, Suburban, and Rural Jefferson County.

Abstract Background Heroin and prescription opioid abuse in the United States is exhibiting a growing geographic ubiquity. Objectives This study characterizes the changing geographic distribution of patients presenting with heroin and prescription opioid abuse to one urban emergency department (ED). Methods A retrospective review of patients with heroin and prescription opioid abuse from 2009–2014 was conducted in one adult urban ED. The primary outcome was the prevalence of heroin and prescription opioid patients residing in urban, suburban, and rural ZIP codes over time. Results From 2009 to 2014, 2695 patients presented for either heroin (N = 1436; 53%) or prescription opioid (N = 1259; 47%) abuse from 32 Jefferson County ZIP codes. Of the 32 ZIP codes, 15 were urban (47%), 13 suburban (41%), and 4 rural (12%). The prevalence of heroin patients (per 10,000 population) increased in each ZIP code from 2009–2014. After 2011, prescription opioid prevalence decreased in urban and suburban ZIP codes but increased in rural ones. Using segmented regression analysis, the increase in patients who used heroin residing in all ZIP codes and the decrease in patients abusing prescription opioids residing in urban areas was statistically significant after 2011. Conclusion From 2009 to 2014, there was an increasing trend in ED patients using heroin who resided in urban, suburban, and rural ZIP codes. There was an increasing trend in prescription opioid prevalence in all regions from 2009 to 2011. After 2011, prescription opioid prevalence decreased in urban and suburban ZIP codes but not rural ZIP codes.
Could a blood test for PTSD and depression be on the horizon

Introduction: Depression and posttraumatic stress disorder (PTSD) are two complex and debilitating psychiatric disorders that result in poor life and destructive behaviors against self and others. ...
On the brink of everything: grace, gravity, and getting old

I have been a reader of Parker Palmer for many years starting back in the 1980’s with his book in educational philosophy entitled To Know As We Are Known. Even 20 years after it was published his h...
A Formative Design Examining the Effects of Elaboration and Question Strategy with Video Instruction in Medical Education

The purpose of this formative design study was to investigate the effects of instructor-created elaborations, learner-created elaborations, and adjunct questions on medical student learning outcomes in an asynchronous learning environment, using pre-recorded video over the course of a semester. The study also investigated the effects of instructor-created elaborations, learner-created elaborations, or adjunct questions on perceived cognitive load. The effect of learning strategy on quality of elaboration was also investigated. Results showed no significant difference in learning outcomes or cognitive load or quality of elaboration, but a post hoc analysis revealed a significant difference in intrinsic cognitive load for students who used generative strategies while having no gain in learning outcomes. Formative design data suggest that additional attention is needed on the learning environment when implementing generative learning strategies.
Young Adult Services

The transition to legal and social adulthood involves not only newfound autonomy and opportunities, but also developmental challenges. This is especially the case for transitioning youth with mental health needs (TYMHN), late adolescents, and emerging adults who are receiving mental health services and experiencing transition-related difficulties. This chapter examines ways in which services and policies in the USA currently address developmental challenges of TYMHN in the transition to adulthood. A developmental-ecological framework is used, in which individuals’ health and maladjustment are seen as explicable only with reference to a particular setting and social environment. Consistent with this perspective, the chapter will focus on strategies for promoting individual adaptation to settings and social environments (positive youth developmental support) or responsiveness of settings to individual needs (ecological support), both among youth with current mental health needs and those who are at risk.
Unpublishing the News: An Analysis of U.S. and South Korean Journalists’ Discourse About an Emerging Practice

One axiom of the digital age is that online is forever. Such imperishability of information has led an increasing number of news subjects and sources to request that stories containing outdated or negative personal information be “unpublished.” These requests confront news practices and ethical guidelines related to privacy, accuracy, harm, and autonomy, which complicates newsroom responses. U.S. and South Korean journalists’ discourses about unpublishing demonstrate that those in a more individualistic culture (U.S.) highlight obligations related to accuracy and autonomy, while those in a more collectivistic culture (South Korea) highlight obligations related to individual privacy and avoidance of harm.
Geometrical logarithmic capacitance

Abstract This paper is devoted to a novel and nontrivial exploration of eight aspects of the geometrical logarithmic capacitance (a very key notion in mathematical physics, quasiconformal geometry and variational calculus) through: (1) identifying with the reduced conformal module; (2) evaluating the minimal log-potential energy; (3) relating to both the volume-radius and the surface-radius; (4) linking with the n-harmonic radius and the log-capacity of the Kevin image of a compact surface; (5) finding the Minkowski inequality and the general variational formula for the log-capacity; (6) pinching the log-isocapacitary inequality from left and solving the left-prescribed problem for the normalized log-capacitary curvature measure; (7) pinching the log-isocapacitary inequality from right and handling the right-prescribed problem for the normalized log-capacitary curvature measure; (8) handling an overdetermination of the n-equilibrium potential of a given convex body via the log-capacitary concavity.
Online MinCut: Competitive and Regret Analysis

In this paper we study the mincut problem in the online setting. We consider two distinct models: A) competitive analysis and B) regret analysis. In the competitive setting we consider the vertex arrival model; whenever a new vertex arrives it's neighborhood with respect to the set of known vertices is revealed. An online algorithm must make an irrevocable decision to determine the side of the cut that the vertex must belong to in order to minimize the size of the final cut. Various models are considered. 1) For classical and advice models we give tight bounds on the competitive ratio of deterministic algorithms. 2) Next we consider few semi-adversarial inputs: random order of arrival with adversarially generated and sparse graphs. 3) Lastly we derive some structural properties of \mc-type problems with respect to greedy strategies. Finally we consider a non-stationary regret setting with a variational budget $V_T$ and give tights bounds on the regret function. Specifically, we show that if $V_T$ is sublinear in $T$ (number of rounds) then there is a deterministic algorithm achieving a sublinear regret bound ($O(V_T)$). Further, this is optimal, even if randomization is allowed.
Prompt Outpatient Care For Older Adults Discharged From The Emergency Department Reduces Recidivism.

Introduction: Older adults present unique challenges to both emergency clinicians and health systems. These challenges are especially evident with respect to discharge after an emergency department (ED) visit as older adults are at risk for short-term, negative outcomes including repeat ED visits. The aim of this study was to evaluate characteristics and risk factors associated with repeat ED utilization by older adults.Methods: ED visits among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003-2016 were examined using linked Medicare claims data to identify such visits and resulting disposition. Multilevel proportional hazards models examined associations of age, comorbidity status, race, gender, Medicaid dual eligibility status, social support characteristics (living alone or caregiver support), and use of ambulatory primary and subspecialty care with repeat ED utilization.Results: Older adults discharged from the ED seen by a primary care provider (hazard ratio [HR] = 0.93, confidence interval [CI], 0.87-0.98, p = 0.01) or subspecialist (HR = 0.91, CI 0.86-0.97, P <0.01) after the ED visit were less likely to return to the ED within 30 days compared to those who did not have such post-ED ambulatory visits. Additionally, comorbidity (HR =1.14, 95% CI ,1.13-1.16, P <0.01) and dual eligibility for Medicare and Medicaid (HR = 1.34, 95% CI, 1.20-1.50, p<0.01) were associated with return to the ED within 30 days. Those who were older (HR = 1.10, 95% CI, 1.05-1.15), had more comorbidities (HR = 1.17, 95% CI 1.15-1.18), Black (HR = 1.23, 95% CI, 1.14-1.33,P <0.01), and dually eligible (HR =1.23, 95% CI, 1.14-1.33, P <0.01) were more likely to return within 31-90 days after their initial presentation. The association of outpatient visits with repeat ED visits was no longer seen beyond 30 days. Patients without a caregiver or who lived alone were no more likely to return to the ED in the time periods evaluated in our study.Conclusion: Both primary care and subspecialty care visits among older adults who are seen in the ED and discharged are associated with less frequent repeat ED visits within 30 days.
Harmonic filter with low coupling capacitance for Medium Voltage, high dv/dt PWM converters

Emerging medium voltage (MV) Silicon Carbide (SiC) 10 kV MOSFETs have low on-state resistance and are capable of very high switching speeds. As a result, a highly efficient and compact MV power conversion system can be realized using these devices, which is desirable for many existing and emerging high power applications. However, at very high switching speeds in MV, leads to extremely high dV/dt during switching transitions. This gives rise to increased attention towards circuit parasitics as the parasitic capacitance of the filter components provides a path for the high-frequency current. Therefore, a very high dV/dt operation imposes a strict requirement on the parasitic capacitance of the filter components to meet the stringent conducted ElectroMangnetic Interference (EMI) standards. A design methodology to reduce the parasitic capacitance of the filter inductor in MV power conversion is proposed. The Analytical model of the parasitic capacitance is developed, and compared with finite element analysis along with actual value measurements through an impedance analyzer. The inductors performance is also evaluated experimentally using an XHV-9 module-based Power Electronic Building Block (PEBB).
Comparative impact of methamphetamine and other drug use on viral suppression among sexual minority men on antiretroviral therapy.

Abstract Background Substance use decreases the likelihood of achieving undetectable HIV viremia; however, the comparative effects by drug have not been fully described. In this study, we compare the effects of methamphetamine use versus other drugs on viremia in sexual minority men on antiretroviral therapy (ART). Methods HIV-positive participants currently on ART (N = 230) were selected from an ongoing cohort of diverse young sexual minority men (mSTUDY) enrolled from August 2014 to May 2018. Substance use and sociodemographic factors associated with viremia outcomes were assessed using ordinal regression analysis with generalized estimating equations. Viremia outcomes were grouped as undetectable ( 20 copies/mL), low level suppressed (21–200 copies/mL), or not suppressed (>200 copies/mL). Results The prevalence of drug use across 825 study visits was 73 %, with methamphetamine use most prevalent (50 %). After adjusting for unstable housing and ART adherence, methamphetamine use, either alone (adjusted OR = 1.87; 95 % CI 1.03−3.40) or with other drugs (adjusted OR = 1.82; 95 % CI 1.12−2.95), was associated with higher odds of increasing viremia compared to no drug use. Other drug use excluding methamphetamine did not show a similar association (adjusted OR = 1.29; 95 % CI 0.80−2.09). Among our study population, nearly half the instances of viremia could be reduced if methamphetamine was discontinued (attributable fraction = 46 %; 95 % CI 3–71 %). Conclusions Methamphetamine use, either alone or in combination with other drugs, is associated with failure of viral suppression among sexual minority men on ART independent of adherence and sociodemographic factors. This accounts for nearly half of the observed instances of unsuppressed viremia in this study.
Comparison of pulse-dose and high-dose corticosteroids with no corticosteroid treatment for COVID-19 pneumonia in the intensive care unit.

Corticosteroid dosing in the range of 0.5-2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID-19 pneumonia based on positive results of randomized trials and a meta-analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID-19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID-19 pneumonia, we compared patients treated with 0.5-2 mg/kg/day in methylprednisolone equivalents (high-dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse-dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU-free days at Day 28, and complications potentially attributable to corticosteroids. Pulse-dose corticosteroid therapy was associated with a significant increase in ICU-free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05-2.02; p = 0.03) and compared with high-dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high-dose corticosteroids-but not of pulse-dose corticosteroids-significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12-0.77; p = 0.01). High-dose corticosteroids reduced mortality compared to pulse-dose corticosteroids (p = 0.04). Pulse-dose corticosteroids-but not high-dose corticosteroids-significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27-9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse-dose group when compared to the high-dose group (p = 0.05 for the comparison). In this single-center study, pulse-dose corticosteroid therapy for COVID-19 pneumonia in the ICU was associated with an increase in ICU-free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high-dose corticosteroids on mortality was favorable.
State of Prebriefing and Debriefing in Virtual Simulation

Abstract Background Virtual simulation-based education is in healthcare education. This study explored nurse educators’ use of the INACSL Standards of Best Practice: Simulation© during facilitation and debriefing of virtual simulation during the pandemic. Design A quantitative exploratory research design with a researcher developed survey was used to the answer the research questions. Results A total of 129 participants responded to the survey. A plethora of strategies were reported regarding pre-briefing and debriefing. Conclusion Overall, nurse educators followed the INACSL Standards of Best Practice: Simulation© either synchronously or asynchronously. However, research is needed on the best method for pre-briefing and debriefing virtual simulation.
Deregulated Manganese Superoxide Dismutase Expression and Resistance to Oxidative Injury in p53-deficient Cells

Loss of function of the tumor suppressor protein p53 represents a very frequent event in human carcinogenesis, but the molecular mechanisms linking impaired p53 activity to increased cell malignancy are still incompletely understood. p53 is normally involved in both cell cycle control and the induction of cell death and is involved in the latter mainly through the transcriptional regulation of pro- and antiapoptotic proteins. Reactive oxygen species are known to be powerful inducers of p53 activity; moreover, they play a role in the execution of p53-dependent apoptosis. Here we show that transformed mouse fibroblasts lacking p53 are significantly more resistant than wild-type (wt) controls to the cytotoxic effect of a number of pro-oxidant treatments. Interestingly, these cells also exhibit deregulated expression of the antioxidant enzyme manganese superoxide dismutase (MnSOD), a protein known to protect cancer cells from the oxidative injury inflicted by antitumoral cytokines and anticancer drugs. MnSOD activity was also increased in liver tissue from p53-deficient mice in comparison with wt tissue. Transient transfection of wt p53 in HeLa cells led to a significant reduction in steady-state MnSOD mRNA levels and enzymatic activity, confirming that the expression of this antioxidant enzyme is negatively regulated by p53. Forced expression of MnSOD rendered HeLa cells resistant to p53-dependent cytotoxic treatments and, in cotransfection experiments, counteracted the growth-inhibitory effect of p53. Taken together, these data identify MnSOD as a potential target for tumor suppressor protein p53 and underscore the relevance of MnSOD modulation in the context of normal p53 functions because it is consistent with many reports of abnormally increased MnSOD expression in human cancers.
Complex-valued neurons with phase-dependent activation functions

In this paper, we observe two artificial neurons with complex-valued weights. There are a multi-valued neuron and a universal binary neuron. Both neurons have activation functions depending on the argument (phase) of the weighted sum. A multi-valued neuron may learn multiple-valued threshold functions. A universal binary neuron may learn arbitrary (not only linearly-separable) Boolean functions. It is shown that a multi-valued neuron with a periodic activation function may learn non-threshold functions by their projection to the space corresponding to the larger valued logic. A feedforward neural network with multi-valued neurons and its learning are also considered.
An adaptive neuro/fuzzy CMOS chip

Summary form only given. A modular chip, Tinychip in 2 micron CMOS process, contains a fuzzy-neuro system that is comprised of the usual fuzzification, inference, and defuzzification blocks. The circuit building blocks consist of single-transistors, differential pairs, transconductance multipliers, and bump circuits. The fuzzification and the defuzzification blocks each uses single-layer neural mapping with nonlinear synapses composed of multipliers and differential pairs. The inference block is realized by a two-layer feedforward network using nonlinear synapses and learning circuitries based on the modified, continuous-time back-propagation and optimal control techniques. The fuzzy-neuro chip can be embedded within a control processing loop and work to preserve the control system's overall stability and performance.
Cooperative thin filament activation of a kinetic model of cardiac sarcomere dynamics

Actin-myosin crossbridges form in a sarcomere under the control of calcium ions binding to the thin filament. Crossbridges first form weak attachments before they transform into strong bonds that generate force. An appropriately simplified model of this action is critical for developing higherlevel models of cardiac function. Models can be simplified by separating slower from faster processes, where the fast processes have achieved equilibrium. Processes in equilibrium can also be analyzed using the Ising model of statistical mechanics, which allows us to study a row of cooperatively interacting units - as occurs along the thin filament. Using these concepts, the sarcomere model was simplified to 3 states: (1) strong crossbridges attached to a regulatory unit (RU) on the thin filament that had calcium bound to it; (2) strong crossbridges attached to an RU without calcium; (3) an equilibrium mixture of detached and weakly attached crossbridges with and without calcium bound. This simplified model predicted steady-state relationships between force and calcium that reproduced the experimentally seen trend toward less cooperativity as force rises to more than half maximum. It also predicted a trend for clustering of strong crossbridges along the thin filament due to cooperative interactions.
Spreading gain control in random access direct-sequence spread spectrum data networks

In this paper, we consider a time-slotted DS-SSMA network consisting of a single radio access point and a finite number of mobile wireless terminals. The terminals generate "bursty" packet data and transmit in a random access fashion over a common broadband channel to the access point using different spreading codes. As in narrowband ALOHA systems, the performance of random access spread spectrum networks can be severely hampered due to saturation effects caused by inherent bistable behavior. We study the affect of dynamic spreading gain control on the stability and throughput properties of the network. We provide an optimal algorithm and establish a necessary and sufficient condition under which the algorithm eliminates bistability. If the condition holds, then the resulting operating point is the best possible; otherwise, the two resulting stability points are, in some sense, the best possible. In either case, the algorithm achieves high throughput.
Cyclical Changes in Susceptibility of A Myeloma Tumor (LPC-1) to Immune Destruction: II. Periodic Fluctuations During Growth in Normal and Nude Mice and in Culture

Cells of the LPC-1 myeloma tumor (of BALB/c origin) were tested periodically for susceptibility to lysis by anti-H-2 cytotoxic T lymphocytes (CTL) and by complement-dependent anti-H-2 antibodies (Ab), and for ability to adsorb these Ab, as the cells grew in culture and in ascites form in nude (BALB/c·nu) and in normal BALB/c mice. Cells harvested from 2 to 8 days after inoculation into the peritoneal cavity had the “early” phenotype: they were extensively lysed by the CTL and Ab and effectively adsorbed the Ab. Cells harvested on day 8 and afterward had the “late” phenotype: they were not lysed by CTL, required more Ab for lysis, and had about 8-fold less ability (per cell) to adsorb the Ab. All of these activities were completely reversed 2 to 4 days after transferring late cells into fresh BALB/c hosts. LPC-1 cells growing in nude BALB/c mice also changed from the early, CTL-susceptible to the late CTL-resistant phenotype. With repeated cell counts and measurements of 125 I-iododeoxiuridine incorporation to estimate growth, it was found that exponentially growing cells had the early phenotype and that cells in stationary phase had the late phenotype. When placed in culture, the early cells retained their phenotype indefinitely (up to 40 days). However, the late cells switched phenotype: initially resistant to CTL and Ab, after 1 to 4 days in culture they became fully susceptible to CTL and highly reactive with the Ab, and these features persisted in culture thereafter. This transition occurred even when the late, resistant cells were prevented from dividing in culture by prior irradiation (10,000 R) or by trinitrophenylation with 2,4,6-trinitrobenzenesulfonic acid. The findings in both nude mice and in culture indicate that the reversible, early-late phenotypic changes are due to changes in individual cells, rather than to immunoselection of preexisting variant cells.
Productivity Convergence: Postwar Economic Performance among Countries of the World

Introduction The term “aggregate convergence” refers to the gradual diminution of differences in productivity levels for the overall economy of countries over time. Previous explanations of the productivity catch-up almost all involve the advantages of backwardness or Gerschenkron effect, by which it is meant that much of the catch-up can be explained by the diffusion of technical knowledge from the leading economies to the more backward ones (see Gerschenkron, 1952, and Kuznets, 1973, for example). From this view, technological progress operates through a mechanism that enables countries whose level of productivity is behind (but not too far behind) that of the leading country(ies) to catch up. Through the constant transfer of knowledge, countries learn about the latest technology from each another, but virtually by definition the followers have more to learn from the leaders than the leaders have to learn from the laggards. On the other hand, those countries that are so far behind the leaders that it is impractical for them to profit substantially from the leaders’ knowledge will generally not be able to participate in the convergence process at all, and many such economies will find themselves falling even further behind. The most important influence underlying this process is the transfer of technology that occurs constantly among many of the world’s economies. There is strong evidence that advanced industrial countries continuously acquire technical ideas from each other. Competitive pressures in the international economy ensure rapid dissemination of superior productive techniques from one country to another. However, in the process of reciprocal exchange of ideas, clearly it is the more backward countries that have more to learn from the leaders than the reverse. That is the heart of the explanation of a convergence process.
A Conservative Test of Genetic Drift in the Endosymbiotic Bacterium Buchnera: Slightly Deleterious Mutations in the Chaperonin groEL

The obligate endosymbiotic bacterium Buchnera aphidicola shows elevated rates of sequence evolution compared to free-living relatives, particularly at nonsynonymous sites. Because Buchnera experiences population bottlenecks during transmission to the offspring of its aphid host, it is hypothesized that genetic drift and the accumulation of slightly deleterious mutations can explain this rate increase. Recent studies of intraspecific variation in Buchnera reveal patterns consistent with this hypothesis. In this study, we examine inter- and intraspecific nucleotide variation in groEL, a highly conserved chaperonin gene that is constitutively overexpressed in Buchnera. Maximum-likelihood estimates of nonsynonymous substitution rates across Buchnera species are strikingly low at groEL compared to other loci. Despite this evidence for strong purifying selection on groEL, our intraspecific analysis of this gene documents reduced synonymous polymorphism, elevated nonsynonymous polymorphism, and an excess of rare alleles relative to the neutral expectation, as found in recent studies of other Buchnera loci. Comparisons with Escherichia coli generally show patterns predicted by their differences in Ne. The sum of these observations is not expected under relaxed or balancing selection, selective sweeps, or increased mutation rate. Rather, they further support the hypothesis that drift is an important force driving accelerated protein evolution in this obligate mutualist.
Sex Differences in Normal Fetuses and Infants: A Commentary

Sex differences in infants warrant attention, not because they clarify the extent to which such differ- ences reflect nature or nurture, but because studying them is likely to illuminate the origins of sex differences later in life and thereby yield manipulations that could influence the development of importan tc ompetences. It is not yet clear how male and female infants come to differ. Testos- terone is influential, but because of the complexity of the developmental systems in which it operates, its effects are not straightforward: Testosterone does different things in different contexts. Simple explanations invoking hormone exposure should not be expected to satisfactorily answer questions about the origins of sex differences, but stan- dardizing protocols to allow meaningful meta-analyses would help bring coherence to the research literature in
Exodus: Structuring Redemption of Captives

The question of how to react to ransom demands in kidnap situations is ancient and persistent. It was asked as far back as Biblical times, and yet modern states have still not found answers. In terrorist kidnapping scenarios, the private victims, including the family, are often used as leverage to pressure the authorities, with the anticipation that the combination of public sympathy and private lobbying will result in excessive concessions. In the kidnap game, the victim’s family is a single-game player and thus operates under a completely different set of considerations than the repeat player: the state. The question is how the repeat player is able to resist the one-off appearance of a particular kidnap victim and the pressure to concede to terrorist demands. The problem is compounded by an inflation effect in that each concession becomes the baseline for the next. Predictably, democracies do not deal well with this issue, and they may find themselves in a vicious cycle where ransom demands are repeatedly raised and conceded to, creating greater incentives toward kidnapping. This article identifies both why precommitment is the necessary solution to repeat kidnapping situations, and why it is a difficult solution to abide by. It argues that the world has so far tested only content-based precommitment strategies such as setting red-lines regarding what prices states will not pay. These policies have largely failed to constrain states’ concessions to terrorists. As an alternative, this article argues that states should adopt only structural-procedural precommitment policies, and explains how this may serve as an antidote to some of the pressure for escalation.
Learning theory with consensus in reproducing kernel Hilbert spaces

This paper describes a problem of distribution free learning theory wherein a collection of n agents make independent and identically distributed observations of an unknown function and seek consensus in their construction of an optimal estimate. The learning objective is expressed in terms of an error defined over a reproducing kernel Hilbert spaces (RKHS) and in terms of a multiplier that enforces the consensus constraint. The multiplier can be interpreted as the information shared by the agents to achieve their joint estimate. A two stage learning dynamic is introduced in which agents alternatively perform local updates based on available measurements and prior mutual information regarding estimates, and then calculate and exchange with other nodes certain information functionals of their estimates. It is shown that the learning problem can be expressed as an abstract saddle point problem over a pair of RKHS. Sufficient conditions for the well-posedness of the optimization problem are derived in the RKHS framework using Schur complement techniques. Probabilistic bounds on the rate of convergence are derived when a stochastic gradient technique is used for the local update and an inexact Uzawa algorithm is employed to define the information exchange. Practical implementation of the method requires an oracle that evaluates the norm of residuals appearing in the learning dynamic.
Periodic Hartree Fock study of the elasticity of pentaerythritol tetranitrate

Abstract We present a study of the pentaerythritol tetranitrate energetic material by means of the ab initio all-electron periodic Hartree–Fock quantum mechanical method with the STO-3G basis set. Our calculations yield the equilibrium lattice vectors a0 and c0, the symmetry-preserving elastic constants (C11 + C12), C33, and C13, the bulk modulus B, and the linear moduli Ba and Bc. With regards to experiment, the average deviation of the calculated lattice vectors is 1% and that of the calculated elastic constants and moduli is 7.4%. In particular, the calculated bulk modulus 9.38 GPa agrees with experiment within 4.8%.