cssi/SciSciGPT-SciSciNet huggingface dataset:
We are chronically sleep deprived

Summary: Data from recent laboratory studies indicate that nocturnal sleep periods reduced by as little as 1.3 to 1.5 hours for 1 night result in reduction of daytime alertness by as much as 32% as measured by the Multiple Sleep Latency Test (MSLT). Other data document that 1) 170/0--57% of normal young adults have MSLT latencies of ::;5.5 minutes, whereas ::;50% have MSLT values of ~ 10 minutes and 2) 28°/0--29% of young adults reported normally sleeping ::;6.5 hours on each weeknight. More extensive reduction of daily sleep amount is seen in night­ shift workers. A minimum of 2%-4% of middle-aged adults have hypersomnolence associated with sleep apnea. Together, these data show that significant sleep loss exists in one-third or more of normal adults, that the effects are large and replicable and that similar effects can be produced in just I night in the laboratory. In light of the magnitude of this sleep debt, it is not surprising that fatigue is a factor in 57% of accidents leading to the death of a truck driver and in 10% of fatal car accidents and results in costs of up to 56 billion dollars per year. A recent sleep extension study suggests that the average underlying sleep tendency in young adults is about 8.5 hours per night. By comparison, the average reported sleep length of 7.2-7.4 hours is deficient, and common sleep lengths of ::;6.5 hours can be disastrous. We must recognize the alertness function of sleep and the increasing consequences of sleepiness with the same vigor that we have come to recognize the societal impact of alcohol. Key Words: Sleep deprivation-Sleepiness-Sleep disorders- Work schedule tolerance. Weare in the midst of a golden age of discovery of the intricate interrelationship between our nocturnal sleep process and our level of daytime function. Fueled by the discovery of the tremendous incidence of sleep apnea and periodic leg movements in the population, the relationship between fragmented sleep and residual sleepiness, as well as the increased ability to measure the level of objective sleepiness with an objective test [the Multiple Sleep Latency Test (MSLT)] and in am­ bulatory environments, the pervasive role of excessive sleepiness in our society is becoming apparent. Much literature documents the negative effects of sleep deprivation on a wide range of psychomotor per­ formance tasks and mood variables. For the sake of simplicity, the primary outcome measure reported in this paper will be MSL T. However, the MSL T findings reported are consistent with similar changes in a broad range of abilities, including reaction time, short-term memory, vigilance and mood (1). Many empirical and applied studies have provided evidence for our national sleep debt. The degree of our
Governing Equations for Mean Quantities

Motion in the atmospheric boundary layer is generally turbulent. The action of turbulence is evident when we observe the smoke plume released from a smokestack. The plume may whirl around, meander sideways, or loop up and down. These erratic patterns are visual clues of eddies at work. If we measure the flow with a fast-responding anemometer, we will find that the velocity fluctuates with time in a seemingly random manner. Air temperature, humidity, and other scalars also exhibit irregular temporal fluctuations. Details of the flow are impossible to predict. We have no way of determining the exact travel path of a smoke puff or predicting how the velocity changes from one second to the next. Rather our goal is to quantify the mean state of the atmosphere by performing averaging operation on the atmospheric properties.
New Treatments for Metastatic Breast Cancer

In the era of next-generation sequencing, knowledge of the genomic drivers of breast cancer and resistance to treatment is expanding. The recognition that these molecular drivers are ubiquitous in all subtypes of breast cancer has resulted in a paradigm shift away from focusing on traditional targets, such as the estrogen receptor or HER2 receptor, to blocking oncogenic signaling pathways, cell-cycle regulatory checkpoints, or epigenetic modulators present in breast cancer in general. These novel therapies appear to be more efficacious when combined with traditional therapeutics, such as anti-HER2 agents, or hormonal therapies, yet the identification of which cancers harbor mutations or protein activation that correlate with tumor response to these innovative therapies still remains a mystery. This section outlines the background data and current clinical investigation of these novel therapies which target more global molecular pathways present in all metastatic breast cancer.
Toward a Metadata Framework for Sharing Sensitive and Closed Data: An Analysis of Data Sharing Agreement Attributes

Legal and policy-oriented restrictions often hamper if not inhibit well-intended efforts to share sensitive or restricted data. The research reported on in this paper is a part of a larger initiative to develop a prototype system for automatically generating data sharing agreements that address privacy, legal concerns, and other restrictions. A content analysis was conducted, examining a sample of 26 data sharing agreements. The results include 6 high level categories, 15 mid-level attributes, and over 90 lower-level specific attributes, a portion of which can help to expeditiously support the automatic development of data sharing agreements. The paper presents background information, research questions and methods, results, and a discussion. The conclusion summarizes our results and identifies next steps.
The Phage f1 Gene VII Start Site and its Mutants Reveal that Translational Coupling can Confer Function to Inherently Inactive Initiation Sites

The abundant mRNA species observed in Escherichia coli infected with the filamentous phages f1, fd or M13 provide a number of interesting cases of post transcriptional and translational controls. The mRNAs all derive from the region of the genome containing the tightly linked genes II, X, V, VII, IX and VIII (Fig. 1; reviewed in Model and Russel, 1988). This series of overlapping RNAs have common 3′ ends generated by termination at the rho-independent site (T) just beyond gene VIII, and unique 5′ ends produced in two ways. Three of the RNAs, which for phage f1 are denoted species A, B and H, are primary transcripts from strong phage promoters. The others, RNAs C, D, E, F and G, are the 3′ products of post-transcriptional cleavage (Cashman and Webster, 1979; Cashman et al., 1980). S1 nuclease protection and primer extension methods have mapped the 5′ ends of the processed RNAs in uridine-rich regions in the f1 sequence: those for RNAs C, D, E and F are within the gene II coding region, and the 5′ endpoint of RNA G is within gene VII (Blumer and Steege, 1984, 1989). The nuclease activity or activities that mediate these cleavages are encoded by the host (Blumer and Steege, 1984), and are distinct from the endonucleases RNase III, RNase P, and RNase E (Cashman and Webster, 1979; Cashman et al., 1980; Smits et al., 1980).
A blueprint for the primary prevention of cancer: Targeting established, modifiable risk factors

In the United States, it is estimated that more than 1.7 million people will be diagnosed with cancer, and more than 600,000 will die of the disease in 2018. The financial costs associated with cancer risk factors and cancer care are enormous. To substantially reduce both the number of individuals diagnosed with and dying from cancer and the costs associated with cancer each year in the United States, government and industry and the public health, medical, and scientific communities must work together to develop, invest in, and implement comprehensive cancer control goals and strategies at the national level and expand ongoing initiatives at the state and local levels. This report is the second in a series of articles in this journal that, together, describe trends in cancer rates and the scientific evidence on cancer prevention, early detection, treatment, and survivorship to inform the identification of priorities for a comprehensive cancer control plan. Herein, we focus on existing evidence about established, modifiable risk factors for cancer, including prevalence estimates and the cancer burden due to each risk factor in the United States, and established primary prevention recommendations and interventions to reduce exposure to each risk factor.
Neural architecture supporting active emotion processing in children: A multivariate approach

Abstract Background Adaptive emotion processing is critical for nearly all aspects of social and emotional functioning. There are distinct developmental trajectories associated with improved emotion processing, with a protracted developmental course for negative or complex emotions. The specific changes in neural circuitry that underlie this development, however are still scarcely understood. We employed a multivariate approach in order to elucidate distinctions in complex, naturalistic emotion processing between childhood and adulthood. Method Twenty-one adults (M±SD age = 26.57 ± 5.08 years) and thirty children (age = 7.75 ± 1.80 years) completed a free-viewing movie task during BOLD fMRI scanning. This task was designed to assess naturalistic processing of movie clips portraying positive, negative, and neutral emotions. Multivariate support vector machines (SVM) were trained to classify age groups based on neural activation during the task. Results SVMs were able to successfully classify condition (positive, negative, and neutral) across all participants with high accuracy (61.44%). SVMs could successfully distinguish adults and children within each condition (ps Conclusions These results point to distributed differences in activation between childhood and adulthood unique to each emotional condition. In the negative condition specifically, there is evidence for a shift in engagement from regions of sensory and socio-emotional integration to emotion regulation regions between children and adults. These results provide insight into circuitry contributing to maturation of emotional processing across development.
Xenon-129 MRI detects ventilation deficits in paediatric stem cell transplant patients unable to perform spirometry.

Background Early detection of pulmonary morbidity following haematopoietic stem cell transplantation (HSCT) remains an important challenge for intervention, primarily due to the insensitivity of spirometry to early change, and in paediatrics, patient compliance provides additional challenges. Regional lung ventilation abnormalities in paediatric HSCT patients were quantified using hyperpolarised xenon-129 (129Xe) magnetic resonance imaging (MRI) and compared to spirometry. Methods Medically stable, paediatric allogeneic HSCT patients (n=23, ages 6–16 years) underwent an outpatient MRI scan where regional ventilation was quantified with a breath-hold of hyperpolarised 129Xe gas. Ventilation deficits, regions of the lung that ventilate poorly due to obstruction, were quantified as a ventilation defect percentage (VDP) and compared to forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and forced expiratory flow at 25–75% of FVC (FEF25–75%) from spirometry using linear regression. Results The mean±sd129Xe VDP was 10.5±9.4% (range 2.6–41.4%). 129Xe VDP correlated with FEV1, FEV1/FVC ratio and FEF25–75% (p≤0.02 for all comparisons). Ventilation deficits were detected in patients with normal spirometry (i.e. FEV1 >80%), supporting the sensitivity of 129Xe MRI to early obstruction reported in other pulmonary conditions. Seven (30%) patients could not perform spirometry, yet ventilation deficits were observed in five of these patients, detecting abnormalities that otherwise may have gone undetected and untreated until advanced. Conclusion Lung ventilation deficits were detected using hyperpolarised 129Xe gas MRI in asymptomatic paediatric HSCT patients and in a subgroup who were unable to perform reliable spirometry. 129Xe MRI provides a reliable imaging-based assessment of pulmonary involvement in this potentially difficult to diagnose paediatric population.
Rethinking Print Periodicals Holdings Retention Policy in Small Academic Libraries

Collection development policies in small academic libraries may lack a formal policy statement about print periodical holdings retention. However, there is a need for a distinct policy about print ...
Distinct Genome Replication and Transcription Strategies within the Growing Filovirus Family.

Abstract Research on filoviruses has historically focused on the highly pathogenic ebola- and marburgviruses. Indeed, until recently, these were the only two genera in the filovirus family. Recent advances in sequencing technologies have facilitated the discovery of not only a new ebolavirus, but also three new filovirus genera and a sixth proposed genus. While two of these new genera are similar to the ebola- and marburgviruses, the other two, discovered in saltwater fishes, are considerably more diverse. Nonetheless, these viruses retain a number of key features of the other filoviruses. Here, we review the key characteristics of filovirus replication and transcription, highlighting similarities and differences between the viruses. In particular, we focus on key regulatory elements in the genomes, replication and transcription strategies, and the conservation of protein domains and functions among the viruses. In addition, using computational analyses, we were able to identify potential homology and functions for some of the genes of the novel filoviruses with previously unknown functions. Although none of the newly discovered filoviruses have yet been isolated, initial studies of some of these viruses using minigenome systems have yielded insights into their mechanisms of replication and transcription. In general, the Cuevavirus and proposed Dianlovirus genera appear to follow the transcription and replication strategies employed by the ebola- and marburgviruses, respectively. While our knowledge of the fish filoviruses is currently limited to sequence analysis, the lack of certain conserved motifs and even entire genes necessitates that they have evolved distinct mechanisms of replication and transcription.
Measurement of forces exerted in the correction of idiopathic scoliosis using three-component dynamometers: The design of compact sensitive measuring units, their incorporation into the Milwaukee brace and the associated instrumentation are discussed

Idiopathic scoliosis is a progressive lateral curvature of the spine usually appearing during early adolescence. It may result in severe deformity with complications that profoundly affect the socio-economic future of the patient. The Milwaukee brace, frequently used in nonsurgical ambulatory treatment of scoliosis, seems to correct the disease by exerting traction and local pressure on the spine. Its lower end girdles the pelvis and the upper end bears on the occiput and mandible. In order to define precisely how the Milwaukee brace acts, and establish rational criteria for its use, a program has been undertaken to measure the forces exerted by the brace during treatment.
Tracking System Behavior from Resource Usage Data

Resource usage data, collected using tools such as TACC_Stats, capture the resource utilization by nodes within a high performance computing system. We present methods to analyze the resource usage data to understand the system performance and identify performance anomalies. The core idea is to model the data as a three-way tensor corresponding to the compute nodes, usage metrics, and time. Using the reconstruction error between the original tensor and the tensor reconstructed from a low rank tensor decomposition, as a scalar performance metric, enables us to monitor the performance of the system in an online fashion. This error statistic is then used for anomaly detection that relies on the assumption that the normal/routine behavior of the system can be captured using a low rank approximation of the original tensor. We evaluate the performance of the algorithm using information gathered from system logs and show that the performance anomalies identified by the proposed method correlates with critical errors reported in the system logs. Results are shown for data collected for 2013 from the Lonestar4 system at the Texas Advanced Computing Center (TACC).
Financial Capability in Later Life

The threat—and reality—of financial insecurity in retirement is a key concern for those in, and approaching, later life. Rates and levels of emergency and retirement savings are low for those throughout the life course, made especially concerning for those who are near or already in retirement and for members of more vulnerable groups. This chapter outlines the goals of one of the 12 Grand Challenges for Social Work—to Build Financial Capability for All—while detailing key areas of importance specific to gerontological social work. These include a focus on older adults’ abilities to increase their emergency and retirement savings and financial literacy as well as older adults’ opportunities to access important economic benefits and protections. Key tools, resources, and research in this area are discussed, with an emphasis on ensuring older adults are receiving the benefits that they are eligible for and preventing financial exploitation. It concludes with a focus on future steps that gerontological social workers can take to advance research using the ability-opportunity framework of financial capability, policy at the state and national levels, and practice by gaining more specialized skills and knowledge in financial management and literacy.
Estimation of SARS-CoV-2 Infection Prevalence in Santa Clara County

To reliably estimate the demand on regional health systems and perform public health planning, it is necessary to have a good estimate of the prevalence of infection with SARS-CoV-2 (the virus that causes COVID-19) in the population. In the absence of wide-spread testing, we provide one approach to infer prevalence based on the assumption that the fraction of true infections needing hospitalization is fixed and that all hospitalized cases of COVID-19 in Santa Clara are identified. Our goal is to estimate the prevalence of SARS-CoV-2 infections, i.e. the true number of people currently infected with the virus, divided by the total population size. Our analysis suggests that as of March 17, 2020, there are 6,500 infections (0.34% of the population) of SARS-CoV-2 in Santa Clara County. Based on adjusting the parameters of our model to be optimistic (respectively pessimistic), the number of infections would be 1,400 (resp. 26,000), corresponding to a prevalence of 0.08% (resp. 1.36%). If the shelter-in-place led to R0
The Relative Economy and Drug Overdose Deaths.

Background Overdose deaths increased exponentially in the United States to be the leading cause of adult injury deaths, and declining economic opportunity may contribute. To our knowledge, there has been no quantitative research into the impact of relative economic measures on overdose risk. Prior longitudinal studies on impact of socioeconomic conditions used fixed effects approaches that can result in biased estimates in the presence of time-varying confounders. Methods We estimated county-level longitudinal associations between drug overdose deaths and unemployment and labor-force nonparticipation rates by gender and racial/ethnic subgroup using longitudinal g-computation and the clustered bootstrap. Results We find evidence for associations between both overall and relative aspects of unemployment and labor-force nonparticipation and drug overdose mortality; patterns of associations differed, sometime qualitatively, across subgroups. For males across racial-ethnic groups, greater overall and relative unemployment rates were generally associated with greater overdose mortality in both the short and long terms [e.g., for white males, increasing the overall percentage of unemployed adults by 5% points in 2000, 2009, and 2015 is associated with an increase of 3.2 overdose deaths (95% confidence interval [CI] = -2.8, 14) in 2015, and increasing the ratio by 0.5 in 2000, 2009, and 2015 is associated with an increase of 9.1 overdose deaths (95% CI = 1.6, 24)]. Conclusions These findings point to important complexity in how the economic and contextual landscape differentially shapes overdose risks, underscoring a need for increased understanding of the mechanisms operating for women and minority groups.
Role of CD8+ T-cell infiltration in breast tumors of Black women compared to White women.

e13608Background: Literature regarding racial differences in tumor immune responses in breast cancer remains sparse. To address this research gap, we assessed CD8+ T-cells in breast tumor samples f...
The Evolution of Resynchronization Therapy

There are around 5.7 million people who suffer from heart failure (CHF) in the USA, and there are 550,000 new cases every year. Worldwide, there are approximately 26 million people with heart failure. One-third of CHF patients have left bundle branch block (LBBB) that produces dyssynchronous activation of the ventricles resulting in heart failure. In this chapter, the author discusses the historical aspects of conduction-related dyssynchrony, Bi-V pacing also referred to as resynchronization, the clinical trials and outcomes of resynchronization, the guidelines for resynchronization, and novel methods for resynchronization.
Metachronal Swimming with Flexible Legs: A Kinematics Analysis of the Midwater Polychaete Tomopteris.

Aquatic animals have developed a wide array of adaptations specific to life underwater, many of which are related to moving in the water column. Different swimming methods have emerged, such as lift-based flapping, drag-based body undulations, and paddling. Patterns occur across scales and taxa, where animals with analogous body features use similar locomotory methods. Metachronal paddling is one such wide-spread propulsion mechanism, occurring in taxa as diverse as ctenophores, crustaceans, and polychaetes. Sequential movement of multiple, near identical appendages allows for steady swimming through phase-offsets between adjacent propulsors. The soft-bodied, holopelagic polychaete Tomopteris has two rows of segmental appendages (parapodia) positioned on opposite sides along its flexible body that move in a metachronal pattern. The outer one-third of their elongate parapodia consist of two paddle-like pinnules that can be spread or, when contracted, fold together to change the effective width of the appendage. Along with metachronal paddling, tomopterid bodies undulate laterally, and by using high speed video and numerical modeling, we seek to understand how these two behaviors combine to generate effective swimming. We collected animals using deep-diving remotely operated vehicles, and recorded video data in shore- and ship-based imaging laboratories. Kinematics were analyzed using landmark tracking of features in the video data. We determined that parapodia are actively moved to generate thrust and pinnules are actively spread and contracted to create differences in drag between power and recovery strokes. At the same time, the body wave increases the parapodium stroke angle and extends the parapodia into undisturbed water adjacent to the body, enhancing thrust. Based on kinematics measurements used as input to a 1 D numerical model of drag-based swimming, we found that spreading of the pinnules during the power stroke provides a significant contribution to propulsion, similar to the contribution provided by the body wave. We conclude that tomopterids combine two different propulsive modes, which are enabled by their flexible body plan. This makes their anatomy and kinematics of interest not only for biologists, but also for soft materials and robotics engineers.
Recurrent clonazepam withdrawal delirium in a postoperative neurosurgical patient: a case report

We present a case of benzodiazepine withdrawal delirium in a middle-aged man undergoing spinal surgery. Benzodiazepines were stopped prior to surgery and on postoperative day 4, the patient exhibited significant paranoia, hyperarousal and ideas of reference. Patient's symptoms resolved after reintroduction of his benzodiazepines. It is important to include benzodiazepine withdrawal in the differential diagnosis for acute delirium even in those patients taking low or moderate doses. Benzodiazepine withdrawal delirium typically responds rapidly to restarting benzodiazepines. In patients with known discontinuation issues, early consultation with consult-liaison psychiatry and preoperative planning for early medication re-initiation is paramount.
Development and Implementation of a Three-Dimensional (3D) Printing Elective Course for Health Science Students.

Three-dimensional (3D) printing technology has become more affordable, accessible, and relevant in healthcare, however, the knowledge of transforming medical images to physical prints still requires some level of training. Anatomy educators can play a pivotal role in introducing learners to 3D printing due to the spatial context inherent to learning anatomy. To bridge this knowledge gap and decrease the intimidation associated with learning 3D printing technology, an elective was developed through a collaboration between the Department of Anatomy and the Makers Lab at the University of California, San Francisco. A self-directed digital resource was created for the elective to guide learners through the 3D printing workflow, which begins with a patient's computed tomography (CT) digital imaging and communication in medicine (DICOM) file to a physical 3D printed model. In addition to practicing the 3D printing workflow during the elective, a series of guest speakers presented on 3D printing applications they utilize in their clinical practice and/or research laboratories. Student evaluations indicated that their intimidation associated with 3D printing decreased, the clinical and research topics were directly applicable to their intended careers, and they enjoyed the autonomy associated with the elective format. The elective and the associated digital resource provided students with the foundational knowledge of 3D printing, including the ability to extract, edit, manipulate, and 3D print from DICOM files, making 3D printing more accessible. The aim of disseminating this work is to help other anatomy educators adopt this curriculum at their institution.
Serious psychological distress and cannabis use among pregnant women in the United States: Findings from the National Survey of Drug Use and Health, 2015-2018

Abstract Background Cannabis use in pregnancy has been shown to be associated with a past diagnosis of mental health disorders. This study aimed to evaluate the association between serious psychological distress (SPD) and cannabis use in pregnant women in the United States. Methods Using cross-sectional data from the 2015–2018 National Survey on Drug Use and Health (NSDUH), we compared likelihood of cannabis use among pregnant women who reported acute, recent or no SPD based on the Kessler K-6 Distress Scale. Weighted analyses were conducted to describe study population and differences in cannabis use patterns in women with SPD compared to those without. Multivariate logistic regression models were fit to determine whether the relationship between SPD and cannabis use differed by acute, recent or no SPD status. Results Our final study sample consisted of 2,277,425 pregnant women. In adjusted analyses, pregnant women with any SPD (acute or recent) had 3.1 (95% confidence interval: 2.1, 4.5) times the odds of being current cannabis users compared to pregnant women without SPD. Compared to those with no SPD, pregnant women adjusted with acute SPD had 3.9 (2.5, 6.1) the adjusted odds and recent SPD had 2.4 (1.3, 4.4) times the odds of being current cannabis users. Cannabis use rates in each trimester were significantly higher in women with SPD compared to women without. Conclusion Women who report recent or acute SPD are significantly more likely to use cannabis during all trimesters of pregnancy than those who report no SPD.
A comparison of tracking step inputs with a piezo stage using model predictive control and saturated linear quadratic Gaussian control

Abstract Compressed Sensing for Atomic Force Microscopy is a newer imaging mode that requires the piezo stage be driven rapidly between measurement locations. In contrast to raster scanning applications, this translates to a setpoint tracking problem. This paper considers the setpoint tracking performance of a piezo nano-positioning stage subject to rate-of-change limitations on the control signal, which is derived from the current limit of the power amplifier. To compensate the vibrational dynamics of the stage, a model predictive control scheme (MPC) and a linear quadratic Gaussian (LQG) controller which saturates the control increment are considered. In both cases, hysteresis and drift are compensated via dynamic inversion. To design the weighting matrices required by the MPC and linear feedback designs, an extension to classic reciprocal root locus ideas is proposed. The robustness of both schemes using classical methods like gain margin, phase margin, and gain of the sensitivity function at low frequencies is analyzed. The overall settle times achieved by both controllers (in both simulation and experiment) across a range of control weights where the reference input is a sequence of step inputs of varying amplitudes are compared. The results show that the best simulation settle time is achieved by MPC using the smallest control weight. However under experimental conditions, the best settle time is achieved by a much larger control weight and the performance of MPC becomes comparable with that of saturated linear feedback. This result is explained by showing that robustness increases with larger control weights.
On-chip bus interleaving revisited

Repeater interleaving is used to reduce the impact of capacitive coupling noise on the worst-case delay in local on-chip RC buses. In this paper, we revisit this interconnect design practice to evaluate it from the viewpoint of signal integrity of global on-chip interconnect used in on-chip high-speed signaling as between a cache and a CPU. Using accurate R(f)L(f)C electrical models of the global bus, we show that the peak crosstalk noise exhibits both monotonic and convex dependence on the interleaving ratio. Furthermore, we show that the worst-case switching pattern used in quantifying the common-mode noise (CMN) on the bus depends on the repeater interleaving ratio. This dependence makes the search of the optimal ratio that minimizes bus CMN quite challenging. The conclusions of this paper are valid for both unidirectional and bidirectional buses.
Rad6 Overexpression Induces Multinucleation, Centrosome Amplification, Abnormal Mitosis, Aneuploidy, and Transformation

We have isolated by differential RNA display a cDNA that is up-regulated in metastatic mammary tumor lines. This cDNA corresponds to HR6B, the yeast homologue of Rad6, a ubiquitin-conjugating enzyme, and a key player in postreplication repair and induced mutagenesis in the yeast. We show that Rad6 protein expressed in metastatic tumor lines is wild type and functional, because it is able to catalyze the transfer of ubiquitin to histone H2b and is predominantly localized in the nucleus as compared with cytoplasmic localization in normal or nonmetastatic mammary cells. This pattern of Rad6 protein expression/localization is not restricted to breast cancer cell lines, because human breast carcinomas display similar patterns of Rad6 up-regulation and nuclear localization suggesting that deregulation in expression of Rad6 may be an important step in transformation to malignant phenotype. Constitutive overexpression of exogenous human HR6B cDNA into normal-behaving MCF10A human breast epithelial cells induced cell-cell fusion that resulted in generation of multinucleated cells, centrosome amplification, multipolar mitotic spindles, aneuploidy, and ability for anchorage-independent growth. Double immunofluorescence labeling experiments demonstrated the colocalization of Rad6 protein with γ-tubulin on centrosomes. This physical association of Rad6 with centrosomes is maintained throughout the interphase and mitotic phases of the cell cycle. The Rad6 protein exhibits notable alterations in distribution during interphase and mitotic stages of the cell cycle that are compatible with its function as a transcription factor. These findings suggest that Rad6 is an important ubiquitin-conjugating enzyme that may play a significant role in the maintenance of genomic integrity of mammalian cells and that an imbalance in the levels and activity of Rad6 could lead to chromosomal instability and transformation in vitro.
Physiologic principles in the application of circulatory assist for the failing heart: Intraaortic balloon circulatory assist and venoarterial phased partial bypass

Abstract Venoarterial pulsatile partial bypass and intraaortic balloon counterpulse techniques produce (1) diastolic augmentation of aortic pressure which improves perfusion of the myocardium, and (2) a sink in presystolic and systolic pressures which lowers the workload of the left ventricle. Both techniques are effective in reversing the shock state in dogs and in man. Regional hemodynamic studies performed before, during and after counterpulsation explain benefits and drawbacks of each technique.
Role of Neuroimaging in the Presurgical Evaluation of Epilepsy

A significant minority of patients with focal epilepsy are candidates for resective epilepsy surgery. Structural and functional neuroimaging plays an important role in the presurgical evaluation of theses patients. The most frequent etiologies of pharmacoresistant epilepsy in the adult population are mesial temporal sclerosis, malformations of cortical development, cavernous angiomas, and low-grade neoplasms. High-resolution multiplanar magnetic resonance imaging (MRI) with sequences providing T1 and T2 contrast is the initial imaging study of choice to detect these epileptogenic lesions. The epilepsy MRI protocol can be individually tailored when considering the patient's clinical and electrophysiological data. Metabolic imaging techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) visualize metabolic alterations of the brain in the ictal and interictal states. These techniques may have localizing value in patients with a normal MRI scan. Functional MRI is helpful in non-invasively identifying areas of eloquent cortex. Developments in imaging technology and digital postprocessing may increase the yield for imaging studies to detect the epileptogenic lesion and to characterize its connectivity within the epileptic brain.
A Policy Analysis of Michigan's Mislabeled Gross Receipts Tax

On January 1, 2008, the State of Michigan implemented a new tax, labeled a modified gross receipts tax (MGRT). The label is misleading. The tax is not on gross receipts but rather on gross receipts reduced by "purchases from other firms," defined generally to include inventory purchased during the taxable year, capital purchases, and material and supplies. In some respects, the tax resembles a value-added tax (VAT), although it has some important features not found in a traditional VAT or in any known variation of that tax. The purpose of the MGRT, other than to raise revenue, is unclear on its face and is not clarified by the legislative history, which is virtually nonexistent. In this article, we undertake to describe this new tax, classify it as best we can within the tax taxonomy, and speculate about its effects on Michigan taxpayers and on the Michigan economy. Section I, by way of introduction, summarizes the tax reform efforts that led to the adoption of the gross receipts tax. Section II discusses the problems of classifying the tax, comparing it to a traditional gross receipts tax and to a tax on value added. Section III begins with an overview of the salient features of the MGRT and then discusses in greater detail three important features of the tax, namely its nexus rules, its apportionment rules, and its unitary business rules. We speculate about the impact of the tax on Michigan and Michigan taxpayers in the conclusion.
Mapping Organizational Dynamics with Body Sensor Networks

This paper demonstrates a novel approach that combines generative models of organizational dynamics and sensor network data with a stochastic method. Generative models specify how organizational performance is related to who interacts with whom and who performs what. Sensor network data track who interacts with whom and who performs what within an organization, and the stochastic methodology fits multi-agent models to data through the Monte Carlo method. The data set used in this paper documents how employees in a data service center handle tasks with different difficulty levels -- tracked with sociometric badges for one month -- and documents links between performance and behavior. This paper demonstrates the potential for improving organizational dynamics with body sensor network data, and therefore also shows the need to systematically benchmark differential organizational dynamics models on data sets for different types of organizations.
Perspective for special Gurdon issue for differentiation: Can cell fusion inform nuclear reprogramming?

Nuclear reprogramming was first shown to be possible by Sir John Gurdon over a half century ago. The process has been revolutionized by the production of induced pluripotent cells by overexpression of the four transcription factors discovered by Shinya Yamanaka, which now enables mammalian applications. Yet, reprogramming by a few transcription factors remains incomplete and inefficient, whether to pluripotent or differentiated cells. We propose that a better understanding of mechanistic insights based on developmental principles gained from heterokaryon studies may inform the process of directing cell fate, fundamentally and clinically.
The Oregon Center for Complementary and Alternative Medicine career development program: innovation in research training for complementary and alternative medicine.

Background: The burgeoning use of complementary and alternative medicine (CAM) highlights the need for high-quality research to discriminate between those approaches based on positive anecdotes or polished marketing and those that are consistently effective and safe. Description: To help meet this need, the Oregon Center for Complementary and Alternative Medicine has developed an innovative program to train researchers. The training program includes an individual mentoring and training plan, group mentoring, a clinical research class, proposal development, completion of an actual study, and journal club participation. Evaluation: After 2 years the fellows have submitted 18 grants, presented 4 posters, submitted 7 articles, developed 2 treatment protocols, and earned 1 master of public health degree and 1 graduate certificate. Conclusions: This program helps experienced CAM practitioners quickly adopt a research perspective. We encourage other career development programs to extend training in research meth...
Business Concerns regarding MBA Education: Effects on Recruiting

Abstract Few empirical studies have been conducted to systematically identify changes necessary in MBA education (Porter & McKibbin, 1988). This study was designed to fill this gap by researching prominent firms that hire MBA graduates. The results indicated that although firms are still hiring MBAs, improvements could be useful in the areas of leadership training, oral and written communication skills, and interpersonal skills.
Scanning electrochemical microscopy of individual single-walled carbon nanotubes.

Here we report on the novel application of scanning electrochemical microscopy (SECM) to enable spatially resolved electrochemical characterization of individual single-walled carbon nanotubes (SWNTs). The feedback imaging mode of SECM was employed to detect a pristine SWNT (∼1.6 nm in diameter and ∼2 mm in length) grown horizontally on a SiO2 surface by chemical vapor deposition. The resulting image demonstrates that the individual nanotube under an unbiased condition is highly active for the redox reaction of ferrocenylmethyltrimethylammonium used as a mediator. Micrometer-scale resolution of the image is determined by the diameter of a disk-shaped SECM probe rather than by the nanotube diameter as assessed using 1.5 and 10 μm diameter probes. Interestingly, the long SWNT is readily detectable using the larger probe although the active SWNT covers only ∼0.05% of the insulating surface just under the tip. This high sensitivity of the SECM feedback method is ascribed to efficient mass transport and facile...
Cartographic Results Of The General Survey Of Russia 1766–1861

The late author (1875–1960), who specialized in the historical geography and mapping of forests, describes the atlases, maps, plans, and notes produced by the General Survey of thirty-five provinces of European Russia in the last half of the 18th and the first half of the 19th century. He discusses the purpose, administration, coverage, and duration of the survey and the content, value, and location of the resultant maps and notes, almost all of which have survived in unpublished form in various Soviet archives. Their value for historical geographers is illustrated by several excerpts. L'auteur, maintenant decede (1875–1960), qui se specialisait dans la geographie historique et la cartographie des forets, decrit les atlas, cartes, notes et plans produits par les services cartographiques de trente-cinq provinces de la Russie d'Europe durant la deuxieme moitie du XVIIIe siecle et la premiere moitie du XIXe siecle. Il traite des buts, de l'administration, de l'etendue et de la duree des leves ainsi que du co...
Mastocytosis: molecular mechanisms and clinical disease heterogeneity

Systemic mastocytosis has one unifying feature: an unexplained and pathologic increase in mast cells in specific tissues. This observation, along with clinical disease heterogeneity has long suggested that mastocytosis is a disease of complex etiology. At the same time, the last decade has witnessed significant progress in identifying the critical elements that regulate mast cell growth and development. Human mast cells are now known to arise from CD34(+) progenitors, particularly under the influence of stem cell factor (SCF). This information in turn led to the critical observation that a substantial number of patients with mastocytosis exhibit activating mutations in c-kit, the receptor for SCF. And while this observation may well be key in understanding mastocytosis, this mutation alone does not explain all heterogeneity. It now appears that other influences such as genetic polymorphisms within the host may influence the course of disease in those with KIT mutations; and that the search for additional molecular events capable of creating disease diversity must continue.
Interactions between glutamate transporters and metabotropic glutamate receptors at excitatory synapses in the cerebellar cortex

Five glutamate transporter genes have been identified; two of these (EAAT3 and EAAT4) are expressed in neurons and are predominantly confined to the membranes of cell bodies and dendrites. At an ultrastructural level, glutamate transporters have been shown to surround excitatory synapses in hippocampus and cerebellum [J. Neurosci. 18 (1998) 3606; J. Comp. Neurol. 418 (2000) 255]. This pattern of localization overlaps the well-described perisynaptic distribution of Group I metabotropic glutamate receptors or mGluRs [Neuron 11 (1993) 771; J. Chem. Neuroanat. 13 (1997) 77]. Both of the principal excitatory synaptic inputs to cerebellar Purkinje neurons, the parallel fiber (PF) and climbing fiber (CF) synapses, express mGluR-dependent forms of synaptic plasticity [Nat. Neurosci. 4 (2001) 467]. Prompted by the colocalization of postsynaptic glutamate transporters and mGluRs, we have examined whether glutamate uptake limits mGluR-mediated signals and mGluR-dependent forms of plasticity at PF and CF synapses in cerebellar slices. We find that, at PF and, surprisingly also at CF synapses, mGluR activation generates a slow synaptic current and triggers intracellular calcium release. At both PF and CF synapses, mGluR responses are strongly limited by glutamate transporters under resting conditions and are facilitated by short trains of stimuli. Nearly every Purkinje neuron expresses an mGluR-mediated synaptic current upon inhibition of glutamate transport. Global applications of glutamate achieved by photolysis of chemically caged glutamate yield similar results and argue that the colocalized transporters can effectively limit glutamate access to the mGluRs even in the face of such a large amount of transmitter. We hypothesize that neuronal glutamate transporters and Group I mGluRs located in the perisynaptic space interact to sense and then regulate the amount of glutamate escaping excitatory synapses. This hypothesis is currently being tested using electrophysiological methods and the introduction of optically tagged glutamate transporter proteins. In the brain, synaptic signals are terminated mainly by neurotransmitter transporters. Families of genes encoding transporters for the major neurotransmitters (dopamine, GABA, glutamate, glycine, norepinephrine and 5-HT) have been identified. Although transporters serve as targets for important classes of therapeutic drugs (e.g. selective serotonin reuptake inhibitors) and drugs of abuse (amphetamine, cocaine), little is known about how they operate at a molecular level or contribute to synaptic transmission.
Quantum criticality in SU(3) and SU(4) antiferromagnets

We study the quantum phase transition out of the N\'eel state in SU(3) and SU(4) generalizations of the Heisenberg antiferromagnet with a sign-problem-free four-spin coupling (so-called $JQ$ model), by extensive quantum Monte Carlo simulations. We present evidence that the SU(3) and SU(4) order parameters and the SU(3) and SU(4) stiffness go to zero continuously without any evidence of a first-order transition. However, we find considerable deviations from simple scaling laws for the stiffness even in the largest system sizes studied. We interpret these as arising from multiplicative scaling terms in these quantities that affect the leading behavior, i.e., they will persist in the thermodynamic limit, unlike the conventional additive corrections from irrelevant operators. We conjecture that these multiplicative terms arise from dangerously irrelevant operators whose contributions to the quantities of interest are nonanalytic.