cssi/SciSciGPT-SciSciNet huggingface dataset:
Palmitoylation of proteins in cancer

Post-translational modification of proteins by attachment of palmitate serves as a mechanism to regulate protein localization and function in both normal and malignant cells. Given the essential role that palmitoylation plays in cancer cell signaling, approaches that target palmitoylated proteins and palmitoyl acyltransferases (PATs) have the potential for therapeutic intervention in cancer. Highlighted here are recent advances in understanding the importance of protein palmitoylation in tumorigenic pathways. A new study has uncovered palmitoylation sites within the epidermal growth factor receptor that regulate receptor trafficking, signaling and sensitivity to tyrosine kinase inhibitors. Global data analysis from nearly 150 cancer studies reveals genomic alterations in several PATs that may account for their ability to function as tumor suppressors or oncogenes. Selective inhibitors have recently been developed that target hedgehog acyltransferase (Hhat) and Porcupine (Porcn), the acyltransferases that modify hedgehog and Wnt proteins, respectively. These inhibitors, coupled with targeted knockdown of Hhat and Porcn, reveal the essential functions of fatty acylation of secreted morphogens in a wide variety of human tumors.
Clinical and Psychosocial Predictors of Urological Chronic Pelvic Pain Symptom Change in 1 Year: A Prospective Study from the MAPP Research Network

Purpose: We examined baseline clinical and psychosocial characteristics that predict 12-month symptom change in men and women with urological chronic pelvic pain syndromes.Materials and Methods: A total of 221 female and 176 male patients with urological chronic pelvic pain syndromes were recruited from 6 academic medical centers in the United States and evaluated at baseline with a comprehensive battery of symptom, psychosocial and illness-impact measures. Based on biweekly symptom reports, a functional clustering procedure classified participant outcome as worse, stable or improved on pain and urinary symptom severity. Cumulative logistic modeling was used to examine individual predictors associated with symptom change as well as multiple predictor combinations and interactions.Results: About 60% of participants had stable symptoms with smaller numbers (13% to 22%) showing clear symptom worsening or improvement. For pain and urinary outcomes the extent of widespread pain, amount of nonurological symptom...
Telomere Length and Pancreatic Cancer Risk-Reply.

Our report ([1][1]) showed that genetic risk scores computed from polymorphic variants previously associated with interindividual variation in leukocyte telomere length ([2–4][2]) are not associated with risk of pancreatic cancer (pancreatic ductal adenocarcinoma). Consistent with our finding, a
Indolizine–Squaraines: NIR Fluorescent Materials with Molecularly Engineered Stokes Shifts

The development of deep red and near infrared emissive materials with high quantum yields is an important challenge. Several classes of squaraine dyes have demonstrated high quantum yields, but require significantly red-shifted absorptions to access the NIR window. Additionally, squaraine dyes have typically shown narrow Stokes shifts, which limits their use in living biological imaging applications due to dye emission interference with the light source. Through the incorporation of indolizine heterocycles we have synthesized novel indolizine squaraine dyes with increased Stokes shifts (up to >0.119 eV, >50 nm increase) and absorptions substantially further into the NIR region than an indoline squaraine benchmark (726 nm versus 659 nm absorption maxima). These materials have shown significantly enhanced water solubility, which is unique for squaraine dyes without water-solubilizing substituents. Absorption, electrochemical, computational, and fluorescence studies were undertaken and exceptional fluorescence quantum yields of up 12 % were observed with emission curves extending beyond 850 nm.
How concentrated is crime among victims? A systematic review from 1977 to 2014

Considerable research shows that crime is concentrated among a few victims. However, no one has systematically compared these studies to determine the level of concentration and its variation across studies. To address this void in our knowledge of repeat victimization, we conducted a systematic review and meta-analysis of the evidence that crime is concentrated among victims. We distinguished between studies of victimization prevalence, which examine both victims and non-victims, and studies of victimization frequency, which only examine subjects that were victimized once or more. We identified 20 prevalence studies and 20 frequency studies that provided quantitative information sufficient for analysis. We organized data using visual binning and fitted logarithmic curves to the median values of the bins. We found that crime is concentrated within a small proportion of the subjects in both the prevalence studies and frequency studies, but also that it is more concentrated in the former. When we compared studies of business victimization to studies of household victimization, we found that victimization is more concentrated among households than among businesses in prevalence studies, but that the reverse is true for frequency studies. A comparison between personal and property victimizations shows that the patterns of re-victimizations are similar. Crime is more concentrated in the United States compared to the United Kingdom in prevalence studies, but the opposite is true when frequency studies are examined. Finally, the concentration of victimization changes over time for both the US and the UK, but the nature of that change depends on whether one is examining prevalence or frequency studies. Not surprisingly, our systemic review supports the notion that a large proportion of victimizations are of a relatively small portion of the population and of a small portion of all those victimized at least once. There is no question that crime is concentrated among a few victims. However, there is also variation in concentration that we also explored.
Feature Selection as Causal Inference: Experiments with Text Classification

This paper proposes a matching technique for learning causal associations between word features and class labels in document classification. The goal is to identify more meaningful and generalizable features than with only correlational approaches. Experiments with sentiment classification show that the proposed method identifies interpretable word associations with sentiment and improves classification performance in a majority of cases. The proposed feature selection method is particularly effective when applied to out-of-domain data.
Applications to Geodynamics

Applications to Computational Geodynamics. A. Example 1: Subduction with BEM and with PIC. B. Example 2: Volcanic Conduits with BEM. C. Example 3: Interaction of Many Faults with BEM. D. Example 4: Benchmark convection with PIC.
Hi-MC: a novel method for high-throughput mitochondrial haplogroup classification

Effective approaches for assessing mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist for mitochondrial haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive for studies with large sample sizes. The purpose of this study was to develop Hi-MC, a high-throughput method for mitochondrial haplogroup classification that is cost effective and applicable to large sample sizes making mitochondrial analysis more accessible in genetic studies. Using rigorous selection criteria, we defined and validated a custom panel of mtDNA single nucleotide polymorphisms that allows for accurate classification of European, African, and Native American mitochondrial haplogroups at broad resolution with minimal genotyping and cost. We demonstrate that Hi-MC performs well in samples of European, African, and Native American ancestries, and that Hi-MC performs comparably to a commonly used classifier. Implementation as a software package in R enables users to download and run the program locally, grants greater flexibility in the number of samples that can be run, and allows for easy expansion in future revisions. Hi-MC is available in the CRAN repository and the source code is freely available at https://github.com/vserch/himc.
The Development of Cultural and Social Complexity in Mongolia

Pastoral nomadic peoples are not usually thought of as architects of complex political organization. Most anthropological and historical literature on nomads repeats a common theme when it comes to their organizational potential—due to their mobility, lack of economic surplus, and fierce independence, herders tend not to organize politically, or do so only on a small-scale or temporary basis. Not surprisingly, such theories have difficulty accounting for the empires of Mongolia which were large, complex, powerful, and numerous. Yet, the dominant explanations for polities of the Asian steppe suggest that they must have been dependent on sedentary neighbors for critical resources and models of organization. This historically embedded concept of nomadic raiders along the frontiers depending on and appropriating the resources of neighboring states is still alive and well in twenty-first century scholarship. Archaeological approaches, however, are changing these stereotypical ideas about nomadic societies in many parts of the Old World and have generated new conceptions of nomads and their complexity. The material record left behind by ancient herding peoples in Mongolia tells a very different story of their lifeways and organization. I review recent archaeological research in Mongolia beginning with the earliest adoption of herd animals and ending with the rise of the first nomadic state. During this time span of more than 3000 years, archaeology has documented sophisticated cultures, advanced technologies, and experiments with many kinds of political formations. These early precedents produced the organizational foundations that underwrote the subsequent empires of Mongolia.
Output capacitance losses in 600 V GaN power semiconductors with large voltage swings at high- and very-high-frequencies

In this paper, we construct three Class-Φ 2 resonant converters with GaN HEMT power devices, 1 kW output power, and switching frequencies of 10 MHz, 30 MHz, and 54.24 MHz. The GaN HEMTs in these converters exhibit losses, approximated thermally, that are significantly higher (up to an order of magnitude) than those predicted by simulation. To investigate, we use a Sawyer-Tower circuit to evaluate the losses in the output capacitance, C OSS , of GaN devices from each manufacturer with commercially-available power devices with voltage ratings over 600 V DS . Losses are reported from 5–35 MHz for sine, square, and Class-Φ 2 waveshapes. Steinmetz curves accurately fit the measured losses across frequency and voltage. C OSS losses for a sine wave with an amplitude equal to the device voltage rating exceed 1 μJ per cycle for two of the three devices tested here, and average C OSS power dissipation with the high-dv/dt Class-Φ 2 waveshape is tens of watts for the best performing device in our study. Higher losses are measured in the cascode device than in the enhancement-mode devices. These losses are not included in manufacturer-provided simulation models or datasheets, and, to our knowledge, were not previously reported in the literature.
Plant Health Management: Soil Fumigation

Soil fumigation is used to rid the soil of diseases and pests before planting. Soil fumigation is globally employed wherever high-value agricultural crops are subjected to repeated monocultures. The chemical compounds used in soil fumigation have low boiling points, high vapor pressures, relatively high Henry's Law constants (a measure of their partition potential between air and water phases), and are toxic to a broad spectrum of biological organisms. Chemical fumigants have been subjected to intense public scrutiny and regulatory restrictions due to their impacts on human health and the environment. Recently, a set of good agricultural practices have been developed for soil fumigation to mitigate worker and bystander exposure to harmful concentrations of chemical fumigants and to alleviate their environmental disruption following application to the soil.
INSTABILITY OF HIGHER PLANT CHROMOSOMAL DNA MOLECULARLY CLONED IN E. COLI VIA RECOMBINANT PLASMIDS

This chapter studies the instability of higher plant chromosomal DNA molecularly cloned in E. coli via recombinant plasmids. High molecular weight DNA from Glycine max (soybean) and Arabidopsis thaliana was highly purified to remove polysaccharide contamination by banding in CsCl-PdI gradients. Restriction fragments were enriched 60-fold for the soybean rDNA genes by preparative agarose gel electrophoresis. Restriction fragments of total DNA from both plants and from fractions enriched for rDNA were inserted into the Hind III and Bam HI sites (tetracycline resistance) of plasmid pBR322 and the Eco RI site (chloramphenicol resistance) of plasmid pBR325. Hundreds of independently isolated transformants containing recombinant plasmids were screened. The vast majority of the plant DNA inserts was less than 10 6 daltons. The size of the input DNA varied from 10 6 to 10 7 daltons with a MW av of 4 × 10 6 daltons. It is shown that the cloned rDNA fragments result from a 60% loss of DNA from within the cloned rDNA fragment.
Exact Cell Decomposition

In this chapter we describe a second approach to motion planning, exact cell decomposition. The principle of this approach is to first decompose the robot’s free space C free into a collection of non-overlapping regions, called cells, whose union is exactly1 C free (or its closure). Next, the connectivity graph which represents the adjacency relation among the cells is constructed and searched. If successful, the outcome of the search is a sequence of cells, called a channel, connecting the cell containing the initial configuration to the cell containing the goal configuration. A path is finally extracted from this sequence.
Applying the child-centred and integrated framework for violence prevention: A case study on physical violence in Viet Nam

ABSTRACTIn 1986, the Government of Viet Nam introduced a package of economic reforms known as Doi Moi (open door) policy that transformed the previously centrally planned, vertically oriented, larg...
KeV astrophysics with GeV beams; blazing a new trail on the summit of Nuclear Astrophysics

GeV beams of light ions and electrons are used for creating a high flux of real and virtual photons, with which some problems in Nuclear Astrophysics are studied. GeV 8B beams are used to study the Coulomb dissociation of 8B and thus the 7Be(p,γ)8B reaction. This reaction is one of the major source of uncertainties in estimating the 8B solar neutrino flux and a critical input for calculating the 8B solar neutrino flux. The Coulomb dissociation of 8B appears to provide a viable method for measuring the 7Be(p,γ)8B reaction rate, with a weighted average of the RIKEN1, RIKEN2, GSI1 and MSU published results of S 17(0)=18.9±1.0 eV-b. This result, however, does not include a theoretical error estimated to be ±10%. GeV electron beams on the other hand, are used to create a high flux of real and virtual photons at TUNL-HIGS and MIT-Bates, respectively, and we discuss two new proposals to study the 12C(α,γ)16O reaction with real and virtual photons. The 12C(α,γ)16O reaction is essential for understanding Type II and Type Ia supernova. It is concluded that virtual and real photons produced by GeV light ions and electron beams are useful for studying some problems in Nuclear Astrophysics.
Low-MSE extraction of permittivity in optical hyperbolic metamaterials

We describe the details of a procedure to obtain low mean-squared-error (MSE) values for the extraction of permittivity tensors of hyperbolic metamaterials (HMMs) using spectroscopic ellipsometry. We have verified our procedure through characterization of three different HMM samples having varying materials, periods, and fill factors. Our procedure eliminates the need for complicated ellipsometric measurements and modeling techniques, as well as the need for any additional optics such as prisms or index-matching gels. Therefore, a time-efficient and cost-effective approach is introduced, which is only dependent on software; hence, it can be easily and widely adopted. All the MSE values obtained in this Letter are below 1.00 while, at the same time, meaningful and reasonable permittivities are extracted from HMMs.
Cross Corpus Emotion Classification Using Survey Data

Although semantic analysis and machine learning are becoming well established parts of Natural Language Processing (NLP), extraction of discrete emotions from text remains an under-developed area. Even less frequently do we see application of these technologies to open-ended survey questions in fields such as political science, psychology, public policy and sociology. In these domains, the need for more fined-grained emotion analysis of text responses has become apparent, particularly for assessing nuanced responses of the population to unexpected high impact events or incidents. Doing such assessments in real time is even more difficult. We report preliminary results on an ambitious attempt to perform a cross-corpus emotion classification that applies data gathered in one survey to text collected at a different time from different sources. This research is one step in a broader agenda to create new NLP methods to code large-scale text data from surveys and social media to improve studies of emotion contagion through social media networks. Our report is based on a medium-scale experiment from a survey conducted in the Fall of 2016 during a crisis event. Preliminary evidence suggests that with careful calibration of survey instruments, and proper understanding of natural language expressions (encoded as machine learning features), a transfer of classification code should be possible for some strongly expressed and potentially actionable emotions, like anger.
Do Global Ability Composites Differentially Predict Academic Achievement Across Gender

The present study examined whether global ability influences on reading, writing, and math achievement are generalizable across gender in children and adolescents in Grades 1 to 4 (n = 1,276), 5 to...
Case 40-2019: A 26-Year-Old Returning Traveler with Headache.

A Returning Traveler with Headache A 26-year-old woman presented to the hospital because of headache that developed during a winter vacation in Europe. Analysis of cerebrospinal fluid revealed 1422...
Preparation and Structural Characterization of ZrO2/CuOx/Cu(111) Inverse Model Catalysts

CO2 hydrogenation to methanol is regarded as a promising reaction to catalytically convert a major greenhouse gas (CO2) into a value-added product (methanol). In the current study, scanning tunneli...
50 Years of Power and the Influence of the National Economic Association: Black Economist Contributions to Economics Profession:

The National Economic Association (NEA) president addresses the membership body at the annual meeting. He reflects on the past presidents of the organization and their accomplishments. He then addr...
Persistence of Veronaea botryosa in marine and freshwater microcosms and susceptibility evaluation to three disinfectants

Abstract Veronaea botryosa is a dematiaceous fungus and the causative agent of systemic mycosis known as “fluid belly’, one of the most important emergent diseases in sturgeon aquaculture. A better understanding of the pathogenesis of the disease requires knowledge of environmental conditions that promote colonization, infection and disease. In this study, both traditional cultured-based methods and qPCR assays were used to evaluate V. botryosa persistence in water microcosms at two different temperatures and salinities, as different environmental factors can predispose poikilotherm animals to infection. Results indicate that V. botryosa persisted significantly greater in fresh than marine water microcosms (p-values
Bridging Social Capital: A Clinical Sociology Approach to Substance Use Intervention

This chapter describes the evolution of a clinical intervention developed by applying social capital theory to address a social problem. The idea for a social intervention for drug treatment purposes emerged from my desire to find solutions that focused on social situations, social environments, and network building. Research shows that people leaving treatment often relapsed due to a lack of bridging social capital (connection to new networks). Grounded in action-oriented goals, ethnographic research, client-centered approaches, community-based engagement, and a social capital framework, my development of the Social Recovery Initiative is an intervention process that mimics life with its successes, setbacks, and failures, but always with the goal of reducing the suffering of individuals through clinical sociology-informed action. The chapter also illustrates the evolving nature of a clinical intervention which includes adjusting to social trends in substance use and treatment.
Higher prevalence of Concomitant Hyperparathyroidism in African American Patients Undergoing Thyroid Surgery.

Abstract Background Hyperparathyroidism (HPT) occurs in about 1% of the general population. Previous studies have suggested that the incidence is higher in those patients with thyroid disease who are undergoing thyroid surgery. The study purpose was to examine the incidence of concomitant HPT in patients already undergoing a thyroid procedure and to identify risk factors. Materials and methods A prospective database of all patients who had thyroidectomy by the endocrine surgery team was reviewed between August 2012 and April 2020. Per institutional protocol, all patients having thyroid surgery were screened for concomitant hyperparathyroidism. ANOVA/T-Test and Chi-square were conducted to compare those with and without hyperparathyroidism. Results The median age was 43 and 79% were female. Of the 481 patients undergoing thyroidectomy, 31 (6%) had HPT. The mean preoperative calcium and parathyroid hormone levels were 10 ± 0 mg/dL and 67 ± 5 pg/mL, respectively. When comparing the groups, patients with concomitant HPT were older (53 ± 4 versus 42 ± 1 y, P = 0.005). African American race was a significant risk factor for concomitant HPT. While African Americans represented only 29% of those undergoing surgery, 58% of those with concomitant HPT were African American (P = 0.007). Conclusion In patients having thyroid surgery, concomitant HPT was present in 6% of the population, higher than estimated general population prevalence. While we understand that primary HPT incidence increases with age, to our knowledge, this is the first report to document that African Americans are at a higher risk for concomitant HPT with thyroid disease. Thus, routine screening for hyperparathyroidism in patients undergoing thyroid surgery, especially in vulnerable populations, such as the older and African American population, is beneficial.
Locoregional Recurrence in p16-Positive Oropharyngeal Squamous Cell Carcinoma After TORS.

OBJECTIVE To analyze the patterns, risk factors, and salvage outcomes for locoregional recurrences (LRR) after treatment with transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC). STUDY DESIGN Retrospective analysis of HPV+ OPSCC patients completing primary TORS, neck dissection, and NCCN-guideline-compliant adjuvant therapy at a single institution from 2007 to 2017. METHODS Features associated with LRR, detailed patterns of LRR, and outcomes of salvage therapy were analyzed. Disease-free survival (DFS) and overall survival (OS) were calculated for subgroups of patients receiving distinct adjuvant treatments. RESULTS Of 541 patients who completed guideline-indicated therapy, the estimated 5-year LRR rate was 4.5%. There were no identifiable clinical or pathologic features associated with LRR. Compared to patients not receiving adjuvant therapy, those who received indicated adjuvant radiation alone had a lower risk of LRR (HR 0.28, 95% CI [0.09-0.83], P = .023), but there was no difference in DFS (P = .21) and OS (P = .86) between adjuvant therapy groups. The 5-year OS for patients who developed LRR was 67.1% vs. 93.9% for those without LRR (P < .001). Patients who initially received adjuvant chemoradiation and those suffering local, in-field, and/or retropharyngeal node recurrences had decreased disease control after salvage therapy. CONCLUSION LRR rates are low for HPV+ OPSCCs completing TORS and guideline-compliant adjuvant therapy. Patients without indication for adjuvant therapy more often suffer LRR, but these recurrences are generally controllable by salvage therapy. Improved understanding of the patterns of recurrence most amenable to salvage therapy may guide treatment decisions, counseling, and adjuvant therapy de-escalation trials. LEVEL OF EVIDENCE 3 Laryngoscope, 131:E2865-E2873, 2021.
Video Games Have Never Been Global: Resituating Video Game Localization History

Mandiberg resituates the origin of video game localization from the late 1970s to the mid-twentieth century when Spacewar! was made local through practices of migration and adaptation. By resituating the origin of game localization this chapter problematizes typical industry and scholarly conceptualizations of game localization as just being a practice of multimodal semiotic alteration—where game industry professionals change linguistic, audio, visual, and ludic elements in order to make an otherwise global product more entertaining for a local audience. Instead, this chapter ultimately argues that game localization is an important practice that enables local texts’ fractured migrations, and in so doing game localization has silently contributed to a very particular twenty-first-century understanding of games as global.
Genetics and Genomics of Cottonseed Oil

The Gossypium genus consists of about 50 diploid species distributed in 8 genome groups (A–G and K) and 7 known tetraploid species derived from the fusion of the A and D genomes. Recently, the genomes of allotetraploid cotton and its progenitors have been sequenced. Cotton (Gossypium sp.) is grown primarily for fiber and to a lesser extent its oilseed. The phenolic compound, gossypol, needs to be removed to make cottonseed oil edible. The oil composition is approximately two-thirds unsaturated to one-third saturated fatty acids. Understanding the genetic network of oil production and genes related to oil traits is important to develop a healthy edible product to fight global food scarcity. Studies pertaining to structural variation in genome and positional cloning have increased with the availability of genome sequence, enormous -omics data, and current low-cost next-generation sequencing techniques. Further, with the availability of functional verification tools like RNA-Seq and gene editing via RNAi or CRISPR/CAS9, one can effectively decipher the function of gene/s and their role in complex biosynthesis process of oil production. Whole-genome sequencing will serve as a foundation in developing cotton germplasm that can improve cottonseed oil without disturbing lint yield components.
Nonnegative spatial factorization

Gaussian processes are widely used for the analysis of spatial data due to their nonparametric flexibility and ability to quantify uncertainty, and recently developed scalable approximations have facilitated application to massive datasets. For multivariate outcomes, linear models of coregionalization combine dimension reduction with spatial correlation. However, their real-valued latent factors and loadings are difficult to interpret because, unlike nonnegative models, they do not recover a parts-based representation. We present nonnegative spatial factorization (NSF), a spatially-aware probabilistic dimension reduction model that naturally encourages sparsity. We compare NSF to real-valued spatial factorizations such as MEFISTO and nonspatial dimension reduction methods using simulations and high-dimensional spatial transcriptomics data. NSF identifies generalizable spatial patterns of gene expression. Since not all patterns of gene expression are spatial, we also propose a hybrid extension of NSF that combines spatial and nonspatial components, enabling quantification of spatial importance for both observations and features. A TensorFlow implementation of NSF is available from this https URL .
A Poetics of Space: William Bronk’s Unhousing of the Universe

The exceptional American poet William Bronk’s life work spans more than three decades and consists of something over four hundred poems, published in nine slender volumes, the first not appearing until he was 37 years old.1 His collected and new poems were published to bicoastal praise in 1981 under the title Life Supports.2 It won for him the American Book Award for poetry in 1982. He has been the subject of near-ecstatic praise — when he has been reviewed at all. The Southwest Review likened him to one of the greatest philosophers who ever lived: “If Aristotle wrote meditative verse, it would sound like William Bronk, only not as good.”3 Yet this poet who can provoke such praise, and justly claim to be among America’s finest, is virtually unknown, even to those who count themselves serious readers of poetry.
Propagation and hormone production by human normal and malignant trophoblast in rats. I. Normal trophoblast from term human placentas in Millipore diffusion chambers.

Abstract Tissue from term and near-term human placentas was transplanted subcutaneously in Millipore diffusion chambers into adult and immature rats. Chambers were removed periodically, and their contents were studied microscopically in histologic sections and in whole mounts of the Millipore filter discs. Cells continued to proliferate within the chambers throughout the 4 week observation period. Human chorionic gonadotropin was produced in these chambers, as evidenced by gonadotropic effects in intact rats but not in ovariectomized female rats. The growth pattern and cell morphology showed differences in adult intact females and immature animals and ovariectomized animals, indicating that steroid hormones might influence proliferation and differentiation of these cells. In adult intact females in 3 weeks, multilayered epithelial cell cultures were achieved. In ovariectomized rats in 4 weeks, mainly monolayer cell cultures were obtained, where epithelial cells were arranged in small clusters between mesenchymal cells. In immature rats the proliferation rate was lower. After 2 weeks, large clusters of aggregated epithelial cells appeared surrounded by undifferentiated cells.
Nonlinear dynamics of the heartbeat: II. Subharmonic bifurcations of the cardiac interbeat interval in sinus node disease

Abstract Changing the coupling of electronic relaxation oscillators may be associated with the emergence of complex periodic behavior. The electrocardiographic record of a patient with the “sick sinus syndrome” demonstrated periodic behavior including subharmonic bifurcations in an attractor of his interbeat interval. Such nonlinear dynamics which may emerge from alterations in the coupling of oscillating pacemakers are not predicted by traditional models in cardiac electrophysiology. An understanding of the nonlinear behavior of physical and mathematical systems may generalize to pathophysiological processes.
Treatment of persistent endometrial hyperplasia with progestins.

Abstract 1. 1. The results of this study indicate a tendency for persistent endometrial hyperplasia to eventuate in cancer, which is related to the degree of atypicality of the initial mucosal alteration. 2. 2. Continuous treatment for 6 weeks with oral synthetic progestational agents was effective in the treatment of persistent adenomatous and atypical hyperplasia of the endometrium in all patients. A normal endometrium was maintained without additional therapy for more than 3 years.
Tandem Mass Spectrometry in the Newborn Screening Laboratory

A common definition of newborn screening is “the presumptive identification of unrecognized congenital disorders by the application of laboratory tests to an entire population.” Newborn screening began in the 1950s, when Robert Guthrie developed a screening test for the metabolic disorder phenylketonuria (PKU) based on measuring the level of the amino acid phenylalanine in dried, whole blood specimens collected on filter paper. The immediate success prompted similar, mandated “PKU Screening” in all states by the mid-1960s. Subsequently, test methods were developed for other congenital or metabolic disorders including hypothyroidism, maple syrup urine disease, galactosemia, and biotinidase. The paradigm involved a separate test procedure for each disorder. In the 1990s, that paradigm radically changed with the introduction of tandem mass spectrometry (MS/MS) into the newborn screening laboratory. Tandem mass spectrometry is a technique which uses 1 blood spot specimen to detect a multiple of potential disorders. MS/MS in the Laboratory The MS/MS technologies for routine use in high production laboratories (ie, newborn screening laboratories) have evolved from liquid chromatography/mass spectrometer (LCMS) systems. The 1970s and 1980s saw several advances in mass spectrometry instrumentation that included improved sample introduction techniques such as fast atom bombardment (FAB) and fast ion bombardment (FIB). Also the development in the 1980s of quadrupole (4 magnetic rods) units, linking them in series, and controlling the function (separation, fragmentation, and detection) of each unit led to today’s tandem mass spectrometry systems. Concurrently, experimentation with sample preparation techniques improved sensitivity and reproducibility by incorporating procedures based on the formation of
Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

Abstract Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical mullerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peri...
The fungus gardens of leaf‐cutter ants undergo a distinct physiological transition during biomass degradation

Leaf-cutter ants are dominant herbivores in ecosystems throughout the Neotropics. Rather than directly consuming the fresh foliar biomass they harvest, these ants use it to cultivate specialized fungus gardens. Although recent investigations have shed light on how plant biomass is degraded in fungus gardens, the cycling of nutrients that takes place in these specialized microbial ecosystems is still not well understood. Here, using metametabolomics and metaproteomics techniques, we examine the dynamics of nutrient turnover and biosynthesis in these gardens. Our results reveal that numerous free amino acids and sugars are depleted throughout the process of biomass degradation, indicating that easily accessible nutrients from plant material are readily consumed by microbes in these ecosystems. Accumulation of cellobiose and lignin derivatives near the end of the degradation process is consistent with previous findings of cellulases and laccases produced by Leucoagaricus gongylophorus, the fungus cultivated by leaf-cutter ants. Our results also suggest that ureides may be an important source of nitrogen in fungus gardens, especially during nitrogen-limiting conditions. No free arginine was detected in our metametabolomics experiments despite evidence that the host ants cannot produce this amino acid, suggesting that biosynthesis of this metabolite may be tightly regulated in the fungus garden. Thesemore » results provide new insights into the dynamics of nutrient cycling that underlie this important ant-fungus symbiosis.« less
Use of Behavioral Therapy and Imipramine A Case of Obsessive-Compulsive Neurosis with Severe Depression

A case of obsessive-compulsive neurosis with severe depression was treated by the combined use of (1) exposure and response prevention and (2) imipramine. While compulsive rituals disappeared after three weeks of behavioral treatment, obsessions and depression diminished only after the introduction of imipramine. The patient remained asymptomatic at a follow-up of six months. The relationship between depression and obsessive-compulsive symptoms, as well as the optimal order in which behavioral and pharmacological interventions are introduced, is discussed.
Ubiquitin-specific Protease 7 Regulates Nucleotide Excision Repair through Deubiquitinating XPC Protein and Preventing XPC Protein from Undergoing Ultraviolet Light-induced and VCP/p97 Protein-regulated Proteolysis

Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating xeroderma pigmentosum complementation group C (XPC) protein, a critical damage recognition factor that binds to helix-distorting DNA lesions and initiates NER. XPC is ubiquitinated during the early stage of NER of UV light-induced DNA lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon UV irradiation. We show that USP7 physically interacts with XPC in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytically inactive or interaction-defective mutants, reduces the ubiquitinated forms of XPC. Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in deubiquitination assays in vitro. We further show that valosin-containing protein (VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC. Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent, affects the repair of 6-4 photoproducts. Taken together, our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by preventing its VCP/p97-regulated proteolysis.
Purchasing's Internal Service Performance: Critical External and Internal Determinants

Summary This article examines the importance of purchasing's level of internal and external cooperation on its internal service performance and how leadership influences both internal and external cooperation. Results found that visionary leadership increases purchasing's internal and external cooperation, which in turn improves purchasing's internal service performance. The data were obtained from a survey of 2,500 Institute for Supply Management™ members, and were analyzed using structural equation modeling. The implications for practicing managers and for future research are discussed.
A deep low-velocity body under the Yellowstone caldera, Wyoming: Delineation using teleseismic P-wave residuals and tectonic interpretation

In previously published papers (Iyer, 1975; Iyer and Stewart, 1977; Iyer, 1979), evidence was presented for the presence of a large body of anomalous material, with compressional velocities considerably lower than normal from the surrounding rock, in the crust and upper mantle under Yellowstone National Park, Wyoming. In this paper, we give a detailed analysis of P-residual data from the 26-element telemetered seismic array and three groups of portable stations operated by the U.S. Geological Survey in the Yellowstone region. Using a variety of analytical techniques, we delineate the shape of the low-velocity body, determine the velocity structure inside the body, and interpret the nature of the material that constitutes the body. We will also outline some tectonic implications of our model. The spectacular surface geothermal phenomena for which Yellowstone is famous result from deep-seated volcanism. The volcanic evolution of Yellowstone is discussed by Christiansen and Blank (1972) and summarized by Eaton and others (1975). Briefly, the geothermal manifestations in Yellowstone are results of three cycles of Quaternary volcanism, each culminating in a devastating pyroclastic eruption and resulting in large collapse calderas and predominantly rhyolitic flows. The oldest cycle ended about 1.9 m.y. ago, forming a caldera from Island Park to, perhaps, the central part of the present Yellowstone caldera. The second cycle climaxed about 1.2 m.y. ago and was confined to the Island Park caldera. The third cycle began soon after the second and is responsible for the 75-by 45-km Yellowstone caldera as it is outlined today. This caldera is the result of a catastrophic eruption approximately 600,000 yr ago. The most recent episode of volcanism probably began about 150,000 yr ago in the western half of the caldera near Old Faithful geyser, and the youngest flows in Yellowstone (about 70,000 yr old) are probably associated with this episode.
Chemistry and Biology of the S-100 Protein

The S-100 protein is specific for the nervous system and, being present in all vertebrates, shows a high degree of stability of structure during evolution. In adult animals it is primarily localized to glial elements, although there is some evidence that a small proportion may be present in neuronal nuclei or their plasma membranes. During development it is synthesized rapidly at a relatively late period of differentiation of the nervous system. In glioma cell cultures there is a control mechanism that seems to involve some kind of signal at the external surface of the plasma membrane, possibly specific cell-cell contact, to stimulate S-100 synthesis. All of these biological properties of S-100 suggest that it is connected with some specific essential function that is common to the nervous system of all vertebrates. Several chemical properties of S-100 provide clues to this function. It is an unusually acidic and soluble protein and, in the absence of Ca2+, has no detectable hydrophobic regions accessible to solvent. It is capable of specifically binding Ca2+, a process that causes S-100 to undergo a conformational change that exposes a hydrophobic region to the solvent and stimulates binding of S-100 to membranes. The conformational change and the membrane-binding properties are reversible when Ca2+ is removed and are antagonized by monovalent cations such as K+ and Na+. These chemical properties suggest that S-100 may, as part of its function in the nervous system, be bound to some hydrophobic site, possibly a membrane, and that the extent of this binding is regulated by concentrations of Ca2+, K+ and Na+. If this is true, then it is important, as the next step in working out its function, to discover the exact site where S-100 binds in the nervous system.
Developing a Forward Collision Warning System Timing and Interface Approach by Placing Drivers in Realistic Rear-End Crash Situations

This paper describes studies which focused on defining when to present drivers with forward collision warning (FCW) alerts and how to present these alerts. In the project, a surrogate target methodology was developed which allowed the experiments to safely place inattentive drivers in a surprise, yet realistic rear-end crash scenario and observe their behavior. The results from the studies lend support for a deceleration-based crash alert timing approach that was developed. They also support coupling the visual and non-speech tone alert components that were evaluated for FCW system implementation.
Size-dependent DNA mobility in nanochannels

Nanofluidic slits are used to investigate surface interactions during electrophoresis between DNA molecules and channel walls. The channels have vertical dimensions of 19 and 70nm and contain no sieving matrix. Size-dependent mobility is observed for DNA in the 19nm channels. We present a model for double stranded DNA mobility in the nanochannels that accurately predicts the size dependence of the DNA mobility in the range of 2000–10000bp. Due to surface interactions, the DNA mobility in the nanochannels scales as N−1∕2. These results suggest that the notion of free solution DNA electrophoresis breaks down due to surface interactions in nanoscale environments.
Biosynthesis of adenosylmethionine from adenosylhomocysteine in Candida utilis

Abstract The mechanism of the biosynthesis of adenosylmethionine from adenosylhomocysteine in Candida utilis involves decomposition of adenosylhomocysteine and reutilization of the products for the synthesis of adenosylmethionine. This conclusion is based on data which showed that the addition of adenine, adenosine, or homocysteine to a medium containing labeled adenosylhomocysteine results in a dilution of the specific radioactivity of the resultant adenosylmethionine only if the unlabeled supplement corresponds to the labeled moiety of the adenosylhomocysteine. The data do not support the hypothesis of an exchange reaction between adenosylhomocysteine and its decomposition products because the specific radioactivity of adenosylmethionine increased as a function of time when labeled adenosylhomocysteine and its decomposition products were added to a culture of C. utilis. While methionine repressed 99.9% of the endogenous incorporation of sulfate into adenosylmethionine, adenosylhomocysteine repressed only 20% of this endogenous incorporation. Adenosylhomocysteine served as a sole source of sulfur, but sulfate repressed 80% of the incorporation of label from adenosyl[carboxy-14C]homocysteine into adenosylmethionine.
Inquiry Island: Social Responsibility and Ecological Sustainability in the Twenty-first Century

(2005). Inquiry Island: Social Responsibility and Ecological Sustainability in the Twenty-first Century. The Social Studies: Vol. 96, No. 3, pp. 127-132.
The Role of DNA Testing in Breast, Ovarian, and Colon Cancers

A proportion of cases of breast and colon cancers are caused by inherited mutations that confer a greatly increased susceptibility to malignancy. Certain clinical features may help distinguish patients with a genetic cause for their cancer from the larger number of patients with sporadic tumors. A thorough family medical history is also necessary to identify those at high risk for developing cancer. Many of the normal functions of these genes are understood, and mutation analysis for patients and their families is now available as a clinical service. Presymptomatic detection of mutations allows the patient to pursue preventive measures to reduce the probability of developing a malignancy. Evidence is now available that some prophylactic measures do reduce the incidence of cancer and reduce mortality in mutation carriers, and the standard of care is evolving rapidly. The essential elements necessary to provide accurate interpretations of molecular genetics test results to patients are described.
Manufactured hexaparental mice show that adults are derived from three embryonic cells.

Two female chimeric mice have been produced by aggregates of three genetically marked eight-cell embryos. All three embryonic genotypes are clearly expressed in the pigment pattern of the adults. These hexaparental mice together with their littermates demonstrate that, in the 64-celled blastocyst, at least three cells, and probably only three, are the source of all adult tissues.