cssi/SciSciGPT-SciSciNet huggingface dataset:
Parkinson disease and related disorders

Abstract Advances in genetic technology have revealed new information about the genetics of Parkinson disease (PD) and related disorders. While numerous genes have been associated with PD, a limited number have been proven to be causal. Mutations in three autosomal dominant genes (SNCA, LRRK2, and VPS35) and seven recessive genes (Parkin, PINK1, DJ1, FBXO7, DNAJC6, ATP13A2, and PLA2G6) are definitively pathogenic. Despite all these findings, the great majority of PD cases are not due to monogenic etiology. Many genetic risk factors have been linked to PD, of which GBA is recognized as the most important. This chapter reviews the current information about the genetics of PD and related disorders, including emerging evidence on genotype–phenotype correlations and biological mechanisms of disease. This information will assist in prognosis and identify pathways for treatment. Yet, because of the complexity of genetic information, genetic counseling is strongly recommended before and after testing.
Vitamin D metabolites, D3 and D2, and their independent associations with depression symptoms among adults in the United States.

Background: The two metabolites of vitamin D; serum 25-hydroxyvitamin D3 (25(OH)D3) and D2 (25(OH)D2), and their independent roles in mood regulation are unexplored. This study aims to examine 25(O...
Abstract 6237: Bone-targeted nanoparticle containing protein therapeutics as an effective delivery system for bone metastasis

Background: Protein drugs are one of the most promising new areas in drug research and development, however, great challenges are still faced in the drug delivery in vivo. Previously, we constructed bone targeted micelles for bone metastases. In order to address the issues of protein delivery in vivo and enhanced cancer bone metastasis treatment, we engineered and evaluated a bone-targeting nanoparticles by using metal organic framework nanoparticles (MOFs), bone-targeting agents (Alendronate) and hyaluronic acid (HA) as materials and a protein toxin as therapeutic. Methods: Alendronate (ALN) were conjugated to HA through PEG as linker and ALN-PEG-HA were obtained. Cytochrome C, as modle proteins, were caged in the MOFs (ZIF-8) by selfassembly of Zn2+ and organic ligands (2-methylimidazole) to form protein-encapsulated nanoparticles (ZIF8-CC). And ALN-PEG-HA were further decorated on the surface of ZIF8-CC nanoparticles via the coordination effect between its carboxyls and metal ions in ZIF-8 to result in active-targeting ALN-HA@ZIF8-CC nanopartilces. The materials and nanoparticles were synthesized and characterized by NMR, FT-IR, TEM, DLS, XRD, TGA and N2 adsorption−desorption isotherms analysis. The in vitro release profiles, stability and cytocompatibility were also studied. Results: The synthesis of ALN-PEG-HA was confirmed by 1H-NMR and FT-IR. TEM, XRD and DLS showed that ALN-HA@ZIF8-CC nanopartilces had been prepared, and the experiment of washing nanoparticles with SDS confirmed that protein was encapsulated in ZIF-8 instead of adsorbed on its surface. TGA and N2 absorption-degradation isotherms analysis also confirmed the formation of the crystal structure and porous structure, respectively. HA coated nanoparticles have good stability while ZIF8-CC were easy to aggregate. The results of in vitro release showed that the nanoparticles have acid sensitive release properties and excellent cell compatibility. In addition, In vitro bone fragment targeting experiment confirmed that nanoparticles have strong bone affinity. Conclusions: Our data demonstrated that bone-targeted protein drug-encapsulated MOFs were constructed. Citation Format: Yimin Niu, Cuicui Gao, Hongbin Yang, Qiang Huo, Andrew Wang, Ming Xu, Yang Liu. Bone-targeted nanoparticle containing protein therapeutics as an effective delivery system for bone metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6237.
The circulatory panopticon: Real names, rail infrastructure and Foucault's realist turn

Abstract This article examines the contemporary Chinese rail system as a circulatory panopticon: an apparatus that uses the “natural” movements of the population to render them legible and safe. The panoptic effect of rail space has emerged only recently. The Chinese state's introduction of the “real-name system” has made a state-legible identity an inextricable part of everyday life, and recent transformations in ticketing and station entry have placed it at the center of mobility practices as well. Synthesizing Foucault's apparatus of security with Karen Barad's realist conception of the apparatus, this article examines how the more-than-human elements of the rail system realize a panoptic assemblage out of the movements of passengers. Based on participant observation and interview data, this article examines three key elements of the rail system: the national identity card, the ticket, and the station entrance. Drawing on Barad's account of diffraction, I analyze how the particular material characteristics of these things both function to realize the circulatory panopticon and also to introduce novel discontinuities and fractures. This paper makes two contributions. First, it argues for a greater attention to the question of reality in Foucault's thinking: just as the art of government increasingly recognizes and calibrates itself against ‘reality,’ Foucault's analysis of governmentality becomes increasingly realist. Second, it shows how infrastructure is simultaneously a font of state power and a source of problems for the state—a contradiction deeply relevant in China today.
Deep significance clustering: a novel approach for identifying risk-stratified and predictive patient subgroups.

Objective Deep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate. Materials and methods Enabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively. Results Compared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes. Discussion DICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps. Conclusion DICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.
The YAP/TAZ antagonist, PTPN14, stabilizes SMAD4 through direct interactions in endothelial cells: Implications for Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular condition caused by germline heterozygous loss-of-function mutations of ENG, AVCRL1, and occasionally SMAD4, encoding components of TGF{beta}/BMP signaling. Telangiectases occur in most HHT patients, and pulmonary, visceral, or cerebral arteriovenous malformations (AVMs) occur in 20-50%, but our understanding of how HHT mutations disrupt down-stream signaling pathways causing clinical manifestations, and why some patients suffer more serious sequelae, is incomplete. We previously showed that genetic variation within PTPN14 at rs2936018 associates with presentation of PAVM in HHT patients. Here we show rs2936018 is a cis-eQTL for PTPN14, with lower expression of the HHT at-risk allele, and that in primary human endothelial cells, PTPN14 physically interacts with the transcription factor, SMAD4, protecting it from ubiquitylation to support higher SMAD4 expression levels. In a panel of 69 lung samples, we find Ptpn14 RNA expression correlates with markers of angiogenesis, lymphangiogenesis, cell-cell interaction, BMP signaling and rho kinase signaling, indicating preferential expression in endothelial cells. RNAScope in situ hybridization analysis and use of transgenic Ptpn14-reporter mice (Ptpn14.tm1(KOMP) Vlcg) show that Ptpn14 is predominantly but not exclusively expressed in lymphatic and vascular ECs of lung, heart and skin. In lung, Ptpn14, Acvrl1, Eng and SMAD4 expression are tightly correlated as well as with Flt1, Ece1, Sash1, and Mapk3k. Additionally, Ptpn14, Acvrl1, Eng and SMAD4 show strong expression correlation with components of G protein coupled receptor (GPCR) signaling pathways impacting rho kinase, Cdc42, a regulator of cell migration. We report, for the first time, that in primary human endothelial cells PTPN14 binds SMAD4, as demonstrated by co-immunoprecipitation studies and confirmed by proximity ligation assay. In the nucleus, PTPN14 stabilizes SMAD4, protecting it from ubiquitylation and turnover and potentiating basal transcriptional activity from BMP and TGF{beta} responsive reporters, whereas in the cytoplasm PTPN14 sequesters phospho-TAZ (pTAZ) leading to TAZ turnover. PTPN14 therefore provides a physical link supporting BMP/ALK-1/SMAD4 signaling while inhibiting YAP/TAZ signaling in ECs to regulate a balance between these two pathways to maintain vascular stability. Polymorphisms in PTPN14 may alter tonic BMP/ALK-1/SMAD4 and TGF{beta}/TGF{beta}RI/SMAD4 signaling to magnify ligand-mediated responses. In this way, genetic variation within PTPN14 may influence clinical outcomes of HHT through its action on SMAD4.
Relevance of Network Organization in SCN Clock Function

The bilateral suprachiasmatic nuclei (SCN) of the hypothalamus are the loci of a circadian pacemaker that coordinates rhythms throughout the body. The ~10,000 cells of each nucleus are organized into distinct core and shell divisions, each of which is comprised of clusters of various cell types. In dispersed cell preparations, individual SCN neurons express a wide range of circadian periods. In a slice preparation, there is a characteristic peak and trough time of clock gene expression in specific subregions, indicating that the networks into which cells are organized are an important aspect of SCN function. Understanding the relationship of individual cells to that of larger neuronal groupings and to brain circuits in which they participate is a problem of general interest in neuroscience. The SCN is an especially tractable system for such queries as the function of this nucleus is known, and circadian rhythms in activity of individual cells and in the SCN as a whole can each be tracked and associated with the overall behavior and physiology of the intact animal.
Primary care physicians' use of publicly reported quality data in hospital referral decisions.

BACKGROUND: Despite government investment in public reporting of hospital quality data, patients still rely on recommendations from their primary care physicians (PCPs). Little is known about how physicians make hospital referrals. OBJECTIVE: To characterize factors that influence PCPs' hospital referral choices. DESIGN: Web-based physician survey. PARTICIPANTS: PCPs affiliated with 3 Massachusetts hospitals. MAIN MEASURES: Physician demographics, familiarity with public reporting, and opinions about which factors would influence hospital referral decisions for an elderly patient with pneumonia. RESULTS: Of 194 PCPs who received invitations, 92 (47%) responded. Although 93% maintained admitting privileges, only 20% admitted patients. The following were considered “very” important in referral decisions: “familiarity with the hospital” (70%), “patient preference” (62%), and “admitting arrangements with a hospitalist group” (62%). “Publicly available quality measures” were “not at all” important to 42%. Only 61% were aware of hospital quality reporting; 16% were familiar with Hospital Compare, a Centers for Medicare and Medicaid Services (CMS) Web site. No physicians reported ever using quality information to make a referral decision or discussing it with patients. No physician factors were associated with awareness of publicly reported data. PCPs identified the following factors as being “very” important in determining the quality of pneumonia care: antibiotics within 6 hours of arrival (66%), appropriate initial antibiotic (63%), and blood cultures performed prior to the administration of antibiotics (51%). CONCLUSIONS: Although PCPs most valued the information available through Hospital Compare, only 16% were aware of it, and none used publicly reported quality data in referral decisions. Medicare and high-performing hospitals should consider marketing Hospital Compare to PCPs. Journal of Hospital Medicine 2012;. © 2012 Society of Hospital Medicine
A Mathematical Analysis of Concomitant Virus Replication and Heat Inactivation

A mathematical analysis of virus production with accompanying heat inactivation, from which the rate of virus release and total virus production are readily calculated, is presented. Applications of this analysis for Sindbis and Chikungunya viruses are discussed.
Negative regulator of sigma G-controlled gene expression in stationary-phase Bacillus subtilis.

Abstract In some media, Bacillus subtilis can maintain a prolonged stationary growth phase; however, in other media, nutrient depletion triggers a complex differentiation that culminates in production of a dormant endospore. This differentiation requires the expression of many genes. We found that during the stationary phase in media in which the cells do not form endospores and do not normally express these sporulation-essential genes, a recessive mutation in spoIIAB caused increased transcription of a set of genes essential for sporulation. Evidently, the wild-type product of spoIIAB acts during the stationary phase to prevent expression of additional sporulation-specific genes.
False reactive nonstress tests in postterm pregnancies

One hundred twenty-five postterm patients with reactive nonstress tests (NSTs) were studied between January, 1978, and September, 1979. Ten poor outcomes occurred for a false reactive rate of 8%. Included were four antepartum deaths, one neonatal death, one brain-damaged infant, and four cases of fetal distress on admission. The NST was misleading by giving false reassurance of fetal well-being. The major mechanism causing acute fetal distress was cord compression, which frequently occurred with uteroplacental insufficiency, but occasionally without it. The oxytocin challenge test (OCT) was useful in unmasking problems of cord compression and may be a more sensitive indicator of fetal well-being and distress in the postterm patient.
Medical Homes for At-Risk Children: Parental Reports of Clinician-Parent Relationships, Anticipatory Guidance, and Behavior Changes

Background. Family-centeredness, compassion, and trust are 3 attributes of the clinician-parent relationship in the medical home. Among adults, these attributes are associated with patients9 adherence to clinicians9 advice. Objectives. The objectives were (1) to measure medical home attributes related to the clinician-parent relationship, (2) to measure provision of anticipatory guidance regarding injury and illness prevention, (3) to relate anticipatory guidance to parental behavior changes, and (4) to relate medical home attributes to anticipatory guidance and parental behavior changes. Methods. A cross-sectional study of data collected among at-risk families when children were 1 year of age, in a randomized, controlled trial of a home-visiting program to prevent child abuse and neglect, was performed. Modified subscales of the Primary Care Assessment Survey were used to measure parental ratings of clinicians9 family-centeredness, compassion, and trust. Parental reports of provision of anticipatory guidance regarding injury and illness prevention topics (smoke alarms, infant walkers, car seats, hot water temperature, stair guards, sunscreen, firearm safety, and bottle propping) and behavior changes were recorded. Results. Of the 564 mothers interviewed when their children were 1 year of age, 402 (71%) had a primary care provider and had complete data for anticipatory guidance items. By definition, poverty, partner violence, poor maternal mental health, and maternal substance abuse were common in the study sample. Maternal ratings of clinicians9 family-centeredness, compassion, and trust were fairly high but ranged widely and varied among population subgroups. Families reported anticipatory guidance for a mean of 4.6 ± 2.2 topics relevant for discussion. Each medical home attribute was positively associated with parental reports of completeness of anticipatory guidance, ie, family-centeredness (β = .026, SE = .004), compassion (β = .019, SE = .005), and trust (β = .016, SE = .005). Parents9 perceptions of behavior changes were positively associated with trust (β = .018, SE = .006). Analyses were adjusted for potential confounding by randomized, controlled trial group assignment, receipt of ≥5 well-child visits, and baseline attributes. Conclusions. Among at-risk families, we found an association between parental ratings of the medical home and parental reports of the completeness of anticipatory guidance regarding selected injury and illness prevention topics. Parents9 trust of the clinician was associated with parent-reported behavior changes for discussed topics.
Genetic Algorithm Difficulty and the Modality of Fitness Landscapes

Abstract We assume that the modality (i.e., number of local optima) of a fitness landscape is related to the difficulty of finding the best point on that landscape by evolutionary computation (e.g., hillclimbers and genetic algorithms (GAs)). We first examine the limits of modality by constructing a unimodal function and a maximally multimodal function. At such extremes our intuition breaks down. A fitness landscape consisting entirely of a single hill leading to the global optimum proves to be harder for hillclimbers than GAs. A provably maximally multimodal function, in which half the points in the search space are local optima, can be easier than the unimodal, single hill problem for both hillclimbers and GAs. Exploring the more realistic intermediate range between the extremes of modality, we construct local optima with varying degrees of “attraction” to our evolutionary algorithms. Most work on optima and their basins of attraction has focused on hills and hillclimbers, while some research has explored attraction for the GA's crossover operator. We extend the latter results by defining and implementing maximal partial deception in problems with k arbitrarily placed global optima. This allows us to create functions, such as the minimum distance function f mdG , with k isolated global optima and multiple local optima attractive to both crossover and hillclimbers. The function f mdG seems to be a powerful new tool for generalizing deception and relating hillclimbers (and Hamming space) to GAs and crossover.
Optimal doping profile for laser-induced diode linking in wafer-scale-integration

The optimum doping profile for the minimum resistance of a laser-induced diode link is studied by using the calculus of variations and the method of Lagrange multipliers. It is shown that the uniform distribution of the carriers in the link gives the minimum link resistance. It is also found that, in a practical laser-induced diode link with Gaussian carrier distribution, the resultant link resistance can approach the optimum resistance value if the carrier diffusion time is chosen properly. If the laser pulse is too short, the link resistance can be much larger than the optimum value. On the other hand, if the duration is too long, the link resistance does not change significantly. >
α,α‐Dimethyl Cyclopropanemethanamine

[172947-13-6] C6H13N (MW 99.2) InChI = 1S/C6H13N/c1-6(2,7)5-3-4-5/h5H,3-4,7H2,1-2H3 InChIKey = OOXIEUXBOSSXJM-UHFFFAOYSA-N (reagent for amide protection1) Alternate Name: dimethylcyclopropylmethylamine, dimethylcyclopropylcarbinylamine, Dmcp-NH2. Physical Data: hydrochloride, mp 223–225 °C (decomposes),2 p-toluenesulfonic acid salt, mp 168–170 °C.1 Solubility: soluble in water and common organic solvents. Analysis of Reagent Purity: 1H NMR, elemental analysis. Preparative Methods: the title reagent can be prepared by hydrolysis of dimethylcyclopropylcarbinyl-N-(dimethylcyclopropylcarbinyl) carbamate by means of concentrated hydrochloric acid2 or, more conveniently, by reduction of the azide via LiAlH4 and conversion to the p-toluenesulfonic acid salt.1 Handling, Storage, and Precautions: stored in its salt form, the reagent is relatively safe and stable.
Why the C-statistic is not informative to evaluate early warning scores and what metrics to use

Metrics typically used to report the performance of an early warning score (EWS), such as the area under the receiver operator characteristic curve or C-statistic, are not useful for pre-implementation analyses. Because physiological deterioration has an extremely low prevalence of 0.02 per patient-day, these metrics can be misleading. We discuss the statistical reasoning behind this statement and present a novel alternative metric more adequate to operationalize an EWS. We suggest that pre-implementation evaluation of EWSs should include at least two metrics: sensitivity; and either the positive predictive value, number needed to evaluate, or estimated rate of alerts. We also argue the importance of reporting each individual cutoff value.
Methotrexate inhibits NF-κB activity via long intergenic (noncoding) RNA-p21 induction

Objective. We sought to determine interrelationships among expression of lincRNA-p21, a long intergenic non-coding RNA, activity of NF-κB, and responses to methotrexate in rheumatoid arthritis (RA) by analyzing patient samples and cell culture models.
Neutron-induced luminescence and activation in neutron shielding and scintillation detection materials at cryogenic temperatures

Abstract The neutron-induced low temperature (below 5 K) luminescence of neutron shielding and scintillation detection materials is studied. Strong luminescence is observed for the neutron absorbing materials boron nitride (BN) and lithium fluoride (LiF). A measurable, but substantially smaller luminescence is observed from boron oxide (B2O3). An upper bound of 10−3 was determined for the fraction of the luminescence due to time-correlated multiphoton events in the BN. Other materials tested – boron carbide (B4C), polymethyl methacrylate (PMMA or acrylic), expanded polytetrafluoroethylene (PTFE) with an evaporated coating of the downconverting fluor tetraphenyl butadiene (TPB) and a boron/lithium loaded glass – displayed no detectable luminescence. The boron/lithium loaded glass was determined to activate, by the secondary reaction 16O(T,n)18F, with the triton produced in the neutron capture reaction 6Li(n,T)4He.
Assessing and overcoming situational obstacles to dietary adherence in adolescents with IDDM

Purpose: To develop and evaluate a tool for assessing selected aspects of dietary adherence in adolescents with diabetes mellitus (IDDM). Methods: The Situational Obstacles to Dietary Adherence Questionnaire (SODA) is a 30-item inventory that yields a total self-efficacy score and scales that measure cognitive and behavioral coping strategies. Alternative forms of the SODA were administered at the beginning and end of a summer camp for youngsters with IDDM in order to obtain evidence for its reliability and validity, and to evaluate the impact of an educational intervention. The program consisted of two 50-minute small group sessions intended to help adolescents with IDDM improve their ability to cope with challenging dietary situations. Using the method of anchored instruction, the campers first viewed a video about a teenager with diabetes who faces common situations that make diabetes self-management difficult. Group problem-solving sessions led by a registered dietitian were used to help campers learn more effective ways to solve dietary problems. Results and conclusions: Results suggested that the SODA has reasonable reliability and validity. In addition, anchored instruction improved dietary self-efficacy and changed young adolescents' estimates of how often they would use selected cognitive and behavioral strategies to solve dietary problems.
Topoisomerase II inhibitors induce DNA double-strand breaks at a specific site within the AML1 locus

Treatment-related acute myeloid leukemia (t-AML) following successful therapy of a primary malignancy has been recognized with increasing frequency among cancer survivors over the past several years. Many of these t-AML cases are associated with the use of intensive chemotherapy regimens that employ one or more agents which target eukaryotic topoisomerase II (topo II), and demonstrate non-random chromosomal translocations involving either the MLL (ALL-1, HRX) gene at 11q23 or the AML1 gene at 21q22. Although many investigators have speculated that these translocations are induced by the therapeutic use of topo II inhibitors, the molecular sequence of events by which topo II inhibitors might induce a chromosomal translocation are not well understood. We describe here the reproducible induction of highly specific, double-strand DNA cleavage at a specific site within the AML1 locus by topo II inhibitors. This DNA cleavage, which maps to a region of the AML1 locus frequently disrupted by chromosomal translocations, can be induced in several cell lines, with multiple different topo II inhibitors, indicating that this phenomenon is not restricted to a specific cell type or specific topo II inhibitor. It is conceivable that site-specific double-strand DNA cleavage within the AML1 locus induced by topo II inhibitors represents the initial molecular event leading to a chromosomal translocation and t-AML.
On Chromospheric Heating Mechanisms of “Basal Flux” Stars*

Several pieces of evidence have been pieced together over recent years to support the notion that the chromospheric emission measured from stars with convection zones results in part from the upward propagation and dissipation of acoustic waves. One argument, based on a statistical analysis of available UV data of such stars across the H-R diagram, suggests the presence of an omnipresent "basal" level of chromospheric heating, which has been postulated as resulting from nonlinear acoustic wave heating. However, with few exceptions, no studies have been made that test more directly the intrinsically dynamic nature of this shock-heating mechanism. Therefore, in order to search for more direct signatures of such upward-propagating shock waves in lines of C II, we examined Goddard High-Resolution Spectrograph spectra of several evolved stars that have "basal" levels of activity. No evidence is found to support the presence of such waves as a dominant component of the heating mechanism. Instead, behavior reminiscent of the solar transition region is seen, suggesting a magnetic heating mechanism for these stars. We conclude that upward-propagating shock waves do not dominate the observed radiative losses from chromospheres of stars exhibiting typical "basal" behavior, and we suggest that the nonmagnetic origin of the basal components of all convective stars must be called into question. New solar data from the SUMER instrument on SOHO also suggest problems with the acoustic-wave interpretation, although further work is warranted. In the course of this work, we also found a simple explanation for previously noted discrepancies between calculated and observed ratios of C II lines in the spectrum of α Ori.
Formation process and preservation of a natural electronic archive

This paper presents a case of formation process study and preservation of the digital archive of a private organization. The archive was created in the late 1980's and maintained until 2005. The study was prompted by the archive's creators concerns about the resources involved, and the need to preserve their electronic records and systems vis-a-vis the presence of the signed and sealed paper documents. The approach used to study the digital archive was to consider it akin to an archaeological site. A formation process study of the archive's components was conducted using interview methods; primary and secondary sources; and metadata extraction, file viewers, and file transformation software. The study revealed information about the technical and social contexts involved in the archives' formation, and how its creators used it and valued it over time. The results informed the design of a preservation strategy aimed at maintaining the archives' integrity and authenticity and continuing documentation of its evolution. The attributes characterizing the archive led to the development of the concept of natural electronic archive.
Spermatogenesis and Germ Cell Transgene Expression in Xenografted Bovine Testicular Tissue

The present study was conducted to evaluate the development of spermatogenesis and utility of using electroporation to stably transfect germ cells with the β-galactosidase gene in neonatal bovine testicular tissue ectopically xenografted onto the backs of recipient nude mice. Bull testicular tissue from 4-wk donor calves, which contains a germ cell population consisting solely of gonocytes or undifferentiated spermatogonia, was grafted onto the backs of castrated adult recipient nude mice. Testicular grafts significantly increased in weight throughout the grafting period and the timing of germ cell differentiation in grafted tissue was consistent with postnatal testis development in vivo relative to the bull. Seminiferous tubule diameter also significantly increased with advancing time after grafting. At 1 wk after grafting, gonocytes in the seminiferous cords completed migration to the basement membrane and differentiated germ cell types could be observed 24 wk after grafting. The presence of elongating spermatids at 24 wk confirmed that germ cell differentiation occurred in the bovine tissue. Leydig cells in the grafted bovine tissue were also capable of producing testosterone in the castrated recipient mice from 4 wk to 24 wk after grafting at concentrations that were similar to levels in intact, nongrafted control mice. The testicular tissue that had been electroporated with a β-galactosidase expression vector showed tubule-specific transgene expression 24 wk after grafting. Histological analysis showed that transgene expression was present in both Sertoli and differentiated germ cells but not in interstitial cells. The system reported here has the potential to be used for generation of transgenic bovine spermatozoa.
Gastrospirillum Hominis—Associated Chronic Active Gastritis

A 16-year-old Caucasian male presented with nausea, vomiting, and abdominal pain. Endoscopy revealed erythematous antral mucosa with four discrete gastric ulcers. Biopsies showed multiple spiral organisms, 4-6 microns in length, lying in the mucous layer on the surface. The organisms were strongly Giemsa positive and weakly CLOtest positive. They did not stain with Warthin-Starry silver or Gram-Weigert stains. Electron microscopy revealed fragments of Gastrospirillum hominis, with its characteristic spiral shape and length of 4 microns in the plane of section. We believe that this is one of the first reported pediatric cases in North America.
Evidence for right-lateral transfer faulting accommodating en echelon Miocene extension, Mojave Desert, California

In the southwestern United States, two early Miocene extensional terranes, one along the Colorado River trough and the other in the central Mojave Desert, have been inferred to be part of an en echelon rift system linked by a ductile detachment at depth. Evidence from pre-Tertiary surface geology in the central and western Mojave Desert suggests that a zone of east- to northeast-trending right-lateral strike-slip faulting may have transferred extension between these two areas. These data include the apparent offsets of the Late Jurassic age Independence dike swarm, a Middle to Late Jurassic age deformation belt, Triassic(?)-Jurassic volcanic rocks, Lower Triassic sedimentary rocks, and late Paleozoic age stratigraphic and tectonic elements. This inferred fault zone probably served as the main shallow-crustal kinematic link between extension in the central Mojave Desert and in the Colorado River trough.
Thrombin is a stimulator of retinal pigment epithelial cell proliferation

Abstract Two preparations of bovine thrombin were found to stimulate DNA synthesis in cultured human retinal pigment epithelial cells. DNA synthesis was assessed by both [3H]thymidine incorporation into TCA precipitable material and nuclear labeling with [3H]thymidine. Cultures grown in the presence of thrombin for 48 hr showed a significant increase in cell number. When the concentrations of the two thrombin preparations were normalized for clotting activity, they had almost identical dose-response curves and both caused a tenfold maximal stimulation of [3H]thymidine incorporation. The EC50 for the preparation with higher specific activity was 20 ng ml−1. Hirudin, a specific high affinity inhibitor of thrombin, completely blocked the mitogenic effect. When a maximally effective concentration of thrombin was used in combination with maximally effective concentrations of other growth factors (insulin, acidic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor), they were found to be strongly synergistic in stimulating DNA synthesis. These data suggest that thrombin may act as an endocrine mediator of retinal pigment epithelial cell proliferation and participate in normal and exaggerated ocular wound healing.
Pulmonary metastasis from liposarcoma: A clinicopathologic and immunohistochemical study of 24 cases

A review of the histologic features of pulmonary metastasis and clinical implications of liposarcoma (LS) is given for 24 cases (8 each) of the 3 types of LS: myxoid LS (ML), pleomorphic LS (PL), and dedifferentiated LS (DDL). Most patients were men. Metastatic ML and PL were distributed almost equally among the lung lobes, whereas DDL was more common in the left lower lobe. The metastatic MLs had variable cellularity ranging from singly scattered cells in a hyalinized stroma (treatment-related effect) to hypercellular ML. Most PLs (6/8) were nonlipogenic and resembled an undifferentiated pleomorphic sarcoma. All metastatic DDLs had high-grade histologic features and were predictably nonlipogenic. After pulmonary metastasectomy, 2 patients with ML and 1 with PL were disease-free. The other 6 patients with ML, 7 with PL, and all with DDL had progressive disease. The morphologic features of LS metastatic to the lungs seem diverse but within the spectrum of the histologic type expected from the primary tumor. Overall, the general trend for these LS subsets is progressive disease, metastatic disease for ML and PL with a much shorter interval for PL, and metastatic disease and local recurrence for DDL.
BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment.

The accurate segregation of chromosomes in mitosis requires the stable attachment of microtubules to kinetochores. The details of this complex and dynamic process are poorly understood. In this study, we report the interaction of a kinetochore-associated mitotic checkpoint kinase, BubR1, with two microtubule plus end–associated proteins, adenomatous polyposis coli (APC) and EB1, providing a potential link in stable kinetochore microtubule attachment. Using immunodepletion from and antibody addition to Xenopus laevis egg extracts, we show that BubR1 and its kinase activity are essential for positioning chromosomes at the metaphase plate. BubR1 associates with APC and EB1 in egg extracts, and the complex formation is necessary for metaphase chromosome alignment. Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules. These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.
Regulation of L-pyruvate kinase activity by insulin and glycolytic intermediates.

Summary The presence of insulin and various carbohydrates in long term cultures of hepatocytes was studied to examine the mechanism by which insulin and glycolytic metabolites regulate L-pyruvate kinase activity. When hepatocytes were isolated from a control rat and cultured in the presence of insulin, a constant level of enzyme activity (16 EU/mg DNA) was maintained for 12 days. The L-pyruvate kinase activity in hepatocytes from refed rats initially was elevated (45 EU/mg DNA) and decreased to control values by the 5th day in culture. Cells isolated from a fasted rat initially contained a low level of L-pyruvate kinase activity (5 EU/mg DNA) which increased to control values by the 8th day in culture. The enzyme activity was 5 EU/mg DNA when control cells were cultured for 4 days in medium containing either glucose, glycerol or fructose without insulin; 10 EU/mg DNA in medium containing galactose and insulin but without glucose, glycerol or fructose; and 20 EU/mg DNA in medium containing both insulin and either glucose, glycerol or fructose. It is suggested that insulin is essential for the induction and maintainance of L-pyruvate kinase activity, that carbohydrates in the absence of insulin are unable to maintain the enzyme activity in cultures of hepatocytes, and that insulin and glycolytic metabolites may act synergistically to increase the activity of L-pyruvate kinase by increasing the synthesis of the enyzme.
Effect of carbon nanofiber heat treatment on physical properties of polymeric nanocomposites: part I

The definition of a nanocomposite material has broadened significantly to encompass a large variety of systems made of dissimilar components and mixed at the nanometer scale. The properties of nanocomposite materials also depend on the morphology, crystallinity, and interfacial characteristics of the individual constituents. In the current work, vapor-grown carbon nanofibers were subjected to varying heat-treatment temperatures. The strength of adhesion between the nanofiber and an epoxy (thermoset) matrix was characterized by the flexural strength and modulus. Heat treatment to 1800°C demonstrated maximum improvement in mechanical properties over that of the neat resin, while heat-treatment to higher temperatures demonstrated a slight decrease in mechanical properties likely due to the elimination of potential bonding sites caused by the elimination of the truncated edges of the graphene layers. Both the electrical and thermal properties of the resulting nanocomposites increased in conjunction with the increasing heat-treatment temperature.
Modeling hazard functions in families

A genetic frailty model is presented for censored age of onset data in nuclear families where individuals carrying a genetic susceptibility gene have an increased risk of becoming affected. We use maximum likelihood via the EM algorithm to estimate the genetic relative risk and the allele frequency under a dominant susceptibility type and a proportional hazards model. When sampling is from a disease registry, likelihood corrections are necessary for reducing bias in the parameter estimates. In these biased samples, the full conditional likelihood is approximated by a likelihood conditional on the proband's age of onset. For unbiased samples, simulations show the distributions of the estimates are similar under both a semiparametric and the correctly specified parametric likelihoods. For biased samples, simulations under the approximate conditional likelihood show the median estimates of the allele frequency and genetic relative risk tend to under- and overestimate, respectively, the true values; however, the approximation is better for rarer allele frequencies (0.0033 vs. 0.01). In practice, large samples or more complex ascertainment corrections are recommended. Using the approximate conditional likelihood on familial breast cancer onset data collected as part of a case-control study at the Fred Hutchinson Cancer Research Center in Seattle, Washington, we estimate an allele frequency of 0.0009 (approximate 95% CI 0.0006-0.002) and a genetic relative risk of 104 (approximate 95% CI 55-181).
Collapse Features and Silica Plugs near Cameron, Arizona

Silica plugs and collapse features occur south and west of the Cameron mining district. The plugs are sharp, dark cones which resist erosion and rise up to 100 feet above the surrounding Plateau strata. They are believed to have been formed by the precipitation of silica from hypogene solutions ascending along vertical conduits. Silica-cemented cores contain breccia fragments, conglomerate pebbles, indurated shale fragments, and coarse sand grains. Collapse features in association with uranium mineralization contain silicified breccia, bleached strata, and argillic alteration. These are attributed to the activity of rising thermal solutions which caused localized collapse in the Permian Kaibab Limestone and overlying Triassic formations by the removal of carbonates. Examination of the mineralization associated with the plugs and collapse features indicates the introduction of U, Cu, S, P, Si, Fe, and Mn. Most of the features are radioactive. Both types of structures are believed related to centers of hydrothermal activity and suggest an original hypogene source of uranium.
Regulation of frequency of luteinizing hormone pulses by magnitude of acute change in circulating concentration of progesterone of female cattle

The hypothesis was the greater the magnitude of acute increase in circulating concentration of progesterone of female cattle, the greater the acute inhibitory effect on frequency of pulsatile LH release. From Day 0 to 4 of the treatment period, females without functional corpora lutea were treated with varying doses of progesterone to result in varying concentrations of progesterone within the typical physiological range in blood. From Day 4 to 7, cattle were treated with a single dose of progesterone to achieve a similar circulating concentration of progesterone among all females in the study. Therefore, from Day 0 to 4 relative to Day 4 to 7 of the treatment period, females had a: (1) large (3.1 ng/ml), (2) moderate (2.5 ng/ml), or (3) small (0.5 ng/ml) increase in concentration of progesterone in blood. Frequency of LH pulses was greater (P <0.10) in females with the greatest magnitude of change in concentration of progesterone during the first 24 h following the change in concentration as compared with females with the moderate or small of change in concentration of progesterone suggesting our working hypothesis should be rejected. The greater the magnitude of acute change in concentration of progesterone, however, the longer time required for re-initiation of release of LH pulses of the amplitude of pulses that preceded the change in concentration of progesterone.
Physically based dispersion curve feature analysis in the NDE of composites

The oblique incidence of longitudinal waves onto a structure generates different wave modes, each one having unique physical characteristics and hence a different degree of sensitivity to the state of the material. The primary focus, thus far, has been to generate acoustical models and to confirm their integrity. In this paper, an attempt is being made to use the mechanics of plate waves with specific emphasis on solving the anomaly estimation problem for composite materials and to device inspection guidelines using a feature based analysis. Theoretical models for anomalies such as porosity, fiber volume fraction, fiber orientation defects, and hybrid ply layup effects, are all built into an effective material stiffness constants model. The results are then coupled to a generalized plate wave dispersion algorithm. Thus material properties with different anomaly content could be generated and their corresponding plate wave dispersion diagrams computed. Several new features from these dispersion curves were defined and shown to correlate quantitatively with anomaly content. The analytical studies were further supplemented with strong experimental observations, thus defining several new viable features. The promising features could improve anomaly presence prediction because they show an increased the sensitivity to subtle variations in material degradation.
Use of Protein Knobs to Characterize the Position of Conserved α-Subunit Regions in Lutropin Receptor Complexes

Efforts to identify the manner in which human choriogonadotropin (hCG) contacts lutropin receptors (LHR) have been stymied by the complex structure of the hormone and the likelihood that it contacts the receptor at multiple sites. During studies of hCG assembly in mammalian cells, we found that addition of a cysteine to the long disordered beta-subunit COOH terminus (betaCT) enabled it to become cross-linked by a disulfide to cysteines that are substituted for residues in loop alpha2 or in the alpha-subunit COOH terminus (alphaCT). This created a "knob" on the alpha-subunit at the location of the cysteine. Knobs of various sizes and charges were useful for probing surfaces of the alpha-subunit thought previously to contact the LHR. Attachment of the betaCT to residues in loop alpha2 facing loops beta1 and beta3 reduced hormone activity only a few fold revealing that this surface does not participate in essential high affinity receptor contacts, a finding inconsistent with our earlier view of the hCG-LHR complex. In contrast, this approach showed that the opposite surface of loop alpha2 appeared to be nearer the receptor interface. Although attachment of knobs to portions of the alphaCT reduced hormone activity substantially, this finding was difficult to interpret. As discussed, this procedure should be adapted readily to other proteins and may facilitate the introduction of fluorophores, enzymes, or other reagents at specific sites on protein surfaces. It may also permit one to cross-link proteins or to obscure specific protein surfaces during the development of "Trojan Horse" therapeutics.
On passive inference attacks against physical-layer key extraction?

Physical-layer key extraction techniques attempt to derive a shared symmetric cryptographic key between two wireless devices based on the principle of channel reciprocity, which states that the signal envelope between two communicating devices is strongly correlated. A key security assumption made in previous literature is that the signal envelope observed by an adversary located greater than a half-wavelength away is uncorrelated with that shared between the two communicating devices; however, this assumption has yet to be rigorously evaluated in previous work on physical-layer key extraction. In this paper, we present an experimental analysis that examines the relationship between the channel measurements used to extract a symmetric key between two devices and those observed by one or more distantly located passive adversaries. We find that, contrary to previous assumptions, there does exist a strong correlation in measurements observed by adversaries located significantly greater than a half-wavelength away from two communicating wireless devices. Further, we provide initial results that show the extent to which the adversary is able to leverage such correlations to infer portions of the key extracted between two devices using previously published physical-layer key extraction techniques.