cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of HIV on the Tumor Microenvironment.

Oncomodulatory viruses can affect the tumor microenvironment (TME) by triggering inflammation, suppressing apoptosis, initiating angiogenesis, altering tumor metabolism, and stimulating tumor cell signaling pathways, leading to tumor growth, proliferation, and invasion. The higher incidence of malignancies among people with HIV (PWH), despite the widespread use of antiretroviral therapy (ART), suggests a more complex relation than HIV-associated immune deregulation. Viral cooperation can have synergistic effect on tumorigenesis. The most relevant oncogenes involved in viral cooperation include the HIV-1-related Tat and Vpu genes, EBV LMP-1 and EBNA-2 genes, and Kaposi’s sarcoma herpesvirus (KSHV) KIE2, Rta, and LANA genes. The TME in HIV-related malignancies is highly angiogenic and characterized by high microvessel density compared to sporadic cases. Tat protein, found in patients with HIV infection regardless of their immune status, has been widely implicated in the increased angiogenesis and has been a target of interest for therapeutic strategies. Similarly, HIV-1 matrix protein p17 can be detected in the plasma and tissues of PWH, including those treated with ART. Studies have found that p17 can cause dysregulation of the biological activity of different immune cells, is involved in aberrant angiogenesis, and exhibits an IL8 chemokine activity, activating multiple intracellular signaling pathways, promoting angiogenic responses in endothelial cells, and forming capillary like structures. In addition, several studies have demonstrated difference in the cellular immune components within the TME in patients with or without HIV infection, as well as cases in pre- and post-ART era. In this chapter, we review the existing literature about the role tumor microenvironment plays in the pathogenesis of HIV-related malignancies. Understanding the functions of each component of the TME and determining how these cellular and noncellular components contribute to tumorigenesis will impact the advancement of interventions and treatment in clinical oncology among PWH.
Haemophilus influenzae Type B

Prior to widespread use of vaccine, Haemophilus influenzae type b (Hib) was the leading cause of bacteremia, pneumonia, and meningitis among US infants and young children. Invasive Hib disease was estimated to infect 1 in 200 children younger than 5 years of age in the USA. Hib vaccines were introduced into the national pediatric immunization schedule in the late 1980s. Almost immediately following their widespread use, there was a dramatic decline in disease incidence. While developed countries were early adopters of the conjugate Hib vaccine, developing countries were slower to do so for a variety of reasons, including but not limited to the perceived lack of disease burden to justify adding another vaccine to the schedule and the associated financial constraints of being able to do so. The African nation of Gambia, however, introduced Hib vaccine in 1997, being among the first African countries to routinely immunize their children against this infection. Prior to vaccine initiation, the incidence of Hib meningitis in The Gambia was 297 per 100,000 children younger than 1 year of age and 60 per 100,000 children younger than 5 years of age. Only 55% of infected children fully recovered (Bijlmer et al., J Infect Dis 161:1210–5, 1990). Although the incidence of Hib meningitis in The Gambia was similar to that in the USA, Gambian children were significantly more likely to have devastating outcomes (Bijlmer et al., J Infect Dis 161:1210–5, 1990). Five years after introduction of conjugate Hib vaccine in The Gambia, the incidence of Hib meningitis decreased to zero in children less than 5 years of age (Oluwalana et al., J Pediatr 163:S4–7, 2013; Adegbola et al., Lancet 366:144–50, 2005). In addition, Hib nasopharyngeal carriage among toddlers decreased from 12% to 0.25% during this time period (Adegbola et al., Lancet 366:144–50, 2005). The data from The Gambia highlight the effectiveness of conjugate Hib vaccines in the prevention of invasive disease. Observations regarding the effectiveness of Hib vaccine are not isolated to the USA and The Gambia. Similar impressive results have been achieved in every part of the world where Hib vaccination has been introduced.
Ambient BTEX exposure and mid-pregnancy inflammatory biomarkers in pregnant African American women

Abstract Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1β, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1β of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1β of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.
PRECIPITATION BEHAVIOR OF(Nb, Ti)C IN COILING PROCESS AND ITS EFFECT ON MICRO-MECHANICAL CHARACTERISTICS OF FERRITE

High strength micro-alloyed steel has been widely used in automobile and machines because of the remarkable high strength and forming property which are attributed to nano-precipitates and refinement of the organization. Since the nano-precipitates are mostly nucleated between austenite/ferrite transition and ferrite can significantly advance strength, it is important to investigate precipitate behavior in coiling process. Nanoindentation technology provides a chance to study the special influence of nano-precipitates on the micro-properties of ferrite. The effect of cooling rate during continuous cooling process and coiling process on microstructural evolution and micro-hardness of Nb-Ti micro-alloyed steel were studied by using the thermal mechanical simulator, micro-hardness instrument, TEM and nanoindentation instrument. The precipitate behaviors of(Nb,Ti)C in coiling process and its effect on nano-hardnesss of ferrite were discussed. Experiments results indicated that the increase of cooling rate in continuous cooling process and coiling process could promote the microstructure transition from ferrite and pearlite to bainite. The micro-hardness of the tested steel increased with the increase of cooling rate in continuous cool-ing process, and decreased with the cooling rate in coiling process because of the large number of the dispersive nano- precipitate in ferrite which could improve the strength of matrix. The smaller cooling rate could promote volume fraction of(Nb, Ti)C particles in ferrite because there was enough time for the nucleation and growth of(Nb,Ti)C precipitates. When the cooling rate in coiling process was 0.1 ℃/s, precipitates were dispersive in ferrite matrix with a diameter of less than 10 nm. The nanohardness and Young's modulus of ferrite were 4.13 and 249.3 GPa for Nb-Ti micro-alloyed steel, 2.64 and 237.4 GPa for C-Si-Mn steel. The contribution of nano-precipitates to nanohardness of ferrite reached 1.49 GPa.
COVID-19 effect on cancer diagnosis: A retrospective comparative analysis

e18506Background: In response to the COVID-19 pandemic, many health systems postponed routine screening and care to conserve resources and reduce patient exposure. As a result, several studies have...
The end of the village: planning the urbanization of rural China: by Nick R. Smith, Minneapolis, MN, USA, University of Minnesota Press Globalization and Community Series, 2021, 336 pp., $108 (hardback), ISBN 9781517910914; $27 (paperback), ISBN: 9781517910921, $27 (eBook), ISBN 9781452965444. Digital editions of most University of Minnesota Press titles are available through a variety of retailers.

In China’s 14th Five-Year Plan (2021–2025), the central government set a target of a 65% urbanization rate and planned to add 10 million new urban residents annually until 2025. Most of the new urb...
Sex Trafficking of Black Girls: A Critical Race Theory Approach to Practice

Child sex trafficking is a troubling, yet hidden, social problem in the United States. Black girls are particularly vulnerable given the intersection of their race and gender as they navigate biolo...
Use of an end-tidal carbon dioxide-guided algorithm during cardiopulmonary resuscitation improves short-term survival in paediatric swine.

Aim To evaluate an algorithm that uses an end-tidal carbon dioxide (ETCO2) target of ≥ 30 torr to guide specific changes in chest compression rate and epinephrine administration during cardiopulmonary resuscitation (CPR) in paediatric swine. Methods Swine underwent asphyxial cardiac arrest followed by resuscitation with either standard or ETCO2-guided algorithm CPR. The standard group received chest compressions at a rate of 100/min and epinephrine every 4 min during advanced life support consistent with the American Heart Association paediatric resuscitation guidelines. In the ETCO2-guided algorithm group, chest compression rate was increased by 10 compressions/min for every minute that the ETCO2 was < 30 torr, and the epinephrine administration interval was decreased to every 2 min if the ETCO2 remained < 30 torr. Short-term survival and physiologic data during active resuscitation were compared. Results Short-term survival was significantly greater in the ETCO2-guided algorithm CPR group than in the standard CPR group (16/28 [57.1%] versus 4/28 [14.3%]; p = 0.002). Additionally, the algorithm group had higher predicted mean ETCO2, chest compression rate, diastolic and mean arterial pressure, and myocardial perfusion pressure throughout resuscitation. Swine in the algorithm group also exhibited significantly greater improvement in diastolic and mean arterial pressure and cerebral perfusion pressure after the first dose of epinephrine than did those in the standard group. Incidence of resuscitation-related injuries was similar in the two groups. Conclusions Use of a resuscitation algorithm with stepwise guidance for changes in the chest compression rate and epinephrine administration interval based on a goal ETCO2 level improved survival and intra-arrest hemodynamics in this porcine cardiac arrest model.
SPAC Governance: In Need of Judicial Review

This paper analyzes the relationship between the economic structure of a SPAC, its corporate governance, and judicial review of SPAC mergers (or "deSPACs"). The core challenge for SPAC governance is to address the inherently conflicting interest of a sponsor and public shareholders. SPACs respond to this conflict by holding proceeds of their IPOs in trust and by granting public shareholders a right to redeem their shares for a pro-rata portion of that trust. For the redemption right to be effective, however, a SPAC's board must provide shareholders with accurate and complete information regarding the merger. Doing so may conflict with the interests of the SPAC’s sponsor, which will profit substantially even in a deal that is bad for SPAC investors. The independence of a SPAC's board is thus necessary for a SPAC to be governed in the interest of shareholders. Unfortunately, SPAC directors often have financial ties to a sponsor and are compensated in ways that align their interests with those of the sponsor. Where this is true, and where SPAC shareholders file suits alleging a breach of the duties of loyalty and candor, a court should affirm that the board has a duty to provide shareholders with the information they need to exercise their redemption right, and review the conduct of the sponsor and the board under an entire fairness standard.
DNA microarray technology used for studying foodborne pathogens and microbial habitats: minireview.

Microarray analysis is an emerging technology that has the potential to become a leading trend in bacterial identification in food and feed improvement. The technology uses fluorescent-labeled probes amplified from bacterial samples that are then hybridized to thousands of DNA sequences immobilized on chemically modified glass slides. The whole gene or open reading frame(s) is represented by a polymerase chain reaction fragment of double-strand DNA, approximately 1000 base pair (bp) or 20-70 bp single-strand oligonucleotides. The technology can be used to identify bacteria and to study gene expression in complex microbial populations, such as those found in food and gastrointestinal tracts. Data generated by microarray analysis can be potentially used to improve the safety of our food supply as well as ensure the efficiency of animal feed conversion to human food, e.g., in meat and milk production by ruminants. This minireview addresses the use of microarray technology in bacterial identification and gene expression in different microbial systems and in habitats containing mixed populations of bacteria.
Calculation of conduction power losses in double flying capacitor multicell converter

This paper proposes a detailed approach to analytically calculate the conduction power losses in double flying capacitor multicell (DFCM) converter. For this purpose, the rms and average current flowing through power switches and diodes in both high-frequency and low-frequency cells of DFCM converter are analytically calculated in detail in terms of the load peak current, load power factor and modulation index. Afterwards, an approach to obtain the parameters of the power switches and diodes from the datasheet and use them for calculation of conduction power losses is discussed. Finally, as an example, a 14MVA 3.3kV three-phase 9-level (line-to-line) DFCM converter is simulated and the obtained simulation results of the rms and average current flowing through the power switches and diodes matched with numerical results of the derived equations which validates the derived equations. Furthermore, its conduction power losses is analytically calculated using the presented equations by considering parameters of high-power switches (IGCT and IGBT modules) available in the market from ABB.
On the power series coefficients of certain quotients of Eisenstein series

In their last joint paper, Hardy and Ramanujan examined the coefficients of modular forms with a simple pole in a fundamental region. In particular, they focused on the reciprocal of the Eisenstein series E 6 (τ). In letters written to Hardy from nursing homes, Ramanujan stated without proof several more results of this sort. The purpose of this paper is to prove most of these claims.
USES FOR A CALCULATED LIMIT DEPTH TO BEACH EROSION

A sediment entrainment parameter is used to calculate maximum water depth for intense bed agitation by shoaling linear waves of given height and period. Calculated limit depths agree with available laboratory measurements of water depth at an erosive wave cut into slopes of quartz and other fine sediments. Ignored variables have small effects on the agreement between calculations and laboratory measurements. On natural seasonal beaches, available measurements of seaward limit to appreciable sand level changes agree with limit depths calculated for extremely high waves expected 12 hours per year. The apparent accuracy and lack of scale effect in the calculated limit depth justify several applications in field and laboratory projects.
Alms to the Rich: The Facade Easement Deduction

This article presents the case for repeal of the facade easement deduction. Proponents of this benefit argue that the deduction encourages historic preservation by reimbursing property owners for relinquishing their right to alter the facade of their property in a way inconsistent with that conservation goal; however, this article shows that there are many reasons to urge its repeal: the revenue loss, the small number of beneficiaries, the financial demographics of that group of beneficiaries; the dubious industries that are supported by the deduction; and the continual marked overvaluation and abuse despite Congressional, court, and administrative review and expense. After the last major reform effort, the Pension Protection Act of 2006 (PPA), in 2009, only 94 taxpayers claimed the facade easement charitable deduction with an average return deduction of $477,225. While there may be a desire to retain a tax benefit with purported charitable aims, the long history of unbridled abuse even with repeated legislative and administrative response should make it clear that amending the facade easement deduction is an unending proposition. In today’s world, real estate is often subject to regulation that buyers and their neighbors accept in order to retain and increase a community’s property values. The very wealthiest of homeowners who purchase homes in historic districts willingly accept local restrictions on their property’s use. There is no evidence that facade easements significantly alter the behavior of property owners. It provides them with huge tax savings for doing what they would do anyway.
Cylinder-Averaged Histories of Nitrogen Oxide in a D.I. Diesel with Simulated Turbocharging,

An experimental study was conducted using the dumping technique (total cylinder sampling) to produce cylinder mass-averaged nitric oxide histories. Data were taken using a four stroke diesel research engine employing a quiescent chamber, high pressure direct ijection fuel system, and simulated turbocharging. Two fuels were used to determine fuel cetane number effects. Two loads were run, one at an equivalence ratio of 0.5 and the other at a ratio of 0.3. The engine speed was held constant at 1500 rpm. Under the turbocharged and retarded timing conditions of this study, nitric oxide was produced up to the point of about 85% mass burned. Two different models were used to simulate the engine mn conditions: the phenomenological Hiroyasu spray-combustion model, and the three dimensional, U.W.-ERO modified KIVA-lI computational fluid dynamic code. Both of the models predicted the correct nitric oxide trend. Although the modified KIVA-lI combustion model using Zeldovich kinetics correctly predicted the shapes of the nitric oxide histories, it did not predict the exhaust concentrations without arbitrary adjustment based on experimental values.
Point vortices exhibit asymmetric equilibria

The equilibrium patterns formed by interacting vortices have been puzzled over in a variety of contexts since Kelvin's theory of vortex atoms1 was debunked by quantum mechanics. These patterns have, for example, appeared in atmospheric and oceanographic flows2,3 and in rotating superfluid helium4,5. For a particular mathematical model, the point vortex equations, a catalogue of equilibria was drawn up some twenty years ago6. We have revisited the point vortex model by a different approach and have discovered a host of new equilibrium states, including asymmetric patterns devoid of rotational or reflectional symmetry.
A Geological Framework for Interpreting Downstream Effects of Dams on Rivers

Despite decades of research and abundant case studies on downstream effects of dams on rivers, we have few general models predicting how any particular river is likely to adjust following impoundment. Here we present a conceptual and analytical framework for predicting geomorphic response of rivers to dams, emphasizing the role of geologic setting and history as first-order controls on the trajectory of change. Basin geology influences watershed and channel processes through a hierarchical set of linkages, extending from the drainage basin to the valley and channel, which determine the sediment transport and discharge regimes. Geology also directly shapes the suite of hillslope processes, landforms, and geomorphic disturbances impinging on the channel and valley floor. These factors, in turn, affect the “lability” or capacity for adjustment of the downstream channel, determining the type, direction, and extent of channel adjustments that occur, including incision, widening, and textural changes. We develop an analytical framework based on two dimensionless variables that predicts geomorphic responses to dams depending on the ratio of sediment supply below to that above the dam (S*) and the fractional change in frequency of sediment-transporting flows (T*). Drawing on examples from the Green, Colorado, and Deschutes Rivers, we explore how trajectories of geomorphic change, as defined by these two variables, are influenced by the geological setting and history of the river. This approach holds promise for predicting the magnitude and trend of downstream response to other dammed rivers, and can identify river systems where geological controls are likely to dominate.
Application of Operational Effectiveness Models in Naval Ship concept exploration and design

Traditionally, the Concept and Requirements Exploration process is the first stage of ship design. Concept and Requirements Exploration responds to a stated mission need with early high-level assessment of a broad range of ship design options and technologies. Our design group uses a Multi-Objective Optimization approach to explore the design space and identify non-dominated designs ranked by cost, risk, and effectiveness. Our method of calculating effectiveness in this approach has, in the past, been based on expert opinion. In this study, the use of a more direct physics-based Operational Effectiveness Model approach is considered to provide greater confidence in the validity of effectiveness results and a perception that results are more unbiased and rational. This approach requires significant early investment. How much analysis is enough and is there significant payoff for this significant effort? This paper presents this approach and explores these questions.
On trip planning queries in spatial databases

In this paper we discuss a new type of query in Spatial Databases, called the Trip Planning Query (TPQ). Given a set of points of interest P in space, where each point belongs to a specific category, a starting point S and a destination E, TPQ retrieves the best trip that starts at S, passes through at least one point from each category, and ends at E. For example, a driver traveling from Boston to Providence might want to stop to a gas station, a bank and a post office on his way, and the goal is to provide him with the best possible route (in terms of distance, traffic, road conditions, etc.). The difficulty of this query lies in the existence of multiple choices per category. In this paper, we study fast approximation algorithms for TPQ in a metric space. We provide a number of approximation algorithms with approximation ratios that depend on either the number of categories, the maximum number of points per category or both. Therefore, for different instances of the problem, we can choose the algorithm with the best approximation ratio, since they all run in polynomial time. Furthermore, we use some of the proposed algorithms to derive efficient heuristics for large datasets stored in external memory. Finally, we give an experimental evaluation of the proposed algorithms using both synthetic and real datasets.
Stresses from flip-chip assembly and underfill; measurements with the ATC4.1 assembly test chip and analysis by finite element method

We report the first measurements of in-situ flip-chip assembly mechanical stresses using a CMOS piezoresistive test chip repatterned with a fine pitch full area array. A special printed circuit board substrate was designed at Sandia and fabricated by the Hadco Corp. The flip-chip solder attach (FCA) and underfill was performed by a SEMATECH member company. The measured incremental stresses produced by the underfill are reported and discussed for several underfill materials used in this experiment. A FEM of a one-quarter section of the square assembly has been developed to compare with the measured as-assembled and underfill die surface stresses. The initial model utilized linear elastic constitutive models for the Si, solder, underfill, and PC board components. Detailed comparisons between theory and experiment are presented and discussed.
Vocal Category Development in Human Infancy: A Commentary on Giulivi et al.'s Critique of the Frames, then Content Model

This is a commentary on the article (this issue) by Giulivi, Whalen, Goldstein, Nam, and Levitt (GW) and on the Frames, then Content (FC) theory that the article critiques. The commentary agrees with GW that the FC theory has not been adequately supported by data to show a developmental pattern of reduction in “frame dominance” across human infancy. The commentary elaborates on another apparent problem highlighted by GW, that is, while expected-to-observed ratios of syllable types appear to support FC theory, raw frequency data (at least the ones from GW) seem to contradict it. The commentary also argues that phonetic transcription, the primary method of the FC model and the critique by GW, has limited reliability and validity and should not be utilized in early vocal development research without additional methods for interpretive guidance. Another weakness of the FC theory, as formulated, is that it offers no useful way to portray precanonical vocal development, which appears to be critical to subsequen...
High-pressure X-ray diffraction study of tungsten diselenide

Abstract Synchrotron X-ray diffraction was used in conjunction with a diamond anvil cell to investigate the properties of a tungsten diselenide (WSe2) sample to 35.8 GPa at room temperature. By fitting the pressure–volume data to the third-order Birch–Murnaghan equation of state, the bulk modulus, K0T, of WSe2 was determined to be 72±1 GPa with its pressure derivative, K 0 T ′ , being 4.1±0.1. It was also found that the c-direction of the hexagonal structure is significantly more compressible than the a-direction. No phase transformation was clearly observed in the pressure range of our measurements.
Pictorial markings and labels for safe transport and handling of packaged goods

This paper presents the various sources of pictorial markings and warning labels that can be used on packaged goods. Lack of appropriate warnings or markings can result in severe hazards that can affect the safety of individuals and the work environment. The paper shows examples of good and poor applications of warnings and also discusses the various standards that assist in developing appropriate package markings for your goods. New markings recently being developed will also be discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Compositional model checking of software product lines using variation point obligations

This paper introduces a technique for incremental and compositional model checking that allows efficient reuse of model-checking results associated with the features in a product line. As the use of product lines has increased, so has the need to verify the models used to construct the products in the product line. However, this effort is currently hampered by the difficulty of composing model-checking results for the features in a way that allows reuse for subsequent products. The contributions of this paper are to remove restrictions on how the features can be sequentially composed, to describe how to generate obligations such that all sequentially composed systems can be verified, and to show how to compositionally model check the product in the product line by reusing the variation-point obligations. The paper develops the technique and its implementation in the context of a medical-device product line.
Using NNAPPS (Nighttime Nurse and Physician Paging System) to Maximize Resident Call Efficiency within 2011 Accreditation Council for Graduate Medical Education (ACGME) Work Hour Restrictions

Objectives To assess if implementing Nighttime Nurse and Physician Paging System (NNAPPS) would improve nurse and physician communication as well as reduce the number of nonurgent pages to residents taking overnight call. Design NNAPPS was implemented on the busiest General Surgery and Transplant wards at our University Hospital. We conducted 2 prospective studies that logged pages received by on call surgery residents for 2-month blocks. The logs captured time, source, reason, and action resulting from pages. Independent reviewers determined urgency of the pages. Primary outcome measures were comparison of average nonurgent pages, total pages and total pages per patient during a night shift between the NNAPPS ward and all other wards that care for surgical patients. Setting University teaching hospital. Participants General surgery residents working overnight call shifts on nine surgical services. Results In both studies combined, there were a total of 107 night shifts during which 771 pages were received. Total census was 1179 patients. Nurses initiated most pages (67%). Eight percent of pages interrupted patient care, while 40% of pages interrupted resident sleep. Most pages resulted in either a “new order” (39%) or “patient assessment” (22%), while 36% resulted in “no action.” Most pages (56%) were “urgent,” 25% “nonurgent,” and 19% “unable to determine urgency.” Regarding the Transplant ward, significant differences (p Conclusions NNAPPS significantly reduced nonurgent pages, total pages and pages per patient during a night shift compared to services with conventional systems. Streamlined paging systems lead to more efficient communication between providers and decrease the nonurgent pages to residents. NNAPPS continued high standards of patient care and improved sleep patterns for residents.
Calcium entry in rat parotid acinar cells.

While it is generally accepted that Ca2+ plays an important regulatory role in the physiology of a number of non-excitable cells, the mechanisms which regulate intracellular [Ca2+ are far from well established. Ca2+ transporting mechanisms which distribute Ca2+ intracellularly as well as those which allow influx of extracellular Ca2+ are involved in mediating intracellular Ca2+ homestasis. In this paper we have described recent studies on the regulation of the Ca2+ influx system in the data, it appears that the process of Ca2+ entry is extremely complex and may involve several levels of regulation. Understanding the molecular basis of these regulatory mechanisms presents a challeging problem for future studies.
7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: roles of NADPH oxidase, mitochondria, and lipid rafts.

Long wavelength solar UVA radiation stimulates formation of reactive oxygen species (ROS) and prostaglandin E2 (PGE2), which are involved in skin photosensitivity and tumor promotion. High levels of 7-dehydrocholesterol (7-DHC), the precursor to cholesterol, cause exaggerated photosensitivity to UVA in patients with Smith-Lemli-Opitz syndrome (SLOS). Partially replacing cholesterol with 7-DHC in keratinocytes rapidly (< 5 min) increased UVA-induced ROS, intracellular calcium, phospholipase A2 activity, PGE2, and NADPH oxidase activity. UVA-induced ROS and PGE2 production were inhibited in these cells by depleting the Nox1 subunit of NADPH oxidase using siRNA or using a mitochondrial radical quencher, MitoQ. Partial replacement of cholesterol with 7-DHC also disrupted membrane lipid raft domains, although depletion of cholesterol, which also disrupts lipid rafts, did not affect UVA-induced increases in ROS and PGE2. Phospholipid liposomes containing 7-DHC were more rapidly oxidized by a free radical mechanism than those containing cholesterol. These results indicate that 7-DHC enhances rapid UVA-induced ROS and PGE2 formation by enhancing free radical-mediated membrane lipid oxidation and suggests that this mechanism might underlie the UVA photosensitivity in SLOS.
Clinical approach to diagnostic endoscopy in patients with upper gastrointestinal bleeding.

The physician faced with a patient with a history of gastrointestinal bleeding must decide at the time that the patient is admitted to the hospital whether the patient can be evaluated by the routine scheduling of diagnostic procedures or if an emergent approach to the problem is indicated. If the patient has bled within 48 hr and if any of the findings shown in Table 1 are present, then an emergent approach is indicated. Emergent endoscopy performed within 24 hr of hospital admission must weigh its timing against the severity of the bleeding, recognizing the advantage of performing procedures during the day when the endoscopist and ancillary personnel are at their best. The emergent approach should increase the accuracy of endoscopic diagnosis by performing the procedure while stigmata of bleeding are present, before tube artifacts are introduced, and before superficial lesions have healed. The information provided should assure that medical or surgical therapy is most appropriately determined by the cause of bleeding.
Probing for prions: recognizing misfolded PrP.

New antibodies specific for the misfolded, and presumably pathogenic, form of the PrP protein have now made their long-awaited debut. These antibodies could provide tools for diagnostics, research and therapy (pages 893–899).
DNA glycosylase recognition and catalysis

Abstract DNA glycosylases are the enzymes responsible for recognizing base lesions in the genome and initiating base excision DNA repair. Recent structural and biochemical results have provided novel insights into DNA damage recognition and repair. The basis of the recognition of the oxidative lesion 8-oxoguanine by two structurally unrelated DNA glycosylases is now understood and has been revealed to involve surprisingly similar strategies. Work on MutM (Fpg) has produced structures representing three discrete reaction steps. The NMR structure of 3-methyladenine glycosylase I revealed its place among the structural families of DNA glycosylases and the X-ray structure of SMUG1 likewise confirmed that this protein is a member of the uracil DNA glycosylase superfamily. A novel disulfide cross-linking strategy was used to obtain the long-anticipated structure of MutY bound to DNA containing an A•oxoG mispair.
The distribution of iron oxidation states in a constructed wetland as an indicator of its redox properties

Wastewater-treatment processes taking place inside constructed wetlands are closely connected with chemical properties of these systems. The aeration of a wetland via the roots of the vegetation (and a subsequent formation of redox-potential gradients) strongly influences the wastewater treatment efficiency, and thus it represents one of the most important characteristics of the wetland. The concentration ratios of individual iron oxidation states (Fe(II) and Fe(III)) were determined as the indicator of the redox properties of the constructed wetland reed bed during this study. Interstitial water from the wetland was sampled eleven times throughout the year 2005. The spectrophotometric method using 1,10-phenanthroline was properly optimized (limits of detection and quantification, sensitivity, linear dynamic range, repeatability, and accuracy values were assessed) and applied for iron determination. Most of iron, ca. 98%, is reduced to the Fe(II) form in raw wastewater and water from the inflow zone of the constructed wetland, however, at the outflow and in the vegetation bed both iron oxidation states are usually detected. The presence of Fe(III) in the reed bed (ca. 10-30% for some samples) demonstrates the aeration of the wetland by the vegetation (Phragmites australis) resulting in a re-oxidation of Fe(II).
Studies of photoexcitations in conducting polymers by the absorption-detected magnetic resonance technique

Abstract The nature of photoexcitations in conducting polymers has been elucidated by the absorption-detected magnetic resonance (ADMR) technique. In this technique we measure changes in the photoinduced absorption (PA) spectrum due to changes in spin-dependent recombination rates induced by resonant absorption of μ-waves in magnetic fields. We have used the ADMR technique at 3 GHz to study spin states in trans -(CH) x , oriented poly( para -phenylene vinylene) (PPV), polythiophene (PT) and polydiethynylsilane (PDES). We have verified that the charged excitations are solitons (S ∓ ) in trans -(CH) x and PDES, and polarons (P ∓ ) and bipolarons (BP 2∓ ) in other nondegenerate ground state polymers. The long-lived neutral excitations, on the other hand, are self-trapped triplet excitons in all polymers, except for trans -(CH) x and PDES in which the triplets dissociate into neutral soliton (S 0 ) pairs due to their backbone degenerate ground state structure.
16,16-Dimethyl prostaglandin E2 reverses focal mucosal ischemia associated with stress ulcers

Focal ischemia is postulated to contribute to gastric mucosal stress ulceration. This study evaluated directly (1) whether or not mucosal ulceration during hemorrhagic shock is preceded by focal gastric mucosal blood flow changes, and (2) whether or not topical Dm-PGE2 (16,16-dimethyl prostaglandin E2) affects focal gastric mucosal blood flow during hemorrhagic shock. Twelve anesthetized miniature swine had pyloric ligation and intragastric infusion of 5 ml/kg autogenous bile in 140 mM HCl. Gastric mucosal blood flow was documented by radiolabeled microspheres during (1) normotension, (2) initial hemorrhagic shock (50 mm Hg), and (3) hemorrhagic shock + 50 μg topical Dm-PGE2. Stable shock was then maintained for 3 hr. During this time ulceration developed, shedding radiolabeled microsphere-bearing mucosa into the lumen. Intact gastric mucosa and luminal contents were collected, weighed, and gamma counted. Blood flow to intact mucosa was calculated by standard techniques. The weight of shed tissue, as well as the blood flow to shed tissue, was calculated from luminal microspheres. Results: gastric mucosal blood flow was decreased 35% with hemorrhagic shock (28.8 ± 4.0 vs 18.7 ± 2.7 ml/100 g/min, P < 0.05). Blood flow to tissue which was subsequently shed averaged 6.4 ± 3.1 ml/100 g/min at the same time period (P < 0.05 vs surrounding tissue). Addition of Dm-PGE2 increased blood flow to shed tissue from 29 ± 8% to 48 ± 10% of blood flow to intact tissue (P < 0.05). Conclusions: (1) gastric mucosal ulceration is preceded by focal decreases in gastric mucosal blood flow, and (2) topical Dm-PGE2 reverses focal mucosal ischemia during hemorrhagic shock. Dm-PGE2's ability to reverse focal ischemia suggests a mechanism for prostaglandin-mediated cytoprotection.
Regionalization of Low-Flow Frequency Estimates: AN Alabama Case Stui)y

: Low-flow estimates, as determined by probabilistic modeling of observed data sequences, are commonly used to describe certain streamflow characteristics. Unfortunately, however, reliable low-flow estimates can be difficult to come by, particularly for gaging sites with short record lengths. The shortness of records leads to uncertainties not only in the selection of a distribution for modeling purposes but also in the estimates of the parameters of a chosen model. In flood frequency analysis, the common approach to mitigation of some of these problems is through the regionalization of frequency behavior. The same general approach is applied here to the case of low-flow estimation, with the general intent of not only improving low-flow estimates but also illustrating the gains that might be attained in so doing. Data used for this study is that which has been systematically observed at 128 streamflow gaging sites across the State of Alabama. Our conclusions are that the log Pearson Type 3 distribution is a suitable candidate for modeling of Alabama low-flows, and that the shape parameter of that distribution can be estimated on a regional basis. Low-flow estimates based on the regional estimator are compared with estimates based on the use of only at-site estimation techniques.
Teacher Key Opinion Leaders and Mental Health Consultation in Low-Income Urban Schools.

Diffusion theory posits that information is disseminated throughout a social network by the persuasion of key opinion leaders (KOLs). This study examined the relative and combined influence of peer-identified KOL teachers (n = 12) and mental health providers (n = 21) on classroom teachers' (n = 61) self-reported use of commonly recommended classroom practices for children with attention-deficit/hyperactivity disorder in 6 low-income urban African American communities, relative to teachers (n = 54) at 4 matched schools who received mental health provider consultation only. Mixed-effects regression models showed that KOLs in collaboration with mental health providers promoted higher rates of teachers' self-reported use of recommended strategies than mental health providers alone, and that these effects were mediated by KOL support but not by mental health provider support. The results suggest an expanded role for KOL teachers as indigenous and natural supports for the dissemination and implementation of school-based mental health programs.
Resistive correction of low output impedance high-speed current-steering DACs

Current-steering digital-to-analog converters are the architecture of choice in high-resolution high-speed applications. However, they are still affected by non-linearity that becomes worse with higher resolutions and higher speeds. This paper proposes a method of correction for one of the sources of non-linearity. This method is analyzed for its robustness to matching and absolute errors. The proposed method is analyzed using Monte-Carlo analysis, and then verified at the transistor level with simulations. A transistor level 12 bit 1GS/s digital-to-analog converter is simulated using a 65nm process. The transistor level simulations show a 20 dB improvement in spurious-free dynamic range.
Functional Identification of Catalytic Metal Ion Binding Sites within RNA

The viability of living systems depends inextricably on enzymes that catalyze phosphoryl transfer reactions. For many enzymes in this class, including several ribozymes, divalent metal ions serve as obligate cofactors. Understanding how metal ions mediate catalysis requires elucidation of metal ion interactions with both the enzyme and the substrate(s). In the Tetrahymena group I intron, previous work using atomic mutagenesis and quantitative analysis of metal ion rescue behavior identified three metal ions (MA, MB, and MC) that make five interactions with the ribozyme substrates in the reaction's transition state. Here, we combine substrate atomic mutagenesis with site-specific phosphorothioate substitutions in the ribozyme backbone to develop a powerful, general strategy for defining the ligands of catalytic metal ions within RNA. In applying this strategy to the Tetrahymena group I intron, we have identified the pro-SP phosphoryl oxygen at nucleotide C262 as a ribozyme ligand for MC. Our findings establish a direct connection between the ribozyme core and the functionally defined model of the chemical transition state, thereby extending the known set of transition-state interactions and providing information critical for the application of the recent group I intron crystallographic structures to the understanding of catalysis.
Loss of the anabolic effect of parathyroid hormone on bone after discontinuation of hormone in rats.

We have previously reported that low doses of hPTH 1–34 given daily to rats exert an anabolic effect on bone. The objective of this study was to determine if the anabolic effect of PTH was dependent upon continued daily administration of the hormone. Young, male rats were given daily subcutaneous injections of either vehicle or 8 μg/100g bw hPTH 1–34 for 12, 16, 20, or 24 days. Additional groups were treated with 8 μg/100g bw hPTH for 12 days followed by vehicle for the next 4, 8, or 12 days, or 8 μg/100g bw hPTH 1–34 for 16 days followed by 4 days of vehicle. We measured calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur, percent of osteoblast (Ob.S/BS) and osteoclast (Oc.S/BS) surface, mineral apposition rate (MAR), double label surface (DLS/BS), and bone formation rate (BFR) in the metaphysis of the proximal tibia, and serum calcium and phosphate. Trabecular and cortical bone Ca and DW and the histologic measures of bone formation increased in all PTH-treated rats. Serum calcium and phosphate were comparable in all rats. The PTH-stimulated bone mass was lost 12 days after discontinuation of PTH. Discontinuation of PTH administration for 4, 8, or 12 days, respectively, resulted in a 72%, 68%, or 50% decrease in Ob.S/BS from the 2- to 3-fold increase associated with PTH treatment (p < .05). Oc.S/BS increased compared to controls after 4 days of PTH withdrawal (NS), but was comparable to controls 8 days after withdrawal of PTH. The loss of new bone mass after discontinuation of hormone was due to an inhibition of PTH-stimulated bone formation and an initial transient phase of increased resorption. Thus, the anabolic effect of PTH was dependent upon daily administration of the hormone in our model.
Atypical squamous cells of undetermined significance--rule out high-grade squamous intraepithelial lesion: cytopathologic characteristics and clinical correlates.

The significance and clinical management of atypical squamous cells of undetermined significance (ASCUS) on cervical cytologic smears has been an area of much controversy. This study compiled a list of criteria useful in identifying the subset of cases that would be categorized as atypical squamous cells of undetermined significance- rule out high-grade squamous intraepithelial lesion (ASC-H) in the new Bethesda System terminology, which eventuate in a diagnosis of cervical intraepithelial neoplasia (CIN). The cytopathology files at Johns Hopkins Hospital were searched for ASC-H cases from the 3-yr period 1996-1998, which had definitive clinicopathologic follow-up (colposcopy and cervical biopsies). The smears were reviewed, cytomorphologic features studied, and clinical correlations performed. ASC-H was diagnosed in 257 of 45,428 gynecologic smears (0.6%), 72 having had clinicopathologic follow-up. Of these 72 cases, 35 (49%) on follow-up had a negative/reactive diagnosis (NR), whereas 37 (51%) turned out to be CIN [CIN-I-18 (49%) and CIN II and III-19 (51%)]. The significant cytomorphologic differences in the ASC-H category with a CIN follow-up (compared with an NR follow-up) were fewer atypical cells, more often discohesive or seen singly, more monomorphic, a higher nuclear-to-cytoplasmic (N/C) ratio, greater nuclear hyperchromasia, more coarse, unevenly dispersed chromatin, more prominent nuclear membrane irregularities, lack of nucleoli, chromocenters or nuclear grooves, and lack of an inflammatory background. Careful attention to subtle cytomorphologic characteristics may be helpful for a more definitive subdivision of ASC-H terminology into a NR and a CIN diagnosis.
Death by rafting

Currently, monoclonal antibodies (mAbs) do not play a major role in the treatment of multiple myeloma (MM). In this issue of Blood , Yang and colleagues show that by disrupting structural cell integrity, mAbs against β2-microglobulin (β2M) have potent anti-MM activity. Monoclonal antibodies have