cssi/SciSciGPT-SciSciNet huggingface dataset:
Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate

TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3) mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx) mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs) were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish this by binding to distinct SBEs, mediating assembly of distinct repressive complexes.
Radical Intradisciplinarity: An Introduction

This forum brings together five essays that explore the potential and the limitations of geography's intradisciplinarity. Each one, authored by a pair of geographers who share a common thematic interest but who come from different subareas of the discipline, represents the results of thinking, speaking, and writing across the methodological, conceptual, and theoretical divides that characterize our discipline and academic knowledge in general. As experiments in doing intradisciplinary work and the difficult pluralism that we hope that work connotes, these essays underline the promise and demonstrate the confines of intradisciplinary work and its radical potential.
Optimum digital pulse shaping filters

We study the design of moderate-length discrete-time pulse-shaping filters used in data communications, focusing on the tradeoff between ISI, out-of-band power, and filter length. Oversampling ratio M=2 and 4 is studied for both symmetric and asymmetric impulse responses. Numerical minimization of out-of-band power, subject to constraints on ISI, is our primary tool.
Serverless and Peer-To-Peer Distributed Interfaces for Musical Control

This paper presents the concept and implementation of a decentralized, server-less and peer-to-peer network for the interchange of musical control interfaces and data using the OSC protocol. Graphical control elements that form the control interface can be freely edited and exchanged to and from any device in the network, doing away with the need for a separate server or editing application. All graphical elements representing the same parameter will have their value synchronized through the network mechanisms. Some practical considerations surrounding the implementation of this idea like automatic layout of control, editing interfaces on mobile touch-screen devices and auto-discovery of network nodes are discussed. Finally, GoOSC, a mobile application implementing these ideas is presented.
Tube Thoracostomy at the Time of Congenital Diaphragmatic Hernia Repair: Reassessing the Risks and Benefits

Abstract Purpose: Postoperative pneumothorax and effusion remain a concern following congenital diaphragmatic hernia (CDH) repair. Despite a recent trend away from intraoperative thoracostomy, few ...
First flight of a high power software defined electronic warfare system

A description and flight test results of the "First Flight" of Raytheon's prototype next-generation, Pod based, airborne Electronic Warfare (EW) system is presented. The system is powered by the airstream flowing through a submerged turbine connected to a generator. The primary recipient of this prime power is a wideband, polarization diverse, Active Electronically Scanned Array (AESA) with Transmit/Receive (T/R) modules that contain efficient Gallium Nitride (GaN) amplifiers capable of operating between 0 to 100% duty cycle in either transmit or receive mode. Also featured is an all-digital, scalable, reprogrammable Software Defined Receiver/Exciter Unit that provides the technique generation. The airborne demonstration missions were flown on a Gulfstream III aircraft. They highlighted the jamming techniques that included Transmit and Receive waveforms, AESA beam agility and control, AESA transmit power, generator speed control/power management, and end-to-end system integration effectiveness against real target emitters.
Anesthesia for Pediatric Thoracic Surgery

The management of pediatric patients requiring chest surgery requires knowledge of the physiology and familiarity with the equipment and specialized techniques. This chapter reviews common clinical conditions uniquely encountered in pediatric thoracic surgery and provides practical guidance for anesthetic management.
Water vapor adsorption and desorption isotherms of biologically active proteins.

Using a protein isolated from soy, a dynamic water adsorption method was developed and the data were compared with those obtained from a static gravimetric procedure. Both methods gave comparable results, showing that Type II isotherms with considerable hysteresis were obtained. However, the dynamic procedure was preferred since it provided data rapidly and used significantly less material. Using the dynamic method, water adsorption isotherms at 25°C were also determined for four biologically active proteins: α-amylase, (β-glucuronidase, lipase, and urease. BET (Brunauer, Emmet, and Teller) parameters were calculated and the specific surface areas for the native, biologically active proteins were found to be similar, 238.4 ± 20.2 m2/g. On the other hand, the specific surface area for the denatured soy protein isolate was 144.6 m2/g. Nevertheless, the heat of absorbance for all of the proteins examined was similar, suggesting that they have comparable degrees of hydrophilicity.
Extensor Mechanism Injuries of the Knee

Injuries to the extensor mechanism (the patellar tendon, the patella, and the quadriceps tendon) are potentially debilitating. A stable, reliable repair performed in a timely fashion in a reliable manner is essential to mobilize patients and return patients to their baseline of function.
Integrated Zero-Index Metamaterials and Waveguides

Integrated Dirac-cone metamaterials enable effective refractive indices near zero in the standard silicon-on-insulator (SOI) platform. We experimentally demonstrate small-footprint (≈λ/2-wide) zero-index structures in the telecom regime.
TOWARD THE COORDINATION OF MULTIPLE COOPERATING ROBOTS

ABSTRACT True multiplication of personal, human power via androids will result from the effective utilization of teams of robotic effecting mechanisms for the accomplishment of a single goal or task. This objective is of identical import for the extension of handicapped persons’ capabilities as well as for the non-handicapped. Such technology would allow a specialization and sharing of the robots between/among problems and problem-solvers (users.) We are using a single-board microcomputer as an onboard, control computer for wheeled and tracked models. These models are an experimental workshop for solving blocks movement, group navigation, and group control problems. Communication between the mobile robots and the central, coordination computer is accomplished with an FM-radio, local-area-network, which has been developed for this purpose. The central, coordination computer being used currently is an IBM-PC, but we are planning to supplement this with a 68000-based machine with one or more processing units organized around the PF474 string-matching chip. Such a computer as this promises to be effective in the execution of PROLOG, which offers an avenue for combining heuristic and factual information into a distributed, multi-robot control system.
Board certification as prerequisite for hospital staff privileges.

Hospitals have a right to restrict staff privileges to board-certified physicians to enhance the quality of medical care and reputation of the hospital. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Does Temperature Quenching in the Early Universe Exist in Part Due to Particle Production? or Quantum Occupation States? and How to Relate This to the Subsequent Deceleration Parameter? as an Open Question?

We examine the role of particle nucleation in the initial universe, and argue that there is a small effect due to particle nucleation in terms of lowering initial temperature, in tandem with energy density and scale factor contributiosn. If such scaling exists as a major order effect, then quenching of temperature proportional to a vacuum nucleation at or before the electroweak era is heavily influenced by a number, n, which is either a quantum number (quantum cosmology) or a ‘particle count at/before the electro weak era. We hope that this temperature quenching so mentioned can be tied into the deceleration parameter as given in the appendix. I.e.how could a slow down of expansion, lead to , much later rapid increase in cosmological expansion a billion years ago.
Relationship between remote cholecystectomy and incident Clostridioides difficile infection

Abstract Objectives Cholecystectomy (CCY) is associated with increased faecal levels of secondary bile acids. Secondary bile acids confer resistance to Clostridioides difficile infection (CDI, formerly Clostridium difficile infection) in animal studies. This study tested the hypothesis that CCY confers protection against CDI by increasing gut levels of secondary bile acids. Methods This was a retrospective case–control study. Adults hospitalized between January 2010 and June 2017 at our institution were included. CDI cases were defined as a positive stool PCR followed by anti-CDI treatment and were matched 1:1:1 with two control groups (those who tested negative for CDI and those who were not tested for CDI) by sex, age group, body mass index (BMI), and exposure to antibiotics. CCY was defined as a history of CCY at least 6 months prior to the index C. difficile test or the index admission date in the untested controls. Conditional logistic regression modelling was used to estimate the relationship between remote CCY and risk for CDI. Results The final study population was 7077 (2359 CDI cases, 2359 matched controls without CDI, and 2359 matched controls not tested for CDI). Rates of remote CCY did not differ among the three groups (14.4% vs. 15.5% vs. 14.2%) and this result was unchanged after adjusting for additional clinical factors (adjusted OR 0.90, 95% CI 0.76–1.06 comparing CDI cases vs. matched controls without CDI; adjusted OR 1.04, 95% CI 0.78–1.39 comparing CDI cases vs. matched controls not tested for CDI). Conclusions There was no association between remote CCY and risk for CDI.
Impact of Specimen Type and Specimen Number on HER2 Status in Gastroesophageal Junction and Gastric Adenocarcinoma.

OBJECTIVES Human epidermal growth factor receptor 2 (HER2) is expressed in some gastric and gastroesophageal junction adenocarcinomas. There were two goals: assess the impact of specimen type on HER2 status and evaluate HER2 concordance with multiple specimens. METHODS All cases were evaluated by immunohistochemistry (IHC) for HER2 and interpreted using established criteria. Fluorescence in situ hybridization (FISH) was performed on a subset. RESULTS Of 460 specimens, 83.9% were IHC negative, 5.4% were equivocal, and 10.7% were IHC positive. Of those with FISH testing, 78.5% were FISH negative, and 21.5% were FISH positive. IHC-FISH concordance for biopsy specimens, resections, and metastases was 82%, 84%, and 86%, respectively. With one vs two vs three or more specimens, the HER2-positive rate increased from 10.5% to 18.1% to 24.1%, respectively. CONCLUSIONS HER2 testing may be performed on biopsy specimens with a relatively high concordance rate with resection specimens, and if multiple samples are analyzed from a single patient, the HER2-positive rate increases over twofold.
Territorial Delegates and Party Balance: House Committee Membership after 1970

Non-voting delegates have represented territories in Congress since 1797, but have only been able to vote in committees in the last half century. The 1970s reforms to expand delegates’ rights and create new seats coincided with other party-driven changes to the committee system, and little is known about the impact delegates had on party ratios in committees. In this paper, I present evidence that the addition of delegates to standing committees in the 1970s, as well as the Committee of the Whole in the 1990s, increased Democrats’ seat share relative to the margin on the floor. In light of this evidence, the disagreements about the scope of delegates’ participation in the House are best understood in the context of increasing polarization and partisanship that increased the stakes of packing committees on the margin.
Why the "sea of same"? A qualitative look at DTCA within the larger context of healthcare marketing.

After over two decades of direct-to-consumer pharmaceutical advertising (DTCA), the ads have changed very little, both within and over the years. One respondent in this exploratory study called it ...
Investigation of deformation induced micro to macro scale surface roughness

Abstract In the present work the relationship between deformation and deformation induced surface roughness of 100 micron thick annealed AISI 304 stainless steel was investigated at the meso scale. This work is a continuation of the previous work by the authors where roughness values were determined at the apex of the bulge test samples at micro scale. The apex is believed to be the region of highest stress and strain in a typical bulge process in a circular die. The material was deformed using a biaxial bulge test through hydraulic fluid pressure. The strains on the workpieces were measured with respect to the forming pressure. The surface roughness was measured by scanning the interior (concave) area of bulge with Bruker GTK-17 optical profilometer over an area of 1.3mm x 1mm. The results show linear relationship between roughness and deformation strain, and it establish a similar trend with roughness measured at micro scale.
The Effects of Anger on Alcohol Demand and Subjective Alcohol Craving.

BACKGROUND Anger and anger-related traits have been related to alcohol use in both cross-sectional and prospective studies. However, only a small number of studies have experimentally manipulated anger to examine whether the manipulation of anger influences alcohol craving or the relative reinforcing value of alcohol. METHODS Participants (N = 231) recruited through Amazon's MTurk were randomly assigned to a provocation condition or a neutral condition prior to completing both the Alcohol Purchase Task and a self-report measure of alcohol craving. Linear regression analyses were conducted to examine the effects of the anger induction, trait hostility, frequency of alcohol use in the past month, and relevant demographic characteristics (gender, age, income) on alcohol craving and indices of alcohol demand. RESULTS Participants assigned to the provocation condition had greater PMax (B = 0.17, p = 0.012) and breakpoint (B = 0.18, p = 0.006) values, less elastic demand (B = -0.15, p = 0.020), and lower drinking intensity (B = -0.14, p = 0.025) than participants assigned to the neutral condition. Trait hostility was positively related to OMax (B = 0.22, p = 0.001), intensity of demand (B = 0.27, p < 0.001), and subjective alcohol craving posttask (B = 0.32, p < 0.001), but did not moderate the relationship between condition and outcomes. CONCLUSIONS Although most persistence indices of alcohol demand were sensitive to the anger induction, we did not observe higher scores on amplitude indices or subjective craving in the provocation condition relative to the neutral condition. Further investigation into the role which anger plays in alcohol use is warranted.
Automated Semantic Segmentation of Cardiac Magnetic Resonance Images with Deep Learning

Machine learning algorithms, especially deep learning architectures, have demonstrated immense potential for biomedical segmentation, often surpassing expert-level performance. For cardiac magnetic resonance (CMR) imaging, semantic segmentation is critical to deriving clinical measures such as myocardial mass and volume. However, challenges still exist. Manual delineation by domain experts is time-consuming and subject to human errors. With semi-automated segmentation techniques, it is challenging to analyze images of the same subject twice, end-diastole and end-systole of the cardiac cycle. To address these challenges, we propose a deep learning-based end-to-end analytical pipeline for automated segmentation of short-axis CMR imaging. The automated pipeline successfully avoids the problem of human subjectivity and achieves expert-level segmentation accuracy. With a large heterogeneous data inclusive of subjects with varying conditions, our model overcomes the data-homogeneity and achieves 99.9% dice similarity score, which outperforms the current state-of-art work.
East kent IT collaborative for healthcare (E-KITCH) – responding to the pandemic through optimising use of information technology

The Never too busy to learn guidance released in April 20201 highlights the benefits of having trainees at the forefront of quality improvement (QI) through digital means. The COVID-19 pandemic led to major disruption in the traditional delivery of services. The East Kent IT Collaborative for Healthcare (E-KITCH) was established to facilitate trainee participation in a number of projects ranging from enhanced handover to QR code posters and education. We demonstrate the success in one such project delivering online medical education following the introduction of social distancing measures. All initiatives exclusively used systems available to the trust. To this end, Webex was used as …
What Makes Epochs? A Comparative Analysis of Technological and Social Explanations of Long Economic Swings

The focus of this conference volume on technological and social explanations of long swings is entirely welcome. These two alternative economic perspectives on long swings have until now received scarcely any comparative attention. We do not yet even know, for example, whether these theories are relatively more complementary or competing since neither their internal logical structure nor their explanatory power has been juxtaposed. It is particularly striking, indeed, that the literature pursuing each approach almost never makes reference to the other. Responding to this overdue occasion, I undertake in this paper a direct comparison of these two alternative approaches to long-term economic fluctuations.
Plasma Entry, Transport, and Loss in the Magnetosphere and Ionosphere

The plasma in the magnetosphere has three main sources: the solar wind, the ionosphere, and secondaries from the extended atmosphere. Although the solar wind has long been considered the most important source, the contribution from the ionosphere is very significant and at certain times and certain locations may dominate. Transport of plasmas through the magnetosphere is predominantly given by ExB convection, but flows along the magnetic field direction are significant, and gradient and curvature drifts are large for energetic particles. The global pattern of convection, as observed in the ionosphere, is to first order controlled by the Interplanetary Magnetic Field (IMF), but time variations are important. In the magnetospheric tail, convection is nonuniform in time and in space; bursty bulk flows may be the dominant method of flux transfer back towards the Earth. Loss of magnetospheric plasmas occurs via several routes: convection paths intersecting the magnetopause, exhaust down the magnetotail, either by parallel flows in the lobes or reconnection-driven antisunward flows and plasmoid ejection; precipitation into the ionosphere; and charge exchange with the extended atmosphere. The spacecraft that will fly during the upcoming solar maximum will provide new eyes to view the plasmas in the magnetosphere, complementing the many exciting discoveries of the ISTP era.
Induction of the Early Growth Response Gene 1 Promoter by TCR Agonists and Partial Agonists: Ligand Potency Is Related to Sustained Phosphorylation of Extracellular Signal-Related Kinase Substrates

Responses to partial agonist TCR signals include positive selection of thymocytes, survival of naive T cells, and homeostatic proliferation. As part of an effort to understand the molecular basis of these processes, we have determined how agonist and partial agonist ligands act differently to induce a change in gene expression. We have found that the early growth response gene 1 (Egr1) promoter is activated by agonist and partial agonist ligands, but the partial agonist induces 10-fold lower promoter activity. Both agonist and partial agonist ligands require all six serum response elements in the Egr1 promoter to reach maximum induction. Although slightly fewer cells respond to the partial agonist, all of the responding cells have reduced activity compared with the cells responding to agonist. The factors binding to the serum response elements of the Egr1 promoter form a ternary complex (TC) consisting of serum response factor and either Elk-1 or serum response factor accessory protein-1a. Formation of a stable TC and inducible promoter activity are both dependent on extracellular signal-related kinase activation. Examination of TC formation over time reveals that this complex is induced well by partial agonist ligands, but it is not sustained, whereas agonist stimulation induces longer lived TCs. Therefore, the data suggest that both agonist and partial agonist ligands can induce formation of multiple TC on the Egr1 promoter, but the ability of the agonist ligand to maintain these complexes for an extended time results in the increased potency of the agonist.
Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (Human antibody targeting vascular endothelial growth factor receptor-1).

The human vascular endothelial growth factor receptor-1 (VEGFR-1, or Flt-1) is widely expressed in normal and pathologic tissue and contributes to the pathogenesis of both neoplastic and inflammatory diseases. In human cancer, VEGFR-1 mediated signaling is responsible for both direct tumor activation and angiogenesis. VEGFR-1 mediated activation of nonmalignant supporting cells, particularly stromal, dendritic, hematopoietic cells, and macrophages, is also likely important for cancer pathogenesis. VEGFR-1 is also hypothesized to enable the development of cancer metastases by means of activation and premetastatic localization in distant organs of bone marrow-derived hematopoietic progenitor cells, which express VEGFR-1. IMC-18F1 is a fully human IgG1 antibody that binds to VEGFR-1 and has been associated with the inhibition of cancer growth in multiple in vitro and human tumor xenograft models. The preliminary results of phase 1 investigations have also indicated a favorable safety profile for IMC-18F1 at doses that confer antibody concentrations that are associated with relevant antitumor activity in preclinical models. Cancer 2010;116(4 suppl):1027–32. © 2010 American Cancer Society.
Blood nucleotides in pregnancy and in the toxemias of pregnancy

Abstract The average blood nucleotide nitrogen in 12 cases of nontoxemic pregnancy with an average hematocrit of 36 per cent was 3.48 mg. per cent. There was no significant difference between this mean and the average blood nucleotide nitrogen determined in 12 cases of toxemias of pregnancy. The nucleoside plus free purine nitrogen was in most cases approximately equal to the uric acid nitrogen.
Reply to Szuwalski and Hilborn: Forage fish require an ecosystem approach.

In response to our recent paper (1), Szuwalski and Hilborn (2) make several points about the timing of recruitment failures, the effect of fishing on productivity, and our choice of using biomass, not recruitment, as the indicator for collapses. We address these points here to show that not only do they not affect our conclusions, but that we are largely in agreement regarding the biological processes and the implications for fisheries and conservation.
Effect of 4β-Arylamino Derivatives of 4′-O-Demethylepipodophyllotoxin on Human DNA Topoisomerase II, Tubulin Polymerization, KB Cells, and Their Resistant Variants

Six 4 beta-arylamino derivatives of 4'-O-demethylepipodophyllotoxin were examined for inhibitory activity against human DNA topoisomerase II and tubulin polymerization, their ability to generate protein-linked DNA breaks in cells, and their cytotoxicity toward the KB cell line and its VP-16- and vincristine-resistant variants. Five of these derivatives were 5- to 10-fold more potent than VP-16 as inhibitors of DNA topoisomerase II in vitro, and all of these derivatives could generate the same amount of or more protein-linked DNA breaks in cells than VP-16 at 1-20 microMs. Tubulin polymerization was inhibited by these compounds to different degrees in the order: podophyllotoxin greater than W73 greater than W87 greater than NPF greater than NPC greater than W68 greater than W38 greater than VP-16. These analogues were cytotoxic not only to KB cells but also to their VP-16-resistant and vincristine-resistant variants which showed decreased cellular uptake of VP-16 and a decrease in DNA topoisomerase II content or overexpression of MDR1 phenotype. These characteristics may cause these derivatives to have different spectrums of antitumor activity.
Control of multiple resonant power processors in a multi-source system

Analysis and test results show that phasor-regulated, Mapham-derived resonant inverters can be paralleled to provide standardizing interfaces for multiple sources on a utility-type, aerospace power distribution bus. The basic sources do not require matching in any way, and may have grossly different characteristics. Fully stable system architectures with multiple sources, parallel/redundant distribution buses, and a wide variety of loads can be easily constructed and controlled. The commands and parameters available for system control allow for tight tolerance bus voltage control, and absolute power-sharing control from the various sources over the full range of possible source and load variations. That level of control enables simplified load power processing hardware and the distribution of losses to optimally load the source thermal control system. Positive control of all system performance and allocation of losses are not required by all missions or vehicles, and overall vehicle considerations do not always require the loads on vehicle energy sources and thermal control systems to be balanced. In those cases, power system control can be simplified, and a hierarchical set of defaults can be substituted for computer-generated or supervisory input commands to allow for stable, autonomous system operation. >
Delivering ease of use [software development]

The uptake of HCI (human-computer interaction) and usability engineering by software development organisations can be terminally impeded by lack of appreciation of their value, even where ease of use is recognised as important. Descriptions of HCI offerings in terms of activities and methods are not readily comprehensible to managers of software products. Similarly, descriptions of HCI activities and methods give little indication of how these are to be managed with reference to the stages and deliverables in a software product development life cycle. This lack of clear association between usability engineering and software engineering in product development contributes to the marginalisation of usability-related activities. Specifying HCI or usability contributions to product development in terms of deliverables, on the other hand, can provide a solid basis for a manageable usability perspective on the development of software products. This article identifies a set of usability deliverables, describes their content and shows how they relate to a software product design and development process.
Inhibition of bacterial growth and biofilm production by constituents from Hypericum spp.

Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. Five of the seven compounds demonstrated growth inhibition against the Gram-positive bacteria with minimum inhibitory concentrations (MIC) ranging from 1.95 µg/mL to 7.81 µg/mL. Four of the secondary metabolites inhibited biofilm production by certain Gram-positive strains at sub-MIC concentrations.
Frameshift mutations induced by three classes of acridines in the lacZ reversion assay in Escherichia coli: potency of responses and relationship to slipped mispairing models.

The frameshift mutagenicity of 9-aminoacridine (9AA) was compared with that of quinacrine, the acridine mustards ICR-191 and quinacrine mustard (QM), and the nitroacridine Entozon in the lacZ reversion assay in Escherichia coli. As intercalating agents, 9AA and quinacrine cause mutations through noncovalent associations with DNA. Mustards and nitroacridines form covalent adducts in DNA and give rise to different spectra of mutations. Quinacrine and 9AA most effectively induced -1 frameshifts in a run of guanine residues, with 9AA being the more potent mutagen. They also induced +G frameshifts. The acridine mustard ICR-191 was a stronger mutagen than 9AA, owing largely to its potent induction of +G frameshifts. QM induced +G frameshifts more strongly than did its nonreactive counterpart quinacrine. The nitroacridine Entozon differed from the other acridines in being a potent inducer of -2 frameshifts, but it was less effective in inducing +/-1 frameshifts. Quinacrine, although a simple intercalator, induced all five kinds of frameshift mutations detected in the assay, as did the acridine mustards. Although +A and -A frameshifts were induced, adenine runs were less susceptible to acridine mutagenesis than guanine runs. The patterns of frameshift mutagenicity in the lacZ assay are similar to those in an assay based on the reversion of mutations in the tetracycline-resistance gene of the plasmid pBR322. The similarity suggests that the responses reflect the inherent bacterial mutagenicity of the compounds in the local sequence context and are not highly dependent on the broader sequence context. The results are interpreted with respect to slipped mispairing models of frameshift mutagenesis.
Perfect Frobenius complements

Let H be a finite Frobenius group with a perfect Frobenius complement G. Two new proofs that G is isomorphic to SL2(5) are given.
Utilization of a real-time PCR approach for Haemophilus influenzae serotype determination as an alternative to the slide agglutination test

Our laboratory has developed a simple two-step multiplex real-time PCR for use on isolates of Haemophilus influenzae for molecular serotype identification and the detection of capsular gene targets. The assay consists of a 2-plex real-time PCR targeting the capsule transport gene (bexA), and serotype b specific gene (bcsB), and a 5-plex real-time PCR detecting serotypes a, c, d, e, and f targeting Region II serotype-specific genes. Both real-time PCR assays are highly sensitive (<8 CFU) for all serotypes and 100% specific when tested by a panel of more than 40 bacterial organisms. A retrospective study of 214 isolates received between 1998 and 2011 were tested and compared against the traditional slide agglutination test (SAT) resulting in 100% concordance. We demonstrate that this two-step real-time PCR approach is more sensitive than previously published PCR assays and provides a simple alternative to the SAT. Reliable, rapid and sensitive H. influenzae serotyping is critical for identifying new emerging strains for epidemiological surveillance.
Field and paleomagnetic characterization of lithic and scoriaceous breccias at Pleistocene Broken Top volcano, Oregon Cascades

Abstract Cirque-wall exposures of cone-forming deposits of Pleistocene Broken Top volcano, Oregon Cascade Range, reveal that the volcano is composed of unconformity-bounded constructional units of coherent lava (lava-flow cores) and breccia. Coarse-grained autoclastic breccias are found above and below lava-flow cores and may extend downslope from coherent lava outcrops where they may or may not be associated with thin lava stringers. Mantle-bedded scoria-fall breccias are recognized by generally good sorting, mantle bedding, and presence of aerodynamically shaped bombs. These breccias vary considerably in thermal oxidation coloration (black, red, orange, purple). Many breccia layers are unsorted mixtures of scoria and lithic (nonvesicular) fragments that grade laterally to unambiguous autoclastic breccia or lava-flow cores. These layers are interpreted as hybrid pyroclastic–autoclastic deposits produced by incorporation of falling or fallen tephra into advancing lava-flow fronts. This latter breccia type is common at Broken Top and offers particular challenges for clast or deposit classification. Progressive thermal demagnetization results for selected examples of different breccia types show that most scoria-fall and autoclastic breccias are emplaced at elevated temperatures (averaging 100–300°C). Clasts within single deposits record different emplacement temperatures ranging, in some cases, from 100 to over 580°C indicating a lack of thermal equilibration within deposits. Magnetization directions for single breccia deposits are more dispersed than data typically reported for lava flows. Settling and rotation of clasts after cooling or incorporation of colder clasts that are not significantly reheated probably accounts for the relatively high dispersion and suggests that paleomagnetic studies demanding low within-site dispersion (e.g., for determining paleomagnetic poles or evaluating tectonic rotation) should avoid volcanic breccias.
Risk Factors for Epilepsy in Children With Neonatal Encephalopathy.

We examined neonatal predictors of epilepsy in term newborns with neonatal encephalopathy (NE) by studying children enrolled in a longitudinal, single center cohort study. Clinical data were obtained through chart review, and MRI was performed in the neonatal period. We administered a seizure questionnaire to parents of children aged ≥ 12 mo (range, 12 mo to 16.5 y) to determine the outcome of epilepsy. The association between clinical predictors and time to onset of epilepsy was assessed using Cox proportional hazards regression. Thirteen of 129 children developed epilepsy: all had neonatal seizures and brain injury on neonatal MRI. Of the newborns with neonatal seizures, 25% (15.8/1000 person-years) developed epilepsy, with the highest hazard ratios (HRs) in the newborns with status epilepticus (HR, 35.8; 95% CI, 6.5-196.5). Children with severe or near-total brain injury were more likely to develop epilepsy compared with those with only mild or moderate injury (HR, 5.5; 95% CI, 1.8-16.8). In a multivariable analysis adjusting for degree of encephalopathy and severe/near-total brain injury, status epilepticus was independently associated with epilepsy. These data add to information regarding epilepsy pathogenesis and further aid clinicians to counsel parents regarding the likelihood that a newborn with NE will develop epilepsy.
Stages of Diagenesis in the Development of Sandstones

On the basis of mineral replacements and intergrowths, four oxide series are recognized among sandstones: (1) alumina, lime-magnesia, iron oxide, (2) silica, lime-magnesia, iron oxide, (3) silica, alumina, iron oxide, (4) silica, alumina, lime-magnesia. Typical reactions are: a, for series (1), hematite + calcite + Mg � siderite + ferro-dolomite + dolomite; b, for series (2), hematite + clay minerals + silica � chlorite + greenalite; c, for series (3), diaspore + silica � clay minerals, and diaspore + silica + K � glauconite + clay minerals; also, during late burial illite + Na + K + Ca → muscovite + biotite + feldspar; d, for series (4), illite or glauconite → chlorite + muscovite; and calcite + Mg + illite → micas + feldspar + dolomite; also, with deep and late burial, clay minerals → chlorite or sericite, K feldspar → sericite, plagioclase → chlorite + chert. From the type of reaction and the principal sequence of occurrence three stages of diagenesis are established: Stage (1), redoxomorphic, which dominates the episodes of deposition and early burial. Reactions principally are reduction and oxidation which form the basis for the name of the stage. Stage (2), identified as locomorphic, involves replacement of one mineral by another, the two minerals not entering into mutual reaction. Such reactions are typical of the early burial stage and are an important part of the process of lithification. Stage (3), identified as phyllomorphic, follows the principal locomorphic replacements and involves development of micas, principally from clays. Among sandstones, the progress of diagenesis may be arrested at either the locomorphic or phyllomorphic stages, in more or less parallel fashion to metamorphic grades. Also, the phyllomorphic stage overlaps the zeolite and chlorite grades of metamorphism.
Identification of Transmembrane Helix 2 (M2) as the Main Pore-Lining Helix of Connexin 43 Gap-Junctional Hemichannels (GJH)

GJH are connexin hexamers that dock head-to-head to form gap-junctional channels. Current GJH models are based on low-resolution structural data showing 4 transmembrane α helices per connexin monomer, with insufficient detail for helix assignment; helices have been named A, B, C and D, with B and C as pore-lining. Here, we used luminescence resonance energy transfer to calculate distances between same-position residues in diametrically-opposed monomers of purified GJH formed by functional single-cysteine Cx43 mutants. Mutants were labeled with one donor (chelated Tb3+)-labeled and one or more fluorescent acceptor-labeled monomers, and distances between donor-acceptor probes were calculated from sensitized acceptor emission lifetimes. The distances allowed for the assignment of M2 (∼45 A) and M3 (∼41 A) as pore-lining, and M1 (∼57 A) and M4 (∼60 A) as peripheral helices. On the extracellular side (narrower side of the pore), the distances were ∼23 and ∼40 A, for M2 and M3 residues, respectively. The shorter M2 extracellular-side distance is evidence of tilting and suggests that M2 is helix C, the primary pore-lining helix. Single-Cys mutants of M1, M2 and M4 (8 per helix) were labeled with BADAN, a probe that displays emission maxima at longer wavelengths in hydrophilic environments. BADAN emission peaked at ≥ 480 nm in five of the M2 residues studied, none of the M1 and only one M4 residue position (probably exposed to the cytoplasm). From these and previous results, we built a new GJH model with the following helix assignment: M1 = A, M2 = C, M3 = B and M4 = D. This work was supported in part by NIH grants DC007150, GM068586 and GM79629, American Heart Association, Texas Affiliate grant 0755002Y, and Texas Advanced Research Program grant 010674-0046-2007.
Ne Hic Saltaveris: The Marxian Theory of Exploitation After Roemer

In his book A General Theory of Exploitation and Class (1982) (hereafter GT), John Roemer employs the tools of mainstream general equilibrium and game-theoretic analysis to develop a fundamental critique and broadbased reformulation of Marxian economic theory. Perhaps Roemer's most striking departure from traditional Marxian tenets lies in his explanation of the material basis of exploitation in capitalist economies. Roemer argues that capitalist exploitation must be understood as essentially the consequence of exchange given differential ownership of relatively scarce productive assets (DORSPA). In particular, Roemer concludes that capitalist exploitation does not fundamentally depend on capitalist domination of production, or what Marx termed the subsumption of labor under capital.
Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing

Bone morphogenic protein 2 (BMP-2) plays a key role in skeletal development, repair and regeneration. To gain a better understanding of the role of BMP-2 in periosteum-mediated bone repair, we deleted BMP-2 postnatally at the initiation stage of healing utilizing a Tamoxifen-inducible CreER mouse model. To mark the mutant cells, we further generated a BMP-2f/f; CreER; RosaR mouse model that enabled the activation of a LacZ reporter gene upon treatment of Tamoxifen. We demonstrated that deletion of BMP-2 at the onset of healing abolished periosteum-mediated bone/cartilage callus formation. In a chimeric periosteal callus with cells derived from both wild type and the mutant, over 90% of the mutant mesenchymal progenitors remained undifferentiated. Within differentiated bone and cartilage tissues, only a few cells could be identified as mutants. Using a bone graft transplantation approach, we further showed that transplantation of a mutant bone graft into a wild type host failed to rescue the deficient differentiation of the mutant cells at day 10 post-grafting. These data strongly suggest that the endogenous expression of BMP-2 plays a critical role in osteogenic and chondrogenic differentiation of periosteal progenitors during repair. To determine whether BMP-2 deficient cells remained responsive to exogenous BMP-2, we isolated periosteal mesenchymal progenitors from BMP-2 deficient bone autografts. The isolated cells demonstrated a 90% reduction of endogenous BMP-2 expression, accompanied by significant decrease in cellular proliferation and a near blockade of osteogenic differentiation. The addition of exogenous BMP-2 partially rescued impaired proliferation and further enhanced osteogenic differentiation in a dose dependent manner. Taken together, our data show that the initiation of the cortical bone repair in vivo is controlled by endogenous BMP-2. Future studies are necessary to determine the mechanisms by which the BMP-2 pathway is activated in periosteal progenitor cells at the onset of cortical bone repair.
Deficiency of heme oxygenase-1 impairs renal hemodynamics and exaggerates systemic inflammatory responses to renal ischemia

Heme oxygenase-1 may exert cytoprotective effects. In this study we examined the sensitivity of heme oxygenase-1 knockout (HO-1−/−) mice to renal ischemia by assessing glomerular filtration rate (GFR) and cytokine expression in the kidney, and inflammatory responses in the systemic circulation and in vital extrarenal organs. Four hours after renal ischemia, the GFR of HO-1−/− mice was much lower than that of wild-type mice in the absence of changes in renal blood flow or cardiac output. Eight hours after renal ischemia, there was a marked induction of interleukin-6 (IL-6) mRNA and its downstream signaling effector, phosphorylated signal transducer and activator of transcription 3 (pSTAT3), in the kidney, lung, and heart in HO-1−/− mice. Systemic levels of IL-6 were markedly and uniquely increased in HO-1−/− mice after ischemia as compared to wild-type mice. The administration of an antibody to IL-6 protected against the renal dysfunction and mortality observed in HO-1−/− mice following ischemia. We suggest that the exaggerated production of IL-6, occurring regionally and systemically following localized renal ischemia, in an HO-1-deficient state may underlie the heightened sensitivity observed in this setting.
Effects of Mine Drainage on Ground Watera

Coal mining in Appalachia has degraded both the surface and ground water. During mining, ground water is drained from the rocks and the pyrite associated with the coal beds is exposed to air. Oxidation of the pyrite produces high iron ana sulfate concentration and a low pH in the water. Some of this polluted water flows directly into nearby streams and some moves into the ground-water system. When the latter occurs, the iron concentration can increase up to several hundred mg/1 and the sulfates to over one thousand mg/1. Unfortunately, in most cases the cessation of mining does not stop the ground-water pollution, and it can take many decades before the ground water again becomes usable. A detailed study of the effects of coal mining on ground water was conducted in the Toms Run drainage basin in northwestern Pennsylvania where coal mining and oil and gas well drilling have occurred for almost 100 years. The rocks of Mississippian and Pennsylvanian Age produce a multiaquifer system–three major aquifers separated by siltstone and shale beds (aquitatdes). The oil and gas wells act as a conduit system permitting acid mine drainage to move downward from the strip mines to underlying aquifers. It then moves laterally down dip and discharges as springs. The acid mine drainage adversely affects the ground-water quality by increasing the iron and sulfate content of the water especially in the vicinity of the strip mines.
Multilevel Challenges and Opportunities in Social Capital Research

Social capital refers to the resources derived from social relationships. Although the concept of social capital has been applied at the individual, group, and organizational levels of analysis, researchers have yet to fully embrace social capital’s potential as a multilevel lens through which we might better understand management and organizational phenomena. With a central objective of advancing social capital’s potential as a multilevel theoretical perspective, the authors make two contributions to the management literature. First, the authors comprehensively review two decades of management research to highlight how social capital has been empirically applied across levels of analysis. Second, based on the shortcomings and challenges revealed through the literature review, the authors identify and discuss avenues for future multilevel research, including suggestions for both macro and micro researchers.