cssi/SciSciGPT-SciSciNet huggingface dataset:
Improved pontic/tissue relationships using porous coralline hydroxyapatite block.

Porous coralline hydroxyapatite blocks were implanted in the anterior region of several patients to improve the pontic/ridge relationship for a fixed prosthesis, thereby improving esthetic appearance and oral hygiene performance. A beveled incision on the palate was used to displace the flap coronofacially without leaving an area of denuded bone or graft. Flap margins were sutured to the adjacent palatal tissues. At the 2½- and 3-year postgrafting follow-up, the implant area was healthy and ridge contours have been maintained. The permanent fixed partial denture is functional, and radiographic evaluation indicates the continued presence of the porous coralline hydroxyapatite implant. Three-year results have been promising enough to warrant continuing the procedure in patients requiring localized ridge augmentation.
4-1BB and Ox40 Are Members of a Tumor Necrosis Factor (TNF)-Nerve Growth Factor Receptor Subfamily That Bind TNF Receptor-Associated Factors and Activate Nuclear Factor κB

Members of the tumor necrosis factor (TNF)-nerve growth factor (NGF) receptor family have been shown to be important costimulatory molecules for cellular activation. 4-1BB and Ox40 are two recently described members of this protein family which are expressed primarily on activated T cells. To gain insight into the signaling pathways employed by these factors, yeast two-hybrid library screens were performed with the cytoplasmic domains of 4-1BB and Ox40 as baits. TNF receptor-associated factor 2 (TRAF2) was identified as an interacting protein in both screens. The ability of both 4-1BB and Ox40 to interact with TRAF2 was confirmed in mammalian cells by coimmunoprecipitation studies. When the binding of the receptors to other TRAF proteins was investigated, 4-1BB and Ox40 displayed distinct binding patterns. While 4-1BB bound TRAF2 and TRAF1, Ox40 interacted with TRAF3 and TRAF2. Using deletion and alanine scanning analysis, we defined the elements in the cytoplasmic domains of both receptors that mediate these interactions. The 4-1BB receptor was found to have two independent stretches of acidic residues that can mediate association of the TRAF molecules. In contrast, a single TRAF binding domain was identified in the cytoplasmic tail of Ox40. The cytoplasmic domains of both receptors were shown to activate nuclear factor kappaB in a TRAF-dependent manner. Taken together, our results indicate that 4-1BB and Ox40 bind TRAF proteins to initiate a signaling cascade leading to activation of nuclear factor kappaB.
Advances in Arabic Speech Transcription at IBM Under the DARPA GALE Program

This paper describes the Arabic broadcast transcription system fielded by IBM in the GALE Phase 2.5 machine translation evaluation. Key advances include the use of additional training data from the Linguistic Data Consortium (LDC), use of a very large vocabulary comprising 737 K words and 2.5 M pronunciation variants, automatic vowelization using flat-start training, cross-adaptation between unvowelized and vowelized acoustic models, and rescoring with a neural-network language model. The resulting system achieves word error rates below 10% on Arabic broadcasts. Very large scale experiments with unsupervised training demonstrate that the utility of unsupervised data depends on the amount of supervised data available. While unsupervised training improves system performance when a limited amount (135 h) of supervised data is available, these gains disappear when a greater amount (848 h) of supervised data is used, even with a very large (7069 h) corpus of unsupervised data. We also describe a method for modeling Arabic dialects that avoids the problem of data sparseness entailed by dialect-specific acoustic models via the use of non-phonetic, dialect questions in the decision trees. We show how this method can be used with a statically compiled decoding graph by partitioning the decision trees into a static component and a dynamic component, with the dynamic component being replaced by a mapping that is evaluated at run-time.
Situational information: Formal ontological categories and research consequences

‘Information’ is presumably the object of study in information science research. However, epistemological assumptions of concepts of information and the uses of the term ‘information’ in information science discourse and their cultural, social, and methodological implications are seldom examined. This study consists in the reconstructive analysis of concepts of information for explicating epistemological assumptions of foundational concepts of information in information science discourse, on the one hand, and for examining the relationship between concepts of information and research method and methodology, on the other. This study also proposes the study of information in our world, that is, rather than information in the, my or your world.
FAMILIAL CEREBELLAR ATAXIA WITH HYDROCEPHALUS IN BULL MASTIFFS

Familial cerebellar ataxia with concurrent hydrocephalus has previously been described in a family of bull mastiff pups, and recently has been identified in a litter from Louisiana. The 4 affected pups had ataxia, hypermetria, conscious proprioceptive deficits, behavioral abnormalities, and a visual deficit. In magnetic resonance imaging of the brain of two of the pups, there were symmetric hydrocephalus and two focal areas of increased signal intensity within the central nuclei of the cerebellum. Histopathologically there was vacuolization and mild astrogliosis within the deep cerebellar nuclei (dentate, interpositus, fastigial), caudal colliculi, and lateral vestibular nuclei. Although the postmortem results were not exactly the same as in the previously published report, the clinical features and histopathologic findings strongly support the diagnosis. This disorder is most likely inherited in an autosomal recessive manner.
Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

Gestational diabetes mellitus is a major complication of human pregnancy. The oral clearance (CL) of glyburide, an oral antidiabetic drug, increases 2-fold in pregnant women during late gestation versus nonpregnant controls. In this study, we examined gestational age-dependent changes in maternal-fetal pharmacokinetics (PK) of glyburide and metabolites in a pregnant mouse model. Nonpregnant and pregnant FVB mice were given glyburide by retro-orbital injection. Maternal plasma was collected over 240 minutes on gestation days (gd) 0, 7.5, 10, 15, and 19; fetuses were collected on gd 15 and 19. Glyburide and metabolites were quantified using high-performance liquid chromatography-mass spectrometry, and PK analyses were performed using a pooled data bootstrap approach. Maternal CL of glyburide increased approximately 2-fold on gd 10, 15, and 19 compared with nonpregnant controls. Intrinsic CL of glyburide in maternal liver microsomes also increased as gestation progressed. Maternal metabolite/glyburide area under the curve ratios were generally unchanged or slightly decreased throughout gestation. Total fetal exposure to glyburide was <5% of maternal plasma exposure, and was doubled on gd 19 versus gd 15. Fetal metabolite concentrations were below the limit of assay detection. This is the first evidence of gestational age-dependent changes in glyburide PK. Increased maternal glyburide clearance during gestation is attributable to increased hepatic metabolism. Metabolite elimination may also increase during pregnancy. In the mouse model, fetal exposure to glyburide is gestational age-dependent and low compared with maternal plasma exposure. These results indicate that maternal glyburide therapeutic strategies may require adjustments in a gestational age-dependent manner if these same changes occur in humans.
Addressing Diverse Needs: Differentiation in Distance Learning

Libraries are playing an increasing role in this shift from place-based to virtual learning environments. While school library media specialists are collaborating with classroom teachers, public librarians are working with home-school parents, and academic librarians are connecting with virtual faculty, all library professionals are dealing with a transition toward virtual patrons who need access to anywhere, anytime materials and support.
Recent advances in Ga N MMIC technology

GaN MMIC technology is now in production and is revolutionizing microwave Radar and Communication systems. In this paper we present an overview of GaN MMIC technology, focusing on device characteristics, reliability, and high frequency performance. We also introduce emerging GaN technologies such as GaN-on-diamond and the heterogeneous integration of GaN with Silicon.
Tubulin Proteomics in Cancer

Human tubulin α/β heterodimers are encoded by six and seven genes for the α- and β-subunit, respectively. Each of these isotypes can undergo various posttranslational modifications. Most of the sequence specificity for each isotype and posttranslational modifications occur at the C-terminal part of tubulin. The biological significance of this so-called “tubulin code” and its regulation are unresolved questions in basic cytoskeleton research and in pathologies such as cancer. βIII-tubulin repeatedly appears as a potential marker of poor prognosis in different tumor types and of drug resistance. Nevertheless, because of limitations in present methods of analysis, it is still unclear if tubulin isotype expression profiles will provide useful biomarkers for the stratification of cancer patients prior to treatments including microtubulo-interacting drugs. Recent progresses in mass spectrometry-based analyses of tubulin isotype expression in cancer cells are presented in this chapter. Such approaches allow the validation of tools such as antibodies used in immunohistochemistry, identifies tubulin sequences expressed in human cells and posttranslational modifications, and offer new avenues for tubulin isotype quantitation in tumor and normal tissues.
Capital Budgeting for Hay Storage Decisions

This article illustrates a capital budgeting tool that Extension agents and specialists can use to assist agriculture producers when contemplating the construction of a hay storage facility. Capital budgeting is a tool for evaluating the effects of an investment choice on a business. The payback method is a quick and simple capital budgeting procedure. Use of this method requires producers to estimate hay price, facility construction cost, and potential hay loss per year assuming no storage.
New Bond Would Offer a Better Way to Secure DC Plans

A looming global retirement crisis threatens the three pillars of retirement due to insufficient funding, improper investment decisions and transferring risk to individuals least capable of bearing it. Many private-sector workers do not have coverage and are not saving enough for retirement. Governments, federal and state, and the financial industry must innovate to stem this multifaceted crisis. Current assets and investment approaches leave a complex menu of choices on how much to save, how to invest, and how to decumulate.The simple solution is to create a U.S. Treasury-issued bond called “bond for financial security,” or BFFS, a single instrument that encompasses both the accumulation and decumulation phases of a defined contribution participant. By matching the desired retirement cash flow pattern, BFFS distill retirement planning into a single decision: how much to save. It eliminates intermediary fees that cut into the retirement income pot. The main characteristics of BFFS would be inflation-indexed, coupon-only, that start to pay only at retirement, and that, too, only for a period tied to average life expectancy. BFFS are a good deal for governments, too. In fact, governments are the biggest beneficiaries. BFFS not only improve retirement outcomes for all defined contribution plans, but also have spillover benefits for the Obama administration and future governments. Cash flows from BFFS reflect synergistic cash flows for infrastructure spending; namely, large cash flows up front for capital expenditure, followed by delayed, inflation-indexed revenue once projects are online. Financing infrastructure has been a challenge and a priority for the Obama administration and other countries. BFFS can help many developed and developing countries achieve two key long-term goals for their citizens: more secure retirement income and better infrastructure.
Optimal Design and Control of Centrifugally Tuned Dynamic Vibration Absorbers

Christian Huygens, Leonhard Euler, Johann Bernoulli, Adrien Legendre and others contributed to the concept of the Brachistochrone [4], the path requiring the least time of descent under gravity. Such paths are cycloids. It is a corollary that this time is indepedent of the starting point. If the path is made symmetrical about the vertical, the descending particle rises once again to its initial elevation. The rise and fall continues in a simple harmonic, oscillatory fashion. In effect, a pendulum type oscillator is created without the non-linear behavior of a pendulum where the period of the oscillation grows larger with the amplitude of the motion. Accordingly, a cycloidal path yields an isochronous oscillator, since the time of descent is constant as well as minimal. It is shown in the Analysis that in the case of the centrifugal force field a tuned centrifugal pendulum de-tunes as the amplitude grows. A formal search for an isochronous oscillator in this case yields higher plane curve paths which are cycloid-like, but not actually cycloids. This follows rust from an approximative solution to the non-linear deferential equation of the path [5]. Then a numerical, digital computer solution method [6] is implemented to generate the needed ordinates of the higher plane curves in actual machine design, structural design applications [7].
Heterogeneous Catalysis on Atomically Dispersed Supported Metals: CO2 Reduction on Multifunctional Pd Catalysts

Because of their heterogeneous nature, supported metal catalysts always contain metal centers in a rather broad dispersion range, and the presence of even atomically dispersed metals has been reported on oxide supports. The role of the atomically dispersed metal centers in the overall catalytic performances of these supported metal catalysts, however, has not been addressed to date. In this study, temperature programmed reaction and scanning transmission electron microscopy experiments were applied to show the fundamentally different reactivity patterns exhibited by Pd metal in atomically dispersed and traditional 3D clusters in the demanding reaction of CO2 reduction. The requirement for two different catalyst functionalities in the reduction of CO2 with hydrogen on Pd/Al2O3 and Pd/MWCNT catalysts was also substantiated. The results obtained clearly show that the oxide support material, even when it is considered inert like Al2O3, can function as a critical, active component of complex catalyst systems.
Comparative Residual Behavior of Pyrethrins and Piperonyl Butoxide on Wheat

Because of difficulty in determining residues of pyrethrins quantitatively in the presence of high concentrations of the usual synergist, piperonyl butoxide, the evaluation of the residual behavior of the readily analyzed piperonyl butoxide alone has heretofore been thought to be adequate for most residue studies with pyrethrins-piperonyl butoxide mixtures. The residual behavior of the pyrethrins has been thought to parallel that of the piperonyl butoxide component of such mixtures. By the use of chromatographic techniques in conjunction with colorimetric procedures, the residual behavior of the pyrethrins and of piperonyl butoxide on stored wheat have been compared. The pyrethrins have an apparent residue half-life of 5.8 weeks in contrast with that of 9.0 weeks for piperonyl butoxide.
Abstract 2106: Regulation of Rb1 and caspase 3/7 by miR-17-5p, miR-132/-212, and miR-337-3p: Oncogenic role of miRNAs in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal forms of cancer. Reasons for the high mortality associated with this disease include a lack of effective treatments and poor early detection methods. Enhanced understanding of the pathways that are deregulated in PDAC could lead to improved therapies and diagnostics. We and others have reported a microRNA expression signature that is associated with PDAC. The purpose of this study was to identify target genes and pathways that are regulated by miRNAs with altered expression in PDAC. We found several miRNAs including miR-17-5p, −132/-212, and −337-3p that have increased expression in clinical specimens of PDAC compared to normal and adjacent benign pancreas. miR-132 and −212 are located within 472 bp of each other on chromosome 17, have the identical seed sequence and should therefore regulate the identical targets. Through a luciferase reporter assay and western blotting, we found that miR-132/-212 directly regulate the expression of the tumor suppressor Rb1 in the pancreatic tumor cell lines HS766T and PANC-1. Over expression of these miRNAs (miR-132/-212) either through stable expression or pre-miR oligos increased the proliferation rate of HS766T and PANC-1 cells. Expression of 18 genes that are transcriptionally regulated by the E2F including Cyclin A, Cyclin B, PCNA, MCM2, MKI67 and others was increased following miR-132/-212 over expression. Additional genes that are predicted to be targeted by these miRNAs include procaspase 3 (miR-337-3P) and procaspase 7 (miR-132/-212 and miR-17-5p). These caspases are essential in executing programmed cell death in tumors. Western blotting and luciferase reporter assays determined that procaspase 3 and procaspase 7 are regulated by miR-337-3P and miR-132/-212 & miR-17-5p, respectively. Our data strongly suggest that over expression of miR-132/-212 contributes to the enhanced proliferation that is observed in pancreatic cancer. Furthermore, this study is the first to discover that main effector caspases, caspase 3 and 7, are post-transcriptionally regulated by miRNAs. Our findings suggest that resistance to chemotherapeutics in pancreatic tumor tissues may be linked to reduced expression of these procaspases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2106.
A fragment of engrailed regulatory DNA can mediate transvection of the white gene in Drosophila.

We have found a fragment of engrailed regulatory DNA that has an unusual effect on expression of a linked marker gene, white, in the P element transposon CaSpeR. Normally, flies homozygous for a given CaSpeR insertion have darker eyes than heterozygotes. However, when a particular engrailed DNA fragment is included in that transposon, homozygotes often have lighter eyes than heterozygotes. Thus, engrailed DNA appears to cause white expression to be repressed in homozygotes. The suppression of white is dependent on the proximity of the two transposons in the genome-either in cis (i.e., on the same chromosome) or in trans (i.e., on homologous chromosomes). Thus, the engrailed fragment is mediating a phenomenon similar to that mediated by the zeste gene at the white locus. However, the interactions we observe do not require, nor are influenced by, mutations of zeste. We suggest that the engrailed DNA contains one or more binding sites for a protein that facilitates interactions between transposons. The normal function of these sites may be to mediate interactions between distant cis-regulatory regions of engrailed, a large locus that extends over 70 kilobases.
Using dynamic adaptive systems in safety-critical domains

The development of safety-critical Cyber-Physical Systems (CPS) is expanding due to the Internet of Things' promise to make high-integrity applications and services part of everyday life. This expansion is seen in the dependencies some connected vehicles have on cloud services that provide guidance and accident avoidance / detection features. Such systems are safety-critical since failure could result in serious injury or death. Due to the severe consequences of failure, fault-tolerance, reliability and dependability should be primary driving qualities in the design and development of these systems. However, the cost of the analysis, evaluation and certification activities needed to ensure that the possibility of failure has been sufficiently mitigated is significantly higher than the cost of developing traditional software. Our group is exploring the addition of dynamic adaptive capabilities to safety-critical systems. We postulate that dynamic adaptivity could provide several enhancements to safety-critical systems. It would allow systems to reason about the environment within which they are sited and about their internal operation enabling decision making that is context-specific and appropriately prioritized. However, the addition of adaptivity with the associated overhead of reasoning is not without drawbacks particularly when hard real-time safety-critical systems are involved. In this brief position paper, we explore some of the questions and concerns that are raised when dynamic adaptive behavior is introduced into safety-critical systems as well as ways that the Architecture Analysis \& Design Language (AADL) can be used to model / analyze such systems.
Analytical Characteristics of Late-Eluting Halogenated Flame Retardants

The analytical characteristics of halogenated flame retardants were studied. Suitable electron capture gas-liquid chromatographic conditions were developed, and retention times and sensitivity responses were obtained. The behavior of these industrial chemicals through the AOAC multiresidue method for nonfatty foods was studied using fish as the test substrate. Of the 24 flame retardants investigated, 23 were recovered (85-110%) using the AOAC method.
Priced Unsecured Intraday Overdraft Facilities

The central banks of the EU are jointly endeavouring to reform their large-value payment systems. The guiding principle is the irrevocability of settlement in all large-value fund transfer systems. Moreover, in order to anticipate the future interconnection of payment systems and to harmonise and reduce the level of risk, the central banks of the EU have thought it necessary to build an RTGS fund transfer system in every country. Despite the zero-settlement lag, real-time gross settlement does not on its own eliminate systemic risk. Indeed, congestion in RTGS systems, due to either voluntary or involuntary actions by system participants as described in Part I, may lead to a generalised payment gridlock with potential systemic consequences. Central banks can eliminate liquidity risk from RTGS systems by standing ready to supply the settlement medium as necessary in the form of explicit overdraft facilities. However, this shifts credit risk on the central bank to a degree that depends on the terms upon which its funds are granted.
Hydrogen Exchange Mass Spectrometry Reveals Allosteric Interactions Between the Distal and the Proximal Domains of Human ADAMTS13

Background: Deletion of the distal C-terminal domains, or a decrease in pH, or the binding of a monoclonal antibody to the C-terminal domains of ADAMTS13 increases its proteolytic activity towards VWF peptide substrate, VWF73, by approximately 2-fold; this suggests an allosteric interaction between the distal and proximal domains of ADAMTS13. However, neither the underlying mechanism of the allosteric interaction nor the exact sites of interaction between the proximal domains and the distal C-terminal domain are fully understood. Objective : To determine the binding sites and kinetic interactions between the proximal and distal domains of ADAMTS13 and to gain insight into the mechanism of allosteric regulation of ADAMTS13 function. Methods: Hydrogen deuterium exchange plus LC-mass spectrometry (HX-MS) and surface plasmon resonance (SPR) were employed to determine conformational changes and direct binding interactions between the proximal and distal domains of ADAMTS13. Results: Recombinant full-length (rFL-A13) and an ADAMTS13 variant truncated after the spacer domain (rMDTCS) were purified to homogeneity. After incubation with deuterium for various times (0-6 hours), both rFL-A13 and rMDTCS were digested with pepsin and fungal protease-13 and then partially resolved by liquid chromatography before being injected into a LTQ ObitrapXL mass spectrometer for peptide identification. Overall, 188 of the total 338 peptides in rFL-A13 were identified, spanning the metalloprotease, cysteine-rich, and spacer domain. Only 16 peptides were found to be less accessible (or protected from deuterium-hydrogen exchange) in rFL-A13 than in rMDTCS. Two of these regions reside in the metalloprotease domain (residue 78-127 and 282-304). The next region is at a loop on the cysteine-rich domain (residue 446-473 and 495-501). The next peptides are in the adjacent loops of the spacer domain with one peptide 596-603, and five overlapping peptides spanning from 632-642, and then finally one peptide from the C-terminal of the MDTCS variant (residue 676 to 688). These results indicate that the distal C-terminal domains interact with multiple discrete sites in the proximal domains of ADAMTS13, resulting in protection from hydrogen-deuterium exchange. Such an interaction was further demonstrated by direct binding experiments with SPR. The distal domains including CUB, T2-CUB, and T5-CUB bound directly to M, MDT, and MDTCS under flow with high affinity. Conclusion : Our findings demonstrate the allosteric interactions between the distal domains and the proximal domains at multiple discrete sites. Such an interaction may regulate catalytic efficiency and substrate specificity of the metalloprotease domain of ADAMTS13 under various conditions. ![Figure][1] Disclosures Zheng: Ablynx: Consultancy; Alexion: Research Funding. [1]: pending:yes
Effect of different feeding levels during three short periods of gestation on sow and litter performance over two reproductive cycles

The present study investigated the effects of different feeding levels during 3 short periods of gestation on sow and litter performance and its impact on subsequent reproductive performance. A total of 160 multiparous sows were allotted to 1 of 4 dietary treatments using a randomized complete block design with initial body weight (BW) and backfat (BF) as the blocking criteria. All sows were fed one common corn-soybean meal-based diet with the amount of 1.0×maintenance energy intake (100×BW0.75kcalME/d) throughout gestation except 3 periods of 7 d when dietary treatments were imposed on d 27, d 55 and d 83 of gestation. During the 3 short periods, sows were fed 1 of 4 different feeding levels: 0.5, 1.0, 1.5 and 2.0×maintenance energy level (0.5M, 1.0M, 1.5M and 2.0M, respectively). Results showed that both BW gain (16.12, 24.74, 30.62 and 36.71kg, respectively) and BF change (-0.27, 0.99, 1.49 and 2.45mm, respectively) from d 27 to 109 of gestation increased linearly (P 0.10) among treatments. Subsequent reproductive performance was not affected (P>0.10) by feeding levels during the previous reproductive cycle. In conclusion, increasing feeding levels during 3 short periods of gestation increased BW and BF gains during gestation and caused less BW gain and more BF loss during lactation due to the reduction of lactation feed intake in response to increasing gestation feeding levels. Increasing feeding levels during 3 short periods of gestation increased piglet birth weight, but did not affect piglet weaning weight. The feeding strategies in the current reproductive cycle did not impact subsequent reproductive performance. It was estimated that requirements of 1.20M, 0.66M and 0.65M feeding levels were needed to maintain a constant BW during d 27-34, d 55-62 and d 83-90 of gestation, respectively, indicating current maintenance energy requirement may underestimate the actual maintenance energy requirement in the early gestation, but overestimate the actual maintenance energy requirement in the mid and late gestation.
Improvement of High‐Density Lipoprotein Function in Patients With Early Rheumatoid Arthritis Treated With Methotrexate Monotherapy or Combination Therapies in a Randomized Controlled Trial

Objective Abnormal function of high-density lipoprotein (HDL) has been implicated as a potential mechanism for the increased incidence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). This study was undertaken to evaluate changes in HDL function and HDL-associated proteins over 2 years of follow-up in patients with early RA receiving either methotrexate (MTX) monotherapy, MTX + etanercept (ETN) combination therapy, or MTX + sulfasalazine (SSZ) + hydroxychloroquine (HCQ) triple therapy in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Methods The antioxidant capacity of HDL, paraoxonase 1 (PON-1) activity, and levels of HDL-associated haptoglobin (Hp), HDL-associated apolipoprotein A-I (Apo A-I), and myeloperoxidase (MPO) were measured in 550 TEAR participants at 4 time points (time 0 [pretreatment] and at 24, 48, and 102 weeks of treatment). Repeated-measures analysis using mixed-effects linear models with an autoregressive covariate structure was performed to model the within-subject covariance over time. Results Mixed-effects models, which were controlled for traditional CV risk factors, treatment regimen, prednisone use, and statin use, demonstrated significant associations between RA disease activity, measured using the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, or C-reactive protein level, and the profile of HDL function over time. Specifically, decreases in RA disease activity over time were associated with increases in PON-1 activity and levels of HDL-associated Apo A-I, and decreases in the HDL inflammatory index and levels of MPO and HDL-associated Hp. Conclusion Reduced disease activity in patients with early RA treated with MTX monotherapy, MTX + ETN combination therapy, or MTX + SSZ + HCQ triple therapy in the TEAR trial was associated with improvements in the HDL function profile. Additional studies are warranted to evaluate abnormal HDL function as a potential mechanism and therapeutic target for CV risk in patients with RA.
Gene amplification during stages of carcinogenesis.

Models of carcinogenesis have developed from extensive observation of clinical and experimental systems. (This summary is based on Pitot, 1981.) The related concepts of promotion and progression describe an essential feature of carcinogenesis, the gradual change from a normal cell to a tumor composed of proliferating, invading, metastasizing cells. Promotion is the gradual conversion of undetectable initiated cells to tumors without the continuing action of a carcinogen. Promotion requires distinct agents and involves both cell proliferation and gradually changing cell properties. In other words, promotion is the process by which an initiated cell evolves from a state of homeostatically regulated proliferation to a state of inadequately regulated proliferation. However, the appearance of a tumor is not really an endpoint in this process, and the more general term, progression, refers to the continuous evolution in characters both before and after a tumor has formed.
Agriculture, the Global Nitrogen Cycle, and Trace Gas Flux

The global budget of nitrous oxide is out of balance, with sources exceeding sinks by 30–40%, and our understanding of the causes of this imbalance is inadequate. Moreover, our knowledge of the budgets of other nitrogen-containing trace gases is worse than that for nitrous oxide. An analysis of the overall global nitrogen cycle and anthropogenic perturbations to it suggest that the global cycle has been altered to a greater extent than has nitrous oxide, in that fluxes of nitrogen across ecosystem boundaries have more than doubled as a consequence of human activity. The dominant sources of change to the overall cycle are agricultural intensification and land-use change, particularly in tropical regions. These processes should be evaluated carefully as causal factors for imbalances in global budgets of nitrogen-containing trace gases.
Current Trends in Localization Techniques for Non-palpable Breast Lesions: Making the Invisible Visible

With ever more sophisticated imaging modalities and screening programs, the incidence of small, non-palpable breast cancers is increasing. This poses a unique challenge to surgeons who seek to obtain negative margins while maintaining a cosmetically acceptable breast. Herein, we review the current localization techniques available and discuss the latest advancements. While wire localization remains the historical gold standard for non-palpable breast lesion localization, many new invasive and non-invasive techniques have been utilized in recent years. These techniques can be performed by the surgeon alone or in conjunction with a radiologist partner. Multiple new techniques employ the insertion or deposit of a radioactive device or substance to identify the lesion. Positive margin status, clinician and patient comfort, and procedural time and ease have been serially evaluated as means to judge differences between localization techniques. However, the literature measuring these variables is heterogeneous with respect to definition across techniques making direct comparisons difficult. Further, the recent widespread adoption of “no tumor” at ink as a negative margin has revolutionized and standardized what constitutes a negative margin in invasive breast cancer. As a result, some of the previously reported benefits to certain localization techniques may not be as relevant today. Localization techniques for non-palpable breast lesions are evolving. Trends away from wire-guided localization to radioactive-implanted sources to surgeon-directed, ultrasound-guided or non-radioactive implantable devices are occurring. Unfortunately, current literature is heterogenous with respect to type of localization technique and outcomes reported, making direct comparison between the multiple localization techniques difficult. As such, the main differences among techniques remain with volume of resection, source radioactivity, institutional resources, and surgeon and radiologist preference. The future will likely see implementation of technology that has the benefits of current techniques but without the associated limitations of tracking radioactive sources.
Land cover classification from multi-temporal, multi-spectral remotely sensed imagery using patch-based recurrent neural networks

Abstract Environmental sustainability research is dependent on accurate land cover information. Even with the increased number of satellite systems and sensors acquiring data with improved spectral, spatial, radiometric and temporal characteristics and the new data distribution policy, most existing land cover datasets are derived from a pixel-based, single-date multi-spectral remotely sensed image with an unacceptable accuracy. One major bottleneck for accuracy improvement is how to develop an accurate and effective image classification protocol. By incorporating and utilizing multi-spectral, multi-temporal and spatial information in remote sensing images and considering the inherit spatial and sequential interdependence among neighboring pixels, we propose a new patch-based recurrent neural network (PB-RNN) system tailored for classifying multi-temporal remote sensing data. The system is designed by incorporating distinctive characteristics of multi-temporal remote sensing data. In particular, it uses multi-temporal–spectral–spatial samples and deals with pixels contaminated by clouds/shadow present in multi-temporal data series. Using a Florida Everglades ecosystem study site covering an area of 771 square kilometers, the proposed PB-RNN system has achieved a significant improvement in the classification accuracy over a pixel-based recurrent neural network (RNN) system, a pixel-based single-image neural network (NN) system, a pixel-based multi-image NN system, a patch-based single-image NN system, and a patch-based multi-image NN system. For example, the proposed system achieves 97.21% classification accuracy while the pixel-based single-image NN system achieves 64.74%. By utilizing methods like the proposed PB-RNN one, we believe that much more accurate land cover datasets can be produced over large areas.
Bezlotoxumab: an emerging monoclonal antibody therapy for prevention of recurrent Clostridium difficile infection

Clostridium difficile infection (CDI) is the most common health care-acquired infection associated with high hospital expenditures. The incidence of subsequent recurrent CDI increases with prior episodes of CDI, 15%-35% risk after primary CDI to 35%-65% risk after the first recurrent episode. Recurrent CDI is one of the most challenging and a very difficult to treat infections. Standard guidelines provide recommendations on treatment of primary CDI. However, treatment choices for recurrent CDI are limited. Recent research studies have focused on the discovery of newer alternatives for prevention of recurrent CDI targeting prime virulence factors involved in C. difficile pathogenesis. Bezlotoxumab is a human monoclonal antibody directed against C. difficile toxin B. Multiple in vitro and in vivo animal studies have demonstrated direct binding of bezlotoxumab to C. difficile toxin B preventing intestinal epithelial damage and colitis. Furthermore, this monoclonal antibody mediates early reconstitution of gut microbiota preventing risk of recurrent CDI. Randomized placebo-controlled trials showed concomitant administration of a single intravenous dose of 10 mg/kg of bezlotoxumab, in patients on standard-of-care therapy for CDI, had no substantial effect on clinical cure rates but significantly reduced the incidence of recurrent CDI (~40%). It shows efficacy against multiple strains, including the epidemic BI/NAP1/027 strain. Bezlotoxumab is a US Food and Drug administration-approved, safe and well-tolerated drug with low risk of serious adverse events and drug-drug interactions. Bezlotoxumab has emerged as a novel dynamic adjunctive therapy for prevention of recurrent CDI. Further studies on real-world experience with bezlotoxumab and its impact in reducing rates of recurrent CDI are needed.
Relational Mindfulness for Psychiatry Residents: a Pilot Course in Empathy Development and Burnout Prevention.

Psychiatry residents face challenges daily that test their capacity to be empathic and attuned to their own self-care. This can have a deleterious impact not only on the residents but also on patient-care. Training to manage the challenges of the work and cultivate stronger patient relationships is needed but often missing in medical education. This study aimed to pilot an empathy training course based in relational mindfulness and assess the impact on burnout and empathy. Seven first-year psychiatry residents (PGY-1) at an academic medical center in a mid-size city in the southeast participated in an eight-week pilot program created by the authors that integrated relational mindfulness and empathy training. Data were gathered from the seven PGY-1s on measures of burnout and empathy and on their experience of the training. The PGY-1s demonstrated a downward trend in means on all three burnout subscales and significant improvement on the measure of empathy (f = 8.98; p = .02). Overall, the PGY-1s reported an increased awareness of their cognitive and emotional experiences and stated that the skills learned in the program increased their ability to care for themselves, their patients, and their families. Training in intrapersonal and interpersonal attunement is often overlooked in medical training, leading to resident burnout and negative patient outcomes. An empathy course based in relational mindfulness may be a viable strategy for programs looking to attend to their residents’ emotional health and bridge the empathy training gap.
Item Parameter Drift in Computer Adaptive Testing Due to Lack of Content Knowledge

This study was conducted to analyze potential item parameter drift (IPD) impact on person ability estimates and classification accuracy when drift affects an examinee subgroup. Using a series of simulations, three factors were manipulated: (a) percentage of IPD items in the CAT exam, (b) percentage of examinees affected by IPD, and (c) item pool targeting. IPD impact on ability estimation was evaluated using bias and root mean square error (RMSE). A multivariate general linear model treating three factors as fixed effects and bias and RMSE as outcome variables are used to investigate both main and interaction effects. The impact on classification accuracy was examined based on number and percentages of misclassifications, their significance, and rank order correlations. The findings revealed that IPD exposed to a sub-group of examinees can affect classification accuracy of those examinees substantially, but IPD impact on average ability estimation was small. The study provides useful information to school...
American Indian, Alaska Native, and Native Hawaiian Bilingual Education

There are nearly two million American Indians, Alaska Natives, and Native Hawaiians in the United States, representing 510 federally recognized tribes and 175 distinct languages. This cultural and linguistic diversity is compounded by inter-and intra-group differences in Native language fluencies and literacy histories, and by the fact that language education for indigenous students is carried out in federal, state, parochial, private, and Indian-controlled schools. The uniqueness of individual tribal and community contexts notwithstanding, all indigenous peoples in the U.S. share a history as the targets of federal policies aimed at eradicating their languages and lifeways. The statement of one Commissioner of Indian Affairs sums up those policies: The goal, he stated, was to remove ‘the stumbling blocks of hereditary customs and manners,’ and of these, ‘language is one of the most important’ (Medicine, 1982, p. 399). The legacy of such policies has been Native language loss and sociocultural dislocation, even as indigenous students have experienced considerable failure in English-only schools. Thus, for indigenous groups in the U.S., bilingual education has been both a reclamation of language rights and control over education, and a bridge to the perceived opportunities associated with English.
Structure Dependence of Kinetic Energy Released in X-ray-Induced Fragmentation

We have analyzed transient structures in deuterated acetylene isomerized by 10 fs 400 eV X-rays, and probed by coulomb explosion with a second delayed X-ray pulse. Structural changes are revealed through fragment kinetic energy release.
Liquid Helium Technology at the National Bureau of Standards

Summary A brief history of the role of NBS in liquid helium technology includes short discussions of the various types and sizes of liquefiers used, starting about 1935 when helium was first liquefied in this country. Highlights of the experimental work are given, including some of the work performed at NBS, Washington, on “second sound” as well as the engineering work at NBS, Boulder, on helium handling and transportation, and the production of liquid helium with a small high-speed turbine expander.
Wartime Work for the British Navy

It was my association with Hermann Bondi that gave me the chance to enter radar research after graduating. Bondi had been hired by Fred Hoyle, the head of the theory division radar research establishment of the Admiralty, the British authority responsible for the command of the Royal Navy. Bondi had asked for me to be brought in as an engineer to join himself and Hoyle. Bondi suggested my name to Hoyle, just on the grounds that he knew me and he thought that I may be able to make a contribution to this most important and, at that time, highly sophisticated and top secret branch of the scientific civil service.
Nicotine Analogs: Structure-Affinity Relationships For Central Nicotinic Acetylcholinergic Receptor Binding

Cholinergic receptors are one of the oldest known populations of neurotransmitter receptors, and acetylcholine is their natural ligand. Shortly after the discovery of acetylcholinergic receptors it was realized that the actions of cholinergic agents could best be described by invoking two distinct populations of receptors: muscarinic acetylcholinergic receptors and nicotinic acetylcholinergic receptors (nAChRs). Investigations during the 1950s to the 1980s identified a number of interesting nAChR agonists and antagonists using, for the most part, isolated peripheral tissue or organ preparations. Indeed, nicotinic pharmacophores were identified and are still the subject of continuing investigations. Relatively less has been done with nAChRs at the level of the central nervous system. However, the last decade has witnessed a significant resurgence of interest in nAChRs, particularly in central nAChRs, for several reasons. Nicotinic receptors were identified in brain homogenates, and techniques and radioligands were developed for their investigation. Furthermore, there exists today a better understanding of the structure of nAChRs. These receptors are pentameric units that are directly associated with an ion channel. The receptors are composed of various a (α2-α9), β (β1β4), y, and δ subunit combinations (see Shacka and Robinson 1996; Holladay et al. 1997) and their exact composition likely dictates their pharmacology and binding characteristics. There is also a difference between peripheral and central nAChRs, and the major population of brain nAChRs appears to be of the α4β2 type. Further fueling the interest in central nAChRs is evidence that such receptors may be involved in appetite, memory, analgesia, and various other physiological processes as well as in anxiety, memory, and certain mental and neurological disorders (Arneric and Brioni 1998). Although nicotine (1a), a naturally occurring nAChR ligand, is associated with a variety of toxic side effects, there is no reason to believe that these side effects are inextricably linked to the beneficial effects of nicotinic ligands. Thus, we and others have begun investigations to identify the structureactivity relationships (SAR) for nicotinic agonist and antagonist activity, and structure-affinity relationships (SAFIR) for central nAChR binding, to ultimately develop novel nicotinic agents with greater selectivity and reduced toxicity that may be useful for disorders involving nAChRs.
Sudden Cardiac Death Risk Stratification and the Role of the Implantable Cardiac Defibrillator

Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death (SCD), although perhaps not as significantly as previously believed. Given the heterogeneous nature of this disease entity, risk stratification of individuals with HCM remains challenging. The recent HCM risk-SCD prediction model seems to perform well in assessing individual SCD risk. Even though implantable cardiac defibrillators (ICDs) are effective in preventing SCD in patients at increased risk, the importance of shared decision making in deciding whether or not to undergo ICD implantation cannot be understated.
Three patterns of extra-testicular venous drainage in the rabbit. Divergence from a traditional concept.

Seventy-eight male New Zealand white rabbits were autopsied and found to have variable left extra-testicular venous anatomy. Our observations reveal that in the rabbit the left testis is drained in one of three ways, identified as either A (18%), B (30%) or C (52%) —type drainage. The right testicular vein in all cases drained directly into the inferior vena cava immediately superior to the right iliolumbar vein.