cssi/SciSciGPT-SciSciNet huggingface dataset:
Surveillance for pathology associated with cancer on endoscopy (SPACE): criteria to identify high-risk gastric polyps in familial adenomatous polyposis.

Background and Aims Gastric cancer is an extracolonic manifestation of familial adenomatous polyposis (FAP) and is associated with high-risk gastric polyps. There are no known endoscopic criteria to identify these high-risk polyps. Our aim was to develop endoscopic criteria to identify high-risk polyps on endoscopy in FAP. Methods We prospectively collected 150 gastric polyps in consecutive patients undergoing surveillance EGD at the Cleveland Clinic. Pictures were taken of each polyp under narrow-band imaging and high-definition white light. In an exploratory phase, 5 endoscopists developed consensus criteria using the images to distinguish high-risk (pyloric gland adenoma, tubular adenoma, hyperplastic) from low-risk (fundic gland with low-grade or no dysplasia) polyps. In the assessment phase, endoscopists were blinded to polyp pathology and used the criteria to predict the individual polyp risk category. To measure diagnostic accuracy, we reported the mean sensitivity, specificity, and interrater agreement (κ). Results Consensus criteria were developed based on 16 low-risk and 9 high-risk polyps. The final 149 polyps consisted of 128 low-risk and 22 high-risk polyps (1 polyp was excluded from analysis). Using the criteria, the 5 endoscopists distinguished high- from low-risk polyps with a mean sensitivity and specificity of 79% (16.3%) and 78.8% (10.8%), respectively. The κ coefficient was .45, indicating moderate agreement. Conclusions We developed endoscopic criteria to distinguish between high- and low-risk polyps associated with gastric cancer in FAP. The criteria provide guidance to endoscopists in targeting high-risk polyps while surveying the stomach of patients with proximal gastric polyposis.
Suppression of p16 alleviates the senescence-associated secretory phenotype

Abstract Oncogene induced senescence (OIS) is characterized by increased expression of the cell cycle inhibitor p16, leading to a hallmark cell cycle arrest. Suppression of p16 in this context drives proliferation, senescence bypass, and contributes to tumorigenesis. OIS cells are also characterized by the expression and secretion of a widely variable group of factors collectively termed the senescence-associated secretory phenotype (SASP). The SASP can be both beneficial and detrimental and affects the microenvironment in a highly context-dependent manner. The relationship between p16 suppression and the SASP remains unclear. Here, we show that knockdown of p16 decreases expression of the SASP factors and pro-inflammatory cytokines IL6 and CXCL8 in both RASG12V-and BRAFV600E-induced senescence. Notably, this is likely not due to suppression of senescence as LMNB1 and cyclin A expression remain low and p21 remains high. Moreover, low p16 expression in both cancer cell lines and patient samples correspond to decreased SASP gene expression, suggesting this is a universal effect of loss of p16 expression. Together, our data suggest that p16 transcriptionally regulates SASP gene expression, which has implications for understanding how p16 modulates both the senescent and tumor microenvironment.
Detection of melanin-mediated false-positive for BaxΔ2 immunohistochemical staining in human skin tissues

Bax{Delta}2 is a pro-apoptotic isoform of the Bax family. We have previously shown that Bax{Delta}2 protein expression is low in most healthy human tissues with the protein mainly scattered in the connective tissues. Surprisingly, in skin tissue, the Bax{Delta}2-positive staining was strikingly strong, especially in the basal layer of the epidermis. It has been documented that melanin in the basal cells displays a brown color that could give false-positive staining in the commonly used DAB-based (3-3-diaminobenzidine) immunostaining. To avoid the false-positive staining from DAB-melanin, we performed immunofluorescent staining on the same set of tissues which were positive for Bax{Delta}2 in the DAB immunostaining. The results from co-immunofluorescent staining of Bax{Delta}2 and a basal cell marker CK-14 showed that the previously detected DAB-stained Bax{Delta}2-positive epidermal cells were CK-14 positive but Bax{Delta}2 negative. Consistent with our previous finding, the Bax{Delta}2-positive cells in the dermis connective tissues are positive in both DAB-based and fluorescence-based immunostainings. These data indicate that the DAB-stained Bax{Delta}2 positive cells in the basal layer of skin tissue are false-positive due to a misinterpretation of the melanin color, but the dermal connective tissue still presents real Bax{Delta}2 positive staining.
Improving the clinical performance of blood-based DNA methylation biomarkers utilizing locus-specific epigenetic heterogeneity

Abstract Background Variation in intracellular methylation patterns can complicate the use of methylation biomarkers for clinical diagnostic applications such as blood-based cancer testing. Here, we describe development and validation of a methylation density binary classification method called EpiClass (available for download at https://github.com/bmill3r/EpiClass), that can be used to predict and optimize the performance of methylation biomarkers, particularly in challenging, heterogeneous samples such as liquid biopsies. This approach is based upon leveraging statistical differences in single-molecule sample methylation density distributions to identify ideal thresholds for samples classification. Results We developed and tested the classifier using reduced representation bisulfite sequencing (RRBS) data derived from ovarian carcinoma tissue DNA and controls. We used these data to perform in silico simulations using methylation density profiles from individual DNA molecules from ZNF154, a genomic locus known to be recurrently methylated in numerous cancer types. From these profiles, we predicted the performance of the classifier in liquid biopsies for the detection of epithelial ovarian carcinomas (EOC). In silico analysis indicated that EpiClass could be leveraged to better identify cancer-positive liquid biopsy samples by implementing precise thresholds with respect to methylation density profiles derived from circulating cell-free DNA (cfDNA) analysis. These predictions were confirmed experimentally by generating cfDNA methylation density profiles from a cohort of low volume (1-mL) plasma samples obtained from 26 EOC-positive and 41 cancer-free women. EpiClass performance was then validated in an independent cohort of plasma specimens from 24 EOC-positive and 12 cancer-free women, attaining a sensitivity/specificity of 91.7%/100.0%. Direct comparison of CA-125 measurements with EpiClass demonstrated that EpiClass outperformed CA-125 by correctly classifying 69.6% of samples as compared to 47.8% by standard CA-125 assessment. Conclusions Our results indicate that assessment of intramolecular methylation densities calculated from cfDNA facilitate the use of methylation biomarkers for diagnostic applications. Furthermore, we demonstrated that EpiClass analysis of ZNF154 methylation was able to outperform CA-125 in the detection of etiologically-diverse ovarian carcinomas, indicating the broad utility of ZNF154 for use as a biomarker of ovarian cancer.
Microbial community response to a decade of simulated global changes depends on the plant community

Author(s): Finks, SS; Weihe, C; Kimball, S; Allison, SD; Martiny, AC; Treseder, KK; Martiny, JBH | Abstract: Global changes such as increased drought and atmospheric nitrogen deposition perturb both the microbial and plant communities that mediate terrestrial ecosystem functioning. However, few studies consider how microbial responses to global changes may be influenced by interactions with plant communities. To begin to address the role of microbial–plant interactions, we tested the hypothesis that the response of microbial communities to global change depends on the plant community. We characterized bacterial and fungal communities from 395 plant litter samples taken from the Loma Ridge Global Change Experiment, a decade-long global change experiment in Southern California that manipulates rainfall and nitrogen levels across two adjacent ecosystems, a grassland and a coastal sage scrubland. The differences in bacterial and fungal composition between ecosystems paralleled distinctions in plant community composition. In addition to the direct main effects, the global change treatments altered microbial composition in an ecosystem-dependent manner, in support of our hypothesis. The interaction between the drought treatment and ecosystem explained nearly 5% of the variation in bacterial community composition, similar to the variation explained by the ecosystem-independent effects of drought. Unexpectedly, we found that the main effect of drought was approximately four times as strong on bacterial composition as that of nitrogen addition, which did not alter fungal or plant composition. Overall, the findings underscore the importance of considering plant–microbe interactions when considering the transferability of the results of global change experiments across ecosystems.
Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies.

Background Although conventional pain relief therapeutics have centered around mu-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states. Objectives We conducted a literature review to identify potential targets for novel analgesic therapies. Study design This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential. Methods A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of "novel analgesics," "novel non-opioid analgesics," "novel pain targets," and "non-opioid analgesics." Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature. Results Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of kappa-opioid, delta-opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether. Limitations Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development. Conclusions We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states.
Ion-temperature determination with a baffled Langmuir probe.

An electrostatic Langmuir probe for real-time measurements of parameters in magnetized plasma is tested in fully ionized, barium, Q-machine plasma. The small-diameter, long-length, tungsten wire sensor, i.e., the probe tip, oriented with its cylindrical axis perpendicular to the magnetic field (B), is partially shielded by ceramic baffles, or masks, that form sensor-access slots between the baffles. Adjusting the azimuthal orientation of the slots, by rotating the probe about its cylindrical axis, changes the fraction of proximity gyro-orbiting electrons, relative to the fraction of proximity gyro-orbiting ions, that can access the recessed sensor along the magnetic field. Thus, the ratio between the electron and ion saturation currents, Iesat and Iisat, can be adjusted without having affected the probe bias voltage Vb. When optimally shielded (Iesat/Iisat=1), accurate, real-time measurements of space potential Vs can be acquired. When maximally shielded (Iesat/Iisat≪1), accurate, real-time measurements of ion temperature Ti can be acquired. Subtracting the floating potential Vf of an optimally shielded baffled probe from Vf of a maximally shielded baffled probe yields Ti (and its fluctuation phase) in real time.
All That Coughs Is Not COVID-19: A Delayed Diagnosis of Disseminated Coccidioidomycosis Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Coccidioides immitis (and Coccidioides posadasii) are endemic fungi of the southwestern United States and northern Mexico. Uncomplicated, symptomatic Coccidioides infection most commonly causes a self-limited pneumonia; however, immunocompromised patients can manifest severe pneumonia with an additional risk of dissemination to bone, joints, soft tissues, and in the most severe cases, the central nervous system. In 2020, clinicians were challenged with a previously unseen volume of acute respiratory complaints as a result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We present a patient with respiratory failure secondary to SARS-CoV-2 who experienced prolonged hypoxia and neurologic deterioration, eventually leading to a diagnosis of occult disseminated coccidiomycosis involving meningitis, miliary-pattern pneumonia, and cutaneous lesions.
Central triage of acute stroke patients across a distributive stroke network is safe and reduces transfer denials

Background and purpose Mechanical thrombectomy has dramatically increased patient volumes transferred to comprehensive stroke centers (CSCs), resulting in transfer denials for patients who need higher level of care only available at a CSC. We hypothesized that a distributive stroke network (DSN), triaging low severity acute stroke patients to a primary stroke center (PSC) upon initial telestroke consultation, would safely reduce transfer denials, thereby providing additional volume to treat severe strokes at a CSC. Methods In 2017, a DSN was implemented, in which mild stroke patients were centrally triaged, via telestroke consultation, to a PSC based upon a simple clinical severity algorithm, while higher acuity/severity strokes were triaged to the CSC. In an observational cohort study, data on acute ischemic stroke patients presenting to regional community hospitals were collected pre- versus post-DSN implementation. Safety outcomes and rate of CSC transfer denials were compared pre-DSN versus post-DSN. Results The pre-DSN cohort (n=150), triaged to the CSC, had a similar rate of symptomatic intracerebral hemorrhage and discharge location compared with the post-DSN cohort (n=150), triaged to the PSC. Time to stroke unit admission was faster post-DSN (2 hours 40 minutes) versus pre-DSN (3 hours 29 minutes; P Conclusions A DSN, triaging mild ischemic stroke patients from community hospitals to a PSC, safely reduced transfer denials to the CSC, allowing greater capacity at the CSC to treat higher acuity stroke patients.
Examining the Impact of Implementation Supports on Goals Set by Students in Inclusive, Secondary Classes

Implementation supports for teachers can significantly impact the degree to which evidence-based practices are used as intended with secondary students across settings and content areas. The presen...
Cleaning Up at the Tracks: Superfund Meets Rails-to-Trails

For more than one hundred years, railroad cars rumbled and roared along tracks in the Coeur d'Alene River Basin, serving the mining industry in the Panhandle of northern Idaho. As in many parts of the American West, the history of railroads in northern Idaho largely reflects the history of mining in the region. The first gold was discovered in this area in 1883, the same year that the area saw its first line of the Northern Pacific Railroad. In 1885, the Bunker Hill mine was established near the present town of Kellogg. Four years later, the first rail line of the Union Pacific Railroad arrived.
Patterns of Academic Help-Seeking in Undergraduate Computing Students

Knowing when and how to seek academic help is crucial to the success of undergraduate computing students. While individual help-seeking resources have been studied, little is understood about the factors influencing students to use or avoid certain resources. Understanding students’ patterns of help-seeking can help identify factors contributing to utilization or avoidance of help resources by different groups, an important step toward improving the quality of resources. We present a mixed-methods study investigating the help-seeking behavior of undergraduate computing students. We collected survey data (n=138) about students’ frequency of using several resources followed by one-on-one student interviews (n=15) to better understand why they use those resources. Several notable patterns were found. Women sought help in office hours more frequently then men did and computing majors sought help from their peers more often than non-computing majors. Additionally, interview data revealed a common progression in which students started from easily accessible but low utility resources (online sources and peers) before moving on to less easily accessible, high utility resources (like instructor office hours).
Opening Schumer’s Box: The Empirical Foundations of Modern Consumer Finance Disclosure Law

This Article explores the fundamental failure of Congress’ twenty-five-year quest to utilize disclosure as the primary tool to both regulate credit card issuers and educate consumers. From inception until present, reforms to this disclosure regime, even when premised on judgment and decision-making behavioralism, were nomothetic in orientation and ignored clear differences in population behavior and the heterogeniety of consumers. Current law prohibits credit card issuers from acquiring consumer socio-demographic data and prevents issuers and regulators from using market and policy experimentation to enhance disclosure’s efficacy. To explain why this regime was structured this way and why it must change, this Article contains four key sections: (1) a comprehensive review of the creation of our modern consumer credit card regulatory scheme; (2) a survey of the empirical evidence used to update and expand that disclosure-centered regime over twenty-five years; (3) an account of why the existing scheme’s disclosure function substantially fails, notwithstanding recent reforms; and (4) an argument that to achieve optimal credit card disclosure efficacy, the law must permit issuers to acquire and utilize customer socio-demographic information, including race, gender, and other characteristics.
Differences in diurnal and nocturnal swimming patterns of olive ridley hatchlings in the Gulf of Fonseca, Honduras

Abstract Sea turtle hatchlings from Honduran beaches along the Pacific coast must swim more than 30 km through the shallow, presumably predator-rich waters of the Gulf of Fonseca before reaching the open ocean. Olive ridley hatchlings from Punta Raton, Honduras, were tracked during the first 2 h of their offshore migration to assess aquatic predation rates. No predation events were observed. The absence of rocky bottom areas and reef structures where predators can refuge, and a decline in the number of predators due to overfishing are two possible reasons for this unexpected result. Additionally, diurnal and nocturnal swimming patterns of recently emerged olive ridley hatchlings were compared with regard to their position in the water column while swimming. At night hatchlings swam near the surface 97.5% of the time, with only sporadic brief dives. During daytime, however, hatchlings spent 78% of the time swimming at depth, going back to the surface for brief periods to breathe. Due to the high turbidity of the Gulf of Fonseca waters, this daytime behavior may serve to keep hatchlings out of sight of predatory sea birds. This newly described differential swimming behavior may have adaptive significance in avoiding aerial predation in the specific conditions of the Gulf of Fonseca.
Path planning in multi-scale ocean flows: Coordination and dynamic obstacles

Abstract As the concurrent use of multiple autonomous vehicles in ocean missions grows, systematic control for their coordinated operation is becoming a necessity. Many ocean vehicles, especially those used in longer-range missions, possess limited operating speeds and are thus sensitive to ocean currents. Yet, the effect of currents on their trajectories is ignored by many coordination techniques. To address this issue, we first derive a rigorous level-set methodology for distance-based coordination of vehicles operating in minimum time within strong and dynamic ocean currents. The new methodology integrates ocean modeling, time-optimal level-sets and optimization schemes to predict the ocean currents, the short-term reachability sets, and the optimal headings for the desired coordination. Schemes are developed for dynamic formation control, where multiple vehicles achieve and maintain a given geometric pattern as they carry out their missions. To do so, a new score function that is suitable for regular polygon formations is obtained. Secondly, we obtain an efficient, non-intrusive technique for level-set-based time-optimal path planning in the presence of moving obstacles. The results are time-optimal path forecasts that rigorously avoid moving obstacles and sustain the desired coordination. They are exemplified and investigated for a variety of simulated ocean flows. A wind-driven double-gyre flow is used to study time-optimal dynamic formation control. Currents exiting an idealized strait or estuary are employed to explore dynamic obstacle avoidance. Finally, results are analyzed for the complex geometry and multi-scale ocean flows of the Philippine Archipelago.
The Influence of Climate and Fertilizer Practices upon the Vitamin and Mineral Content of Vegetables

Publisher Summary This chapter considers factors affecting nutritive value of vegetables. The consideration has been restricted primarily to vegetables. However, data obtained with other plants has been included that aid in clarifying or amplifying the results obtained in the limited field. In discussing the mineral contents of plants, the discussion has been limited to those minerals of particular importance in human nutrition. Climate and fertilizer practices are not the only forces acting to determine the vitamin and mineral content of vegetables. There are other factors that are of equal or greater importance. Some of these are processing, handling, and genetics. Thus, the vitamin or mineral content of canned vegetables at the time they are consumed is determined by a large number of factors. The vitamin content of the vegetables as they are produced at the farm is important, and this is determined by such factors as variety, climate, fertilizer practices, etc. What proportion of the vitamins initially present in the fresh vegetables reaches the consumer depends upon such factors as processing, handling, cooking, etc. The chapter discusses some of the difficulties that are involved, in reference to analytical and sampling methods, as they are essential to a critical evaluation of the published data. These are illustrated by using ascorbic acid studies as an example. Similar criticisms apply to other studies, and have briefly been discussed.
Keep, Toss, or Fix? Assessing U.S. Alliances in East Asia

With strategic circumstances changing in Asia, and with a fiscal imperative to reduce defense spending, the United States will face hard choices about its national security strategy and the alliances that support it. This paper examines the future of U.S. alliances in East Asia during an era of strategic and budgetary change. I describe the U.S. alliance system in the region, and the goals that these alliances are meant to achieve. I next evaluate the extent to which U.S. alliances in East Asia advance these goals, and conclude that they advance many but not all U.S. objectives. I then describe the costs and risks that are associated with U.S. security guarantees in East Asia. I conclude by describing options to reduce these costs and risks: first, the more radical option of shifting to an “offshore balancing” strategy, and second, options for restructuring U.S. alliances and reforming U.S. diplomacy while continuing the current U.S. grand strategy of “global leadership.”
Parallelizing Loops with Indirect Array References of Pointers

This paper presents a hybrid compiler/run-time approach for parallelizing loops with indirections and pointers. A scheduler is generated by the compiler based on information deduced from dependence analysis and program slicing. At run-time, the scheduler records dynamic dependences and allocates work to processors based on the run-time reference patterns. The central point is that compiler analysis can help to make the overhead incurred by the run-time scheduler insignificantly low. Two new techniques are developed: (1) scheduler generation using program slicing and dependence, recording procedures, and (2) redundant reference elimination for reducing both the space and time required to record the dynamic references. The effectiveness of this approach is demonstrated by parallelizing a waveform-relaxation-based circuit simulator, which is a 12,000-line C program.
Considering Therapeutic Antibodies

Unexpected dangerous side effects of antibody-based therapies may be prevented with improved design of monoclonal antibodies and of clinical testing protocols.
Eddy-current phasography

A new concept, phasography, has been developed showing excellent potential for high resolution imaging of flaws using eddy current data. The process may be thought of as an eddy current equivalent to acoustic holography. Phase multiplication of the detected coherent signal is used to simulate a test wavelength one to two orders of magnitude smaller than the actual wavelength, permitting the use of image reconstruction techniques. Since this process is performed on the detected data, the eddy current penetration depth remains unchanged. It is also possible to apply this phase multiplication technique to low frequency acoustic holography, resulting in a test which combines excellent penetration of difficult materials with high resolution images. Preliminary experimental results graphically illustrate this unique imaging technique. Eddy current phasograms and their reconstructed images of small internal simulated defects in 1 mm thick stainless steel plates are presented in this paper.
Generalized Euler and Chu-Vandermonde identities

Abstract The object of this paper is to present two surprisingly general identities involving the generating functions of the number of inversions between multisets (of not necessarily uniform multiplicities). The first identity is a generalization of the Chu-Vandermonde identity, and the second a well-known identity of Euler. Our proofs are based on a one-to-one correspondence between multisubsets and certain permissible paths in a digraph with monomial weights.
An Interdisciplinary Approach to the Prevention and Treatment of Groin Wound Complications After Lower Extremity Revascularization

Background If not effectively treated, groin wound infections following lower extremity revascularization (LER) may result in graft or limb loss. Methods A retrospective review was performed of all patients who underwent muscle flap transposition by a single surgeon after LER between 2006 and 2010. Results Twenty-nine muscle transposition flaps were performed in 24 patients (21 sartorius, 6 rectus femoris, and 2 gracilis). Nineteen were for treatment of groin wound infections, two for treatment of lymphocele, one for coverage of exposed graft in the setting of pyoderma gangrenosum, and seven for infection prophylaxis. Two graft losses followed flap placement. The limb loss rate was 4%. When performed for therapeutic purposes, graft salvage rates were 100% for autogenous and 92% for synthetic grafts. Conclusions Muscle transposition flaps are an effective means of graft salvage in the setting of groin wound complications following LER and should be considered for infection prophylaxis in high-risk patients.
The case study: a useful research method for information management

This paper urges greater recognition of the case study as a research method for information management. It acknowledges concern about the representatives of case studies but by specifying the relationships between epistemology and research methods shows that this concern is misplaced. Representatives is irrelevant for many research purposes, particularly when the distinction is made between logical and statistical inference. The validity of explanations or theory derived from case studies depends on the logic of the analysis and acknowledgement of ceteris paribus conditions, not on how typical the cases may be. Typologies of case studies have been proposed and these are considered, together with recommendations for the conduct of systematic and rigorous case study research. It is stressed that research problems should be addressed using appropriate research methods. Research of the important problems within the management area frequently demands a qualitative research approach, though it would seem that such an approach is often ignored because of a positivist research orientation. An assessment of the strengths and weakness of the case study method, which highlights its potential in the vital role of theory-building, leads to the conclusions that this method has much to commend it to information management researchers (1).
Liver Abscesses Due to Staphylococcus aureus in a Patient with AIDS Who Underwent Small Bowel Biopsy: Case Report and Review

A 36-year-old man with overgrowth of Staphylococcus aureus in the small bowel underwent a biopsy of the small bowel and presented 5 weeks later with multiple liver abscesses. To our knowledge, small bowel biopsy has never been associated with liver abscesses. We discuss the literature on liver abscesses in patients with AIDS and the risks of bacteremia following upper endoscopy and small bowel biopsy and propose that the etiology of the liver abscesses in our patient was seeding of the portal vein following biopsy of a small bowel that had significant bacterial overgrowth.
The mid-latitude F region at the mesoscale: some progress at last

Abstract Almost no new theoretical work has been conducted in the area of mid-latitude F -region plasma instabilities since Perkin's (J. Geophys. Res. 78 (1973) 218) linear theory. New experimental data now suggest that the nonlinear development of mid-latitude F -region structures includes large polarization electric fields which dominate the final state. Airglow and radar data show that Σ P is greatly depleted in some regions, which is in agreement with a polarization hypothesis. We hope these new results will inspire new simulations with some anticipation of solving this perplexing but fascinating problem.
Total-Burn Spectrographic Determination of Silicon in Plutonium

A total-burn spectrographic method has been applied to the determination of trace concentrations of silicon in plutonium. The sample is oxidized to plutonium dioxide, mixed with a germanium dioxide–graphite mixture containing tin internal standard, packed into cupped graphite electrodes, and burned to completion in a high-amperage dc arc. Plutonium spectral interference is avoided by using the less sensitive Si 2506.90-A line. The lower limit of the determination is 25 ppm of silicon in plutonium. The precision of the method is estimated to be ±8% (coefficient of variation) at the 270-ppm level and ±14% at 40 ppm.
Tuned to Resonance: Transfer-Function-Adaptive Filters in Evanescent-Mode Cavity-Resonator Technology

A number of promising technologies can be found today in the marketplace of reconfigurable filter ideas. They range from sub-mm-scale acoustic filters, lumped elements, two-dimensional resonators, and full three-dimensional solutions. From a system perspective, an equally diverse pool of communication, radar, electronic warfare, and sensing systems need reconfigurable filters. Despite a strong demand for such filters though, it is not easy to identify a technology that satisfies all requirements. While it is relatively straightforward to satisfy one or two important specifications such as low loss or high selectivity, it is often quite challenging to simultaneously satisfy all of them. For instance, this is particularly true when low power consumption, small form factor, and low loss become simultaneously critical decision factors. Several combinations of such factors can result in necessary design tradeoffs with no obvious solutions. Table 1 summarizes several common deciding factors in selecting a reconfigurable filter technology.
Characterization of Rat Cytochrome P450 Isozymes Involved in the Covalent Binding of Cyclosporine A to Microsomal Proteins

Cyclosporin A (CsA) is an immunosuppressant drug which is extensively metabolized by the hepatic microsomal monooxygenases. Among other toxicities, CsA is nephrotoxic and hepatotoxic. In the present study, the NADPH-dependent cytochrome P450-supported metabolism of CsA to reactive metabolite(s) capable of covalently binding to proteins was studied. The covalent binding was inhibitable in vitro with classical cytochrome P450 inhibitors. The covalent binding of CsA metabolite(s) was induced six- to eightfold in liver microsomes from rats of both sexes treated with dexamethasone, suggesting that a P450 3A-related protein was involved in the covalent binding of CsA metabolite(s). However, the isozyme responsible was not P450 3A1 or 3A2, since inhibitory monoclonal antibodies to these isozymes did not inhibit the covalent binding. The binding was, however, inhibitable in vitro with cytochrome P450 3A substrates and inhibitors such as erythromycin and triacetyloleandomycin. Greater amounts of CsA covalent binding occurred in liver microsomes from adult uninduced female rats than males or immature rats of either sex. Therefore, a female-specific isozyme of P450 present in adult female rat liver microsomes, which may or may not be identical to a dexamethasone-inducible isozyme, is also involved in the metabolism of CsA to form covalent binding metabolites. The covalent binding of CsA was 50% inhibited by glutathione. However, mannitol and superoxide dismutase did not affect the binding. This suggested that at least some of the metabolites of CsA involved in covalent binding were electrophilic in nature; however, hydroxyl radicals and superoxide anion radicals were not involved.
Glutamate Receptor Signaling Interplay Modulates Stress-sensitive Mitogen-activated Protein Kinases and Neuronal Cell Death

Abstract Glutamate receptors modulate multiple signaling pathways, several of which involve mitogen-activated protein (MAP) kinases, with subsequent physiological or pathological consequences. Here we report that stimulation of theN-methyl-d-aspartate (NMDA) receptor, using platelet-activating factor (PAF) as a messenger, activates MAP kinases, including c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase, in primary cultures of hippocampal neurons. Activation of the metabotropic glutamate receptor (mGluR) blocks this NMDA-signaling through PAF and MAP kinases, and the resultant cell death. Recombinant PAF-acetylhydrolase degrades PAF generated by NMDA-receptor activation; the hetrazepine BN50730 (an intracellular PAF receptor antagonist) also inhibits both NMDA-stimulated MAP kinases and neuronal cell death. The finding that the NMDA receptor-PAF-MAP kinase signaling pathway is attenuated by mGluR activation highlights the exquisite interplay between glutamate receptors in the decision making process between neuronal survival and death.
Abstract 2601: Polymorphisms in oxidative stress genes, physical activity and breast cancer risk

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL BACKGROUND. Reactive oxygen species (ROS) are known to react with DNA resulting in the transformation of normal epithelium to a malignant phenotype. While one functional variant in catalase (CAT) has been shown to be pertinent to breast cancer risk, few other polymorphisms in this gene have been assessed. Genetic variation in CAT or other genes in the oxidative stress pathway may mediate the carcinogenic effect of ROS produced by recreational physical activity (RPA) or result in adaptation of antioxidant capacity. METHODS. We investigated the association between three polymorphisms in CAT (rs4756146, rs2284365, rs480575) and breast cancer risk. We also characterized the joint effects of RPA with CAT, and with other functional oxidative stress variants (COMT, GPX, GSTA1, GSTM1, GSTP1, GSTT1, MnSOD, MPO, and UGT2B7) on breast cancer risk. Data were from the Long Island Breast Cancer Study Project, a population-based case-control study with interview and biomarker data available on 1102 cases and 1141 controls. Adjusted unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS. The presence of at least one CAT variant allele in rs4756146 was associated with a 23% decreased risk of postmenopausal breast cancer (95% CI=0.59-0.99). While rs2284365 and rs480575 were not associated with breast cancer risk, interaction between the two was evident on the multiplicative scale (likelihood ratio test p=0.087) indicating possible antagonism for these CAT polymorphisms. Further, upon combining the CAT genotypes, we observed a positive association between breast cancer risk and the number of putative high-risk alleles. Women with ≤ 4 high-risk alleles were at a 44% increased risk of breast cancer (95% CI=1.04-2.00) compared to women with ≤ 2 high-risk alleles. Finally, two polymorphisms (CAT rs1001179 and GSTP1 rs1695) among the oxidative stress genes considered were found to interact multiplicatively with postmenopausal RPA. Variant alleles in CAT antagonistically reversed the effect of high RPA on breast cancer risk (p=0.043) while variant alleles in GSTP1 synergistically enhanced the effect of low RPA on breast cancer risk (p=0.006). CONCLUSIONS. This study suggests that postmenopausal breast cancer risk may be decreased among women with one variant CAT allele in rs4756146. Risk may be elevated when considering combined effects of multiple high risk alleles in CAT. Variants in both CAT and GSTP1 may modify the association between RPA and breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2601. doi:1538-7445.AM2012-2601
A Routine Method for the In Vitro Assay of Tyrothricin

Several methods are described for the extraction of tyrothricin from products containing oil and ointment bases. A simple decimal dilution type of assay of alcohol and propylene glycol solutions is presented. A supplementary method suitable for use as a check for the routine procedure is also included.
Black hole-neutron star binaries in general relativity: Quasiequilibrium formulation

We present a new numerical method for the construction of quasiequilibrium models of black hole-neutron star binaries. We solve the constraint equations of general relativity, decomposed in the conformal thin-sandwich formalism, together with the Euler equation for the neutron star matter. We take the system to be stationary in a corotating frame and thereby assume the presence of a helical Killing vector. We solve these coupled equations in the background metric of a Kerr-Schild black hole, which accounts for the neutron star's black hole companion. In this paper we adopt a polytropic equation of state for the neutron star matter and assume large black hole-to-neutron star mass ratios. These simplifications allow us to focus on the construction of quasiequilibrium neutron star models in the presence of strong-field, black hole companions. We summarize the results of several code tests, compare with Newtonian models, and locate the onset of tidal disruption in a fully relativistic framework.
Re-Evaluating the Treatment of Nongonococcal Urethritis: Emphasizing Emerging Pathogens–A Randomized Clinical Trial

Background Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy. Methods Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days. Results The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002). Conclusions Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated with azithromycin; however, doxycycline had significantly better efficacy against Chlamydia, whereas azithromycin was superior to doxycycline for the treatment of M. genitalium.
Density-dependent phosphorylation of a specific protein in cultured cells.

THE phosphorylation–dephosphorylation reactions that regulate the biological activities of many proteins are sensitive to changes in physiological conditions1. Hormones regulate the phosphorylation of both membrane-bound2 and cytosolic proteins3,4, while the phosphorylation of histone5 and non-histone chromosomal proteins6 changes during different phases of the cell cycle. The cellular density of mammalian cells grown in culture can affect biological properties such as cell growth7, locomotion8, transport9 and enzyme activity10,11. We have examined the phosphorylation of endogenous proteins in cultured mammalian cells at different cellular densities as a means of determining whether cell–cell interactions might affect protein phosphorylation. We report here that the phosphorylability of a specific protein present in several diverse cell lines exhibits density-dependence.
Work function measurements on indium tin oxide films

Abstract We determined the work function of indium tin oxide (ITO) films on glass substrates using photoemission spectroscopy (PES). The ITO coated glass substrates were chemically cleaned ex-situ, oxygen plasma treated ex-situ, or sputtered in-situ. Our results suggest that the performance of ultraviolet photoemission spectroscopy (UPS) measurements can induce a significant work function reduction on the order of 0.4–0.5 eV, on ex-situ chemically and oxygen-plasma treated ITO samples. This was demonstrated by the use of low intensity X-ray photoemission spectroscopy (XPS) work function measurements before and after the UPS measurements were carried out.
μ and δ-opioid receptor agonists induce mitogen-activated protein kinase (MAPK) activation in the absence of receptor internalization

Agonist-promoted internalization (endocytosis) of G-protein-coupled receptors (GPCRs), including all three opioid receptor types (μ, δ and κ), has been shown to occur via the clathrin endosomal pathway in response to receptor phosphorylation and the actions of the proteins, β-arrestin and dynamin. Many members of the GPCR family stimulate mitogen-activated protein kinases (MAPK or ERK) activity and, in several cases, it appears that MAPK activation is dependent on receptor internalization. We have reinvestigated the question of whether internalization is obligatory for MAPK activation by opioid receptors, using cell lines expressing the cloned μ or δ receptor. Morphine, which is known to activate both μ and δ receptors, does not induce their rapid internalization into clathrin-coated endosomes. However, morphine produced a robust stimulation of MAPK in both cell lines, as demonstrated by the appearance of phosphorylated MAPK. Moreover, pre-exposure of cells to the internalization inhibitors, concanavalin A or hypertonic sucrose, totally blocked DAMGO (μ-selective agonist) and DTLET (δ-selective agonist)-mediated receptor internalization, yet neither treatment affected MAPK phosphorylation induced by these peptides. Our results provide evidence that receptor internalization is not an obligatory requirement for MAPK activation by μ and δ opioid receptors. Hypotheses are presented to explain the seemingly contradictory results obtained from different laboratories.
Reconstructing ellipsoids from projections

Abstract In this paper we examine the problem of reconstructing a (possibly dynamic) ellipsoid from its (possibly inconsistent) orthogonal silhouette projections. We present a particularly convenient representation of ellipsoids as elements of the vector space of symmetric matrices. The relationship between an ellipsoid and its orthogonal projections in this representation is linear, unlike the standard parameterization based on semiaxis length and orientation. This representation is used to completely and simply characterize the solutions to the reconstruction problem. The representation also allows the straightforward inclusion of geometric constraints on the reconstructed ellipsoid in the form of inner and outer bounds on recovered ellipsoid shape. The inclusion of a dynamic model with natural behavior, such as stretching, shrinking, and rotation, is similarly straightforward in this framework and results in the possibility of dynamic ellipsoid estimation. For example, the linear reconstruction of a dynamic ellipsoid from a single lower-dimensional projection observed over time is possible. Numerical examples are provided to illustrate these points.