cssi/SciSciGPT-SciSciNet huggingface dataset:
Diabetic Phenotypes and Late-Life Dementia Risk: A Mechanism-specific Mendelian Randomization Study.

Background Mendelian Randomization (MR) studies have reported that type 2 diabetes (T2D) was not associated with Alzheimer disease (AD). We adopted a modified, mechanism-specific MR design to explore this surprising result. Methods Using inverse-variance weighted MR analysis, we evaluated the association between T2D and AD using data from 39 single nucleotide polymorphisms (SNPs) significantly associated with T2D in DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the corresponding associations of each SNP with AD risk obtained from the International Genomics of Alzheimer's Project (IGAP, n=17,008 AD cases and n=37,154 controls). We evaluated mechanism-specific genetic subscores, including β-cell function, insulin sensitivity, and adiposity, and repeated analyses in 8501 Health and Retirement Study participants for replication and model validation. Results In IGAP, the overall T2D polygenic score did not predict AD [odds ratio (OR) for the T2D polygenic score=1.01; 95% confidence interval (CI), 0.96, 1.06] but the insulin sensitivity polygenic score predicted higher AD risk (OR=1.17; 95% CI, 1.02, 1.34). In the Health and Retirement Study, polygenic scores were associated with T2D risk; the associations between insulin sensitivity genetic polygenic score and cognitive phenotypes were not statistically significant. Conclusions Evidence from polygenic scores suggests that insulin sensitivity specifically may affect AD risk, more than T2D overall.
The Last Years

Diego Portales’ official link with the central government continued even after he retired from the governorship of Valparaiso. On 29 May 1833 he was appointed to the first Consejo de Estado under the new constitution. It is interesting to note that also included with him were Manuel J. Gandarillas and Juan Egana. Obviously Gandarillas’ recent constitutional skirmishes with Mariano Egana did not set him at odds with the administration. But Portales was not active again until 1835. During 1834 he was confronted by two especially irksome problems. Not only was he still far from financial solvency but the government decided that he owed it thirty-seven hundred pesos which supposedly he was not authorized to allocate during the revolution of 1829. Whatever influence he allegedly possessed was ineffective now; he had to pay the sum. “Goodbye my silver!” he wrote to Antonio Garfias in 1834.1 Bothersome also was the incessant pressure directed at him from Santiago to encourage him back into government. President Prieto was having trouble with his ministers, and many people already assumed that Manuel Rengifo would run against him in the 1836 presidential election. But it was difficult to sway Portales. To Prieto he wrote at the end of May 1834 that he was convinced the best service he could perform for the country would be “not to mix in public matters...”2
Bacteremia in Patients with Heterotaxy: A Review and Implications for Management

Heterotaxy (HTX) is a laterality defect resulting in abnormal arrangement of the thoracic and abdominal organs across the right-left axis, and is associated with multiple anatomic and physiologic disruptions. HTX often occurs in association with complex congenital heart disease. Splenic abnormalities are also common and convey an increased risk of bacteremia (bacteremia) with a high associated mortality. We performed a systematic review of the literature studying the risk of infection in HTX patients and strategies that can be utilized to prevent such infections. Studies were identified for inclusion using PubMed, EMBASE, and OVID, as well as hand search of references from previously identified papers. Published studies specifically investigating bacteremia in HTX were identified and included as long as they were in English. Data were extracted by two separate authors independently with review of any findings that differed between the two authors. There were 42 documented cases of bacteremia in 32 patients. Approximately, 79% of these had absence of a spleen. The average age of bacteremia was 17 months. HTX patients are at high risk for bacteremia leading to mortality, regardless of anatomic splenic type. We propose strategies for the evaluation of splenic function in HTX patients, and review management practices to reduce the impact of infection risk in the HTX population.
Sounds of disadvantage: Musical taste and the origins of ethnic difference

Abstract According to Weber, shared cultural differences are fundamental to the formation and identification of ethnic groups. Yet, the origins and trajectory of these differences are rarely interrogated by sociologists of culture. Where do ethnic differences in culture come from and why do some persist while others fade? To address these questions, I bring into focus an ethnic group whose cultural distinctiveness is hotly debated in the U.S. but rarely examined by sociologists of culture: Mexican immigrants and their U.S.-born descendants. Using data from the 2002 Survey of Public Participation in the Arts and the Mexican American Study Project II, I measure differences in musical preference between Mexican-origin and non-Hispanic black and white Americans, and I test four key mechanisms to account for the ethnic differences I observe: nativity, socioeconomic status, ethnic concentration, and ethnic discrimination. I find that Mexican Americans exhibit a wide array of differences in taste that diminish but still persist after the first generation. While some of these differences are tied to experiences of ethnic isolation and discrimination, the majority are attributable to differences in socioeconomic status. This distinguishes the case of Mexican Americans from that of U.S. blacks, for whom racial disadvantage far outweighs socioeconomic difference in accounting for differences in taste. Genre status also plays a key role in determining where ethnic differences in taste persist and where they fade.
Image, Text, Object: Interpreting Documents and Artifacts as ‘Labors of Representation’

How can historical archaeologists best integrate documentary images and texts with archaeological evidence? The concept of “labor of representation” draws attention to the physical efforts, strategic decisions, and political projects inherent in representational practices, allowing archaeologists to rigorously account for the social production of historical documents without negating their evidentiary value. Contextual analysis of Joseph de Urrutia’s plan drawings of Spanish-colonial presidios demonstrates this approach, revealing systematic representational conventions. Overall, Urrutia depicted the settlements as more homogeneous and with more formal spatial order than was likely the case. The plan drawings are also shaped by an ideological boundary between military order and civilian disorder. Archaeological investigations that have taken the Urrutia drawings to be reliable “as-built” plans have tended to neglect or misinterpret those elements of the archaeological record that are most closely related to local, indigenous, and vernacular cultural practices.
Electrochemically sliced low loss AlGaN optical microresonators

High quality single crystal III-Nitride films are often formed over a thick buffer to reduce growth induced defects on a lattice mismatched substrate. However, it is challenging to fabricate nanophotonic waveguiding structures directly from this very top layer. Here, we demonstrate electrochemical slicing of high quality AlGaN thin films and its subsequent transfer to a lower index oxided silicon substrate for lithographic patterning of photonic waveguide and microresonators. TEM analysis of the nanomembrane waveguide demonstrates an AlGaN layer free of misfit dislocations commonly found in conventional epitaxial AlGaN grown on sapphire or Si. We probe the low material optical loss (1.22 dB/cm) of the nanomembrane by measuring the optical quality (Q) factor at 780 nm. High intrinsic quality factors of 680 000 are achieved after optimizing fabrication process. This versatile, low loss AlGaN device opens applications for nonlinear photonics at visible wavelengths.
On the Gan–Gross–Prasad conjecture for U ( p , q )

In this paper, we give a proof of the Gan–Gross–Prasad conjecture for the discrete series of U(p, q). There are three themes in this paper: branching laws of a small $$A_{\mathfrak {q}}(\lambda )$$ , branching laws of discrete series and inductive construction of discrete series. These themes are linked together by a reciprocity law and the notion of invariant tensor product.
Patterns of intra-industry trade and foreign direct investment in agrofood products: implications for East-West integration

implications for East-West integration Siemen van Berkum Agricultural Economics Research Institute (LEI), The Hague, The Netherlands In MOCT-MOST 9:255-271,1999, Kluwer Academic Publishers, Netherlands Abstract Agricultural relations between the EU and CEECs have changed substantially since the reforms of the economic and political system in the CEECs started around 1989/1990. Trade between the two regions has grown significantly and is increasingly of an intra-industry nature, indicating that noncomparative advantage factors, like economies of scale, product differentiation and innovations, are gaining importance as drivers of trade. Trade patterns suggest that the relationship between agriculture in East and West is increasingly complementary. The inflow of FDI from West-European firms to the food sector in the CEEC region enforces this process of complementarity. Both patterns of trade and FDI indicate that big shifts in specialisation and competitiveness among West and East European farmers due to the eastward enlargement of the Union are unlikely to occur.
The Common Sense Cut and the Gendered Body Project: Constructing Existing Norms around Genital Cutting in U.S. Media

The U.S. discourse regarding the practice of genital cutting differs depending on the perceived sex of the body. The authors understand this difference as crucial to the construction of gender normative body projects in the contemporary United States. Using a content analysis of 172 randomly sampled newspaper articles in the United States, we present differences in not only the value position of media but in the framing of genital alteration across sexes or genders and national contexts. We find that U.S. media overwhelmingly exhibits a positive viewpoint regarding the circumcision of male bodies and considers the question to be a fundamentally medical one. Our analysis suggests that while personal narrative is employed to center the personhood of females who have been circumcised, the device is also used to normalize parental choice when discussing male circumcision. Our analysis shows that U.S. media engages almost exclusively white male voices as experts in the discussion of normative male body present...
Satisfaction and Happiness – The Bright Side of Quality of Life

Researchers and policy makers have become increasingly interested in using happiness or subjective wellbeing (SWB) as an index of quality of life. We examine the utility of using SWB as a social indicator, arguing that SWB is intrinsically valuable as a measure of the end goal of all human activities and extrinsically valuable as a predictor of a wide range of positive outcomes and an indicator of the effects of changing societal conditions. Using the examples of wealth and unemployment, we show that changes in objective societal conditions influence individual and national SWB. Because SWB is sensitive to changes in societal conditions, it can be fruitfully used to measure societal progress. Encouraged by strong evidence that societal conditions influence SWB, researchers and policy makers should focus future efforts on identifying and implementing those societal changes that have the greatest potential to enhance happiness.
Glycemic Load reflects dietary intake in hemodialysis (HD) patients

Dietary glycemic load (GL) has not been previously reported in HD patients and may be a holistic indicator reflective of the dietary profile. Study aim was to quantify GL and assess its relationshi...
Mechanisms of Blastema Formation and Growth in Regenerating Urodele Limbs

Abstract Urodele amphibians can regenerate their limbs throughout life by forming a blastema of undifferentiated cells derived from the individual tissues comprising the region of amputation. The blastema forms subjacent to an apical thickening of the epidermis closing the wound called the apical epidermal cap (AEC), a critical signaling center for proximodistal growth of the blastema. Blastema cells are derived by the liberation of cells from tissues by histolysis and dedifferentiation, as well as via stem cells from muscle, but there are species and developmental differences in how myogenic cells are supplied for muscle regeneration. During formation of the blastema, its cells are arrested in G2 of the cell cycle. Breaking G2 arrest requires the synergistic action of mitogens produced by the AEC and communication between anterior and posterior blastema cells mediated by sonic hedgehog and fibroblast growth factor 2 (Fgf2). Candidates for AEC mitogens are Fgf2 and the anterior gradient protein. Production of these mitogens is induced by nerve factors. Candidate nerve factors are glial growth factor 2 and combinations of bone morphogenetic protein/Fgf8. Blastema cells are lineage-restricted in their regeneration of new limb tissues.
Single Cell T Cell Maps of Donor Lymphocyte Infusion (DLI) Response and Resistance

DLI can eradicate leukemic relapse after allogeneic hematopoietic stem cell transplant (allo-SCT), potentially by reversing T cell exhaustion for chronic myelogenous leukemia (CML). Critical questions remain, however, regarding the exact cellular identities and transcriptional states of those T cell subtypes mediating exhaustion, anti-leukemia responses, and DLI resistance. To map evolving phenotypic T cell states in situ at single cell resolution, we obtained single cell transcriptomes from bone marrow mononuclear cells before/after DLI from 6 responders ("R's") and 6 nonresponders ("NR's") with relapsed CML after T-cell depleted allo-SCT. In total, 381,462 cells derived from 43 unique patient-timepoints met our quality metrics; we curated a set of 62 distinct cell states, from T, B, NK, monocyte, and progenitor subtypes, whose identities were determined by both cell type and timepoint. Because DLI's anti-leukemic efficacy derives largely from T cell activity, we evaluated if DLI response associated with distinct T cell transcriptional phenotypes ("states"). We observed a marked separation of T cell clusters based on clinical outcome and a significant increase in the number of T cell clusters after DLI in matched samples after controlling for cell number (pre vs post, p-value We queried global T cell dysfunction between R's vs NR's, observing increased T cell exhaustion signatures in R-pre T cells, consistent with our previously published findings, but also detecting increased tolerance and anergy in NR-post T cells, suggesting multiple forms of T cell dysfunction in DLI resistance. Anergic and tolerant cells constituted distinct clusters, expressing reduced CD8A/CD4 expression, suggesting decreased antigen responsiveness. We will also infer novel gene regulatory networks driving T cell states and clonal expansion by integrating scRNA-seq data with associated ATAC-seq profiles and scTCR repertoires, using novel computational techniques. These findings will be updated at the meeting. Altogether, these data suggest that (1) pretreatment T cell phenotypic diversity may be important for DLI response; (2) that DLI increases such diversity differentially in R's than in NR's; and (3) even in the absence of clinical response, NR's undergo significant T cell phenotypic remodeling.
Political clarity and the limitations of humanistic violence in the U.S. K-12 classroom

I examine the development of my political clarity and its relation to the exercise of humanistic violence as a K-12 teacher in the United States. Reflecting upon my experiences as a classroom and c...
Location-Based Social Simulation

Location-based social networks (LBSNs) have been studied extensively in recent years. However, utilizing real-world LBSN datasets in such studies has severe weaknesses: sparse and small datasets, privacy concerns, and a lack of authoritative ground-truth. Our vision is to create a large scale geo-simulation framework to simulate human behavior and to create synthetic but realistic LBSN data that captures the location of users over time as well as social interactions of users in a social network. While existing LBSN datasets are trivially small, such a framework would provide the first source of massive LBSN benchmark data which would closely mimic the real world, containing high-fidelity information of location, and social connections of millions of simulated agents over several years of simulated time. Therefore, it would serve the research community by revitalizing and reshaping research on LBSNs by allowing researchers to see the (simulated) world through the lens of an omniscient entity having perfect data. These evaluations will guide future research enabling us to develop solutions to improve LBSN applications such as user-location recommendation, friend recommendation, location prediction, and location privacy.
Cost-Effectiveness of Postoperative Drug Rehabilitation for Injection Drug Users.

Background With the opioid crisis showing no sign of abating, strategies are needed to facilitate postoperative care for endocarditis related to injection drug use (IDU). The current standard, 6 weeks of intravenous antibiotics, yields frequent reoperation and IDU relapse. We examined the cost-effectiveness of inpatient drug rehabilitation (DR) postoperatively to optimize outcomes and costs. Methods Two postoperative strategies were assessed: hospital-only care (HC) vs HC plus inpatient DR. Monte Carlo simulation evaluated effectiveness in quality-adjusted life-years (QALY) and cost per patient calculated over a 20-year time horizon in 100,000 iterations. Willingness to pay was set to $100,000/QALY. To determine probabilities of continued postoperative IDU, recurrent infection, and death, best available evidence was combined with institutional data from IDU patients. Baseline probability of postoperative IDU was set to 35% after DR vs 60% after HC, and the cost of inpatient rehabilitation to $30,000. Results Addition of inpatient DR to standard HC is the favorable strategy, with incremental per-patient cost of $36,920 and 0.93 QALYs gained over 20 years. Sensitivity analysis demonstrates DR is within our willingness-to-pay of $100,000/QALY if postoperative IDU is reduced by at least 7% (from 60% to 53%). Conclusions Addition of postoperative inpatient DR for IDU-related endocarditis is cost-effective even if only a modest reduction in IDU is achieved. Collaboration between hospitals and payors to launch pilot programs that provide postoperative addiction treatment and intravenous antibiotics after cardiac operations could dramatically improve endocarditis care.
Water colour and climate

The impacts of climate change on the ecohydrology of forested mountain regions are uncertain. New high-resolution modelling suggests that during a hot, dry summer in the Alps, stressed vegetation capitalizes on downslope water subsidies, amplifying runoff deficits and further depleting water resources.
The Reducing Opioid Use in Children with Clefts Protocol: A Multidisciplinary Quality Improvement Effort to Reduce Perioperative Opioid Use in Patients Undergoing Cleft Surgery.

BACKGROUND Cleft repair requires multiple operations from infancy through adolescence, with repeated exposure to opioids and their associated risks. The authors implemented a quality improvement project to reduce perioperative opioid exposure in their cleft lip/palate population. METHODS After identifying key drivers of perioperative opioid administration, quality improvement interventions were developed to address these key drivers and reduce postoperative opioid administration from 0.30 mg/kg of morphine equivalents to 0.20 mg/kg of morphine equivalents. Data were retrospectively collected from January 1, 2015, until initiation of the quality improvement project (May 1, 2017), tracked over the 6-month quality improvement study period, and the subsequent 14 months. Metrics included morphine equivalents of opioids received during admission, administration of intraoperative nerve blocks, adherence to revised electronic medical record order sets, length of stay, and pain scores. RESULTS The final sample included 624 patients. Before implementation (n =354), children received an average of 0.30 mg/kg of morphine equivalents postoperatively. After implementation (n = 270), children received an average of 0.14 mg/kg of morphine equivalents postoperatively (p < 0.001) without increased length of stay (28.3 versus 28.7 hours; p = 0.719) or pain at less than 6 hours (1.78 versus 1.74; p = 0.626) or more than 6 hours postoperatively (1.50 versus 1.49; p = 0.924). CONCLUSIONS Perioperative opioid administration after cleft repair can be reduced in a relatively short period by identifying key drivers and addressing perioperative education, standardization of intraoperative pain control, and postoperative prioritization of nonopioid medications and nonpharmacologic pain control. The authors' quality improvement framework has promise for adaptation in future efforts to reduce opioid use in other surgical patient populations. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.
Deficits in Glutamic Acid Decarboxylase 67 Immunoreactivity, Parvalbumin Interneurons, and Perineuronal Nets in the Inferior Colliculus of Subjects With Schizophrenia

Aberrant processing of auditory stimuli is a prominent feature of schizophrenia (SZ). Prior studies have chronicled histological abnormalities in the auditory cortex of SZ subjects, but whether deficits exist at upstream, subcortical levels has yet to be established. En route to the auditory cortex, ascending information is integrated in the inferior colliculus (IC), a highly gamma amino butyric acid (GABA) ergic midbrain structure that is critically involved in auditory processing. The IC contains a dense population of parvalbumin-immunoreactive interneurons (PVIs), a cell type characterized by increased metabolic demands and enhanced vulnerability to oxidative stress. During development, PVIs are preferentially surrounded by perineuronal nets (PNNs), specialized extracellular matrix structures that promote redox homeostasis and excitatory/inhibitory balance. Moreover, in SZ, deficits in PVIs, PNNs, and the GABA synthesizing enzyme, glutamic acid decarboxylase (Gad67), have been extensively documented in cortical regions. Yet, whether similar impairments exist in the IC is currently unknown. Thus, we compared IC samples of age- and sex-matched pairs of SZ and unaffected control subjects. SZ subjects exhibited lower levels of Gad67 immunoreactivity and a decreased density of PVIs and PNNs within the IC. These findings provide the first histological evidence of IC GABAergic abnormalities in SZ and suggest that SZ-related auditory dysfunction may stem, in part, from altered IC inhibitory tone.
Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy

Purpose Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy. Methods and Materials The coefficient of determination for MHD and LAD V15Gy was calculated in this retrospective analysis of 701 patients with locally advanced NSCLC treated with radiation therapy. Four groups were defined on the basis of high or low MHD (≥10 Gy vs Results The proportion of variance in LAD V15Gy predictable from MHD was only 54.5% (R2 = 0.545). There was discordance (where MHD was high [≥10 Gy] and LAD low [V15Gy Conclusions MHD is insufficient to predict LAD V15Gy with confidence. When MHD and LAD V15Gy dose exposure is discordant, isolated low LAD V15Gy significantly reduces the risk of MACE in patients with locally advanced NSCLC after radiation therapy, suggesting that the validity of whole heart metrics for optimally predicting cardiac events should be reassessed.
Vaccine-Associated Measles in a Hematopoietic Cell Transplant Recipient: Case Report and Comprehensive Review of the Literature

Measles is a worldwide viral disease that can cause fatal complications in immunocompromised hosts such as hematopoietic cell transplant (HCT) recipients. The live attenuated measles, mumps, and rubella (MMR) vaccine is generally contraindicated post-HCT due to the risk for vaccine-associated measles. This, combined with decreasing vaccination rates due to vaccine hesitancy and the coronavirus disease 2019 pandemic, raises significant concerns for a measles resurgence that could portend devastating consequences for immunocompromised hosts. Multiple guidelines have included criteria to determine which HCT recipients can safely receive the MMR vaccine. Here, we report a case of vaccine-associated measles in a HCT recipient who met guideline-recommended criteria for MMR vaccination. The objective of this article is to query these criteria, highlight the importance of MMR vaccination, and comprehensively review the literature.
Assessing Patient Satisfaction Following Blepharoplasty Using Social Media Reviews.

BACKGROUND As patient satisfaction is a significant qualitative consideration in measuring aesthetic surgery outcome, it is important to characterize the individual factors which shape the patient perspective about blepharoplasty. OBJECTIVES This study analyzed patient reviews following blepharoplasty on the aesthetic surgery social media platform Realself.com to determine which aspects of the surgical process have the most significant impact on patient satisfaction. METHODS Blepharoplasty reviews were gathered from Realself.com using an automated web crawler. These reviews were characterized as positive or negative, then given a specific category that more specifically defined the theme of the review. Additional variables including the specialty of the reviewed physician and any patient self-reported ratings were documented. RESULTS A total of 1991 reviews pertaining to blepharoplasty were collected. Among reviews with self-reported "worth it" ratings, 93.5% were positive. Following categorization of all reviews, 1865 (93.7%) were positive and 126 (6.3%) were negative. Of the positive reviews, the most common overall themes were bedside manner (n=899, 48.2%), aesthetic result (n=859, 46.1%), and overall comfort (n=58, 3.1%). Among negative reviews, most pertained to aesthetic result (n=100, 79.4%), and bedside manner (n=14, 11.1%). The most frequently encountered physician specialties performing blepharoplasty were plastic surgery (n=1101, 55.3%), ophthalmology (n=634, 31.8%), and otolaryngology (n=69, 3.5%). CONCLUSIONS The majority of patient blepharoplasty reviews were positive. The most prominent factor driving positive reviews was bedside manner, followed by aesthetic results. Negative reviews were most frequently attributed to sub-optimal aesthetic results. Most blepharoplasties in our study cohort were performed by plastic and oculoplastic surgeons.
Genetics of Rhizoctonia Species

The genetics of Rhizoctonia solani and related species is complex and remains poorly understood. When R. solani was first studied it was apparent that it was a ubiquitous species, that it could parasitize an enormous host range, and that it occurred in a great variety of cultural forms. The scientific community actively sought an understanding of what mechanisms underlay the organisms successful and broad adaptations as a pathogen. But an understanding did not come easily and I believe that in large part this was due to our confusion in whether to view the organism as a functionally sexual or functionally asexual (non-sexual) species.
Interleukin-13 receptor α2 chain

BACKGROUND Epithelial ovarian cancer demonstrates high mortality due to diagnosis at an advanced stage. In the search for a biomarker for early diagnosis and a target for therapy, the issue of whether interleukin-13 receptor (IL-13R), shown to be expressed on a variety of human cancers, is expressed in ovarian tumor samples was explored. In addition, whether this receptor serves as a biomarker and can be targeted by IL-13 cytotoxin was examined. METHODS IL-13R expression in 15 normal and 68 ovarian tumor tissue samples was determined by immunohistochemistry. Correlation between clinicopathologic features and IL-13R expression was analyzed. The efficacy of IL-13R-directed cytotoxin was determined in mice with subcutaneous, orthotopic, and peritoneal metastatic ovarian cancer. RESULTS Immunohistochemical analyses revealed that 83% of ovarian cancer specimens express IL-13Rα2, a high-affinity IL-13R subunit chain, whereas normal ovary samples expressed none or very low levels. The majority of clear cell ovarian carcinomas with the worst prognosis showed strong staining for IL-13Rα2. IL-13 cytotoxin was highly cytotoxic to the IGROV-1 ovarian cancer cell line in vitro, and it mediated significant antitumor activity against a xenografted tumor model. The antitumor effects were confirmed by treating orthotopically implanted or peritoneal metastatic ovarian tumors, which showed significant extension of survival in immunodeficient mice. IL-13 cytotoxin also prevented cachexia in treated mice. The soluble form of IL-13Rα2 was detected in the serum of mice with peritoneal metastasis, and the level decreased to baseline in the treated group. CONCLUSIONS IL-13Rα2 is a promising target for ovarian cancer therapy, and the soluble form of IL-13R may be a possible surrogate marker for disease monitoring. Cancer. Published 2006 by the American Cancer Society.
Characterization of Nuclear Receptor Ligands by Multiplexed Peptide Interactions

This unit describes a method to evaluate the effect that small molecules have on the binding interactions of a nuclear receptor protein with a series of peptides. The multiplexed microsphere-based system employs peptide-coupled microsphere populations that are fluorescently unique and thereby identifiable by flow cytometric analysis. Up to 100 different peptide-nuclear receptor interactions may be analyzed in a single well of a 96-well microtiter plate. This approach allows rapid and sensitive characterization of nuclear receptor ligands based on nuclear receptor protein-peptide interaction profiles. Since nuclear receptor binding interactions are dynamically related to protein conformation, the approach allows rapid evaluation of nuclear receptor ligands that may impart unique protein structure. The no-wash format and the high surface density of the microsphere-coupled interaction partner offer a moderately high-throughput system to examine low- to high-affinity interactions with excellent sensitivity. This approach, although described for nuclear receptors, may also be applied to other types of molecular interactions.
Hypophyseal regulation of hepatic histidase during postnatal development and adulthood. II. Pituitary-estrogen interrelationship.

Abstract Estrogen, which augments rat liver histidase activity in pre- and postpubertal rats, is ineffective in hypophysectomized animals, in which enzyme activities are already elevated. This failure of estrogen action has been demonstrated in hypophysectomized weanling, as well as adult females, the former of which manifest enzyme activities considerably below maximum possible values. The following agents, which are known to suppress histadase activity under certain conditions, were ineffective in permitting estrogen stimulation of histadase in hypophysectomized rats: glucocorticoid, testosterone, adrenocorticotrophin acting extra-adrenally and via the adrenals, growth, and preparations of whole pituitaries of bovine or female rat origin. The following materials, which do not themselves alter enzymic activity, were likewise incapable of permitting estrogenic enhancement of histadase activity in these animals: follicle-stimulating hormone and luteinizing hormone acting extra-gonadally, thyrotrophic hormone, and bovine posterior pituitary preparations. It is thus concluded that estrogen does not act directly on the liver to induced histadase activity, but requires participation of the hypophysis. However, estrogen does not seem to function by reversing any known pituitary derived suppressors of this enzyme, nor do pituitary factors seem to facilitate estrogen augmentation of the enzyme. These findings, however, would be compatible with the hydrolysis that estrogen may enhance liver histadase activity by inhibiting the secretion of some, as yet, unidentified enzyme-suppressing pituitary factor. Since the uterotrophic action of estrogen does not manifest hydrophyseal dependence, estrogenic effects on the uterus and on hepatic histadase are mediated by distinct mechanisms.
Chapter 37G Mass-spectrometric stable-isotope-dilution analysis for lanthanides in geochemical materials

Publisher Summary This chapter presents the fundamental theory and scope of the stable isotope dilution mass-spectrometry (MSID) method. It describes the chemical preparation and the mass spectrometry of the samples, and explains data calculation and quality. MSID is the most accurate technique for determining lanthanide abundances in geochemical materials. The superior quality of the method may be attributed principally to the inherent sensitivity of mass-spectrometers, and to the use of the ideal internal standard—namely, an artificially enriched isotope of each element to be determined. The utilization of isotopic internal standards virtually eliminates potential analytical problems, such as quantitative recovery and instrument calibration. The sensitivity of the mass spectrometer is such that the lower limit of measurable abundance is usually controlled by the purity of the reagents used in preparing the sample for analysis.
The interaction of interstellar gas with stellar density wave packets

We have numerically studied the interaction between interstellar gas and a gravitational perturbation produced by a fluctuation in the stellar mass distribution. For a simple equation of state, shock waves develop even if the gravitational perturbation is aperiodic and transient. In a medium which can change thermal phase, shocks do not form and the gas makes a transition directly to the cold, dense phase. The cold material has an anomalous velocity imparted to it by the gravitational perturbation and it becomes an accretion front moving through the hot gas and capturing it. The accretion fronts trigger thermal phase change on a large scale and can reproduce the extent of observed cold clouds. Furthermore their high mass is favorable to gravitational instability and subsequent star formation.
Cerenkov Radiation at Microwave Frequencies

Publisher Summary This chapter describes the various aspects of Cerenkov radiation at microwave frequencies. Cerenkov radiation may be considered the electromagnetic analog of the acoustic shock wave which is produced when a projectile moves through a medium at a velocity which exceeds the velocity of wave propagation in the medium. It is found that the energy radiated per unit frequency interval is proportional to frequency and the mass of the particle does not appear. It is observed that whereas the Cerenkov radiation involves a large number of weak interactions between the particle and an infinitely large number of atoms, bremsstrahlung implies a small number of collisions in which large fractions of the particle energy are radiated. The Cerenkov radiation produced by an extended electron beam has been computed. The role played by the medium in the Cerenkov radiation process is examined. It is found that in the Cerenkov case, a large fraction of the field energy is propagated in the dielectric and is thus unavailable for interaction with the beam, so that the impedance of the system is inherently low.
Aspects of Context for Understanding Multi-modal Communication

Context is important for AI applications that interact with users. This is true both for natural language interfaces as well as for multi-modal interfaces. In this paper, we consider aspects of context that are important in a multi-modal interface combining natural language and graphical input to describe locations. We have identified several aspects of contexts in our preliminary study. We describe them here and discuss plans for future work.
Analysis of the Neurotoxin Complex Genes in Clostridium botulinum A1-A4 and B1 Strains: BoNT/A3, /Ba4 and /B1 Clusters Are Located within Plasmids

Author(s): Smith, Theresa J; Hill, Karen K; Foley, Brian T; Detter, John C; Munk, A Christine; Bruce, David C; Doggett, Norman A; Smith, Leonard A; Marks, James D; Xie, Gary; Brettin, Thomas S | Abstract: BackgroundClostridium botulinum and related clostridial species express extremely potent neurotoxins known as botulinum neurotoxins (BoNTs) that cause long-lasting, potentially fatal intoxications in humans and other mammals. The amino acid variation within the BoNT is used to categorize the species into seven immunologically distinct BoNT serotypes (A-G) which are further divided into subtypes. The BoNTs are located within two generally conserved gene arrangements known as botulinum progenitor complexes which encode toxin-associated proteins involved in toxin stability and expression.Methodology/principal findingsBecause serotype A and B strains are responsible for the vast majority of human botulism cases worldwide, the location, arrangement and sequences of genes from eight different toxin complexes representing four different BoNT/A subtypes (BoNT/A1-Ba4) and one BoNT/B1 strain were examined. The bivalent Ba4 strain contained both the BoNT/A4 and BoNT/bvB toxin clusters. The arrangements of the BoNT/A3 and BoNT/A4 subtypes differed from the BoNT/A1 strains and were similar to those of BoNT/A2. However, unlike the BoNT/A2 subtype, the toxin complex genes of BoNT/A3 and BoNT/A4 were found within large plasmids and not within the chromosome. In the Ba4 strain, both BoNT toxin clusters (A4 and bivalent B) were located within the same 270 kb plasmid, separated by 97 kb. Complete genomic sequencing of the BoNT/B1 strain also revealed that its toxin complex genes were located within a 149 kb plasmid and the BoNT/A3 complex is within a 267 kb plasmid.Conclusions/significanceDespite their size differences and the BoNT genes they contain, the three plasmids containing these toxin cluster genes share significant sequence identity. The presence of partial insertion sequence (IS) elements, evidence of recombination/gene duplication events, and the discovery of the BoNT/A3, BoNT/Ba4 and BoNT/B1 toxin complex genes within plasmids illustrate the different mechanisms by which these genes move among diverse genetic backgrounds of C. botulinum.
Tourism and Afro-Antillean Identity in Panama

Throughout its history as a nation, Panama has emphasised its Spanish roots. Having become a postcolonial state, Panama now exploits its multiculturalism for the purpose of attracting tourists. In this context, Afro-Antilleans in the Archipelago of Bocas del Toro – historically marginalised and considered temporary migrants – are developing gendered and racialised identities for tourist consumption, in response to the state's tourism promotion and in pursuit of a complex cultural politics. Tourism provides an occasion for Afro-Antilleans to reposition themselves within the Panamanian nation, vis-a-vis the state and other ethnic groups. ‘Panamanian’ Afro-Antillean identities are also transnational, African and Caribbean; these constructions of difference in the touristic context are inevitably contradictory, at once national and diasporic. This paper explores these complexities and their complex origins: nationalism, regional and trans-Atlantic migration, and tourism. It concludes that so-called globalisat...
Temporal changes in matrix metalloproteinase expression and inflammatory response associated with cardiac rupture after myocardial infarction in mice

We previously found that male mice with myocardial infarction (MI) had a high rate of cardiac rupture, which generally occurred at 3 to 5 days after MI. Since matrix metalloproteinases (MMPs) play an important role in infarct healing, tissue repair and extracellular matrix (ECM) remodeling post-MI, we studied the temporal relationship of MMP expression and inflammatory response to cardiac rupture after acute MI. Male C57BL/6J mice were subjected to MI (induced by ligating the left anterior descending coronary artery) and killed 1, 2, 4, 7 or 14 days after MI. MMP-2 and MMP-9 activity in the heart were measured by zymography. Collagen content was measured by hydroxyproline assay. We found that after MI, MMP-9 activity increased as early as 1 day and reached a maximum by 2-4 days, associated with a similar increase in neutrophil and macrophage infiltration in the infarct area. MMP-2 started to increase rapidly within 4 days, reaching a maximum by 7 days and remaining high even at 14 days. Intense macrophage infiltration appeared by 4 days after MI and then gradually decreased within 7 to 14 days. Collagen content was unchanged until 4 days after MI, at which point it increased and remained high thereafter. Our data suggest that in mice, overexpression of MMP-2 and MMP-9 (possibly expressed mainly by neutrophils and macrophages) may lead to excessive ECM degradation in the early phase of MI, impairing infarct healing and aggravating early remodeling which in turn causes cardiac rupture.
Monitoring bridge health using fuzzy case-based reasoning

Case-based reasoning (CBR), one of the artificial intelligence (AI) learning approaches, is drawing the attention of many researchers in Civil Engineering. However, due to vagueness and uncertainties in knowledge representation, attribute description, and similarity measures in CBR-especially when dealing with similarity assessment-it is difficult to find the cases from a case base which exactly match the query case. Therefore, fuzzy theories have been incorporated into CBR allowing for more robust, flexible, and accurate models. In this study, two fuzzy membership functions (trapezoidal and step-wise) and fuzzy numbers are used to measure the similarity between attribute values. They are integrated into CBR to develop a model used to monitor highway bridge health. This model's learning capabilities have been validated using five different error-metrics, based on the cross-validation method. The code is implemented using the programming language C++, and all the cases used for both training and testing are extracted from the electronic bridge database of the Kansas Department of Transportation. It is shown from the experimental results that it is feasible to apply fuzzy case-based reasoning to monitor bridge health.
Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat

Traumatic brain injury (TBI) can produce chronic cognitive learning/memory deficits that are thought to be mediated, in part, by impaired hippocampal function. Experimentally induced TBI is associated with deficits in hippocampal synaptic plasticity (long-term potentiation, or LTP) at acute post-injury intervals but plasticity has not been examined at long-term survival periods. The present study was conducted to assess the temporal profile of LTP after injury and to evaluate the effects of injury severity on plasticity. Separate groups of rats were subjected to mild (1.1-1.4 atm), moderate (1.8-2.1 atm), or severe (2.2-2.7 atm) fluid percussion (FP) injury (or sham surgery) and processed for hippocampal electrophysiology in the first or eighth week after injury. LTP was defined as a lasting increase in field excitatory post-synaptic potential (fEPSP) slope in area CA1 following tetanic stimulation of the Schaffer collaterals. The fEPSP slope was measured for 60 min after tetanus. Assessment of LTP at the acute interval (6 days) revealed modest peak slope potentiation values (129-139%), which declined in each group (including sham) over the hour-long recording session and did not differ between groups. Eight weeks following injury, slices from all groups exhibited robust maximal potentiation (134-147%). Levels of potentiation among groups were similar at the 5-min test interval but differed significantly at the 30- and 60-min test intervals. Whereas sham slices showed stable potentiation for the entire 60-min assessment period, slices in all of the injury groups exhibited a significant decline in potentiation over this period. These experiments reveal a previously unknown effect of TBI whereby experimentally induced injury results in a chronic inability of the CA1 hippocampus to maintain synaptic plasticity. They also provide evidence that sham surgical procedures can significantly influence hippocampal physiology at the acute post-TBI intervals. The results have implications for the mechanisms underlying the impaired synaptic plasticity following TBI.
Investigation of protein binding affinity and preferred orientations in ion exchange systems using a homologous protein library.

A library of cold shock protein B (CspB) mutant variants was employed to study protein binding affinity and preferred orientations in cation exchange chromatography. Single site mutations introduced at charged amino acids on the protein surface resulted in a homologous protein set with varying charge density and distribution. The retention times of the mutants varied significantly during linear gradient chromatography. While the expected trends were observed with increasing or decreasing positive charge on the protein surface, the degree of change was a strong function of the location and microenvironment of the mutated amino acid. Quantitative structure–property relationship (QSPR) models were generated using a support vector regression technique that was able to give good predictions of the retention times of the various mutants. Molecular descriptors selected during model generation were used to elucidate the factors affecting protein retention. Electrostatic potential maps were also employed to provide insight into the effects of protein surface topography, charge density and charge distribution on protein binding affinity and possible preferred binding orientations. The use of this protein mutant library in concert with the qualitative and quantitative analyses presented in the article provides an improved understanding of protein behavior in ion exchange systems. Biotechnol. Bioeng. 2009; 102: 869–881. © 2008 Wiley Periodicals, Inc.
Soft-Decision-Directed MIMO Channel Estimation Geared to Pipelined Turbo Receiver Architecture

We consider channel estimation specific to turbo equalization for multiple-input multiple-output (MIMO) wireless communication. We develop soft-decision-driven sequential algorithms geared to a specific pipelined turbo equalizer architecture operating on orthogonal frequency division multiplexing (OFDM) symbols. One interesting feature of the pipelined turbo equalizer is that multiple soft-decisions become available at various processing stages. A tricky issue is the fact that these multiple decisions from different pipeline stages have correlated decision errors as well as varying levels of reliability. This paper establishes an optimization strategy for the channel estimator to track the target channel while dealing with observation sets with different qualities. The resulting algorithm is basically a linear sequential estimation algorithm and, as such, is Kalman-like in nature. The main difference here, however, is that the proposed algorithm must deal with the inherent correlation that exist among the multiple module outputs that cannot easily be removed by the traditional innovation approach. The proposed algorithm continuously monitor the quality of the feedback decisions and incorporate it in the channel estimation process. The proposed channel estimation schemes show certain performance and complexity advantages over existing EM-based algorithms.