cssi/SciSciGPT-SciSciNet huggingface dataset:
Not-so-early bursts and the dynamic nature of morphological diversification

In Wonderful Life, Stephen Jay Gould attempted to explain how the bizarre animal fossils from the 500 million-y-old Burgess Shale fauna teach a valuable lesson about the nature of morphological evolution (1). Finding such a remarkable diversity of body plans so early in the history of metazoan life should not be surprising, he argued, for this is an all-too-common pattern. Rather than gradually accumulating, as earlier iconography tended to illustrate, morphological diversity has often generated rapidly during the early phases of clade history. After an initial and rapid exploration of possibilities, successful forms proliferate while those less fortunate are quickly erased by extinction. Gould’s inverted iconography is, in fact, quite consistent with long-standing ideas in paleontology regarding early rapid morphological diversification in higher-level clades (2, 3), and this concept has since become entrenched in modern macroevolutionary biology as the early burst model of adaptive radiation (4). In PNAS, Hopkins and Smith (5) investigate rates of morphological evolution in the post-Paleozoic fossil record of echinoids (sea urchins, sand dollars, and their kin). The authors find that there is no evidence for an early burst of morphological innovation in echinoids as a whole. Instead, Hopkins and Smith document a third way: echinoid evolution is characterized by slow rates and constraints in stem lineages, but later pulses of evolutionary bursts are associated with shifts in feeding morphology.
The 2010 ESPEN Sir David Cuthbertson Lecture: New and old proteins: Clinical implications

The past century had witnessed vast advances in biomedical research, particularly in the fields of genomics and proteomics, yet the translation of these discoveries into clinical practice has been hindered by gaps in mechanistic understanding of variability governing disease susceptibility and pathogenesis. Among the greatest challenges are the dynamic nature of the proteome and the imperfect methodologies currently available to study it. Here, we review key recently developed proteomic techniques that have allowed for dynamic characterization of protein quality, as well as quantity, and discuss their potential applications in understanding aging and metabolic disorders including diabetes. These methodologies revealed that senescence is characterized, in part, by decreased rates of de novo protein synthesis and potentially also degradation, in addition to concomitantly increased levels of oxidative stress, ultimately resulting in excessive accumulation of damaged and dysfunctional proteins. Insulin may be a key mediator in these pathologies, as hyperinsulinemia has been shown to hinder protein degradation while transient insulin deficiency may accelerate oxidative damage. We also discuss two interventions that have been proposed to delay, and possibly reverse, senescence by augmenting protein degradation: chronic caloric restriction and aerobic exercise.
Diagnosis of infected total knee: findings of a multicenter database.

Although total knee arthroplasty (TKA) is an effective and successful procedure, the outcome is occasionally compromised by complications including periprosthetic joint infection (PJI). Accurate and early diagnosis is the first step in effectively managing patients with PJI. At the present time, diagnosis remains dependent on clinical judgment and reliance on standard clinical tests including serologic tests, analysis of aspirated joint fluid, and interpretation of intraoperative tissue and fluid test results. Although reports regarding sensitivity and specificity of all diagnostic tests in the literature are abundant, the interpretation of the available data has been hampered by the low sample size of these studies. In view of the scope of this important problem and the limitations of previous reports, a large database was assembled of all revision TKA performed at three academic referral centers in order to determine the current status of diagnosis of the infected TKA utilizing commonly available tests. Intraoperative cultures should not be used as a gold standard for PJI owing to high percentages of false-negative and false-positive cases. When combined with clinical judgment, total white cell count and percentage of neutrophils in the synovial fluid more accurately reflects PJI and when combined with hematologic exams safely excludes or confirms infection. Level of Evidence: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1.

We recently identified a novel metastasis suppressor gene, BRMS1, in breast cancer. Since the BRMS1 gene maps to chromosome 11q13.1-q13.2 and since chromosome 11q defects have been described in various stages of human melanoma progression, we hypothesized that BRMS1 may function as a tumor or metastasis suppressor in melanomas as well. Quantitative real-time RT-PCR revealed that BRMS1 mRNA expression was high in melanocytes, considerably reduced in early melanoma-derived cell lines, and barely detectable in advanced/metastatic cell lines. Stable transfectants of BRMS1 in the human melanoma cell lines MelJuSo and C8161.9 did not alter the tumorigenicity of either cell line, but significantly suppressed metastasis compared to vector-only transfectants. Orthotopic tumors continued to express BRMS1, but expression was lost in lung metastases. In vitro morphology, growth rate, and histology of BRMS1 transfectants were similar to controls. BRMS1 transfectants were less invasive in a collagen sandwich assay and had restored homotypic gap junctional intercellular communication (GJIC). Thus, BRMS1 functions as a metastasis suppressor in more than one tumor type (i.e., breast carcinoma and cutaneous melanoma) by modifying several metastasis-associated phenotypes.
Commercial simulation over the Web

Modeling and simulation provide objective analysis tools for many fields including manufacturing. This paper presents the requirements and describes the usefulness of a Web-based interface to discrete-event simulation. A description of related efforts is first presented and an approach is then described. The approach develops a Web-based interface to use commercial discrete-event commercial tools.
Confronting the challenge of integrated assessment of climate adaptation: A conceptual framework

Key limitations of integrated assessment models (IAMs) are their highly stylized and aggregated representation of climate damages and associated economic responses, as well as the omission of specific investments related to climate change adaptation. This paper proposes a framework for modeling climate impacts and adaptation that clarifies the relevant research issues and provides a template for making improvements. We identify five desirable characteristics of an ideal integrated assessment modeling platform, which we elaborate into a conceptual model that distinguishes three different classes of adaptation-related activities. Based on these elements we specify an impacts- and adaptation-centric IAM, whose optimality conditions are used to highlight the types of functional relationships necessary for realistic representations of adaptation-related decisions, the specific mechanisms by which these responses can be incorporated into IAMs, and the ways in which the inclusion of adaptation is likely to affect the simulations’ results.
The molecular cloning and characterization of BM1P1 and BM1P2 proteins, putative positive transcription factors involved in barbiturate-mediated induction of the genes encoding cytochrome P450BM-1 of Bacillus megaterium.

Abstract Analysis of a 1.3-kilobase segment of 5′-flanking DNA from the barbiturate-inducible P450BM-1 gene (CYP106) of Bacillus megaterium revealed two open reading frames. One, BM1P1, encodes 98 amino acids and is located 267 base pairs upstream from the sequence encoding cytochrome Pf450BM-1 but in the opposite orientation. The second, BM1P2 (88 amino acids), is 892 base pairs upstream from the P450BM-1 coding sequence and in the same coding strand. The expression of BM1P1 and BM1P2 was strongly stimulated in cells grown in the presence of pentobarbital, and the BM1P1 gene product exerted positive control on expression of P450BM-1. When a 177-base pair fragment encompassing the overlapping promoter regions of the P450BM-1 and BM1P1 genes was used as a probe in DNA binding assays, the BM1P1 and BM1P2 gene products and Bm3R1 (the repressor protein regulating the barbiturate-mediated expression of P450BM-3) could bind individually, but the addition of BM1P1 or BM1P2 to a binding mixture containing Bm3R1 completely prevented the appearance of a Bm3R1 binding band. When a 208-base pair fragment containing a Barbie box sequence and located upstream of the 177-base pair fragment was used as a probe, only a Bm3R1 binding band was detected. Although neither BM1P1 and BM1P2 appeared to bind to this 208-base pair fragment, their presence strongly inhibited the binding of Bm3R1 to the same probe. The evidence suggests that BM1P1 and BM1P2 may, in part, act as positive regulatory proteins involved in the expression of the P450BM-1 gene by interfering with the binding of the repressor protein, Bm3R1, to the regulatory regions of P450BM-1.
Three-dimensional flame measurements using fiber-based endoscopes

Abstract This work describes instantaneous three-dimensional (3D) flame measurements using fiber-based endoscopes (FBEs). The measurement technique used FBEs to gather projections of the target flame from various orientations simultaneously, based on which a 3D tomographic reconstruction was then performed to obtain 3D flame measurements. Both experimental and numerical results are reported to illustrate the capabilities of the measurement technique, and study its limitations. These results demonstrate the feasibility of obtaining instantaneous 3D measurements with sub-mm spatial resolution at kHz temporal resolution using FBEs, and also the practical advantages of FBEs for overcoming optical access and reducing equipment cost.
The Dynamics of Local Markets: A Case Study of Cameras

Longitudinal data on the availability and prices of two related products in a local market are used to assess the dynamic performance of the markets for these products. Consistent with prior research, a large degree of price dispersion was found for both products. There was some evidence of a modest reduction in price dispersion over time, and of the lowest quality models to “drop out” of the market. Store quality differences and likely search costs did not appear to explain the remaining dispersion.
Using Melnikov's method to solve Silnikov's problems*

A function space approach is employed to obtain bifurcation functions for which the zeros correspond to the occurrence of periodic or aperiodic solutions near heteroclinic or homoclinic cycles. The bifurcation function for the existence of homoclinic solutions is the limiting case where the period is infinite. Examples include generalisations of Silnikov's main theorems and a retreatment of a singularly perturbed delay differential equation.
Minimum spanning trees

The minimum spanning tree problem originated in the 1920s when O. Borůvka identified and solved the problem during the electrification of Moravia. This graph theory problem and its numerous applications have inspired many others to look for alternate ways of finding a spanning tree of minimum weight in a weighted, connected graph since Borůvka’s time. This note presents a variant of Borůvka’s algorithm that developed during the graph theory course work of undergraduate students. We discuss the proof of the algorithm, compare it to existing algorithms, and present an implementation of the procedure in Maple.
A Note on the Benefits of Aggregate Evaluation of Budget Proposals

ABSTRACT: Budgeting admits significant management control problems due to information asymmetries within organizations. We extend the Antle, Bogetoft and Stark (1999) principal agent analysis of budgeting, performing comparative statics on the potential benefit of bundling projects. Bundling projects confers a type of diversification benefit similar to portfolio diversification. We find this benefit is maximized at intermediate levels of profitability. The rationale for this finding is that at high levels of profitability the control problem is trivial and at low levels of profitability individual evaluation is necessary to screen for only the most profitable projects. For similar reasons bundling is most beneficial at intermediate levels of slack potential. We further find that when bundling is strictly beneficial to the principal its benefit is decreasing in the correlation between the projects' profitability. The intuition for this finding is (positive) correlation diminishes the diversification benefi...
The Baroreflex in Hypertension

Hypertension is a complex syndrome that increases the risk of developing other medical comorbidities and interacts with other medical conditions to increase the risk of target end-organ damage such as cardiovascular disease, stroke, and renal disease. Hypertension remains under-recognized and poorly controlled in the USA and worldwide. In some patients, hypertension is resistant to optimal medical therapy. Over the last few decades, there has been an increasing understanding of the role of the sympathetic nervous system in the development and maintenance of hypertension. This update reviews the physiology and role of the sympathetic nervous system in hypertension and pharmacological and interventional treatments directed at nervous system involvement in secondary hypertension.
ARE COMMUNITY COLLEGE TRAINING PROGRAMS FOR PARAEDUCATORS FEASIBLE

Paraeducators are vital components of public school educational programs for students with disabilities and those with remedial needs, as well as preschools and residential child care facilities. They are technicians who perform personal care and direct instructional services, and behavior management. Yet, training programs for these important employees are notably absent. This study examined the feasibility of developing training programs in the community college system in Colorado. Directors of special education, teachers, and personnel directors were surveyed to determine their attitudes toward training needs, their perceptions of the levels of support that school districts might offer, and their knowledge of the hiring practices in their own agencies. There was considerable interest in and support for training efforts through the community college system. Yet, a compelling need for local autonomy in the hiring of trained or untrained applicants was illustrated. Conclusions were drawn about the charact...
Five-dimensional quasispin toward a complete classification of the isospin characteristics of shell-model states in the seniority scheme

Abstract A solution is proposed for the inner multiplicity problem associated with the five-dimensional quasispin description of shell-model states. A classification scheme, in terms of an orthonormal basis, leads to tractable results with definite symmetry properties under particle-hole conjugation. Explicit constructions are given for the R(5) irreducible representations (ω1 1), (ω13/2), (t + 1, t) for which the inner multiplicities are never greater than two. For states of seniority v = 2, reduced isospin t = 1, of a configuration jn general expressions are given for the matrix elements of an arbitrary two-body interaction, to determine their n, T dependence, and to isolate those features of the actual interaction among nucleons which are most effective in splitting the isospin degeneracy of such states.
Muscarinic cholinergic receptors in developing rat lung.

ABSTRACT. Muscarinic cholinergic receptors were identified and partially characterized in crude membrane fractions of rat lung and trachea from day 17 of gestation to adulthood using (-)-[3H]quinuclidinyl benzilate (QNB). (–)-[3H]QNB binding to rat lung membrane was characteristic of muscarinic cholinergic receptor sites. Binding capacity of muscarinic receptors sites was relatively low in rat lung compared to that in other tissues. The number of (–)-[3H]QNB-binding sites (binding capacity) decreased progressively and significantly from 79 ± 8 fmol mg−1 protein on days 17–18 of gestation to 21 ± 3 fmol mg−1 mean ± SEM on days 21–22 of gestation, p < 0.01. Binding capacity did not vary thereafter from birth to adulthood. Affinity of (-)-[3H]QNB binding for lung membranes did not change with age (KD approximately 70 pM). (–)-[3H] QNB-binding sites were significantly higher in membrane preparations of trachea or tracheal-bronchial tissue than in lung parenchyma from both the adult and newborn rats. (-)-[3H]QNB binding was undetectable in crude membrane preparations of cultured purified type II epithelial cells isolated from the adult rat lung. Muscarinic cholinergic receptor sites are present in rat lung as early as day 17 of gestation. Since preparations of proximal portions of the lung are relatively enriched in (-)-[3H]QNB binding compared to more peripheral portions of the lung, ontogenic decreases in (-)-[3H]QNB binding may result from the higher contribution of trachealbronchial tissue compared to alveolar tissue in the preparations of early fetal lung, rather than to a specific regulation of muscarinic receptor sites. (Pediatr Res 18:1136- 1140,1984)
tert-Butyl Hydroperoxide-Induced [Ca2+]i in Thymus and Thymoma Cells

The effect of tert-butyl hydroperoxide (t-BOOH) on Ca2+ homeostasis in tumor thymocytes in comparison to normal thymus cells has been studied. t-BOOH induces an early Ca2+ increase which shows different kinetic and extent in normal and tumor thymocytes. However, evidence is reported that in both types of cells it is just an epiphenomenon not directly related to late injury event. The different effects of various compounds (EGTA, dithiothreitol, deferoxamine and glucose) on the early Ca2+ increase and the late LDH release induced by t-BOOH suggest the occurrence, only in tumor cells, of some undefined deleterious process related to Ca2+ movements.
Fischer–Tropsch synthesis: Metal–support interfacial contact governs oxygenates selectivity over CeO2 supported Pt–Co catalysts

Abstract The catalytic performance during Fischer–Tropsch synthesis (FTS) of Pt promoted Co/CeO 2 catalysts at two different cobalt metal loadings was investigated using a slurry-phase reactor. CeO 2 supported Pt–Co catalysts exhibit higher selectivities to oxygenates and especially linear alcohols (14.8%) at lower cobalt loadings. A plausible pathway for the formation of alcohols was proposed based on Co–CeO 2 interfacial catalysis, in which termination of chain growth occurs at the metal-oxide junction and involves bridging OH groups on partially reduced ceria. As cobalt content increases, the selectivity to oxygenates decreases. The resulting increase in cobalt metal particle size accelerates the mechanism involving normal FT termination, since the on-top surface area of cobalt increase at the expense of the interfacial area at the junction with ceria. Compared to γ-Al 2 O 3 , CeO 2 supported Pt–Co catalysts exhibit significantly higher oxygenates at similar CO conversions. Selectivity control is thus achieved by controlling the surface fugacity of bridging OH groups (i.e., located on ceria) in contact with cobalt sites on a per Co surface atom basis.
Cadherin-2 function in the cranial ganglia and lateral line system of developing zebrafish

Cadherins are cell surface molecules that mediate cell-cell adhesion through homophilic interactions. Cadherin-2 (also called N-cadherin), a member of classic cadherin subfamily, has been shown to play important roles in development of a variety of tissues and organs, including the nervous system. We recently reported that cadherin-2 was strongly expressed by the majority of cranial ganglia and lateral line system of developing zebrafish. To gain insight into cadherin-2 role in the formation of these structures, we have used several markers to analyze zebrafish embryos injected with a specific cadherin-2 antisense morpholino oligonucleotide (cdh2MO). We find that development of several cranial ganglia, including the trigeminal, facial, and vagal ganglia, and the lateral line ganglia and neuromasts of the cdh2MO-injected embryos are severely disrupted. These phenotypes were confirmed by analyzing a cadherin-2 mutant, glass onion. Our results suggest that cadherin-2 function is crucial for the normal formation of the zebrafish lateral line system and a subset of cranial ganglia.
The Pulse Wave Velocity as an Early Indicator of Atherosclerosis in Diabetic Subjects

The arterial pulse wave velocity was measured in 87 healthy individuals and in 52 diabetic patients who did not have clinical evidence of atherosclerosis or hypertension. A significant increase in the pulse wave velocity was found in the diabetic subjects. This increase was not correlated with the duration of their illness as judged from clinical history. It is very likely that the high values of pulse wave velocity were indicative of an incipient process of diffuse atherosclerosis and that the measurement of the pulse wave velocity brought this into evidence earlier than the classic signs and symptoms. Serial measurements of the pulse wave velocity in diabetic subjects may permit early detection of atherosclerosis in these patients.
The importance of dynamic performance and testing of industrial thermometers in process control

This paper considers the dynamic performance of instruments in control systems. Errors connected with transient measurements are discussed. It is shown that it is not always proper to assign common statistical properties to these dynamic errors. Emphasis is placed on temperature sensors. Common industrial thermometers are described and factors affecting their response discussed. An a-priori dynamic performance prediction procedure is presented. This permits preinstallation estimation of response characteristics of sensors used in industrial processes. Sensors in service also require performance assessment since they can deteriorate with use. In-situ testing is useful for this purpose and a recently develolped procedure is described.
Interactions of calcium with serum albumin

Abstract Binding of calcium ions by bovine serum albumin has been found to be essentially independent of temperature over the range 0 to 25 °C. On the other hand, pH has a very pronounced effect. No complexes with calcium are detectable until the protein is appreciably above its isoelectric point. Thereafter, uptake increases rapidly from pH 5.5 to about 8 and then seems to approach a plateau. At pH 8 and 0 °C. ΔF1∘ is equal to −3870 cal./mole, ΔH1∘ equals 0, and ΔS1∘ is equal to 14 cal./ mole/deg. Serum albumin with three salicylate groups introduced by a diazonium salt coupling showed no appreciable change in its affinity for calcium.
Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer.

Abstract Objective Pegylated liposomal doxorubicin (PLD) was introduced to reduce the adverse effect of doxorubicin in treating recurrent ovarian cancer. We sought to characterize the efficacy and adverse-effect profile of PLD in different doses and to evaluate predictive factors of palmar-plantar erythrodysesthesia (PPE). Methods Patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinoma treated with single-agent PLD between 1996 and 2006 at The University of Texas M. D. Anderson Cancer Center were retrospectively identified, and charts were reviewed for patient demographics, PLD data, adverse effects, use of cooling mechanisms, and survival. Results Three hundred-thirty patients were included and PPE of any grade occurred in 30.9%. Patients received a median of 3 (mean 4.32) cycles of PLD treatment. The different PLD doses ( 50 mg/m 2 ) were not associated with differences in overall survival (OS), progression-free survival (PFS), or time to progression (TTP). The incidences of mucositis, neutropenia, peripheral neuropathy, and vomiting were significantly higher at doses >50 mg/m 2 than at doses 2 . More patients who used cooling mechanisms (39%) had PPE than those who did not (26%). There was an association between mucositis, neutropenia, and peripheral neuropathy and PPE. More cycles of PLD (>6) also increased the incidence of PPE. In our study, only 7% of women discontinued PLD for toxicity while 74% discontinued for progression. Conclusion There was no association between different doses of PLD and OS, PFS, or TTP. A higher dose and more cycles increased the incidence of several toxicities, including PPE. The use of cooling mechanisms, higher number of PLD cycles, and occurrence of mucositis, neutropenia, and peripheral neuropathy are possible predictors of PPE.
Designer ligands for beryllium

We report the rational design of ligands that selectively bind beryllium. We selected two ligands to design Be based on binding polynulear species with a motif: 2-hydroxyisophthalic acid (HIPA) and 2,3-dihydroxybenzoic acid (DHBA). All previous work has focused on BeL or BeL2 species. The HIPA and DHBA have extremely high binding constants of 17.5 and 18.4, respectively. These ligands outcompete chromotropic acid, which has one the highest binding constants for Be reported in the literature for a simple BeL species. The binding of the second Be to form the motif is so strong that polynuclear species predominates in solution down to micromolar concentrations. Both ligands show a fluorescence response in the presence of beryllium, making them promising candidates for fluorescence-based sensors. In the case of HIPA, there is a fluorescence shift, and in the case of DHBA, the presence of beryllium turns on the fluorescence by removing two OH bonds that otherwise lead to nonradiative decay. The most dramatic ...
Liability and asset uncertainty for banks

Abstract Models of bank behavior are developed which incorporate both deposit and loan demand uncertainty. Extensions of the traditional and simple deposit uncertainty model involve the inclusion of required reserves, fixed penalty costs for reserve deficiencies, limits on normal borrowing, and uncertain spot loan demand and use of lines of credit. Results include normal borrowing limits as a new theoretical constraint on bank size and the existence of small fixed costs as a reason for the real world lack of deficient reserves. Policy conclusions include the effects of current reserve accounting and the effects of various interest rate changes.
Detection of myosin gene expression in the developing heart using probes derived by polymerase chain reaction

Abstract The polymerase chain reaction provides a rapid method for the molecular cloning of DNA probes suitable for the detection of specific messenger RNA. We have used this approach to prepare probes specific for human cardiac myosin messenger RNA and demonstrate here the use of such probes in the analysis of human cardiac development by hybridization in situ to sections of fetal tissue. This combination of techniques is suitable for the detection of any messenger RNA for which sequence data are available, and offers a powerful new apporach to the analysis of cardiac development.
A Historical resumé of indian limnology

A broad categorisation of Indian freshwater investigations published so far is presented. The lacunae are pointed out. Problems and priorities for further limnological researches in the context of India's limited water resources are high-lighted.
Heterogeneous Postprandial Lipoprotein Responses in the Metabolic Syndrome, and Response to Fenofibrate Therapy

Hypertriglyceridemia subjects with metabolic syndrome exhibit variable postprandial triglyceride responses. We investigate the effects of fenofibrate therapy on postprandial triglyceride-containing lipoproteins in subjects with early (3.5 h) versus late (8 h) postprandial triglyceride responses. Fifty-five subjects with fasting hypertriglyceridemia (≥1.7 mmol/L (150 mg/ dL) and <5.8 mmol/L (500 mg/dL)) and ≥2 Adult Treatment Panel III criteria of the metabolic syndrome were randomized to daily fenofibrate (160 mg/d) or placebo for 12 weeks in a double-blind controlled clinical trial. A standardized fat load (50 g/m2) was given orally after a 12 h fast. Blood specimens were obtained at 0 h (fasting), 3.5 h, and 8 h after the test meal. Analysis is confined to the 53 subjects with clearly identifiable early or late triglyceride peaks prior to therapy. Fenofibrate was more effective in late peakers (n = 8) when compared to early peakers (n = 15) with respect to reducing postprandial triglyceride concentrations (−67% vs. −34%, p = 0.0024) and large VLDL (−76% vs. −31%, p = 0.0016), and increasing total HDL particles (20% vs. 11%, p = 0.008) and large HDL particles (185% vs. 88%, p = 0.003). On fenofibrate therapy, 100% of those initially designated as late peakers were reclassified as early peakers; 47% of late peakers assigned to placebo were reclassified as early peakers. Late postprandial triglyceride responders have attenuated clearance of large VLDL particles, but they were more responsive to fenofibrate.
Genome-wide Impact of the BRG1 SWI/SNF Chromatin Remodeler on the Transforming Growth Factor β Transcriptional Program

The transcription factors Smad2 and Smad3 mediate a large set of gene responses induced by the cytokine transforming growth factor β (TGFβ), but the extent to which their function depends on chromatin remodeling remains to be defined. We observed interactions between these two Smads and BRG1, BAF250b, BAF170, and BAF155, which are core components of the SWI/SNF chromatin-remodeling complex. Smad2 and Smad3 have similar affinity for these components in vitro, and their interactions are primarily mediated by BRG1. In vivo, however, BRG1 predominantly interacts with Smad3, and this interaction is enhanced by TGFβ stimulation. Our results suggest that BRG1 is incorporated into transcriptional complexes that are formed by activated Smads in the nucleus, on target promoters. Using BRG1-deficient cell systems, we defined the BRG1 dependence of the TGFβ transcriptional program genome-wide. Most TGFβ gene responses in human epithelial cells are dependent on BRG1 function. Remarkably, BRG1 is not required for the TGFβ-mediated induction of SMAD7 and SNON, which encode key mediators of negative feedback in this pathway. Our results provide a genome-wide scope of the participation of BRG1 in TGFβ action and suggest a widespread yet differential involvement of BRG1 SWI/SNF remodeler in the transcriptional response of many genes to this cytokine.
Incorporation and utilization of radioglucose in the fish embryo Oryzias latipes during teratogenesis.

Malformations have been produced in fish embryos of Oryzias latipes following exposure to the sulfonylurea sodium tolbutamide during day 1 of development (Smithberg '62). Our present objectives were to determine (1) whether glucose 1-14C would be differentially incorporated by embryos after drug treatment; and (2) whether the incorporated radioglucose would be converted to glycogen and lipid following drug treatment Total glycogen and total lipid were also measured in a normal and teratogenic environment. We confirmed the results of others that total glycogen decreased during the first three days of normal development and then slowly regained its initial level. During treatment with tolbutamide significantly more glycogen was utilized during the first three days. Total lipid tended to be lower in embryos after 48 hours of treatment compared to corresponding control embryos. Incorporation of radioglucose was inhibited by the drug, and the degree of inhibition varied with its concentration, although the conversion of glucose (or its products) into glycogen and lipid was not different in control and experimental embryos. It is suggested that tolbutamide may affect the permeability of the fish embryo membrane.
Arginase I levels are decreased in the plasma of pediatric patients with atopic dermatitis

Abstract Background Serum arginase levels have been shown to be elevated in conditions, such as trauma, cancer, chronic wounds, pregnancy, and diabetes. This also has been found to be true in atopic diseases, such as asthma and allergic rhinitis. Objective To study arginase activity in patients with atopic dermatitis (AD). Methods In this pilot study, arginase activity levels in 15 pediatric patients with AD were compared with those in controls to determine whether arginase levels in AD are altered as in patients with other atopic diseases. Results In contrast to the other diseases studied, arginase activity was found to be decreased in granulocytes and in the plasma of patients with AD compared with controls. This finding was coupled with a trend toward higher L-arginine plasma levels. Conclusion In AD, a different mechanism of arginine metabolism seems to be stimulated, leading to the formation of nitric oxide pathway components causing suppression of the arginase pathway and impairment in skin hydration, collagen synthesis, and wound healing.
Specific and heritable gene editing in Arabidopsis.

Targeted gene editing could offer tremendous advantages over traditional plant breeding to create new cultivars with advantageous combinations of alleles, especially when stacking of important traits is needed for crop improvement. Traditional methods of combining desirable alleles of different genes involve time-consuming crosses and selections, and in some cases such as combining closely linked loci, traditional methods are impossible to implement. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) relies on a small guide RNA (gRNA) molecule to direct specific cleavages of DNA sequences, and it has been widely tested for targeted gene editing in many organisms including plant species such as Arabidopsis, sorghum, rice, wheat, and tobacco. CRISPR/Cas can potentially be used to directly and precisely modify genes in the top commercial crop lines within a short period without affecting the existing valuable traits. However, before CRISPR/Cas can be widely used for crop improvement, several fundamental questions need to be addressed. What types of mutations can the CRISPR/Cas system generate in plants? Are the edited genomes stable and heritable? How often does unintended off-target mutagenesis occur and how do we decrease the off-target effects? In PNAS, Feng et al. (1) report a detailed analysis of CRISPR/Cas-mediated gene editing in Arabidopsis to address the aforementioned questions by following several generations of transgenic plants that harbor the CRISPR/Cas system, which was introduced into Arabidopsis by agrobacteria-mediated transformation. They studied seven genes at 12 distinct target sites to elucidate the pattern, specificity, and heritability of mutations induced by CRISPR/Cas. They clearly demonstrated that CRISPR/Cas could be used to generate transgene-free Arabidopsis plants with specific and heritable mutations within two generations (Fig. 1).
A Turning Point for Guohua?: Xu Beihong and Transformative Encounters With the Socialist Spirit, 1933–1953

This article investigates a transformative encounter between the Chinese artist Xu Beihong (徐悲鴻 1895–1953) and audiences in the Soviet Union during his 1933–1934 exhibitions of Chinese art in Europe. While Xu was exchanging perspectives and addressing questions about Chinese painting, a misreading of one of his paintings sparked in him a reconsideration of content and form that eventually led to the creation of some of the earliest Socialist realist ink-and-color paintings in China. This addition to his repertoire is arguably more significant to his legacy than his most popular works because of the way it heralded the coming Socialist realist evolution in guohua (國畫 national painting) and the manner in which Xu's choices would meet the ideological needs of the Communist Party well before it secured authority over the direction of China's arts. Special attention is paid to situating Xu's personal work vis-a-vis Republican and revolutionary art and explaining how the concurrent political milieu paved the way for both the prestige of his art in popular and cultural memory and the unprecedented stature of his art education methodologies in China's revolutionary times.
Sea-Floor Depth and the Lake Wobegon Effect

The ways in which actual measurements of sea-floor depth differ from average depths predicted by models of the solid Earth may provide useful information about how the planetary heat engine works. Actual depth is a function of plate tectonics and planetary heat flow. As S. Stein and C. Stein discuss in their Perspective, there is renewed interest in understanding these depth anomalies that is leading to improved models and extensive data sets.
Abstract P4-11-04: The Influence of Radiation on Survival in Patients with Triple Negative Stage II Breast Cancer

Background: Prospective trials of locally advanced breast cancer patients treated with adjuvant radiation (RT) have demonstrated a survival advantage; however, use of postmastectomy RT in stage II patients is controversial. This study explores the possibility that patients with aggressive variant molecular subtypes [triple receptor negative (TN)] treated with modern chemotherapy, may experience a survival benefit from adjuvant RT. Methods: Billing codes for all breast cancer patients treated with chemotherapy between 1/1998 and 5/2005 at the University of Alabama at Birmingham were reviewed to comprehensively capture all Stage II and III patients with intact data. Patient, tumor, and treatment related variables were recorded and patients were divided into 3 molecular subtypes based on receptor status: hormone receptor (HR) positive, Her2 negative; HR+/− , Her2+; and TN. Kaplan Meier curves to assess survival were performed by dividing the TN group into 2 groups: those who did or did not receive adjuvant RT. Results: 409 patients with stage II-III disease with were identified. Out of this group, 81 patients had TN breast cancer (60 Stage II and 21 Stage III). RT data was known in 79 of these patients. Median age was 49 years. Median follow-up was 72 months. Thirty-seven stage II and 18 stage III patients received adjuvant RT. Of the stage II patients who received radiation, 25 underwent lumpectomy and 11 underwent mastectomy. Stage II patients who received adjuvant RT had a statistically significant improvement in DFS (p=0.03), and had a trend towards improvement in OS (p=0.07) when compared with those who did not receive adjuvant RT. There was no significant difference in survival for the stage III patients with use of RT, however numbers in this group were small. Conclusion: Adjuvant RT was associated with an improvement in DFS and a trend towards improvement in OS in patients with Stage II, TN breast cancers treated with modern chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-04.
COMPLEXES OF 1,8-NAPHTHYRIDINES IX. GROUP VIb METAL CARBONYL COMPLEXES CONTAINING 1,8-NAPHTHYRIDINE, 2-METHYL-1,8-NAPHTHYRIDINE OR trans-DECAHYDRO-1,8-NAPHTHYRIDINE

Abstract Complexes of the type M(CO)5(N-N), M(CO)4(N-N) and M(CO)3(N-N)2, where M is Cr, Mo or W and N-N is 1,8-naphthyridine(napy), 2-methyl-1,8-naphthyridine(2-mnapy) or trans-decahydro-1,8-naphthyridine(dhnapy), have been prepared and characterized by infrared and proton magnetic spectroscopy. Complexes of the type Mo(CO)3(N-N)(napy), where N-N is 1,10-phenanthroline(phen), 2,2′-bipyridine(bipy), 2,9-dimethyl-1,10-phenanthroline(2,9-dmphen) or 2,7-dimethyl-1,8-naphthyridine (2,7-dmnapy), were also prepared and characterized by infrared spectroscopy. In these systems, the various naphthyridine donors exhibit the unique ability to behave as both mono- and bidentate ligands. The mode of bonding between the metal and heterocycles is determined by proton magnetic resonance data.
First Synthesis of a Branched β-C-Tetrasaccharide Using a Triple Ring Closing Metathesis Cyclization

The first synthesis of a branched beta-C-tetrasaccharide has been carried out through the use of an esterification-ring closing metathesis (RCM) strategy. The precursor triacid 2a was readily prepared via standard chemical methods from a known starting material, and dehydrative coupling with an excess of olefin alcohol 1a gave triester 3a in excellent yield. Methylenation of the triester 3a and subsequent triple RCM reaction was followed by an in situ hydroboration-oxidation to furnish the branched beta-C-tetrasaccharide 6a in good overall yield.
Micro-Raman of Cancer Cells: Toward Label-Free Sorting of Circulating Tumor Cells from Whole Blood

Even in the early stages of cancer, circulating tumor cells (CTCs) can travel from a primary tumor site to other organs through the blood and lymphatic system. Detecting and isolating CTCs from the blood has great potential for early cancer detection and studies of metastasis. However, they are notoriously rare (a few CTCs per mL of blood) and difficult to distinguish from epithelial non-tumor cells and leukocytes. Attempts to analyze CTC genetic or protein changes in response to treatment have been hampered by the difficulty in isolating intact clonogenic cells. Toward the goal of developing a rapid, non-invasive tool for detecting and isolating live CTCs from the blood, we measured the Raman spectra of live, unlabeled single cells. Using principal components analysis (PCA), we can distinguish WBCs from cancer cells, and tumorigenic ovarian cancer cells (A2780, OVCAR2, CaOV3) from non-tumorigenic ovarian cancer cells (OV429). Adherent cell lines and suspended (laser trapped) cells from cancer patient fluid samples were measured. A microfluidic platform with pressure control has been implemented to transport such cells single-file through the Raman laser focus. Custom microfluidics are in development and will sort the live, unmarked cancer cells into separate reservoirs for cell culture. Each Raman spectrum requires ∼1-2 minutes, so we are concurrently developing a faster, coherent anti-Stokes Raman scattering (CARS) microscope for higher throughput analysis. Rapid detection and sorting of live CTCs will give prognostic information and allow for observation of the effect of targeted cancer treatments via a minimally invasive blood test and possibly well before the availability of response data.
The Repetitive Behavior Scale-Revised : Independent validation in individuals with autism spectrum disorders

A key feature of autism is restricted repetitive behavior (RRB). Despite the significance of RRBs, little is known about their phenomenology, assessment, and treatment. The Repetitive Behavior Scale-Revised (RBS-R) is a recently-developed questionnaire that captures the breadth of RRB in autism. To validate the RBS-R in an independent sample, we conducted a survey within the South Carolina Autism Society. A total of 320 caregivers (32%) responded. Factor analysis produced a five-factor solution that was clinically meaningful and statistically sound. The factors were labeled "Ritualistic/Sameness Behavior," "Stereotypic Behavior," "Self-injurious Behavior," "Compulsive Behavior," and "Restricted Interests." Measures of internal consistency were high for this solution, and interrater reliability data suggested that the RBS-R performs well in outpatient settings.
V1R Promoters are well Conserved and Exhibit Common Putative Regulatory Motifs

The mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, LogoAlign, designed for this context and more generally for searching large, hierarchical datasets, suggest the existence of common information-rich regulatory motifs that are shared across otherwise divergent V1R subfamilies.
New Web Browser Applications

Summarises new and developing Web browser technologies. Describes three browsers, one with a “tabbed browsing” capability, another which includes a new productivity tool called a “search information manager”, and a voice operated browser which is still in development.
Chronic biloma after right hepatectomy for stage IV hepatoblastoma managed with roux-en-Y biliary cystenterostomy

We report the complex case of a 12-month-old girl with stage IV hepatoblastoma accompanied by thrombosis and cavernous transformation of the portal vein. After neoadjuvant chemotherapy, she underwent right hepatectomy, which was complicated by iatrogenic injury of her left hepatic duct, and subsequently developed a postoperative biloma and chronic biliocutaneous fistula. Concomitant with multiple percutaneous interventions to manage the biloma nonoperatively while the child completed her adjuvant chemotherapy, she progressed to develop chronic malnutrition, jaundice, and failure to thrive. Once therapy was completed and the child was deemed free of disease, she underwent exploratory laparotomy with Roux-en-Y biliary cystenterostomy for definitive management, resulting in resolution of her biliary fistula, jaundice, and marked improvement in her nutritional status. Roux-en-Y biliary cystenterostomy is a unique and efficacious management option in the highly selected patient population with chronic biliary leak refractory to minimally invasive management.
Dioecy and the evolution of sex ratios in ants.

Split sex ratios, when some colonies produce only male and others only female reproductives, is a common feature of social insects, especially ants. The most widely accepted explanation for split sex ratios was proposed by Boomsma and Grafen, and is driven by conflicts of interest among colonies that vary in relatedness. The predictions of the Boomsma–Grafen model have been confirmed in many cases, but contradicted in several others. We adapt a model for the evolution of dioecy in plants to make predictions about the evolution of split sex ratios in social insects. Reproductive specialization results from the instability of the evolutionarily stable strategy (ESS) sex ratio, and is independent of variation in relatedness. We test predictions of the model with data from a long-term study of harvester ants, and show that it correctly predicts the intermediate sex ratios we observe in our study species. The dioecy model provides a comprehensive framework for sex allocation that is based on the pay-offs to the colony via production of males and females, and is independent of the genetic variation among colonies. However, in populations where the conditions for the Boomsma–Grafen model hold, kin selection will still lead to an association between sex ratio and relatedness.