cssi/SciSciGPT-SciSciNet huggingface dataset:
Reprogramming of human peripheral blood cells to induced pluripotent stem cells.

Direct reprogramming of human fibroblasts to induced pluripotent stem cells (iPS) has been achieved by ectopic expression of defined transcription factors. Derivation of human fibroblasts however is a time consuming process and requires punch biopsies or isolation of patient foreskin. Here we use a polycistronic vector encoding Oct4, Klf4, Sox2 and c-Myc to generate iPS cells from from frozen peripheral blood of several donors. Genomic DNA analyses indicated that iPS cells were derived from mature T cells as well as myeloid donor cells. Inducing pluripotency in peripheral blood would allow utilization of easy to get samples from the adult and, more importantly, provide convenient access to numerous patient samples stored in blood banks. The latter is of major interest as frozen blood samples, when reprogrammed to iPS cells, would allow the retrospective molecular analyses of rare diseases.
IM here: public instant messaging on large, shared displays for workgroup interactions

Instant messaging (IM) in the workplace has proven to be a valuable tool for facilitating informal communication. Its benefits, however, are generally limited to times when users are in front of their computers. Because so much work takes place while people are mobile within their workplace, we sought to extend the benefits of IM beyond people's personal machines and into publicly accessible groupware. We first conducted a study of large display groupware applications (LDGAs) to understand the affordances that large displays offer for groupware, and the factors surrounding their adoption. We developed the IM Here system for shared IM on large displays using the lessons learned from the study. In this paper, we present the findings of our LDGA study, the design of IM Here and the preliminary results of our evaluation of IM as a public resource for workgroups.
Fractal geometry applications in description and analysis of patch patterns and patch dynamics

Abstract Fractal geometry applications have recently been paid great attention in ecology. In this paper, I summarize the state of the art and introduce several updated developments in analysis and description of patch patterns and patch dynamics by means of Mandelbrot’s fractal analysis, with an emphasis on my current research results and a personal view. These topics include geometric fractals, statistical fractals, information fractals, the fluctuation-tolerant fractals of dynamic patch size and shape, patch hierarchical scaling, fractal spatial patterns, multiple scale sampling and data analysis, fractal fragmentation of the landscape habitat into patches, fractal correlation in patchy systems, fractal cluster dynamics of vegetation systems, fractal mechanisms and ecological consequences, the spatio-temporal integrated approach and so on. The ecological significance of fractals in patch pattern and patch dynamics is discussed. A case study on fractal analysis of patch dynamics of southern Texas savanna landscape is given. Several limitations of fractal analysis in ecological applications are also addressed.
Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent

Serum Response Factor (SRF) is a transcription factor that is required for the expression of many genes including immediate early genes, cytoskeletal genes, and muscle-specific genes. SRF is activated in response to extra-cellular signals by its association with a diverse set of co-activators in different cell types. In the case of the ubiquitously expressed immediate early genes, the two sets of SRF binding proteins that regulate its activity are the TCF family of proteins that include Elk1, SAP1 and SAP2 and the myocardin-related MKL family of proteins that include MKL1 and MKL2 (also known as MAL, MRTF-A and -B and BSAC). In response to serum or growth factors these two classes of co-activators are activated by different upstream signal transduction pathways. However, it is not clear how they differentially activate SRF target genes. In order to identify the serum-inducible SRF target genes that are specifically dependent on the MKL pathway, we have performed microarray experiments using a cell line that expresses dominant negative MKL1. This approach was used to identify SRF target genes whose activation is MKL-dependent. Twenty-eight of 150 serum-inducible genes were found to be MKL-dependent. The promoters of the serum-inducible genes were analyzed for SRF binding sites and other common regulatory elements. Putative SRF binding sites were found at a higher rate than in a mouse promoter database but were only identified in 12% of the serum-inducible promoters analyzed. Additional partial matches to the consensus SRF binding site were found at a higher than expected rate in the MKL-dependent gene promoters. The analysis for other common regulatory elements is discussed. These results suggest that a subset of immediate early and SRF target genes are activated by the Rho-MKL pathway. MKL may also contribute to the induction of other SRF target genes however its role is not essential, possibly due to other activation mechanisms such as MAPK phosphorylation of TCFs.
Nature and timing of deformation in the Foothills terrane, central Sierra Nevada, California: Its bearing on orogenesis

Detailed mapping and structural analysis combined with new age dates, using U-Pb and ^(40)Ar/^(39)Ar techniques, have allowed us to constrain the timing of pre-ductile and ductile deformation in the Foothills terrane of the central Sierra Nevada. By using strain and other data, it can be shown that rigid rotation of beds (folding/faulting) predated the onset of ductile deformation and probably occurred between 160 and 151 Ma. Ductile structures, consisting of continuous and secondary cleavages and associated folds and lineations, started forming ca. 151 Ma in the Bear Mountains fault zone and then ca. 145 Ma, began moving away from the fault zone, forming diachronously over an ∼30-m.y. period. The last documented ductile structure formed ca. 123 Ma, although some secondary structures may be younger. Metamorphism of these rocks is generally upper greenschist facies, although higher-grade belts (one bearing staurolite, andalusite, and sillimanite) are present. Strain was preferentially partitioned into one of these belts of higher metamorphic grade (and sporadically elsewhere). The structural history here is much more complex, and at least one and locally two complete transpositions of the original cleavage have occurred. In these zones of complex deformation, it is in most cases possible only to identify a composite foliation consisting of new continuous cleavage and relicts of earlier phases, all lying mutually parallel. Timing constraints indicate that the pre-ductile structures may correspond to a very late stage of the Nevadan orogeny (that is, 155 ± 3 Ma), but the ductile structures postdate that orogeny (as defined) by as much as about 25-30 m.y. Models which relate the ductile structures in the central Foothills terrane to Nevadan plate-tectonic events are untenable. In addition, recent work indicates that Late Cretaceous ductile deformation in the central and southern Sierra Nevada may be relatively widespread, indicating that tectonic models for the Sierra Nevada need to be reassessed.
Stimulus control of responding by response-reinforcer temporal contiguity☆

Abstract The stimulus properties of brief disruptions in response-reinforcer temporal contiguity were investigated using a discrete trial conditional discrimination procedure. Key pecking (nondelay) or key pecking followed by a brief interval of nonpecking (delay) in the sample component produced a stimulus change (choice component). Pecks in the choice component to one of two alternatives resulted in food or blackout, conditional upon which response requirement was met in producing the choice component. A baseline condition, in which key pecking always produced the choice component and correct choices were arranged randomly, alternated with experimental conditions that included nondelay and delay values of either 0.2, 0.5, or 1.0 sec between the last key peck and the initiation of the choice component. All subjects accurately discriminated brief temporal delays between a response and stimulus change, with choice accuracy increasing for three of four subjects as the temporal disruption in contiguity increase. Implications of the research for the study of delayed reinforcement, response-independent reinforcement, and the discrimination of causality are discussed.
Hypoxia regulates the expression of the adrenomedullin and HIF-1 genes in cultured HL-1 cardiomyocytes.

Adrenomedullin (AM) is a hypotensive protein expressed in a variety of cells and tissues. We observed previously that the expression of the adrenomedullin gene increases substantially in the developing rat heart and in cultured adult rat ventricular cardiac myocytes in response to hypoxia as a function of time. An adrenomedullin promoter-luciferase reporter construct was used to show that this increase in adrenomedullin mRNA resulted from increased transcription in response to hypoxia. We report here additional evidence documenting that this hypoxia-induced transcription of the adrenomedullin gene is regulated by the hypoxia-inducible factor-1 (HIF-1) transcription factor. We used Northern blot analysis to show an increase in the levels of AM and HIF-1alpha mRNA but not HIF-1beta mRNA in the HL-1 cardiac myocyte cell line in response to hypoxia. Furthermore, Western blot analysis revealed that the levels of both HIF-1alpha and HIF-1beta protein increased under hypoxic conditions. Data from electrophoretic mobility shift assays indicate that the heterodimeric HIF-1 complex binds to the HIF-1-responsive elements. Combined data from these studies demonstrate that the AM gene is regulated by hypoxia-responsive elements localized in the AM promoter region.
The Study of Mentoring in the Learning Environment (SMILE): A Randomized Evaluation of the Effectiveness of School-based Mentoring

The effect of providing youth school-based mentoring (SBM), in addition to other school-based support services, was examined with a sample of 516 predominately Latino students across 19 schools. Participants in a multi-component, school-based intervention program run by a youth development agency were randomly assigned to one of two conditions: (1) supportive services alone or (2) supportive services plus SBM. Compared to community-based mentoring, the duration of the SBM was brief (averaging eight meetings), partly because the agency experienced barriers to retaining mentors. Intent-to-treat (ITT) main effects of SBM were tested using hierarchical linear modeling (HLM) and revealed small, positive main effects of mentoring on self-reported connectedness to peers, self-esteem (global and present-oriented), and social support from friends, but not on several other measures, including grades and social skills. Three-way cross-level interactions of sex and school level (elementary, middle, and high school) revealed that elementary school boys and high school girls benefited the most from mentoring. Among elementary school boys, those in the mentoring condition reported higher social skills (empathy and cooperation), hopefulness, and connectedness both to school and to culturally different peers. Among high school girls, those mentored reported greater connectedness to culturally different peers, self-esteem, and support from friends. Findings suggest no or iatrogenic effects of mentoring for older boys and younger girls. Therefore, practitioners coordinating multi-component programs that include SBM would be wise to provide mentors to the youth most likely to benefit from SBM and bolster program practices that help to support and retain mentors.
Is early joint attention associated with school-age pragmatic language?:

In order to evaluate evidence for the social–cognitive theory of joint attention, we examined relations between initiation of and response to joint attention at 12 and 18 months of age and pragmatic and structural language approximately 6 years later among children with and without autism spectrum disorder. Initiation of joint attention at 18 months was associated with structural, but not pragmatic, language for children with and without autism spectrum disorder. School-age children with autism exhibited difficulties with structural and pragmatic language relative to non-autistic siblings of children with autism and low-risk controls. No evidence of the broader autism phenotype was observed. These findings do not support the social–cognitive theory of joint attention.
Combining tree-structured vector quantization with classification and regression trees

Tree-structured vector quantizers for lossy data compression can be designed by combining clustering techniques with tree-structured methods for classification and regression as are developed in the statistics literature. Compression, on the one hand, and classification or regression, on the other, have differed primarily in the measures of quality and complexity used in the optimization algorithms. Given the similarity of the methods it is natural to consider combinations incorporating both squared error and Bayes risk into the design algorithms in order to simultaneously compress and classify local features accurately. We consider recent results of this type and compare them with other methods including independent design of classifier and compressor and Kohonen's (1989) "likelihood vector quantization"(LVQ). >
Laplacian Equivalents to Subsonic Potential Flows

This paper presents a mapping technique for the solution of Laplacian equivalents to steady subsonic potential flows in the plane. The method employs a coordinate transformation to map a given closed profile and domain in a compressible flow to a related closed profile and domain in a Laplacian flow, with differences in the geometries stemming only from compressibility effects. Unlike certain past methods, the mapping is valid for nonlinear flows with arbitrary density–velocity relations. The theory is implemented in an iterative numerical method in which the Laplacian flow is solved with a boundary element technique, and the compressible flow is then found from a finite difference solution to the mapping. Validation is provided by comparing the resulting subsonic flow solutions to knownresultsintheliteratureforbothacircularcylinderandaNACA0012profile.Themethodisexactinthesense that the inverse mapping of the equivalent Laplacian field recovers the subsonic full-potential solution over the originalprofile,uptonumericalaccuracy.Becauseincompressiblepotential flowsareLaplacian,themappingyields insights into the phenomenon of compressibility itself in the subsonic setting, and it may have utility in certain aerodynamic test applications.
The United Nations Global Compact: An Institutionalist Perspective

The United Nations Global Compact (UNGC) has generated a lively debate among academics, activists, and policy practitioners. Given the scope and ambition of this program, and the prestige of the United Nations associated with it, its supporters believe it will fundamentally reshape how businesses practice corporate social responsibility (CSR). Its critics view it as a flawed program because it does not impose verifiable obligations and does not compel its participants to adhere to their program obligations. We present an approach to study CSR programs grounded in rational-choice institutionalist theory, building on previous work viewing CSR programs as clubs which can produce reputational benefits for members as well as positive societal externalities, provided that they incorporate institutional mechanisms to prevent member shirking. This perspective puts the focus squarely on the institutional rules of the UNGC and their impacts on member behavior. While we conclude that the UNGC has not yet demonstrated a capacity to generate across-the-board improvements in CSR performance beyond what member firms would have done otherwise, we are hopeful that its sponsors and leaders can undertake worthwhile changes in program design to align member incentives with program objectives.
Mapping dooley graphs and commitment causality to the /spl pi/-calculus

Commitments among agents can be used to model business processes in a manner that preserves the autonomy and heterogeneity of the interacting parties. Dooley graphs are widely used in conversation-based multiagent system design. Commitments and their causal relationships can be inferred from Dooley graphs to flexibly model business processes. We present a theoretical foundation for Dooley graphs, commitments, and causality in terms of the π-calculus, a process algebra for specifying concurrent systems, which has found application in business process modeling. This paper expresses the key elements of Dooley graphs (roles, characters, conversations) and of our approach (commitments and causal diagrams) using the π-calculus. Further, we accommodate a new variety of primitives for exception handling termed reentrant connectors. The π-calculus enables us to derive useful properties from a given model and to validate its correctness. We show how these properties assist in building an entire business process model in which agents interact flexibly.
Complications of tympanostomy tubes in an inner city clinic population

Abstract While both prophylactic antibiotics and tympanostomy tube insertion have a role in the treatment of recurrent acute otitis media (AOM) and otitis media with effusion (OME) in children previous work has shown that patients in our urban clinic are not compliant with prophylactic antibiotics. Concerned about the potential for decreased compliance in a non-compliant population, we performed a retrospective review to assess the incidence of complications from the insertion of tympanostomy tubes in the same pediatric clinic population. A total of 391 tubes were placed in 165 patients. Follow-up ranged from 0–49.4 months with a mean of 21.3 months. Three ears (1.14%) had persistent perforations. Tympanosclerosis was found in 30 ears (11.1%). No ear showed a chronic retraction or cholesteatoma. Six ears (1.70%) developed postoperative otorrhea. Thirty-five patients had at least one episode of otorrhea outside of the perioperative period, and a total of 60 episodes (19.6% of ears) occurred during the study period. The mean pure tone average prior to tube placement was 25.0 dB, with tubes in place was 2.44 dB and after the last set of tubes had extruded was 6.97 dB. Our study shows that the incidence of complications of tympanostomy tubes was minimal in our inner city clinic population.
A Kaposi's Sarcoma-Associated Herpesvirus-Encoded Ortholog of MicroRNA miR-155 Induces Human Splenic B-Cell Expansion in NOD/LtSz-scid IL2Rγnull Mice

MicroRNAs (miRNAs) are small noncoding RNA molecules that function as posttranscriptional regulators of gene expression. Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), a B-cell-tropic virus associated with KS and B-cell lymphomas, encodes 12 miRNA genes that are highly expressed in these tumor cells. One viral miRNA, miR-K12-11, shares 100% seed sequence homology with hsa-miR-155, an oncogenic human miRNA that functions as a key regulator of hematopoiesis and B-cell differentiation. So far, in vitro studies have shown that both miRNAs can regulate a common set of cellular target genes, suggesting that miR-K12-11 may mimic miR-155 function. To comparatively study miR-K12-11 and miR-155 function in vivo, we used a foamy virus vector to express the miRNAs in human hematopoietic progenitors and performed immune reconstitutions in NOD/LtSz-scid IL2Rγ(null) mice. We found that ectopic expression of miR-K12-11 or miR-155 leads to a significant expansion of the CD19(+) B-cell population in the spleen. Subsequent quantitative PCR analyses of these splenic B cells revealed that C/EBPβ, a transcriptional regulator of interleukin-6 that is linked to B-cell lymphoproliferative disorders, is downregulated when either miR-K12-11 or miR-155 is ectopically expressed. In addition, inhibition of miR-K12-11 function using antagomirs in KSHV-infected human primary effusion lymphoma B cells resulted in derepression of C/EBPβ transcript levels. This in vivo study validates miR-K12-11 as a functional ortholog of miR-155 in the context of hematopoiesis and suggests a novel mechanism by which KSHV miR-K12-11 induces splenic B-cell expansion and potentially KSHV-associated lymphomagenesis by targeting C/EBPβ.
Acetic Acid, 2‐Azido‐, Methyl Ester; Acetic Acid, 2‐Azido‐, Ethyl Ester; Acetic Acid, 2‐Azido‐, 1,1‐Dimethylethyl Ester

(Acetic acid, 2-azido-methyl ester) [1816-92-8] C3H5N3O2 (MW 115.09) InChI = 1S/C3H5N3O2/c1-8-3(7)2-5-6-4/h2H2,1H3 InChIKey = RXYCUKSOYJWGPE-UHFFFAOYSA-N (Acetic acid, 2-azido-ethyl ester) [637-81-0] C4H7N3O2 (MW 129.12) InChI = 1S/C4H7N3O2/c1-2-9-4(8)3-6-7-5/h2-3H2,1H3 InChIKey = HVJJYOAPXBPQQV-UHFFFAOYSA-N (Acetic acid, 2-azido-1,1dimethylethyl ester) [6367-36-8] C6H11N3O2 (MW 157.17) InChI = 1S/C6H11N3O2/c1-6(2,3)11-5(10)4-8-9-7/h4H2,1-3H3 InChIKey = OUEOSPDVAWGMKX-UHFFFAOYSA-N (reagents are useful precursors to N-heterocycles) Physical Data: [1816-92-8] bp 60 °C (10 Torr);1 [637-81-0] bp 72–73 °C (20 Torr)2; [6367-36-8] bp 70 °C (0.9 Torr).3 Solubility: alkyl 2-azidoacetates are soluble in most organic solvents. Purification: Distillation3. Handling, Storage, and Precautions: store at or below 20 °C.3, 4
Implantable Cardioverter-Defibrillator Shocks: A Double-Edged Sword?⁎

In this issue of the Journal , Daubert et al. ([1][1]) report on the details of inappropriate implantable cardioverter-defibrillator (ICD) shocks in the MADIT II (Multicenter Automatic Defibrillator Trial II). The MADIT II study ([2][2]) was a primary prevention ICD trial in which patients with
Cada Maestrillo Tiene Su Librillo

The popular Spanish saying “Every teacher has his own textbook,” is a recognition that each person has her own way of thinking and acting, every “teacher” has her own way of rationalizing, of seeing, doing, and explaining things. This could not be more true for educators today.
Studies of the effects of radical quenching and flame stretch on mesoscale combustion

The effect of radical quenching on the flame propagation and extinction limit in meso and microscale channels is investigated numerically using a three-step kinetic mechanism. The results showed that at low wall temperatures and large channel widths, the thermal quenching is a dominant mechanism for flame extinction. However, with the increase of the wall temperature and the reduction of the chain-branching temperature, radical quenching becomes an important or dominant mechanism in affecting flame speed, flame structure, and extinction limit. The results also show that the increase of flow velocity enhances the radical quenching effect. In addition, it is found that there are two different radical quenching regimes, the diffusion limited regime and the kinetic limited regime. It is shown that the decrease of radical Lewis number significantly reduces the flame speed and narrows the extinction limit. Moreover, the results also demonstrate that at high flow velocities, the radical quenching in microscale combustion can lead to a radical quenching induced extinction limit.
Analysis on epidemic situation of influenza viruses and dominant strain switchover in Taizhou in 2009

Objective:To provide the information of the flu epidemic situation,we analyze epidemiology characteristic and dominant strain switchover of influenza viruses in TaiZhou in 2009.Methods: The speciments of nasal swabs from flu surveillance and epidemic were identified type and sub-type with real-time RT-PCR method.Results: A total of 633 nucleic acid of influenza virus was positive among 1282 samples.The positive rate was 49.38%.Among them,new subtype of H1N1 was 48.18%,A3 subtype was 39.18%,B type was 9.60%,A1 subtype was 3.0%.Conclution: There were four epidemic types of influenza viruses-H1N1 new subtype,A1 subtype,A3 subtype and B type in TaiZhou.They occurred switchover of dominant strain in different season.The dominant strain was B type from Mar.to June,while from July to September was A3 subtype,the epidemic strain was new subtype of H1N1 from October to December.At the same time influenza epidemic was caused by new subtype of H1N1.
Fetal loss after early detection of heart motion in infertility patients. Prognostic factors.

OBJECTIVE: To evaluate the incidence and prognosticators of spontaneous abortion (<20 weeks' gestation) in an infertile population after early documentation of fetal cardiac activity. STUDY DESIGN: Retrospective chart review. We examined the incidence of spontaneous abortion in 231 clinical pregnancies with 259 fetuses documented to be viable by transvaginal sonography 28-38 days after ovulation. The population was an unselected group of infertility patients with no history of recurrent pregnancy loss. Maternal age and presence of multiple gestations were analyzed as separate variables by X 2 testing. RESULTS: The incidence of spontaneous abortion among all fetuses was 9.6% (95% confidence interval [CI], 6.1-13.2%) and among singleton gestations was 7.7% (95% CI, 4.0-11.3%). Women with multiple gestations were more likely to suffer spontaneous fetal loss as compared to women with singleton gestations (18 vs. 7.6%, P<.05). In addition, women aged 35 and above with singleton pregnancies showed a significantly increased rate of fetal loss (13.4 vs. 4.9%, P <.05) when compared with younger women. CONCLUSION: Women ≥35 years old and those with multiple gestations were significantly more likely to suffer late first- or early second-trimester fetal loss even after detection of fetal cardiac activity. These patients should be counseled differently than younger women with singleton pregnancies, and increased monitoring may be indicated.
Indigocarmine as a Quantitative Indicator of Urothelial Integrity

AbstractThere is increasing evidence that the urothelium of the bladder mucosa prevents the penetration of solutes from the urine into the bladder wall. In the current study, in vivo treatments of rabbit urinary bladder with DMSO, acetone and overdistension resulted in damage to the physical integrity of the bladder mucosa as quantitated by the penetration of the dye indigocarmine (1% in saline) into submucosal tissues. Penetration of the dye can be quantitated, because the dye can be extracted from the tissue and measured spectrophotometrically. Indigocarmine does not penetrate normal, control, bladder mucosae. Bladders treated with gentle 20, 30 and 50% acetone washes for one minute permit dye penetration which is proportional to the acetone concentration utilized. Intravesical 50% DMSO (“RIMSO 50”) administration permits modest dye penetration. Distension by slow filling with saline to volumes 90% of capacity and greater causes a marked increase in dye penetration which is proportional to the magnitude...
Fatty acid abnormalities in hemodialysis patients: Effect of L-carnitine administration

Serum fatty acid profiles were determined using gas chromatography/mass spectrometry in three groups of subjects. Compared to normal controls, eight patients on maintenance hemodialysis had significantly lower proportions of linoleic (28.15 +/- 1.3 vs. 26.5 +/- 1.4%, P less than 0.003), linolenic (0.49 +/- 0.2 vs. 0.21 +/- 0.2%, P less than 0.04) and arachidonic acids (8.42 +/- 0.9 vs. 6.0 +/- 1.5%, P less than 0.0001). Dialysis patients also had higher proportions of oleic (8.9 +/- 1.8 vs. 15.3 +/- 3.5%, P less than 0.0001) and n-9 eicosatrienoic acids (0.26 +/- 0.2 vs. 0.54 +/- 0.3%, P less than 0.04). Ratios between oleic and arachidonic acid and between eicosatrienoic and arachidonic acids were also significantly higher in the dialysis group. In a separate group of either chronic dialysis patients, L-carnitine was given intravenously for a period of 6 to 18 months. In this group linoleic, linolenic and eicosatrienoic acids were not significantly different from normal controls. The ratio between eicosatrienoic and arachidonic acids was also similar to normal controls. However, arachidonic acid remained significantly lower and oleic acid significantly elevated in the carnitine group. The ratio of saturated to unsaturated fatty acid was higher in the untreated dialysis patients compared to L-carnitine treated patients (0.75 +/- 0.07 vs. 0.65 +/- 0.06, P less than 0.01). Significant abnormalities in distribution of fatty acids was seen in hemodialyzed patients. Thus preliminary data suggest significant depletion of essential fatty acids in dialysis patients which is partially corrected by treatment of patients with L-carnitine.
Ultramicro-Analysis of Tubular Fluid by Continuous-Flow Methodology

The measurement of net transepithelial fluxes in isolated perfused tubule experiments requires highly sensitive analytical methods, capable of precise determination of solute concentrations in 1–30 nanoliter samples of collected fluid. The continuous-flow approach to ultramicro-analysis of small aqueous samples, developed by Vurek in the early 1980s, has provided the sensitivity, precision, and speed necessary to dramatically enhance the efficiency of transepithelial flux measurements in isolated perfused tubules. The instruments used, a continuous-flow colorimeter and a continuous-flow fluorometer, are extremely versatile, allowing measurement of any of the major osmotically-active components of either plasma or urine in nanoliter volume samples. Specifically, these two instruments have been used to measure chloride, bicarbonate, sodium, potassium, ammonium, urea, creatinine, glucose, raffinose, lactate, calcium, magnesium, phosphate, and acetaminophen concentrations in 1–30 nanoliter samples with a coefficient of variation in the range 2%–4%. This paper reviews the design and application of these continuous-flow instruments.
Finally, A True Elements Test: Mathis v. U.S. and the Categorical Approach

The fate of defendants facing lengthy federal sentence enhancements often turns on what the U.S. Supreme Court calls the categorical approach. The approach controls whether a federal defendant might face an additional decade or longer in prison based solely on having prior convictions of a certain type. At a time when many question the wisdom of the War on Crime started in the 1980s, the Court has taken great care to delimit the circumstances in which a federal sentencing judge can lengthen sentences based on recidivism. The categorical approach also governs most immigration cases involving deportation for a crime. As Congress has cut back deportation defenses for lawful permanent residents with criminal records, the Court has demanded that convictions used for deportation strictly correspond to a federal removal ground. In both Descamps v. U.S. and Mathis v. U.S., recent Armed Career Criminal Act opinions authored by Justice Kagan, the Supreme Court interpreted the categorical approach as requiring a true elements test, declaring that at least two decades of the Court’s precedent required this result. Yet, Justice Breyer and Justice Ginsburg, two justices who had been in the majority in Descamps, dissented in Mathis. This Essay analyzes the trajectory of the Court’s categorical approach decisions, using the Mathis dissent authored by Justice Breyer, and joined by Justice Ginsburg, to explain an ambiguity in the Court’s jurisprudence that Descamps and Mathis have now settled. While Justice Kagan’s penchant for hyperbole oversimplifies the relationship between the Court’s early and late decisions regarding the categorical approach, the holdings of Descamps and Mathis are not only correct. They are likely constitutionally mandated.
Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

Background —Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic (PD) profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. Methods —In this prospective, randomized, double-blind, double-dummy, cross-over PD study, aspirin-treated DM patients (n=50) with coronary artery disease (CAD) were randomized to receive prasugrel [60mg loading dose (LD)/10mg maintenance dose (MD) qd] or ticagrelor (180mg LD/90mg MD bid) for 1 week. PD assessments were conducted using 4 different assays, including VerifyNow P2Y12, VASP, light transmittance aggregometry and Multiplate, which allowed to explore ADP- and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor activating peptide-induced) platelet signaling pathways. The acute (baseline, 30 min and 2 h post-LD) and maintenance (1-week) effects of therapy were assessed. The primary end-point of the study was the comparison of P2Y12 reaction units (PRU) determined by VerifyNow P2Y12 at 1-week between prasugrel and ticagrelor. Results —ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and MD. PRU defined by VerifyNow were similar between prasugrel and ticagrelor at 30 min and 2 h post-LD. At 1-week PRU was significantly lower with ticagrelor compared with prasugrel (52 [32-72] vs 83 [63-103]; LSM difference: -31; 95% CI: -57 to -4; p=0.022; primary endpoint). PD assessments measured by VASP, light transmittance aggregometry and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1-week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. Conclusions —In DM patients with CAD, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity compared to prasugrel in the acute and chronic phases of treatment, while the inhibition of measures of non-ADP-induced platelet reactivity were not significantly different between the two agents Clinical Trial Registration —URL: http://www.clinicaltrials.gov Unique identifier: [NCT01852214][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01852214&atom=%2Fcirculationaha%2Fearly%2F2016%2F08%2F24%2FCIRCULATIONAHA.116.023402.atom
Brigitte L. Bradley,R. M. Rilkes Neue Gedichte: Ihr Zyklisches Gefüge: Bern und München: Francke, 1967. Pp. 194.

(1969). Brigitte L. Bradley, R. M. Rilkes Neue Gedichte: Ihr Zyklisches Gefuge. The Germanic Review: Literature, Culture, Theory: Vol. 44, No. 1, pp. 64-65.
Insulin Autoimmune Syndrome: a rare cause of postprandial hypoglycemia

A 65-year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels. She did not have any evidence for the use of oral antidiabetic medications, insulin, herbal substances, performing strenuous exercise or history of bariatric surgery. Fingerstick blood glucose readings revealed blood sugar of 35 mg/dL and 48 mg/dL, when she had these symptoms. Her medical history was significant for morbid obesity, hypothyroidism and gastro esophageal reflux disease. Her home medications included levothyroxine, propranolol and omeprazole. A blood sample obtained during the symptoms revealed the following: fingerstick blood sugar 38 mg/dL, venous blood glucose 60 mg/dL (normal (n): 70–99 mg/dL), serum insulin 202 IU/mL (n: 45.4 U/mL (n: <0.4). The result obtained while screening for serum sulfonylurea and meglitinides was negative. The repeated episodes of postprandial hypoglycemia associated with significantly elevated anti-insulin antibodies led to a diagnosis of insulin antibody syndrome (IAS). Significant improvement of hypoglycemic symptoms and lower anti-insulin antibody levels (33 U/mL) was noted on nutritional management during the following 6 months. Based on a report of pantoprazole-related IAS cases, her omeprazole was switched to a H2 receptor blocker. She reported only two episodes of hypoglycemia, and anti-insulin antibody levels were significantly lower at 10 U/mL after the following 12-month follow-up. Learning points: Initial assessment of the Whipple criteria is critical to establish the clinical diagnosis of hypoglycemia accurately. Blood sugar monitoring with fingerstick blood glucose method can provide important information during hypoglycemia workup. Autoimmune hypoglycemia is a rare cause of hypoglycemia, which can be diagnosed on high index of clinical suspicion and systematic evaluation. Background Insulin autoimmune syndrome (IAS) – a rare cause of autoimmune hypoglycemia – was first described in a study by Hirata et al. in Japan in 1970 (1). It is characterized by spontaneous hypoglycemia, elevated insulin levels and elevated anti-insulin antibody levels. Typically, it is known to occur in patients exposed to insulin analogues (1). Other medications such as alpha lipoic acid (2) and sulfa-containing drugs such as procainamide, methimazole and hydralazine have also been found to be associated with IAS (3). We present a rare case of IAS in a patient with morbid obesity and prediabetes and using omeprazole.
Closed form and geometric algorithms for real-time control of an avatar

In a virtual environment with multiple participants, it is necessary that the user's actions be replicated by synthetic human forms. Whole-body digitizers would be the most realistic solution for capturing the individual participant's human form, however the best of the digitizers available are not interactive and are therefore not suitable for real-time interaction. Usually, a limited number of sensors are used as constraints on the synthetic human form. Inverse kinematics algorithms are applied to satisfy these sensor constraints. These algorithms result in slower interaction because of their iterative nature, especially when there are a large number of participants. To support real-time interaction in a virtual environment, there is a need to generate closed-form solutions and fast searching algorithms. In this paper, a new closed-form solution for the arms (and legs) is developed using two magnetic sensors. In developing this solution, we use the biomechanical relationship between the lower arm and the upper arm to provide an analytical, non-iterative solution. We have also outlined a solution for the whole human body by using up to ten magnetic sensors to break the human skeleton into smaller kinematic chains. In developing our algorithms, we use the knowledge of natural body postures to generate faster solutions for real-time interaction.
Age-related deficits in auditory temporal processing: unique contributions of neural dyssynchrony and slowed neuronal processing

This study was guided by the hypothesis that the aging central nervous system progressively loses its ability to process rapid acoustic changes that are important for speech recognition. Specifically, we hypothesized that age-related deficits in neural synchrony and neuronal oscillatory activity occur independently in older adults and disrupt auditory temporal processing. Neural synchrony is largely dependent on phase locking within the central auditory pathway, beginning at the auditory nerve. In contrast, the resonance characteristics of oscillatory activity are dependent on the integrity and structure of long range cortical connections. We tested our hypotheses by assessing age-related differences in electrophysiologic correlates of neural synchrony and peak oscillatory frequency in younger and older adults with normal hearing and determining their associations with a behavioral measure of gap detection. Phase-locking values were smaller (poorer neural synchrony) and peak alpha frequency was lower for older than younger adults and decreased as gap detection thresholds increased; variations in phase-locking values and peak alpha frequency uniquely predicted gap detection thresholds. These effects were driven, in large part, by associations in older adults. These results reveal dissociable neural mechanisms associated with distinct underlying pathology that may differentially be present in older adults and contribute to auditory processing declines.
The cost effectiveness of prenatal care.

This study uses hospital records for 7,000 births in McLennan County, Texas, during the period June 1987-July 1989 to examine the association between prenatal care and birth outcome and the implications for hospital costs of newborn infants. After controlling for a variety of maternal and birth factors, a significant relationship between prenatal care and birth outcome remained. Females who failed to receive prenatal care were almost three times as likely to have a low-birth-weight infant (weighing less than 2,500 grams) than females who did. Using an ordinary least squares (OLS) estimating equation (R2 = .24), the net expected hospital cost savings for females who received prenatal care was over $1,000.
Venous Thromboembolism (VTE) Prophylaxis in the Intensive Care Unit (ICU)

Critical illness puts patients at an increased risk for developing venous thromboembolism (VTE). Contraindications to pharmacologic VTE prophylaxis and/or organ dysfunction can be common in critical illness and can complicate the decision of VTE prophylaxis method or agent being used.
Tamoxifen facilitates translocation of ERα to the cytoplasm and enhances interaction between EGF receptor and ERα in MCF-7 breast cancer cells

419 Patients with hormone-dependent breast cancer experience tumor regression in response to tamoxifen (TAM) treatment. Unfortunately the disease inevitably relapses in 12-18 months. Up-regulation of growth factor signaling pathways is associated with development of tamoxifen resistance but the precise mechanisms are still unclear. To investigate mechanisms responsible for acquired tamoxifen resistance, we cultured MCF-7 breast cancer cells in medium containing TAM (10 -7 M) for up to 12 months. Six months after TAM treatment, growth of these cells was no longer inhibited by TAM. These cells were named tamoxifen resistant cells, TAM-R. While the basal levels of activated MAP kinase in TAM-R cells were similar to that in the control cells, TAM-R cells exhibited enhanced sensitivity to E2 and EGF stimulated activation of MAPK. Blockade of the EGFR/MAPK pathway caused more dramatic inhibition of growth of TAM-R cells than the control cells. It was interestingly found that an increased amount of ERα was co-immunoprecipitated with EGFR from TAM-R cells even though there was no increase in the levels of these receptors compared to the control cells. There was an increased immunoreactivity with ERα antibody in the cytoplasm and plasma membrane of TAM-R cells by fluorescent microscopy and Western analysis of cellular fractions. Interaction between growth factor receptors and ERα usually requires an adaptor protein. In TAM-R cells the amount of c-Src co-precipitated with EGFR or ERα was significantly increased. The interaction between EGFR and ERα could be reduced by the anti-estrogen fulvestrant. Notably the c-Src inhibitor PP2 caused redistribution of ERα back to the nucleus whereas the EGFR tyrosine kinase inhibitor AG1478 did not. Our results suggest that cytoplasmic translocation of ERα increases its interaction with EGFR which may result in enhanced activation of MAPK signaling pathway in TAM-R cells. Activation of the EGFR/MAPK pathway allows the cells to grow in the presence of TAM. Kinase active c-Src plays a critical role in retaining ERα in the cytoplasm and in serving as an adaptor of EGFR/ERα complex.
Numerical comparison of bubbling in a waste glass melter

Abstract Radioactive tank waste is scheduled for vitrification at the Waste Treatment and Immobilization Plant (WTP) being constructed at the Hanford Site. Testing of the pilot-scale DuraMelter 1200 at the Vitreous State Laboratory at the Catholic University of America has demonstrated that bubbling increases the melt rate of the batch material, and as a result, melter throughput. Computational fluid dynamics (CFD) models of this pilot-scale waste glass melter are being developed to improve our understanding of the processes that occur within the melter to aid in process optimization and troubleshooting of the WTP melters. Unfortunately, model validation is complicated by the difficulty of obtaining suitable experimental data for operational melters due to the inaccessibility for direct observation and measurements of the high-temperature, opaque fluid through the water-jacketed, refractory-lined steel vessel. This study focuses on assessing the fidelity of the CFD models to accurately predict the bubbling behavior. Because of the paucity of experimental data at the resolution required for CFD validation, a code comparison was used to evaluate two common approaches for simulating flows of two immiscible Newtonian fluids on numerical grids and resolving multiphase interfaces. Here, the volume of fluid and level set methods are used to resolve the dynamically evolving interfaces between the molten glass and the air bubbles. To aid in the validation of the results of these codes, a comparison of the bubble behavior, growth, and frequency of bubble generation are presented and a grid convergence study is performed for the two approaches. The predictions from the two codes are within 6% for the average bubble radius of curvature within the bubble channels, within 2% for average terminal rise velocity of the bubbles, and within 4% for the area mean of the local maxima at the free surface. These parameters are of interest since they affect the convection within the melter and at the interface between the glass and batch layer. Ultimately, the results of this work can assist in confirming the predictive ability of waste glass melter models and provide a better understanding of the flow patterns within the WTP melters.
Magnetic Exchange in Oxides

In the previous chapter, quenching of cation orbital angular momentum by the anion charges and the origin of the energy stabilization by covalent bonding was introduced by elementary crystal field and molecular orbital theory. In magnetically dilute compounds, the isolated 3d n ions are influenced next by the weakened spin-orbit coupling perturbations and multiplet structures that determine the magnetoelastic properties to be examined in Chap. 5. These effects are initially local but can become cooperative when concentrations increase to levels where percolation can occur, e.g., a cooperative Jahn-Teller effect. However, because the spin alone is the agent of magnetic ordering in this series, the multiplet energies can be largely ignored in the discussion of spontaneous magnetism. Consequently, the next important effective field in a ligand lattice to be addressed is the magnetic exchange field that arises from the transfer integral linking magnetic cations. Magnetic exchange, therefore, is the term used to describe the energy stabilization gained from spin ordering (parallel or antiparallel) of atoms or ions covalently coupled in an ionic crystal lattice.