cssi/SciSciGPT-SciSciNet huggingface dataset:
The scabrous protein can act as an extracellular antagonist of notch signaling in the Drosophila wing.

Abstract Notch (N) is a receptor for signals that inhibit neural precursor specification [1–6]. As N and its ligand Delta (Dl) are expressed homogeneously, other molecules may be differentially expressed or active to permit neural precursor cells to arise intermingled with non-neural cells [7,8]. During Drosophila wing development, the glycosyltransferase encoded by the gene fringe ( fng ) promotes N signaling in response to Dl , but inhibits N signaling in response to Serrate ( Ser ), which encodes a ligand that is structurally similar to Dl. Dorsal expression of Fng protein localizes N signaling to the dorsoventral (DV) wing margin [9–11]. The secreted protein Scabrous (Sca) is a candidate for modulation of N in neural cells. Mutations at the scabrous ( sca ) locus alter the locations where precursor cells form in the peripheral nervous system [12,13]. Unlike fringe , sca mutations act cell non-autonomously [12]. Here, we report that targeted misexpression of Sca during wing development inhibited N signaling, blocking expression of all N target genes. Sca reduced N activation in response to Dl more than in response to Ser. Ligand-independent signaling by overexpression of N protein, or by expression of activated truncated N molecules, was not inhibited by Sca. Our results indicate that Sca can act on N to reduce its availability for paracrine and autocrine interactions with Dl and Ser, and can act as an antagonist of N signaling.
Psychologists in academic health centers: traditions and innovations in education, science, and practice.

Psychologists, interns, and postdoctoral fellows convened in Minneapolis May 3–5, 2007 for the 3rd National Conference of the Association of Psychologists in Academic Health Centers (APAHC): “Psychologists in Academic Health Centers: Traditions and Innovations in Education, Science, and Practice.” This paper reviews the development and organization of the conference, which built upon the two previous conferences of the Association of Medical School Psychologists. The articles in this special issue are based on a selected number of the 32 conference presentations, covering a range of timely topics that reflect the conference theme. Participants’ positive perceptions and satisfaction with the conference reveal the value of such conferences focused on the activities, interests, opportunities, and challenges of psychologists who work in academic health centers (AHCs) and teaching hospitals. Moreover, the content and success of the conference underscores the importance of APAHC as an organization serving the needs and promoting the interests of psychologists affiliated with AHCs.
Management of bleeding peptic ulcer: Current status of intravenous proton pump inhibitors

Over 80% of ulcer bleeding stops spontaneously, but associated mortality and morbidity remain high. Occurrence of re-bleeding increases mortality 10-fold. Endoscopic findings in those that have bled predict the risk of recurrent bleeding. Patients whose ulcers show a ‘flat dot' or clean base (Forrest Class 3) rarely rebleed or need hospitalization. However, actively bleeding ulcers or those with evidence of recent hemorrhage (Forrest Classes 1 and 2) are likely to re-bleed and may need intensive care. Meta-analyses indicate that endoscopic hemostasis has reduced re-bleeding and surgical intervention by over 60% and mortality by 45%. Beyond these reductions, data indicate that (unlike H 2 -receptor antagonists use, largely devoid of benefits in this area) continuous intravenous infusions of high doses of proton pump inhibitors reduce rebleeding, re-endoscopy, blood transfusion and surgical intervention, but have little effect (beyond endoscopic therapy) on associated mortality, much of it due to conditions other than rebleeding.
Power of statistical tests.

When planning a research study, the issue of the necessary sample size is one that is extremely important. In two previous accidental notes, sample size considerations have been discussed – in the ...
Kodak, Fight and the Definition of Civil Rights in Rochester, New York 1966–1967

(1997). Kodak, Fight and the Definition of Civil Rights in Rochester, New York 1966–1967. The Historian: Vol. 60, No. 1, pp. 59-75.
An in situ AFM Study of the Evolution of Surface Roughness for Zinc Electrodeposition within an Imidazolium Based Ionic Liquid Electrolyte

Abstract Zinc deposition within 1-butyl-3-methyl-imidazolium trifluoromethanesulfonate (BMIm OTf) with 0.34 mol kg−1 trifluoromethanesulfonate (Zn(OTf)2) was analyzed by in situ atomic force microscopy (AFM). We describe a compact, textured morphology that has not been reported before. From the height difference correlation of the zinc electrodeposition AFM data, we obtained three parameters to describe the evolution of the zinc surface during electrodeposition: the Hurst exponent, the correlation length, and the saturated surface roughness. It was found that the roughness exponent of the zinc surface remained relatively constant during growth. In addition, the correlation length of the zinc deposition surface increased with continued electrodeposition. The saturated surface roughness, however, appeared to reach a constant value under certain deposition parameters within the ionic liquid electrolyte which is in contrast to scaling behavior typically observed for electrodeposition processes.
CTLA-4 and PD-1 Pathway Blockade: Combinations in the Clinic

Checkpoint blocking antibodies targeting regulatory molecules on T cells such as CTLA-4 and PD-1 have reinvigorated the field of cancer immunotherapy. These agents have demonstrated clinical activity across a variety of tumor types. Now that safety and clinical activity has been demonstrated in the monotherapy setting, the field is moving in the direction of testing novel combinations.
Searching for Components of Conceptual Ecology That Mediate Development of Epistemological Beliefs in Science

This paper articulates the importance of epistemological beliefs (EBs) and draws a parallel between EBs literature in educational psychology and nature of science (NOS) literature in science education. The paper stresses that EBs in science and NOS ideas have common ground and they can be best improved through explicit-reflective instruction informed by conceptual change theory. The paper concludes that future studies should explore the factors that mediate the development of EBs in science and NOS ideas rather than documenting the changes in students’ and teachers’ EBs in science and NOS ideas after explicit-reflective instruction through pre- and post assessments.
Replacing amino acids in translation: expanding chemical diversity with non-natural variants.

Abstract Here, we describe a strategy for synthesis of peptides with multiple unnatural amino acids (UAAs) using in vitro translation. Our method involves removing a natural amino acid and replacing it with an UAA variant in a reconstituted translation system. Whereas other systems require engineered components or chemical synthesis to charge UAAs onto tRNAs prior to translation, our strategy utilizes the wild-type machinery and charging occurs concomitant with translation. The design of the system allows for easy quantification of the UAA’s incorporation efficiency and fidelity.
Distributive Justice in the State of Nature: An Egalitarian View

This paper proposes a novel egalitarian answer to the question: what initial distribution of the world’s resources could possibly count as just? Like many writers in the natural rights tradition, I take for granted that distributive justice consists in conformity to pre-political principles that apply to property regimes. Against the background of that assumption, the paper distinguishes between broadly Lockean and broadly Grotian conceptions of distributive justice in the state of nature. After an extended critique of various versions of the Lockean approach, it argues for a particular, egalitarian version of the Grotian view. My position is based on what I call the common ownership formula, which says: each human being, as an equal co-owner of the world’s resources, may use those resources provided that the terms of their use are in conformity with principles that no co-owner could reasonably reject as the basis of an informed, unforced general agreement between all of the world’s co-owners who sought to find equitable principles of resource division. Using this principle, I suggest how an unequivocally egalitarian view of pre-political entitlement can be justified without recourse to any alleged duty to ameliorate the effects of brute bad luck on people’s lives.
Conducting K-12 outreach to evoke early interest in IT, science, and advanced technology

The Indiana University Pervasive Technology Institute has engaged for several years in K-12 Education, Outreach and Training (EOT) events related to technology in general and computing in particular. In each event we strive to positively influence children's perception of science and technology. We view K-12 EOT as a channel for technical professionals to engage young people in the pursuit of scientific and technical understanding. Our goal is for students to see these subjects as interesting, exciting and worth further pursuit. By providing opportunities for pre-college students to engage in science, technology, engineering and mathematics (STEM) activities first hand, we hope to influence their choices of careers and field-of-study later in life.In this paper we give an account of our experiences with providing EOT: we describe several of our workshops and events; we provide details regarding techniques that we found to be successful in working with both students and instructors; we discuss program costs and logistics; and we describe our plans for the future.
Fluttering of the Mitral Valve in Aortic Insufficiency

Thirty-five patients with clinical evidence of aortic insufficiency were studied by echocardiography. Eleven patients had characteristic diastolic fluttering of the mitral valve (30 to 40 Hz, maximal amplitude 4 mm). In five others the fluttering was classified as equivocal. In a control group of 500 echocardiograms in patients without evidence of aortic insufficiency, there were three examples of equivocal fluttering. Atrial fibrillation also produces diastolic fluttering but of slower frequency.
Choices of stimulation for low responders in IVF

Low responders present a significant challenge for IVF practitioners due to the lower chances of a pregnancy in relation to the usual high cost of treatment. The definition of low responders is not universally agreed upon and the literature is full of articles that have different populations of low responders, which makes comparisons of the different protocols almost impossible. This paper will review the different strategies and protocols that have been reported and discuss the advantages and disadvantages of each. It is of utmost importance to realize that, at the present time, there is no regimen of ovarian stimulation that can change a true low responder into a high responder. Minimal stimulation and natural cycle protocols for IVF appear to be reasonable choices in well-selected cases since they provide simplicity and cost–effectiveness.
Progesterone as a regulator of granulosa cell viability

Progesterone (P4) prevents numerous cells, including uterine, mammary and ovarian cells, from undergoing apoptosis. Interestingly, P4 prevents apoptosis of ovarian granulosa cells (GCs), which do not express the classic nuclear P4 receptor. This review presents data that support a non-genomic action of P4 in granulosa cells. These studies were conducted using both primary rat granulosa cells and rat spontaneously immortalized granulosa cells (SIGCs). Specifically, these studies reveal that (1) 3H-P4 specifically binds to SIGCs; (2) an antibody directed against the ligand binding domain of the nuclear P4 receptor (C-262) detects a 60kDa protein, which localizes to the plasma membrane and binds P4; and (3) treatment with C-262 blocks P4's ability to maintain granulosa cell viability. Additional studies demonstrate that a protein kinase G (PKG) activator, 8-br-cGMP, mimics and PKG antagonists, Rp-8-pcCPT-GMP and KT5823, attenuate P4's action. These studies support the concept that the 60kDa P4 binding protein functions as membrane receptor for P4 which activates a PKG-dependent mechanism to regulate granulosa cell survival.
INCIDENCE OF CORONARY ARTERY ANOMALIES IN PULMONARY ATRESIA WITH MAJOR AORTOPULMONARY COLLATERALS

Pulmonary atresia with Ventricular Septal Defect and Major Aortopulmonary Collaterals (PA/VSD/MAPCA's) is a complex form of congenital heart disease. Although it has been recognized that coronary artery anomalies are frequently associated with many other conotruncal defects, the incidence of
A statistically defined anthropomorphic software breast phantom

Purpose: Digital anthropomorphic breast phantoms have emerged in the past decade because of recent advances in 3D breast x-ray imaging techniques. Computer phantoms in the literature have incorporated power-law noise to represent glandular tissue and branching structures to represent linear components such as ducts. When power-law noise is added to those phantoms in one piece, the simulated fibroglandular tissue is distributed randomly throughout the breast, resulting in dense tissue placement that may not be observed in a real breast. The authors describe a method for enhancing an existing digital anthropomorphic breast phantom by adding binarized power-law noise to a limited area of the breast. Methods: Phantoms with (0.5 mm){sup 3} voxel size were generated using software developed by Bakic et al. Between 0% and 40% of adipose compartments in each phantom were replaced with binarized power-law noise ({beta} = 3.0) ranging from 0.1 to 0.6 volumetric glandular fraction. The phantoms were compressed to 7.5 cm thickness, then blurred using a 3 Multiplication-Sign 3 boxcar kernel and up-sampled to (0.1 mm){sup 3} voxel size using trilinear interpolation. Following interpolation, the phantoms were adjusted for volumetric glandular fraction using global thresholding. Monoenergetic phantom projections were created, including quantum noise and simulated detectormore » blur. Texture was quantified in the simulated projections using power-spectrum analysis to estimate the power-law exponent {beta} from 25.6 Multiplication-Sign 25.6 mm{sup 2} regions of interest. Results: Phantoms were generated with total volumetric glandular fraction ranging from 3% to 24%. Values for {beta} (averaged per projection view) were found to be between 2.67 and 3.73. Thus, the range of textures of the simulated breasts covers the textures observed in clinical images. Conclusions: Using these new techniques, digital anthropomorphic breast phantoms can be generated with a variety of glandular fractions and patterns. {beta} values for this new phantom are comparable with published values for breast tissue in x-ray projection modalities. The combination of conspicuous linear structures and binarized power-law noise added to a limited area of the phantom qualitatively improves its realism.« less
Analytical techniques for characterization of organic molecular assemblies in molecular electronics devices

The analytical techniques used for the physical characterization of organic molecular electronic-based devices are surveyed and discussed. These protocols include methods that are used to probe molecular assemblies such as single wavelength ellipsometry, water contact angle goniometry, cyclic voltammetry, infrared spectroscopy, and X-ray photoelectron spectroscopy, and methods used to measure charge transport properties of devices such as scanning tunneling microscopy, and inelastic electron tunneling spectroscopy. Examples from our laboratory and the literature are given for each of these analytical techniques.
Cleavage of S-(1,2-dichlorovinyl)-L-cysteine by an enzyme of bovine origin.

Abstract A C-S lyase which cleaves S-(1,2-dichlorovinyl)- l -cysteine (DCVC) was observed in bovine liver and kidney. This enzyme from bovine liver was purified about 75-fold. It has quite high substrate specificity for DCVC (the l -isomer only), the sulfoxide(s) prepared from DCVC also being cleaved, but among 29 other potential substrates, only S-sulfo- l -cysteine underwent reaction. The cleavage yields pyruvate, ammonia, and chloride in a 1:1:2 ratio, and another, unknown fragment. Through the use of three differently labeled specimens of radioactive DCVC, it was shown that (a) the C-S bond of the cysteine moiety of DCVC is cleaved, (b) a fragment containing carbon from the vinyl group and sulfur is formed, and (c) this fragment can combine with proteins and with glutathione to form derivatives of unknown structure. The lyase is rapidly inactivated by a product formed from DCVC. GSH retards this inactivation and decreases the extent to which sulfur and vinyl carbon combine with proteins of the enzyme concentrate.
Sex assessment using the proximal tibia

The proximal end of the human tibia is sexually dimorphic. Tibial condyles from 100 individuals in the Hamann-Todd Collection were measured. Regression equations retrodicted known sex with 86-95% accuracy. A test sample of 20 individuals also from the Hamann-Todd Collection was classified with 85-100% accuracy. A sample of 20 prehistoric individuals provisionally sexed by using crania and innominate bones was classified with 85-100% agreement. Thus, the proximal tibia may be useful in determining the sex of a skeleton.
Sedation for cardiac catheterization: A controlled study

In a double-blind study we compared the effectiveness of a meperidine-promethazine-chlorpromazine combination (drug A) and a fentanyl citrate-droperidol combination (drug B) as sedatives for cardiac catheterization and angiography. The doses for drug A were meperidine, 1.84 mg/kg; promethazine, 0.46 mg/kg; and chlorpromazine, 0.46 mg/kg; for drug B they were fentanyl citrate, 1.25μg/kg; and droperidol, 62.5μg/kg. Drug A or B was assigned at random to each of 94 patients aged 3 to 34 years admitted for cardiac catheterization and was given intramuscularly 30 minutes before catheterization. Each patient who required additional sedation was given intravenously (IV) one fourth of the original dose of the same medication used for initial sedation. If still further sedation was required, diazepam, 1 to 2 mg IV, was administered. The effectiveness of sedation or need for additional medication in the group who received drug A were not significantly different from those in the group who received drug B: supplemental sedation was required in 8 of 47 (17%) with drug A and 8 of 47 (17%) with drug B. No significant differences between the two groups were noted for the mean values of heart rate, respiratory rate, oxygen consumption, cardiac index, left ventricular end-diastolic pressure, arterial oxygen saturation, pH,Po 2, andPco 2 measured during catheterization. No side effects were observed in either group, and all patients had a steady, uneventful recovery. We conclude that the meperidine-promethazine-chlorpromazine and the fentanyl-droperidol combinations were equally effective for precatheterization sedation with the dose used.
Map Coloring and Calabi-Yau Vacua

An algorithm for coloring planar graphs is exploited to reveal a connection between Calabi-Yau manifolds and solutions of map coloring problems on a Riemann surface. This connection may shed light on the connection between superstring vacua and topological quantum field theories.
A numerical method for a model of population dynamics with spatial diffusion

Abstract We propose a procedure to approximate the solution of a degenerate parabolic equation describing the dynamics of a one-sex population with spatial diffusion. We use a finite difference method along the characteristic age-time direction combined with finite elements in the spatial variables. Error estimates are derived for this approximation.
An alternative binary model for SN1987A

A class of models for SN1987A is proposed in which the blue supergiant Sk -69 deg 202 is the progenitor and where the supernova evolution of this star is strongly influenced by the accretion of matter from a companion star which was initially the more massive star. Binary stellar evolution calculations show that a model of this type can naturally explain why the apparent progenitor was a blue supergiant rather than a red one. The system became unbound after the supernova event, and the presence of a normal or neutron-star companion will probably be revealed a few years after the explosion. A model of this type can explain all the major observational features of SN1987A and also provides plausible explanations for many of its anomalies.
Measurement and radioautographic localization of albumin in rat tissues after intravenous administration.

Radioautography and conventional counter methods have been used to determine the relative amount and localization of I131 albumin in a number of tissues at 3, 30, and 60 min. after intravenous injection. Certain tissues showed essentially no change in albumin content with time, others contained extravascular albumin which increased with time, and the liver and adrenal evidenced a decreasing level of albumin with time. The transcapillary passage of albumin and its accumulation in extravascular compartments are correlated with tissue structure.
Architectural reliability of split-protocol

HTTP request splitting is a novel concept where the TCP connection and data-transfer phases are dynamically split between servers without the use of a central dispatcher or load balancer. Splitting is entirely transparent to the client and provides security due to the inaccessibility and invisibility of the data servers. This study focuses reliability of Mini Web Server Clusters based on HTTP Request Splitting. Previous work has studied through performance and established a performance improvement range between 6% and 25 % and an improved data transmission time which was 84% better than conventional computing. We believe this higher performance results from inbuilt reliability in the architecture of split protocol. There are plenty of researches, and literatures focusing on component-based reliability. Especially in Software Engineering researches, they assumed that each component has a single Service. Thus, this paper highlights on an inbuilt reliability in a split-protocol due to the dual and interchangeable role of Connection Server (CS) and Data Server (DS). This novel approach introduces a more effective way of offering reliability in cluster computing and in general. To assess the reliability of the system, this paper proposed a simple mathematical model which can capture the reliability of the system. This model is also used to compare the reliability of the split system against dispatcher system. The results show that split system reliability is far better than dispatcher system reliability.
Does processing of emotional stimuli predict symptomatic improvement and diagnostic recovery from major depression

This study was designed to examine whether processing of emotional stimuli predicts both symptomatic improvement and recovery from depression. Participants diagnosed with Major Depressive Disorder (MDD) (N = 63) completed information-processing tasks to assess attention to and memory for sad, physically threatening, socially threatening, and happy stimuli. At a follow-up session an average of nine months later, participants were reassessed to determine diagnostic status and depression severity. None of the measure of attention or memory predicted diagnostic status at follow-up. Those depressed participants who remembered a higher proportion of positive words that they had endorsed as self-descriptive exhibited greater symptomatic improvement. After controlling for memory of positive self-referential words, attentional measures did not predict symptomatic change. These results are consistent with a growing literature highlighting the importance of emotionally relevant memory processes for understanding the course of major depression.
Speaking Giraffe Language

Linguistic violence is violence in the use of language. That would include what we say and how we say it, and its implications. Lying or other misleading language, slander, and malicious gossip could be viewed as linguistic violence. They often do violence to the social fabric, undermine trust, and cause harm in various ways. Shouting into someone's face (especially in situations in which this could predictably escalate into physical violence), name calling, and not allowing others a fair opportunity to be heard could also be regarded as linguistic violence. Some linguistic violence of this sort is obviously intentional, but much linguistic violence is merely habitual and may even seem innocuous. What follows will focus on forms of linguistic violence that are often not seen as such, and on alternatives to such linguistic violence.
The reaction γp → π+π−π+π−p at high energy and photon dissociation into four pions

Abstract The reaction γp → π+π−π+π−p has been studied using the SLAC 2-meter streamer chamber placed in an 18 GeV bremsstrahlung beam. We find evidence for a broad enhancement (ϱ′) in the 4π mass spectrum at a mass of 1620 MeV with a width of about 300 MeV. This state is produced peripherally with a cross section consistent with being energy independent. I-spin = 1 (C = −1) is deduced from the dominant ϱππ decay mode and J ≠ 0 from the observation of a polarization phenomenon. Assuming quantum numbers JP = 1−, s-channel helicity is conserved at the γ−ϱ′ vertex. Further support for the JP assignment is gathered when comparing our results to data from e+e− colliding-beam experiments.
SyMP: an efficient clustering approach to identify clusters of arbitrary shapes in large data sets

We propose a new clustering algorithm, called SyMP, which is based on synchronization of pulse-coupled oscillators. SyMP represents each data point by an Integrate-and-Fire oscillator and uses the relative similarity between the points to model the interaction between the oscillators. SyMP is robust to noise and outliers, determines the number of clusters in an unsupervised manner, identifies clusters of arbitrary shapes, and can handle very large data sets. The robustness of SyMP is an intrinsic property of the synchronization mechanism. To determine the optimum number of clusters, SyMP uses a dynamic resolution parameter. To identify clusters of various shapes, SyMP models each cluster by multiple Gaussian components. The number of components is automatically determined using a dynamic intra-cluster resolution parameter. Clusters with simple shapes would be modeled by few components while clusters with more complex shapes would require a larger number of components. The scalable version of SyMP uses an efficient incremental approach that requires a simple pass through the data set. The proposed clustering approach is empirically evaluated with several synthetic and real data sets, and its performance is compared with CURE.
Stress-Driven In Vivo Selection of a Functional Mini-Gene from a Randomized DNA Library Expressing Combinatorial Peptides in Escherichia coli

A plasmid-borne randomized mini-gene library expressing a population of combinatorial 20-mer peptides with no bias toward any biological function was used as an initial source of genetic variance during stress-driven evolution of Escherichia coli. The transformed bacteria were evolved under multiple rounds of selective pressure imposed by nearly lethal concentrations of NiCl(2), AgNO(3), or K(2)TeO(3). At the final stage, clones conferring resistance to NiCl(2) were found to carry identical functional mini-genes, which conferred significant nickel tolerance on the host cells. Expression of the mini-gene markedly improved growth parameters of the evolved clones at subinhibitory concentrations of NiCl(2) while being slightly detrimental in the absence of the stress. This substantial increase in resistance, as compared with control cultures adapted in the absence of the mini-gene, is shown to be largely due to coadaptation with changes elsewhere in the E. coli genome. Clones resistant to AgNO(3) and K(2)TeO(3) harbored plasmid variants with an inactive mini-gene and with a deleted mini-gene operon, respectively. In those cases, an exploration of the mini-gene sequence space apparently was fruitless, and the developed toxicity tolerance was likely to be exclusively associated with acquired adaptive mutations. Overall, the results demonstrate a very natural outcome in which the mini-genes were expected to be either successfully integrated into the bacterial genetic network or rejected depending on their effect on host fitness. This approach is immediately useful as a laboratory model to study the dynamics of bacterial adaptive evolution at the molecular level and is especially relevant as a rapid method to study cellular response to recently acquired genetic material.
Antidepressants, Psychotherapy or their Combination: Weighing Options for Depression Treatments

Psychotherapy and antidepressant medications are the two preeminent treatment choices for depression. This article puts each of these treatments into perspective by presenting an overview of what is currently known about their effectiveness either singly or in combination. Discussion of placebos, common factors among therapies, relapse rates, depression severity, patient treatment preferences and exaggerations in pharmaceutical advertising provide guidance for clinicians in deciding on the best course of treatment. Overall, research reveals the importance of psychosocial factors, no matter what the mode of treatment, and the need for fostering a collaborative bond between clinicians and their patients. We argue that empirical evidence points to making psychotherapy the initial treatment choice for most cases of depression.
Opening Mechanism of a Cyclic Nucleotide–gated Channel Based on Analysis of Single Channels Locked in Each Liganded State

Cyclic nucleotide–gated channels contain four subunits, each with a binding site for cGMP or cAMP in the cytoplasmic COOH-terminal domain. Previous studies of the kinetic mechanism of activation have been hampered by the complication that ligands are continuously binding and unbinding at each of these sites. Thus, even at the single channel level, it has been difficult to distinguish changes in behavior that arise from a channel with a fixed number of ligands bound from those that occur upon the binding and unbinding of ligands. For example, it is often assumed that complex behaviors like multiple conductance levels and bursting occur only as a consequence of changes in the number of bound ligands. We have overcome these ambiguities by covalently tethering one ligand at a time to single rod cyclic nucleotide–gated channels (Ruiz, ML., and J.W. Karpen. 1997. Nature. 389:389–392). We find that with a fixed number of ligands locked in place the channel freely moves between three conductance states and undergoes bursting behavior. Furthermore, a thorough kinetic analysis of channels locked in doubly, triply, and fully liganded states reveals more than one kinetically distinguishable state at each conductance level. Thus, even when the channel contains a fixed number of bound ligands, it can assume at least nine distinct states. Such complex behavior is inconsistent with simple concerted or sequential allosteric models. The data at each level of liganding can be successfully described by the same connected state model (with different rate constants), suggesting that the channel undergoes the same set of conformational changes regardless of the number of bound ligands. A general allosteric model, which postulates one conformational change per subunit in both the absence and presence of ligand, comes close to providing enough kinetically distinct states. We propose an extension of this model, in which more than one conformational change per subunit can occur during the process of channel activation.
Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

Vertebrate development requires communication among cells of the embryo in order to define the body axis, and the Wnt-signaling network plays a key role in axis formation as well as in a vast array of other cellular processes. One arm of the Wnt-signaling network, the non-canonical Wnt pathway, mediates intracellular calcium release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GTPase-activating proteins (GAPs), however, the possible role of RGS proteins in non-canonical Wnt signaling and development is not known. Here, we identify rgs3 as having an overlapping expression pattern with wnt5b in zebrafish and reveal that individual knockdown of either rgs3 or wnt5b gene function produces similar somite patterning defects. Additionally, we describe endogenous calcium release dynamics in developing zebrafish somites and determine that both rgs3 and wnt5b function are required for appropriate frequency and amplitude of calcium release activity. Using rescue of gene knockdown and in vivo calcium imaging assays, we demonstrate that the activity of Rgs3 requires its ability to interact with Gα subunits and function as a G protein GAP. Thus, Rgs3 function is necessary for appropriate frequency and amplitude of calcium release during somitogenesis and is downstream of Wnt5 activity. These results provide the first evidence for an essential developmental role of RGS proteins in modulating the duration of non-canonical Wnt signaling.
Salvage reconstruction of failed pollicization by distraction lengthening.

Hypoplasia of the thumb can present as an isolated deformity or as part of a systemic process such as thrombocytopenia-absent-radius syndrome, Holt–Oram syndrome, Fanconi’s anemia, and VACTERL syndrome (vertebral abnormality, anal atresia, cardiac abnormality, tracheoesophageal fistula, esophageal atresia, renal abnormality, lower extremity abnormalities). If the hypoplastic thumb is not functional, pollicization of the index finger is the treatment of choice for Blauth type IIIB, IV (floating thumb), and obviously if the thumb is absent (type V). Successful pollicization of the index finger requires meticulous surgical technique, but good long-term results have been reported as high as 81% [23]. Functional limitations have been reported by many studies [1, 2, 5–7, 10–12, 16, 21, 22], but other reports of complications, including failures, are scarce. Reported complications include iatrogenic neurovascular injury, web space contracture, malrotation, functional deficits (decreased pinch and grip strength, lack of opposition), and stiffness [4]. To our knowledge, there is limited literature concerning treatment for a failed pollicization. This could be due to reluctance of surgeons to report their complications and/or small patient numbers. This case report describes a child with left radial longitudinal deficiency and complete thumb aplasia that underwent pollicization of the index finger by another hand surgeon. Unfortunately, the pollicization failed either due to resorption of the proximal phalanx of the index finger (metacarpal of the new thumb) due to infection or ischemia or due to the surgeon inadvertently resecting the proximal phalanx of the index finger, mistaking it for the metacarpal. This resulted in a pollicized index finger that was too short and consequently had limited opposition and tip-to-tip pinch. The objective of this case report is to make the hand surgeons aware of this previously unreported complication of pollicization and describe a method of reconstruction to provide a functional thumb. Informed consent and permission for publication was given by the child and parents.
Life and Death of the Pancreatic β Cells

Pancreatic β cells are responsible for maintaining the body's glucose levels within a very narrow range; their population is dynamic, with compensatory changes to maintain euglycemia. Throughout the lifetime of a mammal, low levels of β-cell replication and apoptosis are balanced and result in a slowly increasing mass of β cells. The emphasis in this review is on recent insights on the natural history of the β cell in a normal pancreas: sources of renewal, survival and changes in differentiation.
Building the visual Earth

Over the past several years there has been a broad effort towards realizing the Digital Earth, which involves the digitization of all earth-related data and the organization of these data into common repositories for wide access. Recently the idea has been proposed to go beyond these first steps and produce a Visual Earth, where a main goal is a comprehensive visual query and data exploration system. Such a system could significantly widen access to Digital Earth data and improve its use. It could provide a common framework and a common picture for the disparate types of data available now and contemplated in the future. In particular mcuh future data will stream in continuously from a variety of ubiquitous, online sensors, such as weather sensors, traffic sensors, pollution gauges, and many others. The Visual Earth will be especially suited to the organization and display of these dynamic data. This paper lays the foundation and discusses first efforts towards building the Visual Earth. It shows that the goal of interactive visualization requires consideration of the whole process including data organization, query, preparation for rendering, and display. Indeed, visual query offers a set of guiding principles for the integrated organization, retrieval, and presentation of all types of geospatial data. These include terrain elevation and imagery data, buildings and urban models, maps and geographic information, geologic features, land cover and vegetation, dynamic atmospheric phenomena, and other types of data.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Laminar shear flow of plastic viscoelastic fluids

The theory of plastic viscoelastic fluids was developed by the author to represent the rheological behavior of polymer melts and solutions with high loading of small particles. The present paper develops an asymptotic formulation of the general theory which applies to laminar shear flows. The formulation is analogous to Criminale, Ericksen and Filbey's theory for viscoelastic fluids. We apply this to study plane Poiseuille and Couette flow.
Reemergence of an Epidemic Coxsackievirus B5 Genotype

Outbreaks of coxsackievirus B5 (CB5) infections occur primarily during peak epidemic years, with comparatively few cases occurring during intervening years. This pattern of periodic CB5 epidemicity is quite distinct from the general endemicity typical of other group B coxsackieviruses. To determine the genetic relationships among CB5 isolates from different outbreaks, we compared viral RNAs by ribonuclease T1 oligonucleotide fingerprinting. Isolates obtained within an epidemic year had very similar fingerprints, an observation indicating that they were closely related variants of a single genotype. CB5 isolates from the major 1972 epidemic were not closely related to the genotype associated with the preceding epidemic of 1967. However, isolates from the most recent CB5 epidemic year, 1983, had fingerprints nearly identical to those of the 1967 strains. These findings provide clear evidence for epidemic reemergence of the 1967 genotype and suggest that the virus was maintained under conditions approaching evolutionary stasis during the intervening 16-year period.
Tardive dyskinesia after short-term treatment with oral metoclopramide in an adolescent

Case The objective of this case report is to report the development of tardive dyskinesia in an African-American adolescent male after short-term treatment with metoclopramide 10 mg orally three times daily secondary to delayed gastric emptying. The patient developed symptoms of tardive dyskinesia after 2 days of therapy with metoclopramide. Metoclopramide was discontinued and diphenhydramine 50 mg was initially administered intravenously followed with 25 mg orally every 4 hours as needed. While there are case reports of drug-induced tardive dyskinesia after intravenous administration of metoclopramide, this is to our knowledge the first report of tardive dyskinesia after short-term treatment with oral metoclopramide in an adolescent. Conclusion Awareness of the risk of development of this adverse effect even with short-term treatment with metoclopramide and in younger patients is important.
A review of auditing methods applied to the content of controlled biomedical terminologies

Although controlled biomedical terminologies have been with us for centuries, it is only in the last couple of decades that close attention has been paid to the quality of these terminologies. The result of this attention has been the development of auditing methods that apply formal methods to assessing whether terminologies are complete and accurate. We have performed an extensive literature review to identify published descriptions of these methods and have created a framework for characterizing them. The framework considers manual, systematic and heuristic methods that use knowledge (within or external to the terminology) to measure quality factors of different aspects of the terminology content (terms, semantic classification, and semantic relationships). The quality factors examined included concept orientation, consistency, non-redundancy, soundness and comprehensive coverage. We reviewed 130 studies that were retrieved based on keyword search on publications in PubMed, and present our assessment of how they fit into our framework. We also identify which terminologies have been audited with the methods and provide examples to illustrate each part of the framework.
Arm-First Method As a Simple and General Method for Synthesis of Miktoarm Star Copolymers

Miktoarm star copolymers containing two or more arm species were synthesized by atom transfer radical polymerization using a simple and general "arm-first" method, that is, one-pot cross-linking a mixture of different linear macroinitiator (MI) species by a divinyl cross-linker, such as divinylbenzene. Using linear MIs with a high degree of bromine chain-end functionality, including polyacrylate, polystyrene, polymethacrylate and poly(ethylene oxide), resulted in high-yield star polymers (>90%). Characterized by liquid adsorption chromatography techniques, which separated star polymers on the basis of the chemical composition of arms, the obtained star product was proved to be miktoarm star copolymers containing two or more arm species in one molecule, instead of mixture of different homoarm star polymers. Within our investigation, the molar ratios of the arms in the miktoarm star copolymers were always in agreement with the composition of the initial MI mixture, indicating the powerful capacity of this arm-first method for synthesis of miktoarm star copolymers with potentially any molar ratios and species of the arms. By using a mixture containing five types of linear MIs with different chemical compositions, miktoarm star copolymers containing five kinds of arms were synthesized for the first time, which significantly expanded the methodologies for synthesis of miktoarm star copolymers by living polymerization techniques.
Stabilizing the foundation of the house that ‘omics builds: the evolving value of cultured isolates to marine microbiology

The value of cultivating microbial strains that are representative of abundant microorganisms in situ is generally acknowledged amongst marine microbial ecologists, primarily because they provide the means to determine phenotypic properties and detailed physiological characteristics of living cells in a controlled setting. In the shadow of the rapid, ongoing expansion in environmental genomic, transcriptomic, and proteomic surveys of marine systems, a minor resurgence in experiments designed to isolate and grow free-living marine microorganisms has met some success. Interestingly, the most immediate impact that many of the resulting strains have had on our understanding of marine microbial communities has not resulted from experiments aimed to interrogate cellular physiology, but rather from their sequenced genomes. It is predicted, however, that their prolonged impact on marine ecology will result from basic laboratory research that links cellular physiology with its molecular underpinnings.
Replication and Non-Quantitative Research

In “Replication, Replication,” Gary King convincingly argues that publications by political scientists should adhere to what he calls a replication standard. Although King's article explicitly embraces qualitative as well as quantitative research, the policy statement that he suggests editors and reviewers of books and journals endorse exclusively imposes standards on studies based on quantitative research. Qualitative work is treated in a simple sentence and one that enforces no standards: “Authors of works relying upon qualitative data are encouraged (but not required) to submit a comparable footnote that would facilitate replication where feasible.”
Gene therapy—the future is here: a guide to the practicing urologist

C lassie solid tumor oncology has relied on the use of surgical excision, chemical poisons, or toxic doses of radiation in an attempt to cure the patient of malignancy. In the presence of metastatic disease, the entire premise of oncology has been to use therapies that are selectively toxic to the tumor cell. These treatments rely on the fact that most cancer cells are rapidly dividing in an unregulated manner and try to kill the cancer cell by poisoning its metabolic or reproductive machinery. Unfortunately, the very nature of these treatments results in injury to normal tissues because of their nonselective nature, with the treatments possibly even killing the host while leaving the tumor unaffected. Crossover of chemotherapy effects to normal, rapidly proliferating cells in the mucosa, epithelia of various organs, and bone marrow is an inevitable consequence that limits the ability of cancer treatment regimens to work. Additionally, this approach will not work in cases in which cellular proliferation is slow and cancer progression is largely due to a failure of apoptotic cell death (such as in prostate cancer). With recent advances in molecular biology, the complex interactions between growth factors, cell surface and nuclear receptors, intercellular adhesion molecules, oncogenes, and tumor suppressor genes are becoming elucidated. The alterations in cellular regulation and gene expression that occur in carcinogenesis are also becoming clearer, with attempts to institute therapy that directly corrects these molecular defects slowly becoming a reality. In simpler disease models in which there is a clearly defined, isolated gene defect, therapeutic trials have already been performed where the defective gene is replaced with the normal (wildtype) gene. Treatment involving replacement of the cystic fibrosis gene and factor IX deficiency have revealed that gene therapy can be performed
Color matching and shift work: An industrial application of the cusp‐difference equation

This paper considers a practical problem involving a multilevel system: color perception of individual human beings, man-machine interactions, and changing social factors. Previous research on individuals found a significant but noncritical decline in performance on a color name interference task from noon to 8 p.m. compared to other times of the day. The hypothesis now tested is whether critical diffences in color-matching efficiency for a group occur over a 24-hour period. Subjects were 13 color matchers and 30 printers who worked rotating shifts. Data were drawn from production records for 38 pairs of multicolor jobs performed over three four-week (accounting) periods. Data were analyzed via a cusp catastrophe model for two criteria: color matching time (R2 =.99) and printing paper wasted (R2 =.98). Job length was the bifurcation factor. Accounting period was the asymmetry factor, which was interpreted in terms of organizational dynamics that were taking place. Thecentral conclusion was that critical differences in color-matching efficiency could be observed over a 24-hour period when certain social or task factors are operating.