cssi/SciSciGPT-SciSciNet huggingface dataset:
Using Patient-Specific Induced Pluripotent Stem Cells to Understand and Treat Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction, loss of peripheral pulmonary arterial (PA) microvessels, and proliferation of vascular cells in proximal PAs, leading to occlusion of the lumen. Loss of function mutations in bone morphogenetic protein receptor (BMPR)2 occur in over 70% of heritable form of PAH (HPAH) patients. Intriguingly, only 20% of the mutation carriers develop clinical symptoms, suggesting that genetic variation may provide modifiers that alleviate the disease. Induced pluripotent stem cell (iPSC)-derived vascular cells provide a new opportunity to further understand the disease mechanisms in a personalized manner. In our study, we demonstrated that iPSC-derived endothelial cell (iPSC-EC) recapitulates the functional and gene expression abnormalities in native PAEC from the same PAH patients compared with healthy controls. Interestingly, PAH PAEC and iPSC-EC also respond similarly to potential PAH therapies elafin and FK506 in terms of improved angiogenesis. We then used iPSC-ECs to further understand the reduced penetrance of the BMPR2 mutation. iPSC-EC was generated from three families with unaffected mutation carriers (UMC), HPAH patients, and gender-matched controls. We identified patient-specific features of preserved function in UMC iPSC-EC attributed to the regulators of BMPR2 signaling or to cell survival gene revealed by RNA-Seq analyses. Our findings therefore highlight protective modifiers for HPAH that could help inform development of future treatment strategies. Despite the site of disease in the lung and the particular vulnerability of the PA vasculature, iPSC-EC is a good surrogate for PAH modeling and drug testing.
Abstract 219: Use of Machine Learning Models to Identify Atherosclerotic Cardiovascular Disease Patients at Very High Risk for Future Events in a Multi-state Health Care System

Background: In the 2018 AHA/ACC Blood Cholesterol Guideline, it is recommended that ASCVD patients be classified as very high-risk (VHR) vs not-VHR (NVHR) to guide treatment decisions. This has imp...
Flashmark: Watermarking of NOR Flash Memories for Counterfeit Detection

Counterfeit electronics represents a significant concern because recycled, over-produced, out-of-spec, or cloned chips can enter globalized supply chains. This paper introduces Flashmark, a technique for watermarking of NOR flash memories for counterfeit detection. Flashmark relies on novel approaches for (a) imprinting watermarks into dedicated blocks of flash memory chips by repeated stressing, thus irreversibly changing physical properties of flash memory cells, and (b) reading out watermarks by sensing the changes in physical properties of flash cells through standard digital interfaces. The paper demonstrates Flashmark on embedded NOR flash memories in a family of low-cost microcontrollers.
Complicated gastric duplication cyst presenting as cystic intraperitoneal collection: a case report

Alimentary tract duplications are rare anomalies and any delay in the diagnosis may develop various complications. Infection, hemorrhage, or perforation of the duplication cyst may lead to an acute presentation. Occasionally, it may lead to a diagnostic and management dilemma. Herein, we report an unusual complication of gastric duplication cyst. A 2.5-year-old girl presented with recurrent abdominal distension, fever, and abdominal pain. The imaging workup revealed a huge intraperitoneal collection. Intraoperatively, a huge pseudocyst was encountered communicating with the gastric duplication cyst. The gastric duplication cyst was sharing a common wall with the greater curvature of the stomach but was not communicating with the gastric lumen. Pseudocyst along with gastric duplication cyst was completely excised. The resultant seromuscular defect of the stomach was also closed. The postoperative period was uneventful. Perforation of the gastric duplication cyst should be kept in differentials of intraperitoneal collection not amenable to multiple aspirations. Huge intraperitoneal collection secondary to perforation of gastric duplication is exceedingly rare and scarcely reported in the literature.
Getting Blood from a Stone: Improving Neural Inferences without Additional Neural Data

In recent years, the cognitive neuroscience literature has come under criticism for containing many low-powered studies, limiting the ability to make reliable statistical inferences. Typically, the suggestion for increas- ing power is to collect more data with neural signals. However, many studies in cognitive neuroscience use parameters estimated from behavioral data in order to make inferences about neural signals (such as fMRI BOLD signal). In this paper, we explore how cognitive neuroscientists can learn more about their neuroimaging signal by collecting data on behavior alone. We demonstrate through simulation that knowing more about the marginal distribution of behavioral parameters can improve inferences about the mapping between cognitive processes and neural data. In realistic settings of the correlation between cognitive and neural parameters, additional behavioral data can lead to the same improvement in the precision of inferences more cheaply and easily than collecting additional data from subjects in a neuroimaging study. This means that when conducting an neuroimaging study, researchers now have two knobs to turn in a design analysis: the number of subjects collected in the scanner and the number of behavioral subjects collected outside the scanner (in the lab or online).
Digital Caudillos: The Use of Social Media in Guatemalan Presidential Campaigns:

This article contributes to the scholarship on Latin American campaigning by presenting data on the use of social media by presidential candidates in Guatemala’s 2019 election, including a content ...
Role of crystallographic orientation on intragranular void growth in polycrystalline FCC materials

Abstract In this work, we study the effect of crystallographic orientation and applied triaxiality on the growth of intragranular voids. Two 3D full-field micromechanics methods are used, the dilatational visco-plastic fast-Fourier transform (DVP-FFT) and the crystal plasticity Finite Elements (CP-FE), both of which incorporate a combination of crystalline plasticity and dilatational plasticity. We demonstrate with several select cases that predictions of void growth from both formulations agree qualitatively. With the more computationally efficient DVP-FFT, additional effects of polycrystalline microstructure and the influence of nearest neighborhood are investigated. Crystals bearing a single intracrystalline void are studied in three types of 3D microstructural environments: isolated single crystals, individual equal-sized grains within a regular polycrystal, and individual variable sized grains within a polycrystal with grains and voids randomly located. We show that loading type plays a significant role. In strain-rate controlled conditions, voids in the hardest [111]-crystals grow the fastest in time, whereas in stress-controlled conditions, voids in the softest [100]-crystal grow the fastest in time. The analysis reveals that on average void growth is slower for the same starting orientation in the polycrystal than in the single crystal. We find that at the highest triaxiality tested that the correlation between crystal orientation and void growth rate in the polycrystal strengthens, drawing closer to that seen in the isolated single crystals. These results and model can help guide the microstructural design of polycrystalline materials with high strength and damage-tolerance in high-rate deformation.
Erratum to “An introduction to methodological challenges in the evaluation of eHealth research: Perspectives from the Health e-Technologies Initiative”: [Evaluation and Program Planning 29 (2006) 386–389]

Ahern, D. K., Phalen, J., & Mockenhaupt, R. E. (2003). Science and the advancement of eHealth: A call to action. American Journal of Preventive Medicine 24(1), 108–109. The Robert Wood Johnson Foundation: Call for Proposals, Health e-Technologies Initiative: Assessing new tools for chronic disease management and health behavior change. Princeton, NJ, The Robert Wood Johnson Foundation, 2002, p 12. Altman, D. G., Schulz, K., & Moher, D. (2001). The CONSORT statement: Revised recommendations for improving the quality of reports of parallel-group randomized trials. Annals of Internal Medicine 134 (8), 657–662. Des Jarlais, D. C., Lyles, C., Crepaz, N., & the TREND Group. (2004). Improving the reporting quality of nonrandomized evaluations of behavioral and public health interventions: The TREND statement. American Journal of Public Health 94, 361–366. Glasgow, R. E., Vogt, T. M., & Boles, S. M. (1999). Evaluating the public health impact of health promotion interventions: The RE-AIM framework. American Journal of Public Health 89, 1323–1327.
Graduate Student Use of Journals

A 17% reduction in the library materials budget and faculty resistance to journal cancellations necessitated a demonstration of journal usage in a large academic library. Analysis of journal citations from theses revealed quantifiable data that differed from the 80/20 rule. Graduate students cited journals almost twice as frequently as do professional psychologists, and 91.9% of journal citations in theses were from locally-owned journals. One-quarter of the library's "psychology" journals were cited not at all, providing a large list of candidates for cancellation consideration. Thesis bibliographies tended to be longer after acquisition of PsycLIT.
Repositioning South Africa in global economic governance: a perspective from Nigeria

This paper adopts a Nigerian perspective to South Africa's position in global economic governance, particularly in relation to its role in the BRICS and G20. It is informed by the challenge of transforming Africa's current marginal role in global economic governance, and the kind(s) of regional partnerships that Africa's largest economies can strategically develop and use to place the continent on a higher economic pedestal globally. The paper places challenges confronting Africa in context, exploring how South Africa, by negotiating a strategic partnership with other continental economic powers outside of the BRICS, such as Nigeria, stands to leverage Africa's role and global position on a ‘win–win’ basis. It concludes by noting the costs and potential benefits of such a partnership, and offers some suggestions on the way forward.
Use of integrated rate equations in estimating the kinetic constants of enzyme-catalyzed reactions.

Methods are described for estimation of kinetic constants from the integrated rate equations for a number of reaction mechanisms. In general, these methods depend upon elimination of either zero order or first order terms between rate curves determined at two initial substrate concentrations or more. This operation is followed by graphic or statistical evaluation of the kinetic constants in the simplified equation and substitution of these values back into the original rate equation to permit evaluation of the remaining kinetic constants.
Molecular Pathology: Role in Improving Patient Outcome

F February 26 through February 28, 1999, the College of American Pathologists held a conference in Bethesda, Md, on the role of molecular pathology in improving patient outcomes. The following articles have resulted from that conference. Our conclusion from that conference and the resulting articles is that molecular pathology plays a significant role in improving patient outcome. Indeed, there can be little argument with the impression that the field of molecular pathology has matured dramatically since the last College of American Pathologists Molecular Pathology Conference, held in August 1992.1 That conference focused mainly on the burgeoning new techniques and potential promise of the field, but few data had yet been accrued in actual practice to draw many conclusions regarding clinical outcomes at that time. Now, in 1999, the profile and impact of the field are quite different. Molecular diagnostic techniques are in routine use in most major medical centers and numerous commercial laboratories, the accelerated success of the Human Genome Project has produced applications hardly conceivable a few years ago, a professional society devoted solely to this discipline has been born (the Association for Molecular Pathology), a new board certification examination in molecular genetic pathology (to be administered jointly by the American Board of Pathology and the American Board of Medical Genetics) has been approved, and the College of American Pathologists itself has devoted increasing resources to the promotion of quality assurance and appropriate utilization of these high-complexity tests. As a further reflection of the impact of the field, its regulatory and ethical aspects have moved into the sometimes unpredictable domain of public discourse, and the College of American Pathologists, through its Governmental and Professional Affairs Office in Washington, DC, and several committees (spearheaded by the sponsoring committee of this conference, the Molecular Pathology Resource Committee), has assumed a leadership role in opposing particularly restrictive policies and legislative ini-
Milk matters: offspring survival in Columbian ground squirrels is affected by nutrient composition of mother's milk

Through maternal effects, information about environmental conditions experienced in the maternal generation can be transmitted to subsequent generations. Although maternal effects have been described and quantified in many mammalian species, the underlying causal links are often under-studied. The close association between mother and neonate during the extended period of lactation in mammals provides a unique opportunity for mothers to influence offspring phenotype through nutrient provisioning of milk. The purpose of this study was to examine sources of inter-individual variation in milk composition and impacts on offspring phenotype and survival. Variation in fat content, protein content, and energy density of mother’s milk was associated with timing of reproduction. Mothers with intermediate birthdates produced milk that was higher in fat and energy density, but lower in protein than females with early or late birthdates. In turn, the pattern of change in milk composition affected juvenile overwinter survival. The protein content of Columbian ground squirrel milk typically increases to peak lactation and then declines before weaning. Pups consuming milk that was lower in protein in early lactation but then relatively high in protein at peak and late lactation had a higher probability of survival overwinter. Our results indicate that the interplay between the timing of reproduction and lactation performance has consequences for maternal and offspring fitness.
Hoph Bifurcation in Viscous, Low Speed Flows About an Airfoil with Structural Coupling

Abstract The locations of Hopf bifurcation points associated with the viscous, incompressible flow about a NACA 0012 airfoil with structural coupling are computed for very low Re ( ). A semi-implicit, first-order-accurate time-integration algorithm is employed to solve the streamfunction-vorticity form of the Navier-Stokes equations. The algorithm is modified to include simple structural elements affixed to the airfoil and the resulting airfoil motion. The equations describing the airfoil motion are integrated in time using a fourth-order Runge-Kutta algorithm. Numerical experiments are performed to determine if the structural model of the airfoil has an effect upon the location of the Hopf bifurcation point when compared with the fixed airfoil. Results are reported for a variety of structural characteristics, including variation of torsional and linear spring constants, inertial properties, structural coupling and structural damping.
Probing ATR activation with model DNA templates.

The ATR kinase is a critical upstream component of a checkpoint pathway that responds to many forms of damaged and incompletely replicated DNA. Cellular processes such as DNA replication and repair are thought to convert these DNA lesions into a common DNA intermediate that activates this signaling pathway. Indeed, numerous studies have shown that two DNA structures formed during these processes – single-stranded DNA (ssDNA) and junctions between double-stranded DNA (dsDNA) and ssDNA – are important components of the ATR-activating structure. However, an unanswered question is whether primed ssDNA is sufficient for activation of the ATR response. We recently demonstrated that primed ssDNA is sufficient to induce a bona fide checkpoint response in Xenopus egg extracts. This is the first well-defined DNA structure capable of eliciting ATR activation. Using this structure, we examined the contribution of ds/ssDNA junctions and ssDNA to checkpoint activation. Our results indicate the context in which the chec...
Intraoperative radiation therapy for locally advanced and recurrent soft-tissue sarcomas in adults.

Purpose To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution. Methods and Materials We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks–5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1–25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600–1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively. Results Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant ( p Conclusions IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients.
Does conditional discrimination learning by pigeons necessarily involve hierarchical relationships

Four experiments demonstrate that when putative conditional and discriminative cues are presented simultaneously in the single reversal procedure, it is not possible to ascribe a uniquely conditional or uniquely discriminative function to either of the cues. In Experiment 1, pigeons were trained to respond to a blue key and not to a red key while the houselight was on; then in a different session they learned the reversal of this discrimination with the houselight off (single reversal). Separate groups were tested for color generalization with houselight conditions alternating in blocks of trials or for houselight intensity generalization with blue and red key colors alternating in blocks of trials. Both test procedures revealed a conditional relationship between houselight and key color conditions. Experiment 2 produced the same result following training in which the key colors were held constant across training sessions while the houselight and no houselight conditions varied within sessions. In Experiment 3, separate groups were trained with the two procedures but were tested with randomly ordered combinations of key colors and houselight intensities. The two groups yielded indistinguishable bidimensional generalization gradients with peaks at both previously reinforced stimulus combinations. In Experiment 4 the subjects were switched from one of these training procedures to the other with no decrement in their discriminative performance. We conclude that for successive discriminations between conditional- and discriminative-stimulus combinations, the notion of a hierarchical relation between conditional and discriminative stimuli must be extended to include a symmetrical relationship or the notion should be abandoned altogether.
Implications of VHDL timing models on simulation and software synthesis

Abstract In this paper, we address the timing semantics of the delay models handled by VHDL. A formal model is used to characterize the runtime work required to resolve multiple assignments to signals for each of these models. Subsets of these timing models which require minimal work at runtime for resolution of multiple assignments are identified. Algorithms for generation of efficient code for simulation and synthesis in these restricted timing models are given. We present runtimes of our implementation of a simulator which uses these algorithms.
Miocene crustal extension and uplift in southeastern Nevada: Constraints from fission track analysis

The Gold Butte block of southeastern Nevada appears to be a cross section through the upper {approximately}17 km of Colorado Plateau crust, tilted eastward and tectonically denuded via top-to-the west normal faulting in Tertiary time. The east side of the block exposes a steeply dipping cratonic Paleozoic section 2 to 3 km thick; Proterozoic basement to the west is continuously exposed for an apparent thickness of {approximately}15 km structurally below the basal Cambrian unconformity. Apatite fission track dating and confirmed track-length distributions have been used to determine the time of unroofing of the Gold Butte block and hence the timing of one episode of extension in this part of the Basin and Range province. Samples collected in as east-west transect along the block indicate an abrupt transition from a period of relative thermal and tectonic stability to the onset of rapid cooling. The fission-track data indicate that the unroofing of the Gold Butte block was rapid and that the crustal section was brought to within a few kilometers of the surface at ca. 15 Ma.
Collagen synthesis and secretion by isolated rat renal glomeruli

Abstract Glomeruli were isolated from rat renal cortex and incubated with radioactive lysine to study in vitro collagen synthesis in these preparations. Glomerular basement membrane was obtained by sonication, and the appearance of [ 14 C]lysine and hydroxylysine in medium, membrane and intracellular proteins was determined. Total glomerular incorporation of [ 14 C]lysine into protein linearly increased for up to 2 h of incubation, as did hydroxy[ 14 C]lysine synthesis. The amount of [ 14 C]lysine and hydroxylysine in basement-membrane protein progressively increased over a 2-h period, and membrane hydroxylysine content gradually rose during this time. Hydroxy[ 14 C]lysine was recovered in the 105 000 × g pellet, reaching a hydroxylysine content of 22% in this intracellular fraction after 90 min of incubation. 60% of the protein secreted into the medium, and about 75% of newly synthesized sonicated basement membrane was acetic acid soluble. Hydroxylysine content was 33% in the acetic acid-insoluble fraction of sonicated membrane, suggesting that basement-membrane collagen was a significant component of total collagen synthesized by these preparation. The ability of isolated glomeruli to synthesize and secrete basement-membrane protein will be useful for studies concerning control of glomerular collagen and basement-membrane synthesis.
POLYPEPTIDE MODELS OF COLLAGEN. SYNTHESIS OF (PRO‐PRO‐β‐ALA)n

The sequential copolymer (Pro-Pro-β-Ala)n has been synthesized as a model for collagen. Preliminary studies indicate that the polymer may bear conformational resemblance to collagen.
Estradiol and testosterone binding in normal and mutant mouse cerebellum: Biochemical and cellular specificity

Abstract Estradiol and testosterone binding macromolecules are demonstrated in normal mouse cerebellum. Identity of the estradiol binder as the ‘receptor’ is provided by its binding to DNA—cellulose, which does not occur for other estradiol binding proteins. The androgen binder is identified as ‘receptor’ by its specific deficiency (85% reduced) in the androgen-insensitive mutant mouse, testicular feminization (Tfm). The relative amounts of these two components are reversed in cerebellum compared to hypothalamus-preoptic area. Neurological mouse mutants, which lack specified neurons, are examined to test for the cells in which these hormone binding proteins are located. Experiments with Purkinje cell degeneration (pcd) weaver (wv) and staggerr (sg), suggest that the majority of these receptors are present in granule cells.
Macromolecular matchmaking: advances in two-hybrid and related technologies

The success of the original yeast two-hybrid system has stimulated the development of a number of 'hybrid technologies' in yeast (and now prokaryotes and mammals) to widen the scope of the protein-protein interactions that can be analyzed, and to enable comparable studies of the interactions of proteins with DNA, RNA or small chemical ligands. In addition, the application of the two-hybrid system to entire genomes is being used to create protein linkage maps which catalog the network of interactions of an organism's complete proteome.
The Making of American Audiences: From Stage to Television, 1750-1990

In The Making of American Audiences, Richard Butsch provides a comprehensive survey of American entertainment audiences from the colonial period to the modern day. Providing coverage of theatre, opera, vaudeville, minstrelsy, movies, radio and television, he examines the evolution of audience practices as each genre supplanted another as the primary popular entertainment. Based on original historical research, this volume exposes how audiences made themselves through their practices - how they asserted control over their own entertainments and their own behaviour. Importantly, Butsch articulates two long-term processes: pacification and privatization. Whereas during the nineteenth century, overactive audiences represented a threat to civic order through their unruly behaviour, in the twentieth century, audiences have become more passive, dependent upon and controlled by media messages. This timely study serves as an important contribution to communication research, as well as American cultural history and cultural studies.
Osteoarthritis: Pathophysiology, Treatment, and What Muslims Need to Know Prior to Joint Replacement Surgery

DOI: http://dx.doi.org/﻿10.5915/40-4-4435 Osteoarthritis is the most common type of arthritis. The joints most commonly involved include the knees, hips, fingers and thumbs, and the spine. Risk factors include age (>50 years), obesity, joint hypermobility/instability, prolonged occupational/sports stress, and previous joint injury. The pathogenesis of osteoarthritis is multifactorial, but the ultimate endpoint is the alteration of the articular cartilage. The diagnosis of osteoarthritis can usually be made by a detailed history and physical examination and reliably confirmed by plain radiographs. The primary goals of treatment for osteoarthritis are improved function and quality of life. Treatment modalities include patient education, physical therapy, pharmacotherapy, intra-articular injections, and surgery. Joint replacement surgery has been steadily growing in frequency and success. Hips and knees are the most commonly replaced joints. After successful joint replacement of a Muslim’s hips or knees, the resulting range of motion under normal circumstances may not allow sufficient motion to perform salat in the standard format.
Parenting style and the vulnerable child syndrome.

TOPIC: Vulnerable child syndrome (VCS) refers to the combination of the parental view that their child is at increased risk for death despite the child's objective health and the resulting behavior problems in the child. Although risk factors for the development of the syndrome have been outlined, the variability in the development of VCS has not been explained. PURPOSE: A theoretical explanation for the variability in the development of VCS utilizing Susan Calkins' model is explored. By considering the development of VCS in light of Calkins' model, variability may be explained and preventative interventions may be instituted. SOURCES USED: Relevant literature pertaining to child development and VCS was reviewed. CONCLUSIONS: By recognizing the risk of the role that parenting sensitivity plays in the development of VCS, team-based interventions involving a developmental approach may be employed, and the long-term behavioral sequelae of the disorder may be prevented or alleviated.
Aroma-Active Compounds in Skipjack Tuna Sauce

Volatile compounds in skipjack tuna (Katsuwonus pelanis) viscera (STV) and tuna sauce (TS) made from STV were analyzed by vacuum simultaneous distillation−solvent extraction/gas chromatography/mass spectrometry/olfactometry and aroma extract dilution analysis. Predominant odorants in STV were lipid-derived compounds, such as (E,E)-2,4-heptadienal (stale/peanut-like), (E,Z)-2,6-nonadienal (cucumber-like), (E,E)-2,4-decadienal (fatty/rancid fat-like), (E)-2-nonenal (stale, bitter), and (Z)-4-heptenal (fishy/rancid), and unidenified compounds having grassy, fresh fish-like odors. In contrast to STV, potent odorants in TS were mostly thermally generated compounds such as 3-(methylthio)propanal (baked potato-/soy sauce-like), dimethyl trisulfide (cooked cabbage-like), and 3-methylbutanal (dark chocolate-like). Additional potent odorants in TS were (E,E)-2,4-heptadienal, (E)-2-nonenal, phenylacetaldehyde (honeysuckle-like), and two unidentified compounds having nutty, baked potato-, vitamin-, and cooked rice-li...
Phage-display evolution of tyrosine kinases with altered nucleotide specificity †

The problem of identifying downstream targets of kinase phosphorylation remains a challenge despite technological advances in genomics and proteomics. A recent approach involves the generation of kinase mutants that can uniquely use "orthogonal" ATP analogs to phosphorylate substrates in vivo. Using structure-based design, mutants of several protein kinase superfamily members have been found; robust and general methods are needed, however, for altering the nucleotide specificity of the remaining kinases in the genome. Here we demonstrate the application of a new phage display technique for direct functional selection to the identification of a tyrosine kinase mutant with the ability to use N6-benzyl-ATP. Our method produces, in five rounds of selection, a mutant identical to the best orthogonal Src kinase found to date. In addition, we isolate from a larger library of kinase mutants a promiscuous clone capable of using many different ATP analogs. This approach to engineering orthogonal kinases, combined with others, will facilitate the mapping of phosphorylation targets of any kinase in the genome.
Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies.

Purpose Paraneoplastic and autoimmune retinopathies are immunologically mediated retinal degenerations that are associated with antibodies directed against any of several retinal proteins, including α-enolase. We report the clinical and electrophysiological features of antienolase retinopathy in contrast to the features of antirecoverin retinopathy. Design Retrospective, observational case series. Methods Patients were referred for evaluation of unexplained acquired visual symptoms, including photopsias, and loss of visual acuity or field considered of possible retinal origin. Full-field and multifocal electroretinograms (ERGs) were performed. Sera from patients were examined for antiretinal antibodies by Western blot analysis using proteins extracted from human retinas and by immunohistochemistry; antienolase was confirmed by incubating patient sera with purified α-enolase. Results Of 87 patients with unexplained retinal visual symptoms associated with abnormal ERGs, 37 (43%) demonstrated autoantibodies to retinal antigens, including 12 against α-enolase, of whom 4 had cancer. Initial visual loss was typically central and often asymmetric. The ERGs demonstrated mostly normal rod responses but central cone abnormalities (evident on multifocal ERG) and, for many, global cone abnormalities. Seven patients developed optic disk pallor. Corticosteroid and immunosuppressive therapy, when attempted, was clinically ineffective. Conclusions Antienolase retinopathy is a protean autoimmune retinopathy that characteristically presents with cone dysfunction. The visual impairment and course vary from relative stability for years to slow progression with loss of central vision. With time, optic disk pallor can evolve, presumably from attrition of ganglion cells.
μ-Bis(cyanotrihydroborato)-tetrakis(triphenylphosphine) dicopper(I). A new, selective, pH dependent reducing agent

Abstract The title compound selectively reduces acid chlorides to aldehydes under neutral conditions and aldehydes and ketones to alcohols in acidic media. 4- tert -Butylcyclohexanone is reduced to the trans alcohol with a high degree of stereoselectivity (94:6).
Using social media for social comparison and feedback-seeking: gender and popularity moderate associations with depressive symptoms

This study examined specific technology-based behaviors (social comparison and interpersonal feedback-seeking) that may interact with offline individual characteristics to predict concurrent depressive symptoms among adolescents. A total of 619 students (57 % female; mean age 14.6) completed self-report questionnaires at 2 time points. Adolescents reported on levels of depressive symptoms at baseline, and 1 year later on depressive symptoms, frequency of technology use (cell phones, Facebook, and Instagram), excessive reassurance-seeking, and technology-based social comparison and feedback-seeking. Adolescents also completed sociometric nominations of popularity. Consistent with hypotheses, technology-based social comparison and feedback-seeking were associated with depressive symptoms. Popularity and gender served as moderators of this effect, such that the association was particularly strong among females and adolescents low in popularity. Associations were found above and beyond the effects of overall frequency of technology use, offline excessive reassurance-seeking, and prior depressive symptoms. Findings highlight the utility of examining the psychological implications of adolescents’ technology use within the framework of existing interpersonal models of adolescent depression and suggest the importance of more nuanced approaches to the study of adolescents’ media use.
A variational calculus approach to the suspension flow problem using the minimal force hypothesis

Analytic expressions for the velocity profile and distribution of neutrally buoyant particles in laminar flow were obtained as functions of the radial distance. A modified Einstein viscosity model and the hypothesis that the total force on all the particles flowing in the tube is a minimum were used. The methods of the variational calculus were used in the mathematical development. A velocity profile differing only slightly from the parabolic form of that for Hagan-Poiseuille flow was obtained. For particle distribution the equations developed predict a maximum concentration along the center-line for some flows and a maximum concentration in a ring some distance from the center line in other flows. Both of these concentration profiles have been observed experimentally. Quantitative predictions from the equations derived must await further experimental work to permit calculation of the parameters included in the equations.
A Perspective on Information Fusion Problems

Information fusion problems have a rich history spanning four centuries and several disciplines as diverse as political economy, reliability engineering, target tracking, bioinformatics, forecasting, distributed detection, robotics, cyber security, nuclear engineering, distributed sensor networks, and others. Over the past decade, the area of information fusion has been established as a discipline by itself with several contributions to its foundations as well as applications. In a basic formulation of the information fusion problem, each component is characterized by a probability distribution. The goal is to estimate a fusion rule for combining the outputs of components to achieve a specified objective such as better performance or functionality compared to the components. If the sensor error distributions are known, several fusion rule estimation problems have been formulated and solved using deterministic methods. In the area of pattern recognition a weighted majority fuser was shown to be optimal in combining outputs from pattern recognizers under statistical independence conditions. A simpler version of this problem corresponds to the Condorcet Jury theorem proposed in 1786. This result was rediscovered since then in other disciplines including by von Neumann in 1959 in building reliable computing devices. The distributed detection problem, studied extensively in the target tracking area, can be viewed as a generalization of the above two problems. In these works, the underlying distributions are assumed to be known, which is quite reasonable in the areas these methods are applied. In a different formulation, we consider estimating the fuser based on empirical data when no information is available about the underlying distributions of components. Using the empirical estimation methods, this problem is shown to be solvable in principle, and the fuser performance may be sharpened based on the specific formulation. The isolation fusers perform at least as good as best component, and the projective fusers perform as good as best combination of components. In a special case of function estimation, each component could be a potential function estimator, radial basis function, nearest neighbor estimator, regressogram, kernel estimator, regression tree or another estimator. A projective fuser based on a nearest neighbor concept has been proposed based on Voronoi regions in this case. Under fairly general smoothness and non-smoothness conditions on the individual estimators, the expected fuser error is close to optimal with a specified probability. This result is purely sample-based and distribution-free in that it does not require the knowledge of underlying distributions and can be computed only using measurements.
Migrant solution to the anammox mystery

Every night a massive migration takes place in ocean waters. Zooplankton and micronekton, a diverse group of organisms <1 mm to 10 cm in size, swim up from midwater depths (200–700 m) to the surface ocean to feed and return down to resting depths before daybreak. The importance of this diel vertical migration to marine biogeochemical cycles has been recognized for some time. Research has primarily focused on the migrant-mediated movement of elements including nitrogen (N) from the surface ocean to midwaters. Such an “active transport” involves feeding at night in the upper ocean and the consequent excretion of ammonium (1) and dissolved organic N (2, 3) at midwater depths during the day. However, within the midwater realm, the effect of such migratory behavior on elemental cycles is less well understood. This “twilight zone” hosts many of the reactions that drive global biogeochemical cycles, including the remineralization of particulate organic matter into nutrients such as nitrate and the production of dinitrogen (N2) gas. In PNAS, Bianchi et al. (4) significantly advance our knowledge of the role of animals in midwater biogeochemistry by linking the activity of migrant zooplankton and micronekton to an important N transformation pathway, anammox.
Hypertrophic Neuropathy of the Cauda Equina: Case Report

Objective and importance Hypertrophic neuropathy of the cauda equina (HNCE) is a rare form of peripheral neuropathy. The diagnosis is complicated by an insidious clinical presentation and complex radiographic images. We present a case of HNCE caused by chronic inflammatory demyelinating polyneuropathy with symptomatic improvement after decompressive lumbar laminectomy and dural expansion. Clinical presentation A 54-year-old woman with a history of back pain since she was in her 20s presented with low back and radicular pain that had increased during a period of 6 months, bilateral lower-extremity weakness, and sensory loss in the right thigh. Magnetic resonance imaging of the lumbosacral spine revealed multiple, poorly enhancing mass lesions and apparent intrathecal nerve root thickening from L1 to L5. Intervention An L1-L5 decompressive laminectomy, performed with continuous somatosensory evoked potential and electromyographic monitoring, revealed multiple segmentally enlarged nerve roots. One nerve root that did not respond to high levels of stimulation was identified. This root was resected and submitted for pathological analysis. The dura was expanded with an 11-cm-long dural patch. The pathological examination revealed hypertrophic neuropathy, with extensive S-100-positive "onion bulb" formation. The patient's symptoms improved postoperatively. Conclusion HNCE is a rare disorder that can cause radicular pain and lower-extremity weakness, sensory loss, and hyporeflexia. One possible cause is demyelinating polyneuropathy. Although medical management is typically effective in the treatment of demyelinating polyneuropathy, it has little effect on compressive symptoms caused by intradural nerve root enlargement. As this case demonstrates, surgical management of symptomatic radiculopathy by lumbar laminectomy is a reasonable and effective approach to the treatment of HNCE.
Nurturing the genome: A-type lamins preserve genomic stability.

A-type lamins provide a scaffold for tethering chromatin and protein complexes regulating nuclear structure and function. Interest in lamins increased after mutations in the LMNA gene were found to be associated with a variety of human disorders termed laminopathies. These include muscular dystrophy, cardiomyopathy, lipodystrophy, peripheral neuropathy and premature aging syndromes such as progeria. In addition, altered expression of A-type lamins is emerging as a contributing factor to tumorigenesis. How different alterations in a gene that is ubiquitously expressed can cause such an array of systemic as well as tissue specific diseases remains an enigma. Several lines of evidence indicate that mutant forms of A-type lamins impact on genome function and integrity. A current model suggests that genomic instability plays a major part in the pathophysiology of some lamin-related diseases. However, this model remains to be fully investigated. Here we discuss recent studies revealing novel functions for A-typ...
(Re)producing Empire: Góngora's Soledades, Productive Space, and the Reversal of Spanish Decline

En este ensayo, demuestro que, lejos de una dura critica del imperialismo, las Soledades de Gongora ofrecen una vision estrategica de un imperio reestructurado capaz de contrarrestar la declinacion de Espana, ya tangible a principios del siglo XVII. Leyendo la Soledad primera en su contexto historico representado por las obras contemporaneas del arbitrista Martin Gonzalez de Cellorigo, sugiero que el milieu social de Gongora estaba inmerso en teoria economica y social que criticaba y reimaginaba activamente el proyecto imperial espanol. En la primera seccion, contextualizo el poema dentro de este imaginario transatlantico que enfatizaba la produccion y circulacion de mercancias. En la segunda, sugiero que la manera en que Gongora representa el espacio, informada por estos proyectos socioeconomicos y el mercantilismo europeo, propone una solucion poetica pero concreta para (re) producir el Imperio Espanol, transformandolo del viejo modelo 'extractivo' a un nuevo modelo 'productivo' � pero no menos imperial.
Fine-needle aspiration cytology in locally advanced breast adenocarcinoma: A case with complete response to preoperative chemotherapy in association with granulomatous inflammatory reaction

Preoperative chemotherapy for locally advanced breast carcinoma (stage IIIA,B) is increasingly utilized demonstrating a 70 to 95% objective response and 15 to 35% complete response. A 70-yr-old woman presented with a 9 cm left upper outer quadrant breast mass associated with overlying skin redness and a 2.5 cm left axillary mass. Fine-needle aspiration cytology (FNA) showed a pleomorphic adenocarcinoma in both the breast and axilla. Following three courses of chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), the patient had a dramatic clinical reduction of tumor, reduction of serum CA 15-3 from 161 to 64 U/ml, and underwent a modified radical mastectomy and axillary dissection. The specimen showed no viable tumor in association with an extensive granulomatous response in both the breast and axillary lymph nodes. This case illustrates two points concerning preoperative chemotherapy for locally advanced breast cancer: (1) The role of FNA v. tissue biopsy is examined. Positive cytology must be conclusive since, as in this case, no viable carcinoma may be present after therapy. (2) Chemotherapy induced host tissue reaction has not been extensively studied. This case showed a remarkable granulomatous reaction in association with tumor elimination. Since this reaction was not present on the original aspiration cytology slides, the chemotherapy treatment must have induced this reaction. Mechanisms for creating this effective host response need further investigation. © 1994 Wiley-Liss, Inc.
Modulation of tissue trace metal concentrations in weanling rats fed different levels of zinc and exposed to oral lead and cadmium

Abstract The effects of varying dietary zinc (Zn) and oral lead (Pb) and cadmium (Cd) exposure on tissue trace metal concentrations were investigated in weanling rats using a 4 X 3 factorial design. Male SD rats (72, 6/group) were fed diets containing either Zn deficient (
HIV-Related Malignant Lymphoma: Clinical Aspects, Treatment, and Pathogenesis

(1988). HIV-Related Malignant Lymphoma: Clinical Aspects, Treatment, and Pathogenesis. Cancer Investigation: Vol. 6, No. 4, pp. 413-416.
Accuracy analysis for the NAD 83 geodetic reference system

The North American Datum of 1983 (NAD 83) provides horizontal coordinates for more than 250,000 geodetic stations. These coordinates were derived by a least squares adjustment of existing terrestrial and space-based geodetic data. For pairs of first order stations with interstation distances between 10km and 100km, therms discrepancy between distances derived fromNAD 83 coordinates and distances derived from independentGPS data may be suitably approximated by the empirical rulee=0.008 K0.7 where e denotes therms discrepancy in meters and K denotes interstation distance in kilometers. For the same station pairs, therms discrepancy in azimuth may be approximated by the empirical rule e=0.020 K0.5. Similar formulas characterize therms discrepancies for pairs involving second and third order stations. Distance and orientation accuracies, moreover, are well within adopted standards. While these expressions indicate that the magnitudes of relative positional accuracies depend on station order, absolute positional accuracies are similar in magnitude for first, second, and third order stations. Adjustment residuals reveal a few local problems with theNAD 83 coordinates and with the weights assigned to certain classes of observations.