cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of Mitochondrial Na+/Ca2+ Exchanger Suppresses Ischemia/Reperfusion-Induced Reentry in Monolayers of Cardiomyocytes

Introduction: Mitochondria are important organelles that regulate cytosolic [Ca2+] ([Ca2+]c) in cardiomyocytes and are thought to play a major role in Ca2+ overload and arrhythmogenesis during ischemia/reperfusion. Previously, we showed that inhibition of the mitochondrial Na+/Ca2+ exchanger (mNCE) using CGP-37157 increases mitochondrial [Ca2+] ([Ca2+]m) retention, and prevents delayed afterdepolarizations and triggered arrhythmias during Na+ overload induced by Na+/K+ ATPase inhibitor, ouabain, in vitro and in vivo. Here, we studied the dynamics of [Ca2+]m and [Ca2+]c during ischemia/reperfusion, and investigated the role of mNCE in ischemia/reperfusion-related reentry in monolayers of neonatal rat ventricular myocytes. Methods: Sarcolemmal electrical activity was recorded with a 464-photodiode array using voltage-sensitive dye, di-4-ANEPPS. Changes in [Ca2+]m and [Ca2+]c were observed using the ratiometric genetically-encoded mitochondrial and cytosolic [Ca2+] indicator, GEM-GECO, respectively. Ischemia was induced by covering the central region of the monolayer with a coverslip and reperfusion was prompted by coverslip removal. Results: As the coverslip was lowered on the monolayer, amplitude and conduction velocity of action potentials decreased over time until the ischemic region became inexcitable. During 1 hour of ischemia, [Ca2+]m and [Ca2+]c increased in a sigmoid fashion. Reperfusion of the monolayers with Tyrode's solution sharply lowered [Ca2+]m back to its initial values in less than 10 minutes. Wavelets and subsequently reentry occurred upon reperfusion in 6/7 monolayers. CGP-37157 (1µM), at reperfusion, prevented or shortened the duration of wavelets, reducing the occurrence of reentry to 2/5 monolayers. Viral overexpression of NCLX, the molecular candidate for mNCE, did not alter the incidence of reentry, compared to controls. Conclusion: The results reveal the kinetics of [Ca2+] during ischemia/reperfusion using a novel genetically encoded probe and demonstrate the cardioprotective effects of inhibition of mNCE, as CGP-37157 decreased dispersion of repolarization and suppressed reentry.
Photometric Ordering Of Ordinary Moire Fringes

A method is described for ordering the fringes in ordinary moire topograms that resolves hill-or-valley ambiguities. A photometric model is used to predict the expected surface brightness for the up and down surface orientation possibilities. Only one of the orientations produces estimates that are consistent with the measured values. The photometric model is based globally upon the moire geometry, and locally upon the surface reflectance properties. Topograms of test objects and human subjects are presented to illustrate the principle of photometric ordering.
The Influence of Certain Synthetic Estrogens on the Serum Calcium of the Chicken

Abstract THE elevation of the calcium content of the blood serum of the chicken when the bird starts egg production, is a well-known phenomenon. In addition, many investigators have shown that the injection of diethylstilbestrol produced the same effect. In the course of our recent work we have had opportunity to obtain certain substances reported to have exhibited estrogenic activity and to investigate the effect of these compounds on the blood-calcium level of the chicken. For the purpose of this investigation the activity (ability to raise the calcium activity of the blood serum) of the following substances has been compared with the activity of dithylstilbestrol; 1 Triphenylbromoethylene a 2 Triphenylchloroethylene a 3 α-methyl-α,α-diphenyl-acetophenone b 4 α-ethyl-α,α-diphenyl-acetophenone b 5 Triphenylethoxethylene b 6 Triphenyl-β-N-piperidino-ethoxy-ethylene, hydrochloride b 7 Estradiolcyclopentylpropionate (E.C.P.) c Compound 1 has been reported by Hixon and Thompson (1951) to be of value in the fattening of turkeys when given orally, whereas compound 2 was reported by Jaap (1945) …
Male Gibbon (Hylobates agilis) Singing Behavior: Natural History, Song Variations and Function

Male gibbons engage in elaborate singing performances during which they emit a variety of song types. Field observations, acoustic analyses and experimental playbacks were conducted to investigate the communicative significance of song variations and to test the hypothesis that unmated male gibbons use song to attract potential mates. Singing is progressively elaborated during the course of a performance, with louder, longer, syllabically more complex songs produced at the end compared to the start. Similarly, song complexity increases during vocal interactions with territorial neighbors. Field playbacks showed that complex songs elicit significantly faster approaches than the simple songs used to initiate performances. Additional observations and experiments revealed few differences between the singing performances of mated and unmated males, and that the reproductive status of singing males did not affect the responsiveness of gibbons to songs. These results suggest that increasing song complexity during performances represents a series of graded signals used intrasexually in territorial defense; current evidence does not support the hypothesis that male song performs an intersexual mate attraction function.
A note on the solution of a communication jamming problem of root

Root recently considered some problems in binary transmission in the presence of unknown additive noise, and reduced them to infinite games. For these he derived mixed strategies which in this note are shown to be optimal, providing the values of the games.
Feasibility of sternal intraosseous access by emergency medical technician students.

Objective. Emergency medical technician–basic (EMT-B) providers are not trained to establish vascular or intraosseous (IO) access on critically ill patients. This study was conducted to examine the feasibility of training EMT-B students to correctly place a commercial sternal IO infusion device (FAST-1). Methods. Twenty-nine EMT-B students attended a two-hour training session. Subjects were subsequently tested in FAST-1 application using a modified resuscitation mannequin permitting IO needle deployment. Two observers assessed correct IO application andtechnique. Results were analyzed using descriptive statistics (binomial proportions andmedians with 95% confidence intervals). Inter-rater agreement of observations was evaluated using kappa statistics andintraclass correlation coefficients (ICCs). Results. Inter-rater agreement ranged from fair to excellent (kappa = 0.37–1.00) for all parameters except sternal notch identification (kappa = −0.03). Reliabilities of elapsed times were good (ICC = 0.83, 0.31)...
Studies of anti-F(ab′)2 antibodies and VH region distribution among SLE kindreds

Abstract Genomic DNA samples from kindreds of patients with systemic lupus erythematosus were examined for VH region genotypes using probes representing J H and representative members of the human V H gene families (V H I-V H VI) in parallel with distribution of high levels of anti-F(ab′) 2 (generic anti-idiotype) in some non-affected SLE family members. Identical VH region genotypes were present in an SLE female proband and one unaffected normal male sibling. Three normal unaffected family members with elevated anti-F(ab′) 2 showed AB, AD, and AC (non-identical) V H genotypes. V H region genotype pattern distributions do not appear to directly correlate with production of high levels of anti-F(ab′) 2 in SLE families.
Marketing factors impacting imported wood products in Central America

AbstractIncreasing environmental pressures against deforestation in Central America has increased harvesting restrictions and subsequently caused disruption in the supply of raw materials to primary and secondary industries. A conceptual model was developed based on literature review to describe perceptions of wood products distributors, retailers, and manufacturers regarding supplier and product attributes, retailer/manufacturer and supplier promotion strategies, potential importing barriers and company performance. After verifying internal reliability with Cronbach’s alpha, confirmatory factor analysis was conducted to confirm the structure of proposed marketing constructs. Results supported only one of the proposed factors in the model, (i.e. supplier attribute). Exploratory factor analysis was conducted to determine the structure of the remaining factors. The strongest correlations were between product attributes and retailer/manufacturing marketing factors, and the second strongest correlation found ...
The use of configurable computing for computational kernels in scientific simulations

In many scientific simulation codes, the bulk of the floating-point arithmetic required is done by a small number of compact computational kernels. In this paper, we explore the potential use of configurable computers to instantiate the hardware required for such kernels and, thus, improve their performance. We present algorithms and analysis for two such kernels: fast, problem-specific multipliers and the efficient evaluation of Taylor series. A novel aspect of the algorithm for Taylor series evaluation is that it takes advantage of the variable precision arithmetic available to a configurable computer. Experimental results obtained on a Xilinx field-programmable gate array (FPGA) are presented for the proposed algorithms.
CU(II) SENSITIZES pBR322 PLASMID DNA TO INACTIVATION BY UV‐B(280–315 nm)

— Copper(II), in the presence of UV-B radiation(280–315 nm), can generate single-strand breaks in the sugar-phosphate backbone of pBR322 plasmid DNA. A low level of single-strand backbone breaks occurs in the presence of Cu(II) alone, but UV-B irradiation increases the rate by the more than 100-fold. Concomitant with the damage to the DNA backbone is a loss of transforming activity. Oxygen is required for generation of the single-strand breaks but not for the loss of transforming activity. A DNA glycosylase (Fpg), which participates in the repair of certain DNA nitrogenous base damage, does not repair plasmid DNA damaged by Cu(II). The hydroxyl radical scavenging compound DMSO is only somewhat effective at protecting the physical and biological properties of the DNA. These results with Cu(II) are compared to those obtained previously with pBR322 plasmid DNA in the presence of Fe(III) and UV-A.
Personal Transformations in the Group

The psychotherapy group is often portrayed with a maternal image and the conductor who relates to the group frequently has a maternal role. In the experience of group members, merging and separating and associated fears of annihilation resemble those of the mother—child couple in their individuation process. Structures and self-images change and in each context there may be fears of engulfment, intrusion or abandonment. This paper considers these psychosocial changes as having some analogy to changes in our physical and biological environment and reviews analogies in traditional shamanic practices and group primordial experience.
The Structure of the Cytidine Deaminase−Product Complex Provides Evidence for Efficient Proton Transfer and Ground-State Destabilization†,‡

Crystal structures of the cytidine deaminase−uridine product complex prepared either by cocrystallizing enzyme with uridine or by diffusing cytidine into ligand-free crystals show that the product binds as a 4-ketopyrimidine. They reveal four additional features of the catalytic process. (1) A water molecule bound to a site previously observed to bind the incoming 4-NH2 group represents the site for the leaving ammonia molecule. The conserved Pro 128 accommodates both moieties by orienting the carbonyl group of the previous residue. (2) The Glu 104 carboxylate group rotates from its hydrogen bond to the O4 hydroxyl group in transition-state analog complexes, forming a new hydrogen bond to the leaving group moiety. Thus, after stabilizing the hydroxyl group in the transition state, Glu 104 transfers a proton from that group to the leaving amino group, promoting enol-to-keto isomerization of the product. (3) Difference Fourier comparisons with transition-state complexes indicate that the pyrimidine ring rot...
Effects of hypothermia on myocardial substrate selection

Abstract Background . Hypothermia lowers the metabolic rate and increases ischemic tolerance but the effects of temperature on myocardial substrate selection are not well defined. Methods . Isolated rat hearts were perfused with physiologic concentrations of 13 C labeled lactate, pyruvate, acetoacetate, mixed long-chain fatty acids, and glucose. Hearts were cooled over 5 to 10 minutes to one of four target temperatures (37°, 32°, 27°, or 17°C), then perfused for an additional 30 minutes, freeze-clamped, and extracted. 13 C NMR spectra were obtained and substrate oxidation patterns were determined by isotopomer analysis. Results . Although hearts in all groups were supplied with identical substrates, the percentage of acetyl-CoA oxidized within the citric acid cycle that arose from fatty acids decreased significantly from 53.8% ± 0.8% in the 37°C group to 33.1% ± 3.3% in the 17°C group. Lactate or pyruvate utilization increased from 3.3% ± 0.5% to 25.7% ± 3.6%, respectively ( p Conclusions . These data suggest that moderate hypothermia suppresses fatty acid oxidation and deep hypothermia significantly increases utilization of lactate and pyruvate. These effects may result from relative inhibition of catabolism of complex molecules such as fatty acids, or stimulation of pyruvate dehydrogenase. These effects on substrate metabolism may play a role in myocardial protection afforded by hypothermia.
Afterword: in and out of the archives

This Afterword to the papers in the ARCS special issue on Knowledge Cultures assesses the historical approach contained in most of the essays in light of current concerns in archival science and among contemporary scholars in the field.
God, Determinism, and Action: Perspectives from Physics

Recent articles by Michael Heller, Carl Helrich, Peter Hodgson, Jeffrey Koperski, and Nicholas Saunders present a challenge to much current thinking on God, divine action, and cosmology. In the process, they also reveal underlying assumptions and current problems, especially in the debate over physics and divine action. In particular, three issues come up that need to be addressed further. First, what is the status of determinism, and what can physics contribute? Second, what kind of divine action are we talking about? Third, what is the relationship between God and time, and how does this affect claims about the personhood of God? While these essays present necessary critiques and interesting, positive proposals, they also reveal unresolved tensions that need to be addressed.
Rapid assessment and intervention at specialist outpatient clinics-time for a new standard in TIA care?

Rapid assessment and intervention at specialist outpatient clinics—time for a new standard in TIA care?
Ethnocultural differences in sleep complaints among adolescents

Data from a school survey (N = 5423) were used to examine differences in sleep complaints among adolescents from nine ethnocultural groups. Compared with Anglo youths, Chinese American youths were at significantly lower risk for insomnia, whereas Mexican American youths had an elevated risk, adjusting for the effects of age, gender, and socioeconomic status. Adjusting for the same three covariates, African, Mexican and Central American youths were at elevated risk for hypersomnia. No group was at lower risk for hypersomnia than the Anglos. The results suggest minority status may affect risk for sleep problems but that the direction and the magnitude of the effects vary depending on the outcome examined, severity of the problem, and the ethnic group studied. Given the paucity of data on culture and risk for disturbed sleep among adolescents, more research is needed on the role of ethnocultural background on sleep.
Ximelagatran: a new oral anticoagulant

Vitamin K antagonists are effective oral anticoagulants, but they have limitations related to a narrow therapeutic range, food and drug interactions, slow onset of action and the need for routine coagulation monitoring. Ximelagatran is a promising new oral anticoagulant under investigation in advanced clinical trials. It is a prodrug that is converted after oral administration to melagatran, a direct thrombin inhibitor, with a peak effect after 2 hours and a half-life of approximately 3 hours with primarily renal excretion. Administration results in prolongation of coagulation tests, but routine monitoring is not required because of reliable absorption and predictable effects. A large clinical trials program has demonstrated effectiveness in prophylaxis of deep vein thrombosis (DVT) following major orthopedic surgery, treatment of symptomatic DVT, prevention of embolism in patients with atrial fibrillation, and prophylaxis of recurrent events after acute myocardial infarction. Bleeding complications have been similar to those with standard therapy, with no unexpected adverse effects except for elevation of serum transaminase levels in over 6% of patients beginning after 1 month of therapy. Ximelagatran may be an alternative oral anticoagulant for patients currently taking vitamin K antagonists.
Finite element simulation of a self-healing shape memory alloy composite

Abstract A self-healing, metal matrix composite reinforced by shape memory alloy wires is simulated using finite element analysis. A one-dimensional constitutive model for SMA behavior is implemented as a user-defined truss element in ABAQUS. The matrix is brittle and a mode I crack is allowed to propagate through the specimen upon loading. During the loading process the wires undergo a martensitic phase transformation, bridging the crack. To heal the composite, simple heating is required which reverse transforms the wires and brings the crack faces back into contact. When using pre-strained SMA wires for reinforcement, the reverse transformation of the wires during heating causes a closure force across the crack. The method to simulate cracking and “healing” behaviors of the composite allow assessment of the effects of component properties and composite geometry. The results shed light on design of self-healing composites using shape memory alloys.
Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria

Approximately 70% of the initial ferriprotoporphyrin IX polymerizing activity in cell-free preparations of erythrocytes infected with Plasmodium berghei was recovered in a chloroform extract. No polymerizing activity remained in the residue. In studies to identify substances that promote FP polymerization, arachidonic, linoleic, oleic, and palmitoleic acids, 1-mono- and di-oleoylglycerol, and the detergents, SDS, Tween 80, and n-octyl-glucopyranoside, were active. Tri-oleoylglycerol, cholesterol, di-oleoylphosphatidylethanolamine, and stearic and palmitic acids were inactive. The model lipid, mono-oleoylglycerol (250 nmol), co-precipitated with FP from a 0.09 M acetate medium at pH 5 and promoted the polymerization of 215 nmol (61%) of the ferriprotoporphyrin IX in the precipitate during a 24-h incubation at 37 degrees C. Polymerization was maximal at pH 5, it was approximately linear for 2 h, and it continued at a decreasing rate for 24 h. The polymer contained exclusively ferriprotoporphyrin IX (97+/-1.3%, mean+/-S.E., n=4) and exhibited the solubility and the electronic absorption and infrared spectral characteristics of the sequestered ferriprotoporphyrin IX of hemozoin. Detergents presumably promote polymerization in an acid medium by helping to dissolve monomeric FP. We suggest that unsaturated lipids co-precipitate with FP in the parasite's acidic food vacuole and also dissolve sufficient monomeric FP to allow polymerization.
Some recent studies of random noise between metals and dielectrics

The purpose of these studies was to investigate the source of noise which is generated when thin dielectrics are subjected to relatively low D.C. voltages(1,2). If the measured noise voltage is caused by the movement of ions or electrons in the volume of the dielectric between electrodes as shown by Haworth and Bozorth(3), then a semi-quantitative measurement of this noise might be a means whereby prebreakdown avalanches could be studied.
A note on binary template matching

Abstract This paper considers some generalizations of binary template matching procedures which enable one to weight matches according to both statistical and spatial information.
Analyses of 5' regulatory region polymorphisms in human SLC22A6 (OAT1) and SLC22A8 (OAT3).

Kidney excretion of numerous organic anionic drugs and endogenous metabolites is carried out by a family of multispecific organic anion transporters (OATs). Two closely related transporters, SLC22A6, initially identified by us as NKT and also known as OAT1, and SLC22A8, also known as OAT3 and ROCT, are thought to mediate the initial steps in the transport of organic anionic drugs between the blood and proximal tubule cells of the kidney. Coding region polymorphisms in these genes are infrequent and pairing of these genes in the genome suggests they may be coordinately regulated. Hence, 5′ regulatory regions of these genes may be important factors in human variation in organic anionic drug handling. We have analyzed novel single nucleotide polymorphisms in the evolutionarily conserved 5′ regulatory regions of the SLC22A6 and SLC22A8 genes (phylogenetic footprints) in an ethnically diverse sample of 96 individuals (192 haploid genomes). Only one polymorphism was found in the SLC22A6 5′ regulatory region. In contrast, seven polymorphisms were found in the SLC22A8 5′ regulatory region, two of which were common to all ethnic groups studied. Computational analysis permitted phase and haplotype reconstruction. Proximity of these non-coding polymorphisms to transcriptional regulatory elements (including potential sex steroid response elements) suggests a potential influence on the level of transcription of the SLC22A6 and/or SLC22A8 genes and will help define their role in variation in human drug, metabolite and toxin excretion. The clustering of OAT genes in the genome raises the possibility that nucleotide polymorphisms in SLC22A6 could also effect SLC22A8 expression, and vice versa.
Structure determination of the platinum (111) crystal face by low-energy-electron diffraction

An analysis of low-energy-electron-diffraction intensity profiles from the clean (111) face of platinum is carried out. Calculated intensities are compared with experimental results for specular and nonspecular beams at several angles of incidence for electron energies \ensuremath{\le}100 eV. The calculations are based on a $T$-matrix multiple-scattering theory with corrections for lattice vibrations. The scattering from a single atomic site is modeled with a conventional band-structure potential parametrized by six partial-wave phase shifts. The constant inner potential ${V}_{0}$ determined from addition of the Fermi energy and a measured value of the work function is found to predict the peak positions accurately. The calculations adequately describe the shapes and relative intensities of primary and secondary features in the experimental intensity profiles. Analysis of the data indicates that the spacing of the topmost atomic layer is the same as the bulk value to within 5% (or approximately 0.1 \AA{}).
Medium access control protocol design for sensors powered by wireless energy transfer

Wireless transfer of energy will help realize perennially operating sensors, where dedicated transmitters replenish the residual node battery level through directed radio frequency (RF) waves. However, as this radiative transfer is in-band, it directly impacts data communication in the network, requiring a fresh perspective on medium access control (MAC) protocol design for appropriately sharing the channel for these two critical functions. Through an experimental study, we first demonstrate how the placement, the chosen frequency, and number of the RF energy transmitters affect the sensor charging time. These studies are then used to design a MAC protocol called RFMAC that optimizes energy delivery to desirous sensor nodes on request. To the best of our knowledge, this is the first distributed MAC protocol for RF energy harvesting sensors, and through a combination of experimentation and simulation studies, we demonstrate 112% average network throughput improvement over the modified unslotted CSMA MAC protocol.
Manometric study of the voluntary inhibition action in normal volunteers

PURPOSE: A voluntary inhibition action whereby a voluntary squeeze of the external sphincter causes reflex relaxation of the rectum has been previously proposed but not proven. Such a reflex would enable the subject to defer defecation to a socially acceptable time. The purpose of this study was to determine whether or not such a reflex exists. METHODS: We measured rectal compliance with and without a voluntary squeeze using a specially designed balloon catheter in nine subjects. RESULTS: When corrected for increased intra-abdominal pressure caused by inadvertent Valsalva's maneuver during voluntary squeezing, there was a significant increase in rectal compliance during voluntary contraction of the external sphincter (P<0.01). CONCLUSION: This lends support to the proposed existence of the voluntary inhibition action.
SMADs and YAP Compete to Control Elongation of β-Catenin:LEF-1-Recruited RNAPII during hESC Differentiation

The Wnt3a/β-catenin and Activin/SMAD2,3 signaling pathways synergize to induce endodermal differentiation of human embryonic stem cells; however, the underlying mechanism is not well understood. Using ChIP-seq and GRO-seq analyses, we show here that Wnt3a-induced β-catenin:LEF-1 enhancers recruit cohesin to direct enhancer-promoter looping and activate mesendodermal (ME) lineage genes. Moreover, we find that LEF-1 and other hESC enhancers recruit RNAPII complexes (eRNAPII) that are highly phosphorylated at Ser5, but not Ser7. Wnt3a signaling further increases Ser5P-RNAPII at LEF-1 sites and ME gene promoters, indicating that elongation remains limiting. However, subsequent Activin/SMAD2,3 signaling selectively increases transcription elongation, P-TEFb occupancy, and Ser7P-RNAPII levels at these genes. Finally, we show that the Hippo regulator, YAP, functions with TEAD to regulate binding of the NELF negative elongation factor and block SMAD2,3 induction of ME genes. Thus, the Wnt3a/β-catenin and Activin/SMAD2,3 pathways act in concert to counteract YAP repression and upregulate ME genes during early hESC differentiation.
Stuxnet: What Has Changed?

This paper considers the impact of Stuxnet on cyber-attacks and cyber-defense. It first reviews trends in cyber-weapons and how Stuxnet fits into these trends. Because Stuxnet targeted an industrial control system in order to wreak physical damage, the focus is on weapons that target systems of that type and produce physical effects. The paper then examines the impact of Stuxnet on various domains of action where cyber-attacks play a role, including state-level conflict, terrorism, activism, crime, and pranks. For each domain, it considers the potential for new types of cyber-attacks, especially attacks against industrial control systems, and whether such attacks would be consistent with other trends in the domain. Finally, the paper considers the impact of Stuxnet on cyber-defense.
Retrospective future perfect: history, black holes and time warps in the films of Los Hijos and Luis López Carrasco

This article analyzes the “imperfect” cinema of the Madrid-based filmmaking collective Los Hijos and the individual work of one of their members, Luis Lopez Carrasco. Focusing primarily on disrupted and disruptive temporalities, it argues that filmic materiality and its evolution are key factors in the political critique to which these pieces point. Drawing upon the work of Jacques Derrida and J. Hillis Miller on aporia, the essay maintains that Los Hijos’ films (Los materiales [2009] and Arboles [2013]) weave complex passages between the traditional conceptual binary of physis and technē and in doing so complicate temporal paradigms of legacy, heritage and generation. These films, moreover, precisely because of their filmic literacy and political awareness disturb not only the “natural” but also the “national” and its representation. The performative quality of their work, its futurity, is incompatible with claims to national allegory. In the same vein, the question of collective filmmaking and the indiv...
Comments on s-rule violating configurations in field theory

Abstract We explicitly construct a configuration of N = 4 supersymmetry Yang–Mills theory with gauge group U ( N ) on an interval on length L with a D5-like boundary condition on one end and an NS5-like boundary condition on the other. For N > 1 , such a configuration violates the s -rule and is non-supersymmetric. We compute the energy relative to the BPS bound of these configurations and find that it is proportional to N ( N 2 − 1 ) g YM 4 − 2 L − 3 .
NMR investigations of allosteric processes in a two-domain Thermus thermophilus Hsp70 molecular chaperone.

Hsp70 chaperones are two-domain proteins that assist in intra-cellular protein (re) folding processes in all species. The protein folding activity of the substrate binding domain of the Hsp70s is regulated by nucleotide binding at the nucleotide-binding domain through an as yet undefined heterotropic allosteric mechanism. The available structures of the isolated domains of Hsp70s have given very limited indications of nucleotide-induced conformational changes that could modulate the affinity for substrate proteins. Here, we present a multi-dimensional NMR study of a prokaryotic Hsp70 homolog, Thermus thermophilus DnaK, using a 54 kDa construct containing both nucleotide binding domain and most of the substrate binding domain. It is determined that the nucleotide binding domain and substrate binding domain are closely associated in all ligand states studied. Comparison of the assigned NMR spectra of the two-domain construct with those of the previously studied isolated nucleotide binding domain, allowed the identification of the nucleotide binding domain-substrate binding domain interface. A global three-dimensional structure was obtained for the two-domain construct on the basis of this information and of NMR residual dipolar couplings measurements. This is the first experimental elucidation of the relative positioning of the nucleotide binding domain and substrate binding domain for any Hsp70 chaperone. Comparisons of NMR data between various ligand states including nucleotide-free, ATP, ADP.Pi and ADP.Pi+ peptide bound, identified residues involved in the allosteric inter-domain communication. In particular, peptide binding to the substrate binding domain was found to cause conformational changes in the NBD extending to the nucleotide binding pocket. Detailed analysis suggests that the inter-domain interface becomes tighter in the (nucleotide binding domain ligation/substrate binding domain ligation) order ATP/apo, ADP.Pi/apo ADP.Pi/peptide.
Expression of thrombopoietin and its receptor (c-mpl) in chronic myelogenous leukemia: Correlation with disease progression and response to therapy

BACKGROUND Chronic myelogenous leukemia (CML) represents a paradigm of the stepwise increment in disease aggressiveness, resistance to therapy, and transformation. Thrombopoietin (TPO) and its receptor, c-mpl, support the proliferation of multiple types of immature hematopoietic progenitor cells, and induce clonal growth of leukemic cells. The authors investigated whether TPO or c-mpl overexpression might correlate with progression of CML, disease aggressiveness, or response to therapy. METHODS Expression of c-mpl and TPO was measured in bone marrow samples from 208 patients with CML by Western blot analysis and solid-phase plate radioimmunoassay (used for quantification). Samples obtained from individuals without evidence of hematologic abnormalities were used as controls. RESULTS There were no significant differences in TPO or c-mpl expression among patients in different phases of CML or between patients with Philadelphia chromosome positive and negative CML. When TPO and c-mpl levels were analyzed in relation to prognostically important host and disease characteristics in early chronic phase CML, platelet and white blood cell counts demonstrated significant differences in both TPO and c-mpl expression, but age and spleen size demonstrated significant differences in TPO expression only. Responses to interferon (INF)-α-based therapy and survival were not influenced by TPO or c-mpl levels. CONCLUSIONS TPO or c-mpl overexpression did not correlate with different CML phases, suggesting that they were not involved in CML progression from early to advanced phase. Neither TPO nor c-mpl overexpression was particularly evident in any risk group, suggesting lack of correlation between their expression and disease aggressiveness. This was supported by the finding of similar response to IFN-α-based therapy and survival regardless of the level of TPO or c-mpl expression. Cancer 2000;88:570–6. © 2000 American Cancer Society.
Target detection and classification using a deformable template

Two common image processing problems are determining the location of an object using a template when the size and rotation of the true target are unknowns and classifying an object into one of a library of objects again using a template-based matching technique. When employing a maximum likelihood approach to these problems, complications occur due to local maxima on the likelihood surface. In previous work, we demonstrated a technique for object localization which employs a library of templates starting from the smooth approximation and adding detail until the exact template is reached. Successively estimating the geometric parameters (i.e. size and rotation) using these templates achieves the accuracy of the exact template while remaining within a well-behaved 'bowl' in the search space which allows standard maximization techniques to be used. In this work, we show how this technique can be extended to solve the classification problem using a multiple template library. We introduce a steering parameter which at every scale, allows us to compute a template as a linear combination of templates in the library. The algorithm begins the template matching using a smooth blob which is the smooth approximation common to all templates in the library. As the location and geometric parameter estimates are improved and detail is added, the smooth template is 'steered' towards the most likely template in the library and thus classification is achieved.
Cross-linked low molecular weight glycopeptide-mediated gene delivery: relationship between DNA metabolic stability and the level of transient gene expression in vivo.

DNA co-condensates were formed by reacting [125I]DNA with an admixture of a high-mannose glycopeptide (Man9-CWK(18)) and either of two poly(ethylene glycol) peptides (PEG-VS-CWK(18) or PEG-SS-CWK(18)) followed by cross-linking with 6-50 mol equiv of glutaraldehyde. [125I]DNA co-condensates were administered intravenously in mice to determine the influence of peptide DNA formulation parameters on specific targeting to Kupffer cells. Optimal targeting to Kupffer cells required the combined use of 50 mol % Man9-CWK(18) and PEG-CWK(18) to mediate specific recognition by the mannose receptor to Kupffer cells. The cellular uptake of cross-linked Man9-CWK(18)/PEG-CWK(18) DNA co-condensates was receptor mediated since Kupffer cell targeting was inhibited by pre-administration of Man-bovine serum albumin (BSA) but not BSA. An optimized formulation targeted 60% of the dose to the liver, with 80% of the liver-targeted DNA localized to Kupffer cells. Cross-linking with either 6, 15, or 50 mol equiv of glutaraldehyde led to a corresponding decrease in the metabolism rate of DNA in liver as measured by half-live- of 4, 6, and 39 h, respectively. Tail vein dosing of 50 microg of DNA co-condensates cross-linked with 6 mol equiv of glutaraldehyde produced detectable levels of human alpha1-antitrypsin in blood after 12 h, which peaked at day six and persisted for 10 days. The level of human alpha1-antitrypsin was elevated two-fold each day when dosing with DNA co-condensates cross-linked with 15 mol equiv of glutaraldehyde, revealing a correlation between the metabolic stability of the DNA in liver and level of gene expression. In addition to possessing greater metabolic stability, DNA co-condensates cross-linked with 50 mol equiv of glutaraldehyde, but lacking a targeting ligand, avoided rapid liver uptake and possessed a prolonged pharmacokinetic half-life, providing insight into a means to target DNA condensates to peripheral tissues.
Genetics of the type I interferon pathway in systemic lupus erythematosus

Genetic studies of systemic lupus erythematosus (SLE) have been successful, identifying numerous risk factors for human disease. While the list is not yet complete, it is clear that important immune system pathways are represented, one of which being type I interferon (IFN). Circulating type I IFN levels are high in SLE patients and this IFN pathway activation is heritable in families with SLE. We summarize our current understanding of the genetics of the type I IFN pathway in SLE, with an emphasis on studies that demonstrate an impact of the SLE-risk alleles upon type I IFN pathway activation in SLE patients. These studies illustrate that variations in type I IFN pathway genes represent a common genetic feature of SLE. By understanding the genetic regulation of type I IFN, we may be able to intervene in a more personalized fashion, based upon the molecular dysregulation present in a given individual.
From Protest to Change of Regime: The 4–19 Revolt and The Fall of the Rhee Regime in South Korea

L'A. s'efforce de savoir dans quelles conditions sur le plan economique et social un mouvement social peut ebranler un regime politique. Il presente un certain nombre de donnees concernant la revolte du 19 avril 1960 en Coree du Sud qui a vu la chute du gouvernement dirige par Syngman Rhee. Il montre que la situation economique defavorable a exerce une influence considerable en ce domaine
Non-selective cation channels, transient receptor potential channels and ischemic stroke

Several pathways to neural cell death are involved in ischemic stroke, and all require monovalent or divalent cation influx, implicating non-selective cation (NC) channels. NC channels are also likely to be involved in the dysfunction of vascular endothelial cells that leads to formation of edema following cerebral ischemia. Two newly described NC channels have emerged as potential participants in ischemic stroke, the acid sensing ion channel (ASIC), and the sulfonylurea receptor-1 (SUR1)-regulated NC(Ca-ATP) channel. Non-specific blockers of NC channels, including pinokalant (LOE 908 MS) and rimonabant (SR141716A), have beneficial effects in rodent models of ischemic stroke. Evidence is accumulating that NC channels formed by members of the transient receptor potential (TRP) family are also up-regulated in ischemic stroke and may play a direct role in calcium-mediated neuronal death. The nascent field of NC channels, including TRP channels, in ischemic stroke is poised to provide novel mechanistic insights and therapeutic strategies for this often devastating human condition.
Diagnosis and Treatment of Myocarditis in Children in the Current Era

Myocarditis has been defined by the World Health Organization/International Society and Federation of Cardiology as an inflammatory disease of the heart muscle diagnosed by established histological, immunologic, and immunohistological criteria.1 Insights into its clinical manifestation and treatment in both adults2–7 and children8–12 have been the subject of a number of recent reviews. It is caused primarily by numerous infectious agents, but it may also accompany autoimmune disease, hypersensitivity reactions, and toxins (Table 1). In North America and developed countries, it primarily has a viral origin. In Central and South America, Trypanosoma cruzi (Chagas disease) is a common cause. Diphtheria often causes myocarditis in countries without widespread immunization.13 Although enteroviruses have classically been identified as the prime viral agent, new techniques to extract viral genome from myocardium with polymerase chain reaction techniques have in both children and adults revealed previously unrecognized viruses such as adenovirus, parvovirus B19, human herpesvirus 6, hepatitis C, Epstein-Barr virus, and cytomegalovirus.2,3,14–19 Interestingly, the pattern of identified viral pathogens in myocarditis has evolved over the last 20 years from enteroviruses and adenoviruses to primarily parvovirus and herpesvirus 6. Endomyocardial fibroelastosis, a once frequent cause of infantile dilated cardiomyopathy that is now rarely seen, was linked to the mumps virus via viral polymerase chain reaction analysis of archived pathological sample, suggesting that its reduced prevalence might be attributed to immunization.20 View this table: Table 1. Various Causes of Myocarditis3,5 In a somewhat confusing fashion, the American Heart Association’s contemporary definitions of cardiomyopathies classify myocarditis as an inflammatory cardiomyopathy but also lists the same infectious causes of dilated cardiomyopathy as those found with myocarditis.21 This conundrum typifies myocarditis. Its myriad presentations range from minimal symptoms to severe heart failure and sudden death. It is commonly associated …
The 90,92Zrd(p,p′) reactions at Ep = 800 MeV+

Abstract Angular distributions of analyzing powers and differential cross sections have been measured for elastic and inelastic scattering of 800 MeV protons from 90 Zr and 92 Zr. The data have been interpreted using both the collective-model distorted-wave Born approximation and the semimicroscopic distorted-wave impulse approximation with the Love and Franey t -matrix. Clear differences in the data for transitions to both the 2 + 1 and the 4 + states in the two nuclei, attributable to differences in the microscopic structures of the states, have been observed. These differences are only partially explained by the semimicroscopic analyses. Interpreting the A y data with the help of recent data-to-data relations suggests that the free L · S interaction used at 800 MeV is incorrect.
Venous Thromboembolism: A Need for More Public Awareness and Research Into Mechanisms

Articles in this Series: Heit J. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol. 2008;28:370-372. Moll S. A clinical perspective of venous thromboemobolism. Arterioscler Thromb Vasc Biol. 2008;28:373-379. Gross P and Weitz J. New anticoagulants for treatment of venous thromboemobolism. Arterioscler Thromb Vasc Biol. 2008;28:380-386. Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol. 2008;28:387-391. Link RP. National heart, lung, and blood institute programs for deep vein thrombosis. Arterioscler Thromb Vasc Biol. 2008;28:392-393. Beckman MG, Critchley SE, Hooper WC, Grant AM, Kulkarni R. CDC division of blood disorders: public health research activities in venous thromboembolism. Arterioscler Thromb Vasc Biol. 2008;28:394-395. Fenninger R. Patient advocacy to promote public awareness about thrombosis and thrombophilia. Arterioscler Thromb Vasc Biol. 2008;28:396-397. Hunt BJ. The awareness and politics of venous thromboembolism in the United Kingdom. Arterioscler Thromb Vasc Biol. 2008;28:398-399. In 2005, the US Senate declared March as deep vein thrombosis (DVT) awareness month in the United States to increase the American public’s understanding of deep vein thrombosis.1 This was triggered by the death of 39-yr-old David Bloom, a National Broadcasting Company (NBC) reporter who died on April 6, 2003 from a massive pulmonary embolism (PE), and the activities of his widow, Melanie Bloom.2 Two days before his death David Bloom had developed cramping leg pain that was not recognized as a DVT2—leg DVT was only found postmortem. He had several risk factors for DVT and PE (collectively called venous thromboembolism [VTE)]): (1) prolonged immobility (working and sleeping in a cramped position in a tank in the war in Iraq); (2) long distance flights between the US and Kuwait, (3) dehydration, and (4) postmortem the discovery that he was heterozygous for the prothrombotic variant of factor V called factor V …
Landscape and environmental controls over leaf and ecosystem carbon dioxide fluxes under woody plant expansion

Summary 1. Many regions of the globe are experiencing a simultaneous change in the dominant plant functional type and regional climatology. We explored how atmospheric temperature and precipitation control leaf- and ecosystem-scale carbon fluxes within a pair of semi-arid shrublands, one upland and one riparian, that have undergone woody plant expansion. 2. Through a combination of leaf-level measurements on individual bunchgrasses and mesquites shrubs and ecosystem-scale monitoring using eddy covariance techniques, we sought to quantify rates of net carbon dioxide (CO2) flux, CO2 flux temperature sensitivity and the responsiveness of these parameters to seasonal rains and periods of soil dry-down. 3. We found significant differences in physiological acclimation between the two plant functional types, in that the shrubs consistently conducted photosynthesis across a broader temperature range than co-occurring grasses during dry periods, yet maximum photosynthetic rates in grasses were twice that of mesquites during the wetter monsoon season. Landscape position modulated these temperature sensitivities, as the range of functional temperatures and maximum rates of photosynthesis were two to three times greater within the riparian shrubland in dry times. 4. Also, it was unexpected that ecosystem-scale CO2 uptake within both shrublands would become most temperature sensitive within the monsoon, when mesquites and grasses had their broadest range of function. This is probably explained by the changing contributions of component photosynthetic fluxes, in that the more temperature sensitive grasses, which had higher maximal rates of photosynthesis, became a larger component of the ecosystem flux. 5. Synthesis: Given projections of more variable precipitation and increased temperatures, it is important to understand differences in physiological activity between growth forms, as they are likely to drive patterns of ecosystem-scale CO2 flux. As access to stable subsurface water declines with decreased precipitation, these differential patterns of temperature sensitivity among growth forms, which are dependent on connectivity to groundwater, will only become more important in determining ecosystem carbon source/sink status.
Modeling pneumatic bubble displacements with membrane theory

We have fabricated a small array of pneumatically actuated bubbles intended as a tactile stimulator that can be worn on the fingertip. While device operation is quite promising, we notice that the perceptibility of stimuli is a strong function of how much force a user applies. We surmise that membrane deflection is affected not only by valve-controlled pressure but by finger-applied pressure as well. With the eventual aim of developing an analytical model of membrane deflection as a function of multiple types of load, applied from both sides of the membrane and including varying contact area between membrane substrate and skin, we are developing expanded membrane equilibrium equations. In this paper, we present equilibrium equations suitable for obtaining the displacement of a thin, circular membrane of polydimethylsiloxane (PDMS) subjected to a uniform pressure on one side. A comparison of numerical solutions to an analytic solution available for linearized equations confirms operation of the numerical solver and singularity handling. Initial results from measurements made under an inverted microscope are also presented and compared to theory.