Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of Mcl-1·Bim Complex in Granzyme B-mediated Mitochondrial Apoptosis*

Recently, we reported the identification of a novel mitochondrial apoptotic pathway for granzyme B (GrB) (Han, J., Goldstein, L. A., Gastman, B. R., Froelich, C. J., Yin, X. M., and Rabinowich, H. (2004) J. Biol. Chem. 279, 22020–22029). The newly identified GrB-mediated mitochondrial cascade was initiated by the cleavage and subsequent degradation of Mcl-1, resulting in the release of mitochondrial Bim from Mcl-1 sequestration. To investigate the biological significance of Mcl-1 cleavage by GrB, we mapped the major GrB cleavage sites and evaluated the apoptotic potential of the cleavage products. GrB cleaves Mcl-1 after aspartic acid residues 117, 127, and 157, generating C-terminal fragments that all contain BH-1, BH-2, BH-3, and transmembrane domains. These fragments accumulate at an early apoptotic phase but are eliminated by further degradation during the apoptotic process. The major Mcl-1 C-terminal fragment generated by GrB (residues 118–350) was unable to induce or enhance apoptosis when transfected into tumor cells. Instead, this Mcl-1 C-terminal fragment maintained a partial protective capability against GrB-mediated apoptosis via its lower affinity to Bim. In comparison with ectopically expressed full-length Mcl-1, the stably transfected C-terminal fragments of Mcl-1 were less efficiently localized to the mitochondria. Knockdown of Mcl-1, as achieved by transfection with Mcl-1-specific short interfering RNA, resulted in a significant level of apoptosis in the absence of external apoptotic stimulation and, in addition, enhanced the susceptibility of breast carcinoma cells to GrB cytotoxicity. The significance of Bim in this GrB apoptotic cascade was indicated by the marked protection against GrB-mediated apoptosis endowed on these cells through Bim knockdown. Our studies suggest that the disruption of the Mcl-1·Bim complex by GrB initiates a major Bim-mediated cellular cytotoxic mechanism that requires the elimination of Mcl-1 following its initial cleavage.
Racial disparities in preterm births. The role of urogenital infections.

OBJECTIVES To evaluate the impact of urogenital infections on the racial gap between black and white women in preterm birth rates. METHODS A computer-assisted search of the medical literature was conducted through MEDLINE aided by a manual bibliographic search of published articles and relevant books. Estimates of the relative risk for preterm birth were extracted from published studies for the following infections: N. gonorrhea, syphilis, trichomoniasis, Chlamydia trachomatis, Group B streptococcal vaginal colonization, asymptomatic bacteriuria, genital mycoplasmas, and bacterial vaginosis. Estimates of the prevalence among black and white women by race for each of these infections were extracted from published studies. The attributable risk for preterm birth for selected infections was then calculated for the black and white populations and the impact on the racial gap in preterm births was estimated. RESULTS Only bacterial vaginosis and bacteriuria appear to be established risk factors for preterm births. Significantly higher rates of bacterial vaginosis among black women may account for nearly 30% of the racial gap in preterm births. Higher rates of bacteriuria among black women may account for roughly 5% of the gap. CONCLUSION Although these findings are limited by the reliability of published estimates of prevalence and relative risk for these infections, treatment of infections during pregnancy, particularly bacterial vaginosis, offers hope for reducing the racial gap in preterm births.
Magnetic monopoles, duality and supersymmetry

These notes present a pedagogical introduction to magnetic monopoles and exact electromagnetic duality in supersymmetric gauge theories. They are based on lectures given at the 1995 Trieste Summer School in High Energy Physics and Cosmology and at the 1995 Busstepp Summer School at Cosener's House.
High expression levels of receptor activator of nuclear factor-kappa B ligand associated with human chronic periodontitis are mainly secreted by CD4+ T lymphocytes.

BACKGROUND Chronic periodontitis is an infectious disease characterized by alveolar bone destruction and teeth loss. Receptor activator of nuclear factor-kappa B ligand (RANKL) is an osteoclastogenic cytokine, a central regulatory factor in the osteoclast's lifespan, and a participant in physiological and pathological bone resorption. Gingival T cells synthesize RANKL, contributing to molecular local imbalance that entails the alveolar bone resorption seen in periodontitis. Our study was aimed at associating the levels of RANKL with the CD4(+) T-cell activity present in gingival tissues of chronic periodontitis patients. METHODS Gingival biopsies were obtained from 33 chronic periodontitis patients and 20 healthy controls. Specimens were either formalin fixed and paraffin embedded for real-time reverse transcription-polymerase chain reaction (RT-PCR) and histologic analysis or tissue digestion processed for cell culture and flow-cytometry analysis. RANKL mRNA and protein levels were determined by quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) in gingival-cell culture supernatants. Gingival leukocytes were quantified by flow cytometry. RANKL and CD4 immunoreactivity were analyzed by flow cytometry and confocal microscopy. RESULTS RANKL mRNA levels were higher in patients with periodontitis than in healthy subjects, and spontaneous and lipopolysaccharide (LPS)- and phytohemagglutinin (PHA)-stimulated RANKL synthesis were higher also in patients than controls. CD4(+) T lymphocytes were the predominant infiltrate cell subset present in gingival tissues of periodontitis patients. Furthermore, an association between RANKL and CD4(+) T cells was determined by double-staining flow cytometry and confocal microscopy. CONCLUSION Taken together, these data demonstrate that gingival CD4(+) T cells are the main cells responsible for higher levels of RANKL observed in human chronic periodontitis patients.
Decentralized Adaptive Control: Structural Conditions for Stability

Decentralized adaptive control schemes are presented for a class of large scale interconnected systems. These schemes have the advantage that in addition to the standard assumption about the uncertainty of the subsystems, the strength of interconnections is assumed unknown. Provided certain structural constraints are satisfied, the adaptation gains automatically adjust to levels that assure stability of the overall system.
Repeated Activation of a CS-US-Contingency Memory Results in Sustained Conditioned Responding

Individuals seem to differ in conditionability, i.e., the ease by which the contingent presentation of two stimuli will lead to a conditioned response. In contemporary learning theory, individual differences in the etiology and maintenance of anxiety disorders are, among others, explained by individual differences in temperamental variables (Mineka and Zinbarg, 2006). One such individual difference variable is how people process a learning experience when the conditioning stimuli are no longer present. Repeatedly thinking about the conditioning experience, as in worry or rumination, might prolong the initial (fear) reactions and as such, might leave certain individuals more vulnerable to developing an anxiety disorder. However, in human conditioning research, relatively little attention has been devoted to the processing of a memory trace after its initial acquisition, despite its potential influences on subsequent performance. Post-acquisition processing can be induced by mental reiteration of a conditioned stimulus-unconditioned stimulus (CS-US)-contingency. Using a human conditioned suppression paradigm, we investigated the effect of repeated activations of a CS-US-contingency memory on the level of conditioned responding at a later test. Results of three experiments showed more sustained responding to a “rehearsed” CS+ as compared to a “non-rehearsed” CS+. Moreover, the second experiment showed no effect of rehearsal when only the CS was rehearsed instead of the CS-US-contingency. The third experiment demonstrated that mental CS-US-rehearsal has the same effect regardless of whether it was cued by the CS and a verbal reference to the US or by a neutral signal, making the rehearsal “purely mental. ” In sum, it was demonstrated that post-acquisition activation of a CS-US-contingency memory can impact conditioned responding, underlining the importance of post-acquisition processes in conditioning. This might indicate that individuals who are more prone to mentally rehearse information condition more easily.
Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling

ABCG2 belongs to the ATP-binding cassette superfamily of transmembrane proteins and is ubiquitously expressed in stem cells including those in the developing nervous system. The ability of ABCG2 to preferentially exclude DNA-intercalating dyes is regarded to be the basis for the enrichment of stem cells or progenitors as dyelow side population (SP) cells. However, the role of ABCG2 in neural stem cells remains speculative and poorly understood. Here, we demonstrate using retinal stem cells, that ABCG2 is the molecular determinant of SP cell phenotype of neural stem cells and plays an important role in their maintenance. Overexpression of ABCG2 prevents the SP cell phenotype and adversely affects the lineage commitment of retinal stem cells. By contrast, targeted attenuation of ABCG2 depletes retinal SP cells and promotes their differentiation along pan neural and retinal lineages. In addition, we demonstrate for the first time that ABCG2 is a target of Notch signaling, and as such, constitutes one of the genes in the regulatory network of Notch signaling, involved in the maintenance of stem cells.
LONG RANGE ORDER AND GIANT COMPONENTS OF QUANTUM RANDOM GRAPHS

Mean field quantum random graphs give a natural generalization of classical Erdős-Rényi percolation model on complete graph GN with p = β/N . Quantum case incorporates an additional parameter λ > 0, and the short-long range order transition should be studied in the (β, λ)-quarter plane. In this work we explicitly compute the corresponding critical curve γc, and derive results on two-point functions and sizes of connected components in both short and long range order regions. In this way the classical case corresponds to the limiting point (βc, 0) = (1, 0) on γc.
Heterogenity in the Intergenerational Transmission of Educational Attainment: Evidence from Switzerland on Natives and Second

This study applies rich data from the 2000 Swiss census to investigate the patterns of intergenerational education transmission for natives and second generation immigrants. The level of secondary schooling attained by youth aged 17 is related to their parents' educational outcomes using data on the entire Swiss population. Based on economic theories of child educational attainment we derive hypotheses regarding the patterns in intergenerational education transmission. The data yields substantial heterogeneity in intergenerational transmission across population groups. Only a small share of this heterogeneity is explained by the predictions of economic theory.
Art-based rendering of fur, grass, and trees

Artists and illustrators can evoke the complexity of fur or vegetation with relatively few well-placed strokes. We present an algorithm that uses strokes to render 3D computer graphics scenes in a stylized manner suggesting the complexity of the scene without representing it explicitly. The basic algorithm is customizable to produce a range of effects including fur, grass and trees, as we demonstrate in this paper and accompanying video. The algorithm is implemented within a broader framework that supports procedural stroke-based textures on polyhedral models. It renders moderately complex scenes at multiple frames per second on current graphics workstations, and provides some interframe coherence. CR
The Sortase A Enzyme That Attaches Proteins to the Cell Wall of Bacillus anthracis Contains an Unusual Active Site Architecture*

The pathogen Bacillus anthracis uses the Sortase A (SrtA) enzyme to anchor proteins to its cell wall envelope during vegetative growth. To gain insight into the mechanism of protein attachment to the cell wall in B. anthracis we investigated the structure, backbone dynamics, and function of SrtA. The NMR structure of SrtA has been determined with a backbone coordinate precision of 0.40 ± 0.07 Å. SrtA possesses several novel features not previously observed in sortase enzymes including the presence of a structurally ordered amino terminus positioned within the active site and in contact with catalytically essential histidine residue (His126). We propose that this appendage, in combination with a unique flexible active site loop, mediates the recognition of lipid II, the second substrate to which proteins are attached during the anchoring reaction. pKa measurements indicate that His126 is uncharged at physiological pH compatible with the enzyme operating through a “reverse protonation” mechanism. Interestingly, NMR relaxation measurements and the results of a model building study suggest that SrtA recognizes the LPXTG sorting signal through a lock-in-key mechanism in contrast to the prototypical SrtA enzyme from Staphylococcus aureus.
Effects of progressive resistance exercise in akinetic-rigid Parkinson's disease patients: a randomized controlled trial.

BACKGROUND Progressive resistance exercise (PRE) can have a positive effect in individuals with Parkinson's disease (PD). However, the effect of PRE may vary with the clinical subtype of PD. To date, no study has assessed the effects of PRE in the different subtypes of PD. AIM The aim of the present study was to assess the effects of PRE in PD patients with akinesia and rigidity (AR-subtype). DESIGN A randomized controlled trial was conducted. SETTING Outpatients clinics of the Bierzo Parkinson Association (Ponferrada, Spain) and the Asturias Parkinson Association (Oviedo, Spain). POPULATION Twenty-eight patients with AR-subtype PD were randomized into an Experimental Group (EG, N.=13) and Control Group (CG, N.=15). METHODS Static posturography (Centre of Pressure -CoP- parameters), gait (the Ten-Meter Walk Test [TMWT]), freezing of gait (the Freezing of Gait Questionnaire [FOG-Q]), the motor portion of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and patient-perceived quality of life (the 39-item Parkinson's disease Questionnaire [PDQ39]), were assessed at pre-test, post-test, and re-test. Ratings of perceived exertion (RPE) (Borg >6-20 Scale) were recorded at the end of each PRE training session. RESULTS The EG displayed significant ameliorations in Length (CoP parameters) from pre- to post-test (P=0.048), in speed of fast rhythm walking (TMWT) from pre- to post-test (P=0.000), and from pre- to re-test (P=0.027), and in the PDQ39 Score from pre- to post-test (P=0.024). No significant differences were detected in Area or Speed (CoP parameters), speed of preferred rhythm walking (TMWT), FOG-Q scores, or the motor portion of the MDS-UPDRS scores. The EG reported a mean RPE of 9.95 (between "very light" and "fairly light") for the whole training program. CONCLUSIONS These findings provide support for the use of PRE training in the rehabilitation of individuals with AR-subtype PD, as it can improve static posturography, gait, and quality of life. Furthermore, RPE scores showed that individuals with AR-subtype PD consider that PRE training require only light efforts. CLINICAL REHABILITATION IMPACT The PRE training can be a helpful and fruitful rehabilitation tool for AR-subtype PD patients.
Strengthening Emotional Ties through Parent-Child-Dyad Art Therapy: Interventions with Infants and Preschoolers

Forewords, Lee Tidmarsh and Joyce Canfield. 1. Clinical issues in parent-child dyad art therapy. 2. The role of the parent as partners in child art therapy. 3. The sensory experience and internalization. 4. The art therapy attachment metaphor. 5. Symbols and metaphors in art making. 6. The role of the art therapist as facilitator. 7. Conclusion. Appendices. References. Index.
Cytogenetically invisible microdeletions involving PITX2 in Rieger syndrome

Axenfeld–Rieger syndrome (ARS) is a genetically heterogeneous autosomal dominant disorder mainly characterized by developmental defects of the anterior segment and extraocular anomalies. ARS shows great clinical variability and encompasses several conditions with overlapping phenotypes, including Rieger syndrome (RS). RS is characterized by developmental defects of the eyes, teeth and umbilicus, and the main causative gene is PITX2 (paired‐like homeodomain transcription factor 2, or RIEG1) at 4q25. PITX2 mutations show great variety, from point mutations to microscopic or submicroscopic deletions, and apparently balanced translocations in few cases. We identified cytogenetically undetectable submicroscopic deletions at 4q25 in two unrelated patients diagnosed with RS. One patient had a t(4;17)(q25;q22)dn translocation with a deletion at the 4q breakpoint, and the other patient had an interstitial deletion of 4q25. Both deletions included only the PITX2 and ENPEP (glutamyl aminopeptidase) genes.
Effects of Peanut Processing on Masticatory Performance during Variable Appetitive States

Background. Current evidence indicates that peanut consumption reduces cardiovascular disease risk, while posing little threat to positive energy balance. However, questions have been raised as to whether inter- and intraindividual variability in mastication in response to peanut form and processing properties may influence these health effects, since mastication has the potential to alter the bioaccessibility of nutrients within the nut matrix. Objective. To explore the relationship between peanut form and processing and masticatory function. Subjects/Methods. Thirty nine adults (16 M, 23 F; BMI: 30.4 ± 4.0 kg/m2; age: 27 ± 8 y) with healthy dentition chewed four different forms of peanuts until they would normally swallow and then expectorated the bolus. Surface electromyograms (EMGs) were obtained from the masseter and temporalis muscles during chewing of the four test foods. The maximum and mean bite forces, duration of chewing sequence, number of chews, and total muscle work for the complete chewing cycle were measured on the integrated EMG in fasted and sated states. Results. While no significant differences were noted in response to appetitive state, peanut form and processing had a significant influence on masticatory efficiency, as measured by proportional particle size distributions. The processed peanuts (honey roasted, roasted salted, and roasted unsalted) were chewed significantly fewer times compared to the unprocessed form (raw). Further, the proportional particle sizes within the swallowing bolus were significantly larger for the processed forms compared to the unprocessed form. Conclusion. These observations may have implications for bioaccessibility of energy and cardioprotective nutrients as well as endocrine responses, following peanut consumption.
Dynamic fault-tolerant clock synchronization

This paper gives two simple efficient distributed algorithms: one for keeping clocks in a network synchronized and one for allowing new processors to join the network with their clocks synchronized. Assuming a fault-tolerant authentication protocol, the algorithms tolerate both link and processor failures of any type. The algorithm for maintaining synchronization works for arbitrary networks (rather than just completely connected networks) and tolerates any number of processor or communication link faults as long as the correct processors remain connected by fault-free paths. It thus represents an improvement over other clock synchronization algorithms such as those of Lamport and Melliar Smith and Welch and Lynch, although, unlike them, it does require an authentication protocol to handle Byzantine faults. Our algorithm for allowing new processors to join requires that more than half the processors be correct, a requirement that is provably necessary.
Living in sin: Cohabiting as husband and wife in nineteenth-century England

Acknowledgements Introduction 1. Cohabitation, illegitimacy, and the law in England, 1750-1914 2. Violence and cohabitation in the courts 3. Affinity and consanguinity 4. Bigamy and cohabitation 5. Adulterous cohabitation 6. The 'other Victorians': the demimonde and the very poor 7. Cross-class cohabitation 8. Radical couples, 1790-1850 9. Radical couples, 1850-1914 Conclusion Bibliography Index
Low-power asynchronous Viterbi decoder for wireless applications

This paper describes the implementation of an asynchronous 64-state, 1/2-rate Viterbi decoder using an original architecture and design methodology. The decoder is intended for wireless communications applications, where bit rates over 100 Mb/s and minimum power consumption are sought. The choice of an asynchronous design was predicated by the power and speed advantages of such a methodology. Asynchronous designs are inherently data driven and are active only when doing useful work, enabling considerable savings in power and operating at the average speed of all components. The decoder, implemented in a 0.18 /spl mu/m CMOS technology, occupies an area of 2 mm/sup 2/ and operates above 200 Mb/s while consuming 85 mW: a 55% power reduction when compared to state of the art synchronous design implemented in a 0.25 /spl mu/m technology.
A theoretical analysis of cellulase product inhibition: Effect of cellulase binding constant, enzyme/substrate ratio, and β‐glucosidase activity on the inhibition pattern

Theoretical analysis of cellulase product inhibition (by cellobiose and glucose) has been performed in terms of the mathematical model for enzymatic cellulose hydrolysis. The analysis showed that even in those cases when consideration of multienzyme cellulase system as one enzyme (cellulase) or two enzymes (cellulase and β‐glucosidase) is valid, double‐reciprocal plots, usually used in a product inhibition study, may be nonlinear, and different inhibition patterns (noncompetitive, competitive, or mixed type) may be observed. Inhibition pattern depends on the cellulase binding constant, enzyme concentration, maximum adsorption of the enzyme (cellulose surface area accessible to the enzyme), the range in which substrate concentration is varied, and β‐glucosidase activity. A limitation of cellulase adsorption by cellulose surface area that may occur at high enzyme/substrate ratio is the main reason for nonlinearity of double‐reciprocal plots. Also, the results of calculations showed that material balance by substrate, which is usually neglected by researchers studying cellulase product inhibition, must be taken into account in kinetic analysis even in those cases when the enzyme concentration is rather low. © 1992 John Wiley & Sons, Inc.