Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic and Therapeutic Potential of Amyloid-Reactive IgG Antibodies Contained in Human Sera1

Passive immunotherapy using fibril-reactive mAbs has been shown experimentally to reduce amyloid formation and also accelerate amyloidolysis. We now report that human sera, as well as various sources of pooled human IgG, including pharmacologic formulations of immune globulin i.v. (IGIV), contain Abs that specifically recognize fibrils formed from light chains and other amyloidogenic precursor proteins, including serum amyloid A, transthyretin, islet amyloid polypeptide, and amyloid β 1–40 peptide, but notably, do not react with these molecules in their native nonfibrillar forms. After isolation of the Abs from IGIV via fibril-conjugated affinity column chromatography, the EC50-binding value for light chains and amyloid β 1–40 peptide fibrils was ∼15 nM–a magnitude ∼200 and 70 times less than that of the unbound fraction and unfractionated product, respectively. Comparable reactivity was found in the case of those formed from serum amyloid A, transthyretin, and islet amyloid polypeptide. The purified Abs immunostained human amyloid tissue deposits and could inhibit fibrillogenesis, as shown in fibril formation and extension assays. Most importantly, in vivo reactivity was evidenced in a murine model when the enriched Abs were used to image amyloid, as well as expedite its removal. These promising experimental results suggest that fibril affinity-purified IGIV has potential as a diagnostic and therapeutic agent for patients with amyloid-associated disease.
Load recovery in demand response scheduling

Load recovery is a major problem in scheduling demand response (DR) in a power system where they significantly increase the cost of electricity supply during off-peak periods. This paper analyses such intertemporal recovery effects on each customer and each involved stakeholder, using a novel financial valuation method termed `securitization'. Based on this local analysis, a global market clearing system is designed with the aim of maximizing a total market surplus, derived from the recovery-based DR, for all customers and stakeholders. The proposed DR scheduling approach via the securitization and market clearing is tested and its efficiency reported. Its potential applications as part of the future smart grid is also discussed.
Experimental observation of noise-induced synchronization of bursting dynamical systems

Can bursts in dynamical systems be synchronized by a weak, common, noise background? We observe large, uncorrelated bursts of intensity fluctuations in two almost identical erbium-doped fiber ring lasers, initiated by common injection of a weak, constant intensity optical signal. Significant synchronization of the bursts is obtained for noise and sinusoidal modulation of the injected light intensity. Measurements of the burst statistics and synchronization are presented.
Positive Illusions in Marital Relationships: A 13-Year Longitudinal Study

This study examined the long-term consequences of idealization in marriage, using both daily diary and questionnaire data collected from a sample of 168 newlywed couples who participated in a 4-wave, 13-year longitudinal study of marriage. Idealization was operationalized as the tendency for people to perceive their partner as more agreeable than would be expected based on their reports of their partner's agreeable and disagreeable behaviors. Spouses who idealized one another were more in love with each other as newlyweds. Longitudinal analyses suggested that spouses were less likely to suffer declines in love when they idealized one another as newlyweds. Newlywed levels of idealization did not predict divorce.
Who You Know versus What You Know: The Uses of Government Experience for Washington Lobbyists

Private interest representatives in Washington are often said to exploit prior experience with the federal government, especially their contacts with officials, to gain advantage for their client groups. Data on 776 interest representatives are examined to estimate the frequency and institutional location of prior governmental experience. Just over half of the respondents had had some such service; twice as many in the executive branch as in the milieu of Capitol Hill. For those with experience, the extent and character of its advantages for their work as lobbyists are assessed. In general, representatives assign greater value to the knowledge gained of both substantive policy and decision-making processes than to contacts with officials or other lobbyists.
Functional Role of Residues Corresponding to Helical Domain II (Amino Acids 35 to 46) of Human Immunodeficiency Virus Type 1 Vpr

ABSTRACT Vpr, encoded by the human immunodeficiency virus type 1 genome, contains 96 amino acids and is a multifunctional protein with features which include cell cycle arrest at G2, nuclear localization, participation in transport of the preintegration complex, cation channel activity, oligomerization, and interaction with cellular proteins, in addition to its incorporation into the virus particles. Recently, structural studies based on nuclear magnetic resonance and circular dichroism spectroscopy showed that Vpr contains a helix (HI)-turn-helix (HII) core at the amino terminus and an amphipathic helix (HIII) in the middle region. Though the importance of helical domains HI and HIII has been defined with respect to Vpr functions, the role of helical domain HII is not known. To address this issue, we constructed a series of mutants in which the HII domain was altered by deletion, insertion, and/or substitution mutagenesis. To enable the detection of Vpr, the sequence corresponding to the Flag epitope (DYKDDDDK) was added, in frame, to the Vpr coding sequences. Mutants, expressed through the in vitro transcription/translation system and in cells, showed an altered migration corresponding to deletions in Vpr. Substitution mutational analysis of residues in HII showed reduced stability for VprW38S-FL, VprL42G-FL, and VprH45W-FL. An assay involving cotransfection of NLΔVpr proviral DNA and a Vpr expression plasmid was employed to analyze the virion incorporation property of Vpr. Mutant Vpr containing deletions and specific substitutions (VprW38S-FL, VprL39G-FL, VprL42G-FL, VprG43P-FL, and VprI46G-FL) exhibited a negative virion incorporation phenotype. Further, mutant Vpr-FL containing deletions also failed to associate with wild-type Vpr, indicating a possible defect in the oligomerization feature of Vpr. Subcellular localization studies indicated that mutants VprΔ35-50-H-FL, VprR36W-FL, VprL39G-FL, and VprI46G-FL exhibited both cytoplasmic and nuclear localization, unlike other mutants and control Vpr-FL. While wild-type Vpr registered cell cycle arrest at G2, mutant Vpr showed an intermediary effect with the exception of VprΔ35-50 and VprΔ35-50-H. These results suggest that residues in the HII domain are essential for Vpr functions.
The effect of water fluoridation and social inequalities on dental caries in 5-year-old children.

BACKGROUND Many studies have shown that water fluoridation dramatically reduces dental caries, but the effect that water fluoridation has upon reducing dental health inequalities is less clear. The aim of this study is to describe the effect that water fluoridation has upon the association between material deprivation and dental caries experience in 5-year-old children. METHODS It is an ecological descriptive study of dental caries experience using previously obtained data from the British Association for the Study of Community Dentistry's biennial surveys of 5-year-old children. This study examined the following data from seven fluoridated districts and seven comparable non-fluoridated districts in England: 1) dental caries experience using the dmft (decayed, missing, filled teeth) index; 2) the Townsend Deprivation Index of the electoral ward in which the child lived; 3) whether fluoride was present at an optimal concentration in the drinking water or not. RESULTS A statistically significant interaction was observed between material deprivation (measured by the Townsend Deprivation Index) and water fluoridation (P < 0.001). This means that the social class gradient between material deprivation and dental caries experience is much flatter in fluoridated areas. CONCLUSION Water fluoridation reduces dental caries experience more in materially deprived wards than in affluent wards and the introduction of water fluoridation would substantially reduce inequalities in dental health.
Correlation of p53 and KI-67 expression with grade and subtype of ependymoma.

INTRODUCTION The morphological criteria for grading ependymomas were always felt subjective. Recently some studies have showed that Ki-67 and p53 immunolabeling are important prognostic markers in ependymomas. MATERIALS AND METHODS All the cases of ependymomas diagnosed from 2005 to 2010 were graded according to WHO classification for central nervous system (CNS) tumors 2007. Two tissue microarray (TMA) blocks were prepared. Immunohistochemical analysis with glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), Ki-67 and p53 was performed. The difference in expression of p53 and Ki-67 in various tumor grades and subtypes was evaluated using Student's t test. RESULTS There were 54 cases with a M: F ratio of 1.34 : 1, age ranging from 7 years to 65 years (mean 29.35 years). There were 33 intracranial and 21 spinal cases. There were 9 grade I ependymomas, 32 grade II ependymomas and 13 grade III ependymomas. GFAP immunopositivity was seen in all the cases and EMA was positive in 49% cases. The mean p53 indices were higher in grade III and grade II tumors (26.26% and 26.08%) as compared to subependymomas (7.25%). But these values did not show statistical significance (P = 0.2). The Ki-67 labeling index increased from grade I to grade III tumors. The difference was highly significant between grade II and grade III (0.5% vs. 2.75, P = 0.016). CONCLUSION Ki-67 labeling index correlates with grade of ependymoma (P = 0.016). There is no correlation between p53 expression and grade of ependymomas.
Ciliary Neurotrophic Factor Is Required for Motoneuron Sprouting

We used mutant mice that lack the gene for ciliary neurotrophic factor (CNTF) to test the hypothesis that it is an endogenous sprouting factor. Fibers in the lateral gastrocnemius muscle were either partially denervated by transection of one of the branches of its nerve or paralyzed by intramuscular injection of botulinum toxin. This results in a significant sprouting response at the terminals of intact motoneurons in normal animals. We did not detect sprouting produced by either stimulus in mice lacking CNTF. When exogenous CNTF was administered to CNTF knockout mice following partial muscle denervation, they mounted a typical sprouting response. Thus CNTF is a critical factor in the process of sprout formation after both partial denervation injury and neuromuscular paralysis. It may function as part of a cellular compensatory mechanism after neuronal injury.
Automatic differentiation of melanoma from melanocytic nevi with multispectral digital dermoscopy: a feasibility study.

BACKGROUND Differentiation of melanoma from melanocytic nevi is difficult even for skin cancer specialists. This motivates interest in computer-assisted analysis of lesion images. OBJECTIVE Our purpose was to offer fully automatic differentiation of melanoma from dysplastic and other melanocytic nevi through multispectral digital dermoscopy. METHOD At 4 clinical centers, images were taken of pigmented lesions suspected of being melanoma before biopsy. Ten gray-level (MelaFind) images of each lesion were acquired, each in a different portion of the visible and near-infrared spectrum. The images of 63 melanomas (33 invasive, 30 in situ) and 183 melanocytic nevi (of which 111 were dysplastic) were processed automatically through a computer expert system to separate melanomas from nevi. The expert system used either a linear or a nonlinear classifier. The "gold standard" for training and testing these classifiers was concordant diagnosis by two dermatopathologists. RESULTS On resubstitution, 100% sensitivity was achieved at 85% specificity with a 13-parameter linear classifier and 100%/73% with a 12-parameter nonlinear classifier. Under leave-one-out cross-validation, the linear classifier gave 100%/84% (sensitivity/specificity), whereas the nonlinear classifier gave 95%/68%. Infrared image features were significant, as were features based on wavelet analysis. CONCLUSION Automatic differentiation of invasive and in situ melanomas from melanocytic nevi is feasible, through multispectral digital dermoscopy.
Lessons That Last: LeaderShape-Related Gains in Student Leadership Capacity over Time.

The LeaderShape Institute is a popular immersion-based leadership program that is hosted on dozens of university campuses and conducted nationally each year. As part of a comprehensive research effort, a sample of 1,279 students at 21 participating institutions completed a pre-test prior to participating, as well as a post-test immediately after and a followup test three to four months later. Tests included measures of leadership skills, leadershiporiented self-efficacy, motivation to lead, and motivation to advocate for social issues. Results suggest students make gains in skill, confidence, and motivation to advocate for social issues, but that not all gains emerged similarly across social identity groups. Several differences emerged when comparing gains measured from pre-test to post-test and gains that included follow-up tests. This study provides support for the effectiveness of the LeaderShape Institute, and possesses several implications for the methods used in assessing the development of leadership capacity.
Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome

MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1&bgr; was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1&bgr; or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3′ untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1&bgr; release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation.
Temporary Relocation of the Testes in Anteromedial Thigh Pouches Facilitates Delayed Primary Scrotal Wound Closure in Fournier Gangrene With Extensive Loss of Scrotal Skin—Experience With 12 Cases

Aims and ObjectivesTo share our experience on the use of temporary testicular thigh pouches to facilitate scrotal wound closure in Fournier gangrene with extensive loss of scrotal skin. Patients and MethodsPatients seen over a 10-year period who had extensive (>50%) loss of scrotal skin precluding delayed primary closure of the residual scrotal skin over the testes were documented. Patients had serial debridement as required with scrotal wound dressing until healthy granulation tissue was achieved. The testes were placed temporarily in anteromedial thigh pouches to allow for scrotal wound closure. In the postoperative period, the testes were gradually massaged back into the residual scrotal pouch, thus acting as natural tissue expanders. ResultsMean patient age was 38.1 ± 10.0 years. Mean duration of admission was 24.4 ± 4.7 days. Identified predisposing factors were ischiorectal fossa abscess in 2 patients and urethral stricture in 1 patient. The rest were idiopathic. Mean Fournier gangrene severity index was 6.0 ± 1.3. Mean number of debridements was 2.3 ± 0.5. There was no mortality. The residual scrotal pouches expanded sufficiently over time (3–8 months) to accommodate the testes. Normal testicular volume was maintained in all patients. Mean testicular volume was 19.0 ± 3.2 cm3. Follow-up was for 14.8 ± 9.7 months. ConclusionsTemporarily relocating the testes in anteromedial thigh pouches facilitates scrotal wound closure in Fournier gangrene with extensive loss of scrotal skin and obviates the need for specialized reconstructive surgery.
Possible involvement of CD81 in acrosome reaction of sperm in mice

Tetraspanin CD81 is closely homologous in amino acid sequence with CD9. CD9 is well known to be involved in sperm–egg fusion, and CD81 has also been reported to be involved in membrane fusion events. However, the function of CD81 as well as that of CD9 in membrane fusion remains unclear. Here, we report that disruption of the mouse CD81 gene led to a reduction in the fecundity of female mice, and CD81−/− eggs had impaired ability to fuse with sperm. Furthermore, we demonstrated that when CD81−/− eggs were incubated with sperm, some of the sperm that penetrated into the perivitelline space of CD81−/− eggs had not yet undergone the acrosome reaction, indicating that the impaired fusibility of CD81−/− eggs may be in part caused by failure of the acrosome reaction of sperm. In addition, we showed that CD81 was highly expressed in granulosa cells, somatic cells that surround oocytes. Our observations suggest that there is an interaction between sperm and CD81 on somatic cells surrounding eggs before the direct interaction of sperm and eggs. Our results may provide new clues for clarifying the cellular mechanism of the acrosome reaction, which is required for sperm–egg fusion. Mol. Reprod. Dev. 75: 150–155, 2008. © 2007 Wiley‐Liss, Inc.
How big is small?

Document on Standards for Acquisition, Measurement and reporting of Intravascular Ultrasound Studies clearly defines lesion and reference segment borders. Proximal or distal reference sites are defined as the site with the largest lumen proximal or distal to a stenosis but within the same segment (usually within 10 mm of the stenosis but with no major intervening branches), which may not be the site with the least plaque. Vessel size is determined by the area surrounded by the external elastic membrane, which in most cases can be easily identified by intravascular ultrasound. Nevertheless, this consensus document does not provide quantitative measures to define a small coronary artery. In this issue Briguori et al. report on the discrepancy in reference vessel dimensions, measured by intravascular ultrasound and quantitative coronary angiography, for small ( 2·75 mm angiographic diameter) or larger coronary vessels (>2·75 mm angiographic diameter). It is remarkable that 96% of the evaluated cases in the smaller vessel group and 80% in the larger vessel group showed a minimum difference of 0·5 mm between angiographic and intravascular ultrasound results. These percentages are reduced to 71% in the smaller vessel group and to 49% in the larger vessel group, if the threshold is increased to 1·0 mm difference between angiographic and intravascular ultrasound images. Proximal or middle lesion site, female sex and lesion length were identified as predictors for this large discrepancy. The results additionally showed that this mismatch is more pronounced in angiographically smaller vessels which were frequently identified by intravascular ultrasound as larger vessels with a high plaque burden. This message is well taken. The clinical implications of these findings are directed towards the use of larger balloon sizes or higher balloon to artery ratios. This strategy has been followed in the past. The authors came to the conclusion that in about 70% of lesions a balloon to artery ratio of 1·4 is appropriate. This strategy appears quite aggressive and needs additional support before it can be safely applied in general clinical practice without increased complication rates (dissections, perforations). The authors state that with the use of intravascular ultrasound to guide balloon sizes, this aggressive strategy can be safely performed in small coronary arteries. This idea of balloon sizing by intravascular ultrasound was originally proclaimed by Stone et al. Data from prospective randomized See page 247, doi:10.1053/euhj.2001. 2730 for the article to which this Editorial refers
Base excision repair pathway is involved in the repair of lesions generated by flavonoid‐enriched fractions of pepper tree (Schinus terebinthifolius, Raddi) stem bark

Cell‐free and bacterial assays indicate that flavonoid‐enriched fractions and the flavonoids of pepper tree stem bark from Schinus terebinthifolius Raddi have genotoxic rather than antigenotoxic properties. In the present report, we have examined the ability of flavonoid‐enriched fractions to damage plasmid DNA and the repair pathways involved in the recognition of these DNA lesions. High concentrations of two flavonoid‐enriched fractions were able to break phosphodiester bonds in DNA. In addition, studies using bacterial strains deficient in nucleotide excision repair and base excision repair (BER) enzymes indicated that the flavonoid‐enriched fractions generated lesions that were substrates for enzymes belonging to the BER pathway. In addition, in vitro studies indicated that the DNA damage produced by the flavonoid‐enriched fractions was also a substrate for exonuclease III and that the phosphodiester breakage was amplified by copper ions. These results indicate that flavonoids from the pepper tree (Schinus terebinthifolius, Raddi) generate lesions on DNA that are potential targets of FPG and MutY glycosylase from the BER pathway. Chromatographic and spectral analyses helped to support the hypothesis that the flavonoids of the Brazilian pepper tree bark are the main factors involved in the fraction's damage potential. The isolated flavonoids from Fraction II were also tested in vitro and support the oxidative damage potential of these flavonoids. Environ. Mol. Mutagen. , 2007. © 2007 Wiley‐Liss, Inc.
Effects of sex steroids on the development of sexual dimorphism in mouse innominate bone

The sexual dimorphism of the innominate bone was examined in 14 strains of mice. In female mice of all strains, the pubis was significantly longer and thinner than that in the strain‐matched males. In 13 of 14 strains, the ischium in the male was longer and thicker than in the female. In the testicular‐feminized male (Tfm) mouse, the ischium was longer and thinner than that in the wild‐type male, resembling that of the wild‐type female. The pubis of the Tfm mouse was longer than in the wild‐type males. The pubis width in the Tfm mouse was between those of the wild‐type male and female. Gonadectomy at ages of 5, 10, 20, 30, and 60 days in both sexes showed that the ischium develops as the female type when sex hormones are absent. In contrast, postnatal testicular androgen induces the male‐type ischium. Gonadectomy at 60 days had a slight effect on the pubis, indicating that sexual dimorphism of the pubis was determined before 60 days of age. Estrogen receptors (ER) were immunohistochemically demonstrated in bone cells of 0‐ to 60‐day‐old mice. ER was found exclusively in the periosteum of the pubis at the day of birth; however, it appeared in bone cells of all parts of pelvis at 10–60 days. These results indicate that sexual dimorphism of the pubis is consistent for the 14 mouse strains examined, and that the shape of the pubis is determined by sex steroids before 60 days of age. Since ER exist in the bone cells, morphogenesis of the pelvis may be regulated by these sex steroids. © Willey‐Liss, Inc.