Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein Composition of Catalytically Active Human Telomerase from Immortal Cells

Telomerase is a ribonucleoprotein enzyme complex that adds 5′-TTAGGG-3′ repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for ∼90% of human cancers. We have purified human telomerase ∼108-fold, with the final elution dependent on the enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA, and dyskerin.
Genetic Antagonism and Hypermutability inMycobacterium smegmatis

ABSTRACT Multidrug-resistant strains of Mycobacterium tuberculosis are a serious and continuing human health problem. Such strains may contain as many as four or five different mutations, and M. tuberculosis strains that are resistant to both streptomycin and rifampin contain mutations in the rpsL andrpoB genes, respectively. Coexisting mutations of this kind in Escherichia coli have been shown to interact negatively (S. L. Chakrabarti and L. Gorini, Proc. Natl. Acad. Sci. USA 72:2084–2087, 1975; S. L. Chakrabarti and L. Gorini, Proc. Natl. Acad. Sci. USA 74:1157–1161, 1977). We investigated this possibility in Mycobacterium smegmatis by analyzing the frequency and nature of spontaneous mutants that are resistant to either streptomycin or rifampin or to both antibiotics. Mutants resistant to streptomycin were isolated from characterized rifampin-resistant mutants of M. smegmatis under selection either for one or for both antibiotics. Similarly, mutants resistant to rifampin were isolated from streptomycin-resistant strains. The second antibiotic resistance mutation occurred at a lower frequency in both cases. Surprisingly, in both cases a very high rate of reversion of the initial antibiotic resistance allele was detected when single antibiotic selection was used; the majority of strains resistant to only one antibiotic were isolated by this process. Determinations of rates of mutation to antibiotic resistance in M. smegmatis showed that the frequencies were enhanced up to 104-fold during stationary phase. If such behavior is also typical of slow-growing pathogenic mycobacteria, these studies suggest that the generation of multiply drug-resistant strains by successive mutations may be a more complex genetic phenomenon than suspected.
Hyperuricemia in mongolism.

MONGOLISM has recently been investigated for disorders of purine metabolism. Although the numbers of patients studied is small, a correlation appears to exist between hyperuricemia and mongolism. Mertz, Fuller and Concon,1 in 25 patients with mongolism, two to twelve years of age, found a mean serum uric acid of 5.42 mg. as compared to 3.87 mg. per 100 ml. in mentally retarded controls without mongolism from the same institution. This seemed to be a highly significant increase (p less than 0.005). Earlier, Fuller, Luce and Mertz2 reported similar results in 40 older patients with mongolism. Appleton et al.3 discovered similar .
Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification

We have studied the occurrence and association of 11q deletions with other chromosomal imbalances in Stage 4 neuroblastomas. To this purpose we have performed comparative genomic hybridization (CGH) analysis on 50 Stage 4 neuroblastomas and these data were analyzed together with those from 33 previously published cases. We observed a high incidence of 11q deletion in Stage 4 neuroblastoma without MYCN amplification (59%) whereas 11q loss was only observed in 15% of neuroblastomas with MYCN‐amplification (p = 0.0002) or 11% of cases with 1p deletion detected by CGH (p = 0.0001). In addition, 11q loss showed significant positive correlation with 3p loss (p = 0.0002). Event‐free survival was poor and not significantly different for patients with or without 11q deletion. Our study provides further evidence that Stage 4 neuroblastomas with 11q deletions represent a distinct genetic subgroup that typically shows no MYCN‐amplification nor 1p deletion. Moreover, it shows that neuroblastomas with 11q deletion also often present 3p deletion. This genetic subgroup shows a similar poor prognosis as MYCN amplified 4 neuroblastomas. © 2001 Wiley‐Liss, Inc.
Diagnostic Value of Immunoglobulin G (IgG) and IgM Anti-Hepatitis E Virus (HEV) Tests Based on HEV RNA in an Area Where Hepatitis E Is Not Endemic

ABSTRACT Acute hepatitis E (AHE) has rarely been reported in industrialized countries, but the rate of seroprevalence of hepatitis E virus (HEV) antibodies (anti-HEV) is inappropriately high. The sensitivity and specificity of the assay used to test for immunoglobulin G (IgG) and IgM anti-HEV have not been well established in areas where hepatitis E is not endemic (hereafter referred to as “nonendemic areas”). We collected serum samples from 13 AHE patients, 271 healthy subjects, and 160 other liver disease patients in Taiwan to test for HEV RNA by reverse transcription (RT)-PCR and for IgG and IgM anti-HEV by enzyme-linked immunosorbent assays. The sensitivities of IgG and IgM anti-HEV (relative to RT-PCR) were 86.7 and 53.3%, respectively. The specificities of IgG and IgM anti-HEV assays for diagnosing AHE were 92.1 and 98.6%, respectively. The rate of seroprevalence of IgG anti-HEV was 11% among healthy subjects in this nonendemic area, and it increased with age. In summary, IgG anti-HEV is a good diagnostic test for screening for AHE in nonendemic areas. The high rate of prevalence of anti-HEV in healthy subjects indicates that subclinical infection may exist.
Meibomian Gland Alterations in Polycystic Ovary Syndrome

Purpose: Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by chronic anovulation and hyperandrogenism where hyperinsulinemia can be seen. Hormonal changes can affect meibomian gland function. In this study, we evaluated tear function in PCOS. Materials and Methods: Twenty-seven women having PCOS and 22 normal individuals aged between 18–42 years were enrolled in the study. Patients were asked about dry eye symptoms. Schirmer test, tear film breakup time, and rose Bengal staining were performed. Conjunctival brush cytology specimens were obtained and goblet cell count was done. Results: Dry eye symptoms were more frequent in subjects with PCOS (p = 0.025). Mean breakup time was shorter in women with PCOS (p = 0.034). Schirmer test results, rose Bengal staining scores, and goblet cell count were not different between groups (p = 0.48, p = 0.18, p = 0.82, respectively). Conclusion: Meibomian gland function and tear film lipid layer can be affected in cases with PCOS.
Effect of local drug delivery in chronic periodontitis patients: A meta-analysis

Periodontal diseases are multi-factorial in etiology, and bacteria are one among these etiologic agents. Thus, an essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing (SRP)), which is time-consuming, difficult, and, sometimes, ineffective. From about the past 30 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal. This systematic review is an effort to determine the efficacy of the currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis. Four studies were included, which were all randomized controlled trials, incorporating a total patient population of 80, with 97 control sites and 111 test sites. A meta-analysis completed on these four studies including SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive probing depth (PD) reduction for 10% Doxycycline hycylate (ATRIDOX), minocycline hydrochloride (ARESTIN), tetracycline hydrochloride (PERIODONTAL PLUS AB), and chlorhexidine gluconate (PERIOCHIP). Essentially, all studies reported substantial reductions in gingival inflammation, plaque scores, and bleeding indices, which were similar in both the control and the experimental groups. Use of antimicrobial sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events. Local drug delivery combined with SRP appears to provide additional benefits in PD reduction compared with SRP alone.
Southern Ocean seasonal temperature and Subtropical Front movement on the South Tasman Rise in the late Quaternary

[1] The Subtropical Front (STF) marking the northern boundary of the Southern Ocean has a steep gradient in sea surface temperature (SST) of approximately 4C over 0.5 of latitude. Presently, in the region south of Tasmania, the STF lies nominally at 47S in the summer and 45S in the winter. We present here SST reconstructions in a latitudinal transect of cores across the South Tasman Rise, southeast of Australia, during the late Quaternary. SST reconstructions are based on two paleotemperature proxies, alkenones and faunal assemblages, which are used to assess past changes in SST in spring and summer. The north-south alignment in core locations allows reconstruction of movement of the STF over the last 100 ka. Surface water temperatures during the last glaciation in this region were � 4C colder than today. Additional temperature changes greater in magnitude than 4C seen in individual cores can be attributed to changes in the water mass overlying the core site caused by the movement of the front across that location. During the penultimate interglacial, SST was � 2C warmer and the STF was largely positioned south of 47S. Movement of the STF to the north occurred during cool climate periods such as the last marine isotope stages 3 and 4. In the last glaciation, the front was at its farthest north position, becoming pinned against the Tasmanian landmass. It moved south by 4 latitude to 47S in summer during the deglaciation but remained north of 45S in spring throughout the early deglaciation. After 11 ka B.P. inferred invigoration of the East Australia Current appears to have pushed the STF seasonally south of the East Tasman Plateau, until after 6 ka B.P. when it achieved its present configuration.
An assessment of the influence of clinical demonstrations on the confidence of undergraduate dental students, when treating patients requiring removable partial dentures.

AIM This study was designed to assess the influence of clinical demonstrations, on the confidence of undergraduate dental students, when treating patients requiring removable partial dentures. METHOD The confidence of 45 undergraduate dental students treating their first patient requiring removable partial dentures was assessed using questionnaires. 23 students were given demonstrations prior to carrying out the treatment; the remainder did not receive a demonstration. Outcome was assessed by the time taken to complete the procedures to a clinically acceptable standard. RESULTS All the students indicated high levels of agreement with a statement expressing their confidence in coping with the clinical procedures undertaken. The more confident students completed their clinical procedures more quickly than other students, irrespective as to whether they had received a demonstration or not. There was a higher proportion of more confident students in the groups who had received a clinical demonstration; it can therefore be concluded that these groups performed better, as measured by the time taken to achieve the required clinical standard. All the students who had received a demonstration believed they had benefited from it, whilst 67% of the students who had not received a demonstration believed they would have benefited from one. Analysis of the students' comments indicated that demonstrations facilitated confidence, communication skills, understanding and recall in the clinical situation. Students who did not perceive a benefit from the demonstrations believed that they had more time for one to one teaching. CONCLUSION This study showed that those students who had received a clinical demonstration immediately prior to treating their patients believed they were more confident and as a result their performance was improved. Clinical demonstrations are time consuming, but they would appear to be time well spent.
Device-level transient fault modeling

This paper examines the accuracy of a discrete logic-level fault model often assumed in gate-level or discrete timing simulation. The analysis is done by comparing the faulty behavior predicted by the discrete model to that predicted by a circuit-level SPICE model whose accuracy is generally accepted. The comparison is made at both the subcircuit level, by measuring latch errors, and the system level, by measuring pin errors and data register errors, using the Motorola MC68000 as the target system. The results of the analysis show that the behavior predicted by the discrete model varies significantly from that of the circuit-level model when the injection site has multiple propagation paths to the circuit outputs (or latches) or is an internal node of one of the logic gates, even if the pulse width of the discrete transient is carefully chosen. However, the two models can be made to match for injection sites that are gate inputs or outputs and have only a single propagation path to circuit outputs. The differences in the latch errors predicted by the two models at the subcircuit level lead to over a 40% difference in the number of predicted pin errors and a 50% difference in the number of data errors predicted at the system level. <<ETX>>
Event-triggered cooperative control

Future multi-agent systems will include embedded microprocessors with limited resources to gather information and actuate the individual agent controller updates. In this paper we examine the stability of such scheme in a cooperative control problem where the actuation updates are event-driven, depending on the ratio of a certain measurement error with respect to the norm of the state. In the centralized case, we obtain a strictly positive lower bound in the inter-event times, while relevant, yet more conservative, results are obtained in the decentralized case.
Aminoacyl Transfer Rate Dictates Choice of Editing Pathway in Threonyl-tRNA Synthetase*

Aminoacyl-tRNA synthetases hydrolyze aminoacyl adenylates and aminoacyl-tRNAs formed from near-cognate amino acids, thereby increasing translational fidelity. The contributions of pre- and post-transfer editing pathways to the fidelity of Escherichia coli threonyl-tRNA synthetase (ThrRS) were investigated by rapid kinetics. In the pre-steady state, asymmetric activation of cognate threonine and noncognate serine was observed in the active sites of dimeric ThrRS, with similar rates of activation. In the absence of tRNA, seryl-adenylate was hydrolyzed 29-fold faster by the ThrRS catalytic domain than threonyl-adenylate. The rate of seryl transfer to cognate tRNA was only 2-fold slower than threonine. Experiments comparing the rate of ATP consumption to the rate of aminoacyl-tRNAAA formation demonstrated that pre-transfer hydrolysis contributes to proofreading only when the rate of transfer is slowed significantly. Thus, the relative contributions of pre- and post-transfer editing in ThrRS are subject to modulation by the rate of aminoacyl transfer.
Dose-related vestibular and cochlear effects of transtympanic gentamicin.

HYPOTHESIS To test the relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected gentamicin in the Mongolian gerbil. BACKGROUND Transtympanic gentamicin is gaining favor as a relatively noninvasive treatment for Meniere's disease (MD). Few basic science studies exist regarding the vestibular and cochlear toxicities and dosage and administration schedules, however. The absence of standardized procedures and use of different species as animal models may account for the variable outcomes and lack of agreement found in the literature. METHODS Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1x) and five (5x) daily injections of gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected controls. RESULTS Two weeks after injection, qualitative and quantitative changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin injected groups. Statistically significant decreases in hair cells were seen when 5x injected ears were compared with 1x injected ears and when 1x injected ears were compared with control ears. When damage was observed in the posterior crista sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS Our results suggest that in the gerbil, gentamicin is ototoxic but not selectively vestibulotoxic. In general, increasing the number of transtympanic injections increases the damage to sensory hair cells in both the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in both cochlear and vestibular hair cells from the same animal.
Cutting Edge: Naturally Occurring Soluble Form of Mouse Toll-Like Receptor 4 Inhibits Lipopolysaccharide Signaling1

Toll-like receptors (TLRs) are a family of proteins playing important roles in host defense. Mice defective of functional TLR4 are hyporesponsive to LPS, suggesting that TLR4 is essential for LPS signaling. Here we report the cloning of an alternatively spliced mouse TLR4 (mTLR4) mRNA. The additional exon exists between the second and third exon of the reported mTLR4 gene and contains an in-frame stop codon. The alternatively spliced mRNA encodes 86 aa of the reported mTLR4 and an additional 36 aa. This alternatively spliced mTLR4 mRNA expressed a partially secretary 20-kDa protein, which we named soluble mTLR4 (smTLR4). In a mouse macrophage cell line, the exogenously expressed smTLR4 significantly inhibited LPS-mediated TNF-α production and NF-κB activation. Additionally, in mouse macrophages, LPS increased the mRNA for smTLR4. Taken together, our results indicate that smTLR4 may function as a feedback mechanism to inhibit the excessive LPS responses in mouse macrophages.
ENZYME IMMUNOASSAY FOR CONJUGATED 7α-HYDROXY-3-OXO-4-CHOLENOIC ACID IN HUMAN URINE

A microplate enzyme immunoassay (EIA) was developed for the measurement of glycine- and taurine-conjugated 7α-hydroxy-3-oxo-4-cholenoic acids (CDCA-Δ4-3-one) in human urine. The antiserum was prepared by immunizing rabbits with N-(7α-hydroxy-3-oxo-4-cholen-24-oyl)-3-aminopropionic acid - bovine serum albumin conjugate. A colorimetric EIA was established using horseradish peroxidase-labeled antigen having a shorter bridge length than that of the immunogen, and 3, 3', 5, 5'-tetramethylbenzidine/hydrogen peroxide for the measurement of the enzyme activity. The reactivities of the antiserum for glycine and taurine conjugates of CDCA-Δ4-3-one was almost the same. The specificity of the antiserum was investigated by determining the cross-reactivities of various bile acids and related compounds. An appropriate dose-response curve for conjugated CDCA-Δ4−3-one was obtained in the range of 0.05–10 ng/well. This method was used for direct analysis of conjugated CDCA-Δ4−3-one in urine of healthy infants and patients with liver diseases.
Do Falls Predict Institutionalization in Older Persons?

Data from the Longitudinal Study of Aging (LSOA) were analyzed to estimate the subsequent risk of institutionalization associated with a report of one or more falls, and to determine if the association is affected by controlling for demographic traits, chronic conditions, and disabilities present at baseline. Risk was estimated at two time points, 2 years and 4years after baseline interview. A report of multiple falls at baseline was associated with an increased risk of institutionalization at both 2 years (odds ratio [OR] 3.1; 1.9-5.3) and 4 years (OR 2.6; 1.64.4) of follow-up. The risk was decreased but remained significant in a model controlling for age, sex, marital status, and selected chronic conditions associated with both report of falls and institutionalization. However, multiple falls were not significantly associated with institutionalization when measures of disability (number of difficulties with activities of daily living) were added to the model. These analyses suggest that multiple falls should be regarded as an important sentinel event to alert caregivers to the presence of underlying disease and disability that may require intervention.
Visual impairment, uncorrected refractive error, and objectively measured balance in the United States.

IMPORTANCE Further research is crucial to better understand the reason for falls in individuals with visual impairment (VI) and to develop appropriate fall prevention strategies. OBJECTIVE To compare balance measures in individuals with normal vision, VI, and uncorrected refractive error (URE). DESIGN AND SETTING Cross-sectional study based on a national survey sample. PARTICIPANTS A total of 4590 adults, 40 years or older, participating in the 2001 through 2004 National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES Participants completed tests of standing balance with eyes open or eyes closed on a firm or compliant (foam) surface. Eyes-closed testing on a foam surface primarily assessed vestibular balance by minimizing visual and proprioceptive inputs. The main outcome measure was time to balance failure on firm and foam surface testing. Participants also self-reported difficulty with falling during the last year. RESULTS Failure during eyes-open balance testing conditions or eyes-closed balance testing on a firm surface was not more common among participants with VI-associated or URE-associated vision loss (P > .22). In eyes-closed foam surface balance testing, multivariable models demonstrated higher rates of balance loss with VI-associated vision loss (P = .02) and with URE-associated vision loss (P = .04) (hazard ratio, 1.7 per logarithm of the minimum angle of resolution [logMAR] unit change [10 lines] for both). Self-reported falling difficulty was associated with worse VI (odds ratio, 3.7 per logMAR unit change; P = .03) but not with worse URE (odds ratio, 3.4 per logMAR unit change; P = .14). CONCLUSIONS AND RELEVANCE The vestibular contribution to balance (measured with eyes closed on a foam surface) was worse for individuals with VI or URE. Reduced visual inputs may weaken the vestibulo-ocular reflex, an important system that maintains the effectiveness of vestibular balance. Alternately, common degenerative pathways or lower physical activity levels may affect balance, particularly among those with VI.