Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular correlates of progressive hearing loss in 129S6/SvEv mice

Several strains of mice hear well initially but show progressive sensorineural hearing loss. Affected cochlear cell types include all those known to be affected in human age‐related hearing loss (ARHL), or presbycusis. Thus these mice have been offered as models of human ARHL. At present, however, few mouse ARHL models are sufficiently well described to serve as the basis for specific hypotheses about human ARHL. We examined 1‐month‐old and 15‐month‐old 129S6/SvEv (129S6) mice and compared them with BALB/cJ and CBA/J mice. Age‐related elevation of compound action potential thresholds was interpreted in the light of endocochlear potentials and changes in hair cells, afferent neurons, fibrocytes in spiral limbus and ligament, and supporting cells within the organ of Corti. Aging in 129S6 mice was associated with high‐frequency hearing loss. Four components of age‐related cochlear degeneration emerged from quantitative analyses, including 1) basal loss of outer hair cells; 2) basal loss of type IV fibrocytes in the spiral ligament; 3) apical loss of fibrocytes in spiral limbus, and 4) anomalies of supporting cells in the cochlear base. Although neuronal loss was not consistently found, two mice showed loss of afferent dendrites and cell bodies in the cochlear apex without inner hair cell loss. Despite multifaceted degeneration, hearing loss in 129S6 mice appears to be best explained by degenerative changes in outer hair cells and in the organ of Corti, conforming to human sensory ARHL. Age‐related changes in the apical spiral limbus may promote pathology of the medial organ of Corti and eventual loss of afferent neurons, with possible implications for human neural ARHL. J. Comp. Neurol. 469:377–390, 2004. © 2004 Wiley‐Liss, Inc.
Isolation of clonal axenic strains of the symbiotic dinoflagellate Symbiodinium and their growth and host specificity1

The cnidarian‐dinoflagellate mutualism is integral to the survival of the coral‐reef ecosystem. Despite the enormous ecological and economic importance of corals, their cellular and molecular biology and the ways in which they respond to environmental change are still poorly understood. We have been developing a proxy system for examining the coral mutualism in which the dinoflagellate symbiont Symbiodinium is introduced into a clonal population of the host Aiptasia, a small sea anemone closely related to corals. To further develop the tools for this system, we generated five clonal, axenic strains of Symbiodinium and verified the lack of contaminants by growth on rich medium, microscopic examination, and PCR analysis. These strains were assigned to clades A (two strains), B, E, and F based on their chloroplast 23S rDNA sequences. Growth studies in liquid cultures showed that the clade B strain and one of the clade A strains were able to grow photoautotrophically (in light with no fixed carbon), mixotrophically (in light with fixed carbon), or heterotrophically (in dark with fixed carbon). The clade E strain, thought to be free‐living, was able to grow photoautotrophically but not heterotrophically. Infection of an aposymbiotic Aiptasia host with the axenic strains showed consistent patterns of specificity, with only the clade B and one of the clade A strains able to successfully establish symbiosis. Overall, the Aiptasia‐Symbiodinium association represents an important model system for dissecting aspects of the physiology and cellular and molecular biology of cnidarian‐dinoflagellate mutualism and exploring issues that bear directly on coral bleaching.
Total Ionizing Dose Effects on a 12-bit 40kS/s SAR ADC Designed With a Dummy Gate-Assisted n-MOSFET

A 12-bit 40kS/s successive approximation register analog-to-digital converter (ADC) designed with a dummy gate-assisted (DGA) n-MOSFET is presented for space applications requiring high resolution, low power consumption, and moderate conversion speed. Additionally, a custom-designed metal finger capacitor and a body-tied p-MOSFET protected by guard ring in a bootstrapping circuit were used to mitigate the performance degradation caused by radiation-induced leakage current. The designed ADC was fabricated in a commercial standard 0.35 $\mu {\mathrm { m}}$ CMOS process. In order to evaluate its radiation hardness, the fabricated ADC was exposed to 60Co gamma rays with a dose of up to 300krad (Si). The measured signal-to-noise-and-distortion ratio (SNDR) and spurious-free dynamic range (SFDR) were 67.9dB and 78.7dB, respectively. Although a small amount of degradation of the SNDR was observed after radiation exposure, it corresponds to only about a 0.1 effective-number-of-bit (ENOB) drop from the measured result of an unirradiated chip.
The effect of triacylglycerol fatty acid positional distribution on postprandial plasma metabolite and hormone responses in normal adult men

The present study has examined the possibility that the positional distribution of fatty acids on dietary triacylglycerol (TAG) influences the postprandial response to a liquid meal in adult subjects. Postprandial TAG, non-esterified fatty acids (NEFA), ketones, glucose, insulin and gastric inhibitory polypeptide (GIP) responses were monitored in sixteen normal adult male subjects over 6 h following consumption of test meals containing dietary TAG in which palmitic acid was predominantly on the sn-1 (Control) or sn-2 positions (Betapol). Plasma total TAG, chylomicron-rich TAG and chylomicron-poor TAG concentrations were identical in response to the two test meals. The peak increase (mean (sd)) in chylomicron TAG was 0 85 (0 46) mmol/l after the Control meal and 0 85 (0 42) mmol/l after the Betapol meal. Plasma glucose, insulin, GIP, NEFA and ketone concentrations were also very similar following the two meals. It is concluded that dietary TAG containing saturated fatty acids on the sn-2 position appear in plasma at a similar level and over a similar timescale to TAG in which saturated fatty acids are predominantly located on sn-1 or sn-3 positions. The results reported in the present study demonstrate that the positional distribution of fatty acids on dietary TAG is not an important determinant of postprandial lipaemia in adult male subjects, but do not exclude the possibility that different responses may occur when these dietary TAG are given long term.
TIMI and GRACE Risk Scores Predict Both Short-Term and Long-Term Outcomes in Chinese Patients with Acute Myocardial Infarction.

Background Little is known about the long-term prognostic values of both thrombolysis in myocardial infarction (TIMI) and Global Registry of Acute Cardiac Events (GRACE) risk scores (RSs) to the Asian ethnicity. The purpose of this study is to compare the usefulness of these two scores in risk stratification and prediction of long-term (up to 3 years) outcomes for Chinese patients with myocardial infarction (MI). Methods We calculated the TIMI and GRACE RSs for 726 consecutive patients with MI [55.6% with ST-segment elevation (STEMI) and 44.4% with non-ST-segment elevation (NSTEMI)]. Results Although the risk profile of our population (median TIMI score = 5 for STEMI, 4 for NSTEMI, and median GRACE score = 164) was higher, the in-hospital mortality (7.1% for NSTEMI and 6.7% for STEMI) was comparable to that predicted by GRACE RS. The GRACE RS worked well in predicting short-term and long-term death (C-statistics range 0.710 to 0.789) and triple (death, MI, and stroke) endpoints (C-statistics range 0.695 to 0.764) in both subsets of MI. GRACE RS performed significantly better than the TIMIRS in predicting 3-year mortality in NSTEMI (p = 0.035) and 1-year and 3-year mortality in STEMI (p = 0.028 and 0.009, respectively). Stratification by tertiles of GRACERS furnished greater prognostic information versus risk assessment by the TIMI RS. Conclusions The use of RSs revealed a fair to good discriminatory accuracy in predicting both short-term and long-term major adverse cardiac events in Asian patients with MI. Compared with the simpler TIMI RS, the GRACERS was more accurate in predicting long-term mortality.
DNA repair deficiency leads to susceptibility to develop arsenic‐induced premalignant skin lesions

In West Bengal, India, although more than 6 million people are exposed to arsenic through drinking water, only 15–20% showed arsenic‐induced skin lesions, including premalignant hyperkeratosis. This indicates toward some factors that confer susceptibility to arsenic‐induced carcinogenicity. In this work, we wanted to explore whether differences in DNA repair capacity could impart arsenic‐induced carcinogenicity, through Comet assay, chromosomal aberration (CA) assay and challenge assay. Sixty arsenic exposed (30 individuals with arsenic‐induced premalignant hyperkeratosis and 30 without skin lesion, but drinking similar arsenic contaminated water) and 30 arsenic unexposed individuals were recruited as study participants. Alkaline comet assay, and challenge assay were carried out in whole blood and CA study in lymphocytes to find out the DNA damage and DNA repair capacity in both hyperkeratotic and without skin lesion individuals. DNA damage as well as CA were found to be significantly higher in the arsenic‐exposed individuals compared to unexposed individuals (p < 0.001). Within the exposed group, there was no significant difference as far as the level of DNA damage is concerned (p > 0.05), but CA was significantly higher in exposed individuals with hyperkeratosis than exposed individuals without hyperkeratosis (p < 0.01). Challenge assay showed that upon induction of DNA damage, the repair capacity in the exposed individuals with premalignant hyperkeratosis is significantly less (p < 0.001) than that of individuals without skin lesion, although the basal level of DNA damage was similar in both. Thus, the deficiency in DNA repair capacities in the hyperkeratotic individuals emerges as a prime contender for arsenic carcinogenicity. © 2008 Wiley‐Liss, Inc.
Decreased CD4 Lymphocyte Count as a Marker Predicting High Mortality Rate in Managing ANCA Related Rapidly Progressive Glomerulonephritis

As antineutrophil cytoplasmic antibody positive rapidly progressive glomerulonephritis (ANCA-RPGN) has a high risk of end stage renal failure and is a potentially life threatening disease, early aggressive therapy is recommended. However, aggressive immunosuppressive therapy may lead to immunodeficiency and subsequent mortality in the patients with this disease. Therefore, we need the index of immunodeficiency to cure the disease. To evaluate any risk factors, including therapies, on mortality in ANCA-RPGN, we conducted a retrospective investigation on patient survival in 32 patients with ANCA-RPGN by Kaplan-Meier analysis and the Cox regression model. Fourteen patients were treated with leucocytapheresis (LAP group) and the 18 patients were treated by steroid pulse therapy (steroid pulse group) as initial treatment. The patients were chosen for the different therapies at random. Two patients in the LAP group, and eight patients in the steroid pulse group had died within 6 months. The lymphocyte counts and CD4 cell counts after complete course of therapy were lower in the patients who died than in those who survived in the steroid pulse group. Patient survival was higher in the LAP group than in the steroid pulse group, but did not reach statistical significance. Multivariate Cox regression analysis showed that the factors influencing patient survival were initial serum creatinine, LAP therapy, CD4 cell counts, and lymphocytes at the end of treatment. Age, titer of MPO-ANCA, and percent of glomerular crescents were not found to have an effect on the patient survival. We recommend: that early diagnosis should be established, and immunosuppressive therapy may be done with monitoring of the lymphocyte and CD4 cell count.
Epidemiologic Analysis of Invasive and Noninvasive Group A Streptococcal Isolates in Hong Kong

ABSTRACT Since the mid-1980s, there has been a resurgence of severe forms of invasive group A streptococcal (GAS) disease in many Western countries. In Hong Kong, a similar increase has also been observed in recent years. One hundred seven GAS isolates collected from 1995 to 1998 from individuals with necrotizing fasciitis, toxic shock syndrome, meningitis, or other type of bacteremic sepsis (invasive group, n = 24) as well as from individuals with minor skin and throat infections (noninvasive group, n = 83) were characterized through serologic and/or emm sequence typing. Thirty-two M protein gene sequence types were identified. Types M1, M4, and M12 were the most prevalent in both the invasive group and the noninvasive group; together they accounted for 70.8 and 37.3% of the isolates, respectively. No clear pattern of skin and throat infection M types was observed. Type M1 was overrepresented in the invasive and pharyngeal isolates. The same pulsed-field gel electrophoresis pattern was shared by most invasive and all pharyngeal M1 isolates. Overall, resistance to erythromycin (32%) and tetracycline (53%) was high, but M1 isolates were significantly less likely to have resistance to either antimicrobial agent than non-M1 isolates. One novel emm sequence type, stHK, was identified in an isolate from a patient with necrotizing fasciitis. Minor emm gene sequence alterations were noted for 31 isolates, and for 13 of these isolates, deletion, insertion, or point mutations were seen in the hypervariable 50 N-terminal residues.
On A Priori Error Analysis of Fully Discrete Heterogeneous Multiscale FEM

Heterogeneous multiscale methods have been introduced by E and Engquist [Commun. Math. Sci., 1 (2003), pp. 87--132] as a methodology for the numerical computation of problems with multiple scales. Analyses of the methods for various homogenization problems have been done by several authors. These results were obtained under the assumption that the microscopic models (the cell problems in the homogenization context) are analytically given. For numerical computations, these microscopic models have to be solved numerically. Therefore, it is important to analyze the error transmitted on the macroscale by discretizing the fine scale. We give in this paper H1 and L2 a priori estimates of the fully discrete heterogeneous multiscale finite element method. Numerical experiments confirm that the obtained a priori estimates are sharp.
Cytotaxonomic description of Simulium kaffaense, a new member of the S. damnosum complex (Diptera: Simuliidae) from south–western Ethiopia

Abstract Although Ethiopia is one of the countries worst affected by human onchocerciasis, the exact taxonomic identity of the blackflies acting as the main vectors in the endemic areas has never been determined. A cytotaxonomic analysis of Simulium damnosum s.l. collected from three endemic sites in south–western Ethiopia has now revealed the existence of the 'Kisiwani' form (a non-anthropophilic cytoform that is common in East Africa) and a newly recognized species, Simulium kaffaense. Simulium kaffaense sp. nov. is differentiated from other members of the S. damnosum complex by six fixed inversions and dozens of 'new' floating inversions. The rearing of egg batches from some of the biting adult females, to larvae or adults, indicated that the human-biting blackflies were all S. kaffaense. As S. kaffaense is not only highly anthropophilic but also, apparently, the only anthropophilic member of the S. damnosum complex present, it is likely to be the main (if not the only) vector of Onchocerca volvulus in the study area. The presence of inversion 1S-1 and a complex inversion possibly involving 1L-3 indicates that S. kaffaense either belongs or is close to the 'Nile' phylogenetic group of S. damnosum s. l. The karyotype frequencies of the inversions in the collections from the three study sites indicate that at least two forms of S. kaffaense, here designated 'Bebeka' and 'Jimma', were caught. The taxonomy and medical importance of S. kaffaense are discussed.
Characterization of Multiple Signaling Pathways of Insulin in the Regulation of Vascular Endothelial Growth Factor Expression in Vascular Cells and Angiogenesis*

The effects of insulin on vascular endothelial growth factor (VEGF) expression in cultured vascular cells and in angiogenesis were characterized. Insulin increased VEGF mRNA levels in mouse aortic smooth muscle cells from 10–9 to 10–7 m with an initial peak of 3.7-fold increases at 1 h and a second peak of 2.8-fold after 12 h. The first peak of VEGF expression was inhibited by LY294002, an inhibitor of phosphatidylinositol (PI) 3-kinase, and by the overexpression of dominant negative forms of p85 subunit of PI 3-kinase or Akt. Inhibitors of MEK kinase, PD98059, or overexpression of dominant negative forms of Ras was ineffective. In contrast, the chronic effect of insulin on VEGF expression was partially inhibited by both LY294002 or PD98059 as well as by the overexpression of dominant negatives of PI 3-kinase or Ras. The importance of PI 3-kinase-Akt pathway on VEGF expression was confirmed in mouse aortic smooth muscle cells isolated from insulin receptor substrate –1 knockout (IRS-1–/–) mice that showed parallel reductions of 46–49% in insulin-stimulated VEGF expression and PI 3-kinase-Akt activation. Insulin-induced activation of PI 3-kinase-Akt on hypoxia-induced VEGF expression and neovascularization was reduced by 40% in the retina of neonatal hypoxia model using IRS-1–/– mice. Thus, unlike other cells, insulin can regulate VEGF expression by both IRS-1/PI 3-kinase-Akt cascade and Ras-MAPK pathways in aortic smooth muscle cells. The in vivo results provide direct evidence that insulin can modulate hypoxia-induced angiogenesis via reduction in VEGF expression in vivo.
Pathways to recovery (PTR): impact of peer-led group participation on mental health recovery outcomes.

OBJECTIVE This study examined the positive effects on recovery outcomes for people with severe and persistent mental illness using peer-led groups based on Pathways to Recovery: A Strengths Recovery Self-Help Workbook (PTR). PTR translates the evidence-supported practice of the Strengths Model into a self-help approach, allowing users to identify and pursue life goals based on personal and environmental strengths. METHODS A single-group pretest-posttest research design was applied. Forty-seven members in 6 consumer-run organizations in one Midwestern state participated in a PTR peer-led group, completing a baseline survey before the group and again at the completion of the 12-week sessions. The Rosenberg Self-Esteem Scale, the General Self-Efficacy Scale, Multidimensional Scale of Perceived Social Support, the Spirituality Index of Well-Being, and the Modified Colorado Symptom Index were employed as recovery outcomes. Paired Hotelling's T-square test was conducted to examine the mean differences of recovery outcomes between the baseline and the completion of the group. RESULTS Findings revealed statistically significant improvements for PTR participants in self-esteem, self-efficacy, social support, spiritual well-being, and psychiatric symptoms. CONCLUSIONS This initial research is promising for establishing PTR as an important tool for facilitating recovery using a peer-led group format. The provision of peer-led service has been emphasized as critical to integrating consumers' perspectives in recovery-based mental health services. Given the current federal funding stream for peer services, continued research into PTR and other peer-led services becomes more important.
Reverse cholesterol transport in plasma of patients with different forms of familial HDL deficiency.

HDLs encompass structurally heterogenous lipoproteins that fulfill specific functions in reverse cholesterol transport. Two-dimensional nondenaturing gradient gel electrophoresis (2D-PAGGE) of normoalphalipoproteinemic plasma and subsequent immunoblotting with anti-apoA-I-antibodies differentiates pre-beta 1-LpA-I, pre-beta 2-LpA-I, pre-beta 3-LpA-I, alpha-LpA-I2, and alpha-LpA-I3. Immunodetection with anti-apoE antibodies differentiates gamma-LpE and alpha-LpE. Pulse-chase incubations of plasma with [3H]unesterified cholesterol ([3H]UC)-labeled fibroblasts and subsequent 2D-PAGGE revealed that cell-derived [3H]UC is taken up by pre-beta 1-LpA-I and gamma-LpE. From these initial acceptors, [3H]UC is transferred to LDL via pre-beta 2-LpA-I-->pre-beta 3-LpA-I-->alpha-LpA-I. Some UC is esterified in pre-beta 3-LpA-I, and some is esterified in alpha-LpA-I after its retransfer from LDL. In this study we investigated the effect of various forms of familial HDL deficiency on reverse cholesterol transport. Plasma samples of patients with various forms of HDL deficiency are characterized by the lack of specific HDL subclasses. ApoE-containing HDLs, including gamma-LpE, are present in all kinds of HDL deficiency. However, all forms of LpA-I are absent in apoA-I-deficient plasma, pre-beta 3-LpA-I and alpha-LpA-I from the plasma of patients with Tangier disease (TD), and pre-beta 3-LpA-I and large alpha-LpA-I from the plasma of patients with lecithin:cholesterol acyltransferase (LCAT) deficiency and fish-eye disease (FED). After a 1-minute pulse with labeled fibroblasts, efflux of [3H]UC into HDL-deficient plasmas decreased, compared with normal plasma, by 49% (apoA-I deficiency), 36% (TD), 21% (LCAT deficiency), and 28% (FED). In apoA-I deficiency, only gamma-LpE takes up cell-derived [3H]UC. In the three other HDL-deficiency states, cell-derived [3H]UC is initially taken up by both pre-beta 1-LpA-I and gamma-LpE. The four HDL deficiencies are also characterized by differences in the esterification of cell-derived [3H]UC. No esterification occurs in LCAT-deficient plasma. In FED plasma, [3H]UC is esterified in LDL. In apoA-I deficiency and TD, however, [3H]UC is esterified in lipoproteins free of apoA-I and apoB. In the two latter cases, the transfer of [3H]cholesteryl ester to LDL is enhanced compared with normal plasma. The lack of specific HDL subclasses and the consequent changes in reverse cholesterol transport pathways differently affect net mass efflux of cholesterol from fibroblasts into HDL-deficient plasma. (ABSTRACT TRUNCATED AT 400 WORDS)
Oral Picropodophyllin ( PPP ) Is Well Tolerated In Vivo and Inhibits IGF-1 R Expression and Growth of Uveal Melanoma

PURPOSE. The cyclolignan picropodophyllin (PPP) efficiently blocks the activity of insulinlike growth factor-1 receptor (IGF1R) and inhibits the growth of uveal melanoma cells in vitro and in vivo. In this study, the authors investigated the efficiency of orally administered PPP on the growth of uveal melanoma xenografts. In addition, they focused on the effect of PPP on vascular endothelial growth factor (VEGF) in vivo and evaluated its effects in combination with other established antitumor agents in vitro.