Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Disruption of Fibulin-4 Abolishes Elastogenesis and Causes Perinatal Lethality in Mice

ABSTRACT Elastic fibers provide tissues with elasticity which is critical to the function of arteries, lungs, skin, and other dynamic organs. Loss of elasticity is a major contributing factor in aging and diseases. However, the mechanism of elastic fiber development and assembly is poorly understood. Here, we show that lack of fibulin-4, an extracellular matrix molecule, abolishes elastogenesis. fibulin-4−/− mice generated by gene targeting exhibited severe lung and vascular defects including emphysema, artery tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages. All the homozygous mice died perinatally. The earliest abnormality noted was a uniformly narrowing of the descending aorta in fibulin-4 −/− embryos at embryonic day 12.5 (E12.5). Aorta tortuosity and irregularity became noticeable at E15.5. Histological analysis demonstrated that fibulin-4 −/− mice do not develop intact elastic fibers but contain irregular elastin aggregates. Electron microscopy revealed that the elastin aggregates are highly unusual in that they contain evenly distributed rod-like filaments, in contrast to the amorphous appearance of normal elastic fibers. Desmosine analysis indicated that elastin cross-links in fibulin-4 −/− tissues were largely diminished. However, expression of tropoelastin or lysyl oxidase mRNA was unaffected in fibulin-4 −/− mice. In addition, fibulin-4 strongly interacts with tropoelastin and colocalizes with elastic fibers in culture. These results demonstrate that fibulin-4 plays an irreplaceable role in elastogenesis.
Metabolic dependence of photoreceptors on the choroid in the normal and detached retina.

PURPOSE This article assesses the hypothesis that the high blood flow rate and low O(2) extraction associated with the choroidal circulation are metabolically necessary and explores the implications of the spatial relationship between the choroid and the photoreceptors for metabolism in the normal and detached retina. METHODS The O(2) distribution across the retinal layers was previously measured with O(2)-sensitive microelectrodes in cat. Profiles were fitted to a diffusion model to obtain parameters characterizing photoreceptor O(2) demand. This was a study of simulations based on those parameters. RESULTS Photoreceptor inner segments have a high O(2) demand (QO(2)), and they are far (20 to 30 microm) from the choroid. These unusual conditions require a large O(2) flux to the inner segments, which in turn requires high choroidal oxygen tension (PO(2)), high choroidal venous saturation (ScvO(2)), low choroidal O(2) oxygen extraction per unit volume of blood, and a choroidal blood flow (ChBF) of at least 500 ml/100 g-min. Movement of the inner segments further from the choroid, which occurs in a retinal detachment, severely reduces the ability of the inner segments to obtain O(2), even for detachment heights as small as 100 microm. Depending on detachment height and assumptions about choroidal and inner retinal PO(2) during elevation of inspired O(2) (hyperoxia), hyperoxia is predicted to partially or fully restore photoreceptor QO(2) during a detachment. CONCLUSIONS The choroid is not overperfused, but requires a high flow rate to satisfy the normal metabolic demand of the retina. Because the oxygenation of the photoreceptors is barely adequate under normal conditions, detachment has serious metabolic consequences. Hyperoxia is predicted to have clinical benefit during detachment.
PRIMARY HEALTHCARE SERVICE QUALITY MEASUREMENT: SERVQUAL SCALE

The purpose of this study is to examine customers’ perceptions of primary healthcare service quality in public institutions in the city of Sibenik. The research was aimed at investigating whether there is difference between customers` expectations and their satisfaction with received medical services. The findings suggest that primary healthcare public institutions need to improve all the dimensions of SERVQUAL service quality from the gap analysis carried out. Furthermore, the research analyzed whether there is difference in the perception of given healthcare service between examinees considering their gender, age, employment status and frequency of using the mentioned services. It was established that demographic variables of age and gender do not generate significant differences in the perception of healthcare service quality while there is significant difference in satisfaction regarding employment status and frequency of services usage. The given results partially differ from the data acquired in other relevant and similar studies. The factor analysis which was conducted did not confirm “a priori” accepted theoretical model of Parasuraman et al. (1988) which claims that the concept of quality has five dimensions. On the contrary, it reached the conclusion that three highly reliable factors were identified regarding the perceived quality of primary healthcare services. Keywords: primary healthcare sector, SERVQUAL, factor analysis, reliability analysis
How autosegmental is phonology?

Abstract In this paper I raise the following questions: (i) How appropriate/effective are traditional autosegmental representations? (ii) What insights do autosegmental representations help us express? (iii) Where do autosegmental representations fall short? (iv) What does this all mean for phonology? Although there is still general acceptance of the “basic autosegmental insight”, i.e. that certain features are semi-autonomous from each other and their anchors (e.g. tones vs. tonebearing units), there has been decreasing interest in representational issues in some current approaches to phonology, as well as proposed frameworks which abandon some of the key properties of autosegmental phonology. In this paper I will be particularly interested in the intersection of the following properties assumed in traditional autosegmental phonology: (i) assimilation = spreading; (ii) no line-crossing; (iii) branching elements ≠ successive linking of identical elements. I will first review these three autosegmental assumptions – and the good things they do for us – and then present some unexpected tonal data which are potentially problematic for one or another of these assumptions. After identifying what makes the cited cases problematic and the choices we have in accounting for them, I will conclude with a discussion of the implications such facts have concerning phonology in general.
Timing and Synchronization of the Breeding Period in Pilumnus vespertilio (Crustacea: Pilumnidae) in Subtropical Okinawa, Japan

Observations on the temporal occurrence of copulating pairs, ovigerous females, monthly brooding periods, and embryo development stages in Pilumnus vespertilio Fabricius were carried out in the wild on Okinawa Island, Japan. The relationship between the female gonad and hepatopancreas during a reproductive period was also studied. These reproductive activities were observed in relation to the lunar cycles. An inverse relationship between mass of the hepatopancreas and development of the gonad was observed. Mating and breeding activities were perfectly synchronized with the lunar periodicity. Five broods from May to September were observed in a single breeding period, and the average brooding period was 21.2 days with an interlude of 8.5 ′ 3.1 days between broods/months. The shortest interlude was between May and June (4 days). A sixth brood that started in October was not followed to the end because it started with very few ovigerous females. Embryo development time in days decreased with each stage and averaged 5.3 days per stage. Copulating activity and appearance of ovigerous females during successive broods (months) were clearly synchronized with the lunar cycle. Although copulating frequency was highest after the full moon, nearly 100% of females were ovigerous around the new moon. All females of any one sample carried eggs of the same development stage. All females released their larvae 1-3 days before full moon, coinciding with a high tide. Larvae are probably released during this time as a survival strategy against predators such as planktivorous fish and against adverse intertidal conditions during other times.
Assessment of the Type A Behavior Pattern in Adolescents

&NA; 213 adolescents were assessed for the Type A behavior pattern by means of the Adolescent Structured Interview (ASI) and the Bortner Adjective Rating scale (BARS). The concordance of these two measures of Pattern A was examined, as well as the association of each of these measures with independent self‐report indices of the major behavioral components of Pattern A (e.g., competitive‐achievement striving, aggressiveness‐hostility, and time urgency). Although the concordance of the ASI and BARS was low, both measures demonstrated validity in terms of the association between the Type A rating and the indices of the components of Pattern A.
Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration

Inflammation is implicated in the progressive nature of neurodegenerative diseases, such as Parkinson's disease, but the mechanisms are poorly understood. A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFα, 0.25 mg/kg, i.p.) injection was administered in adult wild‐type mice and in mice lacking TNFα receptors (TNF R1/R2−/−) to discern the mechanisms of inflammation transfer from the periphery to the brain and the neurodegenerative consequences. Systemic LPS administration resulted in rapid brain TNFα increase that remained elevated for 10 months, while peripheral TNFα (serum and liver) had subsided by 9 h (serum) and 1 week (liver). Systemic TNFα and LPS administration activated microglia and increased expression of brain pro‐inflammatory factors (i.e., TNFα, MCP‐1, IL‐1β, and NF‐κB p65) in wild‐type mice, but not in TNF R1/R2−/− mice. Further, LPS reduced the number of tyrosine hydroxylase‐immunoreactive neurons in the substantia nigra (SN) by 23% at 7‐months post‐treatment, which progressed to 47% at 10 months. Together, these data demonstrate that through TNFα, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated pro‐inflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self‐propelling nature of Parkinson's disease. © 2007 Wiley‐Liss, Inc.
Ultraviolet B Radiation of Human Skin Generates Platelet‐activating Factor Receptor Agonists

Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production. In addition to cytokines, such as tumor necrosis factor‐alpha (TNF‐α), UVB generates bioactive lipids including platelet‐activating factor (PAF). Our previous in vitro studies in keratinocytes or epithelial cell lines have demonstrated that UVB‐mediated production of PAF agonists is due primarily to the pro‐oxidative effects of this stimulant, resulting in the nonenzymatic production of modified phosphocholines (oxidized glycerophosphocholines). The current studies use human skin to assess whether UVB irradiation generates PAF‐receptor agonists, and the role of oxidative stress in their production. These studies demonstrate that UVB irradiation of human skin results in PAF agonists, which are blocked by the antioxidant vitamin C and the epidermal growth factor receptor inhibitor PD168393. Inasmuch as UVB‐generated PAF agonists have been implicated in animal model systems as being involved in photobiologic processes including systemic immunosuppression and cytokine (TNF‐α) production, these studies indicate that this novel activity could be involved in human disease.
Combined force and visual control of an industrial robot

This work proposes control structures that efficiently combine force control with vision servo control of robot manipulators. Impedance controllers are considered which are based both on visual servoing and on physical or fictitious force feedback, the force and visual information being combined in the image space. Force and visual servo controllers included in extended hybrid control structures are also considered. The combination of both force and vision based control allows the tasks range of the robot to be extended to partially structured environments. The proposed controllers, implemented on an industrial SCARA-type robot, are tested in tasks involving physical and virtual contact with the environment.
5-lipoxygenase (5LOX)-deficient mice express reduced anxiety-like behavior.

PURPOSE 5-Lipoxygenase (5LOX) is an enzyme critical for leukotriene synthesis from arachidonic acid. In addition to its role in peripheral inflammation, this enzyme is also expressed in the brain but its functional role in the central nervous system is poorly understood. An upregulated expression of brain 5LOX, for example during aging and in multiple sclerosis, has been associated with increased vulnerability to neurodegeneration. Moreover, the 5LOX pathway has been associated with the neurotoxicity of the prion peptide. 5LOX-deficient mice [5LOX(-); B6129S(Alox5tm1Fun)] and their controls (B6129SF2/J) have not been behaviorally characterized. METHODS The following behavioral tests were used for behavioral characterization of 5LOX(-) mice: elevated plus-maze, marble burying, locomotor activity, rota-road, and the spontaneous alternations in T-maze. RESULTS We found that in an elevated plus-maze, 5LOX(-) mice spent a shorter time in the "safe" closed arms, a longer time in the "anxiogenic" open arms, and entered the open arms more frequently. They also covered fewer marbles in the marble-burying anxiety test. No difference was observed between 5LOX(-) and 5LOX(+) mice in other tests. CONCLUSION These results indicate that 5LOX(-) mice are less prone to anxiety and point to a possible role for 5LOX in affective behaviors. We propose that creating congenic 5LOX(-) mice by backcrossing into inbred strains would provide additional tools to further elucidate this putative role.
Beta-Cell Dysfunction in Nondiabetic HLA Identical Siblings of Insulin-Dependent Diabetics

B-cell function was tested in siblings of insulin-dependent diabetics (IDD). From previous studies, it is now recognized that the risk of developing IDD is highest in those sharing both haplotypes (S2H) and lowest in those sharing neither haplotype (SOH) with the diabetic. Insulin secretion in response to intravenous arginine and glucose was evaluated in S2H, SOH, and matched controls. Intravenous arginine and glucose elicited an exaggerated acute phase of insulin secretion in S2H compared with controls when analyzed as incremental insulin area 0–10′, peak level attained, and mean insulin levels postinjection. Insulin responses to arginine and glucose in SOH and matched controls were identical. We hypothesize that the increased beta-cell activity found in S2H predisposes their beta-cells to damage by environmental factors and may be part of the mechanism conferring the increased risk of IDD in S2H.
Transcription Factor IIA Mutations Show Activator-specific Defects and Reveal a IIA Function Distinct from Stimulation of TBP-DNA Binding (*)

The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and mediates transcriptional activation by distinct classes of activators. To elucidate the function of TFIIA in transcriptional activation, point mutants were created in the human TFIIA- subunit at positions conserved with the yeast homologue. We have identified a class of TFIIA mutants that stimulate TBP-DNA binding (T-A complex) but fail to support transcriptional activation by several different activators, suggesting that these mutants are defective in their ability to facilitate an activation step subsequent to TBP promoter binding. Point mutations of the hydrophobic core of conserved residues from 65 to 74 resulted in various activation-defective phenotypes. These residues were found to be important for TFIIA - interactions, suggesting that - interactions are critical for TFIIA function as a coactivator. A subset of these TFIIA- mutations disrupted transcriptional activation by all activators tested, except for the Epstein-Barr virus-encoded Zta protein. The Y65F, W72A, and W72F mutants mediate Zta activation, but not GAL4-AH, AP-1, GAL4-CTF, or GAL4-VP16 activation. The W72A mutant failed to stimulate TFIID-DNA binding (D-A complex) but was able to form a complex with TFIID and DNA in the presence of Zta (Z-D-A complex). Thus, the ability of Zta to activate transcription with W72A appears to result from a unique ability to form the stable Z-D-A complex with this mutant. Our results show that different activators utilize the general factor TFIIA in unique ways and that TFIIA contributes transcription activation functions in addition to the facilitation of TBP-DNA binding.
Cutoff wavelengths of metallic waveguides with elliptical cross section

The cutoff wavelengths λcmn of metallic waveguides with elliptical cross section are determined analytically. Two alternative methods, namely, a field and a shape perturbation method are used in the proposed analysis. Exact, closed form expressions, free of Mathieu as well as of Bessel functions, are obtained for the cutoff wavelengths, when the solution is specialized to small values of the eccentricity of the elliptical cross section. Numerical results for all types of modes are also included.
Performance of taylor-kuznetsov memories under timing errors

Lowering the power supply of a circuit can induce transient errors in the memory cells and timing errors in the computation units. In this paper, we consider the Taylor-Kuznetsov (TK) memory architecture with transient errors in the memory cells and with timing errors in the correction circuit. We provide a theoretical analysis of the performance of TK memories under transient errors and timing errors. Our study is based on the analysis of the computation trees of the equivalent Gallager B decoders with and without timing errors. As a main result, we show that as the number of iterations goes to infinity, the error probability of the decoder with timing errors converges to the error probability of the decoder without timing errors. Monte Carlo simulations confirm this result even for moderate code lengths.
Nebivolol vs Amlodipine as First-line Treatment of Essential Arterial Hypertension in the Elderly

The antihypertensive efficacy of nebivolol and amlodipine and their tolerability were compared in a multicentre, randomized, active-controlled, double-blind parallel-group trial in elderly patients with mild to moderate essential arterial hypertension. One hundred and eighty-four subjects aged S 65 years were screened. After a run-in phase of 4 weeks, only 168 of these were randomized with either nebivolol 2.5- 5 mg daily ( n = 81) or amlodipine 5-10 mg daily ( n = 87) over a period of 12 weeks. The response rate to treatment and the changes of sitting diastolic blood pressure (BP) at week 12 were similar between the two groups. A lower sitting systolic BP (SBP) was detected with amlodipine at week 4 ( p < 0.05) and at week 8 ( p < 0.05). Standing BP showed no changes between the two groups; only SBP was lower with amlodipine at week 8 ( p < 0.05). Heart rate was lower at all treatment visits with nebivolol ( p < 0.001). The incidence of adverse events was no different between the two groups; however the incidence of headache and ankle oedema was significantly higher with amlodipine ( p < 0.05). In elderly subjects with essential hypertension, the antihypertensive efficacy of nebivolol and amlodipine was similar. Both drugs were well tolerated, although amlodipine was accompanied by higher incidence of drug-related adverse events.
Snail Destabilizes Cell Surface Crumbs3a

During epithelial to mesenchymal transition (EMT), cells modulate expression of proteins resulting in loss of apical‐basal polarity. Effectors of this EMT switch target the polarity protein Crumbs3a, a small transmembrane protein that is essential for generation of the apical membrane and tight junctions of mammalian epithelial cells. We previously showed that the Crumbs3 gene is a direct target of transcriptional regulation by Snail, a potent inducer of EMT. However, Snail has also been shown to have multiple non‐transcriptional roles, including regulation of cell adhesion, proliferation and survival. Using SNAP‐tag labeling, we determined that cell surface Crumbs3a has a half‐life of approximately 3 h and that this cell surface half‐life is significantly reduced when EMT is induced by Snail. We further observe that Snail induces differential glycosylation of Crumbs3a, including sialylation, suggesting a mechanism by which Crumbs3a may be destabilized. These results indicate that Crumbs3a is a post‐translational target of Snail, in addition to being a transcriptional target. We conclude that Snail's ability to post‐translationally modify and destabilize Crumbs3a augments the depolarizing process of EMT.
The comparative effects of methanol extract of Phyllanthus amarus leaves and Vitamin E on the Sperm parameters of Male guinea pigs

The effects of the methanol extracts of the leaves of Phyllanthus amarus on the sperm parameters of male Guinea pigs were investigated. The effects of Vitamin E on the sperm parameters were also investigated and compared to that of Phyllanthus amarus. The phytochemical screening of the leaves of Phyllanthus amarus was also carried out. The methanol extract of the Phyllanthus amarus leaf (50-200mg/kg) caused a decrease in the sperm count and motility, from 65.0± 2.80 and 66.7±0.33 to 46.0± 2.10 and 37.7± 1.50 respectively. However, this effect was less pronounced at higher doses of Phyllanthus amarus (400 and 800mg/kg). At 400 and 800mg/kg, P. amarus caused a decrease in sperm motility and count from 65.0±2.50 and 66.7± 1.5 to 52.7± 0.50 and 56.7± 0.80 : to 43.3±1.70 and 48.3±1.70 respectively . These effects were dose- dependent and comparable to the observed effects of Vitamin E (500IU) on sperm parameters of male guinea pigs. These were significant at P < 0.05 (ANOVA). In timedependent study, the observed effect of P. amarus (800mg/kg) and Vitamin E on the values of sperm count and motility at 28 day were almost the same. These values are 56.7± 3.30 and 48.3± 1.70 for vitamin E; 47.5±2.50 and 47.5± 2.50 for P.amarus respectively for sperm motility and count. These effects were time- dependent and statistically significant at P < 0.05 (ANOVA). Finally, the phytochemical screening of the leaves of Phyllanthus amarus revealed the presence of flavonoids, tannins, alkaloids, terpenoids, steroids, saponins and cardiac glycosides. This shows that the leaves of P . amarus do not largely contribute direct to the claims on the use of the aerial part of this plant by traditional medicine practitioners to increase/improve libido in men but it may have some indirect beneficial effects on this claim (like antioxidant activity) that mimic Vitamin E in both action and mechanism of action. However, further studies need to be done to investigate the contribution of the seeds of this plant in the improvement of libido in men and to isolate and characterize the active principles in the extracts of this plant. @ JASEM