Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphologic and Biochemical Changes of the Masseter Muscles Induced by Occlusal Wear: Studies in a Rat Model

Occlusal alterations may result in changes in the functional performance of masticatory muscles. In this study, we set up an experimental model in rats to examine whether masticatory muscle abnormalities occur after a malocclusion is induced. Rats underwent unilateral amputation of the molar cusps to simulate an occlusal wear situation. The masseter muscles ipsilateral and contralateral to the amputated molars were excised at different experimental times. Sham-operated rats were used as controls. The tissue samples were studied by light and electron microscopy and morphometry. Tissue calcium content, a biochemical index of muscle injury, was also determined. The results show that occlusal dysfunction leads to microvessel constriction and clear-cut morphologic damage of muscular fibers and blood capillary endothelium, as well as to elevation of tissue calcium content, in the ipsilateral masseter muscle. These changes are likely related to muscle fatigue and ischemia. The early signs of injury do not involve the entire muscle but are mostly restricted to tissue areas rich in type I (slow) muscle fibers, which are characterized by a predominantly aerobic metabolism. The muscle damage becomes more extended and severe with time. On the other hand, the contralateral muscles show only slight alterations which are reversible with time, possibly due to an adaptive response.
Assembly of fibrin. A light scattering study.

Using stopped flow light scattering, we show that assembly of fibrin following activation with non-rate-limiting amounts of thrombin or reptilase occurs in two steps, of which the first is end-to-end polymerization of fibrin monomers to protofibrils and the second is lateral association of protofibrils to fibers, in agreement with Ferry's original proposal. Polymerization is found to proceed as a bimolecular association of bifunctional monomers; the overall rate varies as the inverse first power of the concentration; end-to-end association of two monomers, of a monomer and an oligomer, and of two oligomers occurs with the same rate constant. The value of the rate constant is 8.2 C 10(5) M-1 s-1 in 0.5 M NaCl, is three times larger in 0.1 M NaCl (0.05 M Tris, pH 7.4), and is the same following activation by reptilase and by thrombin. The onset of growth of fibers from protofibrils takes 12 times longer in 0.5 than in 0.1 M salt, i.e. thick fibers ("coarse" gels) form from short protofibrils, and thin fibers ("fine" gels) form from longer protofibrils. Jumps of salt concentration at times when protofibrils, but not fibers, have formed result in immediate growth of thick fibers at low salt from long protofibrils formed at high salt. The rate of fiber growth in these experiments varies as the inverse first power of the concentration. 3the instant of gelation (formation of a network of fibers) falls in the later half of the time during which the scattering rises due to fiber growth; the rise of gel rigidity after gelation is found to continue beyond the end of this period. Jumps from low to high salt result in retention of whatever fibers have formed at low salt and a very small additional increase of the scattering due to further fiber growth at high salt. From a variety of evidence, we conclude that the properties of fibrin are determined by kinetics and not equilibria of assembly steps. Results obtained here agree with the following scheme of fibrin assembly: monomers polymerize to protofibrils; long protofibrils associate laterally to fibers; occasionally a long protofibril associates with two different fibers to form an interfiber connection; fiber growth does not reverse to yield stabler, more compact, structures and terminates in formation of a network of fibers. The typical delay of fiber growth is the time during which protofibrils form from monomers. Measurements at rate-limiting concentrations of thrombin have allowed estimation of turnover rates of fibrinopeptides that agree with kinetic parameters obtained with direct assay of fibrinopeptide. Release of fibrinopeptide B causes more rapid fiber formation. Addition of thrombin after activation by reptilase, at a time when protofibrils, but not fibers, have formed, is followed rapidly by fiber formation; this proves that thrombin readily removes fibrinopeptide B from protofibrils. On the basis of these new results and earlier work (in particular, Blombäck, B. , Hessel, B. , Hogg, D. , and Therkildsen, L.
Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7–dependent

Significance Preterm birth is a leading cause of neonatal mortality, with a poorly understood etiology. The maintenance of uterine quiescence across gestation is fundamental for term parturition. At the molecular level, an integrated uterine endoplasmic reticulum stress-unfolded protein response (UPR-ERSR) regulates both caspase-3 (CASP3) and caspase-7 (CASP7), preserving myometrial quiescence throughout gestation. Here we show that prolonged ERSR diminishes the tocolytic potential of uterine CASP3 and 7, causing an increase in myometrial contractile responsiveness and onset of preterm labor in pregnant mice. Prophylaxis with 4-phenylbutrate, however, maintains active uterine CASP3 and 7 and prolongs gestational length. This study establishes a critical role for UPR-ERSR in the regulation of pregnant uterine myocyte quiescence. We previously identified myometrial caspase-3 (CASP3) as a potential regulator of uterine quiescence. We also determined that during pregnancy, the functional activation of uterine CASP3 is likely governed by an integrated endoplasmic reticulum stress response (ERSR) and is consequently limited by an increased unfolded protein response (UPR). The present study examined the functional relevance of uterine UPR-ERSR in maintaining myometrial quiescence and regulating the timing of parturition. In vitro analysis of the human uterine myocyte hTERT-HM cell line revealed that tunicamycin (TM)-induced ERSR modified uterine myocyte contractile responsiveness. Accordingly, alteration of in vivo uterine UPR-ERSR using a pregnant mouse model significantly modified gestational length. We determined that “normal” gestational activation of the ERSR-induced CASP3 and caspase 7 (CASP7) maintains uterine quiescence through previously unidentified proteolytic targeting of the gap junction protein, alpha 1(GJA1); however, surprisingly, TM-induced uterine ERSR triggered an exaggerated UPR that eliminated uterine CASP3 and 7 tocolytic action precociously. These events allowed for a premature increase in myometrial GJA1 levels, elevated contractile responsiveness, and the onset of preterm labor. Importantly, a successful reversal of the magnified ERSR-induced preterm birth phenotype could be achieved by pretreatment with 4-phenylbutrate, a chaperone protein mimic.
Mechanism of stimulation of T cells by Streptococcus pyogenes: isolation of a major mitogenic factor, cytoplasmic membrane-associated protein

Our previous studies established that heat-killed Streptococcus pyogenes, as well as other gram-positive cocci, when incubated with human peripheral blood leukocytes (PBLs) in culture, induced polyclonal activation of T lymphocytes. The activated T lymphocytes included CD4+ CD8- helper T cells and CD3+ and CD4- CD8- double-negative T cells with gamma delta T-cell receptors. In the present study, we isolated a major factor with this unique mitogenic activity against human T lymphocytes from S. pyogenes. This active fraction was found in the cytoplasmic membrane (CM) of the heat-killed organisms but not in other cellular fractions such as cell walls, peptidoglycan, lipoteichoic acids, or cytoplasmic soluble fractions. An active molecule(s) was further isolated from the CM by cholic acid extraction followed by Sephacryl S-200 chromatography. The molecule was protease labile but highly resistant to heat, had a pI of greater than or equal to 9.3 and a molecular weight of 10,000 to 15,000 according to gel filtration experiments, and was termed CM-associated protein. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the protein purified by anion-exchange chromatography showed a single band with a molecular weight of 15,000, corresponding to mitogenically active regions. Purified CM-associated protein induced activation of T lymphocytes, which consisted of CD4+ CD8- T cells and CD4- CD8- double-negative T-cell receptor gamma/delta + T-cell populations, as did the whole cells of S. pyogenes.
CK2 Oppositely Modulates l-DOPA-Induced Dyskinesia via Striatal Projection Neurons Expressing D1 or D2 Receptors

We have previously shown that casein kinase 2 (CK2) negatively regulates dopamine D1 and adenosine A2A receptor signaling in the striatum. Ablation of CK2 in D1 receptor-positive striatal neurons caused enhanced locomotion and exploration at baseline, whereas CK2 ablation in D2 receptor-positive neurons caused increased locomotion after treatment with A2A antagonist, caffeine. Because both, D1 and A2A receptors, play major roles in the cellular responses to l-DOPA in the striatum, these findings prompted us to examine the impact of CK2 ablation on the effects of l-DOPA treatment in the unilateral 6-OHDA lesioned mouse model of Parkinson's disease. We report here that knock-out of CK2 in striatonigral neurons reduces the severity of l-DOPA-induced dyskinesia (LID), a finding that correlates with lowered pERK but unchanged pPKA substrate levels in D1 medium spiny neurons as well as in cholinergic interneurons. In contrast, lack of CK2 in striatopallidal neurons enhances LID and ERK phosphorylation. Coadministration of caffeine with a low dose of l-DOPA reduces dyskinesia in animals with striatopallidal knock-out to wild-type levels, suggesting a dependence on adenosine receptor activity. We also detect reduced Golf levels in the striatonigral but not in the striatopallidal knock-out in response to l-DOPA treatment. Our work shows, in a rodent model of PD, that treatment-induced dyskinesia and striatal ERK activation are bidirectionally modulated by ablating CK2 in D1- or D2-positive projection neurons, in male and female mice. The results reveal that CK2 regulates signaling events critical to LID in each of the two main populations of striatal neurons. SIGNIFICANCE STATEMENT To date, l-DOPA is the most effective treatment for PD. Over time, however, its efficacy decreases, and side effects including l-DOPA-induced dyskinesia (LID) increase, affecting up to 78% of patients within 10 years of therapy (Hauser et al., 2007). It is understood that supersensitivity of the striatonigral pathway underlies LID, however, D2 agonists were also shown to induce LID (Bezard et al., 2001; Delfino et al., 2004). Our work implicates a novel player in the expression of LID, the kinase CK2: knock-out of CK2 in striatonigral and striatopallidal neurons has opposing effects on LID. The bidirectional modulation of dyskinesia reveals a central role for CK2 in striatal physiology and indicates that both pathways contribute to LID.
Age-related response to lidocaine-prilocaine (EMLA) emulsion and effect of music distraction on the pain of intravenous cannulation.

OBJECTIVE To compare the efficacy of a local anesthetic cream and music distraction in reducing or preventing pain from needle puncture (intravenous cannulation) in children. A secondary aim was to examine the influence of age on the pain report and behavior and on the therapeutic outcome. METHODOLOGY Children aged 4 to 16 years (N = 180) who were to undergo surgery under general anesthesia via intravenous cannulation were randomly allocated to one of three interventions. The comparison of lidocaine-prilocaine emulsion (EMLA, Astra) and a placebo emulsion was double-blind. Stratification by age group (4 to 6, 7 to 11, 12 to 16) ensured an equal number of children (20) in each intervention/age group category. A global assessment of the behavioral reaction to the procedure was made by the principal investigator, taking into account vocal, verbal, facial, and motor responses. The child was asked to assess pain severity on the Faces Pain Scale (FPS) and a visual analogue toy (VAT). The scales were applied conservatively as ordinal scales: FPS 0 to 6; VAT 0 to 10. RESULTS Children who received lidocaine-prilocaine emulsion reported less pain (mean FPS score = 1.42) compared with placebo emulsion (mean FPS score = 2.58) and with music distraction (mean FPS = 2.62). There was a highly significant therapeutic effect (P < .001) on the self-report and behavioral scores. Younger children, regardless of intervention, reported significantly more pain than the older children (mean FPS scores: 2.85, 2.33, 1.43 for age groups 4 to 6, 7 to 11, and 12 to 16 respectively; P < .001). The superiority of the local anesthetic emulsion was maximal in the youngest age group (4 to 6) almost eliminating pain-related behavior, and multiple regression analysis confirmed significant age and treatment effects and revealed interaction between therapeutic effect and age. Although a trend favoring the active emulsion was evident in the older children (7 to 11, 12 to 16) the differences were not significant. The pain scores were influenced by the type (gauge) of cannula, but this did not affect the conclusion regarding therapeutic and age effects. There was no influence of sex, experience with venipuncture, or whether the child was anxious on arrival in the operating room. CONCLUSIONS The results show that lidocaine-prilocaine emulsion is highly effective in preventing pain from venipunctures in young children, the group in most need of prevention.
Characterization of the octopaminergic and tyraminergic neurons in the central brain of Drosophila larvae

Drosophila larvae are able to evaluate sensory information based on prior experience, similarly to adult flies, other insect species, and vertebrates. Larvae and adult flies can be taught to associate odor stimuli with sugar reward, and prior work has implicated both the octopaminergic and the dopaminergic modulatory systems in reinforcement signaling. Here we use genetics to analyze the anatomy, up to the single‐cell level, of the octopaminergic/tyraminergic system in the larval brain and subesophageal ganglion. Genetic ablation of subsets of these neurons allowed us to determine their necessity for appetitive olfactory learning. These experiments reveal that a small subset of about 39 largely morphologically distinguishable octopaminergic/tyraminergic neurons is involved in signaling reward in the Drosophila larval brain. In addition to prior work on larval locomotion, these data functionally separate the octopaminergic/tyraminergic system into two sets of about 40 neurons. Those situated in the thoracic/abdominal ganglion are involved in larval locomotion, whereas the others in the subesophageal ganglion and brain hemispheres mediate reward signaling. J. Comp. Neurol. 522:3485–3500, 2014. © 2014 Wiley Periodicals, Inc.
Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate.

PURPOSE To determine if iridium implant (IM) and external-beam radiation therapy (EBRT) is better than standard EBRT in locally advanced prostate cancer. METHODS Patients with T2 and T3 prostate cancer with no evidence of metastatic disease were randomly assigned to EBRT of 66 Gy in 33 fractions during 6.5 weeks or to IM of 35 Gy delivered to the prostate during 48 hours plus EBRT of 40 Gy in 20 fractions during 4 weeks. The primary outcome consisted of biochemical or clinical failure (BCF). BCF was defined by biochemical failure, clinical failure, or death as a result of prostate cancer. Secondary outcomes included 2-year postradiation biopsy positivity, toxicity, and survival. RESULTS Between 1992 and 1997, 51 patients were randomly assigned to receive IM plus EBRT, and 53 patients were randomly assigned to receive EBRT alone. The median follow-up was 8.2 years. In the IM plus EBRT arm, 17 patients (29%) experienced BCF compared with 33 patients (61%) in the EBRT arm (hazard ratio, 0.42; P = .0024). Eighty-seven patients (84%) had a postradiation biopsy; 10 (24%) of 42 in the IM plus EBRT arm had biopsy positivity compared with 23 (51%) of 45 in the EBRT arm (odds ratio, 0.30; P = .015). Overall survival was 94% in the IM plus EBRT arm versus 92% in the EBRT arm. CONCLUSION The combination of IM plus EBRT was superior to EBRT alone for BCF and postradiation biopsy. This trial provides evidence that higher doses of radiation delivered in a shorter duration result in better local as well as biochemical control in locally advanced prostrate cancer.
UvA-DARE (Digital Academic Repository) Motivational sensitivities linked to impulsive motor errors in Parkinson’s disease

Objectives: We investigated how broad motivational tendencies are related to the expression and suppression of action impulses in Parkinson ’ s disease (PD). Methods: Sixty-nine participants with PD completed a Simon response con ﬂ ict task and Behavioral Inhibition System ( BIS ) and Behavioral Activation System ( BAS ) scales based on Gray ’ s (1987) reinforcement sensitivity theory. Analyses determined relationships between BIS , BAS , and the susceptibility to making impulsive action errors and the pro ﬁ ciency of inhibiting interference from action impulses. Results: BIS scores correlated positively with rates of impulsive action errors, indicating that participants endorsing low BIS tendencies were much more susceptible to acting on strong motor impulses. Analyses of subgroups with high versus low BIS scores con ﬁ rmed this pattern and ruled out alternative explanations in terms of group differences in speed-accuracy tradeoffs. None of the scores on the BIS or BAS scales correlated with reactive inhibitory control. Conclusions: PD participants who endorse diminished predilection toward monitoring and avoiding aversive experiences (low BIS ) show much greater dif ﬁ culty restraining fast, impulsive motor errors. Establishing relationships between motivational sensitivities and cognitive control processes may have important implications for treatment strategies and positive health outcomes in participants with PD, particularly those at risk for falling and driving dif ﬁ culties related to impulsive reactions. ( JINS , 2018, 24 , 128 – 138)
Effect of clipping on the achievable rate of non-orthogonal multiple access with DCO-OFDM

Non-orthogonal multiple access (NOMA) has been studied in visible light communication (VLC) systems such as direct current biased optical orthogonal frequency division multiplexing (DCO-OFDM) for higher spectral efficiency. To ensure the unipolarity of optical signals, clipping is adopted and makes a difference. However, few works on the NOMA with DCO-OFDM (NOMA-DCO-OFDM) system pay attention to the impact of clipping noise. In this paper, the double-sided clipping process and the achievable rate region are depicted and analyzed in the NOMA-DCO-OFDM system. The issue of obtaining the boundary of the achievable rate region in a two-user NOMA scenario can be transformed into two optimization problems. Comparison of achievable rates between NOMA-DCO-OFDM and orthogonal multiple access with DCO-OFDM (OMA-DCO-OFDM) is performed by analytic and simulation results. Numerical results demonstrate that the boundary of achievable rate region cannot be achieved at a fixed DC-offset, and the NOMA-DCO-OFDM system is superior in achievable rate to the OMA-DCO-OFDM system. Moreover, different total power constraint and clipping levels influence the achievable rate region of NOMA-DCO-OFDM system.
Causal relationship between internet use and economic development for selected Central Asian economies

The aim of this study is to examine the effects of information and communications technology (ICT) on economic development of several Central Asian countries. Dumitrescu and Hurlin (DH) panel causality test has been used for the relationship between ICT and economic development. The DH test results indicate that a unidirectional causality exists from GDP per capital to Inter-net use. These results suggest that an increase in GDP per capita can stimulate internet use. In addition, the cross-sectional dependence is examined using LM test of Breusch and Pagan and CD-LM and CD test of Pesaran. The results suggest that the null-hypothesis, no crosssectional dependence exists among countries, is rejected for all the tests, suggesting an economic shock in a one country may have spillover effects on other countries.
New Evidence on the Effects of Quantitative Easing

Have the macroeconomic effects of QE programs been overestimated empirically? Using a large set of model specifications that differ in the degree of time-variation in parameters, the answer is yes. Our forecasting exercise suggests that it is crucial to allow for time-variation in parameters, but not for stochastic volatility to improve the fit with data. Having a more reliable specification, we find that the portfolio balance and signaling channels had sizable contributions to the transmission of QE programs. Finally, our identified structural shocks show that QE1 had larger macroeconomic effects than QE2 and QE3, but much smaller than usually found in the literature.
Amyloidogenic and anti-amyloidogenic properties of recombinant transthyretin variants

Most transthyretin (TTR) mutations lead to TTR amyloid depositions in patients with familial amyloidotic polyneuropathy and familial amyloidotic cardiomyopathy. However, though an amyloidogenic protein itself, TTR inhibits aggregation of Alzheimer's amyloid beta protein (Aβ) in vitro and in vivo. The pathogenic relationship between two amyloidogenic processes remains unclear. To understand how TTR mutations influence the ability of TTR to inhibit Aβ amyloidosis, forty-seven recombinant TTR variants were produced and analyzed. We showed that all recombinant proteins formed tetramers and were functional in thyroxine binding. Acid denaturation at pH 3.8 resulted in aggregation and fibril formation of all TTR variants. However, only TTR G42 and TTR P55 formed fibrils at pH 6.8. Most TTR variants bound to Aβ and inhibited Aβ aggregation in vitro. TTR variants S64, A71, Q89, V107, H114 and I122 revealed decreased binding to Aβ and decreased inhibition of Aβ aggregation. Only TTR G42 and TTR P55 completely failed to bind Aβ and to inhibit Aβ aggregation. We suggest that TTR variants characterized by decreased binding to Aβ or by decreased inhibition of Aβ aggregation in vitro may contribute to Aβ amyloid formation in vivo. These TTR variants might be important targets for epidemiological studies in Alzheimer's disease.
Equity Financing at Islamic Banks: Do Competition and Bank Fundamentals Matter?

ABSTRACT This article investigates the effects of market competition and Islamic banks’ fundamental conditions on Islamic banks’ equity (profit and loss sharing [PLS]) financing. We use a monthly data set on nine Indonesian Islamic banks from 2009 to 2014. Our empirical results show that competition significantly increases Islamic banks’ PLS financing activities, suggesting that Islamic banks use this mode of financing to attract more entrepreneurs. This argument is also strengthened by the negative association between bank fundamentals and equity financing. In addition, we also find that the effects of competition on equity financing decrease when Islamic banks are more stable. Our results call on policymakers to monitor the practices in Islamic banks’ equity financing because of the risk embedded in that mechanism and Islamic banks’ tendency to use such instruments in poor fundamental conditions.