Miracle-dz/UniFAR-FTUs huggingface dataset:
The importance of age to the motoric effects of striatal dopamine depletion in an experimental model of Parkinson's Disease /

Two experiments explored the neurobioiogica! basis of the different rates of recovery from motor deficits in adult and weanling rats following selective depletion of nigrostriatal dopamine (DA) with 6 -hydroxydopamine (6 -OHDA). First, adult rats that had been DA-depleted as weanlings and age-matched sham-treated controls received acute striatal infusions of the D2-like DA antagonist sulpiride (0, 3.0, and lO.Opg), resulting in dose-dependent akinesia and catalepsy in both groups. This demonstrated that at this age these DA-depleted rats continue to rely on striatal DA transmission for the sensorimotor behavior expressed following recovery of function. Also, 6 -OHDA treated weanlings did not exhibit behavioral supersensitivity to this acute antagonist. Second, when sensorimotor recovery differed most dramatically between rats DAdepleted as adults or weanlings (5-8 days following the lesion), in-vivo microdialysis was used to assess both relative basal extracellular striatal DA concentrations and DA modulation of striatal acetylcholine (ACh) as indicated by the response to intrastriatal administration o f the D2-like DA antagonist sulpiride (10 & 100 |iM). DA-depleted adult rats exhibited significantly reduced basal extracellular striatal DA compared with sham-treated controls, while DA-depleted weanling rats exhibited DA concentrations similar to their age-matched sham-treated controls. DA-depleted adult rats exhibited a trend toward the expected decrease in sulpirideinduced ACh efflux when compared to age-matched sham-treated controls. Interestingly, weanling rats exhibited reduced sulpiride-induced ACh efflux compared with adult rats, despite the higher basal extracellular ACh found in the weanlings. These results suggest that adult rats exhibit a reduction in striatal DA transmission at a time prior to recovery of motoric function following DA depletion. Weanling rats exhibited control-levels of extracellular striatal DA at a time when they show no signs of motoric deficit. However decreased sulpiride-induced striatal ACh efflux rendered this test of postsynaptic DA transmission less useful, so this component of the correlation remains unclear. Weanling rats exhibit control levels of extracellular striatal DA which may underlie their feilure to show behavioral supersensitivity to acute intrastriatal DA antagonist infusion. However the critical postsynaptic activity mediated by this increased striatal DA remains to be determined.
Productively Lindelöf Spaces May All Be D

Abstract We give easy proofs that (a) the Continuum Hypothesis implies that if the product of $X$ with every Lindelöf space is Lindelöf, then $X$ is a $D$ -space, and (b) Borel's Conjecture implies every Rothberger space is Hurewicz.
Conduits of innovation or imitation?assessing the effect of alliances on the persistence of profits in U.S. firms

Abstract This paper examines if a firm’s alliances affect the persistence of its financial performance. The literature suggests two conflicting views concerning this effect. In particular, access to resources and innovation and the risk of imitation from alliances can have different impacts on performance. In our empirical analysis, based on a panel of 509 firms covering the years 1992 to 2002, return on assets was regressed on the number of alliances and other control variables using hierarchical linear modeling. Results support the positive view of alliances as mechanisms to sustain competitive advantage and escape from competitive disadvantage through access to external, valuable resources held by other firms. Alliances also help firms to constantly innovate and buffer themselves from external shocks that erode existing advantages. Our results, however, may be specific to the period and the institutional context under consideration and we do not distinguish between types, purposes and “strength” of alliances. We contribute to the debate about profit persistence by examining one particular factor that has been neglected in the literature: the extent to which firms engage in alliances with other actors. From a managerial perspective, our study shows that alliances can be used as an effective tool to support superior performance or avoid lock-in into inferior performance.
Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ 2 = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.
Behavioral/systems/cognitive Effective Connectivity Reveals Important Roles for Both the Hyperdirect (fronto-subthalamic) and the Indirect (fronto-striatal-pallidal) Fronto-basal Ganglia Pathways during Response Inhibition

Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with the subthalamic nucleus or, alternatively, via the indirect pathway between the cortex and caudate. To test the relative contribution of these two pathways to inhibitory action control, we applied an innovative quantification method for effective brain connectivity. Functional magnetic resonance imaging data were collected from 20 human participants performing a Simon interference task with an occasional stop signal. A single right-lateralized model involving both the hyperdirect and indirect pathways best explained the pattern of brain activation on stop trials. Notably, the overall connection strength of this combined model was highest on successfully inhibited trials. Inspection of the relationship between behavior and connection values revealed that fast inhibitors showed increased connectivity between rIFG and right caudate (rCaudate), whereas slow inhibitors were associated with increased connectivity between preSMA and rCaudate. In compliance, connection strengths from the rIFG and preSMA into the rCaudate were correlated negatively. If participants failed to stop, the magnitude of experienced interference (Simon effect), but not stopping latency, was predic-tive for the hyperdirect–indirect model connections. Together, the present results suggest that both the hyperdirect and indirect pathways act together to implement response inhibition, whereas the relationship between performance control and the fronto-basal ganglia connections points toward a top-down mechanism that underlies voluntary action control.
Implications of the Admixture Process in Skin Color Molecular Assessment

The understanding of the complex genotype-phenotype architecture of human pigmentation has clear implications for the evolutionary history of humans, as well as for medical and forensic practices. Although dozens of genes have previously been associated with human skin color, knowledge about this trait remains incomplete. In particular, studies focusing on populations outside the European-North American axis are rare, and, until now, admixed populations have seldom been considered. The present study was designed to help fill this gap. Our objective was to evaluate possible associations of 18 single nucleotide polymorphisms (SNPs), located within nine genes, and one pseudogene with the Melanin Index (MI) in two admixed Brazilian populations (Gaucho, N = 352; Baiano, N = 148) with different histories of geographic and ethnic colonization. Of the total sample, four markers were found to be significantly associated with skin color, but only two (SLC24A5 rs1426654, and SLC45A2 rs16891982) were consistently associated with MI in both samples (Gaucho and Baiano). Therefore, only these 2 SNPs should be preliminarily considered to have forensic significance because they consistently showed the association independently of the admixture level of the populations studied. We do not discard that the other two markers (HERC2 rs1129038 and TYR rs1126809) might be also relevant to admixed samples, but additional studies are necessary to confirm the real importance of these markers for skin pigmentation. Finally, our study shows associations of some SNPs with MI in a modern Brazilian admixed sample, with possible applications in forensic genetics. Some classical genetic markers in Euro-North American populations are not associated with MI in our sample. Our results point out the relevance of considering population differences in selecting an appropriate set of SNPs as phenotype predictors in forensic practice.
Plasminogen Activator Inhibitor-1 4G/5G Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis

Background The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. Objective and Methods The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. Results The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P<0.0001). Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017), study region (P = 0.014), control group sample size (P = 0.011), total sample size (P = 0.011), and ratio of the case to the control group sample size (RR) (P = 0.019). In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02). Conclusions In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.
The Organizational Life Cycle: Review and Future Agenda

Purpose: The review summarizes major research that contributed to the organizational life cycle theory, discusses major issues and contradictions of the theory and offers additional assumptions about the organizational life cycle. Based on that, it attempts to offer a future research agenda for the theory.Methodology/Approach: The paper uses narrative review; the list of included life cycle models stems from previous summaries of the theory and subsequent snowball search through reference lists of individual reviewed papers.Findings: The theory is rich with various life cycle models that nevertheless converge on some major characteristics. Organizational life cycle can be described with classical five stages: (i) founding, (ii) growth, (iii) maturity, (iv) decline, and (v) revival. However, the stages do not necessarily follow in such an order, and therefore the research establishes likely paths in their development. Also, it appears that growth rate (relative to a market) and change in formalism are major factors distinguishing in the theory individual stages.Research Limitation/implication: Organizational life cycle theory is often neglected based on simplifying presumptions like determinism of organizational development. On the other hand, there is a growing evidence that factors stemming from particular life cycle stages alter organizational behavior and therefore should be considered in behavioral research on an organizational level.Originality/Value of paper: The paper represents up to date review of major theoretical models from the perspective of the current state of the field. Since the theory flourished in 70’s and 80’s it is inevitably limited in some aspects. The new review may spark renewed interest in implications stemming from the theory and enrich analytical tools of management scholars.
B-type natriuretic peptide following thoracic surgery: a predictor of postoperative cardiopulmonary complications.

OBJECTIVES B-type natriuretic peptides (BNPs) are secreted by the human heart in response to ventricular wall stretch or myocardial ischaemia, and predict adverse cardiovascular events and death in the general population. Following non-cardiac surgical procedures, there is growing evidence supporting BNP measurement as a powerful independent predictor of death and perioperative complications. However, the clinical implication of elevated BNP measurements after pulmonary resection has not been completely defined. This study aimed to evaluate the role of BNP in predicting adverse cardiopulmonary events after thoracic surgery. METHODS A prospective, short-term, observational cohort study was conducted in a tertiary care hospital, including consecutive patients undergoing scheduled pulmonary resection between April 2012 and October 2013. Baseline clinical details were obtained; serum BNP levels were measured at baseline and on postoperative days 1 and 4. RESULTS We enrolled 294 consecutive patients, median age 66 [interquartile range (IQR): 57-73], 67% male. There were 2 perioperative deaths, and 52 patients experienced one or more cardiopulmonary complications. The baseline median BNP value was normal (29.5 pg/ml, IQR: 16-57.2), and showed significant postoperative increase, peaking on day 1. Patients who developed postoperative complications had a significantly greater BNP increase (P < 0.0001) when compared with those without complications. A postoperative day 1 BNP measurement of ≥118.5 [receiver operating characteristic area: 0.654; 95% confidence interval (CI): 0.57-0.74; P = 0.001] was associated with a 3-fold risk of developing postoperative cardiopulmonary complications [odds ratio (OR): 2.94; 95% CI: 1.32-6.57; P = 0.008]. Logistic regression analysis showed major pulmonary resections (lobectomies or pneumonectomies), BNP ≥ 118.5 and age ≥ 65 to be the only independent predictive variables. In the subset of patients undergoing lobectomy or pneumonectomy (n = 226), BNP was the strongest independent predictor of complications (OR: 3.49; 95% CI: 1.51-8.04). CONCLUSIONS Our results show that BNP elevation, measured in the first days after thoracic surgery, is independently associated with postoperative adverse events. In patients undergoing major pulmonary resections, a postoperative BNP elevation is the strongest independent predictor of cardiopulmonary complications.
Evaluating e-Learning Initiatives: A Literature Review on Methods and Research Frameworks

Evaluation aspects, in relation to e-learning initiatives, are gaining substantial attention. As technology continuously influences learning, technical as well as organizational requirements need to be thoroughly investigated across a variety of stakeholders. In this paper, an outline of those aspects is presented, which occurred from a literature review on methods and research frameworks utilized toward the evaluation of e-learning initiatives. The review identified a series of studies that take advantage of well-established theories in the area of users' acceptance of technology combined with additional, e-learning context-specific factors. Results of the review are presented, according to the adopted research model, to ease the process of locating and retrieving e-learning evaluation paradigms per theoretical model. In addition, research findings are discussed and future implications for e-learning evaluation initiatives as well as potential stakeholders are highlighted.
Presynaptic inhibitory effect of acetylcholine in the hippocampus

(1) In order to investigate the effects of acetylcholine (ACh) on synaptic transmission in the rat hippocampus, extracellular and intracellular recordings were made from pyramidal neurons in an in vitro slice preparation while synaptic inputs to the cell population were stimulated. ACh was applied ionophoretically into somatic and dendritic layers of the slice. (2) ACh applied into the apical dendritic layer of the CA1 region reduced the size of the locally evoked field excitatory postsynaptic potential (EPSP) without altering the size of the afferent fiber volley. Likewise, dendritically applied ACh reduced the size of intracellularly recorded EPSPs. This effect of ACh appeared to be muscarinic since it was not affected by hexamethonium (up to 3 X 10–5 M) but was antagonized by atropine in a dose-dependent manner. (3) The distribution of Ach-sensitive sites matched closely the spatial distribution of activated synapses on the pyramidal cell dendrites as shown by ionophoretic mapping experiments. (4) In contrast to the effects of dendritic applications of ACh, ionophoresis of ACh into the cell layer resulted in an increase and prolongation of EPSPs and a transient decrease in the size of recurrent somatic inhibitory postsynaptic potentials (IPSPs). These effects on synaptic potentials could not be explained by the observed changes in membrane potential and input resistance following somatic application of ACh. (5) Short dendritic applications of ACh had no consistent effect on the membrane potential or slope conductance of pyramidal neurons and did not attenuate the depolarization evoked by brief dendritic applications of glutamate. In addition, the time course of ACh-reduced EPSPs was not different from control. (6) We conclude that ACh exerts a presynaptic inhibitory effect on both excitatory and inhibitory afferents to hippocampal pyramidal neurons. This effect of ACh is widespread, occurring in all regions of Ammon's horn tested as well as in stratum moleculare of fascia dentata.
Little impact of hatchery supplementation that uses native broodstock on the genetic structure and diversity of steelhead trout revealed by a large-scale spatio-temporal microsatellite survey

Artificial breeding programs initiated to enhance the size of animal populations are often motivated by the desire to increase harvest opportunities. The introduction of non‐native genotypes, however, can have negative evolutionary impacts. These may be direct, such as introgressive hybridization, or indirect via competition. Less is known about the effects of stocking with native genotypes. We assayed variation at nine microsatellite loci in 902 steelhead trout (Oncorhynchus mykiss) from five rivers in British Columbia, Canada. These samples were collected over 58 years, a time period that spanned the initiation of native steelhead trout broodstock hatchery supplementation in these rivers. We detected no changes in estimates of effective population size, genetic variation or temporal genetic structure within any population, nor of altered genetic structure among them. Genetic interactions with nonmigratory O. mykiss, the use of substantial numbers of primarily native broodstock with an approximate 1:1 male‐to‐female ratio, and/or poor survival and reproductive success of hatchery fish may have minimized potential genetic changes. Although no genetic changes were detected, ecological effects of hatchery programs still may influence wild population productivity and abundance. Their effects await the design and implementation of a more comprehensive evaluation program.
Disease-Related Cardiac Troponins Alter Thin Filament Ca2+ Association and Dissociation Rates

The contractile response of the heart can be altered by disease-related protein modifications to numerous contractile proteins. By utilizing an IAANS labeled fluorescent troponin C, , we examined the effects of ten disease-related troponin modifications on the Ca2+ binding properties of the troponin complex and the reconstituted thin filament. The selected modifications are associated with a broad range of cardiac diseases: three subtypes of familial cardiomyopathies (dilated, hypertrophic and restrictive) and ischemia-reperfusion injury. Consistent with previous studies, the majority of the protein modifications had no effect on the Ca2+ binding properties of the isolated troponin complex. However, when incorporated into the thin filament, dilated cardiomyopathy mutations desensitized (up to 3.3-fold), while hypertrophic and restrictive cardiomyopathy mutations, and ischemia-induced truncation of troponin I, sensitized the thin filament to Ca2+ (up to 6.3-fold). Kinetically, the dilated cardiomyopathy mutations increased the rate of Ca2+ dissociation from the thin filament (up to 2.5-fold), while the hypertrophic and restrictive cardiomyopathy mutations, and the ischemia-induced truncation of troponin I decreased the rate (up to 2-fold). The protein modifications also increased (up to 5.4-fold) or decreased (up to 2.5-fold) the apparent rate of Ca2+ association to the thin filament. Thus, the disease-related protein modifications alter Ca2+ binding by influencing both the association and dissociation rates of thin filament Ca2+ exchange. These alterations in Ca2+ exchange kinetics influenced the response of the thin filament to artificial Ca2+ transients generated in a stopped-flow apparatus. Troponin C may act as a hub, sensing physiological and pathological stimuli to modulate the Ca2+-binding properties of the thin filament and influence the contractile performance of the heart.