Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of cyclin E in resting and activated B‐chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target

Disease progression in B‐cell chronic lymphocytic leukaemia (B‐CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B‐CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B‐CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin‐dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B‐CLL cells. Cyclin E and cdk2 expression was increased in B‐CLL cells stimulated with a CpG‐oligodeoxynucleotide and interleukin‐2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine‐inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B‐CLL.
Resource allocation‐based life histories: A conceptual basis for studies of ecological toxicology

Whereas ecological assessments of contaminants are concerned with populations and higher levels of organization, most mechanistic work in toxicology is directed at effects on individuals and their parts. We propose that studies based on individuals can be useful in ecological analysis of polluted systems when based on the concepts of resource allocation‐based life history analysis. At the heart of the resource allocation approach is the concept of operative environments of individuals (i.e., environmental factors influencing birth, death, or migration). Contaminants can have strong influences on operative environments, modifying resource allocation strategies that reflect changes in energy assimilation and demands. By examining contaminant‐induced responses of individuals from the perspective of changing operative environments, individual‐based changes and population dynamics can be addressed in an ecologically rigorous manner.
Increased resting functional connectivity in spike‐wave epilepsy in WAG/Rij rats

Functional magnetic resonance imaging (fMRI)–based resting functional connectivity is well suited for measuring slow correlated activity throughout brain networks. Epilepsy involves chronic changes in normal brain networks, and recent work demonstrated enhanced resting fMRI connectivity between the hemispheres in childhood absence epilepsy. An animal model of this phenomenon would be valuable for investigating fundamental mechanisms and testing therapeutic interventions.
On the red fluorescence emission of Aggregatibacter actinomycetemcomitans

A number of studies have indicated that bacteria able to emit red fluorescence can be detected by light in-duced fluorescence technique and killed by photodynamic therapy. The objective of this study was to investigate the red fluorescence properties of the single gram negative capnophilic bacterium Aggregatibacter actinomycetemcomitans, ATCC 33384, and to investigate if these properties were related to the growth, morphology and size of the bacterial colonies. Time trend assessment was made with red fluorescence by QLF (Quantitative Light-induced Fluorescence), as well as with white light digital imaging. It was demonstrated that A. actinomycetemcomitans, a single capnophilic bacterium, is able to produce red fluorescence on its own, i.e. in the absence of other bacteria strains, and that blood agar is necessary to obtain red fluorescence from this bacterium on culture plates. This bacterium formed smooth circular, bell/dome like colonies increasing in size with time exhibiting various red fluorescence behaviors. A large variation in the fluorescence behavior points out an inhomogeneous distribution of red fluorescence within and between the colonies, i.e. the size of the investigated colonies did not correlate with the red fluorescence area, suggesting a dependence on the colony morphology such as the colony growth in height. To our knowledge this is the first study that have shown that A. actinomycetemcomitans on its own is able to produce fluorescence in the red spectral region.
Amino-terminal fragment of urokinase-type plasminogen activator inhibits HIV-1 replication.

CD8+ T lymphocytes have been shown to produce unidentified soluble factors active in suppressing HIV-1 replication. In this study, we purified an HIV-1 suppressing activity from the culture supernatant of an immortalized CD8+ T cell clone, derived from an HIV-1 infected long-term nonprogressor, and identified this activity as the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA). ATF is catalytically inactive, but suppresses the release of viral particles from the HIV-1 infected cell lines via binding to its receptor CD87. In contrast, cell proliferation and the secretion of an HIV-1 LTR driven reporter gene product were not affected by ATF. These findings suggest that ATF may inhibit the assembly and budding of HIV-1, which provides a novel therapeutic strategy for AIDS.
Management of massive and submassive pulmonary embolism: focus on recent randomized trials

Purpose of review Although early pulmonary revascularization is the treatment of choice for patients with high-risk (massive) pulmonary embolism, it remains controversial in patients with intermediate-risk (submassive) pulmonary embolism until recently. Recent published data on the management of high-risk and intermediate-risk pulmonary embolism patients will be the main focus of this review. Recent findings The PEITHO trial supports the rationale of risk stratification in normotensive patients with pulmonary embolism. Patients with right ventricular dilation on echocardiography and positive cardiac troponin test have a high intermediate risk of complication and death. Thrombolysis prevents hemodynamic collapse in these patients but with an increased risk of major bleeding particularly in older patients (>75 years). Reduced dose of thrombolysis and catheter-based reperfusion with or without fibrinolysis have shown promising results. Summary Thrombolysis is the treatment of choice for patients with high-risk pulmonary embolism. Surgical embolectomy is recommended in case of absolute contra-indication to thrombolysis. In patients with acute right ventricular dysfunction on cardiac imaging and myocardial injury, thrombolysis should be considered if they are 75 years or less of age and are at low risk of bleeding. Full-dose thrombolysis may be excessively risky in patients over 75 years. In patients with either RV dilation or elevated cardiac biomarker, thrombolysis is not recommended.
On the First Law of Geography: A Reply

D aniel Sui has sent me a written version of comments presented by five geographers at a panel on the first law of geography organized by him at the 2003 AAG meeting in New Orleans. The comments seem to fall into two camps: some reject the idea of ‘‘laws’’ in geography, and others feel that my notion has been of some merit. Interestingly, several other laws are cited in the comments; two by Isaac Newton (gravity, motion), two additional ‘‘first’’ laws (ecology, social science), four additional laws applying to people (utility maximization, primate city, human behavior, and Gresham’s), and three ‘‘second’’ laws (thermodynamics, spatial heterogeneity, things are never equal—the last two being only suggestions). Curiously, they do not mention other well-known laws, such as those of Zipf (1949), or Ravenstein’s (1885) 10 laws, or a second law of geography by proposed by Arbia, Benedetti, and Espa (1996) and one by myself (Tobler 1999, 87). The comments then focus on three topics. One is a discussion of what constitutes a law, and whether ‘‘the first law of geography’’ fits into the appropriate definition. Much of the remaining material examines the concepts of ‘‘related’’ and ‘‘near. ’’ Smith is quite correct in pointing out that this discussion would never have taken place if the specific word law had not been used. And Barnes is also correct when he puts it into context and observes that, by restricting myself to local effects, I used the notion to parse the possible complexities of simulating urban growth. I am a great believer in simplicity, when this is possible. For example, the point in science is to achieve as many results as possible with the fewest hypotheses. So, in order to simplify the problem of depicting the growth of population in the Detroit region, I tried to eliminate complicating factors. This is when I invoked ‘‘the first law of geography: everything is related to everything else but near things are more related than distant things. ’’ Doing this allowed me to concentrate on local effects— using the idea of a change in the ‘‘unit inhabitant,’’ and ignoring many other possible influences. As a result, Miller calls my simulation effort ‘‘crude,’’ whereas Barnes considers that it invokes complex ideas. Miller would undoubtedly consider economics, transportation, geology, and other factors to produce a much richer, but also more involved, model. Curiously there is no discussion of other concepts from the 1970 paper.
Amyloid β‐protein fragment 31–35 suppresses long‐term potentiation in hippocampal CA1 region of rats in vivo

Effects of fragment 31–35 of amyloid β‐protein (AβP31–35) on the baseline synaptic transmission, shown as fEPSPs, and the long‐term potentiation (LTP) induced by high‐frequency stimuli (HFS) were investigated in vivo in the hippocampal CA1 region of rats; a longer fragment of AβP, i.e., AβP25–35, which had been generally accepted as the active center in AβP, was also tested comparatively along with AβP31–35. The results showed that: (1) the baseline fEPSPs induced by test stimuli were not changed by i.c. v. injection of AβP31–35, while application of either AβP31–35 or AβP25–35 with the same molar concentration (50 nmol) significantly and similarly suppressed the HFS‐induced LTP; (2) higher concentration of AβP31–35 or longer time of AβP exposure exhibited stronger suppression on LTP, indicating a dose‐ and time‐dependent trends; (3) no significant effects could be found on the paired‐pulse facilitation (PPF) following AβP31–35 injection; (4) pretreatment with verapamil (2.5 mg/kg, i.p., 1 h prior to HFS), a blocker of L‐type Ca2+ channels, did not affect the baseline fEPSPs, while it exhibited a significant suppression on LTP induced by HFS; and (5) surprisingly enough, coapplication with verapamil and AβP31–35 exhibited a similar suppression on LTP just as both of these two agents were used alone. These results indicate that: (1) AβP31–35, similar to AβP25–35, possesses potent suppressive effects on hippocampal LTP in vivo, supporting our proposal that the fragment AβP31–35 might be to date the shortest active sequence in full‐length of AβP molecule; (2) AβP31–35‐induced LTP suppression is not mediated by affecting the presynaptic processes; and (3) L‐type Ca2+ channels might be one of the main pathways by which AβP31–35 insults LTP. Synapse 60:307–313, 2006. © 2006 Wiley‐Liss, Inc.
The Keystone Island Flap: Use in Large Defects of the Trunk and Extremities in Soft-Tissue Reconstruction

Background: Microsurgical perforator flaps are useful in an array of reconstructive scenarios, but their technical complexity, steep learning curves, and prolonged operative times may limit their widespread adoption. Alternatively, the keystone island flap combines perforator-based vascularity with relative simplicity of nonmicrosurgical tissue rearrangement. This article reviews the authors' reconstructive experience using the keystone flap to reconstruct large trunk and extremity defects. Methods: The authors performed a retrospective chart review of patients undergoing keystone flap reconstruction between 2002 and 2008. Patient demographic data, medical histories, comorbidities, surgical indications, defect characteristics and locations, hospitalization, complications, and follow-up care were evaluated and are presented in this article as an uncontrolled case series. Results: Twenty-eight patients underwent keystone flap reconstruction. The average wound size measured 15.0 ± 11.7 × 13.0 ± 7.9 cm (250.5 ± 379.4 cm2). The average length of stay, including tumor resection, was 6.36 ± 6.68 days. A 35.7 percent overall complication rate was noted; partial and total flap loss was observed in only 7 percent of patients. One patient (3 percent) failed reconstruction and required alternative wound closure. Conclusions: The keystone flap can be applied to large defects of the trunk and extremities, obviating the need for either microsurgical techniques or extensive operative time while achieving primary wound healing. Despite minor complications, the 97 percent reconstructive success rate compares well to published rates of microsurgical tissue transfers but has several advantages: short operative times, high reproducibility, ease of use, and favorable aesthetic outcome. The authors conclude that the keystone flap is a reliable and effective reconstructive surgical technique for reconstruction of soft-tissue defects.
An experimental study of behavioural coping strategies in free-ranging female Barbary macaques (Macaca sylvanus)

A fundamental goal of stress research is to understand how individuals cope with challenges. Studies on a range of vertebrate species suggest that three groups of behaviour—affiliative, aggressive and self-directed behaviours—serve as coping strategies. To date, experimental studies of coping behaviour have tended to be conducted in captive conditions; the limited number of studies in free-ranging or wild settings have been observational in nature. We investigated coping behaviours in free-ranging female Barbary macaques (Macaca sylvanus) at Trentham Monkey Forest, UK, using an experimental playback approach to quantify subjects' responses to mildly aversive threat-grunts. Compared to silent control trials, playbacks of threat-grunts increased aggressive behaviours and one of the two self-directed behaviours examined (self-scratching). No such differences were seen for self-grooming, or for any affiliative behaviour. Elevations in the rate of one measure of aggression, lunging, were positively related to an average measure of adrenocortical activity (median faecal glucocorticoid metabolite levels over the study period). Evidence from females in a variety of Old World monkey species, including Barbary macaques, indicates that affiliative behaviours have an important role in coping with stressful events in the medium to longer term. Our results suggest that, in the short term, female Barbary macaques may use aggressive rather than affiliative behaviours in response to mild stress. These findings highlight the importance of considering how coping mechanisms may vary over time after a stressor, and how coping mechanisms relate to adrenocortical activity. Playback approaches like ours provide a powerful, flexible tool to explore issues such as this in free-ranging and wild animal populations.
Factors affecting choice and image of ethnic restaurants in Serbia

Purpose – With the expansion of dining out, visiting ethnic restaurants is becoming one of dominant trends worldwide. Given the fact that ethnic restaurants involve a number of peculiar elements that are not present when visiting regular “local” restaurants, the purpose of this paper is to identify the key determinants of choosing a particular ethnic-themed restaurant, as well as factors that have an impact on an ethnic restaurant’s perceived image. Design/methodology/approach – Research was done by conducting two separate studies. The first study identified factors that were generally the most significant to respondents when making a choice of an ethnic restaurant in which to dine. For the second study, a new sample of respondents – consisting of those who had just visited such an establishment – was used in order to determine which factors have the most significant impact on creating an image of ethnic restaurants. The research was therefore directed toward those restaurants where the customers can experience a unique atmosphere and ambiance that are synonymous within a given culture. Findings – The results obtained from the first study show that quality of food and price are the two most significant factors that determine which restaurant will be visited. On the other hand, the interior and exterior ranked as the two least important factors. In addition, the second study revealed that following the visit, the strongest impact on the restaurant’s image was its interior. Following interior, service quality surfaced as the most important antecedent of perceived image, while the impacts of price and exterior were weaker, but still statistically significant. Research limitations/implications – The study itself was done in two stages. In the first stage the analytical hierarchical process (AHP) model was used for ranking factors significant for choosing an ethnic restaurant, while in the second stage, structural equation modeling (SEM) model was used to identify triggers of perceived image after a visit to an ethnic restaurant. Future research should utilize both models to determine antecedents of the variables used. Apart from this, it is recommended to employ new variables that further explore the uniqueness of the ethnic restaurants. Originality/value – One of the main contributions of this work is related to combining of the AHP and SEM models, with the objective of completing a comparative results analysis, identifying in the process the positive aspects of both models and building a foundation for their coordination in terms of future use. This is significant, given that only a few prior studies have used such synergy.
Biomarker Optimization to Track the Antithrombotic and Hemostatic Effects of Clopidogrel in Rats

We determined the dose response of the ADP antagonist clopidogrel (0.3-50 mg/kg p.o.) in rat models of thrombosis and provoked bleeding and correlated these activities to ex vivo platelet activation. Carotid artery thrombosis was induced by FeCl2. Bleeding time was measured by mesenteric vessel puncture and renal cortex or cuticle incision. Platelet biomarkers included standard ADP-induced aggregation, P2Y12 receptor occupancy, and phosphorylation of vasodilator-stimulated phosphoprotein. Clopidogrel decreased thrombus weight up to 78%, caused maximal prolongation of cuticle and mesenteric bleeding, but had little effect on renal bleeds. Due to the steep mesenteric dose response, further comparisons concentrated on cuticle bleeding. The half-maximal inhibitory dose (ED50) for thrombus reduction was 2.4 ± 0.4 mg/kg, with 10 mg/kg providing optimal blood flow preservation and thrombus reduction. The ED50 for bleeding was 10.5 ± 3.4 mg/kg. Increased bleeding was intermediate (3-fold) at 10 mg/kg and maximal (6-fold) at 30 mg/kg. All biomarkers were affected, but with differing sensitivity. ED50s for peak platelet aggregation to 10 μM ADP (11.9 ± 0.4 mg/kg) and the vasodilator-stimulated phosphoprotein index (16.4 ± 1.3 mg/kg) approximated the higher ED50 for bleeding. ED50s for ligand binding (3.0 ± 0.3 mg/kg) and late aggregation (5.1 ± 0.4 mg/kg) better matched the lower ED50 for antithrombotic activity. Aspirin exerted lesser effects on bleeding (42-70% increase in all models) and thrombosis (24% inhibition). In summary, antithrombotic doses of clopidogrel have limited effects on bleeding and standard measures of platelet aggregation. Other biomarkers may be more sensitive for tracking antithrombotic efficacy.
Building corporate associations: Consumer attributions for corporate socially responsible programs

Corporate social responsibility (CSR) is often used as a key criterion in gauging corporate reputation. This research examined the influence of consumers’ attributions on corporate outcomes in response to CSR. Researchers and managers have considered consumers’ beliefs about CSR initiatives to be simplistic, serving either economic ends or reflecting sincere social concerns. The results of two studies established that consumers’ attributions were more complex than traditionally viewed, mirroring many of the motives ascribed to companies by managers and researchers. Rather than viewing corporate efforts along a self- or other-centered continuum, consumers differentiated four types of motives: self-centered motives that are strategic and egoistic and other-centered motives that are values driven and stakeholder driven. Consumers responded most positively to CSR efforts they judged as values driven and strategic while responding negatively to efforts perceived as stakeholder driven or egoistic. Attributions were shown to affect purchase intent as well as mediate the structure of an offer.
Market Structure and Advance Selling

When products are sold in advance, i.e. prior to consumption, consumers trade off an early, uninformed purchase at a low price against a late, informed purchase at a high price. This paper considers the effect of market structure on the prevalence of advance selling. We show that in an oligopolistic market with multi-product firms, advance selling (with its associated allocative inefficiency) is decreasing in market concentration when the consumers’ preference uncertainty is high but can be increasing when uncertainty is low.
Benetton – Global Logistics in Action

Explores the development and operations of Benetton, an Italian‐based fashion designer and manufacturer. In order to maintain its fast response time – a necessity to stay a leader in the highly transient world of international fashion – Benetton has developed unique relationships and operational processes, and employs state‐of‐the‐art technology. It still manages, however, to keep logistics costs contained.
Impact of Relational Dynamics on Customer Loyalty in Higher Education Sector: The Moderating Role of Long Term Orientation

Recent development in the higher education sector warrants that business marketing tools be employed to make academic institutions efficient and competitive. In this study, a model of the impact of relational dynamics on customer loyalty is proposed and empirically validated in an attempt to fill literature gaps. A sample of 416 Nigerian university students, derived based on a multi-stage cluster sampling, participated in the survey which was analyzed using PLS structural equation modelling. Findings suggest that relational dynamics of bonding, personalization, customer satisfaction and trust have significant positive impact on customer loyalty. Further, long term orientation at the level of individual customer moderates the relationship between satisfaction and customer loyalty. Hence, applying a relationship marketing approach in the management higher educational institutions enhances institutional performance.