Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscarinic Regulation of Ether-a-go-go-Related Gene K+ Currents in Interstitial Cells of Cajal

The interstitial cells of Cajal (ICC) of the myenteric plexus generate a set of currents that evoke a pacemaker potential that sets the initial conditions for the contraction frequency and duration of the electrically coupled intestinal musculature. The synapse-like contacts between ICC and myenteric motor nerves highlight the potential role of the enteric nervous system in regulating the pacemaking currents in ICC. The objective of the present study was to investigate muscarinic regulation of the ether-a-go-go-related gene (ERG) K+ current. Immunoreactivity of the M3 receptor (M3R) but not the M2 receptor was detected on murine jejunal ICC-Auerbach's plexus (ICC-AP). The muscarinic agonist bethanechol reduced hyperpolarization-evoked peak ERG currents at –100 mV by 23 ± 1% and increased both fast and slow time constants of deactivation, resulting in increased steady-state currents between –55 and –35 mV. Bethanechol also increased depolarization-evoked steady-state currents by 59 ± 10% at –40 mV, whereas currents were decreased at potentials positive to 0 mV. The half-maximal voltage of activation was shifted 11.9 mV leftward. Interestingly, the time constant of activation increased only at –40 mV. Atropine prevented and 2 μM E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl-4-(methylsulfonylaminobenzoyl)piperidine] inhibited bethanechol-affected currents. The effect of bethanechol was mimicked by protein kinase C (PKC) activation and diminished by PKC inhibition. Our results indicate that the ERG K+ channel in ICC is affected by stimulation of muscarinic receptors, probably the M3R, via a PKC-dependent mechanism. Modulation of the ERG K+ current in ICC-AP will affect the kinetics of pacemaking in the intestinal musculature.
Subtype-Dependence of NMDA Receptor Channel Open Probability

NMDA receptor-mediated calcium transients play a critical role in synaptogenesis, synaptic plasticity, and excitotoxicity. NMDA receptors are heteromeric complexes of NR1A combined with NR2A, NR2B, NR2C, and/or NR2D subunits. The NR2 subunits determine a variety of electrophysiological and pharmacological properties of the NMDA receptor complex. In this report, we provide evidence for the first time that there is also a significant difference in peak channel open probability (Po) between NMDA receptors composed of NR1A/NR2A and those of NR1A/NR2B subunits. First, whole-cell patch-clamp recordings from human embryonic kidney (HEK) 293 cells expressing NMDA receptors revealed that NR1A/NR2A-mediated peak current densities are approximately four times larger than those of NR1A/NR2B. We show that this fourfold difference is unlikely caused by differences in receptor surface expression, since these levels were similar for the two subtypes by Western blot analysis. To determine whether Po contributed to the difference in peak current densities, we used two different open channel antagonists, MK-801 and 9-aminoacridine, in a variety of experimental paradigms. Our results indicate that peak Po is significantly higher (twofold to fivefold) for NR1A/NR2A than NR1A/NR2B, with estimated values of ∼0.35 and 0.07, respectively. These results suggest that a change in the relative expression levels of NR2A and NR2B can regulate peak amplitude of NMDA receptor-mediated excitatory postsynaptic potentials and therefore may play a role in mechanisms underlying synaptic plasticity.
Smoking-related correlates of depressive symptom dimensions in treatment-seeking smokers.

INTRODUCTION The symptomatic heterogeneity of depression poses a barrier to understanding the smoking-depression relationship. Different types of depressive symptoms have evidenced disparate relations to smoking. Yet, depression measures employed in past depression-smoking research yield symptom subdimensions, which may not be sufficiently comprehensive or distinct. The Inventory of Depression and Anxiety Symptoms (IDAS; Watson, D., O'Hara, M. W., Chmielewski, M., McDade-Montez, E. A., Koffel, E., Naragon, K., et al. (2008). Further validation of the IDAS: Evidence of convergent, discriminant, criterion, and incremental validity. Psychological Assessment, 20, 248-259. doi:10.1037/a0012570) produce 8 distinguishable depressive symptom dimensions: dysphoria (anhedonia, sadness, psychomotor disturbance, worthlessness, worry, and cognitive difficulty), lassitude (anergia and hypersomnia), suicidality (self-harm thoughts/behaviors), ill temper (anger), well-being (positive thinking), appetite loss, appetite gain, and insomnia. The present study examined common and unique relations of IDAS depression subdimensions to (a) smoking rate (cigarettes perday), (b) tobacco dependence, and (c) smoking motivation. METHODS Secondary analysis of cross-sectional associations in baseline data collected from 338 daily smokers enrolled in a larger cessation study. RESULTS In individual models examining each symptom dimension in isolation, each symptom dimension was significantly with associated smoking rate, tobacco dependence, and/or various aspects of smoking motivation (e.g., subjective addiction, habit, appetite control, affect modulation). In combined models including all 8 dimensions as simultaneous regressor variables, dysphoria was the only dimension to retain most of its significant associations to smoking characteristics. CONCLUSIONS Relations of depressive symptoms to tobacco dependence, smoking rate, and motivation may be explained by (a) variance specific to dysphoria symptoms and (b) shared variance across depressive symptom subdimensions. Dysphoria symptoms, which contain core DSM-IV depression criteria, may be central to depression-smoking comorbidity, whereas other symptoms may play a less prominent role.
Polysaccharide antigens of the capsule of Cryptococcus neoformans

The major significance of the capsular polysaccharide of C. neoformans is its role in potentiating opportunistic infections by the yeast. It has the ability to exert a broad spectrum of influences on the immune response, from activation of phagocytic cells and complement components of the alternative pathway, to the induction of specific antibody, T-suppressor cells, DTH responses, and cytokines (51). These biological properties along with the serotype specificities are all determined by the physical properties and chemical structures of the polysaccharide antigens that compose the capsule. There is evidence not only for an association of lethal infections with serotype A in patients with advanced AIDS (34, 56), but also for a role for the capsule in directly influencing the infection of CD4+ cells by HIV (57). Together, these phenomena raise intriguing questions about the possible connection between the chemistry of these capsular antigens and cryptococcal infections in AIDS patients. One speculation is that AIDS creates the optimal physiological conditions for the establishment and spread of cryptococcosis. It has been observed that during the progression of AIDS there is a shift towards a T-2 response (14). This could lead to conditions that would inhibit the cellular immune responses that block dissemination of cryptococcal infections. Thus, an important consideration in the application of vaccine or immune modulation therapies in the treatment of cryptococcosis in AIDS victims would be the design of vaccines that could boost the T-1 immune response. It has been shown that the form and dose of an antigenic challenge can influence the induction of a T-1 or T-2 immune response (61). Recently, Murphy has reported that gamma interferon and interleukin 2 are up-regulated in the spleens of mice that produce anticryptococcal TDH and TAMP cells in response to immunogenic doses of cryptococcal culture filtrate antigen given with Freund's complete adjuvant (49). Perhaps purified cryptococcal antigens (e.g., MP) conjugated to an appropriate carrier or adjuvant could be used in therapeutic strategies to limit cryptococcosis in immunocompromised individuals. Future investigations of virulence and pathogenicity in the context of defined polysaccharide antigens from encapsulated strains of C. neoformans will contribute to a better understanding of the regulation of cryptococcal infection and immunity at the cellular and molecular levels. (ABSTRACT TRUNCATED AT 400 WORDS)
Treatment of human pancreatic cancer using combined ultrasound, microbubbles, and gemcitabine: a clinical case study.

PURPOSE The purpose of this study was to investigate the ability and efficacy of inducing sonoporation in a clinical setting, using commercially available technology, to increase the patients' quality of life and extend the low Eastern Cooperative Oncology Group performance grade; as a result increasing the overall survival in patients with pancreatic adenocarcinoma. METHODS Patients were treated using a customized configuration of a commercial clinical ultrasound scanner over a time period of 31.5 min following standard chemotherapy treatment with gemcitabine. SonoVue(®) ultrasound contrast agent was injected intravascularly during the treatment with the aim to induce sonoporation. RESULTS Using the authors' custom acoustic settings, the authors' patients were able to undergo an increased number of treatment cycles; from an average of 9 cycles, to an average of 16 cycles when comparing to a historical control group of 80 patients. In two out of five patients treated, the maximum tumor diameter was temporally decreased to 80 ± 5% and permanently to 70 ± 5% of their original size, while the other patients showed reduced growth. The authors also explain and characterize the settings and acoustic output obtained from a commercial clinical scanner used for combined ultrasound microbubble and chemotherapy treatment. CONCLUSIONS It is possible to combine ultrasound, microbubbles, and chemotherapy in a clinical setting using commercially available clinical ultrasound scanners to increase the number of treatment cycles, prolonging the quality of life in patients with pancreatic adenocarcinoma compared to chemotherapy alone.
Individualized screening interval for prostate cancer based on prostate-specific antigen level: results of a prospective, randomized, population-based study.

BACKGROUND The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen (PSA) in blood and to determine whether this information could be used to individualize the PSA testing interval. METHODS The study included 5855 of 9972 men (aged 50-66 years) who accepted an invitation to participate in a prospective, randomized study of early detection for prostate cancer. We used a protocol based on biennial PSA measurements starting from 1995 and 1996. Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies. RESULTS Among the 5855 men, 539 cases of prostate cancer (9.2%) were detected after a median follow-up of 7.6 years (up to July 1, 2003). Cancer detection rates during the follow-up period in relation to PSA levels were as follows: 0 to 0.49 ng/mL, 0% (0/958); 0.50 to 0.99 ng/mL, 0.9% (17/1992); 1.00 to 1.49 ng/mL, 4.7% (54/1138); 1.50 to 1.99 ng/mL, 12.3% (70/571); 2.00 to 2.49 ng/mL, 21.4% (67/313); 2.50 to 2.99 ng/mL, 25.2% (56/222); 3.00 to 3.99 ng/mL, 33.3% (89/267); 4.00 to 6.99 ng/mL, 38.9% (103/265); 7.00 to 9.99 ng/mL, 50.0% (30/60); and for men with an initial PSA of 10.00 ng/mL or higher, 76.8% (53/69). Not a single case of prostate cancer was detected within 3 years in 2950 men (50.4% of the screened population) with an initial PSA level less than 1 ng/mL. CONCLUSIONS Retesting intervals should be individualized on the basis of the PSA level, and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval.
Open Educational Resources: Innovation, Research and Practice

Yes Describe the content of the resource in as much detail as possible. Teaching and Learning Context No Describe the recommended learning context or prerequisites for the appropriate use of the teaching and learning tool. This can be as simple as sharing a story of how the material has been used in your own teaching. Funded by No In the case of a resource being an outcome of a funded project, please specify the funding institution. OER Image No You are encouraged to attach an image which represents the resource. This may be an image from within the material, a screenshot of the cover, or a relevant graphic which represents the contents. If you do not provide an image, a suitable one will be selected for you on moderation. Creative Commons Licence Yes Submitting a resource to the UCT OpenContent directory implies the desire to share your educational resource with the world. OER UCT recommends the Creative Commons licence because it protects the attribution rights of the creator while allowing others to make free use of the material. Faculty Yes Select the faculty in which the material was created or the faculty the material most cohesively represents. Department Yes Select the department in which the material was created or the department the material most cohesively represents. Media Types Yes Select the item which best describes the document type of your resource. Material Type Yes Select the item which best describes the material type of your resource. Language Yes Select the language in your resource is written. Level Yes Select the recommended student level for which your resource is intended. Tags Yes Please add tags which describe your resource in more detail. For instance, if you selected the Faculty of Science and the Department of Physics, you might want to tag this resource with something like “Newton’s Laws” if the material is specifically about that topic. Another specification that emerged from this process was to include Google Analytics within the planned directory so that the OER team could track users, what they were searching for and which resources were accessed most frequently. Figure 3.2 illustrates the type of directory (sometimes also called a “referatory”) that the UCT OER team created in relation to those created by other institutional or global OER entities curating OER content and metadata.
SOME STUDIES ON PSEUDOMONAS SPECIES IN CHICKEN EMBRYOS AND BROILERS IN ASSIUT GOVERNORATE

One hundred, dead-Inshell embryos from balady hatcheries, eighty-five, (2-15 days baby chicks) and sixty broilers 5–8 weeks old (diseased and freshly dead) were collected from different location in Assiut Governorate. pseudomonas aeruginosa (Ps. aeruginosa) was isolated from these sample at rates of 21%, 17.6 %, and 3.3% respectively. Experimental infection with isolated Ps. aeruginosa revealed deaths of all embryos inoculated via yolk sac route, 80% mortality of 3-days old chicks inoculated subcutaneouslly. No mortality recorded between 3-days old chicks and 9-weeks old broilers inoculated orally and intramuscullary respectively but mild swollen of head was observed in 3-days chicks. Antibiotics sensitivity test showed that the isolated ps. aeruginosa was highly sensitive to the norfloxacin, chloramphenicol and streptomycin.
A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis

Objectives The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment. Methods In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration–time curve from study drug infusion to infinity (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24. Results The 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. Conclusions Three-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX. Trial registration number NCT01274182; Results.
Innovating by Doing: Promoting On-the-Job Experimentation Through a Climate for Innovation

Firms’ innovation performance and productivity depend on engaging the entire organization in the innovation process. Going beyond the typical focus on R&D, the focus of this article is on engaging those employees who are active in “productive” activities in innovation. This article explores how a firm can create an environment in which those employees can build on their local needs and knowledge to learn and innovate through a process of experimentation and problem solving during “on-the-job” activities. I draw on innovation, creativity and organizational climate research to explore the determinants and effects of such innovative behavior. I develop a theoretical framework of how organizational practices affect employees’ willingness and ability to experiment — a behavioral integral to innovation. I furthermore argue that the relationship between such “climate for innovation” and the ultimate performance is inverse U-shaped. The framework implies that managers can turn the entire organization into an innovation lab but they need to balance the tension between productive and innovative practices.
Physical Fitness Qualities of Professional Volleyball Players: Determination of Positional Differences

Marques, MC, van den Tillaar, R, Gabbett, TJ, Reis, VM, and González-Badillo, JJ. Physical fitness qualities of professional volleyball players: Determination of positional differences. J Strength Cond Res 23(4): 1106-1111, 2009-The purpose of this study was to investigate the anthropometric and strength characteristics of elite male volleyball athletes and to determine if differences exist in these characteristics according to playing position. A group of 35 professional male team volleyball players (mean ± SD age: 26.6 ± 3.1 years) participated in the study. Players were categorized according to playing position and role: middle blockers (n = 9), opposite hitters (n = 6), outside hitters (n = 10), setters (n = 6), and liberos (n = 4). Height, body mass, muscular strength (4 repetition maximum bench press and 4 repetition maximum parallel squat tests), and muscular power (overhead medicine ball throw, countermovement jump) were assessed. Significant differences (p < 0.05) were found among the 5 positional categories. The results indicated that the middle blockers and opposite hitters were the tallest and heaviest players, whereas the libero players were the lightest. Differences were also found in bench press maximal strength, with the middle blockers and opposite players significantly stronger (p < 0.05) than the setters and liberos. The setter positional group had significantly poorer (p < 0.05) parallel squat performances than the outside hitter and opposite hitter groups. No other significant differences (p > 0.05) were found among groups for the strength and power parameters. These results demonstrate that significant anthropometric and strength differences exist among playing positions in elite male volleyball players. In addition, these findings provide normative data for elite male volleyball players competing in specific individual playing positions. From a practical perspective, sport scientists and conditioning professionals should take the strength and anthropometric characteristics of volleyball players into account when designing individualized position-specific training programs.
Electroconvulsive Therapy and Complaints of Memory Dysfunction: A Prospective Three-Year Follow-up Study

Summary Self-reports of memory problems have been evaluated prospectively in depressed patients receiving bilateral ECT or unilateral ECT, and in depressed patients receiving treatments other than ECT. Depressed patients did not complain of poor memory at seven months after hospitalization. Compared to bilateral ECT, right unilateral ECT was associated with only mild memory complaints. At three years after treatment approximately one-half of the persons who had received bilateral ECT reported poor memory. These reports seemed to be influenced by three factors: (1) recurrence or persistence of conditions that were present before ECT; (2) the experience of amnesia initially associated with ECT and a subsequent tendency to question if memory had ever recovered; and (3) impaired memory for events that had occurred up to six months before treatment and up to about two months afterwards.
COMPARATIVE STUDY OF ARTHROCENTESIS WITH OR WITHOUT USING PIROXICAM IN THE MANAGEMENT OF TEMPOROMANDIBULAR JOINT DISORDERS

INTRODUCTION: Temporomandibular joint dysfunction (TMD) is a clinically significant condition which can be a source of acute or chronic orofacial pain and dysfunction including limitation of mandibular movement. Arthrocentesis is joint lavage which washes out these inflammatory mediators, thereby, relieving pain. OBJECTIVE : To to evaluate the efficacy of arthrocentesis with and without the injection of piroxicam on TMD. MATERIALS AND METHODS: This study was conducted on twenty patients with clinical and radiological diagnosis of TMD included in the study divided into equal groups. Ten patients were subjected to conventional arthrocentesis with saline solution alone, other ten patients underwent arthrocentesis by injection of piroxicam. Patient's evaluation will be preoperatively and postoperatively following the procedure and after 1 st , 2 nd week, 1 and 6 months. Magnetic resonance imaging (MRI) was performed in both groups before starting the treatment. CONCLUSION: Arthrocentesis combined with piroxicam injections is superior to arthrocentesis alone in reducing impairment in patients with TMD on its clinical outcome.
Nonlinear spacing policy based vehicle platoon control for local string stability and global traffic flow stability

Adaptive Cruise Control (ACC) aims to increase traffic throughput and traffic safety. A typical application of ACC vehicles is creating a platoon system, in which a series of vehicles moves longitudinally in an automated manner. For platooning vehicles, we need to define the inter-vehicle spacing policy and the control law for each and every vehicle. In this work, a new nonlinear spacing policy and a linear feedback controller related to the policy are proposed to achieve string stability and traffic flow stability. Moreover, we show that the proposed policies provide a higher traffic flow capacity compared with a conventionally used constant time gap policy. Finally, a generalized linear feedback controller is used to derive a more relaxed condition for ensuring string stability requirement.