Miracle-dz/UniFAR-FTUs huggingface dataset:
A Possible Predocking Attachment Site for N-Ethylmaleimide-sensitive Fusion Protein

N-Ethylmaleimide-sensitive fusion protein (NSF) is an ubiquitous protein required for multiple vesicular transport events. We have investigated the role of the two nucleotide-binding regions of NSF in endosomal fusion by analyzing NSF mutants in a cell-free system. Our results indicate that mutations on the first ATP-binding domain, that render a protein defective in either ATP binding or ATP hydrolysis, results in almost complete inhibition of endosomal fusion. A mutation in the second ATP-binding site of NSF was only slightly inhibitory. The inhibitory effect was observed only when the mutant proteins were added at early times during the fusion reaction indicating that NSF may be required for an early step during the docking/fusion process. Binding studies using Western blotting reveal that the binding of NSF mutants to endosomal membranes is differentially affected by Ca2+. Our results indicate that NSF, depending on its nucleotide state, may interact with membranes via an alternate mechanism. Our findings suggest the existence of a predocking binding site either independent of the docking complex or a site that leads to the formation of the SNAP-SNARE complex (e.g. 20 S particle).
Application for determining the modulation transfer function of the smartphone built-in camera

Considering the fact of both smartphones popularity and their built-in camera quality improvement the problem of measuring the cameras quality seems to be quite important and up to date. As smartphone computing capacities are quite high today so it can be used to measure the camera quality itself. In this paper the application for smartphone is developed to determine the built-in camera modulation transfer function. The slanted edge is used as a test pattern as this method is the simplest and fastest.
Involvement of the pentose phosphate pathway and redox regulation in fertilization in the mouse

Glucose metabolism is necessary for successful fertilization in the mouse. Both spermatozoa and oocytes metabolize glucose through the pentose phosphate pathway (PPP), and NADPH appears required for gamete fusion. The aims of this study were to further characterize the utilization of glucose by the fertilizing spermatozoon and the fertilized oocyte, to demonstrate the importance of the PPP in different steps of fertilization, and to examine whether the beneficial effect of glucose could be mediated by a NADPH‐dependent enzyme involved in redox regulation. By using a fluorescent analog of 2‐deoxyglucose, glucose uptake was evidenced in both the head and flagellum of motile spermatozoa. After sperm–oocyte fusion, an increase in glucose uptake by the fertilized oocyte was observed but not before the formation of the male and female pronuclei. By using a microphotometric technique, activity of glucose 6‐phosphate dehydrogenase (G6PDH), the key enzyme of the PPP, was localized to the sperm head and midpiece. When epididymal spermatozoa were released into a glucose‐containing medium, the NADPH/NADP ratio increased with capacitation. Sperm–oocyte fusion and meiosis reinitiation of the fertilized oocyte was inhibited by the PPP inhibitor 6‐aminonicotinamide (6‐AN); inhibition of sperm–oocyte fusion was relieved by NADPH. Sperm–oocyte fusion and meiosis reinitiation were also inhibited by diphenylamine iodonium, which is a flavoenzyme inhibitor reported to prevent reactive oxygen species (ROS) generation in mouse spermatozoa and embryos. These findings indicate that the PPP is involved in different steps of fertilization. Subsequent regulation of a NADPH‐dependent flavoenzyme responsible of ROS production is envisaged. Mol. Reprod. Dev. 70: 494–503, 2005. © 2005 Wiley‐Liss, Inc.
New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression

This review outlines new concepts that are emerging for the functions of matrix metalloproteinases in colorectal cancer development and progression. The two main concepts that will be discussed are the role of matrix metalloproteinases in the early stages of colorectal tumour development and the functional mechanisms by which matrix metalloproteinases contribute to colorectal tumour invasion and metastasis. The matrix metalloproteinases are a group of enzymes, which have been best characterized for their ability to degrade extracellular matrix proteins and thus they have been extensively studied in tumour invasion. It is now becoming recognized that the matrix metalloproteinases have key roles in a variety of biological processes that are distinct from their well‐defined role in matrix degradation. This group of enzymes has been shown to interact with a broad range of non‐matrix proteins including growth factors and their receptors, mediators of apoptosis, and cell adhesion molecules. The elucidation of novel biological roles for the matrix metalloproteinases also challenges the current predominant concept of matrix metalloproteinases as enzymes only involved in matrix degradation. Recent studies have shown that several matrix metalloproteinases, especially matrilysin (MMP‐7), interact with the specific molecular genetic and signalling pathways involved in colorectal cancer development. In particular, matrilysin is activated at an early stage of colorectal tumourigenesis by the beta‐catenin signalling pathway. Furthermore, studies are now elucidating specific mechanisms by which individual matrix metalloproteinases, especially membrane‐type matrix metalloproteinases, interact with specific cell adhesion molecules and cytoskeletal proteins and thus contribute dynamically to colorectal tumour invasion. Copyright © 2003 John Wiley & Sons, Ltd.
N2O emission rates in a California meadow soil are influenced by fertilizer level, soil moisture and the community structure of ammonia‐oxidizing bacteria

The response of nitrous oxide (N2O) emission rates and β‐proteobacterial ammonia‐oxidizing (AOB) communities to manipulations of temperature, soil moisture and nitrogenous fertilizer concentration were studied for 16–20 weeks in a multifactorial laboratory experiment using a California meadow soil. Interactions among these three environmental factors influenced the N2O emission rates, and two patterns of N2O emission rates due to nitrification (NitN2O) were observed. First, in soils receiving low or moderate amounts of fertilizer, the rates decreased sharply in response to increasing soil moisture and temperature. Second, in soils receiving high amounts of fertilizer, the rates were influenced by an interaction between soil moisture and temperature, such that at 20 °C increasing soil moisture resulted in an increase in the rates, and at 30 °C the highest rate was observed at moderate soil moisture. We used path analysis to identify the interrelationships that best explain these two patterns. Path analysis revealed that in the high fertilizer (HF) treatment, the major path by which ammonia influenced NitN2O rates was indirect through an influence on the abundance of one particular phylogenetic group (AOB ‘cluster 10’). In contrast, in the low and moderate fertilizer treatments soil moisture influenced the rates both directly (the major path) and indirectly through AOB community structure. Although terminal restriction fragment length polymorphism (T‐RFLP) analysis revealed shifts in the community structure of AOB in all treatments, the shifts at HF concentrations were particularly striking, with dominance by three different phylogenetic groups under different combinations of the three environmental factors. The high emission rates observed at the lowest soil moistures suggest that bacterial nitrifiers may use denitrification as a stress response.
Cannabis use amongst patients with inflammatory bowel disease

Background Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. Methods One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn’s disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. Results A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); P<0.001], complimentary alternative medicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); P<0.001 vs. users] to express an interest in participating in a hypothetical therapeutic trial of cannabis for IBD. Conclusion Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.
Experience of 13 C-Urea Breath Test in Eight Children

Urea breath test ( 13 C-UBT) is a non-invasive diagnostic test for Helicobacter pylori infection. A preliminary retrospective study was conducted in the use of 13 C-UBT in paediatric patients in Hong Kong. The study was conducted in Kwong Wah Hospital, a regional public hospital in urban Hong Kong. Eight asymptomatic paediatric patients who underwent 13 C-UBT were analyzed retrospectively. Positive 13 C-UBT was found in two (25%) of these eight paediatric patients. There was positive paternal history of dyspepsia in both patients.
The Influence of Positive Experiences on Depression and Quality of Life in Persons With Multiple Sclerosis

Purpose: This correlational study determined the extent to which positive, rather than negative, experiences influence depressive symptoms and quality of life in persons with multiple sclerosis (MS). Method: Data collected during the 7th year of an ongoing longitudinal study of quality of life in community-dwelling persons with MS were used for this analysis. Findings: Higher number of positive experiences was associated with fewer depressive symptoms, less functional limitations, and better quality of life. Using hierarchical multiple regression, age, education, functional limitations, and positive experiences accounted for 21.7% of the variance in depressive symptoms, and functional limitations, positive experiences, and depressive symptoms explained 58% of the variance in quality of life. Conclusions: Higher number of positive experiences predicted lower levels of depressive symptoms, even while taking disease-related functional limitations into account. Incorporating positive experiences into daily life may improve quality of life, even when battling depression and substantial limitations in functioning.
A comparison of radiography versus computed tomography in the diagnosis of middle ear disease in the dog

The purpose of this study was to compare CT and radiography for diagnosing the presence and severity of middle ear disease in dogs with chronic otitis externa. Thirty-one dogs that were presented for a total ear canal ablation and bulla osteotomy were recruited. Three normal dogs served as controls. All dogs were examined using radiography and CT. Three radiologists independently evaluated imaging studies in random order. A visual analog scale method was used for scoring certainty and severity of middle ear disease. Surgical findings were recorded intra-operatively. Bulla lining samples were submitted for histopathology and scored by a single pathologist who also used a visual analog scale system. Findings from both modalities agreed more closely with surgical findings than with histopathology findings. With either surgery or histopathology as the gold standard, CT was more sensitive than and as specific as radiographs for predicting presence and severity of middle ear disease. Overall severity of middle ear disease was lower in the right versus the left ears. For CT, inter-observer variance of middle ear certainty was 217.04 while radiographic variance was 126.14 on the side with lower severity estimates. Both radiography and CT were more accurate for predicting the severity of the disease than its presence. Findings indicate that CT is more accurate and reliable than radiography in diagnosing middle ear disease for dogs with chronic otitis externa, but only when severity of disease is moderate or high. With low severity of disease, reader diagnostic certainty for both modalities becomes more variable.
When Disagreement Gets Ugly: Perceptions of Bias and the Escalation of Conflict

It is almost a truism that disagreement produces conflict. This article suggests that perceptions of bias can drive this relationship. First, these studies show that people perceive those who disagree with them as biased. Second, they show that the conflict-escalating approaches that people take toward those who disagree with them are mediated by people's tendency to perceive those who disagree with them as biased. Third, these studies manipulate the mediator and show that experimental manipulations that prompt people to perceive adversaries as biased lead them to respond more conflictually—and that such responding causes those who engage in it to be viewed as more biased and less worthy of cooperative gestures. In summary, this article provides evidence for a “bias-perception conflict spiral,” whereby people who disagree perceive each other as biased, and those perceptions in turn lead them to take conflict-escalating actions against each other (which in turn engender further perceptions of bias, continuing the spiral).
Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer.

BACKGROUND Metastatic prostate cancer is a leading cause of cancer-related death in men. The rate of response to androgen ablation is high, but most patients relapse as a result of the outgrowth of androgen-independent tumor cells. The androgen receptor, which binds testosterone and stimulates the transcription of androgen-responsive genes, regulates the growth of prostate cells. We analyzed the androgen-receptor genes from samples of metastatic androgen-independent prostate cancers to determine whether mutations in the gene have a role in androgen independence. METHODS Complementary DNA was synthesized from metastatic prostate cancers in 10 patients with androgen-independent prostate cancer, and the expression of the androgen-receptor gene was estimated by amplification with the polymerase chain reaction. Exons B through H of the gene were cloned, and mutations were identified by DNA sequencing. The functional effects of the mutations were assessed in cells transfected with mutant genes. RESULTS All androgen-independent tumors expressed high levels of androgen-receptor gene transcripts, relative to the levels expressed by an androgen-independent prostate-cancer cell line (LNCaP). Point mutations in the androgen-receptor gene were identified in metastatic cells from 5 of the 10 patients examined. One mutation was in the same codon as the mutation found previously in the androgen-independent prostate-cancer cell line. The mutations were not detected in the primary tumors from of the two patients. Functional studies of two of the mutant androgen receptors demonstrated that they could be activated by progesterone and estrogen. CONCLUSIONS Most metastatic androgen-independent prostate cancers express high levels of androgen-receptor gene transcripts. Mutations in androgen-receptor genes are not uncommon and may provide a selective growth advantage after androgen ablation.
Hoop Net Escapes and Influence of Traps Containing Turtles on Texas Spiny Softshell ( Apalone spinifera emoryi ) Captures

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Improvement in Char Strength with an Open Cage Silsesquioxane Flame Retardant

Different characterization techniques were used to study the hydrolysis and condensation reaction kinetics of 3-methacryloxypropyltrimethoxysilane (MAPTMS) to obtain open cage silsesquioxane oligomers. The formation of hydrogen bonds, which condition the chemical structures of the resulting products, was identified. Improved thermal and fire resistant behavior of unsaturated polyester (UP) composites prepared with aluminium trihydroxide (ATH) and the synthesized oligomer were registered. Opened silsesquioxane structures also showed an improvement in the mechanical properties of the char formed after firing.
Myelodysplasia-associated immunophenotypic alterations of bone marrow cells in myeloma: are they present at diagnosis or are they induced by lenalidomide?

Increased risk of acute myeloid leukemia/myelodysplastic syndromes following treatment has been reported in multiple myeloma, but whether dysplastic features are already present at diagnosis remains to be investigated. Using multiparameter flow cytometry, we analyzed the distribution and phenotype of bone marrow hematopoietic cells from 47 multiple myeloma patients (15 symptomatic and 32 high-risk smoldering). From the 32 smoldering myeloma patients, 18 were studied at baseline and 22 after nine cycles of lenalidomide/dexamethasone treatment following the QUIREDEX trial (including 8 from baseline). Phenotypic alterations of bone marrow cells of 7 (47%) symptomatic and 6 (33%) smoldering myeloma patients were detected at baseline; there was no difference in the frequency and extent of phenotypic alterations between symptomatic versus smoldering cases. Likewise, no difference was seen between smoldering myeloma patients studied at baseline versus after lenalidomide/dexamethasone treatment. Our results suggest that phenotypic alterations of bone marrow hematopoietic cells are often present in newly diagnosed symptomatic and smoldering multiple myeloma patients. QUIREDEX trial (NCT00480363)
Novel pharmacological inhibitors demonstrate the role of the tyrosine kinase Pyk2 in adhesion and aggregation of human platelets

Summary Pyk2 is a Ca2+-regulated kinase predominantly expressed in neuronal and in haematopoietic cells. Previous studies on Pyk2-null mice have demonstrated that Pyk2 plays a crucial role in platelet activation and thrombus formation, thus representing a possible target for antithrombotic therapy. Very limited information is available about the role of Pyk2 in human platelets, mainly because of the lack of specific pharmacological inhibitors. In this work, we have tested two novel Pyk2 inhibitors, PF-4594755 and PF-4520440, to validate their specificity and to investigate their ability to modulate platelet activation. Both molecules were able to efficiently block Pyk2 activity in human and mouse platelets stimulated with thrombin or with the Ca2+-ionophore. In wild-type murine platelets, PF-4594755 and PF-4520440 reduced thrombin-induced aggregation to the level observed in Pyk2 knockout platelets, but did not affect aggregation induced by GPVI stimulation. Importantly, neither compounds affected the residual thrombin-induced aggregation of Pyk2-null platelets, thus excluding possible off-target effects. In human platelets, PF-4594755 and PF-4520440 significantly reduced aggregation stimulated by thrombin, but not by the GPVI agonist convulxin. Both inhibitors reduced platelet adhesion on fibrinogen and prevented Akt phosphorylation in adherent cells, indicating that Pyk2 regulates PI3K and cell spreading downstream of integrins in human platelets. Finally, the Pyk2 inhibitors significantly inhibited thrombus formation upon blood perfusion on immobilized collagen under arterial flow rate. These results demonstrate that PF-4594755 and PF-4520440 are specific inhibitors of Pyk2 in intact platelets and allowed to reliably document that this kinase plays a relevant role in human platelet activation. Supplementary Material to this article is available online at www.thrombosis-online.com.
Physical background for parameters of the quantum Rabi model

We investigate the applicability of the two major approximations which are most commonly employed in the study of the quantum Rabi model, namely the description of a resonant cavity mode as a single-mode quantized field and the use of the rotating wave approximation. Starting from the Hamiltonian of a two-level system interacting with a multi-mode quantized field, we perform the canonical transformation of the field operators. This allows one to partition the Hamiltonian of the system into two parts. The first part is the interaction of the two-level system with a single collective field mode, while the second one describes the interaction with field fluctuations. The first part is usually associated with the resonant cavity mode. This division enables us to determine the applicability condition of the single-mode approximation. In addition we identify simple approximate relations for the description of the eigenstates, eigenfunctions and the time evolution of the quantum Rabi model beyond the rotating wave approximation.