Miracle-dz/UniFAR-FTUs huggingface dataset:
A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase.

A minimal model for the mitotic oscillator is presented. The model, built on recent experimental advances, is based on the cascade of post-translational modification that modulates the activity of cdc2 kinase during the cell cycle. The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation, and in the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. That cyclin activates cdc2 kinase while the kinase triggers the degradation of cyclin has suggested that oscillations may originate from such a negative feedback loop [Félix, M. A. , Labbé, J. C. , Dorée, M. , Hunt, T. & Karsenti, E. (1990) Nature (London) 346, 379-382]. This conjecture is corroborated by the model, which indicates that sustained oscillations of the limit cycle type can arise in the cascade, provided that a threshold exists in the activation of cdc2 kinase by cyclin and in the activation of cyclin proteolysis by cdc2 kinase. The analysis shows how miototic oscillations may readily arise from time lags associated with these thresholds and from the delayed negative feedback provided by cdc2-induced cyclin degradation. A mechanism for the origin of the thresholds is proposed in terms of the phenomenon of zero-order ultrasensitivity previously described for biochemical systems regulated by covalent modification.
Extrinsic multi-sensor calibration for mobile robots using the Gauss-Helmert model

Most state estimation procedures in mobile robotics require information about the locations of the individual sensors on the platform. In this paper, we study the motion-based multi-sensor extrinsic calibration problem and point out an overlooked defect of traditional least squares estimation in this context. We present a novel calibration approach based-on the Gauss-Helmert estimation paradigm, together with a formulation for multi-sensor motion constraint. Our approach estimates not only the extrinsic parameters but also the pose observation errors, thus recovering the underlying sensor movements that exactly fulfill the motion constraints. Compared to traditional least squares approaches that estimate only the parameters, our approach is statistically optimal, thus is more accurate and robust. We implemented our approach and tested it on real robot. The experiments show that our approach is able to accurately determine the extrinsic configuration of each sensor and can largely improve the accuracy when the noise level is high.
The Binding Site for Channel Blockers That Rescue Misprocessed Human Long QT Syndrome Type 2 ether-a-gogo-related Gene (HERG) Mutations*

Mutations in the humanether-a-gogo-related gene (HERG) K+ channel gene cause chromosome 7-linked long QT syndrome type 2 (LQT2), which is characterized by a prolonged QT interval in the electrocardiogram and an increased susceptibility to life-threatening cardiac arrhythmias. LQT2 mutations produce loss-of-function phenotypes and reduceI Kr currents either by the heteromeric assembly of non- or malfunctioning channel subunits with wild type subunits at the cell surface or by retention of misprocessed mutant HERG channels in the endoplasmic reticulum. Misprocessed mutations often encode for channel proteins that are functional upon incorporation into the plasma membrane. As a result the pharmacological correction of folding defects and restoration of protein function are of considerable interest. Here we report that the trafficking-deficient pore mutation HERG G601S was rescued by a series of HERG channel blockers that increased cell surface expression. Rescue by these pharmacological chaperones varied directly with their blocking potency. We used structure-activity relationships and site-directed mutagenesis to define the binding site of the pharmacological chaperones. We found that binding occurred in the inner cavity and correlated with hydrophobicity and cationic charge. Rescue was domain-restricted because the trafficking of two misprocessed mutations in the C terminus, HERG F805C and HERG R823W, was not restored by channel blockers. Our findings represent a first step toward the design of pharmacological chaperones that will rescue HERG K+ channels without block.
Altered semantic integration in autism beyond language: a cross-modal event-related potentials study

Autism spectrum disorders (ASDs) are characterized by impaired communication, particularly pragmatic and semantic language, resulting in verbal comprehension deficits. Semantic processing in these conditions has been studied extensively, but mostly limited only to linguistic material. Emerging evidence, however, suggests that semantic integration deficits may extend beyond the verbal domain. Here, we explored cross-modal semantic integration using visual targets preceded by musical and linguistic cues. Particularly, we have recorded the event-related potentials to evaluate whether the N400 and late positive potential (LPP) components, two widely studied electrophysiological markers of semantic processing, are differently sensitive to congruence with respect to typically developing children. Seven ASD patients and seven neurotypical participants matched by age, education and intelligence quotient provided usable data. Neuroelectric activity was recorded in response to visual targets that were related or unrelated to a preceding spoken sentence or musical excerpt. The N400 was sensitive to semantic congruence in the controls but not the patients, whereas the LPP showed a complementary pattern. These results suggest that semantic processing in ASD children is also altered in the context of musical and visual stimuli, and point to a functional decoupling between the generators of the N400 and LPP, which may indicate delayed semantic processing. These novel findings underline the importance of exploring semantic integration across multiple modalities in ASDs and provide motivation for further investigation in large clinical samples.
Induced Membrane Technique for Reconstruction To Manage Bone Loss

&NA; Multiple surgeries are often required to manage segmental bone loss because of the complex mechanics and biology involved in reconstruction. These procedures can lead to prolonged recovery times, poor patient outcomes, and even delayed amputation. A twostage technique uses induced biologic membranes with delayed placement of bone graft to manage this clinical challenge. In the first stage, a polymethyl methacrylate spacer is placed in the defect to produce a bioactive membrane, which appears to mature biochemically and physically 4 to 8 weeks after spacer placement. In the second, cancellous autograft is placed within this membrane and, via elution of several growth factors, the membrane appears to prevent graft resorption and promote revascularization and consolidation of new bone. Excellent clinical results have been reported, with successful reconstruction of segmental bone defects >20 cm.
Feasibility and safety comparison of laparoscopy-assisted versus open gastrectomy for advanced gastric carcinoma with D2 lymphadenectomy.

OBJECTIVE Laparoscopy-assisted gastrectomy for advanced gastric cancer still remains controversial. The aim of this study is to compare oncologic feasibility and technical safety of laparoscopic versus open gastrectomy for advanced gastric cancer with D2 lymphadenectomy by comparing patients' short-term postoperative outcomes. METHODS One hundred and one patients with laparoscopy-assisted gastrectomy and 101 patients with open gastrectomy were one-to-one matched and then compared in terms of operative outcomes and hospital courses. RESULTS The laparoscopic group showed significantly longer operating time (297.4 vs. 198.1 min, P < 0.001), earlier first flatus time (2.8 vs. 3.6 days, P < 0.001), earlier diet start time (3.8 vs. 4.6 days, P < 0.001), shorter hospital stay (10.5 vs. 11.9 days, P < 0.001) and less morbidity (21.8 vs. 37.6%, P = 0.019). However, retrieval lymph nodes, intraoperative blood loss, transfused patients, postoperative fever and mortality were similar in the two groups. As for complications, incision infection (1.0 vs. 8.9%, P = 0.021) was significantly more common in the open group than in the laparoscopic group. In the subgroup comparisons of outcomes of laparoscopy-assisted gastrectomy, the tumor, node, metastasis III group showed significantly increased retrieval lymph nodes (37.2 vs. 31.0, P < 0.001), increased intraoperative blood loss (147.2 vs. 120.5 ml, P = 0.010), increased length of hospital stay (11.1 vs. 9.9 days, P < 0.001) and increased morbidity (32.6 vs. 13.8%, P = 0.024) when compared with the tumor, node, metastasis II group. CONCLUSIONS Laparoscopy-assisted gastrectomy is feasible and safe for the treatment of advanced gastric cancer with D2 lymphadenectomy compared with open gastrectomy. Higher-level tumor stage (tumor, node, metastasis III) may increase the operative risk and should be performed with caution by surgeons with considerable experience of laparoscopic gastrectomy.
System Characterization of a Highly Integrated Preclinical Hybrid MPI-MRI Scanner

Magnetic particle imaging (MPI) is a novel tracer-based in vivo imaging modality allowing quantitative measurements of the spatial distributions of superparamagnetic iron oxide (SPIO) nanoparticles in three dimensions (3D) and in real time using electromagnetic fields. However, MPI lacks the detection of morphological information which makes it difficult to unambiguously assign spatial SPIO distributions to actual organ structures. To compensate for this, a preclinical highly integrated hybrid system combining MPI and Magnetic Resonance Imaging (MRI) has been designed and gets characterized in this work. This hybrid MPI-MRI system offers a high grade of integration with respect to its hard- and software and enables sequential measurements of MPI and MRI within one seamless study and without the need for object repositioning. Therefore, time-resolved measurements of SPIO distributions acquired with MPI as well as morphological and functional information acquired with MRI can be combined with high spatial co-registration accuracy. With this initial phantom study, the feasibility of a highly integrated MPI-MRI hybrid systems has been proven successfully. This will enable dual-modal in vivo preclinical investigations of mice and rats with high confidence of success, offering the unique feature of precise MPI FOV planning on the basis of MRI data and vice versa.
Towards Spectral Sparsification of Simplicial Complexes Based on Generalized Effective Resistance

As a generalization of the use of graphs to describe pairwise interactions, simplicial complexes can be used to model higher-order interactions between three or more objects in complex systems. There has been a recent surge in activity for the development of data analysis methods applicable to simplicial complexes, including techniques based on computational topology, higher-order random processes, generalized Cheeger inequalities, isoperimetric inequalities, and spectral methods. In particular, spectral learning methods (e.g. label propagation and clustering) that directly operate on simplicial complexes represent a new direction emerging from the confluence of computational topology and machine learning. Similar to the challenges faced by massive graphs, computational methods that process simplicial complexes are severely limited by computational costs associated with massive datasets. To apply spectral methods in learning to massive datasets modeled as simplicial complexes, we work towards the sparsification of simplicial complexes based on preserving the spectrum of the associated Laplacian operators. We show that the theory of Spielman and Srivastava for the sparsification of graphs extends to simplicial complexes via the up Laplacian. In particular, we introduce a generalized effective resistance for simplexes; provide an algorithm for sparsifying simplicial complexes at a fixed dimension; and give a specific version of the generalized Cheeger inequality for weighted simplicial complexes. Finally, we demonstrate via experiments the preservation of the up Laplacian during sparsification, as well as the utility of sparsification with respect to spectral clustering.
Intraocular pressure-raising potential of 1.0% rimexolone in patients responding to corticosteroids.

OBJECTIVE To compare the intraocular pressure (IOP) elevating potential of 1.0% rimexolone and 0.1% fluorometholone alcohol ophthalmic suspensions in patients known to have responded to corticosteroids. DESIGN In a double-masked, randomized, single-eye, crossover protocol, corticosteroid responsiveness initially was verified in 40 asymptomatic known steroid responders by challenge with either 0.1% dexamethasone sodium phosphate or 1.0% prednisolone acetate for up to 6 weeks. After a 1-month medication washout, subjects randomly received either rimexolone or fluorometholone for 6 weeks. Medications were again discontinued for 1 month, and subjects then received the alternate drug for 6 weeks. RESULTS There was no significant difference between rimexolone and fluorometholone in the number of subjects demonstrating a 10-mm Hg increase in IOP or in the mean number of weeks required to achieve a 10-mm Hg response. Responses occurred in significantly more subjects receiving dexamethasone sodium phosphate (P = .001) or prednisolone acetate (P < .001) and in a significantly shorter interval than in subjects receiving rimexolone. CONCLUSIONS Rimexolone has a low IOP-elevating potential, comparable to that of fluorometholone and less than that of dexamethasone sodium phosphate and prednisolone acetate.
In Vivo Imaging of Human Cholinergic Nerve Terminals with (–)-5-18F-Fluoroethoxybenzovesamicol: Biodistribution, Dosimetry, and Tracer Kinetic Analyses

(–)-5-18F-fluoroethoxybenzovesamicol (18F-FEOBV) is a vesamicol derivative that binds selectively to the vesicular acetylcholine transporter (VAChT) and has been used in preclinical studies to quantify presynaptic cholinergic nerve terminals. This study presents, to our knowledge, the first-in-human experience with 18F-FEOBV, including radiation dosimetry, biodistribution, tolerability and safety in human subjects, and brain kinetics and methods for quantitative analysis of 18F-FEOBV. Methods: Whole-body 18F-FEOBV scans were obtained in 3 healthy human volunteers. Seven additional subjects underwent dynamic brain imaging 0–120, 150–180, and 210–240 min after bolus injection of 18F-FEOBV. Arterial blood sampling was performed with chromatographic identification of authentic 18F-FEOBV to determine the arterial plasma input function. Analysis methods included nonlinear least-squares fitting of a 2-tissue-compartmental model, reference tissue modeling, and late single-scan imaging. Results: No pharmacologic or physiologic changes were observed after intravenous administration of up to 1.3 μg of 18F-FEOBV. Radiation dosimetry estimates indicate that more than 400 MBq may be administered without exceeding regulatory radiation dose limits. Kinetic analysis showed brain uptake to be relatively high with single-pass extraction of 25%–35%. VAChT binding estimates varied by a factor of greater than 30 between the striatum and cortex. Coefficients of variation in k3 estimates varied from 15% to 30%. Volume of distribution measures yielded a dynamic range of approximately 15 but with little reduction in variability. Reference tissue approaches yielded more stable estimates of the distribution volume ratio (1 + BPND), with coefficients of variation ranging from 20% in the striatum to 6%–12% in cortical regions. The late static distribution of 18F-FEOBV correlated highly with the distribution volume ratio estimates from reference tissue models (r = 0.993). Conclusion: 18F-FEOBV PET confirms that the tracer binds to VAChT with the expected in vivo human brain distribution. Both reference tissue modeling and late static scanning approaches provide a robust index of VAChT binding.
Quest for anti-inflammatory substances using IL-1β-stimulated gingival fibroblasts.

BACKGROUND We have previously reported that azulene-related compounds, and alkaline extract of Sasa senanensis Rehder potently inhibited nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophages. We investigated here whether they can inhibit pro-inflammatory cytokine production, by activated human gingival fibroblast (HGF). MATERIALS AND METHODS HGF was established from the periodontal tissues of extracted tooth. Viable cell number was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Production of Prostaglandin E(2) (PGE(2)) and cytokines was determined by enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. RESULTS Interleukin (IL)-1β did not inhibit, but rather slightly stimulated the growth of HGF cells. IL-1β stimulated the production of PGE(2), IL-6, IL-8 and monocyte chemotactic protein-1 very potently, but not that of nitric oxide and tumor necrosis factor-α. Native LPS and synthetic lipid A from E. coli and P. gingivalis was much less stimulatory. Dexamethasone, not indomethacin, was an efficient inhibitor of IL-8 production. Among five azulene-related compounds, benzo[b]cyclohepta[e][1,4]thiazine most potently inhibited the IL-8 production by HGF cells, as well as NO production by activated RAW264.7 cells. The alkaline extract of Sasa senanensis Rehder significantly inhibited IL-8 production, without affecting the cell viability. CONCLUSION The present system may be applicable for use in the search for anti-gingivitis substances.
A performance analysis of page retrieval with HTTP-MPLEX on asymmetric links

HTTP-MPLEX [1] is a header compression and response encoding scheme for HTTP. It is intended to speed up response time for multiple simultaneous HTTP transactions and improve application layer use of TCP by reducing the number of parallel connections and sustaining response bursts. HTTP- MPLEX achieves these objectives by reducing request size and prioritizing responses during multiplexing. To evaluate the performance of HTTP-MPLEX relative to HTTP 1.1 [2] in an asymmetric network environment; we developed a client and server in C++ with plug-in versions of our HTTP 1.1 and HTTP-MPLEX engines. We present in this paper a performance evaluation of our hypertext transfer engines using both the simulated network environment ns (2.29-snapshot- 20050921) and an Asymmetric Digital Subscriber Line (ADSL) connection to the Internet. We used snap-shots of www.cnn. com, www.whitehouse. gov, www.latrobe. edu.au and a photo gallery of forty eight tiles as sample web pages to retrieve using our hypertext transfer engines.
Transmission elasticity in communities hyperendemic for tuberculosis.

BACKGROUND Despite consistently meeting international performance targets for tuberculosis case detection and treatment success, areas where tuberculosis is hyperendemic fail to achieve the predicted epidemiological impact. In this article, we explore the anomalous relationship between defined performance targets and actual reduction in tuberculosis transmission. METHODS In areas where tuberculosis is endemic, poorly ventilated social gathering places such as shebeens (informal alcohol drinking places), minibus taxis, and clinic waiting rooms are all potential transmission hot spots. We modeled the transmission reduction achieved by removal of infectious persons in settings with different tuberculosis prevalence rates to demonstrate the concept of transmission elasticity. We then applied this concept to real-life data from a hyperendemic community in Cape Town, South Africa. RESULTS In a hyperendemic area, reducing the number of infectious people by a given percentage results in a smaller percentage decrease in the annual risk of infection (ARI) compared with a nonendemic area; for example, removing 10% of infectious persons could result in as little as a 5% reduction in the ARI. With use of real-life data and removal of 60% of infectious individuals with tuberculosis, as would be achieved by meeting current performance targets of 70% case detection and 85% cure, the estimated ARI reduction is 50%. CONCLUSIONS The relationship between the number of infectious people removed and the decrease in ARI is nonlinear. The concept of transmission elasticity has important implications for the formulation of universal performance targets, since hyperendemic areas would require more stringent targets to achieve comparable transmission reduction.
Levels of Community Ambulation Ability in Patients with Stroke Who Live in a Rural Area.

BACKGROUND Community ambulation is essential for patients with stroke. Apart from treatments, an assessment with a quantitative target criterion is also important for patients to clearly demonstrate their functional alteration and determine how close they are to their goal, as well as for therapists to assess the effectiveness of the treatments. The existing quantitative target criteria for community ambulation were all derived from participants in a developed country and ability was assessed using a single-task test. To explore cutoff scores of the single-task and dual-task 10-meter walk test (10MWT) in ambulatory patients with stroke from rural areas of a developing country. METHODS Ninety-five participants with chronic stroke were interviewed concerning their community ambulation ability, and assessed for their walking ability using the single- and dual-task 10MWT. RESULTS A walking speed of at least 0.47 m/s assessed using the single-task 10MWT, and at least 0.30 m/s assessed using the dual-task 10MWT, could determine the community ambulation ability of the participants. CONCLUSION Distinct contexts and anthropometric characteristics required different target criteria for community walking. Thus, when establishing a target value for community ambulation, it needs to be specific to the demographics and geographical locations of the patients.
Identification of simian virus 40 protein A

A large simian virus 40 (SV40)-specific protein can be efficiently immunoprecipitated from infected cell extracts with antisera obtained from hamsters bearing SV40-induced tumors. The protein has an apparent molecular weight of 88,000 to 100,000 with respect to markers with known molecular weights, but behaves anomalously on sodium dodecyl sulfate (SDS)-polyacrylamide gels. Cell lines infected by two different strains of SV40 synthesize immunoreactive proteins that differ slightly in mobility during SDS-polyacrylamide gel electrophoresis, evidence that the protein is coded for by the virus. These differences in protein size correlate with differences in the electrophoretic mobility of viral DNA fragments obtained by digestion with HindII and III restriction enzymes. The size of the viral capsid proteins VP2 and VP3 also varies with the strain of virus. dl-1001, a constructed deletion mutant that lacks part of the SV40A gene, directs the synthesis of a 33,000-dalton polypeptide that is not detected in cells infected with wild-type virus. The deletion fragment, like the larger protein, is phosphorylated. Maps of tryptic peptides from the 88,000- to 100,000-dalton protein and the 33,000-dalton fragment show common peptides and provide strong direct evidence that the proteins are products of the SV40 A gene. The deletion fragment reacts with antitumor sera and binds to double-stranded DNA in the presence of the complete A protein.