Miracle-dz/UniFAR-FTUs huggingface dataset:
Postsynaptic effects of magnesium and calcium at the mouse neuromuscular junction

The effects of elevated magnesium and calcium concentrations on height and time course of miniature endplate currents (MEPCs) at the mouse neuromuscular junction were studied. With both ions, MEPC height was decreased; the rate of decay of MEPCs was reduced in high magnesium and was unchanged in high calcium. Raised Mg2+ or Ca2+ both acted to modify the effects on MEPC time course of procaine, scopolamine, atropine, lidocaine, and quinidine, all of which act to cause biphasic decay of MEPCs in a manner consistent with reversible “plugging” of endplate channels, with rate constants for blocking and unblocking that are sensitive to postsynaptic transmembrane potential. Both the blocking and unblocking rate constants were decreased by increasing divalent ion concentration. No such reduction of rate constants was observed using menthol or pentobarbital, which appear to block channels in a voltage- independent manner. It is concluded that the divalent ions act to alter the channel environment via interactions with charged groups in or near the endplate channels.
Phrenic Long-Term Facilitation Requires Spinal Serotonin Receptor Activation and Protein Synthesis

Respiratory long-term facilitation (LTF) is a form of serotonin-dependent plasticity induced by intermittent hypoxia. LTF is manifested as a long-lasting increase in respiratory amplitude (and frequency) after the hypoxic episodes have ended. We tested the hypotheses that LTF of phrenic amplitude requires spinal serotonin receptor activation and spinal protein synthesis. A broad-spectrum serotonin receptor antagonist (methysergide) or protein synthesis inhibitors (emetine or cycloheximide) were injected intrathecally in the cervical spinal cord of anesthetized rats. Control rats, injected with vehicle (artificial CSF), exhibited an augmented phrenic burst amplitude after three 5 min episodes of hypoxia (78 ± 15% above baseline, 60 min after hypoxia; p < 0.05), indicating LTF. Pretreatment with methysergide, emetine, or cycloheximide attenuated or abolished phrenic LTF (20 ± 4, 0.2 ± 11, and 20 ± 2%, respectively; allp > 0.05). With protein synthesis inhibitors, phrenic LTF differed from control by 15 min after intermittent hypoxia. As an internal control against unintended drug distribution, we measured respiratory LTF in hypoglossal (XII) motor output. At 60 min after intermittent hypoxia, all treatment groups exhibited similar XII LTF (artificial CSF, 44 ± 10%; methysergide, 40 ± 5%; emetine, 35 ± 9%; and cycloheximide, 57 ± 29%; allp < 0.05), suggesting that drugs were restricted at effective doses to the spinal cord. We conclude that phrenic LTF requires spinal serotonin receptor activation and protein synthesis. Serotonin receptors on phrenic motoneuron dendrites may induce new protein synthesis, thereby giving rise to phrenic LTF.
Evolution of Cryptosporidium parvum lactate dehydrogenase from malate dehydrogenase by a very recent event of gene duplication.

We have expressed the L-lactate dehydrogenase (LDH) and L-malate dehydrogenase (malDH) genes from the apicomplexan Cryptosporidium parvum (CpLDH1 and CpMalDH1) as maltose-binding protein (MBP) fusion proteins in Escherichia coli. The substrate specificities, enzymatic kinetics, and oligomeric states of these two parasite enzymes have been characterized. By taking advantage of recently completed and ongoing apicomplexan genome sequencing projects, we identified additional MalDH genes from Plasmodium spp. , Toxoplasma gondii, and Eimeria tenella that were previously unavailable. All apicomplexan MalDHs appeared to be cytosolic and no organellar homologs were identified from the completely sequenced P. falciparum genome and other ongoing apicomplexan genome-sequencing projects. Using these expanded apicomplexan LDH and MalDH sequence databases, we reexamined their phylogenetic relationships and reconfirmed their relationship to alpha-proteobacterial MalDHs. All LDH and MalDH enzymes from apicomplexans were monophyletic within the LDH-like MalDH group (i.e., MalDH resembling LDH) as a sister to alpha-proteobacterial MalDHs. All apicomplexan LDHs, with the exception of CpLDH1, formed a separate clade from their MalDH counterparts, indicating that these LDHs were evolved from an ancestral apicomplexan MalDH by a gene duplication coupled with functional conversion before the expansion of apicomplexans. Finally, CpLDH1 was consistently placed together with CpMalDH1 within the apicomplexan MalDH cluster, confirming an early working hypothesis that CpLDH1 was probably evolved from the same ancestor of CpMalDH1 by a very recent gene duplication that occurred after C. parvum diverged from other apicomplexans.
Effect of oligofructose or dietary calcium on repeated calcium and phosphorus balances, bone mineralization and trabecular structure in ovariectomized rats*

We investigated the effects of dietary oligofructose and Ca on bone structure in ovariectomized rats, using microradiography and histomorphometry. Ninety-six animals were allocated to seven experimental groups: G1, sham-operated; G2–G7, ovariectomized. Semi-purified diets containing 5 g Ca/kg (recommended content) without oligofructose (G1, G2) or with 25, 50 or 100 g oligofructose/kg (G3, G4, G5) or 10 g Ca/kg (high content) without oligofructose (G6) or with 50 g oligofructose/kg (G7) were fed for 16 weeks. At the recommended level of Ca, high oligofructose (G5) increased femur mineral levels in ovariectomized rats, while medium oligofructose did so at high Ca. Increasing Ca in the absence of oligofructose did not increase femur mineral content. Trabecular bone area (%) analysed in the tibia was 10·3 (SEM 1·2) (G1), 7·7 (SEM 0·6) (G2), 9·3 (SEM 0·7) (G3), 9·4 (SEM 1·0) (G4), 9·5 (SEM 0·7) (G5), 10·2 (SEM 0·8) (G6), and 12·6 (SEM 0·8) (G7). At the recommended level of Ca, 25 g oligofructose/kg prevented loss of trabecular area due to increased trabecular thickness, while 50 or 100 g oligofructose/kg increased trabecular perimeter. At high Ca, oligofructose prevented loss of bone area due to increased trabecular number but similar thickness (G7 v. G6). When Ca was raised in the presence of oligofructose (G7), trabecular area and cortical thickness were highest, while loss of trabecular connectivity was lowest of all groups. At the same time, lumbar vertebra Ca was higher; 44·0 (SEM 0·8) (G7) compared with 41·6 (SEM 0·8) (G2), 41·4 (SEM 0·7) (G4), and 40·5 (SEM 1·0) mg (G6). We conclude that ovariectomy-induced loss of bone structure in the tibia was prevented but with different trabecular architecture, depending on whether dietary Ca was increased, oligofructose was incorporated, or both. Oligofructose was most effective when dietary Ca was high.
A methodology for energy-quality tradeoff using imprecise hardware

Recent studies have demonstrated the potential for reducing energy consumption in integrated circuits by allowing errors during computation. While most proposed techniques for achieving this rely on voltage overscaling (VOS), this paper shows that Imprecise Hardware (IHW) with design-time structural parameters can achieve orthogonal energy-quality tradeoffs. Two IHW adders are improved and two IHW multipliers are introduced in this paper. In addition, a simulation-free error estimation technique is proposed to rapidly and accurately estimate the impact of IHW on output quality. Finally, a quality-aware energy minimization methodology is presented. To validate this methodology, experiments are conducted on two computational kernels: DOT-PRODUCT and L2-NORM - used in three applications - Leukocyte Tracker, SVM classification and K-means clustering. Results show that the Hellinger distance between estimated and simulated error distribution is within 0.05 and that the methodology enables designers to explore energy-quality tradeoffs with significant reduction in simulation complexity.
Inhibition of basement membrane formation by a nidogen-binding laminin γ1-chain fragment in human skin-organotypic cocultures

Basement membranes generally determine different tissue compartments in complex organs, such as skin, playing not only an important structural but also a regulatory role. We have previously demonstrated the formation of a regular basement membrane in organotypic three-dimensional (3D)-cocultures of human skin keratinocytes and fibroblasts by indirect immunofluorescence and transmission electron microscopy. In this assembly process, cross-linking of type IV collagen and the laminin γ1 chain by nidogen is considered a crucial step. For a functional proof, we have now competitively inhibited nidogen binding to laminin in 3D-cocultures with a recombinant laminin γ1 fragment (γ1III3-5 module) spanning this binding site. Repeated treatment abolished the deposition of nidogen at the epithelial-matrix interface but also greatly perturbed the presence of other matrix constituents such as laminin and perlecan. This effect persisted over the entire observation period of 10 to 21 days. In contrast, some components of the basement membrane zone were only moderately affected, with the laminin-5 isoform (γ2 chain), type IV collagen and integrin α6ß4 still showing a distinct staining at their regular position, when seen by light microscopy. Furthermore, epidermal morphology and differentiation remained largely normal as indicated by the regular location of keratins K1/K10 and also of late differentiation markers. Ultrastructural examination demonstrated that the γ1 fragment completely suppressed any formation of basement membrane structures (lamina densa) and also of hemidesmosomal adhesion complexes. As a consequence of hemidesmosome deficiency, keratin filament bundles were not attached to the ventral basal cell aspect. These findings were further substantiated by immuno-electron microscopy, revealing either loss or drastic reduction and dislocation of basement membrane and hemidesmosomal components. Taken together, in this simplified human skin model (representing a `closed system') a functional link has been demonstrated between compound structures of the extra- and intracellular space at the junctional zone providing a basis to interfere at distinct points and in a controlled fashion.
Implantable Intrathecal Pumps for the Treatment of Noncancer Chronic Pain in Elderly Population: Drug Dose and Clinical Efficacy

Objective. This study aims to assess long‐term follow‐up of efficacy and quality of life for 34 geriatric patients (10 men, 24 women, mean age 72.3 ± 11.6 years) with intrathecal (IT) drug delivery systems (IDDS), implanted between 1994 and 2002, for the treatment of severe noncancer chronic pain.
ASSOCIATION OF MITOCHONDRIAL ALLELE 4216C WITH INCREASED RISK FOR SEPSIS-RELATED ORGAN DYSFUNCTION AND SHOCK AFTER BURN INJURY

Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15% of their total body surface area or greater than or equal to 5% full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score ≥16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95% confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.
Microstructural Study, Tensile Properties, and Scanning Electron Microscopy Fractography Failure Analysis of Various Agricultural Residue Fibers

This paper presents an approach to examine the microstructural properties and mechanical behavior of coconut husks, banana pseudo-stem, pineapple leaf, and sugarcane bagasse fibers by scanning electron microscope and mini-tensile tester, respectively. Single fiber bundles were examined by using scanning electron microscope. Tensile tests were performed at different diameters (0.15–0.55 mm) and gauge lengths (10, 15, 20, and 30 mm/min) to assess the effects of diameter and gauge length on tensile properties. It was found that fibers consisted of different types of regularly arranged cells. The tensile strength (310 MPa) and Young’s modulus (7.4 GPa) of pineapple leaf fiber bundles showed the highest value compared to the other fibers. The tensile strength and Young’s modulus decreased with the increase of diameter and gauge length of fiber bundles. Scanning electron microscopic fractography analysis showed comparatively heterogeneous ruptures associated with more participants of microfibrils for pineapple leaf and banana pseudo-stem fibers compared to coconut husk and sugarcane bagasse fibers. These fractographic observations were discussed in the light of current knowledge of the microstructure of each fiber and the corresponding mechanical properties.
Altered Ca2+ Homeostasis and Endoplasmic Reticulum Stress in Myotonic Dystrophy Type 1 Muscle Cells

The pathogenesis of Myotonic Dystrophy type 1 (DM1) is linked to unstable CTG repeats in the DMPK gene which induce the mis-splicing to fetal/neonatal isoforms of many transcripts, including those involved in cellular Ca2+ homeostasis. Here we monitored the splicing of three genes encoding for Ca2+ transporters and channels (RyR1, SERCA1 and CACN1S) during maturation of primary DM1 muscle cells in parallel with the functionality of the Excitation-Contraction (EC) coupling machinery. At 15 days of differentiation, fetal isoforms of SERCA1 and CACN1S mRNA were significantly higher in DM1 myotubes compared to controls. Parallel functional studies showed that the cytosolic Ca2+ response to depolarization in DM1 myotubes did not increase during the progression of differentiation, in contrast to control myotubes. While we observed no differences in the size of intracellular Ca2+ stores, DM1 myotubes showed significantly reduced RyR1 protein levels, uncoupling between the segregated ER/SR Ca2+ store and the voltage-induced Ca2+ release machinery, parallel with induction of endoplasmic reticulum (ER) stress markers. In conclusion, our data suggest that perturbed Ca2+ homeostasis, via activation of ER stress, contributes to muscle degeneration in DM1 muscle cells likely representing a premature senescence phenotype.
The Canadian Methotrexate and Etanercept Outcome Study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis

Objective To determine if withdrawing methotrexate (MTX) after 6 months of combination etanercept (ETN)+MTX, in MTX-inadequate responders with active rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX. Methods Tumour necrosis factor-inhibitor naïve RA patients with disease activity score 28 (DAS28)≥3.2, swollen joint count≥3, despite stable MTX, were treated with ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or switch to ETN monotherapy for an additional 18 months. The primary endpoint was change in DAS28 from 6-month randomisation to 12 months. The non-inferiority margin of change in DAS28 was 0.6, with prespecified analyses (DAS28<3.2 vs DAS28≥3.2). Results 205 patients were randomised. DAS28 was stable in patients on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12 months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1 to 0.7) between the ETN and the ETN+MTX groups, for the month 6–12 change in DAS28. However, patients who achieved low disease activity (LDA; DAS28<3.2) at 6 months had a similar disease activity at 12 months, whether on monotherapy or combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely, for patients who did not reach LDA at 6 months, those on ETN monotherapy had increased disease activity at 12 months, while disease activity continued to decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN vs −0.4 ETN+MTX, p=0.0023). Conclusions Non-inferiority was not achieved. Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate responders did not yield the same degree of improvement between 6 and 12 months compared with continuing ETN+MTX. Trial Registration ClinicalTrials.gov−NCT00654368.
Evaluation of monkey intraocular pressure by rebound tonometer

Purpose To evaluate the usefulness of the TonoVet™ rebound tonometer in measuring intraocular pressure (IOP) of monkeys. Methods The accuracy of the TonoVet™ rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. Results IOP readings generated by the TonoVet™ tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922±0.014 (mean±SEM, n=4), a y-intercept of 3.04±0.61, and a correlation coefficient of r2=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 μg) of the rho kinase inhibitor, H1152, produced a 5–6 mmHg reduction (p<0.001) in IOP, lasting at least 4 h. In addition, topical administration of Travatan®, a prostaglandin agonist, induced a small transient IOP increase (1.1 mmHg versus vehicle control; p=0.26) at 2 h after treatment followed by a pressure reduction at 23 h (−2.4 mmHg; p<0.05). Multiple daily dosing with the drug produced a persistent IOP-lowering effect. Three consecutive days of Travatan treatment produced ocular hypotension of −2.0 to −2.2 mmHg (p<0.05) the following day. Conclusions The rebound tonometer was easy to use and accurately measured IOP in the rhesus monkey eye.
Proximal Riemannian Pursuit for Large-Scale Trace-Norm Minimization

Trace-norm regularization plays an important role in many areas such as computer vision and machine learning. When solving general large-scale trace-norm regularized problems, existing methods may be computationally expensive due to many high-dimensional truncated singular value decompositions (SVDs) or the unawareness of matrix ranks. In this paper, we propose a proximal Riemannian pursuit (PRP) paradigm which addresses a sequence of trace-norm regularized subproblems defined on nonlinear matrix varieties. To address the subproblem, we extend the proximal gradient method on vector space to nonlinear matrix varieties, in which the SVDs of intermediate solutions are maintained by cheap low-rank QR decompositions, therefore making the proposed method more scalable. Empirical studies on several tasks, such as matrix completion and low-rank representation based subspace clustering, demonstrate the competitive performance of the proposed paradigms over existing methods.
Greedy Forwarding in Dynamic Scale-Free Networks Embedded in Hyperbolic Metric Spaces

We show that complex (scale-free) network topologies naturally emerge from hyperbolic metric spaces. Hyperbolic geometry facilitates maximally efficient greedy forwarding in these networks. Greedy forwarding is topology-oblivious. Nevertheless, greedy packets find their destinations with 100% probability following almost optimal shortest paths. This remarkable efficiency sustains even in highly dynamic networks. Our findings suggest that forwarding information through complex networks, such as the Internet, is possible without the overhead of existing routing protocols, and may also find practical applications in overlay networks for tasks such as application-level routing, information sharing, and data distribution.
Delay of vortex ring pinchoff by an imposed bulk counterflow

The Kelvin–Benjamin variational principle has been previously used to predict that vortex ring pinchoff can be delayed if the energy of the leading vortex ring is decreased during formation and/or the energy delivered by the vortex generator is increased. We present experimental results in which the former and latter energy effects were simultaneously accomplished by imposing a bulk axisymmetric counterflow during vortex ring formation. Measurements indicate that the formation number is retarded sufficiently to allow increased ingestion of fluid circulation by the leading vortex ring. This serves as a first demonstration of artificial manipulation of vortex ring formation for potential propulsive benefits in starting jets.
International Journal of Occupational Safety and Ergonomics a Biomechanical Analysis of Manual Lifting Tasks Performed in Restricted Workspaces a Biomechanical Analysis of Manual Lifting Tasks Performed in Restricted Workspaces

Taylor & Francis makes every effort to ensure the accuracy of all the information (the " Content ") contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This paper describes the results of an experimental study aimed at evaluating the biomechanical effects of working in a spatially restricted environment on manual lifting tasks. The main objective of the study is to estimate the biomechanical loading (in terms of peak compression and shear forces) on the lumbar spine for the selected combinations of limited headroom heights and twisting angles. A three-dimensional dynamic biomechanical model was utilized to assess peak compression and shear forces at the L5/S1 lum-bosacral joint. The results indicated that by reducing the headroom height, the participants were forced to stand with their trunks fully flexed forward which, by increasing the mechanical disadvantage at the lumbosacral disc, increased the compression forces. Both compression and shear forces were affected by the increase in twisting angle. The greater the twisting angle, the higher the compression and shear forces. Regression models were developed and validated, which demonstrated high accuracy of predicting the psycho-physical and biomechanical lifting capacities. manual lifting tasks restricted workspaces compression and shear forces regression modeling