Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comparative Study of the Hodgkin-huxley and Fitzhugh-nagumo Models of Neuron Pulse Propagation

The four-dimensional Hodgkin–Huxley equations are considered as the prototype for description of neural pulse propagation. Their mathematical complexity and sophistication prompted a simplified two-dimensional model, the FitzHugh–Nagumo equations, which display many of the former's dynamical features. Numerical and mathematical analysis are employed to demonstrate that the FitzHugh–Nagumo equations can provide quantitative predictions in close agreement with the Hodgkin–Huxley equations. The two most important parameters of a neural pulse are its speed c(T) and pulse height vmax(T) and so numerical computations of these quantities predicted by the Hodgkin–Huxley equations are given over the entire temperature range T for stability of a neural pulse. Similarly, the FitzHugh–Nagumo equations are parameterized by two dimensionless quantities: a which determines the dynamics of the pulse front, and b whose departure from zero tailors the front to form the resultant pulse. Parallel computations are presented for the FitzHugh–Nagumo pulse whose relative simplicity permits analytic determination to close approximation of the dimensionless speed θ(a, b) and pulse height Vmax(a, b). It is shown that the two models are numerically identified by scaling according to c = 4904 θ cm/sec and vmax = 115 VmaxmV where the numbers are a consequence of the experimental parameter values inherent to the Hodgkin–Huxley equations. With this connection, at a given temperature the Hodgkin–Huxley speed and pulse height determine unique values for the two FitzHugh–Nagumo parameters a and b. Approximate analytic solution for θ(a, b) allows construction of a three-dimensional [a, b, θ] state plot upon which a unique ridge defines, as a function of temperature, the speed and associated pulse height predicted by the Hodgkin–Huxley equations. The generality of the state plot suggests its application to other conductance models. Comparison of the Hodgkin–Huxley with the FitzHugh–Nagumo models highlight the quantitative limitations of the latter in the region of the minimum characterizing the back portion of the pulse. To overcome this limitation would require analytic extension of the FitzHugh–Nagumo dynamics to higher dimensionality.
Human Neuroscience

the ability to resolve response interference within a trial which may involve selective inhibition of the automatic response to reduce interference between competing actions (Simon and Wolf, 1963; Simon and Rudell, 1967; Forstmann et al., 2008a,b). Interestingly, when zooming in on trial-by-trial adjustments, it becomes evident that the interference effect is reduced after I compared to C trials (Gratton et al., 1992). This fi nding refers to the so-called confl ict adaptation effect, or Gratton effect, which can be quantifi ed as the difference of the interference effect following incongruent trials (iI–iC), subtracted from the interference effect following congruent trials (cI–cC). For brevity, in the following text we will use a lower case to denote the previous trial and an upper case to denote the current trial. An infl uential theory capturing the confl ict adaptation effect is the confl ict monitoring hypothesis (Botvinick et al., 1999, 2001, 2004; but see also Mansouri et al., 2009). It proposes that in order to resolve response confl ict, the presence of this confl ict must fi rst be detected and evaluated. Subsequently, cognitive control is implemented in order to overcome the detected confl ict. Once control processes are activated they can also act on the following trial: when the subsequent trial is again incongruent, the already implemented control processes lead to an advantage in overcoming confl ict. Hence, faster reaction times (RTs) are observed on iI trials compared to cI trials which results in an overall reduction of the interference effect after I trials compared to C trials. The activation of confl icting response tendencies is typically accompanied by activation of posterior brain areas within the medial frontal cortex, most prominently the rostral cingulate zone (RCZ; for review see Ridderinkhof et al., 2004a). Selecting the task-appropriate action is more demanding when competing alternative actions are activated on the basis of task-irrelevant stimulus
Skin-Derived Mesenchymal Stem Cells Help Restore Function to Ovaries in a Premature Ovarian Failure Mouse Model

Skin-derived mesenchymal stem cells (SMSCs) can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs) and male skin-derived mesenchymal stem cells (M-SMSCs) from red fluorescence protein (RFP) transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH) antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.
Comparison of nerve cell and nerve cell plus Schwann cell cultures, with particular emphasis on basal lamina and collagen formation

The availability of cultures of normal cells (NCs) and Schwann cells (SCs) with and without fibroblasts has allowed us to investigate the sources of endoneurial and perineurial constituents of peripheral nerve. NCs cultured alone, devoid of ensheathment but healthy in appearance, lack basal lamina and extracellular fibrils. In contrast, when SCs accompany NCs, basal lamina and extracellular fibrils are consistently visible around SCs in outgrowth areas formed de novo in culture. These fibrils average 18 nm in diameter, exhibit a repeating banding pattern, and are trypsin-resistant and collagenase-sensitive. Collagen synthesis is also indicated by the incorporation of [14C]proline into peptide-bound hydroxy-proline in NC + SC or SC cultures. That the [14C]hydroxyproline polypeptides formed in NC + SC cultures are collagenous was determined in part by pepsin digestion- ammonium sulfate precipitation-polyacrylamide gel electrophoresis techniques; the 14C-polypeptides migrate to the positions of alpha 1 (I), alpha 2, alpha 1 (III), and alpha B chains of type I, type III, and A-B collagens. Also formed are thin, ruthenium red-preserved strands interconnecting basal laminae. SC ensheathment of axons is similar to that found in the animal; one SC is related to a number of unmyelinated axons or a single myelinated axon. This proclivity to ensheathe and myelinate axons indicates that SC function is not lost during the preparative procedures or after lengthy isolation in culture and provides the most reliable means for SC identification. Perineurial ensheathment and macrophages are lacking in NC + SC culture preparations divested of fibroblasts. We conclude that SCs do not form perineurium or the larger diameter collagen fibrils typical of endoneurium but that in combination with neurons they generate biochemically detectable collagens and morphologically visible basal lamina and thin collagenous fibrils.
Characterization of Mesenchymal Stem Cells of “No-Options” Patients with Critical Limb Ischemia Treated by Autologous Bone Marrow Mononuclear Cells

Background Application of autologous bone marrow mononuclear cells to “no option” patients with advanced critical limb ischemia (CLI) prevented major limb amputation in 73% patients during the 6-month follow-up. We examined which properties of bone marrow stromal cells also known as bone-marrow derived mesenchymal stem cells of responding and non-responding patients are important for amputation-free survival. Methods and Findings Mesenchymal stem cells of 41 patients with CLI unsuitable for revascularisation were isolated from mononuclear bone marrow concentrate used for their treatment. Based on the clinical outcome of the treatment, we divided patients into two groups: responders and non-responders. Biological properties of responders’ and non-responders’ mesenchymal stem cells were characterized according to their ability to multiply, to differentiate in vitro, quantitative expression of cell surface markers, secretion of 27 cytokines, chemokines and growth factors, and to the relative expression of 15 mesenchymal stem cells important genes. Secretome comparison between responders (n=27) and non-responders (n=14) revealed significantly higher secretion values of IL-4, IL-6 and MIP-1b in the group of responders. The expression of cell markers CD44 and CD90 in mesenchymal stem cells from responders was significantly higher compared to non-responders (p<0.01). The expression of mesenchymal stem cells surface markers that was analyzed in 22 patients did not differ between diabetic (n=13) and non-diabetic (n=9) patient groups. Statistically significant higher expression of E-cadherin and PDX-1/IPF1 genes was found in non-responders, while expression of Snail was higher in responders. Conclusions The quality of mesenchymal stem cells shown in the expression of cell surface markers, secreted factors and stem cell genes plays an important role in therapeutic outcome. Paracrine mechanisms are main drivers in the induction of reparatory processes in CLI patients. Differences in mesenchymal stem cells properties are discussed in relation to their involvement in the reparatory process.
Development of an objective, semiautomated method for assessment of sperm motility

Summary Study of sperm motility is associated to the development of precise and economical systems of evaluation. The purpose of this work was to develop an Objective Semi‐Automated Method (MOSA) to evaluate the sperm motility. Human semen samples were registered by video‐microscopy. The same videofilms were analysed with the MOSA, the subjective method and the automated CellSoft® method. The percentages of motile and immotile sperms were equivalent with the three methods. The percentages of rapidly and slowly motile sperms were similar both with the MOSA and the subjective method. The curvilinear and linear velocities as well as the linearity values obtained with the MOSA were different to those obtained with the CellSoft®, although such differences would be biologically acceptable. MOSA is an inexpensive, objective and precise method that does not require trained technicians and allows evaluation of several parameters of sperm motility.
Semi-Supervised Learning with GANs: Revisiting Manifold Regularization

GANS are powerful generative models that are able to model the manifold of natural images. We leverage this property to perform manifold regularization by approximating the Laplacian norm using a Monte Carlo approximation that is easily computed with the GAN. When incorporated into the feature-matching GAN of Improved GAN, we achieve state-of-the-art results for GAN-based semi-supervised learning on the CIFAR-10 dataset, with a method that is significantly easier to implement than competing methods.
Recent advances in the angiotensin‐converting enzyme 2–angiotensin(1–7)–Mas axis

In the past few years, the classical concept of the renin–angiotensin system (RAS) has experienced substantial conceptual changes. The identification of: the renin/prorenin receptor; the angiotensin‐converting enzyme homologue, ACE2, as an angiotensin peptide‐processing enzyme and a virus receptor for severe acute respiratory syndrome, the Mas as a receptor for angiotensin (1–7) [Ang(1–7)], and the possibility of signaling through ACE have contributed to switch our understanding of the RAS from the classical limited‐proteolysis linear cascade to a cascade with multiple mediators, multiple receptors and multifunctional enzymes. With regard to Ang(1–7), the identification of ACE2 and of Mas as a receptor implicated in its actions contributed to decisively establish this heptapeptide as a biologically active member of the RAS cascade. In this review, we will focus on the recent findings related to the ACE2–Ang(1–7)–Mas axis and, in particular, on its putative role as an ACE–Ang II–AT1 receptor counter‐regulatory axis within the RAS.
Effects of In Vitro Exposure to Diarrheic Toxin Producer Prorocentrum lima on Gene Expressions Related to Cell Cycle Regulation and Immune Response in Crassostrea gigas

Background Crassostrea gigas accumulates diarrheic shellfish toxins (DSP) associated to Prorocentrum lima of which Okadaic acid (OA) causes specific inhibitions of serine and threonine phosphatases 1 and 2A. Its toxic effects have been extensively reported in bivalve mollusks at cellular and physiological levels, but genomic approaches have been scarcely studied. Methodology/Principal Findings Acute and sub-chronic exposure effects of P. lima were investigated on farmed juvenile C. gigas (3–5 mm). The Pacific oysters were fed with three dinoflagellate concentrations: 0.3, 3, and 30×103 cells mL−1 along with a nontoxic control diet of Isochrysis galbana. The effects of P. lima on C. gigas were followed by analyzing expression levels of a total of four genes, three involved in cell cycle regulation and one in immune response by polymerase chain reaction and real time quantitative PCR, where changes in time and cell concentration were found. The highest expression levels were found in oysters fed 3×103 cells mL−1 at 168 h for the cycle regulator p21 protein (9 fold), chromatin assembly factor 1 p55 subunit (8 fold), elongation factor 2 (2 fold), and lipopolysaccharide/β-1, 3 glucan binding protein (13 fold above base line). Additionally, the transcript level of all the genes decreased in oysters fed wich the mixed diet 30×103 cells mL−1 of dinoflagellate after 72 h and was lowest in the chromatin assembly factor 1 p55 subunit (0.9 fold below baseline). Conclusions On C. gigas the whole cell ingestion of P lima caused a clear mRNA modulation expression of the genes involved in cell cycle regulation and immune system. Over-expression could be related to DNA damage, disturbances in cell cycle continuity, probably a genotoxic effect, as well as an activation of its innate immune system as first line of defense.
Toxicant content, physical properties and biological activity of waterpipe tobacco smoke and its tobacco-free alternatives

Objectives Waterpipe smoking using sweetened, flavoured tobacco products has become a widespread global phenomenon. In this paper, we review chemical, physical and biological properties of waterpipe smoke. Data sources Peer-reviewed publications indexed in major databases between 1991 and 2014. Search keywords included a combination of: waterpipe, narghile, hookah, shisha along with names of chemical compounds and classes of compounds, in addition to terms commonly used in cellular biology and aerosol sizing. Study selection The search was limited to articles published in English which reported novel data on waterpipe tobacco smoke (WTS) toxicant content, biological activity or particle size and which met various criteria for analytical rigour including: method specificity and selectivity, precision, accuracy and recovery, linearity, range, and stability. Data extraction Multiple researchers reviewed the reports and collectively agreed on which data were pertinent for inclusion. Data synthesis Waterpipe smoke contains significant concentrations of toxicants thought to cause dependence, heart disease, lung disease and cancer in cigarette smokers, and includes 27 known or suspected carcinogens. Waterpipe smoke is a respirable aerosol that induces cellular responses associated with pulmonary and arterial diseases. Except nicotine, smoke generated using tobacco-free preparations marketed for ‘health conscious’ users contains the same or greater doses of toxicants, with the same cellular effects as conventional products. Toxicant yield data from the analytical laboratory are consistent with studies of exposure biomarkers in waterpipe users. Conclusions A sufficient evidence base exists to support public health interventions that highlight the fact that WTS presents a serious inhalation hazard.
A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

Background: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies. Methods: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed. Results: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse. Conclusion: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.
A combinatorial approach to protein docking with flexible side-chains

Rigid body docking approaches are not sufficient to predict the structure of a protein complex from the unbound (native) structures of the two proteins. Accounting for side—chain flexibility is an important step towards fully flexible protein docking. This work describes an approach that allows conformational flexibility for the side—chains while keeping the protein backbone rigid. Starting from candidates created by a rigid docking algorithm, we demangle the side—chains of the docking site, thus creating reasonable approximations of the true complex structure. These structures are ranked with respect to the binding free energy. We present two new techniques for side—chain demangling. Both approaches are based on a discrete representation of the side—chain conformational space by the use of a rotamer library. This leads to a combinatorial optimization problem. For the solution of this problem we propose a fast heuristic approach and an exact, albeit slower method using branch—&—cut techniques. As a test set we use the unbound structures of three proteases and the corresponding protein inhibitors. For each of the examples the highest—ranking conformation produced was a good approximation of the true complex structure.
Orbital periods and accretion disc structure of four AM CVn systems

Phase-resolved spectroscopy of four AM CVn systems obtained with the William Herschel Telescope and the Gran Telescopio de Canarias is presented. SDSS J120841.96+355025.2 was found to have an orbital period of 52.96 ± 0.40 min and shows the presence of a second bright spot in the accretion disc. The average spectrum contains strong Mg i and Si i/ii absorption lines most likely originating in the atmosphere of the accreting white dwarf. SDSS J012940.05+384210.4 has an orbital period of 37.555 ± 0.003 min. The average spectrum shows the Stark-broadened absorption lines of the DB white dwarf accretor. The orbital period is close to the previously reported superhump period of 37.9 min. Combined, this results in a period excess ϵ = 0.0092 ± 0.0054 and a mass ratio q = 0.031 ± 0.018. SDSS J164228.06+193410.0 displays an orbital period of 54.20 ± 1.60 min with an alias at 56.35 min. The average spectrum also shows strong Mg i absorption lines, similar to SDSS J120841.96+355025.2. SDSS J152509.57+360054.50 displays a period of 44.32 ± 0.18 min. The overall shape of the average spectrum is more indicative of shorter period systems in the 20–35 min range. The accretor is still clearly visible in the pressure-broadened absorption lines most likely indicating a hot donor star and/or a high-mass accretor. Flux ratios for several helium lines were extracted from the Doppler tomograms for the disc and bright spot region, and compared with single-slab Local Thermodynamic Equilibrium (LTE) models with variable electron densities and path lengths to estimate the disc and bright spot temperature. Good agreement between data and the model in three out of four systems was found for the disc region. All three systems show similar disc temperatures of ∼10 500 K. In contrast, only weak agreement between observation and models was found for the bright spot region.
Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes

OBJECTIVE Blockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated. RESEARCH DESIGN AND METHODS Renal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4–6 mmol/l) and hyperglycemia (9–11 mmol/l). RESULTS In response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng · ml−1 · h−1, P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 ± 6 to 20 ± 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 ± 0.6 to 6.8 ± 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 ± 1.13 to 5.55 ± 0.81%) and hyperglycemia (from 1.86 ± 0.98 to 5.63 ± 0.62) as did the vasodilatory response to sublingual nitroglycerin. CONCLUSIONS DRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 diabetes.