Miracle-dz/UniFAR-FTUs huggingface dataset:
Technical Performance of Percutaneous and Laminectomy Leads Analyzed by Modeling

The objective of this study was to compare the technical performance of laminectomy and percutaneous spinal cord stimulation leads with similar contact spacing by computer modeling. Monopolar and tripolar (guarded cathode) stimulation with both lead types in a low‐thoracic spine model was simulated using UT‐SCS software. Dorsal column and dorsal root fiber thresholds were calculated as well as the area of recruited fibers in the dorsal columns, the rostrocaudal span of recruited dorsal root fibers and the energy consumption at discomfort threshold. Tripolar stimulation is superior to monopolar stimulation in the recruitment of the dorsal columns, a percutaneous lead recruits a ∼12% larger dorsal column area than a laminectomy lead does. This difference is reduced when the contact spacing of the lead models is the same. A percutaneous lead with significant wire impedance (140 Ohms) consumes ∼115–240% more energy, whereas the same lead with negligible wire impedance consumes ∼40–85% more energy. A deterioration of all performance parameters is predicted when a percutaneous lead is placed more dorsally in the epidural tissue. When positioned next to the dura mater, a percutaneous lead has a similar performance (fiber recruitment in the dorsal columns and the dorsal roots) as a laminectomy lead with similar contact spacing, but substantially higher energy consumption. The superior clinical performance of the laminectomy lead is most probably due to the difference in volume and insertion technique of the two lead types.
A major 125‐kd membrane glycoprotein of Saccharomyces cerevisiae is attached to the lipid bilayer through an inositol‐containing phospholipid.

A number of plasma membrane glycoproteins of mammalian and protozoan origin are released from cells by phosphatidylinositol‐specific phospholipase C. Some of these proteins have been shown to be attached to the lipid bilayer via a covalently linked, structurally complex glycophospholipid. Here we establish the existence of similarly linked glycoproteins in the yeast Saccharomyces cerevisiae. The most abundant of these is a tightly membrane‐bound glycoprotein of 125 kd. The detergent‐binding moiety of this protein can be removed by phosphatidylinositol‐specific phospholipase C of bacterial origin or from Trypanosoma brucei. Metabolic labeling indicates that the protein contains covalently attached fatty acid and inositol. It also contains the cross‐reacting determinant (CRD), an antigen found previously on the glycophospholipid anchor of protozoan and mammalian origin. Treatment of the protein with endoglycosidases F and H results in a 95‐kd species. In the secretion mutant sec18, grown at 37 degrees C, the vesicular transport of glycoproteins is reversibly blocked between the rough endoplasmic reticulum and the Golgi apparatus. We find that sec18 cells, when grown at 37 degrees C, do add phospholipid anchors to newly synthesized glycoproteins. This indicates that these anchors are added in the rough endoplasmic reticulum.
A novel method for splice sites prediction using sequence component and hidden Markov model

With increasing growth of DNA sequence data, it has become an urgent demand to develop new methods to accurately predict the genes. The performance of gene detection methods mainly depend on the efficiency of splice site prediction methods. In this paper, a novel method for detecting splice sites is proposed by using a new effective DNA encoding method and AdaBoost.M1 classifier. Our proposed DNA encoding method is based on multi-scale component (MSC) and first order Markov model (MM1). It has been applied to the HS3D dataset with repeated 10 fold cross validation. The experimental results indicate that the new method has increased the classification accuracy and outperformed some current methods such as MM1-SVM, Reduced MM1-SVM, SVM-B, LVMM, DM-SVM, DM2-AdaBoost and MS C+Pos(+APR)-SVM.
Importance of genetic influences on chronic widespread pain.

OBJECTIVE To estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences. METHODS Data were collected from a national sample of twins > or = 42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer-assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain. RESULTS Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic, and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences. CONCLUSION Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.
Evidence That 3-Phosphoinositide-dependent Protein Kinase-1 Mediates Phosphorylation of p70 S6 Kinase in Vivoat Thr-412 as well as Thr-252*

Protein kinase B and p70 S6 kinase are members of the cyclic AMP-dependent/cyclic GMP-dependent/protein kinase C subfamily of protein kinases and are activated by a phosphatidylinositol 3-kinase-dependent pathway when cells are stimulated with insulin or growth factors. Both of these kinases are activated in cells by phosphorylation of a conserved residue in the kinase domain (Thr-308 of protein kinase B (PKB) and Thr-252 of p70 S6 kinase) and another conserved residue located C-terminal to the kinase domain (Ser-473 of PKB and Thr-412 of p70 S6 kinase). Thr-308 of PKBα and Thr-252 of p70 S6 kinase are phosphorylated by 3-phosphoinositide-dependent protein kinase-1 (PDK1)in vitro. Recent work has shown that PDK1 interacts with a region of protein kinase C-related kinase-2, termed the PDK1 interacting fragment (PIF). Interaction with PIF converts PDK1 from a form that phosphorylates PKB at Thr-308 alone to a species capable of phosphorylating Ser-473 as well as Thr-308. This suggests that PDK1 may be the enzyme that phosphorylates both residues in vivo. Here we demonstrate that PDK1 is capable of phosphorylating p70 S6 kinase at Thr-412 in vitro. We study the effect of PIF on the ability of PDK1 to phosphorylate p70 S6 kinase. Surprisingly, we find that PDK1 bound to PIF is no longer able to interact with or phosphorylate p70 S6 kinase in vitro at either Thr-252 or Thr-412. The expression of PIF in cells prevents insulin-like growth factor 1 from inducing the activation of the p70 S6 kinase and its phosphorylation at Thr-412. Overexpression of PDK1 in cells induces the phosphorylation of p70 S6 kinase at Thr-412 in unstimulated cells, and a catalytically inactive mutant of PDK1 prevents the phosphorylation of p70 S6K at Thr-412 in insulin-like growth factor 1-stimulated cells. These observations indicate that PDK1 regulates the activation of p70 S6 kinase and provides evidence that PDK1 mediates the phosphorylation of p70 S6 kinase at Thr-412.
Gibberellin: inhibitor of an inhibitor of...?

Gibberellin is an endogenous plant growth regulator. Here, we describe our present understanding of how gibberellin regulates plant growth, using recent results gained from studies of gibberellin‐signalling mutants of Arabidopsis. These results show that a signalling pathway represses plant growth and that gibberellin releases this repression. In consequence, the well‐known growth‐promoting properties of gibberellin are due to its activity as an “inhibitor of an inhibitor” [Brian Pw. Sym Soc. Exp Bio 1957; 11:166–182 (Ref.1)] of plant growth. BioEssays 20:1001–1008, 1998. © 1998 John Wiley & Sons, Inc.
Association of central pulse pressure with contrast-induced nephropathy and clinical outcomes in patients undergoing coronary intervention

Objective: The increase in pulse pressure (PP) may be transmitted to the glomerulus and thus impair renal blood flow autoregulation. This subtle change could predispose patients to the detrimental effect of contrast media. We sought to determine whether elevated central PP is associated with increased contrast-induced nephropathy (CIN) and future cardiovascular events in patients undergoing percutaneous coronary intervention (PCI). Methods: In total, 448 consecutive patients receiving PCI were enrolled. In each patient, central and peripheral blood pressures were measured before PCI. The occurrence of CIN was identified and defined as a rise in serum creatinine of 0.5 mg/dl or a 25% increase from the baseline value within 48 h after the procedure. All patients were then followed up for at least 3 years or until the occurrence of a major adverse cardiovascular event (MACE) including death, nonfatal myocardial infarction, and ischemic stroke after coronary intervention. Results: Overall, CIN occurred in 52 (11.6%) patients. Patients developing CIN had higher baseline central PP (P = 0.004). Patients were then stratified into three groups (low/intermediate/high) according to baseline central PP. Compared to that with the lowest tertile of central PP, patients with the highest tertile of central PP had a significantly increased incidence of CIN after PCI (odds ratio, 2.94; 95% confidence interval, CI 1.02–8.51). By Cox regression analysis, elevated central PP was an independent predictor of future MACE in all patients undergoing PCI (hazard ratio, 2.07; 95% CI 1.04–4.12). Conclusion: Elevated baseline central PP was associated with an increased risk of CIN and future cardiovascular events in patients with PCI. Further clinical study may be indicated to determine whether pharmacological modulation on baseline central PP could prevent CIN and future MACE after PCI.
Cellular Mechanism Underlying Hypothermia-Induced Ventricular Tachycardia/Ventricular Fibrillation in the Setting of Early Repolarization and the Protective Effect of Quinidine, Cilostazol, and Milrinone

Background—Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Methods and Results—Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 &mgr;mol/L) and verapamil (1 &mgr;mol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 &mgr;mol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C–34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 &mgr;mol/L) or the phosphodiesterase III inhibitors cilostazol (10 &mgr;mol/L) or milrinone (5 &mgr;mol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions—Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.
Beyond macrophages: the diversity of mononuclear cells in tuberculosis

Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is an intracellular pathogen of mononuclear phagocytes. Although M. tuberculosis has traditionally been thought to survive and replicate in macrophages, recent work in our laboratory and others has revealed that M. tuberculosis infects multiple subsets of mononuclear phagocytes in vivo and in vitro. In experimental animals, M. tuberculosis infects no fewer than five distinct cell subsets in the lungs, including resident alveolar macrophages and 4 types of cells that recruited to the lungs in response to inflammatory signals: neutrophils, monocytes, interstitial macrophages, and dendritic cells. A characteristic of the adaptive immune response in TB is that it is delayed for several weeks following infection, and we have determined that this delay is due to prolonged residence of the bacteria in lung phagocytes prior to acquisition of the bacteria by dendritic cells. Among the mechanisms used by M. tuberculosis to delay acquisition by dendritic cells is to inhibit apoptosis of alveolar macrophages and neutrophils, which sequester the bacteria and prevent their acquisition by dendritic cells in the early stages of infection. We hypothesize that each infected cell subset makes a distinct contribution to the overall biology of M. tuberculosis and allows the bacteria to evade elimination by T‐cell responses and to avoid rapid killing by antimycobacterial drugs.
Different Plasma Levels of Vascular Endothelial Growth Factor and Nitric Oxide between Patients with Choroidal and Retinal Neovascularization

Because the blood flow is much more intense in the choroid than in the retina, it is interesting to explore whether choroidal neovascularization (CNV) is more influenced by plasma angiogenic factors than retinal neovascularization. The aim of this study was to investigate plasma profiles of vascular endothelial growth factor (VEGF) and nitric oxide (NO) in patients with CNV due to age-related macular degeneration (AMD) and in those with retinal neovascularization due to proliferative diabetic retinopathy (PDR). Seventy-seven subjects with AMD, 22 with PDR, and 42 nondiabetic, non-AMD controls were enrolled in this comparative case series. AMD subjects were classified into three groups: dry type (dry AMD, n = 17), wet type with active CNV (CNV/AMD, n = 42), and disciform scar due to advanced wet AMD (scar/AMD, n = 18). Plasma VEGF and NO levels of each subject were measured with enzyme-linked immunosorbent assay and chemiluminescence, respectively. Plasma VEGF level in CNV/AMD (median 256.0 pg/ml, interquartile range 146.4–375.3 pg/ml) was significantly higher than in PDR (124.8 pg/ml, 75.7–215.3 pg/ml; p = 0.004) and controls (120.3 pg/ml, 82.8–168.2 pg/ml, p =0.001). CNV/AMD also had the highest VEGF level among the AMD subgroups. Plasma NO level was significantly elevated in PDR (137.4 µM, 63.7–240.1 µM) when compared with CNV/AMD (71.8 µM, 42.4–113.3 µM; p = 0.004) and controls (62.6 µM, 39.0–114.9 µM; p = 0.002). There was no significant difference in NO levels among the AMD subgroups. No significant correlation between VEGF and NO levels was noted. These findings indicate that both circulating VEGF and NO may play different roles in the pathogenesis of retinal neovascularization and CNV.
Zebrafish models of orofacial clefts

Zebrafish is a model organism that affords experimental advantages toward investigating the normal function of genes associated with congenital birth defects. Here we summarize zebrafish studies of genes implicated in orofacial cleft (OFC). The most common use of zebrafish in this context has been to explore the normal function an OFC‐associated gene product in craniofacial morphogenesis by inhibiting expression of its zebrafish ortholog. The most frequently deployed method has been to inject embryos with antisense morpholino oligonucleotides targeting the desired transcript. However, improvements in targeted mutagenesis strategies have led to widespread adoption of CRISPR/Cas9 technology. A second application of zebrafish has been for functional assays of gene variants found in OFC patients; such in vivo assays are valuable because the success of in silico methods for testing allele severity has been mixed. Finally, zebrafish have been used to test the tissue specificity of enhancers that harbor single nucleotide polymorphisms associated with risk for OFC. We review examples of each of these approaches in the context of genes that are implicated in syndromic and non‐syndromic OFC. Developmental Dynamics 246:897–914, 2017. © 2017 Wiley Periodicals, Inc.
Performance analysis for improved RAM utilization for Android applications

Memory management is a vital parameter in efficient working of any operating system. In the mobile devices, internal memory plays an important role in managing the running of process, services and applications which are either installed by the user or which are already present in the device. Thus this paper aims towards giving an approach for better utilization of the internal memory present in Android operating system for mobile phones. The memory architecture for the Android device has been studied and has been observed that the device comes loaded with many applications which require high RAM consumption for efficient working. Thus taking into consideration running of so many applications processes and services, it is important to efficiently use and manage the internal memory space present inside the mobile operating system. For this purpose, a dictionary based application called SMSLingo has been developed for compression of SMS texting. This application requires less memory space and less RAM consumption as compared to the default SMS messaging service provided by Android. Memory management of Android system has been compared with the one in Linux System. It has been observed that Mapped Memory, Anonymous Memory and Slab Memory is present in Android which is used for allotting temporary storage space for the data frequently used.
The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: A magnetoencephalographic study

Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to (i) assess cerebrocortical insulin effects in humans, (ii) compare these effects between 10 lean and 15 obese subjects, and (iii) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity (P = 0.046) and the beta and theta band of spontaneous cortical activity (P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < −0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent (P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.
Effects of Na+ Current and Mechanogated Channels in Myofibroblasts on Myocyte Excitability and Repolarization

Fibrotic remodeling, characterized by fibroblast phenotype switching, is often associated with atrial fibrillation and heart failure. This study aimed to investigate the effects on electrotonic myofibroblast-myocyte (Mfb-M) coupling on cardiac myocytes excitability and repolarization of the voltage-gated sodium channels (VGSCs) and single mechanogated channels (MGCs) in human atrial Mfbs. Mathematical modeling was developed from a combination of (1) models of the human atrial myocyte (including the stretch activated ion channel current, I SAC) and Mfb and (2) our formulation of currents through VGSCs (I Na_Mfb) and MGCs (I MGC_Mfb) based upon experimental findings. The effects of changes in the intercellular coupling conductance, the number of coupled Mfbs, and the basic cycle length on the myocyte action potential were simulated. The results demonstrated that the integration of I SAC, I Na_Mfb, and I MGC_Mfb reduced the amplitude of the myocyte membrane potential (V max) and the action potential duration (APD), increased the depolarization of the resting myocyte membrane potential (V rest), and made it easy to trigger spontaneous excitement in myocytes. For Mfbs, significant electrotonic depolarizations were exhibited with the addition of I Na_Mfb and I MGC_Mfb. Our results indicated that I SAC, I Na_Mfb, and I MGC_Mfb significantly influenced myocytes and Mfbs properties and should be considered in future cardiac pathological mathematical modeling.
Census Web Service Architecture for e-Governance Applications

Citizen information needs depend on central data warehouse integrated with state level and central level e-Governance applications. Data integration presents core issues like interoperability, technical heterogeneity and flexibility. Census Web Service is an open standard based Web application that interacts with other web applications for the purpose of sharing citizen data. This will help in using uniform and consistent census data across various e-Governance applications. This paper presents a census data integration mechanism based on the Service Oriented Architecture (SOA) with various e-Governance applications. The proposed architecture consists of three layers; Web Service Provider, Service Broker and Web Service Consumers. Web Service providers publish services to a service broker. Web Service Consumers find required services using a service broker and bind to them. These layers are implemented based on a set of standards including EXtensible Markup Language (XML), Simple Object Access Protocol (SOAP), Web Services Description Language (WSDL) and Universal Description, Discovery, and Integration (UDDI) to deal with technical heterogeneity. A prototype of the framework is implemented and validated with e-Governance applications for issuing Caste Certificate and Rural Area Certificate. It is concluded that census web service can be effective and efficient in all types of e-Governance applications as it can provide accurate and timely information within reasonable amount of time.