Miracle-dz/UniFAR-FTUs huggingface dataset:
The bioelectric field pattern in the salamander and its simulation by an electronic analog.

The dc field potential has been determined on the surface of the intact salamander, Trituris viridescens. A complex field was found which did not correspond to a simple dipole. The field was found to vary in a dynamic fashion with changes in the level of anesthesia. The spatial organization of the field correlated well with the anatomical organization of the central nervous system of the animal, in that areas of nerve cell aggregations within the central nervous system appeared to serve as both sources and sinks of the potential, with transmission of the steady potential along major nerve trunks. An analog model of the central nervous system was constructed utilizing several bimetallic junctions and a conducting network. This model produced a field in a modified electrolytic tank which corresponded well with the field found in the intact animal. It was concluded that the dc bioelectric potential in organisms may be generated within and conducted by portions of the central nervous system. The possibility that this is a means of data transmission and/or control (in addition to the usual action potential system) is being evaluated.
Direct Transcriptional Regulation of Human Hepatic Cytochrome P450 3A4 (CYP3A4) by Peroxisome Proliferator–Activated Receptor Alpha (PPARα)

The nuclear receptor peroxisome proliferator–activated receptor (PPAR)α is known primarily as a regulator of fatty acid metabolism, energy balance, and inflammation, but evidence suggests a wider role in regulating the biotransformation of drugs and other lipophilic chemicals. We investigated whether PPARα directly regulates the transcription of cytochrome P450 3A4, the major human drug-metabolizing enzyme. Using chromatin immunoprecipitation in human primary hepatocytes as well as electrophoretic mobility shift and luciferase reporter-gene assays, we identified three functional PPARα-binding regions (PBR-I, -II, and -III) within ∼12 kb of the CYP3A4 upstream sequence. Furthermore, a humanized CYP3A4/3A7 mouse model showed in vivo induction of CYP3A4 mRNA and protein by [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY14,643) in liver but not in intestine, whereas hepatic occupancy of PBRs by PPARα was ligand independent. Using lentiviral gene knock-down and treatment with WY14,643 in primary human hepatocytes, PPARα was further shown to affect the expression of a distinct set of CYPs, including 1A1, 1A2, 2B6, 2C8, 3A4, and 7A1, but not 2C9, 2C19, 2D6, or 2E1. Interestingly, the common phospholipid 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-PC), previously proposed to reflect nutritional status and shown to be a specific endogenous ligand of PPARα, induced CYP3A4 (up to 4-fold) and other biotransformation genes in hepatocytes with similar selectivity and potency as WY14,643. These data establish PPARα as a direct transcriptional regulator of hepatic CYP3A4. This finding warrants investigation of both known and newly developed PPARα-targeted drugs for their drug-drug interaction potential. Furthermore, our data suggest that nutritional status can influence drug biotransformation capacity via endogenous phospholipid signaling.
In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) on whole virions is heterogeneous, so molecular analysis of Env with monoclonal antibodies (MAbs) is challenging. Virus capture assays (VCAs) involving immobilized MAbs are typically used, but these assays suffer from immobilization artifacts and do not provide binding constants. Furthermore, we show here that certain HIV-1 neutralizing MAbs, including 2G12, 4E10, 2F5, Z13e1, and D5, will capture virion particles completely devoid of Env. We modified the VCA such that MAbs and virions are incubated in solution, and unbound MAbs are removed prior to the capture step. This modification nearly eliminated evidence of Env-independent binding by MAbs to virions and allowed determination of apparent affinity constants in solution. Three important qualitative observations were further revealed. First, neutralizing MAbs 2F5, 4E10, and Z13e1 against the membrane-proximal external region (MPER) of HIV-1 gp41 were found to capture virions efficiently only if a significant amount of uncleaved gp160 or synthetic MPER peptide was present. Second, we show how non-native forms of Env vary by Env genotype and that Env from HIV-1JR-FL is more homogeneously trimeric than that from HIV-1JR-CSF. Third, we determined that Env containing all or parts of gp41, including uncleaved gp160, binds spontaneously to free virions. This exogenous Env is an indiscriminate molecular “bridge” between Env-specific Ab and virions and can affect VCA analyses, particularly using pseudotyped virions. Heterogeneity in Env from endogenous and exogenous sources might also subvert humoral immunity to HIV-1, so in-solution VCAs may help to dissect this heterogeneity for vaccine design purposes.
The isolation and characterization of the vitamin D-binding protein from rat serum.

The binding protein for vitamin DB (and its hydroxylated metabolites) was isolated from rat serum. The molecular weight was estimated to be 52,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and on gel filtration on agarose or Sephadex G-75. A sedimentation coefficient of 4.1 S was found on sucrose gradient ultracentrifugation. Vitamin D-binding protein has an isoelectric point of 5.2 on isoelectric focusing and has mainly an az-globulin mobility on cellulose acetate electrophoresis. The isolated protein has a tendency to polymerize during storage. Heating at 60” slowly destroys the vitamin D-binding protein but its thermostability can be enhanced by the presence of excess ligand (vitamin DB, 25-hydroxyvitamin Da, or 1,25-dihydroxyvitamin D3). The binding protein has a single binding site for 25-hydroxyvitamin DS and its association constant at 4” for this compound is about 5 x 10’ M-~. Its amino acid content is also reported. Specific antisera against rat vitamin D-binding protein were raised in rabbits and were used for measuring its serum concentration by single radial immunodiffusion. A high serum concentration was found, with the values in adult males (13 pM) being significantly higher than in adult females (9 PM). This implies that the vitamin Dbinding protein is present in normal serum in large molar excess to vitamin Ds and its hydroxylated metabolites and, therefore, mainly circulates as an apoprotein. The y-globulin fraction of monospecific antiserum raised against the binding protein was able to precipitate 52% of vitamin DI and 90% of 25-hydroxyvitamin Da or 1,25-dihydroxyvitamin DI suggesting that vitamin D-binding protein is the common transport protein for these secosteroids.
The Satisfaction, Motivation, and Future of Community Preceptors: The North Carolina Experience

Purpose To measure satisfaction and motivation of community-based preceptors, and to examine differences between degree groups of physicians, pharmacists, advanced-practice nurses (nurse practitioners and certified nurse midwives), and physician assistants. Method In spring 2005, the authors mailed a four-page, 24-item survey to all 2,061 community-based primary care preceptors served by the North Carolina Area Health Education Centers system. The survey measured preceptor satisfaction, likelihood of continuing as a preceptor, influence of having students, motivation for teaching, satisfaction in professional practice, satisfaction with incentives, and value of incentives. Results Response rate was 69.3%, or 1,428 preceptors. Most preceptors (93.0%) reported high satisfaction with their precepting experience, and 90.9% indicated high likelihood of continuing to precept for the next five years. Almost all preceptors (93.7%) reported they were satisfied with their professional life. Many community preceptors (57.2%) were satisfied with incentives. They placed greater value on the intrinsic reasons for precepting (i.e., enjoyment of teaching) rather than extrinsic rewards (such as no-cost online library resources). Degree groups placed differing values on intrinsic and extrinsic rewards. Physicians reported more negativity about the influence of students and regarding aspects of their professional lives. Conclusions Tailoring support to better meet individual degree groups' preferences can maximize resources and may encourage preceptor retention. Special attention to physicians' needs may be warranted to avoid decreased preceptor numbers in this at-risk group. Future studies are needed to determine whether these findings are unique to North Carolina, which has a strong infrastructure to support preceptors.
An s-domain model of an HVDC converter

This paper describes a technique to model an HVDC power converter installation in the s-domain. A system equivalent is developed, utilising a frequency-domain model, allowing the closed loop frequency response to be expressed. A rational function approximation of the closed loop frequency response is found by writing an overdetermined equation set, solved directly using singular value decomposition. System poles and zeros in the s-domain are extracted through the solution of the rational function roots. Validation of the model at two power converter operating points is obtained via time-domain simulation and step response techniques for an inverter voltage perturbation.
The skin as a target for allergic diseases

Over the past two decades, it has been clearly shown that the skin is much more than just a covering and protecting coat. Indeed, it represents an integral component of the immune system, and, like other interface organs such as the lungs or gut, it could in many ways be considered the front line of immune defense. The mechanisms of skin immune defense can be broadly divided into two categories: innate, or nonadaptive, immune responses and adaptive immune responses (1, 2). The innate immune response of the skin is achieved through the presence of evolutionary, highly conserved antimicrobial peptides such as bdefensin (3). The adaptive component contains the full repertoire of immune mechanisms employed by the immune system in the other organ systems. In contrast to innate immunity, this type of immune defense is antigen-speci®c and is ampli®ed upon re-exposure to the same antigen. Thus, speci®city and memory are key features of the adaptive immune system and are mediated by various cellular components of the epidermal and dermal compartments.
Histamine Receptor – Mediated Activation of Protein Kinase C α Inhibits the Growth of Cholangiocarcinoma In vitro and In vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP3)/Ca /protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(α)-(−)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP3 and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKCα was visualized by immunofluorescence in cell smears and immunoblotting for PKCα in cytosol and membrane fractions. Following knockdown of PKCα, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal–regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKCα, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP3 levels and PKCα phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKCα expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKCα prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKCα expression was increased. RAMH inhibits cholangiocarcinoma growth by PKCα-dependent ERK1/2 dephosphorylation. Modulation of PKCα by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res
Flexible bronchoscopic management of airway foreign bodies in children.

OBJECTIVES To evaluate experience with the flexible bronchoscopic management of tracheobronchial foreign bodies (TFBs) in children (age < or = 16 years). DESIGN All pediatric bronchoscopies performed by the bronchoscopy section at Mayo Clinic Rochester from 1990 through June 2001 for the suspicion of TFBs were reviewed. Information analyzed included the types of bronchoscope (rigid vs flexible) and techniques used, success rates of extraction of TFBs, and complications. RESULTS Of the 94 children suspected of having TFBs, 39 children (28 boys and 11 girls; mean age, 47.3 months) were found to have 40 TFBs. The flexible bronchoscope was used exclusively to extract TFBs in 24 patients, and in 2 patients in whom the rigid bronchoscopic procedure was unsuccessful. Flexible bronchoscopy was performed through an endotracheal tube in 19 children. In the other five children, the procedure was accomplished through a laryngeal mask airway (LMA). In two additional patients in whom the rigid bronchoscopic procedure was unsuccessful, the instrument served as a conduit for the passage of the flexible bronchoscope. The extraction instruments employed included ureteral stone baskets and stone forceps. Since 1994, all extractions of TFBs were successfully accomplished with the flexible bronchoscope. Complications occurred in four patients who underwent rigid bronchoscopy, and included postbronchoscopy laryngeal edema manifested by stridor, cough, and respiratory distress. These resolved quickly with medical therapy. CONCLUSIONS Flexible bronchoscopic extraction of pediatric TFBs can be performed safely with minimal risks and complications. In our experience, it was successful in all children in whom it was employed. Nevertheless, we caution that provisions be made to provide immediate rigid bronchoscopic management, should the attempts at flexible bronchoscopic extraction fail.
Unified approach for simulation of statistical reliability in nanoscale CMOS transistors from devices to circuits

In this paper we will present integrated time dependent variability tool flow that links statistical TCAD simulations, statistical compact model extraction and statistical circuit simulation. This allows the concepts of Design-Technology Co-Optimization (DTCO) to be extended into the reliability domain. The simulations are based on Gold Standard Simulations' (GSS) 3-D Kinetic Monte Carlo TCAD technology, which enables the simulation and analysis of the trapping/de-trapping history of large ensembles of microscopically different transistors. The results of the physical simulation are than captured in accurate time dependent statistical compact models. As a result, accurate statistical circuit simulation can trace the statistical impact of the degradation on the functionality of the underlying circuits and systems.
Research of digital control bidirectional DC/DC converter based on ultra-capacitor

In this paper, the character of the ultra-capacitor was discussed, the charging and discharging characters of super capacitor, the differences of the bidirectional dc/dc converter topologies were also discussed, the non-solution bidirectional dc/dc converter was chosen as the main circuit. This paper also stated the control strategy of bidirectional dc/dc converter, the small signal analysis was also given. At last, a simulation with MATLAB was established to prove the feasibility of this method.
Orographic Enhancement of Precipitation in Midlatitudes : Results from MAP and IMPROVE II

When midlatitude baroclinic systems move over a mountain range, the precipitation from the system intensifies over and sometimes upwind of the slope of the mountain barrier. The maximum precipitation occurs on the lower windward slopes in almost immediate response to the orographically induced lifting of the air such that the maximum precipitation may occur well below the summit of the range (e.g., Frei and Schaer 1998). How this rapid response to the orographic lifting occurs is the central question of orographic enhancement of midlatitude baroclinic precipitation. Smith (1979) called attention to this question by expressing the rapid fallout of the condensate produced by the orographic component of the lifting in terms of an efficiency. This efficiency may be thought of as the ratio of rainfall on the mountainside to the amount of water condensed in the upslope flow. Reviewing the literature, he noted that this ratio was typically high: “. It is.surprising in light of the difficulties in forming precipitation-size particles, to find release efficiencies of 70% to 100%, . ” That is, this high efficiency could only occur if there was a rapid conversion of the condensate generated by the orographic uplift to particles large enough to fall out quickly before being advected over the crest of the mountain range. He asked further, how “is it possible to convert such a high fraction of the condensed water into precipitation? ” Since microphysical processes control the growth rate of precipitation particles, the answer to this question is a matter of determining how the microphysical processes accelerate the growth of precipitation particles in the upslope flow. Current research on orographic enhancement of precipitation focuses on answering the question of how microphysical processes are invigorated to account for the efficiency of the orographic precipitation enhancement. This paper reviews some recent progress toward this end.
Learning crowd behavior for event recognition

This paper presents a new method for event recognition based on machine learning techniques. One machine is trained per kind of event using color, texture and shape features. Testing is performed on the PETS 2009 dataset. We evaluate accuracy of our automatic system with six different kind of events and then compare the results with human classification.
Selective Delivery of PEGylated Compounds to Tumor Cells by Anti-PEG Hybrid Antibodies

Polyethylene glycol (PEG) is attached to many peptides, proteins, liposomes, and nanoparticles to reduce their immunogenicity and improve their pharmacokinetic and therapeutic properties. Here, we describe hybrid antibodies that can selectively deliver PEGylated medicines, imaging agents, or nanomedicines to target cells. Human IgG1 hybrid antibodies αPEG:αHER2 and αPEG:αCD19 were shown by ELISA, FACS, and plasmon resonance to bind to both PEG and HER2 receptors on SK-BR-3 breast adenocarcinoma and BT-474 breast ductal carcinoma cells or CD19 receptors on Ramos and Raji Burkitt's lymphoma cells. In addition, αPEG:αHER2 specifically targeted PEGylated proteins, liposomes, and nanoparticles to SK-BR-3 cells that overexpressed HER2, but not to HER2-negative MCF-7 breast adenocarcinoma cells. Endocytosis of PEGylated nanoparticles into SK-BR-3 cells was induced specifically by the αPEG:αHER2 hybrid antibody, as observed by confocal imaging of the accumulation of Qdots inside SK-BR-3 cells. Treatment of HER2+ SK-BR-3 and BT-474 cancer cells with αPEG:αHER2 and the clinically used chemotherapeutic agent PEGylated liposomal doxorubicin for 3 hours enhanced the in vitro effectiveness of PEGylated liposomal doxorubicin by over two orders of magnitude. Hybrid anti-PEG antibodies offer a versatile and simple method to deliver PEGylated compounds to cellular locations and can potentially enhance the therapeutic efficacy of PEGylated medicines. Mol Cancer Ther; 14(6); 1317–26. ©2015 AACR.
Egicoccus halophilus gen. nov., sp. nov., a halophilic, alkalitolerant actinobacterium and proposal of Egicoccaceae fam. nov. and Egicoccales ord. nov.

A novel Gram-stain-positive, non-motile, moderately halophilic and alkalitolerant actinobacterium, designated EGI 80432T, was isolated from a saline-alkaline soil of Xinjiang province, north-west China. Cells were non-endospore-forming cocci with a diameter of 0.5-0.8 μm. Strain EGI 80432T grew in the presence of 0-9 % (w/v) NaCl (optimum at 3-5 %), and also grew within the pH range 6.0-10.0 (optimum at pH 8.0-9.0) on marine 2216E medium. The peptidoglycan type was A1γ. The whole-cell hydrolysates contained glucose, galactose, mannose and three unknown sugars as major sugars. The predominant menaquinone was MK-9(H4). The major fatty acids were C17 : 1ω8c, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C18 : 1ω9c and iso-C15 : 0 The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, one unknown phosphoglycolipid, three unknown phospholipids and four unknown polar lipids. The genomic DNA G+C content was 75.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EGI 80432T clustered within the radius of the class Nitriliruptoria. Levels of sequence similarity between strain EGI 80432T and its phylogenetic neighbours Nitriliruptor alkaliphilus ANL-iso2T and Euzebya tangerina F10T were 94.1 and 88.1 %, respectively. Based on morphological, physiological and chemotaxonomic characteristics and phylogenetic analysis, a novel species of a new genus, Egicoccus halophilus gen. nov., sp. nov., is proposed, within the new family and new order Egicoccaceae fam. nov. and Egicoccales ord. nov. in the class Nitriliruptoria. The type strain of Egicoccus halophilus is EGI 80432T ( = CGMCC 1.14988T = KCTC 33612T).