gebhart/patrepeval huggingface dataset:
Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease (2009)

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) neurons. In this study, we explored the involvement of an abnormal mitochondrial dynamics by investigating the changes in the expression of mitochondrial fission and fusion proteins in AD brain and the potential cause and consequence of these changes in neuronal cells. We found that mitochondria were redistributed away from axons in the pyramidal neurons of AD brain. Immunoblot analysis revealed that levels of DLP1 (also referred to as Drp1), OPA1, Mfn1, and Mfn2 were significantly reduced whereas levels of Fis1 were significantly increased in AD. Despite their differential effects on mitochondrial morphology, manipulations of these mitochondrial fission and fusion proteins in neuronal cells to mimic their expressional changes in AD caused a similar abnormal mitochondrial distribution pattern, such that mitochondrial density was reduced in the cell periphery of M17 cells or neuronal process of primary neurons and correlated with reduced spine density in the neurite. Interestingly, oligomeric amyloid-beta-derived diffusible ligands (ADDLs) caused mitochondrial fragmentation and reduced mitochondrial density in neuronal processes. More importantly, ADDL-induced synaptic change (i.e., loss of dendritic spine and postsynaptic density protein 95 puncta) correlated with abnormal mitochondrial distribution. DLP1 overexpression, likely through repopulation of neuronal processes with mitochondria, prevented ADDL-induced synaptic loss, suggesting that abnormal mitochondrial dynamics plays an important role in ADDL-induced synaptic abnormalities. Based on these findings, we suggest that an altered balance in mitochondrial fission and fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction in AD brain.
Pseudarthrosis Rate After Allograft Posterior Lumbar Interbody Fusion With Pedicle Screw and Plate Fixation (1994)

Although the mechanical principles of posterior lumbar interbody fusion were affirmed, the adequacy of ethylene oxide-sterilized allograft bone in meeting the mechanical and biologic needs of posterior lumbar interbody fusion was questioned.
Microfluidic Directed Formation of Liposomes of Controlled Size (2007)

A new method to tailor liposome size and size distribution in a microfluidic format is presented. Liposomes are spherical structures formed from lipid bilayers that are from tens of nanometers to several micrometers in diameter. Liposome size and size distribution are tailored for a particular application and are inherently important for in vivo applications such as drug delivery and transfection across nuclear membranes in gene therapy. Traditional laboratory methods for liposome preparation require postprocessing steps, such as sonication or membrane extrusion, to yield formulations of appropriate size. Here we describe a method to engineer liposomes of a particular size and size distribution by changing the flow conditions in a microfluidic channel, obviating the need for postprocessing. A stream of lipids dissolved in alcohol is hydrodynamically focused between two sheathed aqueous streams in a microfluidic channel. The laminar flow in the microchannel enables controlled diffusive mixing at the two liquid interfaces where the lipids self-assemble into vesicles. The liposomes formed by this self-assembly process are characterized using asymmetric flow field-flow fractionation combined with quasi-elastic light scattering and multiangle laser-light scattering. We observe that the vesicle size and size distribution are tunable over a mean diameter from 50 to 150 nm by adjusting the ratio of the alcohol-to-aqueous volumetric flow rate. We also observe that liposome formation depends more strongly on the focused alcohol stream width and its diffusive mixing with the aqueous stream than on the sheer forces at the solvent-buffer interface.
The effect of electron irradiation on the structure and mechanical properties of highly drawn polyethylene fibers (1987)

Abstract Two very different high‐modulus polyethylene fiber samples, a low molecular weight melt‐spun and drawn fiber, and a high molecular weight gel‐spun and drawn fiber, have been subjected to electron beam irradiation to various doses in vacuum and in the presence of acetylene. The gel content after irradiation in acetylene was found to be much greater than for an equivalent dose in vacuum. The gel content–dose relationship could not be described by either Charlesby–Pinner analysis or the Inokuti equation. This is attributed to the polydispersity and the complications introduced by the unique morphologies of highly drawn fibers. Following previous studies, the tensile creep behavior was interpreted in terms of a model comprising two thermally activated processes in parallel, a low stress process relating to the amorphous network, and a high stress process relating to the continuous crystal fraction. Analysis of the creep behavior of the melt‐spun, low molecular weight fiber irradiated in vacuum revealed crosslinking in the amorphous regions and chain scission in the crystal. Chain scission was found to be much reduced when irradiating in acetylene, for which a mechanism has been proposed. The creep rates and activation volumes of the high molecular weight, gel‐spun fiber were found to be significantly lower, probably due to the unique morphology. In this case the dominant effect of irradiation on the mechanical properties can be attributed to chain scission rather than crosslinking.
Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics (1996)

NMDA receptor antagonists can induce a schizophrenia-like psychosis, but the role of NMDA receptors in the pathophysiology of schizophrenia remains unclear. Expression patterns of mRNAs for five NMDA receptor subunits (NR1/NR2A-D) were determined by in situ hybridization in prefrontal, parieto-temporal, and cerebellar cortex of brains from schizophrenics and from neuroleptic-treated and nonmedicated controls. In the cerebral cortex of both schizophrenics and controls, mRNAs for NR1, NR2A, NR2B, and NR2D subunits were preferentially expressed in layers II/III, Va, and VIa, with much higher levels in the prefrontal than in the parieto-temporal cortex. Levels of mRNA for the NR2C subunit were very low overall. By contrast, the cerebellar cortex of both schizophrenics and controls contained very high levels of NR2C subunit mRNA, whereas levels for the other subunit mRNAs were very low, except NR1, for which levels were moderate. Significant alterations in the schizophrenic cohort were confined to the prefrontal cortex. Here there was a shift in the relative proportions of mRNAs for the NR2 subunit family, with a 53% relative increase in expression of the NR2D subunit mRNA. No comparable changes were found in neuroleptic-treated or untreated controls. These findings indicate regional heterogeneity of NMDA receptor subunit expression in human cerebral and cerebellar cortex. In schizophrenics, the alterations in expression of NR2 subunit mRNA in prefrontal cortex are potential indicators of deficits in NMDA receptor-mediated neurotransmission accompanying functional hypoactivity of the frontal lobes.
Pharmacokinetics of Testosterone in Hypogonadal Men After Transdermal Delivery: Influence of Dose (1996)

To assess the pharmacokinetics of testosterone after application of one, two, or three testosterone transdermal delivery systems to hypogonadal patients, 12 hypogonadal men (mean age 46.6 +/- 10.5 years) were enrolled in an open-label, randomized, crossover study. Each application period comprised 4 days: a 2-day washout period with no exogenous testosterone therapy followed by 2 days of therapy with one, two, or three transdermal systems applied daily to the patient's back. On day 4 of each period, serial blood samples were collected for determination of total and non-sex hormone binding globulin (non-SHBG) bound serum testosterone concentrations. Serum concentrations of testosterone were determined using validated radioimmunoassay methods. Residual testosterone analysis of used transdermal systems was used to estimate testosterone delivery through the skin. In general, serum concentrations of testosterone rose in accordance with an increase in dose. Using a strict bioequivalence approach to dose proportionality, the increases in area under the concentration-time curve (AUC) and morning concentrations were proportional to the increase in dose from two to three transdermal systems, but somewhat less than proportional with an increase from one to two transdermal systems. Results from the non-SHBG bound serum testosterone concentrations closely paralleled those of total serum testosterone. Use of three transdermal systems yielded serum concentrations of testosterone that tended to be above the upper limit of the normal range. The AUC and cumulative release of testosterone were linearly related to the number of applied systems. If necessary, the standard recommended dose of two testosterone transdermal delivery systems can be modified to accommodate interindividual differences in testosterone requirements of hypogonadal men.
Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action (2016)

In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals.
The need for neuroprotective therapies in Parkinson’s disease (2006)

Slowing of disease progression remains a major unmet need in the treatment of Parkinson's disease (PD). Multiple factors are responsible for progression of disability in this disorder including worsening of cardinal motor features due to progressive nigral pathology, the evolution of poorly levodopa-responsive symptoms like freezing, postural instability and falls as well as motor complications of sustained treatment with levodopa. In addition, non-motor symptoms including cognitive decline, autonomic failure, sleep disorders and pain become increasingly prevalent with advancing disease and add to the overall burden of this disease. So far no treatment has been shown to significantly retard the progression of overall disability, and neuroprotective trials have been limited by design issues and a narrow focus on rates of decline of motor scores or imaging markers of nigrostriatal dysfunction only. Current evidence suggests that it may soon be possible to define populations at increased risk to develop PD and thus to target the "preclinical" phase of PD for neuroprotection. Such future trials will test intervention for their ability to prevent or retard the development of clinically overt PD in at-risk individuals.
Consed: A Graphical Tool for Sequence Finishing (1998)

Sequencing of large clones or small genomes is generally done by the shotgun approach (Anderson et al. 1982). This has two phases: (1) a shotgun phase in which a number of reads are generated from random subclones and assembled into contigs, followed by (2) a directed, or finishing phase in which the assembly is inspected for correctness and for various kinds of data anomalies (such as contaminant reads, unremoved vector sequence, and chimeric or deleted reads), additional data are collected to close gaps and resolve low quality regions, and editing is performed to correct assembly or base-calling errors. Finishing is currently a bottleneck in large-scale sequencing efforts, and throughput gains will depend both on reducing the need for human intervention and making it as efficient as possible. We have developed a finishing tool, consed, which attempts to implement these principles. A distinguishing feature relative to other programs is the use of error probabilities from our programs phred and phrap as an objective criterion to guide the entire finishing process. More information is available at http:// www.genome.washington.edu/consed/consed. html.
[Differentiation of rat adipose-derived stem cells into smooth-muscle-like cells in vitro]. (2009)

ADSCs displayed obvious characteristics of smooth muscle cells after induction, and could be a new source of cells in the tissue engineering studies of smooth muscle related diseases.
Bacterial Fruit Blotch of Watermelon (1999)

Although symptoms can occur on foliage, they may be subtle or mistaken for another disease. The earliest symptom is water-soaking between the veins on the underside of the seedling cotyledons (seed leaves). These areas eventually dry up and die. On true leaves, the disease can form distinctive, brown, elongated lesions on and next to the veins, which also may appear water-soaked. The bacteria also produce brown, circular spots on the leaves, but similar circular lesions can be caused by a number of other agents.
Bronchoscopic Lung Volume Reduction Using Tissue Engineering Principles (2003)

Bronchoscopic lung volume reduction (BLVR), a minimally invasive procedure based on tissue engineering principles, was performed in six sheep with papain-induced experimental emphysema (EMPH). Physiologic measurements, at baseline, after generation of EMPH, and at 3 and 9 weeks after BLVR, included lung volumes, diffusing capacity (DL(CO)), pressure-volume relationships for the lung and chest wall, pleural pressures generated during active respiratory muscle contraction, lung resistance and dynamic elastance. The animal model displayed hyperinflation (change in total lung capacity +8%; change in residual volume +66%), reduced DL(CO) (-21%), and elevated airway resistance (+76%) that resembled advanced human EMPH. BLVR was well tolerated without complications, and it reduced lung volumes (change in total lung capacity -16%; change in residual volume -55%) in a pattern that resulted in significant improvements in vital capacity (10%). At autopsy, well-organized, peripheral scars associated with tissue contraction were observed at 33 of the 36 (91%) treated sites. There was no evidence of infection, abscess, or granuloma formation, or allergic reaction. Scar tissue, generated by BLVR, replaced hyperinflated lung, reduced overall lung volume, and improved respiratory function safely and consistently. The BLVR technology employed in this study addresses the limitations identified in our prior attempt at BLVR therapy and appears safe and effective enough to justify a trial in humans.
Computational virology: From the inside out (2016)

Viruses typically pack their genetic material within a protein capsid. Enveloped viruses also have an outer membrane made up of a lipid bilayer and membrane-spanning glycoproteins. X-ray diffraction and cryoelectron microscopy provide high resolution static views of viral structure. Molecular dynamics (MD) simulations may be used to provide dynamic insights into the structures of viruses and their components. There have been a number of simulations of viral capsids and (in some cases) of the inner core of RNA or DNA packaged within them. These simulations have generally focussed on the structural integrity and stability of the capsid and/or on the influence of the nucleic acid core on capsid stability. More recently there have been a number of simulation studies of enveloped viruses, including HIV-1, influenza A, and dengue virus. These have addressed the dynamic behaviour of the capsid, the matrix, and/or of the outer envelope. Analysis of the dynamics of the lipid bilayer components of the envelopes of influenza A and of dengue virus reveals a degree of biophysical robustness, which may contribute to the stability of virus particles in different environments. Significant computational challenges need to be addressed to aid simulation of complex viruses and their membranes, including the need to integrate structural data from a range of sources to enable us to move towards simulations of intact virions. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
Measured electrical constitutive parameters of soil as functions of frequency and moisture content (1992)

The measured electrical constitutive parameters (effective relative permittivity and effective conductivity) for Georgia red clay are presented. These results are for the frequency range 50 MHz-1.25 GHz and for six samples with water contents by dry weight ranging from approximately 0-30%. These electrical parameters should be useful in designing and characterizing broadband systems whose performance is dependent upon or affected by the Earth, such as ground-penetrating radars.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Syndecan-1 regulates αvβ5 integrin activity in B82L fibroblasts (2006)

B82L mouse fibroblasts respond to fibronectin or vitronectin via a syndecan-1-mediated activation of the alphavbeta5 integrin. Cells attached to syndecan-1-specific antibody display only filopodial extension. However, the syndecan-anchored cells extend lamellipodia when the antibody-substratum is supplemented with serum, or low concentrations of adsorbed vitronectin or fibronectin, that are not sufficient to activate the integrin when plated alone. Integrin activation is blocked by treatment with (Arg-Gly-Asp)-containing peptides and function-blocking antibodies that target alphav integrins, as well as by siRNA-mediated silencing of beta5 integrin expression. In addition, alphavbeta5-mediated cell attachment and spreading on high concentrations of vitronectin is blocked by competition with recombinant syndecan-1 ectodomain core protein and by downregulation of mouse syndecan-1 expression by mouse-specific siRNA. Taking advantage of the species-specificity of the siRNA, rescue experiments in which human syndecan-1 constructs are expressed trace the activation site to the syndecan-1 ectodomain. Moreover, both full-length mouse and human syndecan-1 co-immunoprecipitate with the beta5 integrin subunit, but fail to do so if the syndecan is displaced by competition with soluble, recombinant syndecan-1 ectodomain. These results suggest that the ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the alphavbeta5 integrin and regulates alphavbeta5 integrin activity.
Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome (2009)

Although obesity is associated with multiple features of the metabolic syndrome (insulin resistance, leptin resistance, hepatic steatosis, chronic inflammation, etc.), the molecular changes that promote these conditions are not completely understood. Here, we tested the hypothesis that elevated ceramide biosynthesis contributes to the pathogenesis of obesity and the metabolic syndrome. Chronic treatment for 8 wk of genetically obese (ob/ob), and, high-fat diet-induced obese (DIO) mice with myriocin, an inhibitor of de novo ceramide synthesis, decreased circulating ceramides. Decreased ceramide was associated with reduced weight, enhanced metabolism and energy expenditure, decreased hepatic steatosis, and improved glucose hemostasis via enhancement of insulin signaling in the liver and muscle. Inhibition of de novo ceramide biosynthesis decreased adipose expression of suppressor of cytokine signaling-3 (SOCS-3) and induced adipose uncoupling protein-3 (UCP3). Moreover, ceramide directly induced SOCS-3 and inhibited UCP3 mRNA in cultured adipocytes suggesting a direct role for ceramide in regulation of metabolism and energy expenditure. Inhibition of de novo ceramide synthesis had no effect on adipose tumor necrosis factor-alpha (TNF-alpha) expression but dramatically reduced adipose plasminogen activator inhibitor-1 (PAI-1) and monocyte chemoattactant protein-1 (MCP-1). This study highlights a novel role for ceramide biosynthesis in body weight regulation, energy expenditure, and the metabolic syndrome.
Understanding Ultra Wide Band Radio Fundamentals (2004)

Preface. Approach. Organization of the Book. Audience and Course Use. Web Site and Use of MATLAB. Acknowledgments. References. 1. Ultra Wide Band Radio Definition. Fractional Bandwidth. UWB vs. Non-UWB. Further Reading. References. Appendix 1.A. 2. The UWB Radio Signal. Generation of TH-UWB Signals. Generation of DS-UWB Signals. Generation of Multi-Band UWB Signals. Further Reading. References. Appendix 2.A. 3. The PSD of TH-UWB Signals. Borrowing from PPM. The PPM-TH-UWB Case. Further Reading. References. Appendix 3.A. 4. The PSD of DS-UWB Signals. DS-UWB. The Case of PAM-TH-UWB. Further Reading. References Appendix 4.A. 5. The PSD of MB-UWB Signals. Spectral Characteristics of OFDM Signals. The MB IEEE 802.15.TG3a Proposal. Further Reading. References. 6. Performance Analysis for the UWB Radio Link. Power Limits and Emission Masks. Link Budget. Further Reading. References. Appendix 6.A. Appendix 6.B. 7. The Pulse Shaper. The Pulse. Pulse Width Variation and Pulse Differentiation. Meeting the Emission Masks. Further Reading. References. Appendix 7.A. 8. The UWB Channel and Receiver. Multi-Path-Free AWGN Channel. Propagation over a Multi-Path-Affected UWB Radio Channel. Synchronization Issues in IR-UWB Communications. Further Reading. References. Appendix 8.A. 9. Multi-User UWB Wireless Communications. Multiple Access and Multi-User Interference. Multi-User IR-UWB System Performance Based on the SGA. Multi-User Interference Modeling Based on Packet Collision. Further Reading. References. Appendix 9.A. 10. UWB Ranging and Positioning. Ranging vs. Positioning. Ranging. Positioning. Positioning Protocols. An Application: A MAgiC World. Further Reading. References. Appendix 10.A. 11. UWB Networks: Principled Design of MAC. MAC: General Principles. MAC Functions. MAC with QoS Management. An Example of an UWB-Tailored MAC Algorithm: (UWB)2. Further Reading. References. Appendix. Current Trends in UWB Standardization Activities. List of MATLAB Functions. List of Acronyms. Index. For The Curious Reader.
Proposal for a 50 nm proximity x-ray lithography system and extension to 35 nm by resist material selection (2000)

In this article, a 50 nm generation proximity x-ray lithography (PXRL) system is proposed using shorter wavelengths of exposure light down to around 3 Å. The illumination system uses a mirror at 1° incidence angle such as in the Canon stepper XRA-1000, which can be realized by coating with a fourth or fifth period metal such as Co or Rh. The resist containing chemical elements such as Cl, S, P, Si, and Br whose x-ray absorption edge lies in the wavelength band of the exposure light can yield a strong absorption using this system. Therefore, a resist material containing such elements is highly sensitive when applied to the 50 nm system. The average wavelength of power absorbed by the resist depends on the elements contained in the resist. This suggests that the resolution limits also depend on the resist material even for the same exposure system. Therefore, this system should be extendible down to the 35 nm generation by using such a resist and a thick diamond mask membrane. The system described assumes that the mask–wafer gap is the currently available 10 μm. In the future, an additional gain in resolution can be expected from a narrower gap. With these improvements, it is foreseeable that PXRL technology can be applied to the 20 nm regime, down to the operational limits of silicon devices at room temperature.