gebhart/patrepeval huggingface dataset:
Signal processing methods for heart rate variability (2002)

Heart rate variability (HRV), the changes in the beat-to-beat heart rate calculated from the electrocardiogram (ECG), is a key indicator of an individual's cardiovascular condition. Assessment of HRV has been shown to aid clinical diagnosis and intervention strategies. However, the variety of HRV estimation methods and contradictory reports in this field indicate that there is a need for a more rigorous investigation of these methods as aids to clinical evaluation. This thesis investigates the development of appropriate HRV signal processing techniques in the context of pilot studies in two fields of potential application, sleep and head-up tilting (HUT).A novel method for characterising normality in the ECG using both timing information and morphological characteristics is presented. A neural network, used to learn the beat-to-beat variations in ECG waveform morphology, is shown to provide a highly sensitive technique for identifying normal beats.Fast Fourier Transform (FFT) based frequency-domain HRV techniques, which require re-sampling of the inherently unevenly sampled heart beat time-series (RR tachogram) to produce an evenly sampled time series, are then explored using a new method for producing an artificial RR tachogram. Re-sampling is shown to produce a significant error in the estimation of an (entirely specified) artificial RR tachogram. The Lomb periodogram, a method which requires no re-sampling and is applicable to the unevenly sampled nature of the signal is investigated. Experiments demonstrate that the Lomb periodogram is superior to the FFT for evaluating HRV measured by the LF/HF-ratio, a ratio of the low to high frequency power in the RR tachogram within a specified band (0.04-0.4 Hz). The effect of adding artificial ectopic beats in the RR tachogram is then considered and it is shown that ectopic beats significantly alter the spectrum and therefore must be removed or replaced. Replacing ectopic beats by phantom beats is compared to the case of ectopic-realted RR interval removal for the FFT and Lomb methods for varying levels of ectopy. The Lomb periodogram is shown to provide a signficantly better estimate of the LF/HF- ratio under these conditions and is a robust method for measuring the LF/HF-ratio in the presence of (a possibly unknown number of) ectpoic beats or artefacts.The Lomb peridogram and FFT-based techniques are applied to a database of sleep apnoeic and normal subjects. A new method of assessing HRV during sleep is proposed to minimise the confounding effects on HRV of changes due to changing mental activity. Estimation of LF/HF-ratio using the Lomb technique is shown to separate these two patient groups more effectively than with FFT-based techniques. Results are also presented for the application of these methods to controlled (HUT) studies on subjects with syncope, an autonomic nervous system problem, which indicate that the techniques developed in this thesis may provide a method for differentiating between sub-classes of syncope.
Pressure-Driven Laminar Flow in Tangential Microchannels:  an Elastomeric Microfluidic Switch (2001)

This paper describes laminar fluid flow through a three-dimensional elastomeric microstructure formed by two microfluidic channels, fabricated in layers that contact one another face-to-face (typically at a 90 degree angle), with the fluid flows in tangential contact. There are two ways to control fluid flow through these tangentially connected microchannels. First, the flow profiles through the crossings are sensitive to the aspect ratio of the channels; the flow can be controlled by applying external pressure and changing this aspect ratio. Second, the flow direction of an individual laminar stream in multiphase laminar flow depends on the lateral position of the stream within the channel; this position can be controlled by injecting additional streams of fluid into the channel. We describe two microfluidic switches based on these two ways for controlling fluid flow through tangential microchannels and present theoretical arguments that explain the observed dependence of the flow profiles on the aspect ratio of the channels.
Automated Vehicle Mobile Guidance System for Parking Assistance (2007)

A new concept that a vehicle, which does not have fully automated functions but has partial intelligent functions, is manually or automatically guided to an assigned destination position with a guidance system has been proposed. This paper describes the concept of the system and reports the experimental results of the guidance to a parking space with the proposed system. The experimental study has been conducted to show the feasibility of the system proposed. In the experiments, a vehicle was guided with a mobile guidance system that measures the position and the heading of a guided vehicle to instruct it the steering and the velocity to its goal. The system is featured by that a few intelligent mobile guidance systems will assist many ordinary vehicles in dedicated areas including parking lots.
How to tolerate half less one Byzantine nodes in practical distributed systems (2004)

The application of dependability concepts and techniques to the design of secure distributed systems is raising a considerable amount of interest in both communities under the designation of intrusion tolerance. However, practical intrusion-tolerant replicated systems based on the state machine approach (SMA) can handle at most f Byzantine components out of a total of n = 3f + 1, which is the maximum resilience in asynchronous systems. This paper extends the normal asynchronous system with a special distributed oracle called TTCB. Using this extended system we manage to implement an intrusion-tolerant service based on the SMA with only 2f + 1 replicas. Albeit a few other papers in the literature present intrusion-tolerant services with this approach, this is the first time the number of replicas is reduced from 3f + 1 to 2f + 1. Another interesting characteristic of the described service is a low time complexity.
The Origins, Specificity, and Potential Biological Relevance of Human Anti-IgG Hinge Autoantibodies (2011)

Human anti-IgG hinge (HAH) autoantibodies constitute a class of immunoglobulins that recognize cryptic epitopes in the hinge region of antibodies exposed after proteolytic cleavage, but do not bind to the intact IgG counterpart. Detailed molecular characterizations of HAH autoantibodies suggest that they are, in some cases, distinct from natural autoantibodies that arise independent of antigenic challenge. Multiple studies have attempted to define the specificity of HAH autoantibodies, which were originally detected as binding to fragments possessing C-terminal amino acid residues exposed in either the upper or lower hinge regions of IgGs. Numerous investigators have provided information on the isotype profiles of the HAH autoantibodies, as well as correlations among protease cleavage patterns and HAH autoantibody reactivity. Several biological functions have been attributed to HAH autoantibodies, ranging from house-cleaning functions to an immunosuppressive role to restoring function to cleaved IgGs. In this review, we discuss both the historic and current literature regarding HAH autoantibodies in terms of their origins, specificity, and proposed biological relevance.
Half‐scan cone‐beam CT fluoroscopy with multiple x‐ray sources (2001)

To develop volumetric micro-CT fluoroscopy for small animal imaging, we have proposed a cone-beam system with multiple x-ray sources. In this paper, we extend Parker's single-source half-scan weighting scheme to the case of an odd number of x-ray sources that are equiangularly distributed, and apply it for half-scan Feldkamp-type reconstruction in this unique geometry. In the numerical simulation with the Shepp-Logan phantom, representative images indicate that the proposed half-scan Feldkamp-type algorithm produces temporal resolution significantly superior to that with a single x-ray source cone-beam system.
Chemical and semisynthesis of posttranslationally modified proteins (2012)

Posttranslational modifications of proteins play crucial roles in health and disease by affecting numerous aspects of protein structure, function, stability and sub cellular localization. Yet understanding the effects of these modifications on several of these processes at the molecular level has been hindered by the lack of homogeneously modified proteins obtained via traditional biochemical and molecular biology approaches. Moreover, the preparation of such bioconjugates at a workable level is highly demanding. Recent advances in protein chemistry applying chemical and semisynthetic approaches are becoming increasingly beneficial to overcome these challenges. These methods allow site-specific modifications of a desired protein and afford the product in large quantities for biochemical and structural analyses. In this review, we survey these efforts and their importance in dissecting the role of several posttranslational modifications in various proteins. Several examples are presented where glycosylated, phosphorylated, ubiquitinated, lipidated, acetylated and methylated proteins were prepared.
Large Neutral Amino Acid Transporter Enables Brain Drug Delivery via Prodrugs (2008)

The blood-brain barrier efficiently controls the entry of drug molecules into the brain. We describe a feasible means to achieve carrier-mediated drug transport into the rat brain via the specific, large neutral amino acid transporter (LAT1) by conjugating a model compound to L-tyrosine. A hydrophilic drug, ketoprofen, that is not a substrate for LAT1 was chosen as a model compound. The mechanism and the kinetics of the brain uptake of the prodrug were determined with an in situ rat brain perfusion technique. The brain uptake of the prodrug was found to be concentration-dependent. In addition, a specific LAT1 inhibitor significantly decreased the brain uptake of the prodrug. Therefore, our results reveal for the first time that a drug-substrate conjugate is able to transport drugs into the brain via LAT1.
HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy–Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice (2019)

Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells <i>in vitro</i> and <i>in vivo</i>. Curative effects <i>in vivo</i> were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. SIGNIFICANCE: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
Surpassing the TLB performance of superpages with less operating system support (1994)

Many commercial microprocessor architectures have added translation lookaside buffer (TLB) support for superpages . Superpages differ from segments because their size must be a power of two multiple of the base page size and they must be aligned in both virtual and physical address spaces. Very large superpages (e.g., 1MB) are clearly useful for mapping special structures, such as kernel data or frame buffers. This paper considers the architectural and operating system support required to exploit medium-sized superpages (e.g., 64KB, i.e., sixteen times a 4KB base page size). First, we show that superpages improve TLB performance only after invasive operating system modifications that introduce considerable overhead. We then propose two subblock TLB designs as alternate ways to improve TLB performance. Analogous to a subblock cache, a complete-subblock TLB associates a tag with a superpage-sized region but has valid bits, physical page number, attributes, etc., for each possible base page mapping. A partial-subblock TLB entry is much smaller than a complete-subblock TLB entry, because it shares physical page number and attribute fields across base page mappings. A drawback of a partial-subblock TLB is that base page mappings can share a TLB entry only if they map to consecutive physical pages and have the same attributes. We propose a physical memory allocation algorithm, page reservation , that makes this sharing more likely. When page reservation is used, experimental results show partial-subblock TLBs perform better than superpage TLBs, while requiring simpler operating system changes. If operating system changes are inappropriate, however, complete-subblock TLBs perform best.
Estradiol Metabolites Attenuate Renal and Cardiovascular Injury Induced by Chronic Nitric Oxide Synthase Inhibition (2005)

Our previous studies in rodent models of nephropathy demonstrate that 2-hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity, exerts renoprotective effects. In vivo, 2HE is readily converted to 2-methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity. The goal of this study was to determine whether 2ME has renal and cardiovascular protective effects in vivo. First, the acute (90 minutes) and chronic (14 days) effects of 2ME (10 microg/kg/h) on blood pressure and renal function were examined in normotensive and spontaneously hypertensive rats (SHR). Second, a rat model of cardiovascular and renal injury induced by chronic nitric oxide synthase inhibition (N-nitro-L-arginine; 40 mg/kg/d; LNNA group) was used to examine the protective effects of estradiol metabolites. Subsets of LNNA-treated rats were administered either 2HE or 2ME (10 microg/kg/h via osmotic minipump; LNNA+2ME and LNNA+2HE groups, respectively. 2-Methoxyestradiol had no acute or chronic effects on blood pressure or renal function in normotensive animals or on hypertension in SHR. Prolonged, 5-week NOS inhibition induced severe cardiovascular and renal disease and high mortality (75%, LNNA group). 2ME, but not 2HE, significantly decreased elevated blood pressure and attenuated the reduction in GFR. 2HE delayed the onset of proteinuria, whereas no proteinuria was detected in the 2-ME group. 2HE and 2ME reduced mortality rate by 66% and 83%, respectively (P < 0.001). In the kidney, 2HE and 2ME abolished LNNA-induced interstitial and glomerular inflammation, attenuated glomerular collagen IV synthesis, and inhibited glomerular and tubular cell proliferation. In the heart, 2HE and 2ME markedly reduced vascular and interstitial inflammation and reduced collagen synthesis and vascular/interstitial cell proliferation. This study provides the first evidence that, in a model of severe cardiovascular and renal injury, 2-methoxyestradiol (a major nonestrogenic estradiol metabolite) exerts renal and cardiovascular protective effects and reduces mortality.
Scanning tunneling microscopy and atomic force microscopy studies of biomaterials at a liquid–solid interface (1993)

We have compared the scanning tunneling microscopy (STM) and atomic force microscopy (AFM) using a clean gold surface under electrochemical potential control, finding that the STM usually yields higher resolution, although this may be a consequence of better production methods for STM tips. New methods for tethering DNA molecules to substrates have yielded many excellent AFM images of DNA, even under water. The highest resolution has been obtained with specially sharpened tips, but recent work suggests that this may not be necessary. Control of contamination, and tip–sample interactions (i.e., adhesion) are also important factors. We describe a scheme of magnetic control of AFM cantilevers which should overcome the mechanical instability that places a lower limit on contact force. This should permit active control of interaction forces with the instrument operated in water. We illustrate local force measurements made under water with examples of the measurements of the microelastic properties of bone and of the electrostatic interactions between pairs of colloidal particles. The STM has been used to image small DNA oligomers on a gold electrode in water at high resolution. STM images of DNA bases show that the purines form stacked aggregates with the same base-stacked structure as found in DNA. There is evidence of a connection between the macroscopically measured electrochemical properties of thymine and its STM contrast. Such electronic sensitivity might be useful for chemical identification of molecules.
Performance issues in WWW servers (2002)

This paper evaluates techniques for improving operating system and network protocol software support for high-performance World Wide Web servers. We study approaches in three categories: i.e., new socket functions, per-byte optimizations, and per-connection optimizations. We examine two proposed socket functions, i.e., acceptex( ) and send-file( ), comparing send-file( )'s effectiveness with a combination of mmap( ) and writev( ). We show how send-file( ) provides the necessary semantic support to eliminate copies and checksums in the kernel, and quantify the benefit of the function's header and close options. We also present mechanisms to reduce the number of packets exchanged in an HTTP transaction, both increasing server performance and reducing network utilization, without compromising interoperability. Results using WebStone show that our combination of mechanisms can improve server throughput by up to 64%, and can eliminate up to 33% of the packets in an HTTP exchange. Results with SURGE show an aggregate increase in server throughput of 25%.
Cytotoxic T-cell response to respiratory syncytial virus in mice (1985)

The role of the humoral and cellular arms of the immune response in protection against respiratory syncytial virus (RSV) infection and in the pathogenesis of the severe forms of this disease is poorly understood. The recent demonstration that some inbred mouse strains can be infected with RSV has opened the way to a detailed investigation of RSV immunity. We report here the finding of major histocompatibility complex-restricted, RSV-specific memory cytotoxic T cells in the spleens of BALB/c and C57BL mice after intranasal infection; these T cells recognize the Long, A2, and 8/60 (human) strains of RSV. Both K and D locus major histocompatibility complex alleles can restrict the cytotoxic response; however, in the two haplotypes tested, Dd is a low-responder allele and Kb is a nonresponder allele for RSV. UV-inactivated RSV (when given intraperitoneally) can prime mice for development of cytotoxic T cell memory, restimulate cytotoxic T cell cultures in vitro, and form a target for the cytotoxic cells.
Endothelial Cell Adhesion Molecules and Their Role in Organ Preference of Metastasis. (1992)

Endothelial cell adhesion molecules expressed in distinct vascular branches of select organs are implicated in organ preference of metastasis. Two constitutively expressed adhesion molecules of the lung vasculature are described here. The first is the murine B 16 melanoma cell-binding endothelial cell adhesion molecule Lu-ECAM-1. The 90kDa Lu-ECAM-1 selectively promotes adhesion and lung metastasis of B 16 melanoma cells. Melanoma cell attachment to immobilized Lu-ECAM-1 is inhibited in a dose dependant manner by anti-Lu-ECAM-1 mAb 6D3, soluble Lu-ECAM-1, and lacto-N-fucopentose. In vivo blocking of Lu-ECAM-1 by its mAb 6D3 prevents lung colonization of B16-F10. However, Lu-ECAM-1 either binds nor affects metastasis of other lung colonizing tumor cells (e.g., KLN205 carcinoma cells), or tumor cell lines that metastasize to other organs than the lung (e.g., liver-metastatic B16-L8-F10, RAW117-H10), and does not bind lymphocytes and neutrophils. The second adhesion molecule is rat dipeptidyl peptidase IV(DPP IV). This sialoglycoprotein binds lung-metastatic rat prostate and breast carcinoma cells via fibronectin which is expressed in significantly higher amounts on the surface of metastatic than non-metastatic tumor cells. Increased fibronectin expression is associated with increases in tumor cell β1 and β3 integrins. DPP IV binding is mediated by a fibronectin sequence other than RGD and is independent of its peptidase domain. These constitutively expressed adhesion molecules are believed to be responsible for site-specific vascular arrest of blood-borne cancer cells and, through as yet unknown signaling events, may cause upregulation of other (transiently expressed) adhesion molecules to enhance tumor cell binding to endothelium and/or initiate gap junctional communication to promote extravasation and secondary tumor growth.
Thermostable inhibitor of cAMP-dependent protein kinase enhances the rate of export of the kinase catalytic subunit from the nucleus. (1994)

The catalytic (C) subunit of cAMP-dependent protein kinase is inhibited by the regulatory (R) subunit and by a thermostable inhibitor (PKI). Both inhibitors also affect the intracellular distribution of the C subunit. Whether injected into the cytoplasm or into the nucleus, free C subunit can enter and exit the nucleus freely. After 30 min its distribution is identical and is independent of the initial site of injection. In contrast, when C is injected into the cytoplasm complexed with R or PKI, the complexes are restricted to the cytoplasm (1-3). However, unlike the R subunit, which is restricted to the cytoplasm like the holoenzyme, free PKI enters the nucleus rapidly following its injection into the cytoplasm. When holoenzyme is injected directly into the nucleus, it cannot exit and return to the cytoplasm. In contrast, nuclear injection of a C.PKI complex results in the rapid exit of the C subunit from the nucleus. In equilibrated cells previously injected with the C subunit, subsequent cytoplasmic injection of either PKI or type 1 R depletes the nucleus of C although PKI does so faster, consistent with its ability to enter the nucleus. Both inhibitors block the cAMP response element-regulated gene expression. Hence PKI may serve as a nuclear scavenger of C providing a mechanism not only for inhibition but also for subcellular localization in the presence of cAMP by restricting the access of the C subunit to the nucleus.
Enhanced Hydrophobicity of Fluorinated Lipid Bilayer: A Molecular Dynamics Study (2008)

A molecular dynamics simulation of a partially fluorinated phospholipid bilayer has been carried out to understand the effects of fluorination of the hydrophobic chains on the structure and water permeability across the membrane. Fluorocarbon chains typically have an all-trans conformation, showing a highly ordered structure in the membrane core compared to ordinary hydrocarbon chains. The free energy profiles of water across the bilayers were successfully estimated by a revised cavity insertion Widom method. The fluorinated bilayer showed a higher free energy barrier than an ordinary nonfluorinated lipid bilayer by about 1.2 kcal/mol, suggesting a lower water permeability of the fluorinated bilayer membrane. A cavity distribution analysis elucidated the reduced free volume in the fluorinated membrane due to the neatly packed chains, which should account for the higher free energy barrier.