gebhart/patrepeval huggingface dataset:
An Adaptor Domain‐Mediated Autocatalytic Interfacial Kinase Reaction (2009)

This paper describes a model system for studying the autocatalytic phosphorylation of an immobilized substrate by a kinase enzyme. This work uses self-assembled monolayers (SAMs) of alkanethiolates on gold to present the peptide substrate on a planar surface. Treatment of the monolayer with Abl kinase results in phosphorylation of the substrate. The phosphorylated peptide then serves as a ligand for the SH2 adaptor domain of the kinase and thereby directs the kinase activity to nearby peptide substrates. This directed reaction is intramolecular and proceeds with a faster rate than does the initial, intermolecular reaction, making this an autocatalytic process. The kinetic non-linearity gives rise to properties that have no counterpart in the corresponding homogeneous phase reaction: in one example, the rate for phosphorylation of a mixture of two peptides is faster than the sum of the rates for phosphorylation of each peptide when presented alone. This work highlights the use of an adaptor domain in modulating the activity of a kinase enzyme for an immobilized substrate and offers a new approach for studying biochemical reactions in spatially inhomogeneous settings.
Flow cytometric analysis of mature adipocytes (1989)

Flow cytometry is an excellent method for studying the physiological function in adipocytes because their response to hormones, especially insulin, varies with cell maturity and therefore size. Adipocytes present a unique technical challenge. A freshly prepared adipocyte suspension contains cells and fat droplets ranging from 10 to greater than 120 microns in diameter. Stored fat occupies 90-98% of the cell volume, making it difficult to distinguish cells from fat droplets. Other difficulties include buoyancy, large size, fragility, and tendency to aggregate and clog the sample tube and nozzle. These obstacles were overcome by 1) maintaining the sample, sample line, sheath fluid, reservoir, and nozzle assembly at 37 degrees C; 2) using a 200 microns diameter orifice; 3) using a short, 300 microns inside diameter Teflon sample delivery line; 4) injecting the sample at constant flow rate into the sheath fluid at low pressure; and 5) using the pH-sensitive vital stain, biscarboxyethylcarboxyfluorescein (BCECF) to distinguish cells from fat droplets. Stained cells are brightly fluorescent when excited at 488 nm. Because fat droplets do not fluoresce, they can be distinguished from fat cells by gating on the BCECF emission. The cytosolic pH of intact, viable, mature adipocytes was derived from the ratio of the fluorescent emission intensities at 520 and 620 nm and was estimated to be 7.2. Unlike BCECF, several other useful fluorescent probes of cell function, e.g., the intracellular calcium indicator, indo-1, label both fat cells and fat droplets.(ABSTRACT TRUNCATED AT 250 WORDS)
Safe and effective fine-grained TCP retransmissions for datacenter communication (2009)

This paper presents a practical solution to a problem facing high-fan-in, high-bandwidth synchronized TCP workloads in datacenter Ethernets---the TCP incast problem. In these networks, receivers can experience a drastic reduction in application throughput when simultaneously requesting data from many servers using TCP. Inbound data overfills small switch buffers, leading to TCP timeouts lasting hundreds of milliseconds. For many datacenter workloads that have a barrier synchronization requirement (e.g., filesystem reads and parallel data-intensive queries), throughput is reduced by up to 90%. For latency-sensitive applications, TCP timeouts in the datacenter impose delays of hundreds of milliseconds in networks with round-trip-times in microseconds. Our practical solution uses high-resolution timers to enable microsecond-granularity TCP timeouts. We demonstrate that this technique is effective in avoiding TCP incast collapse in simulation and in real-world experiments. We show that eliminating the minimum retransmission timeout bound is safe for all environments, including the wide-area.
Translating Christine de Pisan (1997)

The ability to deliver therapeutically relevant amounts of drugs directly from the nasal cavity to the central nervous system to treat neurological diseases is dependent on the availability of efficient drug delivery systems. Increased delivery and/or therapeutic effect has been shown for drugs encapsulated in nanoparticles; however, the factors governing the transport of the drugs and/or the nanoparticles from the nasal cavity to the brain are not clear. The present study evaluates the potential transport of nanoparticles across the olfactory epithelium in relation to nanoparticle characteristics. Model systems, 20, 100, and 200 nm fluorescent carboxylated polystyrene (PS) nanoparticles that were nonmodified or surface modified with polysorbate 80 (P80-PS) or chitosan (C-PS), were assessed for transport across excised porcine olfactory epithelium mounted in a vertical Franz diffusion cell. Assessment of the nanoparticle content in the donor chamber of the diffusion cell, accompanied by fluorescence microscopy of dismounted tissues, revealed a loss of nanoparticle content from the donor suspension and their association with the excised tissue, depending on the surface properties and particle size. Chitosan surface modification of PS nanoparticles resulted in the highest tissue association among the tested systems, with the associated nanoparticles primarily located in the mucus, whereas the polysorbate 80-modified nanoparticles showed some penetration into the epithelial cell layer. Assessment of the bioelectrical properties, metabolic activity, and histology of the excised olfactory epithelium showed that C-PS nanoparticles applied in pH 6.0 buffer produced a damaging effect on the epithelial cell layer in a size-dependent manner, with fine 20 nm sized nanoparticles causing substantial tissue damage relative to that with the 100 and 200 nm counterparts. Although histology showed that the olfactory tissue was affected by the application of citrate buffer that was augmented by addition of chitosan in solution, this was not reflected in the bioelectrical parameters and the metabolic activity of the tissue. Regarding transport across the excised olfactory tissue, none of the nanoparticle systems tested, irrespective of particle size or surface modification, was transported across the epithelium to appear in measurable amounts in the receiver chamber.
Using Internet Searches for Influenza Surveillance (2008)

The Internet is an important source of health information. Thus, the frequency of Internet searches may provide information regarding infectious disease activity. As an example, we examined the relationship between searches for influenza and actual influenza occurrence. Using search queries from the Yahoo! search engine ( http://search.yahoo.com ) from March 2004 through May 2008, we counted daily unique queries originating in the United States that contained influenza-related search terms. Counts were divided by the total number of searches, and the resulting daily fraction of searches was averaged over the week. We estimated linear models, using searches with 1-10-week lead times as explanatory variables to predict the percentage of cultures positive for influenza and deaths attributable to pneumonia and influenza in the United States. With use of the frequency of searches, our models predicted an increase in cultures positive for influenza 1-3 weeks in advance of when they occurred (P < .001), and similar models predicted an increase in mortality attributable to pneumonia and influenza up to 5 weeks in advance (P < .001). Search-term surveillance may provide an additional tool for disease surveillance.
Advanced Shortest Paths Algorithms on a Massively-Multithreaded Architecture (2007)

We present a study of multithreaded implementations of Thorup's algorithm for solving the Single Source Shortest Path (SSSP) problemfor undirected graphs. Our implementations leverage thefledgling MultiThreaded Graph Library (MTGL) to perform operations such as finding connected components and extracting induced subgraphs. To achieve good parallel performance from this algorithm, we deviate from several theoretically optimal algorithmic steps. In this paper; we present simplifications that perform better in practice, and we describe details of the multithreaded implementation that were necessary for scalability. We study synthetic graphs that model unstructured networks, such as social networks and economic transaction networks. Most of the recent progress in shortest path algorithms relies on structure that these networks do not have. In this work, we take a step back and explore the synergy between an elegant theoretical algorithm and an elegant computer architecture. Finally, we conclude with a prediction that this work will become relevant to shortest path computation on structured networks.
Differences of RNA Expression in the Tendon According to Anatomic Outcomes in Rotator Cuff Repair (2017)

The downregulation of inflammatory response genes and the upregulation of cell differentiation genes in torn rotator cuffs at the time of surgery are related to rotator cuff healing. These results provide useful baseline information for future biological studies on rotator cuff healing.
Chirp Optical Coherence Tomography of Layered Scattering Media (1998)

A new noninvasive technique that reveals cross sectional images of scattering media is presented. It is based on a continuous wave frequency modulated radar, but uses a tunable laser in the near infrared. As the full width at half maximum resolution of 16 μm is demonstrated with an external cavity laser, the chirp optical coherence tomography becomes an alternative to conventional short coherence tomography with the advantage of a simplified optical setup. The analysis of two-layer solid phantoms shows that the backscattered light gets stronger with decreasing anisotropic factor and increasing scattering coefficient, as predicted by Monte Carlo simulations. By introducing a two-phase chirp sequence, the combination of lateral resolved perfusion and depth resolved structure is shown. © 1998 Society of Photo-Optical Instrumentation Engineers.
Genetic evidence that mutants of the methoprenetolerant gene of Drosophila melanogaster are null mutants (1996)

The Methoprene-tolerant (Met) mutation of Drosophila melanogaster results in resistance to juvenile hormone (JH) or JH analogs and appears to alter JH reception during late larval development. Several alleles of Met have been recovered from methoprene selection screens after mutagenesis with ethyl methanesulfonate, X-rays, or transposable genetic elements. The phenotype of flies carrying any of these alleles is similar—resistance to the toxic and morphogenetic effects of methoprene—but otherwise is essentially wild-type. Understanding the function of the Met gene requires that we know whether these alleles are hypomorphic, producing some functional gene product, or amorphic, producing no functional gene product. This determination was made by comparing the methoprene-resistance phenotype produced by representative Met alleles with that produced by a chromosome carrying a deficiency that deletes the Met gene. The level of resistance to either the toxic or the morphogenetic effect of methoprene was similar among flies heterozygous for either the deficiency chromosome or for any of the alleles. The results provide genetic evidence that the Met alleles recovered to date are amorphic and suggest that the Met gene may not be mutable to a more severe Met allele that affects the viability, development, or reproduction of the flies. © 1996 Wiley-Liss, Inc.
Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat (2009)

Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Long-term visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients.
How protein reads the stop codon and terminates translation (1998)

Translation termination requires two codon-specific protein-release factors in prokaryotes and one factor in eukaryotes. The underlying mechanism for stop codon recognition, as well as the biological meaning of the conservation of one or two release factors in the evolutionary kingdoms, are not known. The recent discovery of release factor genes and the molecular mimicry between translational factors and tRNA provide us with clues to the mechanisms of how proteins read the stop codon and terminate translation, shedding some light on the evolutionary aspect of release factors.
Yaksha: augmenting Kerberos with public key cryptography (2002)

The Kerberos authentication system is based on the trusted third-party Needham-Schroeder (1978) authentication protocol. The system is one of the few industry standards for authentication systems and its use is becoming fairly widespread. The system has some limitations, many of which are traceable to the decision of the Kerberos designers to solely use symmetric key cryptosystems. Using asymmetric (public-key) cryptosystems in an authentication protocol would prevent some of the shortcomings. Several such protocols have been proposed and some have been implemented. However, all these designs are either completely different from the Kerberos system, or require major changes to the basic system. Any attempts to improve Kerberos would do so with only minimal impact to the protocol and the source tree. In this work, we describe Yaksha, a new approach to achieving these goals. Yaksha uses as its building block an RSA (Rivest, Shamir & Adelman, 1978) algorithm variant independently invented by Boyd (1989) and by Ganesan and Yacobi (1994), in which the RSA private key is split into two portions. One portion becomes a user's Yaksha password, and the other the Yaksha server's password for that user. Using this simple but useful primitive, we show how we can blend the Kerberos system with a public-key infrastructure to create Yaksha, a more secure version of Kerberos, with minimal changes to the protocol.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Antimicrobial Synergistic Effect of Linolenic Acid and Monoglyceride against Bacillus cereus and Staphylococcus aureus (2002)

The antimicrobial effect of linolenic acid with or without monoglyceride (glycerol laurate or glycerol myristate) against six food-borne microorganisms was determined in broth medium. Minimum inhibitory concentration of linolenic acid on Bacillus cereus and Staphylococcus aureus was 20 and 50 ppm, respectively. The growth of B. cereus treated with linolenic acid at 10 ppm with 10 ppm monoglyceride was more inhibitory than that of linolenic acid alone, and the viable cell population was reduced 2-4 log cycles compared to that of the control. When linolenic acid was added at that level, the adenosine triphosphate (ATP) concentration of extracellular fluid was drastically increased compared with that of the control, and the combined effect with monoglyceride was higher than that with linolenic acid alone. However, the intracellular ATP concentration decreased compared with that of the control. From these results, we concluded that linolenic acid has a strong antimicrobial activity against B. cereus and S. aureus, and that linolenic acid combined with monoglyceride showed stronger antimicrobial activity than using linolenic acid alone.
Features involved in the diagnostic delay of cluster headache (2003)

<b>Background:</b> Cluster headache (CH) is a comparatively rare, very severe primary headache. Although circumscript and recognisable criteria are available, the diagnosis is often missed or delayed. Besides, while adequate and evidence based treatment is available in diagnosed cases, CH seems to be poorly managed. The authors performed a nationwide survey among CH patients, and looked for factors involved in the diagnostic delay. <b>Methods:</b> The authors performed a nationwide mailing to all Dutch general practitioners (about 5800), and neurologists (about 560) and invited them to refer patients in whom the diagnosis CH was made or considered. Patients could also apply via the Dutch Headache Patients Society. A variety of clinical characteristics were assessed by means of questionnaires. Specifically, patients were asked about the time between their first episode and the diagnosis. <b>Results:</b> The IHS criteria for CH were met by 1429 of 2001 responders, and 1163 of these filled in an extended questionnaire. The male to female ratio was 3.7:1. Mean age at onset was 32 (SD 14) years. Seventy three per cent had episodic CH, 21% had chronic CH, and in 6% the periodicity was undetermined. The time between the first episode and the diagnosis ranged from 1 week to 48 years (median 3 years): 34% had consulted a dentist and 33% an ENT specialist before the diagnosis was established. Among factors that increased the diagnostic delay were the presence of photophobia or phonophobia, nausea, an episodic attack pattern and a low age at onset (p&lt;0.01). Sex or presence of restlessness during episodes did not influence the diagnostic delay. <b>Conclusion:</b> CH remains unrecognised or misdiagnosed in many cases for many years. Photophobia or phonophobia and nausea were in part responsible for this delay, and should be recognised as part of the clinical spectrum of CH. Many patients were first seen by a dentist or ENT specialist for their CH episodes, so more attention should be paid to educate first line physicians to recognise CH, to improve the diagnostic process and so to expose patients to earlier and better treatment of CH.
Soluble Forms of Toll-Like Receptor (TLR)2 Capable of Modulating TLR2 Signaling Are Present in Human Plasma and Breast Milk (2003)

Dysregulation of the initial, innate immune response to bacterial infection may lead to septic shock and death. Toll-like receptors (TLRs) play a crucial role in this innate immune response, and yet the regulatory mechanisms controlling microbial-induced TLR triggering are still to be fully understood. We have therefore sought specific regulatory mechanisms that may modulate TLR signaling. In this study, we tested for the possible existence of a functionally active soluble form of TLR2. We demonstrated the existence of natural soluble forms of TLR2 (sTLR2), which we show to be capable of modulating cell activation. We found that blood monocytes released sTLR2 constitutively and that the kinetics of sTLR2 release increased upon cell activation. Analysis of cells expressing the human TLR2 cDNA or its c-myc-tagged version indicated that sTLR2 resulted from the posttranslational modification of the TLR2 protein in an intracellular compartment. Moreover, an intracellular pool of sTLR2 is maintained. sTLR2 was found naturally expressed in breast milk and plasma. Milk sTLR2 levels mirrored those of the TLR coreceptor soluble CD14. Depletion of sTLR2 from serum resulted in an increased cellular response to bacterial lipopeptide. Notably, serum sTLR2 was lower in tuberculosis patients. Coimmunoprecipitation experiments and computational molecular docking studies showed an interaction between sTLR2 and soluble CD14 in plasma and milk. These findings suggest the existence of a novel and specific innate immune mechanism regulating microbial-induced TLR triggering, and may lead to new therapeutics for the prevention and/or treatment of severe infectious diseases.
Advances in Microbial Biofilm Prevention on Indwelling Medical Devices with Emphasis on Usage of Acoustic Energy (2009)

Microbial biofilms are a major impediment to the use of indwelling medical devices, generating device-related infections with high morbidity and mortality. Major efforts directed towards preventing and eradicating the biofilm problem face difficulties because biofilms protect themselves very effectively by producing a polysaccharide coating, reducing biofilm sensitivity to antimicrobial agents. Techniques applied to combating biofilms have been primarily chemical. These have met with partial and limited success rates, leading to current trends of eradicating biofilms through physico-mechanical strategies. Here we review the different approaches that have been developed to control biofilm formation and removal, focusing on the utilization of acoustic energy to achieve these objectives.
Conjugated Platinum(IV)−Peptide Complexes for Targeting Angiogenic Tumor Vasculature (2007)

The integrins alpha vbeta3 and alpha vbeta5 and the membrane-spanning surface protein aminopeptidase N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing RGD, (CRGDC)c, (RGDfK)c, or NGR, is appended as a "tumor-homing device" to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with nonspecific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to cell lines containing alpha vbeta3 and alpha vbeta5, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin alpha vbeta3 mediated, at least in part, the anti-proliferative effect of a Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of alpha vbeta3/alpha vbeta5-specific RGD pentapeptides or (2) transfected with RNAi for beta 3, but not beta 1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment.