gebhart/patrepeval huggingface dataset:
Next Generation Technology for Epidemic Prevention and Control: Data-Driven Contact Tracking (2018)

Contact tracking is one of the key technologies in prevention and control of infectious diseases. In the face of a sudden infectious disease outbreak, contact tracking systems can help medical professionals quickly locate and isolate infected persons and high-risk individuals, preventing further spread and a large-scale outbreak of infectious disease. Furthermore, the transmission networks of infectious diseases established using contact tracking technology can aid in the visualization of actual virus transmission paths, which enables simulations and predictions of the transmission process, assessment of the outbreak trend, and further development and deployment of more effective prevention and control strategies. Exploring effective contact tracking methods will be significant. Governments, academics, and industries have all given extensive attention to this goal. In this paper, we review the developments and challenges of current contact tracing technologies regarding individual and group contact from both static and dynamic perspectives, including static individual contact tracing, dynamic individual contact tracing, static group contact tracing, and dynamic group contact tracing. With the purpose of providing useful reference and inspiration for researchers and practitioners in related fields, directions in multi-view contact tracing, multi-scale contact tracing, and AI-based contact tracing are provided for next-generation technologies for epidemic prevention and control.
Cancer Theranostics with Near-Infrared Light-Activatable Multimodal Nanoparticles (2011)

Nanomaterials that interact with light provide a unique opportunity for applications in biophotonic nanomedicine. Image-guided therapies could be designed based on multifunctional nanoparticles (NPs). Such NPs have a strong and tunable surface plasmon resonance absorption in the near-infrared region and can be detected using multiple imaging modalities (magnetic resonance imaging, nuclear imaging, and photoacoustic imaging). These novel nanostructures, once introduced, are expected to home in on solid tumors either via a passive targeting mechanism (i.e., the enhanced permeability and retention effect) or via an active targeting mechanism facilitated by ligands bound to their surfaces. Once the NPs reach their target tissue, their activity can then be turned on using an external stimulus. For example, photothermal conducting NPs primarily act by converting light energy into heat. As a result, the temperature in the treatment volume is elevated above the thermal damage threshold, which kills the cells. This process, termed photothermal ablation therapy (PTA), is effective, but it is also unlikely to kill all tumor cells when used alone. In addition to PTA, photothermal conducting NPs can also efficiently trigger the release of drugs and activate RNA interference. A multimodal approach, which permits simultaneous PTA therapy, chemotherapy, and therapeutic RNA interference, has the potential to completely eradicate residual diseased cells. In this Account, we provide an up-to-date review of the synthesis and characterization, functionalization, and in vitro and in vivo evaluation of NIR lightactivatable multifunctional nanostructures used for imaging and therapy. We emphasize research on hollow gold nanospheres, magnetic core-shell gold nanoshells, and semiconductor copper monosulfide NPs. We discuss three types of novel drug delivery systems in which hollow gold nanospheres are used to mediate controlled drug release.
Multi-paragraph segmentation of expository text (1994)

This paper describes TextTiling, an algorithm for partitioning expository texts into coherent multi-paragraph discourse units which reflect the subtopic structure of the texts. The algorithm uses domain-independent lexical frequency and distribution information to recognize the interactions of multiple simultaneous themes. Two fully-implemented versions of the algorithm are described and shown to produce segmentation that corresponds well to human judgments of the major subtopic boundaries of thirteen lengthy texts.
Mechanism of Binding of Prothioconazole to Mycosphaerella graminicola CYP51 Differs from That of Other Azole Antifungals (2010)

Prothioconazole is one of the most important commercially available demethylase inhibitors (DMIs) used to treat Mycosphaerella graminicola infection of wheat, but specific information regarding its mode of action is not available in the scientific literature. Treatment of wild-type M. graminicola (strain IPO323) with 5 μg of epoxiconazole, tebuconazole, triadimenol, or prothioconazole ml(-1) resulted in inhibition of M. graminicola CYP51 (MgCYP51), as evidenced by the accumulation of 14α-methylated sterol substrates (lanosterol and eburicol) and the depletion of ergosterol in azole-treated cells. Successful expression of MgCYP51 in Escherichia coli enabled us to conduct spectrophotometric assays using purified 62-kDa MgCYP51 protein. Antifungal-binding studies revealed that epoxiconazole, tebuconazole, and triadimenol all bound tightly to MgCYP51, producing strong type II difference spectra (peak at 423 to 429 nm and trough at 406 to 409 nm) indicative of the formation of classical low-spin sixth-ligand complexes. Interaction of prothioconazole with MgCYP51 exhibited a novel spectrum with a peak and trough observed at 410 nm and 428 nm, respectively, indicating a different mechanism of inhibition. Prothioconazole bound to MgCYP51 with 840-fold less affinity than epoxiconazole and, unlike epoxiconazole, tebuconazole, and triadimenol, which are noncompetitive inhibitors, prothioconazole was found to be a competitive inhibitor of substrate binding. This represents the first study to validate the effect of prothioconazole on the sterol composition of M. graminicola and the first on the successful heterologous expression of active MgCYP51 protein. The binding affinity studies documented here provide novel insights into the interaction of MgCYP51 with DMIs, especially for the new triazolinethione derivative prothioconazole.
Respiratory Rate and Flow Waveform Estimation from Tri-axial Accelerometer Data (2010)

There is a strong medical need for continuous, unobstrusive respiratory monitoring, and many shortcomings to existing methods. Previous work shows that MEMS accelerometers worn on the torso can measure inclination changes due to breathing, from which a respiratory rate can be obtained. There has been limited validation of these methods. The problem of practical continuous monitoring, in which patient movement disrupts the measurements and the axis of interest changes, has also not been addressed. We demonstrate a method based on tri-axial accelerometer data from a wireless sensor device, which tracks the axis of rotation and obtains angular rates of breathing motion. The resulting rates are validated against gyroscope measurements and show high correlation to flow rate measurements using a nasal cannula. We use a movement detection method to classify periods in which the patient is static and breathing signals can be observed accurately. Within these periods we obtain a close match to cannula measurements, for both the flow rate waveform and derived respiratory rates, over multi-hour datasets obtained from wireless sensor devices on hospital patients. We discuss future directions for improvement and potential methods for estimating absolute airflow rate and tidal volume.
PACAP and Type I PACAP Receptors in Human Prostate Cancer Tissue (2006)

We characterized the expression and localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific type I receptor variants in prostatic, hyperplastic, and carcinomatous tissue collected from patients undergoing prostate biopsy and surgery for benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The immunohistochemical studies using an indirect immunoperoxidase technique evidenced positive immunostaining for PACAP in the cytoplasm of epithelial cells of hyperplastic and carcinomatous prostate specimens and in some scattered cells of the stroma. Type I PACAP receptors (PAC1 R) in healthy and BPH tissues were localized in all epithelial cells lining the lumen of the acini and in some stromal cells, while in specimens from PCa the anti-PAC1 R antibody stained the apical portion of a large percentage of cells. Furthermore, our molecular studies provide evidence that several PAC1 R isoforms (null, SV1/SV2) are present in normal, hyperplastic, and neoplastic tissue, the null variant being the most intensely expressed in PCa. These observations provide additional evidence for a role of PACAP and PAC1 R in the events determining the outcome of PCa.
Unraveling the cytoplasmic interactions of the cadherin superfamily. (1994)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Antisense phosphorothioate oligodeoxynucleotides targeted to the vpr gene inhibit human immunodeficiency virus type 1 replication in primary human macrophages (1993)

The replication of human immunodeficiency viruses (HIV) in human macrophages is influenced by genetic determinants which have been mapped predominantly to the viral envelope. However, in HIV-2, the vpr gene has also been suggested as an important modulator of viral expression in human macrophages. We synthesized five antisense phosphorothioate oligodeoxynucleotides complementary to the vpr mRNA of HIV-1Ba-L, a highly macrophage-tropic viral strain, and measured their effect on HIV-1Ba-L replication in primary human macrophages. All of the oligodeoxynucleotides displayed some level of non-sequence-specific inhibition of viral replication; however, only the antisense one had an additional effect on viral production in primary macrophages. Of the five antisense oligodeoxynucleotides tested, only one did not show any additional effect on viral production, whereas all the others inhibited viral replication to a similar degree (70 to 100%). Variation in the degree of inhibition was observed by using five different donors of human primary macrophages. The phosphorothioate oligonucleotides, targeted to the initiating methionine of the Vpr protein, had an inhibitory effect at both 20 and 10 microM only when the size was increased from 24 to 27 bases. Thus, HIV-1 replication in human macrophages is modulated by the expression of the vpr gene, and it is conceivable that vpr antisense oligodeoxynucleotides could be used in combination with antisense oligodeoxynucleotides against other HIV-1 regulatory genes to better control viral expression in human macrophages.
An optically induced cell lysis device using dielectrophoresis (2009)

This letter reports an optically induced cell lysis device that can selectively lyse a single cell within a group of cells, a function which cannot be performed using traditional tools. This chip-scale device was made of a photoconductive material, which can induce a nonuniform electric field at a specific position under illumination of a beam spot generating a transmembrane potential in the cell. With this approach, cell lysis can be performed using the optically induced electric field. Fibroblast cells and oral cancer cells were used to demonstrate the capability of the developed chip. In addition to lysing the whole cell, the developed method also allowed one to selectively disrupt the cell membrane without damaging the nucleus. Operating parameters such as illumination power density and beam spot diameter for cell lysis were systematically investigated.
Well-Defined Protein−Polymer Conjugates via in Situ RAFT Polymerization (2007)

Biotechnology, biomedicine, and nanotechnology applications would benefit from methods generating well-defined, monodisperse protein-polymer conjugates, avoiding time-consuming and difficult purification steps. Herein, we report the in situ synthesis of protein-polymer conjugates via reversible addition-fragmentation chain transfer polymerization (RAFT) as an efficient method to generate well-defined, homogeneous protein-polymer conjugates in one step, eliminating major postpolymerization purification steps. A water soluble RAFT agent was conjugated to a model protein, bovine serum albumin (BSA), via its free thiol group at Cys-34 residue. The conjugation of the RAFT agent to BSA was confirmed by UV-visible spectroscopy, matrix-assisted laser desorption ionization--time of flight (MALDI-TOF), and 1H NMR. BSA-macroRAFT agent was then used to control the polymerization of two different water soluble monomers, N-isopropylacrylamide (NIPAAm) and hydroxyethyl acrylate (HEA), in aqueous medium at 25 degrees C. The growth of the polymer chains from BSA-macroRAFT agent was characterized by size exclusion chromatography (SEC), 1H NMR, MALDI-TOF, and polyacrylamide gel electrophoresis (PAGE) analyses. The controlled character of the RAFT polymerizations was confirmed by the linear evolution of molecular weight with monomer conversion. The SEC analyses showed no detectable free, nonconjugated polymer formation during the in situ polymerization. The efficiency of BSA-macroRAFT agent to generate BSA-polymer conjugates was found to be ca. 1 by deconvolution of the SEC traces of the polymerization mixtures. The structural integrity and the conformation-related esterase activity of BSA were found to be unaffected by the polymerization conditions and the conjugation of the polymer chain. BSA-poly(NIPAAm) conjugates showed hybrid temperature-dependent phase separation and aggregation behavior. The lower critical solution temperature values of the conjugates were found to increase with the decrease in molecular weight of poly(NIPAAm) block conjugated to BSA.
An Isotopically Coded CID-cleavable Biotinylated Cross-linker for Structural Proteomics (2010)

Successful application of cross-linking combined with mass spectrometry for structural proteomics demands specifically designed cross-linking reagents to address challenges in the detection and assignment of cross-links. A combination of affinity enrichment, isotopic coding, and cleavage of the cross-linker is beneficial for detection and identification of the peptide cross-links. Here we describe a novel cross-linker, cyanurbiotindipropionylsuccinimide (CBDPS), that allows affinity enrichment of cross-linker-containing peptides with avidin. Affinity enrichment eliminates interfering non-cross-linked peptides and allows the researcher to focus on the analysis of the cross-linked peptides. CBDPS is also isotopically coded and CID-cleavable. The cleaved fragments still contain a portion of the isotopic label and can therefore be distinguished from unlabeled fragments by their distinct isotopic signatures in the MS/MS spectra. This cleavage information has been incorporated into a program for the automatic analysis of the MS/MS spectra of the cross-links. This allows rapid determination of cross-link type in addition to facilitating identification of the individual peptides constituting the interpeptide cross-links. Thus, affinity enrichment combined with isotopic coding and CID cleavage allows in-depth mass spectrometric analysis of the peptide cross-links. We have characterized the performance of CBDPS on the 120-kDa protein heterodimer of HIV reverse transcriptase.
Synthesis of 2′‐Deoxyribofuranosides of 8‐Aza‐7‐deazaguanine and Related Pyrazolo[3,4‐d]pyrimidines (1986)

Abstract The N (1)‐ and N (2)‐(2′‐deoxyribofuranosides) 1 and 2 , respectively, of 8‐aza‐7‐deazaguanine were prepared via phase‐transfer glycosylation in the presence or absence of Bu 4 NHSO 4 as catalyst of 6‐amino‐4‐methoxy‐l H ‐pyrazolo[3,4‐ d ]pyrimidine ( 7c ) with 2‐deoxy‐3,5‐di‐ O ‐( p ‐toluoyl)‐α‐ D ‐erythro‐pentofuranosyl chloride ( 10 ). On a similar route, but without catalyst and employing THF as organic phase, the 6‐amino‐4‐chloronucleosides 11b and 12b were synthesized from 7a and converted into the N (1)‐and N (2)‐substituted 4‐thioxo analogues 17a and 18a , respectively. The ratio of N (1)‐ to N (2)‐glycosylation was 2:1 for 7c and 1:1 for 7a , viz. depending on the nucleobase structure. The rate of the H + ‐catalyzed N‐glycosyl hydrolysis was strongly decreased for the N (2)‐(β‐ D ‐2′‐deoxyribofuranosides) as compared to the N (1)‐compounds. However, the N (1)‐nucleoside 1 , which is an isostere of 2′‐deoxyguanosine, is sufficiently stable to be employed later in solid‐phase oligonucleotide synthesis.
A Role for Mac-1 (CDIIb/CD18) in Immune Complex–stimulated Neutrophil Function In Vivo: Mac-1 Deficiency Abrogates Sustained Fcγ Receptor–dependent Neutrophil Adhesion and Complement-dependent Proteinuria in Acute Glomerulonephritis (1997)

Mac-1 (alphambeta2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcgamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1- deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-FcgammaR interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-FcgammaR interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice.
MultiRep (2011)

Nowadays, people increasingly use multiple devices to manage and share information anywhere anytime. Users are increasingly spreading large sets of files and folders among several devices. Since users cannot know at one device which files/folders are stored by other devices, data management across multiple devices has become a very difficult task. For instance, when one user needs an object that is not stored on the device being used, he/she needs to manually explore the entire object collection, which is spread across multiple devices. Additionally, different versions of files are created on multiple devices raising a consistency problem. Most current solutions ensure data management and consistency across devices through central servers or Internet services. Since portable devices have intermittent network connection or no connection at all to access these services, it is essential to take advantage of proximity between devices to synchronize data among them. This paper introduces MultiRep, a single-user file synchronizer middleware that provides the user with information about the location of files and folders stored on multiple devices. MultiRep is a totally decentralized system based on optimistic replication. It ensures eventual consistency among multiple devices through pair-wise interactions, reporting all relevant information about conflicts to the users.
Evaluation of SMN Protein, Transcript, and Copy Number in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study (2012)

Clinicaltrials.gov NCT00756821.
Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk (2011)

Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3(R102G)), factor B (fB(R32Q)), and factor H (fH(V62I)) are associated with age-related macular degeneration (AMD) and other pathologies. Our published work showed that fB(R32Q) influences C3 convertase formation, whereas fH(V62I) affects factor I cofactor activity. Here we show how C3(R102G) (C3S/F) influences AP activity. In hemolysis assays, C3(102G) activated AP more efficiently (EC(50) C3(102G): 157 nM; C3(102R): 191 nM; P < 0.0001). fB binding kinetics and convertase stability were identical, but native and recombinant fH bound more strongly to C3b(102R) (K(D) C3b(102R): 1.0 μM; C3b(102G): 1.4 μM; P < 0.0001). Accelerated decay was unaltered, but fH cofactor activity was reduced for C3b(102G), favoring AP amplification. Combining disease "risk" variants (C3(102G), fB(32R), and fH(62V)) in add-back assays yielded sixfold higher hemolytic activity compared with "protective" variants (C3(102R), fB(32Q), and fH(62I); P < 0.0001). These data introduce the concept of a functional complotype (combination of polymorphisms) defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.
Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor (1999)

In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-alpha or IL-1beta on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-alpha or IL-1beta plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-alpha- or IL-1beta-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-alpha or IL-1beta plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-alpha for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-alpha and IL-1beta.