gebhart/patrepeval huggingface dataset:
Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab' fragments via disulfide bonds (1981)

An efficient method for covalently cross-linking 50K Fab' antibody fragments to the surface of lipid vesicles is reported. Coupling up to 600 microgram of Fab'/mumol of phospholipid (about 6000 Fab' molecules per 0.2-micrometer vesicle) is achieved via a disulfide interchange reaction between the thiol group exposed on each Fab' fragment and a pyridyldithio-derivative of phosphatidylethanolamine present in low concentration in the membranes of preformed large unilamellar vesicles. The coupling reaction is efficient, proceeds rapidly under mild conditions, and yields well-defined products. Each vesicle-linked Fab' fragment retains its original antigenic specificity and full capacity to bind antigen. We have used Fab' fragments, coupled to vesicles by this method, to achieve immunospecific targeting of liposomes to cells in vitro. Vesicles bearing antihuman erythrocyte Fab' fragments bind quantitatively to human erythrocytes (at multiplicities up to 5000 0.2-micrometer vesicles per cell) while essentially no binding is observed to sheep or ox red blood cells. Vesicle-cell binding is stable over a pH range from 6 to 8 and is virtually unaffected by the presence of human serum (50%). Cell-bound vesicles retain their aqueous contents and can be eluted intact from cells by treatment with reducing agents (dithiothreitol or mercaptoethanol) at alkaline pH.
Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome (2003)

We report here 7 new mutations in the ADAMTS13 gene responsible for Upshaw-Schulman syndrome (USS), a catastrophic phenotype of congenital thrombotic thrombocytopenic purpura, by analyzing 5 Japanese families. There were 3 mutations that occurred at exon-intron boundaries: 414+1G>A at intron 4, 686+1G>A at intron 6, and 1244+2T>G at intron 10 (numbered from the A of the initiation Met codon), and we confirmed that 2 of these mutations produced aberrantly spliced messenger RNAs (mRNAs). The remaining 4 mutations were missense mutations: R193W, I673F, C908Y, and R1123C. In expression experiments using HeLa cells, all mutants showed no or a marginal secretion of ADAMTS13. Taken together with the findings in our recent report we determined the responsible mutations in a total of 7 Japanese patients with USS with a uniform clinical picture of severe neonatal hyperbilirubinemia, and in their family members, based on ADAMTS13 gene analysis. Of these patients, 2 were homozygotes and 5 were compound heterozygotes. The parents of one homozygote were related (cousins), while those of the other were not. Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants.
Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. (1991)

We have examined at the molecular level the CDR3 and adjacent regions in peripheral blood B lymphocytes of normal individuals. A total of 111 sequences (12-28 sequences from six individuals) were obtained after cloning of the polymerase chain reaction-amplified segments into plasmids or phage. The average length of the VDJ joining was 109 nucleotides, with a range from 79 to 151. Approximately 75% of the sequences were in frame when translated into amino acids. Among the JH segments, JH4 was found most frequently (in 52.5% of the sequences), and JH1 and JH2 segments the least frequently (approximately 1% of the clones). A polymorphic JH6 gene with a one-codon deletion accompanied by a base change was present in two of six patients. Preferential breakpoints were found for JH2, JH3, JH4, and JH5, although the breakpoints of JH6 were distributed more heterogenously. In approximately 90% of the cases, significant homology of the D regions with published D sequences was found. Preferential usage of a particular coding frame was observed in in-frame sequences utilizing DA, D21/9, and DM1 segments. However, in general, all coding frames of germline D genes were used to generate CDR3s. Eight sequences that have a DN1-like D sequence with two base changes at the same positions were identified, suggesting the likely existence of a new germ line D gene belonging to the DN families. Using probes specific for a particular CDR3, the frequency of a specific B cell clone in the peripheral blood of normal individuals was estimated to be at most as high as 1/20,000.
Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. (1976)

Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells following incorporation of hematoporphyrin and exposure to red light. This photodynamic inactivation can be completely inhibited by intracellular 1,3-diphenylisobenzofuran. This very efficient singlet oxygen trap is not toxic to the cells nor does it absorb the light responsible for hematoporphyrin activation. We have found that the singlet oxygen-trapping product, o-dibenzoylbenzene, is formed nearly quantitatively intracellularly when both the furan and hematoporphyrin are present during illumination but not when only the furan is present during illumination. The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that singlet oxygen is the probable agent responsible for toxicity in this system.
The use of enhanced half‐life coagulation factor concentrates in routine clinical practice: guidance from UKHCDO (2016)

Enhanced half-life factor VIII and IX products are being introduced into routine clinical practice. Published data report on clinical trials and there are limited data available on how to use these products in routine clinical practice. Many patients, for example, those with a past history of an inhibitor, have been excluded from clinical trials and there are limited data published on children. This guidance document is a consensus statement from the UK Haemophilia Centres Doctors' Organisation and aims to give pragmatic advice on the use of these products in routine practice.
Application-layer anycasting: a server selection architecture and use in a replicated Web service (2000)

Server replication improves the ability of a service to handle a large number of clients. One of the important factors in the efficient utilization of replicated servers is the ability to direct client requests to the "best" server, according to some optimality criteria. In the anycasting communication paradigm, a sender communicates with a receiver chosen from an anycast group of equivalent receivers. As such, anycasting is well suited to the problem of directing clients to replicated servers. This paper examines the definition and support of the anycasting paradigm at the application-layer, providing a service that uses an anycast resolver to map an anycast domain name and a selection criteria into an IP address. By realizing anycasting in the application-layer, we achieve flexibility in the optimization criteria and ease the deployment of the service. As a case study, we examine the performance of our system for a key service: replicated Web servers. To this end, we develop an approach for estimating the response time that a client will experience when accessing given servers. Such information is maintained in the anycast resolver that clients query to obtain the identity of the server with the best estimated response time. Our performance collection technique combines server push with resolver probes to estimate the expected response time without undue overhead. Our experiments show that selecting a server using our architecture and estimation technique can improve the client response time by a factor of two over nearest server selection and by a factor of four over random server selection.
Integration of hardware into the LabVIEW environment for rapid prototyping and the development of control design applications (2004)

The paper explains how LabVIEW Real-Time and National Instruments (NI) real-time hardware targets can be used for the deployment of industrial control applications and the development of embedded control applications. LabVIEW Real-Time and NI real-time hardware targets, such as PXI, cRIO, FPGA and cFP, leverage the powerful graphical programming and measurement capabilities of LabVIEW for HIL applications. The LabVIEW platform approach gives seamless integration so that you can concentrate on solving your control design problems rather than having to spend time validating your results. For industrial control applications, LabVIEW Real-Time provides a single software development tool that can implement the functions of both traditional PLCs and PC-based control systems, thus acting as a programmable automation controller.
Intermittent Hypoxia Improves Endurance Performance and Submaximal Exercise Efficiency (2003)

The purpose of the present study was to elucidate the influence of intermittent hypobaric hypoxia at rest on endurance performance and cardiorespiratory and hematological adaptations in trained endurance athletes. Twelve trained male endurance runners were assigned to either a hypoxic group (n = 6) or a control group (n = 6). The subjects in the hypoxic group were exposed to a simulated altitude of 4500 m for 90 min, three times a week for 3 weeks. The measurements of 3000 m running time, running time to exhaustion, and cardiorespiratory parameters during maximal exercise test and resting hematological status were performed before (Pre) and after 3 weeks of intermittent hypoxic exposure (Post). These measurements were repeated after the cessation of intermittent hypoxia for 3 weeks (Re). In the control group, the same parameters were determined at Pre, Post, and Re for the subjects not exposed to intermittent hypoxia. The athletes in both groups continued their normal training together at sea level throughout the experiment. In the hypoxic group, the 3000 m running time and running time to exhaustion during maximal exercise test improved. Neither cardiorespiratory parameters to maximal exercise nor resting hematological parameters were changed in either group at Post, whereas oxygen uptake (.V(O2)) during submaximal exercise decreased significantly in the hypoxic group. After cessation of intermittent hypoxia for 3 weeks, the improved 3000 m running time and running time to exhaustion tended to decline, and the decreased .V(O2) during submaximal exercise returned to Pre level. These results suggest that intermittent hypoxia at rest could improve endurance performance and submaximal exercise efficiency at sea level in trained endurance athletes, but these improvements are not maintained after the cessation of intermittent hypoxia for 3 weeks.
Loss of imprinting of a paternally expressed transcript, with antisense orientation to K V LQT1, occurs frequently in Beckwith–Wiedemann syndrome and is independent of insulin-like growth factor II imprinting (1999)

Genomic imprinting plays a fundamental role in cancer and some hereditary diseases, including Beckwith-Wiedemann syndrome (BWS), a disorder of prenatal overgrowth and predisposition to embryonal malignancies such as Wilms tumor. We have previously shown that the KVLQT1 gene on chromosomal band 11p15 is imprinted, with expression of the maternal allele, and that the maternal allele is disrupted in rare BWS patients with balanced germ-line chromosomal rearrangements. We now show that an antisense orientation transcript within KVLQT1, termed LIT1 (long QT intronic transcript 1) is expressed normally from the paternal allele, from which KVLQT1 transcription is silent, and that in the majority of patients with BWS, LIT1 is abnormally expressed from both the paternal and maternal alleles. Eight of sixteen informative BWS patients (50%) showed biallelic expression, i.e., loss of imprinting (LOI) of LIT1. Similarly, 21 of 36 (58%) BWS patients showed loss of maternal allele-specific methylation of a CpG island upstream of LIT1. Surprisingly, LOI of LIT1 was not linked to LOI of insulin-like growth factor II (IGF2), which was found in 2 of 10 (20%) BWS patients, even though LOI of IGF2 occurs frequently in Wilms and other tumors, and in some patients with BWS. Thus, LOI of LIT1 is the most common genetic alteration in BWS. We propose that 11p15 harbors two imprinted gene domains-a more centromeric domain including KVLQT1 and p57(KIP2), alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterations in which are more common in cancer.
Inspiration from the mirror: D-amino acid containing peptides in biomedical approaches (2016)

Abstract D-amino acids, the enantiomers of naturally abundant L-amino acids, bear unique stereochemistry properties that lead to the resistance towards most of the endogenous enzymes. Previous works have demonstrated applications of D-amino acids in therapeutic development with the aid of mirror-image phage display and retro-inverso peptide synthesis. In this review, we highlight the recent progress and challenges in the exploration of D-amino acids at the interface of chemistry and life science. First, we will introduce some progress made in traditional application of D-amino acids to enhance biostability of peptide therapeutics. Then, we discuss some works that explore the relatively underexplored interactions between the enzyme and D-amino acids and enzymatic reactions of D-amino acids. To highlight the enzymatic reactions of D-amino acids, we will describe several emerging works on the enzyme-instructed self-assembly (EISA) and their potential application in selective anti-inflammatory or anticancer therapies. At the end, we briefly mention the challenges and possible future directions.
A new method for speech denoising and robust speech recognition using probabilistic models for clean speech and for noise (2001)

We present a new method for speech denoising and robust speech recognition. Using the framework of probabilistic models allows us to integrate detailed speech models and models of realistic non-stationary noise signals in a principled manner. The framework transforms the denoising problem into a problem of Bayes-optimal signal estimation, producing minimum mean square error estimators of desired features of clean speech from noisy data. We describe a fast and efficient implementation of an algorithm that computes these estimators. The effectiveness of this algorithm is demonstrated in robust speech recognition experiments, using the Wall Street Journal speech corpus and Microsoft Whisper large-vocabulary continuous speech recognizer. Results show significantly lower word error rates than those under noisy-matched condition. In particular, when the denoising algorithm is applied to the noisy training data and subsequently the recognizer is retrained, very low error rates are obtained.
The Chemical Biology of Aptamers (2009)

Aptamers are small single-stranded nucleic acids that fold into a well-defined three-dimensional structure. They show a high affinity and specificity for their target molecules and inhibit their biological functions. Aptamers belong to the nucleic acids family and can be synthesized by chemical or enzymatic procedures, or a combination of the two. They can, therefore, be considered as both chemical and biological substances. This Review summarizes the most convenient approaches to their preparation and new developments in the field of aptamers. The application of aptamers in chemical biology is also discussed.
CD38 Disruption Impairs Glucose-induced Increases in Cyclic ADP-ribose, [Ca2+] , and Insulin Secretion (1999)

Increases in [Ca2+]i in pancreatic beta cells, resulting from Ca2+ mobilization from intracellular stores as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated in beta cells by glucose stimulation, has been postulated to serve as a second messenger for intracellular Ca2+ mobilization for insulin secretion, and CD38 is thought to be involved in the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here we created "knockout" (CD38(-/-)) mice by homologous recombination. CD38(-/-) mice developed normally but showed no increase in their glucose-induced production of cADPR in pancreatic islets. The glucose-induced [Ca2+]i rise and insulin secretion were both severely impaired in CD38(-/-) islets, whereas CD38(-/-) islets responded normally to the extracellular Ca2+ influx stimulants tolbutamide and KCl. CD38(-/-) mice showed impaired glucose tolerance, and the serum insulin level was lower than control, and these impaired phenotypes were rescued by beta cell-specific expression of CD38 cDNA. These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion.
Extraction of peak-to-peak and RMS sinusoidal jitter using an analytic signal method (2002)

This paper proposes a new method based on analytic signal theory for extracting both instantaneous and RMS sinusoidal jitter from PLL output signals. The method relies on the extension of a real signal into an analytic signal by utilizing the Hilbert transform. Both the theoretical basis and fundamental concepts of the proposed method are explained. A review of conventional testing methods is also presented. Results of Matlab simulations validate the performance of the proposed method for measuring random jitter. The method is further validated by comparing experimental sinusoidal jitter results with those measured with a time interval analyzer.
Δ 12 -Prostaglandin J 2 Is a Potent Inhibitor of Influenza A Virus Replication (2000)

9-Deoxy-Delta(9),Delta(12)-13,14-dihydro-prostaglandin D(2) (Delta(12)-PGJ(2)), a natural cyclopentenone metabolite of prostaglandin D(2), is shown to possess therapeutic efficacy against influenza A virus A/PR8/34 (H1N1) infection in vitro and in vivo. The results indicate that the antiviral activity is associated with induction of cytoprotective heat shock proteins and suggest novel strategies for treatment of influenza virus infection.
Genome Sequence of the Plant Growth Promoting Endophytic Bacterium Enterobacter sp. 638 (2010)

Enterobacter sp. 638 is an endophytic plant growth promoting gamma-proteobacterium that was isolated from the stem of poplar (Populus trichocarpaxdeltoides cv. H11-11), a potentially important biofuel feed stock plant. The Enterobacter sp. 638 genome sequence reveals the presence of a 4,518,712 bp chromosome and a 157,749 bp plasmid (pENT638-1). Genome annotation and comparative genomics allowed the identification of an extended set of genes specific to the plant niche adaptation of this bacterium. This includes genes that code for putative proteins involved in survival in the rhizosphere (to cope with oxidative stress or uptake of nutrients released by plant roots), root adhesion (pili, adhesion, hemagglutinin, cellulose biosynthesis), colonization/establishment inside the plant (chemiotaxis, flagella, cellobiose phosphorylase), plant protection against fungal and bacterial infections (siderophore production and synthesis of the antimicrobial compounds 4-hydroxybenzoate and 2-phenylethanol), and improved poplar growth and development through the production of the phytohormones indole acetic acid, acetoin, and 2,3-butanediol. Metabolite analysis confirmed by quantitative RT-PCR showed that, the production of acetoin and 2,3-butanediol is induced by the presence of sucrose in the growth medium. Interestingly, both the genetic determinants required for sucrose metabolism and the synthesis of acetoin and 2,3-butanediol are clustered on a genomic island. These findings point to a close interaction between Enterobacter sp. 638 and its poplar host, where the availability of sucrose, a major plant sugar, affects the synthesis of plant growth promoting phytohormones by the endophytic bacterium. The availability of the genome sequence, combined with metabolome and transcriptome analysis, will provide a better understanding of the synergistic interactions between poplar and its growth promoting endophyte Enterobacter sp. 638. This information can be further exploited to improve establishment and sustainable production of poplar as an energy feedstock on marginal, non-agricultural soils using endophytic bacteria as growth promoting agents.
On the switch architecture for fibre channel storage area networks (2002)

The fast growth of data intensive applications has caused a change in the traditional storage model. The server-to-disk approach is being replaced by storage area networks (SANs), which enable storage to be externalized from servers, thus allowing storage devices to be shared among multiple servers. Nowadays, the majority of SANs use fibre channel. The standard for fibre channel defines several issues related to the switch interface, but does not make any suggestion about the internal switch architecture to be implemented by manufacturers. We analyze the key architectural switch characteristics for building fibre channel storage area networks. To do so, our starting point is the performance analysis of two different switch architectures, identifying their strongest and weakest points, and thus taking advantage of the best features from both of them. After this first analysis, we introduce several other features in the switch, concluding with a proposed architecture that doubles network throughput while reducing response delay.
Magnetism from conductors and enhanced nonlinear phenomena (1999)

We show that microstructures built from nonmagnetic conducting sheets exhibit an effective magnetic permeability /spl mu//sub eff/, which can be tuned to values not accessible in naturally occurring materials, including large imaginary components of /spl mu//sub eff/. The microstructure is on a scale much less than the wavelength of radiation, is not resolved by incident microwaves, and uses a very low density of metal so that structures can be extremely lightweight. Most of the structures are resonant due to internal capacitance and inductance, and resonant enhancement combined with compression of electrical energy into a very small volume greatly enhances the energy density at critical locations in the structure, easily by factors of a million and possibly by much more. Weakly nonlinear materials placed at these critical locations will show greatly enhanced effects raising the possibility of manufacturing active structures whose properties can be switched at will between many states.
Handbook of Thin Film Deposition Techniques Principles, Methods, Equipment and Applications, Second Editon (2002)

The Handbook of Thin Film Deposition Techniques: Principles, Methods, Equipment and Applications, Second Edition explores the technology behind the spectacular growth in the silicon semiconductor industry and the continued trend in miniaturization over the last 20 years. This growth has been fueled in large part by improved thin film deposition tec