gebhart/patrepeval huggingface dataset:
A single-molecule characterization of p53 search on DNA (2010)

The tumor suppressor p53 slides along DNA while searching for its cognate site. Central to this process is the basic C-terminal domain, whose regulatory role and its coordination with the core DNA-binding domain is highly debated. Here we use single-molecule techniques to characterize the search process and disentangle the roles played by these two DNA-binding domains in the search process. We demonstrate that the C-terminal domain is capable of rapid translocation, while the core domain is unable to slide and instead hops along DNA. These findings are integrated into a model, in which the C-terminal domain mediates fast sliding of p53, while the core domain samples DNA by frequent dissociation and reassociation, allowing for rapid scanning of long DNA regions. The model further proposes how modifications of the C-terminal domain can activate "latent" p53 and reconciles seemingly contradictory data on the action of different domains and their coordination.
Progress towards the treatment of Ebola haemorrhagic fever (2006)

Being highly pathogenic for human and nonhuman primates and the subject of former weapon programmes makes Ebola virus one of the most feared pathogens worldwide today. Due to a lack of licensed pre- and postexposure intervention, the current response depends on rapid diagnostics, proper isolation procedures and supportive care of case patients. Consequently, the development of more specific countermeasures is of high priority for the preparedness of many nations. Over the past years, enhanced research efforts directed to better understand virus replication and pathogenesis have identified potential new targets for intervention strategies. The authors discuss the most promising therapeutic approaches for Ebola haemorrhagic fever as judged by their efficacy in animal models. The current development in this field encourages discussions on how to move some of the experimental approaches towards clinical application.
Naproxen suppositories in combination with oral naproxen, indomethacin and ibuprofen in the treatment of rheumatoid arthritis (1980)

A single-blind, crossover trial was carried out in 30 rheumatoid arthritis patients to compare the effectiveness and tolerance of 250 mg naproxen, 400 mg ibuprofen and 25 mg indomethacin twice daily in patients treated concurrently with a night-time 500 mg naproxen suppository. Each day-time drug was given for 3 weeks. Naproxen suppositories were used for the whole 9 weeks of the study. No difference between the combination treatments was seen in pain and morning stiffness, while articular index and P.I.P. joint size tended to improve most during the naproxen tablet and suppository phase. Patients' and physician's preferences were both significantly in favour of the naproxen tablet and suppository phase. Side-effects were similar during all treatment phases, except for vertigo which occurred during the indomethacin capsule and naproxen suppository phase. Combinations of two non-steroidal, anti-inflammatory drugs have been shown to be effective and well tolerated but to have no advantage over treatment with only one drug. Naproxen suppositories have been shown to be well tolerated over a 9-week period.
The HARPY speech recognition system (1976)

Abstract : The Harpy connected speech recognition system is the result of an attempt to understand the relative importance of various design choices of two earlier speech recognition systems developed at Carnegie-Mellon University: The Hearsay-1 system and the Dragon system. Knowledge is represented in the Hearsay- 1 system as procedures and in the Dragon system as a Markov network with a- priori transition probabilities between states. Systematic performance analysis of various design choices of these two systems resulted in the HARPY system, in which knowledge is represented as a finite state transition network but without the a-priori transition probabilities. Harpy searches only a few 'best' syntactic (and acoustic) paths in parallel to determine the optimal path, and uses segmentation to effectively reduce the utterance length, thereby reducing the number of state probability updates that must be done. Several new heuristics have been added to the HARPY system to improve its performance and speed: detection of common sub-nets and collapsing them to reduce overall network size and complexity, eliminating the need for doing an acoustic match for all phonemic types at every time sample, and semi-automatic techniques for learning the lexical representations (that are needed for a steady-state system of this type) and the phonemic templates from training data, thus automatically accounting for the commonly occurring intra-word coarticulation and juncture phenomena. Inter-word phenomena are handled by the use of juncture rules which are applied at network generation time, thereby eliminating the need for repetitive and time consuming application of phonological rules during the recognition phase.
Monotreme Tactile Mechanisms: From Sensory Nerves to Cerebral Cortex (2004)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Detection of Ureaplasma urealyticum by Polymerase Chain Reaction in the Urogenital Tract of Adults, in Amniotic Fluid, and in the Respiratory Tract of Newborns (1993)

On the basis of the nucleotide sequence of the urease genes of Ureaplasma urealyticum serotype 8, polymerase chain reaction (PCR) primers were selected, evaluated for specificity and sensitivity, and tested for their ability to detect U. urealyticum in the adult urogenital tract, amniotic fluid, and endotracheal aspirates of newborns. All 14 reference serotypes of U. urealyticum were detected with equal sensitivity (1-10 cfu), whereas multiple strains of 12 other mycoplasma species found in humans as well as eukaryotic DNA were not detected. A total of 638 clinical specimens was evaluated. Results indicate that PCR is equal to if not more sensitive than culture for detection of U. urealyticum. Faster detection of U. urealyticum by PCR (< 24 h) compared to culture (2-5 days) will be particularly important in management of very low birth-weight infants in whom this organism has been shown to be a significant cause of meningitis, respiratory disease, and death. This method of detection will also be helpful in further determining the role of this organism in intraamniotic infection and premature birth.
Impaired ribosome biogenesis in Diamond-Blackfan anemia (2006)

The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits.
An Emerging Role for Ca2+/Calcineurin/NFAT Signaling in Cancerogenesis (2007)

The NFAT proteins are a family of Ca2+/calcineurin-responsive transcription factors primarily recognized for their central roles in T lymphocyte activation. Recent studies, however, have demonstrated that the vital role of NFAT signaling is by no means restricted to the immune system. NFAT proteins are potent mediators of Ca2+ signals in many mammalian cells and tissues and control, among others, important steps in myogenesis, chondrocyte differentiation and the development of the cardiovascular system. Owing to the broad spectrum of target genes and the fundamental nature of the cellular processes they control, it comes as no surprise that NFAT proteins are increasingly being recognized as central players in the development of a number of very different human malignancies.
Intravenous Ferric Carboxymaltose in Patients with Type 2 Diabetes Mellitus and Iron Deficiency: CLEVER Trial Study Design and Protocol (2017)

GWT-TUD GmbH acts as sponsor of the clinical trial. Financial support is provided by Vifor Pharma.
Surgical Manipulation of the Gut Elicits an Intestinal Muscularis Inflammatory Response Resulting in Postsurgical Ileus (1998)

The data support the hypothesis that the degree of gut paralysis to cholinergic stimulation is directly proportional to the degree of trauma, the activation of resident gut muscularis phagocytes, and the extent of cellular infiltration. Therefore, postsurgical ileus may be a result of an inflammatory response to minimal trauma in which the resident macrophages, activated by physical forces, set an inflammatory response into motion, leading to muscle dysfunction.
Improved delivery of radiolabeled anti-B1 monoclonal antibody to Raji lymphoma xenografts by predosing with unlabeled anti-B1 monoclonal antibody. (1992)

A human B-cell lymphoma xenograft model was used to test whether the administration of unlabeled MoAb prior to injection of radiolabeled monoclonal antibody (MoAb) improves delivery of the radiolabeled MoAb to tumor prior to testing in clinical radioimmunotherapy trials. The anti-B1/CD20 pan-B-cell MoAb reactive with human B-cell lymphomas and leukemias but not reactive with mouse B-cells was used in this study. Athymic nude mice bearing human Raji Burkitt lymphoma xenografts were given injections of 2.5 muCi (0.3 microgram) 131I-labeled anti-B1 with or without a 2-h prior single injection of 100 micrograms of unlabeled anti-B1 antibody. Four days later the animals given injections of 131I-labeled anti-B1 and the unlabeled anti-B1 predose had a tumor uptake of 12.72 +/- 1.17% (SEM) of injected dose/g which was 44% greater than the animals receiving the 131I-labeled anti-B1 alone (P = 0.014). The uptake in most normal tissues was unchanged, although the blood level of 131I-labeled anti-B1 appeared to be greater following unlabeled anti-B1 predosing (P = 0.067). Predosing with isotype matched irrelevant MoAb did not result in a greater tumor uptake or blood concentration of 131I-labeled anti-B1 compared to the administration of 131I-labeled anti-B1 alone. In studies using 111In-labeled anti-B1, the effect of unlabeled antibody predosing was more pronounced. For animals given injections of 4.5 muCi (0.4 microgram) 111In-labeled anti-B1 and the unlabeled anti-B1 predose, the uptake in tumor was 12.37 +/- 2.07% of injected dose/g which was 162% greater than the animals receiving the 111In-labeled anti-B1 alone (P = 0.009). Predosing decreased 111In-labeled anti-B1 uptake in spleen, while the blood level was significantly greater. Predosing was more effective than simultaneous injection in improving tumor delivery. When tumor-bearing mice were either simultaneously given injections of 36 micrograms of unlabeled anti-B1 and 4 micrograms 111In-labeled anti-B1 or were given preinjections of 36 micrograms unlabeled anti-B1 3 h prior to injection of 4 micrograms 111In-labeled anti-B1, tumor uptake 3 days later was 1.3-fold higher in the animals which received the preinjection of unlabeled antibody (P = 0.011). As the quantity of unlabeled anti-B1 was increased (36, 96, 996 micrograms) in the predose, significantly greater uptake in tumor was observed, although this uptake appeared to plateau at the highest predoses.(ABSTRACT TRUNCATED AT 400 WORDS)
An Extracellular Nuclease from Serratia marcescens (1969)

The specificity of an extracellular nuclease from Serratia marcescens was examined with both RNA and DNA as substrates. The enzyme was found to act in a predominantly endonucleolytic manner with less than 2% of the degradation products being mononucleotides. Both DNA and RNA were degraded to di-, tri-, and tetranucleotides terminating in 5'-phosphoryl ends. The enzyme had the unusual property of hydrolyzing both single-stranded and doublestranded DNA and RNA at similar rates. No base preference was exhibited at either the 5' or 3' end of the oligonucleotide fragments. When the S. marcescens nuclease was used in conjunction with venom phosphodiesterase, RNA and DNA were rapidly degraded to 5'-mononucleotides. The enzyme is thus potentially useful as a reagent for the study of polynucleotide structure and sequence.
Sliding window query processing over data streams (2006)

Database management systems (DBMSs) have been used successfully in traditional business applications that require persistent data storage and an efficient querying mechanism. Typically, it is assumed that the data are static, unless explicitly modified or deleted by a user or application. Database queries are executed when issued and their answers reflect the current state of the data. However, emerging applications, such as sensor networks, real-time Internet traffic analysis, and on-line financial trading, require support for processing of unbounded data streams. The fundamental assumption of a data stream management system (DSMS) is that new data are generated continually, making it infeasible to store a stream in its entirety. At best, a sliding window of recently arrived data may be maintained, meaning that old data must be removed as time goes on. Furthermore, as the contents of the sliding windows evolve over time, it makes sense for users to ask a query once and receive updated answers over time. &lt;br /&gt;&lt;br /&gt; This dissertation begins with the observation that the two fundamental requirements of a DSMS are dealing with transient (time-evolving) rather than static data and answering persistent rather than transient queries. One implication of the first requirement is that data maintenance costs have a significant effect on the performance of a DSMS. Additionally, traditional query processing algorithms must be re-engineered for the sliding window model because queries may need to re-process expired data and "undo" previously generated results. The second requirement suggests that a DSMS may execute a large number of persistent queries at the same time, therefore there exist opportunities for resource sharing among similar queries. &lt;br /&gt;&lt;br /&gt; The purpose of this dissertation is to develop solutions for efficient query processing over sliding windows by focusing on these two fundamental properties. In terms of the transient nature of streaming data, this dissertation is based upon the following insight. Although the data keep changing over time as the windows slide forward, the changes are not random; on the contrary, the inputs and outputs of a DSMS exhibit patterns in the way the data are inserted and deleted. It will be shown that the knowledge of these patterns leads to an understanding of the semantics of persistent queries, lower window maintenance costs, as well as novel query processing, query optimization, and concurrency control strategies. In the context of the persistent nature of DSMS queries, the insight behind the proposed solution is that various queries may need to be refreshed at different times, therefore synchronizing the refresh schedules of similar queries creates more opportunities for resource sharing.
Plant‐made oral vaccines against human infectious diseases—Are we there yet? (2015)

Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches.
High-Throughput Single-Molecule Spectroscopy in Free Solution (2000)

A high-speed high-throughput single-molecule imaging technique for identifying molecules in free solution based on differences in their fluorescence emission spectra is presented. Unlike previous reports, the entire spectrum, rather than selected wavelengths through optical filters, is recorded. Furthermore, the millisecond data acquisition time means that the molecules do not need to be immobilized or spatially confined. In one example, individual lambdaDNA molecules labeled with YOYO-I, POPO-III, or a combination of the two dyes can be distinguished from one another. In another example, biotinylated 2.1-kb DNA labeled with YOYO-I was reacted with avidin-conjugated R-phycoerythrin. The two different reactant molecules and the product molecule can be simultaneously imaged and identified by their spectroscopic characteristics. This technique can therefore be used for screening single molecules for disease markers and for monitoring individual molecular interactions at a rate of thousands of molecules per second.
Performance comparison of different encoding schemes in chaotic optical communication systems (2003)

This study aims to determine the best encryption technique to assure the security of transmitted information. The authors concentrate on three main encryption schemes: CSK (chaos shift keying), CMO (chaos modulation) and CMA (chaos masking). In CSK the message is encoded by switching the transmitter injected current between two states, CMO is based on the modulation of chaotic carrier generated by the transmitter laser and finally in CMA the encoding is achieved by adding the message to the chaotic transmitter output. This study also evaluates the efficiency of the masking and its dependence on the message amplitude and bit rate. The quality of the message recovery is investigated through the correlation coefficient technique. Particular attention is paid to the influence of the parameter mismatch between emitter and receiver.
Stochastic Models for Combined Security and Dependability Evaluation (2007)

Security is a topic of ever increasing interest. Today it is widely accepted that, due to the unavoidable presence of vulnerabilities, design faults and administrative errors, an ICT system will never be totally secure. Connecting a system to a network will necessarily introduce a risk of inappropriate access resulting in disclosure, corruption and/or loss of information. Therefore, the security of a system should ideally be interpreted in a probabilistic manner. More specifically, there is an urgent need for modelling methods that provide operational measures of the security. Dependability, on the other hand, is the ability of a computer system to deliver service that can justifiably be trusted. In a dependability context one distinguishes between accidental faults, which are modelled as random processes, and intentional faults, i.e., attacks, which in most cases are not considered at all. A major drawback of this approach is that attacks may in many cases be the dominating failure source for today’s networked systems. The classical way of dependability evaluation can therefore be very deceptive: highly dependable systems may in reality fail much more frequently than expected, due to the exploitation from attackers. To be considered trustworthy, a system must be both dependable and secure. However, these two aspects have so far tended to be treated separately. A unified modelling framework for security and dependability evaluation would be advantageous from both points of view. The security community can benefit from the mature dependability modelling techniques, which can provide the operational measures that are so desirable today. On the other hand, by adding hostile actions to the set of possible fault sources, the dependability community will be able to make more realistic models than the ones that are currently in use. This thesis proposes a stochastic modeling approach, which can be used to predict a system’s security and dependability behavior. As will be seen, the basic model has a number of possible applications. For example, it can be used as a tool for trade-off analysis of security countermeasures, or it can be used as a basis for real-time assessment of the system trustworthiness.