gebhart/patrepeval huggingface dataset:
A first-in-human, first-in-class phase I trial of the anti-CD47 antibody Hu5F9-G4 in patients with advanced cancers. (2016)

3019 Background: Hu5F9-G4 is a humanized monoclonal antibody that binds to CD47 and blocks its anti-phagocytic “don’t-eat-me” signal, leading to tumor phagocytosis and cross-presentation to T cells. CD47 is highly expressed on red blood cells (RBCs) and many human cancers, and less on normal tissues. Inhibition of CD47-SIRPα signaling by Hu5F9-G4 has broad antitumor activity in human tumor xenografts. In primate toxicology, Hu5F9-G4 caused a transient anemia that was mitigated by a single low Priming Dose enabling subsequent higher Maintenance Doses. Methods: Adults with solid tumors were enrolled in this two part dose-escalation study: Part A to determine the optimal Priming Dose and Part B to determine the optimal Maintenance Dose. Primary objectives were to assess safety and tolerability; secondary objectives were to assess PK and pharmacodynamics (PD). CD47 receptor occupancy was evaluated as a PD marker on peripheral blood RBCs. Results: To date, 16 patients have been enrolled, 11 in Part A and 5 in Part B. In Part A, 0.1, 0.3, and 1 mg/kg doses were well-tolerated. 2/2 pts at 3 mg/kg had G3 DLTs: G3 abdominal pain; and G1 RBC hemagglutination [H] with G2 headache. The 1 mg/kg dose resulted in a mean RBC CD47 receptor occupancy of 91% ± 3% [95% CI 86 – 93%], indicating target saturation with no G3 anemia, and was selected as the Priming Dose. In Part B, the 1 mg/kg Priming Dose followed by 3 mg/kg Maintenance Dose was well tolerated. The study is ongoing with the current cohort at 1 mg/kg followed by 10 mg/kg weekly. Hu5F9-G4-related AEs include anemia (11 G1, 5 G2), hyperbilirubinemia (5 G1, 3 G2, 1 G3), headache (9 G1, 1 G2), H on peripheral blood smears (9 G1), nausea (3 G1), and retinal toxicity on serial retinal imaging (1 G2 cotton wool spot). Most adverse events were associated with the Priming Dose and were reversible. Mean peak Cmax levels were 78 ± 32 μg/mL on the 3 mg/kg Maintenance Dose. Two patients (adenoid cystic ca) receiving weekly doses in Part A (0.1 mg/kg and 1 mg/kg) had stable disease for 16 and 8 months on continuous weekly drug dosing, respectively. Conclusions: Hu5F9-G4 was well tolerated at 3 mg/kg weekly, with a 1 mg/kg Priming Dose. No G3 anemia has occurred. Testing of higher Maintenance Doses is ongoing. Clinical trial information: NCT02216409.
Gene therapy for ocular angiogenesis (2003)

Ocular neovascularization is a central feature of diabetic retinopathy and age-related macular degeneration. These conditions are the major causes of blindness in the developed world. Current treatments are of limited efficacy and associated with significant adverse effects. Characterization of the molecular and cellular events involved in angiogenesis has led to the identification of a number of angiostatic molecules with potential therapeutic value. The systemic administration of small molecule angiostatic proteins risks significant systemic adverse effects and the effect of their intraocular injection is short-lived. Local gene transfer, however, offers the possibility of targeted, sustained and regulatable delivery of angiostatic proteins to the retina after a single procedure to introduce a vector to an intraocular site. The effect of intra-ocular delivery of recombinant viruses carrying genes encoding angiostatic proteins has been demonstrated in rodent models of ocular neovascularization. Recombinant adeno-associated virus-mediated local gene transfer of a vascular endothelial growth factor inhibitor controls both retinal and choroidal neovascularization. The clinical application of this approach may require the means to regulate gene expression in order to minimize the potential for adverse effects. Regulation of transgene expression by means of a hypoxia-responsive promoter offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of ischaemia-induced ocular neovascularization. Preclinical studies of gene transfer in a large animal model following subretinal delivery of a recombinant adeno-associated virus vector have demonstrated efficient sustained reporter gene expression in cells of the outer retina. Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascular disorders.
Membranes in Clean Technologies: Theory and Practice (2008)

Development of Clean Technology Concept ENGINEERING OF MEMBRANE PROCESSES Theory of Membrane Separation Processes Membranes Membrane Processes MEMBRANES IN CLEAN INDUSTRY Water Industry Textile Industry Tannery Industry Paper Industry Metal Plating Industry Electronic Industry Pharmaceutical Industry Food Industry MATERIALS IN MANAGEMENT WITH MEMBRANES - SEPARATION OF METALS, ACIDS, AND HYDROCARBONS Metals Separation Acids Separation Hydrocarbon Separations Membrane Selection Chart Symbols
The Transcriptional Program of Sporulation in Budding Yeast (1998)

Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis. DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation. At least seven distinct temporal patterns of induction were observed. The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase. Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes. The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis.
The effect of heat setting on the structure and mechanical properties of poly(ethylene terephthalate) fiber. III. Anelastic properties and their dependence on structure (1981)

Abstract Viscoelastic parameters for poly(ethylene terephthalate) (PET) fibers heat set under different conditions were determined at 110 Hz between room temperature and about 200°C. The correlation of dynamic mechanical properties with structure and their dependence on the temperature of the measurement are discussed. It was found that in addition to the structural parameters such as degree of crystallinity, crystallite and amorphous orientation, etc., morphological factors such as size and distribution of crystallites also influence the dynamic mechanical properties. The activation energy of the α‐transition is reported, and the effect of the distribution of relaxation times on the activation energy is discussed.
Chronic pruritus – pathogenesis, clinical aspects and treatment (2010)

Chronic pruritus is a major symptom in numerous dermatological and systemic diseases. Similar to chronic pain, chronic pruritus can have a dramatic impact on the quality of life and can worsen the general condition of the patient considerably. The pathogenesis of itch is diverse and involves a complex network of cutaneous and neuronal cells. In recent years, more and more itch-specific mediators and receptors, such as interleukin-31, gastrin-releasing peptide receptor or histamine H4 receptor have been identified and the concept of itch-specific neurons has been further characterized. Understanding of the basic principles is important for development of target-specific treatment of patients with chronic pruritus. In this review, we summarize the current knowledge about the pathophysiological principles of itch and provide an overview about current and future treatment options.
The Biochemical and Molecular Basis for the Divergent Patterns in the Biosynthesis of Terpenes and Phenylpropenes in the Peltate Glands of Three Cultivars of Basil (2004)

Surface glandular trichomes distributed throughout the aerial parts of sweet basil (Ocimum basilicum) produce and store monoterpene, sesquiterpene, and phenylpropene volatiles. Three distinct basil chemotypes were used to examine the molecular mechanisms underlying the divergence in their monoterpene and sesquiterpene content. The relative levels of specific terpenes in the glandular trichomes of each cultivar were correlated with the levels of transcripts for eight genes encoding distinct terpene synthases. In a cultivar that produces mostly (R)-linalool, transcripts of (R)-linalool synthase (LIS) were the most abundant of these eight. In a cultivar that synthesizes mostly geraniol, transcripts of geraniol synthase were the most abundant, but the glands of this cultivar also contained a transcript of an (R)-LIS gene with a 1-base insertion that caused a frameshift mutation. A geraniol synthase-LIS hybrid gene was constructed and expressed in Escherichia coli, and the protein catalyzed the formation of both geraniol and (R)-linalool from geranyl diphosphate. The total amounts of terpenes were correlated with total levels of terpene synthase activities, and negatively correlated with levels of phenylpropanoids and phenylalanine ammonia lyase activity. The relative levels of geranyl diphosphate synthase and farnesyl diphosphate synthase activities did not correlate with the total amount of terpenes produced, but showed some correlation with the ratio of monoterpenes to sesquiterpenes.
The Effect of 25-Hydroxy Vitamin D3 in the Osteomalacia of Chronic Renal Failure (1977)

1. Five patients with the osteomalacia of chronic renal failure were given 50--100 nmol of 25-hydroxy vitamin D3 intravenously per day for 24--28 days. 2. In all five patients, during administration of 25-hydroxy vitamin D3 there was a substantial rise in the plasma concentration of 25-hydroxy vitamin D from initially abnormally low values. 3. Significant improvement in bone mineralization, intestinal calcium absorption and muscle strength occurred in the three patients with the greatest rise in plasma 25-hydroxy vitamin D.
Small CRISPR RNAs Guide Antiviral Defense in Prokaryotes (2008)

Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
3D machine vision system for inspection of contact strips in railway vehicle current collectors (2014)

Construction and technical condition of current collectors is crucial to reliability and safety of railway transportation. According to the Technical Specifications for Interoperability railway vehicles in the European Union should be equipped with carbon contact strips. Excessive wear or defects of contact strips degrade the capability of undisturbed power transmission, cause faster wear of contact wire, and can even result in catenary rupture. The technical condition of contact strips is assessed manually during periodical services performed by rolling stock operators. However, rail infrastructure companies are also interested in pantographs inspection of the vehicles running within their network. A novel inspection system for current collectors contact strips is presented. The system uses a specialized camera and a laser line generator to scan the contact strips surface. The scanning is performed on a railway line, when a vehicle passes the inspection point. A prototype of the system was tested in the target conditions and sample scanning results were recorded. Basic algorithms for automatic analysis of contact strips wear were introduced. Accuracy and repeatability of the measurement were assessed. The potential of commercial implementation of the system was confirmed.
Data transfer performance issues for a web services interface to synchrotron experiments (2007)

The Common Instrument Middleware Architecture (CIMA) defines a web services interface to scientific instruments. We have been experimenting with the use of CIMA web services for remote monitoring of synchrotron experiments and real-time data download, processing and storage. Here we discuss some performance issues with data transfer using CIMA web services, particularly for long-distance, high-latency transfers. We explore alternative approaches for improving the performance and robustness of data transfer with CIMA, and provide some experimental results.
An asynchronous multiuser CDMA detector based on the Kalman filter (1998)

We introduce a multiuser receiver based on the Kalman filter, which can be used for joint symbol detection and channel estimation. The proposed algorithm has the advantage of working even when the spreading codes used have a period larger than one symbol interval ("long codes"), unlike adaptive equalizer-type detectors. Simulation results which demonstrate the performance advantage of the proposed receiver over the conventional detector, the minimum mean squared error (MMSE) detector and a recursive least squares (RLS) multiuser detector are presented. A thorough comparison of the MMSE detector and the proposed detector is attempted because the Kalman filter also solves the MMSE parameter estimation problem, and it is concluded that, because the state space model assumed by the Kalman filter fits the code division multiple access (CDMA) system exactly, a multiuser detector based on the Kalman filter must necessarily perform better than a nonrecursive, finite-length MMSE detector. The computational complexity of the detector and its use in channel estimation are also studied.
TNFα—A PIVOTAL ROLE IN RHEUMATOID ARTHRITIS? (1992)

This review seeks to describe data which support the concept that TNFα has a pivotal role in the pathogenesis of RA. There is now compelling evidence from in vitro studies and in animal models that this is the case. The in vitro studies suggest that the direct pathogenic effects of TNFα are amplified by its potential to act as a potent paracrine molecule, by inducing other pro-inflammatory molecules such as IL-1, and GM-CSF. It has yet to be established whether similar paracine effects of TNF-α are observed in the collagen type II mouse, or in human TNFα transgenic mice, where (as discussed in this review), TNFα undoubtedly has a pathogenic involvement. During the ongoing inflammation in RA, TNFα (and other mediators?) induce the production of soluble TNF-R which can act as natural inhibitors. This process is, however, inadequate within the inflamed synovium, due to the fact that cytokine interactions are very local, through autocrine and paracrine mechanisms. In this environment there is a continuous competition between the interactions of surface or soluble receptor with TNFα. It may well be that soluble TNF-Rs play a more important role in the periphery where they act as an essential clearance mechanism for the ligand. If, as the available data suggest, TNFα does indeed have a pivotal role in the pathogenesis of RA, this needs to be verified by demonstrating that removal of TNFα locally in the synovial joint of RA patients has a significant effect on clinical parameters of disease, and the progression of the disease process itself.
Studies on Streptomyces Antibiotic, Cycloheximide. XVI. Synthesis of Cycloheximide Analogous Compounds. (1963)

By condensing aliphatic and alicyclic ketones with glutarimide-β-acetaldehyde, several cycloheximide analogous compounds listed in Table I were synthesized. The paper also dealt with improved synthesis of glutarimide-β-acetaldehyde.
A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agents (2006)

In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-kappaB activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.
A novel, high-performance random array platform for quantitative gene expression profiling (2004)

We have developed a new microarray technology for quantitative gene-expression profiling on the basis of randomly assembled arrays of beads. Each bead carries a gene-specific probe sequence. There are multiple copies of each sequence-specific bead in an array, which contributes to measurement precision and reliability. We optimized the system for specific and sensitive analysis of mammalian RNA, and using RNA controls of defined concentration, obtained the following estimates of system performance: specificity of 1:250,000 in mammalian poly(A(+)) mRNA; limit of detection 0.13 pM; dynamic range 3.2 logs; and sufficient precision to detect 1.3-fold differences with 95% confidence within the dynamic range. Measurements of expression differences between human brain and liver were validated by concordance with quantitative real-time PCR (R(2) = 0.98 for log-transformed ratios, and slope of the best-fit line = 1.04, for 20 genes). Quantitative performance was further verified using a mouse B- and T-cell model system. We found published reports of B- or T-cell-specific expression for 42 of 59 genes that showed the greatest differential expression between B- and T-cells in our system. All of the literature observations were concordant with our results. Our experiments were carried out on a 96-array matrix system that requires only 100 ng of input RNA and uses standard microtiter plates to process samples in parallel. Our technology has advantages for analyzing multiple samples, is scalable to all known genes in a genome, and is flexible, allowing the use of standard or custom probes in an array.
Conditional Random Fields: Probabilistic Models for Segmenting and Labeling Sequence Data (2001)

We present Conditional Random Fields, a framework&#13;\nfor building probabilistic models to segment&#13;\nand label sequence data. Conditional random&#13;\nfields offer several advantages over hidden&#13;\nMarkov models and stochastic grammars&#13;\nfor such tasks, including the ability to relax&#13;\nstrong independence assumptions made in those&#13;\nmodels. Conditional random fields also avoid&#13;\na fundamental limitation of maximum entropy&#13;\nMarkov models (MEMMs) and other discriminative&#13;\nMarkov models based on directed graphical&#13;\nmodels, which can be biased towards states&#13;\nwith few successor states. We present iterative&#13;\nparameter estimation algorithms for conditional&#13;\nrandom fields and compare the performance of&#13;\nthe resulting models to HMMs and MEMMs on&#13;\nsynthetic and natural-language data.
MBT Timing Detection and its Closed-Loop Control Using In-Cylinder Pressure Signal (2003)

&lt;div class="htmlview paragraph"&gt;MBT timing for an internal combustion engine is also called minimum spark timing for best torque or the spark timing for maximum brake torque. Unless engine spark timing is limited by engine knock or emission requirements at a certain operational condition, there exists an MBT timing that yields the maximum work for a given air-to-fuel mixture. Traditionally, MBT timing for a particular engine is determined by conducting a spark sweep process that requires a substantial amount of time to obtain an MBT calibration. Recently, on-line MBT timing detection schemes have been proposed based upon cylinder pressure or ionization signals using peak cylinder pressure location, 50 percent fuel mass fraction burn location, pressure ratio, and so on. Because these criteria are solely based upon data correlation and observation, both of them may change at different engine operational conditions. Therefore, calibration is still required for each MBT detection scheme. This paper shows that MBT timing can be achieved by locating the maximum net pressure acceleration point at top dead center. This result is developed based upon the physical aspects of the combustion process, and therefore, it should be independent of engine operational conditions and valid for all spark-ignited engines that have one peak heat release rate during the combustion process. Experimental validation of this result over certain engine operational conditions is completed, and validation of this result over whole engine operational map is the subject of future work.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The second part of this paper develops an MBT timing closed-loop control using the detected MBT timing criteria as a feedback signal. The benefit of closed loop control of MBT timing is improved robustness over open-loop MBT timing calibration with respect to engine-to-engine variations, engine aging, engine operational conditions, etc. A two-way filtering algorithm, combined with the derivative calculation, is developed to improve the robustness of MBT timing detection scheme without the penalty of filter phase delay. A PI (proportional and integral) controller is used to illustrate closed-loop control of MBT timing, where the reference signal is used to control the engine ignition timing at its set point. The closed-loop control system is implemented in dSpace and prototyped on a two liter four cylinder engine. The test results show that the closed-loop MBT timing controller based upon the maximum net pressure acceleration point not only maintains the engine average ignition timing at its MBT timing but also reduces the cycle-to-cycle variations. For comparison purpose, three MBT timing feedback signals are used in the study: peak cylinder pressure location, 50 percent burn location, and maximum net pressure acceleration location.&lt;/div&gt;
Elevations of Inflammatory and Procoagulant Biomarkers in Elderly Persons With Renal Insufficiency (2003)

Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.