gebhart/patrepeval huggingface dataset:
Delayed internucleosomal DNA fragmentation in programmed cell death (1993)

DNA fragmentation was evaluated in three instances of programmed cell death, interdigital cell death in embryonic mouse limbs, and metamorphic death of both the labial glands and intersegmental muscle in the tobacco hornworm Manduca sexta. In the mouse, we evaluated both developmental cell death and expanded-range cell death induced by retinoic acid. The status of DNA was examined in several ways. Nuclei were examined by electron microscopy and Feulgen staining. Quantitative assessment of total DNA content in Feulgen-stained degenerating nuclei was made for the gland. In the labial gland, DNA content does not drop during the early phases of cell death; nor is an endonucleolytic ladder seen when DNA was examined by ethidium bromide staining or prelabeling with [3H]thymidine. Only by using end labeling of DNA could we detect DNA fragmentation at a very late stage in cell death, day 4 of the collapse of the gland. In contrast, WEHI 7.1 lymphoma cells display an early and extensive ladder after treatment with glucocorticoids. In mouse limb, for which cell death follows a more classic apoptotic morphology, a ladder is likewise not seen. We conclude that activation of an endonuclease is neither a trigger nor a necessary or defining component of the early phases of developmental programmed cell death, and that reported failure by others to find such a ladder may depend on limitations in the system that is under investigation.
Ballistocardiogaphic studies with acceleration and electromechanical film sensors (2009)

The purpose of this research is to demonstrate and compare the utilization of electromechanical film (EMFi) and two acceleration sensors, ADXL202 and MXA2500U, for ballistocardiographic (BCG) and pulse transit time (PTT) studies. We have constructed a mobile physiological measurement station including amplifiers and a data collection system to record the previously mentioned signals and an electrocardiogram signal. Various versions of the measuring systems used in BCG studies in the past are also presented and evaluated. We have showed the ability of the EMFi sensor to define the elastic properties of the cardiovascular system and to ensure the functionality of the proposed instrumentation in different physiological loading conditions, before and after exercise and sauna bath. The EMFi sensor provided a BCG signal of good quality in the study of the human heart and function of the cardiovascular system with different measurement configurations. EMFi BCG measurements provided accurate and repeatable results for the different components of the heart cycle. In multiple-channel EMFi measurements, the carotid and limb pulse signals acquired were detailed and distinctive, allowing accurate PTT measurements. Changes in blood pressure were clearly observed and easily determined with EMFi sensor strips in pulse wave velocity (PWV) measurements. In conclusion, the configuration of the constructed device provided reliable measurements of the electrocardiogram, BCG, heart sound, and carotid and ankle pulse wave signals. Attached EMFi sensor strips on the neck and limbs yield completely new applications of the EMFi sensors aside from the conventional seat and supine recordings. Higher sensitivity, ease of utilization, and minimum discomfort of the EMFi sensor compared with acceleration sensors strengthen the status of the EMFi sensor for accurate and reliable BCG and PWV measurements, providing novel evaluation of the elastic properties of the cardiovascular system.
Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica. (1994)

Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.
Untersuchungen über die Verwertung von Harnstoff beim Wiederkäuer (1972)

In einem über 75 Wochen geführten Versuch mit sechs Jungbullen der Rasse “Deutsche Schwarzbunte” wurden bei zweimaliger und achtmaliger Verabreichung einer konzentratreichen Trockenfutterration die Verdaulichkeit der Rohnährstoffe und die Verwertung hoher Harnstoff-N-Mengen (57% vom Gesamt-N der Ration, bis 216 g Harnstoff/Tier und Tag) im Vergleich zu Sojaeiweiß und einer eiweißarmen Ration geprüft. Der Rohproteingehalt der Rationen betrug im Mittel des Versuches: Sojagruppe: 18,84% in Trockensubstanz; Harnstoffgruppe: 18,94% in Trockensubstanz; Kontroll gruppe: 9,22% in Trockensubstanz. Rohnährstoff verdaulichkeit. Die Verdaulichkeit des Roheiweißes zeigte sich als abhängig von der Höhe der Roheiweißzufuhr. Die Verdaulichkeit der Rohfaser wurde durch Harnstoffeinsatz nicht verbessert. N-Stoffwechsel. In der Harnstoffgruppe wurde mit ca. 33 g/Tag im I. Versuchsabschnitt und mit ca. 46 g/Tag im II. Versuchsabschnitt die höchste N-Retention gefunden (Sojagruppe 26 g/Tag bzw. 40 g/Tag, Kontrollgruppe 20 g/Tag bzw. 27 g/Tag). Die Kontrollgruppe zeigte die beste Verwertung des verd. N mit 49%, im I. und 55% im II. Versuchsabschnitt (Sojagruppe 25% bzw. 31%, Harnstoffgruppe 31% bzw. 37%). In Soja- und Harnstoffgruppe konnte eine deutliche Verbesserung der Verwertung des verd. Stickstoffs in Abhängigkeit von der Fütterungshäufigkeit festgestellt werden.
Receptor Cell Habituation in the a1 Auditory Receptor of Four Noctuoid Moths (1998)

Moths of both sexes of Empyreuma affinis (=pugione) and Syntomeida epilais (Arctiidae, Ctenuchinae), Maenas jussiae (Arctiidae, Arctiinae) and Spodoptera frugiperda (Noctuidae, Amphipyrinae) were studied. Spike activity in the A1 cell was recorded using a stainless-steel hook electrode from the tympanic nerve in the mesothorax. Acoustic stimuli consisting of 25 and 100 ms pulses at the best frequency for the species and at intensities that evoke A1 cell saturation response were used at repetition rates of 0.5 and 5 Hz for 100 ms stimuli, and between 2 and 20 Hz for 25 ms stimuli. Stimuli at a repetition rate corresponding to a duty cycle of 5 % (25 ms at 2 Hz and 100 ms at 0.5 Hz) did not evoke monotonic changes in the responses of the A1 cell. With 25 ms pulses, rates above 5 Hz evoked an exponential decrease in the number of spikes and an increase in the latency of the responses of all the 37 specimens tested. The response duration showed no apparent change with stimulus repetition rates even at the highest duty cycle used (50 %), i.e. 25 ms at 20 Hz and 100 ms at 5 Hz. The higher the rate of stimulus repetition, the more marked were the changes in the A1 cell responses. In 16 of 17 preparations from two species, habituation had no effect on the adaptation rate in each response, while in seven of eight specimens of another species, the adaptation rate decreased with stimulus repetition. These results, and those from another mechanoreceptor cell, indicate that receptor cell adaptation (changes evoked in the response by a stimulus of constant intensity) and habituation (changes in the responses due to stimulus repetition rate) are two distinctive phenomena. The A1 cell in its habituated state showed an increase in its response to incremental increases in stimulus intensity of 10 dB. This result supports the idea that receptor cell habituation does not seem to be due to fatigue, i.e. to a temporary loss of the ability to respond to stimulation induced in a sensory receptor by continued stimulation.
Transplantation of Genetically Modified Autologous Hepatocytes into Nonhuman Primates: Feasibility and Short-Term Toxicity (1992)

Ex vivo gene therapy directed to the liver is being developed for the treatment of inherited metabolic diseases. Transplantation of hepatocytes that have been transduced with a low-density lipoprotein (LDL) receptor gene is a potential form of therapy for familial hypercholesterolemia (FH). We have demonstrated efficacy of ex vivo gene therapy for familial hypercholesterolemia in a rabbit animal model of this disease. In preparation for human trials, we describe in this report experiments in baboons for documentation of the feasibility and safety of autologous hepatocyte transplantation. Three baboons underwent a partial hepatectomy and their hepatocytes were isolated, cultured, and transduced with a retrovirus containing the human LDL receptor gene. The hepatocytes were harvested and infused into an indwelling catheter that had been placed into the inferior mesenteric vein at the time of liver resection. The baboons tolerated the procedures well and are being maintained and clinically evaluated for an indefinite time period. Follow-up evaluations have ranged from 3 to 8 months. Clinical evaluations have been unremarkable and blood chemistry and hematology determinations have stayed within normal limits.
A Sound Velocity Method for Determining the Compressibility of Finely Divided Substances (1947)

A method is presented whereby the adiabatic compressibility of a finely divided material can be found from sound velocity and density measurements of a suspension of the particles in a liquid. The method is based on the assumption that the velocity of sound in a suspension is the same as it would be in an ideal solution of the two substances. This is verified experimentally by measurements of sound velocity in kaolin-water suspensions and xylene-water emulsions, and the method is illustrated by the determination of compressibility of the oil droplets in an oil emulsion and of the blood corpuscles in horse blood. Considerable accuracy is attainable for materials which are not too incompressible compared to the suspending liquid.
[URE3] as an Altered URE2 Protein: Evidence for a Prion Analog in Saccharomyces cerevisiae (1994)

A cytoplasmically inherited element, [URE3], allows yeast to use ureidosuccinate in the presence of ammonium ion. Chromosomal mutations in the URE2 gene produce the same phenotype. [URE3] depends for its propagation on the URE2 product (Ure2p), a negative regulator of enzymes of nitrogen metabolism. Saccharomyces cerevisiae strains cured of [URE3] with guanidium chloride were shown to return to the [URE3]-carrying state without its introduction from other cells. Overproduction of Ure2p increased the frequency with which a strain became [URE3] by 100-fold. In analogy to mammalian prions, [URE3] may be an altered form of Ure2p that is inactive for its normal function but can convert normal Ure2p to the altered form. The genetic evidence presented here suggests that protein-based inheritance, involving a protein unrelated to the mammalian prion protein, can occur in a microorganism.
Influence of UDP-GlcNAc 2-Epimerase/ManNAc Kinase Mutant Proteins on Hereditary Inclusion Body Myopathy (2006)

Hereditary inclusion body myopathy (HIBM), a neuromuscular disorder, is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of sialic acid biosynthesis. To date, more than 40 different mutations in the GNE gene have been reported to cause the disease. Ten of them, representing mutations in both functional domains of GNE, were recombinantly expressed in insect cells (Sf9). Each of the mutants that was analyzed displayed a reduction in the two known GNE activities, thus revealing that mutations may also influence the function of the domain not harboring them. The extent of reduction strongly differs among the point mutants, ranging from only 20% reduction found for A631T and A631V to almost 80% reduction of at least one activity in D378Y and N519S mutants and more than 80% reduction of both activities of G576E, underlined by structural changes of N519S and G576E, as observed in CD spectroscopy and gel filtration analysis, respectively. We therefore generated models of the three-dimensional structures of the epimerase and the kinase domains of GNE, based on Escherichia coli UDP-N-acetylglucosamine 2-epimerase and glucokinase, respectively, and determined the localization of the HIBM mutations within these proteins. Whereas in the kinase domain most of the mutations are localized inside the enzyme, mutations in the epimerase domain are mostly located at the protein surface. Otherwise, the different mutations result in different enzymatic activities but not in different disease phenotypes and, therefore, do not suggest a direct role of the enzymatic function of GNE in the disease mechanism.
Proteome Analysis of the Penicillin Producer Penicillium chrysogenum (2010)

Proteomics is a powerful tool to understand the molecular mechanisms causing the production of high penicillin titers by industrial strains of the filamentous fungus Penicillium chrysogenum as the result of strain improvement programs. Penicillin biosynthesis is an excellent model system for many other bioactive microbial metabolites. The recent publication of the P. chrysogenum genome has established the basis to understand the molecular processes underlying penicillin overproduction. We report here the proteome reference map of P. chrysogenum Wisconsin 54-1255 (the genome project reference strain) together with an in-depth study of the changes produced in three different strains of this filamentous fungus during industrial strain improvement. Two-dimensional gel electrophoresis, peptide mass fingerprinting, and tandem mass spectrometry were used for protein identification. Around 1000 spots were visualized by "blue silver" colloidal Coomassie staining in a non-linear pI range from 3 to 10 with high resolution, which allowed the identification of 950 proteins (549 different proteins and isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951, Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a penicillin high producer) strains indicated that global metabolic reorganizations occurred during the strain improvement program. The main changes observed in the high producer strains were increases of cysteine biosynthesis (a penicillin precursor), enzymes of the pentose phosphate pathway, and stress response proteins together with a reduction in virulence and in the biosynthesis of other secondary metabolites different from penicillin (pigments and isoflavonoids). In the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and other carbon sources that have been lost in the high penicillin producer strains. Changes in the levels of a few specific proteins correlated well with the improved penicillin biosynthesis in the high producer strains. These results provide useful information to improve the production of many other bioactive secondary metabolites.
"Footprint" titrations yield valid thermodynamic isotherms. (1986)

A central issue in gene regulation is the mechanism, and biological function, of the cooperative binding of regulatory protein ligands to specific sites on DNA. To elucidate the physical-chemical basis of these interactions we have developed a thermodynamically rigorous method for conducting DNase I "footprint" (protection) titration experiments. The intrinsic binding constants and also those for cooperative interactions between various sites can be resolved from the individual-site binding curves determined by this technique. Experimental studies of cI-repressor-operator binding have demonstrated that the method provides an accurate representation of the fractional saturation of a binding site. We present individual-site binding curves for a lambda operator with two competent sites that demonstrate the presence of cooperative interactions between the sites. These curves set a lower limit to the magnitude of the cooperative free energy without comparison to single-site mutant operators.
Potent inhibition of DOT1L as treatment of MLL-fusion leukemia (2013)

Rearrangements of the MLL gene define a genetically distinct subset of acute leukemias with poor prognosis. Current treatment options are of limited effectiveness; thus, there is a pressing need for new therapies for this disease. Genetic and small molecule inhibitor studies have demonstrated that the histone methyltransferase DOT1L is required for the development and maintenance of MLL-rearranged leukemia in model systems. Here we describe the characterization of EPZ-5676, a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase activity. The compound has an inhibition constant value of 80 pM, and demonstrates 37 000-fold selectivity over all other methyltransferases tested. In cellular studies, EPZ-5676 inhibited H3K79 methylation and MLL-fusion target gene expression and demonstrated potent cell killing that was selective for acute leukemia lines bearing MLL translocations. Continuous IV infusion of EPZ-5676 in a rat xenograft model of MLL-rearranged leukemia caused complete tumor regressions that were sustained well beyond the compound infusion period with no significant weight loss or signs of toxicity. EPZ-5676 is therefore a potential treatment of MLL-rearranged leukemia and is under clinical investigation.
EDDD: Event-Based Drowsiness Driving Detection Through Facial Motion Analysis With Neuromorphic Vision Sensor (2020)

Drowsiness driving is a principal factor of many fatal traffic accidents. This paper presents the first event-based drowsiness driving detection (EDDD) system by using the recently developed neuromorphic vision sensor. Compared with traditional frame-based cameras, neuromorphic vision sensors, such as Dynamic Vision Sensors (DVS), have a high dynamic range and do not acquire full images at a fixed frame rate but rather have independent pixels that output intensity changes (called events) asynchronously at the time they occur. Since events are generated by moving edges in the scene, DVS is considered as an efficient and effective detector for the drowsiness driving-related motions. Based on this unique output, this work first proposes a highly efficient method to recognize and localize the driver's eyes and mouth motions from event streams. We further design and extract event-based drowsiness-related features directly from the event streams caused by eyes and mouths motions, then the EDDD model is established based on these features. Additionally, we provide the EDDD dataset, the first public dataset dedicated to event-based drowsiness driving detection. The EDDD dataset has 260 recordings in daytime and evening with several challenging scenes such as subjects wearing glasses/sunglasses. Experiments are conducted based on this dataset and demonstrate the high efficiency and accuracy of our method under different illumination conditions. As the first investigation of the usage of DVS in drowsiness driving detection applications, we hope that this work will inspire more event-based drowsiness driving detection research.
Asymmetric epoxidation of olefins catalyzed by Ti(salan) complexes using aqueous hydrogen peroxide as the oxidant (2008)

Abstract Ti(salan) complexes were found to be efficient catalysts for asymmetric epoxidation with aqueous hydrogen peroxide as the oxidant. In the presence of pH 7.4 phosphate buffer, the reaction of various conjugate olefins proceeded smoothly to afford the corresponding epoxides in high yield with high enantioselectivity, even on a multigram scale. Ti(salan) complexes could be prepared from Ti(O i Pr) 4 and the corresponding salan ligand and directly used without isolation and purification.
Chimeric Antigen Receptor Engineering: A Right Step in the Evolution of Adoptive Cellular Immunotherapy (2015)

Cancer immunotherapy comprises different therapeutic strategies that exploit the use of distinct components of the immune system, with the common goal of specifically targeting and eradicating neoplastic cells. These varied approaches include the use of specific monoclonal antibodies, checkpoint inhibitors, cytokines, therapeutic cancer vaccines and cellular anticancer strategies such as activated dendritic cell (DC) vaccines, tumor-infiltrating lymphocytes (TILs) and, more recently, genetically engineered T cells. Each one of these approaches has demonstrated promise, but their generalized success has been hindered by the paucity of specific tumor targets resulting in suboptimal tumor responses and unpredictable toxicities. This review will concentrate on recent advances on the use of engineered T cells for adoptive cellular immunotherapy (ACI) in cancer.
Synthetic peptide derived from the epstein‐barr virus encoded early diffuse antigen (ea‐d) reactive with human antibodies (1987)

Abstract Primary infection with Epstein‐Barr virus (EBV) and reactivation of latent virus are associated with increased antibody titers against the diffuse early antigen (EA‐D). In order to better define the antigenic epitopes recognized by antibodies from patients with infectious mononucleosis (IM) and with other disease states, a series of synthetic peptides were prepared based on the DNA sequence encoding the EA‐D molecule. One synthetic peptide (K7b) was reactive with the majority of sera from patients with acute IM. Anti‐K7b activity was most readily detected among IgM and IgA antibodies and to a lesser extent among IgG antibodies. In contrast, significant elevations of anti‐K7b activity were observed in less than 5% of healthy adults. Serial analysis of samples from individuals prior to and after exposure to EBV demonstrated increased anti‐K7b reactivity associated with the symptoms of acute IM. Elevated anti‐peptide K7b titers also were found in sera of patients with nasopharyngeal carcinoma and with Sjogren's syndrome (an autoimmune disease involving the salivary glands). Four different synthetic peptides from other regions of the EA‐D molecule were not reactive with antibodies from these patients nor from IM patients. These results suggest that peptide K7b defines an antigenic epitope recognized during primary EBV infection and during viral reactivation occurring in patients with autoimmune and neoplastic disease.
Clinical experience with the automatic implantable defibrillator. (1985)

Since February 1980, worldwide, over 400 survivors of sudden arrhythmic death have been treated with the automatic implantable defibrillator. Recently, the device has been further improved; it is now a cardioverter-defibrillator (AICD), able to treat ventricular tachycardias as well as ventricular fibrillation. There are two defibrillating electrodes which are used also for waveform analysis; one is located in the superior vena cava, the other is placed over the cardia apex. A third bipolar right ventricular electrode serves for rate counting and R-wave synchronization. When ventricular fibrillation occurs, a 25-joule pulse is delivered; when ventricular tachycardia faster than a preset rate is detected, the discharge is R-wave synchronized. Special batteries can deliver over 100 shocks or provide a three-year monitoring life. Implantation of the device can be achieved through a thoracotomy or by a subxiphoid or a subcostal approach. Thus far, the longest follow-up period has been 58 months. Actuarial analysis shows the one-year mortality attributed to arrhythmias reduced to less than 2%. Thus, the automatic cardioverter-defibrillator can reliably identify and correct potentially lethal ventricular tachyarrhythmias, leading to a substantial increase in survival in properly selected high-risk patients.