gebhart/patrepeval huggingface dataset:
Structure, Assembly and Homeostatic Regulation of the 26S Proteasome (2010)

The 26S proteasome is the major protease responsible for degradation of regulatory and abnormal proteins in the cell. Proteasomal degradation controls many cellular processes including, but not limited to, cell cycle control, transcription, DNA repair, apoptosis, quality control and antigen presentation. To elucidate how the proteasome is regulated is crucial to our understanding of the molecular details of proteasomal degradation and its functions in diverse biological pathways. In this article, I will highlight recent advances in understanding the proteasome structure and assembly and the regulation of proteasome gene expression. The implications of these new developments in cancer therapy will also be discussed.
Libraries of Composite Polyfluors Built from Fluorescent Deoxyribosides (2002)

We report on a new class of water-soluble fluorescent molecules (polyfluors) that are composed of multiple individual fluorophores assembled on a DNA-like backbone. Four fluorophore deoxyribosides were synthesized, and these individual molecules were assembled into oligofluor strings on a DNA synthesizer. A library of 256 tetrafluors was generated by split and pool methods on polystyrene beads. Images of the library under a fluorescence microscope revealed at least 40-50 different hues and intensities. Selected tetrafluors were resynthesized in pure form in solution and displayed properties, such as large Stokes shifts, that individual fluorophores do not have.
Protein kinase C inhibitors prevent induction and continued expression of cell memory in Hermissenda type B photoreceptors. (1991)

Injections of cAMP-dependent, Ca2+/calmodulin-dependent, or Ca2+/phospholipid-dependent protein kinases into Hermissenda crassicornis type B photoreceptors are sufficient to induce many of the changes in B-cell excitability produced by associative conditioning. We report that inhibitors of Ca2+/phospholipid-dependent protein kinases, but not inhibitors of cyclic nucleotide- or Ca2+/calmodulin-dependent protein kinases, prevent the induction as well as continued expression of learning-produced changes in type-B-cell excitability: reductions of voltage-dependent and Ca2(+)-activated K+ currents. Our results represent a direct demonstration of long-term (days) experientially induced modulation of ion-channel activity that is dependent upon persistent kinase activity.
Performance evaluation of the SGI Origin2000 (1997)

In this paper we compare single-processor performance of the SGI Origin and PowerChallenge and utilize a previously-reported performance model for hierarchical memory systems to explain the results. Both the Origin and PowerChallenge use the same microprocessor (MIPS R10000) but have significant differences in their memory subsystems. Our memory model includes the effect of overlap between CPU and memory operations and
Target Site Selection in Transposition of Phage Mu (1993)

The backbone of double-stranded DNA has a structure that is to a large extent independent of the base sequence, although minor variations in local conformational parameters certainly occur. Consequently, the intrinsic chemical reactivity of each phosphodiester bond (or sugar ring) is independent of its position in the polynucleotide chain, as is evidenced by the near-random distribution of sites of modification or cleavage by small chemical reagents (Nielsen 1990). On the other hand, the reactivity of phosphodiester bonds in double-stranded DNA to enzymes such as nucleases can vary widely from position to position. This reflects the relatively large surface of interaction between DNA and proteins, which permits sequence preferences through a number of sequence- or conformation-sensitive bonds. Thus, many proteins have been found to act on DNA only at sites with unique nucleotide sequences. Even "sequence nonspecific" enzymes frequently display some degree of sequence preference. The structural basis of sequence-specific interactions...
Volatile Fatty Acid, Metabolic By-Product of Periodontopathic Bacteria, Induces Apoptosis in WEHI 231 and RAJI B Lymphoma Cells and Splenic B Cells (1998)

The ability of butyric acid, an extracellular metabolite from periodontopathic bacteria, to induce apoptosis in murine WEHI 231 cells, splenic B cells, and human RAJI cells was examined. The culture filtrate of Porphyromonas gingivalis, Prevotella loescheii, and Fusobacterium nucleatum, which contains high a percentage of butyric acid, induced DNA fragmentation in WEHI 231 cells. Volatile fatty acid, especially butyric acid, significantly suppressed B-cell viability in a concentration-dependent fashion. The DNA fragmentation assay indicated that butyric acid rapidly induced apoptosis in WEHI 231 cells (with 1.25 mM butyric acid and 6 h after treatment), splenic B cells (with 1.25 mM butyric acid), and RAJI cells (with 2.5 mM butyric acid). Incubation of WEHI 231 cells with butyric acid for 16 h resulted in the typical ladder pattern of DNA fragmentation and the apoptoic change such as chromatin condensation and hypodiploid nuclei. Cell cycle analysis implied that butyric acid arrested the cells at the G1 phase. The inhibitory assay suggested that butyric acid-induced apoptosis of WEHI 231 and splenic B cells was inhibited by W-7, a calmodulin inhibitor. These results suggest that calmodulin-dependent regulation is involved in the signal transduction pathway of butyric acid.
Molecular Mechanism of Pregnenolone Sulfate Action at NR1/NR2B Receptors (2004)

NMDA receptors are highly expressed in the CNS and are involved in excitatory synaptic transmission and synaptic plasticity as well as excitotoxicity. They have several binding sites for allosteric modulators, including neurosteroids, endogenous compounds synthesized by the nervous tissue and expected to act locally. Whole-cell patch-clamp recording from human embryonic kidney 293 cells expressing NR1-1a/NR2B receptors revealed that neurosteroid pregnenolone sulfate (PS) (300 microm), when applied to resting NMDA receptors, potentiates the amplitude of subsequent responses to 1 mm glutamate fivefold and slows their deactivation twofold. The same concentration of PS, when applied during NMDA receptor activation by 1 mm glutamate, has only a small effect. The association and dissociation rate constants of PS binding and unbinding from resting NMDA receptors are estimated to be 3.3 +/- 2.0 mm(-1)sec(-1) and 0.12 +/- 0.02 sec(-1), respectively, corresponding to an apparent affinity K(d) of 37 microm. The results of experiments indicate that the molecular mechanism of PS potentiation of NMDA receptor responses is attributable to an increase in the peak channel open probability (P(o)). Responses to glutamate recorded in the continuous presence of PS exhibit marked time-dependent decline. Our results indicate that the decline is induced by a change of the NMDA receptor affinity for PS after receptor activation. These results suggest that the PS is a modulator of NMDA receptor P(o), the effectiveness of which is lowered by glutamate binding. This modulation may have important consequences for the neuronal excitability.
On the cloning of eukaryotic total poly(A)-RNA populations in Escherichia coli. (1980)

A total clone bank of cDNAs synthesized from mouse liver poly(A)-RNA was constructed in Escherichia coli K-12 RR1 using the plasmid pBR322. Sequences of cDNAs were inserted into the PST-I site of pBR322 by the "G-C-tailing" method. Bulk preparations of these cDNA sequences were obtained by treatment of the resultant total hybrid plasmid population with PST-I. Aliquots of this cDNA material were then labeled with 32P by "nick translation" using E. coli DNA polymerase I for the preparation of hybridization probes. Experiments involving the back-hybridization of these probes to the total hybrid-plasmid clone bank population revealed that virtually all of the liver poly(A)-RNA sequences were represented in the total clone bank. The long term stability of these sequences residing in RR1 host cells was then examined through extensive serial passage of the initial total clone cell population culture. The results showed: 1) that the small percentage of natural pBR322 molecules (containing no cDNA inserts) usually present in such total clone bank preparations do not outgrow the respectively hybrid specie of plasmids in these populations: 2) few, if any, cDNA sequences are completely lost; and 3) some redistribution of the abundant and more unique DNA sequences probably does occur. The use of total clone hybrid-plasmid populations (constructed from poly(A)-RNA isolated from different tissues) described here should allow the identification of tissue-specific RNA sequences through the use of cross-hybridizaton techniques.
Strain-dependent sequence heterogeneity in the nuclear group I introns and large subunit ribosomal RNA inPhysarum polycephalum (1991)

The DNA sequence of an internal EcoRI fragment in the large subunit ribosomal RNA gene from the myxomycete Physarum polycephalum, strain M3C, has been determined. This ribosomal DNA fragment contain two group I introns. Sequence heterogeneity in the two introns and in the coding region of the ribosomal RNA were identified upon comparison to the strain PPO-1 sequence. The nature of the sequence variations is discussed.
In vitro synergism between daptomycin and fosfomycin against Enterococcus faecalis isolates with high-level gentamicin resistance (1989)

Daptomycin and fosfomycin are two agents which inhibit different steps in peptidoglycan synthesis. We studied the in vitro activities of these drugs, alone and in combination, by time-kill techniques against 21 clinical isolates of Enterococcus (Streptococcus) faecalis demonstrating high-level resistance to gentamicin. Combinations of fosfomycin and daptomycin exhibited synergistic bactericidal activity (100-fold decrease in CFU per milliliter at 24 h compared with daptomycin alone) against all strains (mean +/- standard deviation of increment in killing = 2.7 +/- 0.7 log10 CFU/ml). In a subgroup of strains against which daptomycin (5 micrograms/ml) alone was bactericidal (greater than 3 log10 killing), synergistic activity was demonstrable only when the concentration of daptomycin was lowered to 0.25 to 0.5 microgram/ml. A 50% dilution of human serum diminished the bactericidal activity of daptomycin alone at 24 h but did not affect killing observed with the daptomycin-fosfomycin combination. The inhibition of peptidoglycan synthesis by the combination was greater than the inhibition observed with either drug alone. The combination of daptomycin and fosfomycin exhibited consistent synergistic bactericidal activity against strains of E. faecalis possessing high-level resistance to gentamicin. This synergism may be the result of sequential inhibition of early steps in peptidoglycan synthesis.
Video-assisted thoracoscopic lobectomy for treating lung cancer. (1997)

Our objective was to evaluate the usefulness and safety of video-assisted thoracoscopic surgery (VATS) for performing pulmonary lobectomy in 11 patients with clinical NO stage I primary non-small-cell lung cancer compared with 11 patients who underwent a conventional thoracotomy. Treatment was switched to conventional thoracotomy in three VATS patients because of the involvement of interlobar nodes or incomplete lobar fissure. None of the eight VATS patients died or experienced serious complications during 12 months of follow-up. There were no significant differences in the intraoperative blood loss, duration of operation, or duration of chest tube drainage between the VATS group and the standard lobectomy group. We conclude that although VATS lobectomy appears to be safe for use in managing patients with primary lung cancer, it does not seem to offer any advantages over standard lobectomy.
Superoxide dismutase mimic, MnTE-2-PyP5+ ameliorates acute and chronic proctitis following focal proton irradiation of the rat rectum (2013)

Radiation proctitis, an inflammation and damage to the lower part of colon, is a common adverse event of the radiotherapy of tumors in the abdominal and pelvic region (colon, prostate, cervical). Several Mn(III) porphyrin-based superoxide dismutase mimics have been synthesized and successfully evaluated in preclinical models as radioprotectants. Here we report for the first time the remarkable rectal radioprotection of frequently explored Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+). A batch prepared in compliance with good manufacturing practice (GMP), which has good safety/toxicity profile, was used for this study. MnTE-2-PyP(5+) was given subcutaneously at 5 mg/kg, either 1 h before or 1 h after irradiation, with additional drug administered at weekly intervals thereafter. MnTE-2-PyP(5+) ameliorated both acute and chronic radiation proctitis in male Sprague-Dawley rats irradiated with 20-30 Gy protons delivered to 2.5 cm span of rectum using spread-out Bragg peak of a proton treatment beam. Focal irradiation of the rectum produced acute proctitis, which healed, followed by chronic rectal dilation and symptomatic proctitis. MnTE-2-PyP(5+) protected rectal mucosa from radiation-induced crypt loss measured 10 days post-irradiation. Significant effects were observed with both pre- and post-treatment regimens. However, only MnTE-2-PyP(5+) pre-treatment, but not post-treatment, prevented the development of rectal dilation, indicating that proper dosing regimen is critical for radioprotection. The pre-treatment also prevented or delayed the development of chronic proctitis depending on the radiation dose. Further work aimed at developing MnTE-2-PyP(5+) and similar drugs as adjunctive agents for radiotherapy of pelvic tumors is warranted. The present study substantiates the prospects of employing this and similar analogs in preserving normal tissue during cancer radiation as well as any other radiation exposure.
The liver - biology and pathobiology. Second edition (1988)

This book contains 76 chapters. Some of the titles are: Nucleus, DNA, and chromatin; Hepatic gene expression and mRNA metabolism; Protein synthesis and gene control in pathophysiologic states; and hormonal control of gene expression.
Angelman Syndrome, a Genomic Imprinting Disorder of the Brain (2010)

Harry Angelman, an English pediatrician, reported three cases of “Puppet Children” in 1965 ([Angelman, 1965][1]). These individuals displayed severe intellectual disability, ataxia, absent speech, jerky arm movements and bouts of inappropriate laughter. More cases were described as “Happy
Composite Polymer Electrolytes with Li7La3Zr2O12 Garnet-Type Nanowires as Ceramic Fillers: Mechanism of Conductivity Enhancement and Role of Doping and Morphology (2017)

Composite polymer solid electrolytes (CPEs) containing ceramic fillers embedded inside a polymer-salt matrix show great improvements in Li<sup>+</sup> ionic conductivity compared to the polymer electrolyte alone. Lithium lanthanum zirconate (Li<sub>7</sub>La<sub>3</sub>Zr<sub>2</sub>O<sub>12</sub>, LLZO) with a garnet-type crystal structure is a promising solid Li<sup>+</sup> conductor. We show that by incorporating only 5 wt % of the ceramic filler comprising undoped, cubic-phase LLZO nanowires prepared by electrospinning, the room temperature ionic conductivity of a polyacrylonitrile-LiClO<sub>4</sub>-based composite is increased 3 orders of magnitude to 1.31 × 10<sup>-4</sup> S/cm. Al-doped and Ta-doped LLZO nanowires are also synthesized and utilized as fillers, but the conductivity enhancement is similar as for the undoped LLZO nanowires. Solid-state nuclear magnetic resonance (NMR) studies show that LLZO NWs partially modify the PAN polymer matrix and create preferential pathways for Li<sup>+</sup> conduction through the modified polymer regions. CPEs with LLZO nanoparticles and Al<sub>2</sub>O<sub>3</sub> nanowire fillers are also studied to elucidate the role of filler type (active vs passive), LLZO composition (undoped vs doped), and morphology (nanowire vs nanoparticle) on the CPE conductivity. It is demonstrated that both intrinsic Li<sup>+</sup> conductivity and nanowire morphology are needed for optimal performance when using 5 wt % of the ceramic filler in the CPE.
Dual mode mobile unit for next generation digital narrow channel cellular telephone system (2003)

The topology required of a dual mode cellular telephone mobile unit, which can operate either in the conventional US 30 kHz analog FM mode or in a proposed 10 kHz digital channel is described. This 10 kHz channel is envisioned to be an important step in cellular mobile telephony because it triples the number of channels/MHz of bandwidth and provides error-controlled voice/data transmission with an ISDN-like interface. A transceiver block diagram is shown and performance specifications are presented. Parameters for 10 kHz radio transmission parameters, modulation formats, and voice coding techniques are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria (2018)

The association of α-synuclein (α-syn) with mitochondria occurs through interaction with mitochondrial complex I. Defects in this protein have been linked to the pathogenesis of Parkinson disease (PD). Overexpression of α-synuclein in cells has been suggested to cause elevations in mitochondrial oxidant radicals and structural and functional abnormalities in mitochondria. Asiatic acid (AA), a triterpenoid, is an antioxidant that is used for depression, and we have shown that pretreatment with AA can prevent PD-like damage, but its therapeutic effects in PD and mechanism remain unknown. In this study, we found that 0.5-2 mg AA/100 g diet significantly improves climbing ability in drosophila and extends their life-span-effects that we attributed to its antioxidant properties. AA also protected mitochondria against oxidative stress and apoptosis in a rotenone-induced cellular model. In an isolated mitochondria model, AA attenuated the decline in mitochondrial membrane potential that was induced by α-syn. Consequently, AA maintained membrane integrity and ATP production. Finally, we demonstrated that AA protects by blocking the translocation of α-syn into mitochondria. Our results suggest that mitochondria are crucial in PD and that AA is an excellent candidate for the prevention and therapy of this disease.
A critical role of neural-specific JNK3 for ischemic apoptosis (2003)

c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.
The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion (1996)

Many paramyxoviruses express small basic C proteins, from an alternate, overlapping open reading frame of the P gene mRNA, which were previously found to inhibit mRNA synthesis. During recent experiments in which infectious Sendai virus (SeV) was recovered from cDNA via the initial expression of the viral N, P, and L genes from plasmids, the abrogation of C protein expression from the plasmid P gene was found to be necessary for virus recovery. We have investigated the effect of C coexpression on the amplification of an internally deleted defective interfering (DI) genome directly in the transfected cell, for which, in contrast to virus recovery experiments, genome amplification is independent of mRNA synthesis carried out by the SeV polymerase. We find that C protein coexpression also strongly inhibits the amplification of this DI genome but has little or no effect on that of a copy-back DI genome (DI-H4). We have also characterized the C protein from a mutant SeV and found that (i) it had lost most of its inhibitory activity on internally deleted DI genome amplification and (ii) its coexpression no longer prevented the recovery of SeV from DNA. However, consistent with the insensitivity of copy-back DI genomes to C protein inhibition, C coexpression did not prevent the recovery of copy-back nondefective viruses from DNA. The inhibitory effects of C coexpression thus appear to be promoter specific.
Static Estimation of Test Coverage (2009)

Test coverage is an important indicator for unit test quality. Tools such as Clover compute coverage by first instrumenting the code with logging functionality, and then logging which parts are executed during unit test runs. Since computation of test coverage is a dynamic analysis, it presupposes a working installation of the software. In the context of software quality assessment by an independent third party, a working installation is often not available. The evaluator may not have access to the required libraries or hardware platform. The installation procedure may not be automated or documented. In this paper, we propose a technique for estimating test coverage at method level through static analysis only. The technique uses slicing of static call graphs to estimate the dynamic test coverage. We explain the technique and its implementation. We validate the results of the static estimation by statistical comparison to values obtained through dynamic analysis using Clover. We found high correlation between static coverage estimation and real coverage at system level but closer analysis on package and class level reveals opportunities for further improvement.
Translational research: from pot to plot (2014)

Plant molecular biology has been the key driver to elucidate molecular pathways underlying plant growth, development and stress responses during the past decades. Although this has led to a plethora of available data, the translation to crop improvement is lagging behind. Here, we argue that plant scientists should become more involved in converting basic knowledge into applications in crops to sustainably support food security and agriculture. As the translatability from model species to crops is rather poor, this kind of translational research requires diligence and a thorough knowledge of the investigated trait in the crop. In addition, the robustness of a trait depends on the genotype and environmental conditions, demanding a holistic approach, which cannot always be evaluated under growth chamber and greenhouse conditions. To date, the improved resolution of many genome-wide technologies and the emerging expertise in canopy imaging, plant phenotyping and field monitoring make it very timely to move from the pathway specifics to important agronomical realizations, thus from pot to plot. Despite the availability of scientific know-how and expertise, the translation of new traits to applications using a transgene approach is in some regions of the world, such as Europe, seriously hampered by heavy and nontranslucent legislation for biotech crops. Nevertheless, progress in crop improvement will remain highly dependent on our ability to evaluate improved varieties in field conditions. Here, we plead for a network of protected sites for field trials across the different European climates to test improved biotech traits directly in crops.