gebhart/patrepeval huggingface dataset:
Non‐native N‐Aroyl L‐Homoserine Lactones Are Potent Modulators of the Quorum Sensing Receptor RpaR in Rhodopseudomonas palustris (2013)

Quorum sensing (QS) is a process by which bacteria use low-molecular-weight signaling molecules (or autoinducers) to assess their local population densities and alter gene expression levels at high cell numbers. Many Gram-negative bacteria use N-acyl L-homoserine lactones (AHLs) with aliphatic acyl groups as signaling molecules for QS. However, bacteria that utilize AHLs with aroyl acyl groups have been recently discovered; they include the metabolically versatile soil bacterium Rhodopseudomonas palustris, which uses p-coumaroyl HL (p-cAHL) as its QS signal. This autoinducer is especially unusual because its acyl group is believed to originate from a monolignol (i.e., p-coumarate) produced exogenously by plants in the R. palustris environment, rather than through the endogenous fatty acid biosynthesis pathway like other native AHLs. As such, p-cAHL could signal not only bacterial density, but also the availability of an exogenous plant-derived substrate and might even constitute an interkingdom signal. Like other Gram-negative bacteria, QS in R. palustris is controlled by the p-cAHL signal binding its cognate LuxR-type receptor, RpaR. We sought to determine if non-native aroyl HLs (ArHLs) could potentially activate or inhibit RpaR in R. palustris, and thereby modulate QS in this bacterium. Herein, we report the testing of a set of synthetic ArHLs for RpaR agonism and antagonism by using a R. palustris reporter strain. Several potent non-native RpaR agonists and antagonists were identified. Additionally, the screening data revealed that lower concentrations of ArHL are required to strongly agonize RpaR than to antagonize it. Structure-activity relationship analyses of the active ArHLs indicated that potent RpaR agonists tend to have sterically small substituents on their aryl groups, most notably in the ortho position. In turn, the most potent RpaR antagonists were based on either the phenylpropionyl HL (PPHL) or the phenoxyacetyl HL (POHL) scaffold, and many contained an electron-withdrawing group at either the meta or para positions of the aryl ring. To our knowledge, the compounds reported herein represent the first abiotic chemical modulators of RpaR, and more generally, the first abiotic ligands capable of intercepting QS in bacteria that utilize native ArHL signals. In view of the origins of the p-cAHL signal in R. palustris, the largely unknown role of QS in this bacterium, and R. palustris' unique environmental lifestyles, we anticipate that these compounds could be valuable as chemical probes to study QS in R. palustris in a range of fundamental and applied contexts.
Cdk5 Regulates the Organization of Nestin and Its Association with p35 (2003)

The intermediate filament protein nestin is characterized by its specific expression during the development of neuronal and myogenic tissues. We identify nestin as a novel in vivo target for cdk5 and p35 kinase, a critical signaling determinant in development. Two cdk5-specific phosphorylation sites on nestin, Thr-1495 and Thr-316, were established, the latter of which was used as a marker for cdk5-specific phosphorylation in vivo. Ectopic expression of cdk5 and p35 in central nervous system progenitor cells and in myogenic precursor cells induced elevated phosphorylation and reorganization of nestin. The kinetics of nestin expression corresponded to elevated expression and activation of cdk5 during differentiation of myoblast cell cultures and during regeneration of skeletal muscle. In the myoblasts, a disassembly-linked phosphorylation of Thr-316 indicated active phosphorylation of nestin by cdk5. Moreover, cdk5 occurred in physical association with nestin. Inhibition of cdk5 activity-either by transfection with dominant-negative cdk5 or by using a specific cdk5 inhibitor-blocked myoblast differentiation and phosphorylation of nestin at Thr-316, and this inhibition markedly disturbed the organization of nestin. Interestingly, the interaction between p35, the cdk5 activator, and nestin appeared to be regulated by cdk5. In differentiating myoblasts, p35 was not complexed with nestin phosphorylated at Thr-316, and inhibition of cdk5 activity during differentiation induced a marked association of p35 with nestin. These results demonstrate that there is a continuous turnover of cdk5 and p35 activity on a scaffold formed by nestin. This association is likely to affect the organization and operation of both cdk5 and nestin during development.
The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells (2017)

Disease recurrence is the major problem in the treatment of acute myeloid leukemia (AML). Relapse is driven by leukemia stem cells, a chemoresistant subpopulation capable of re-establishing disease. Patients with p53 mutant AML are at an extremely high risk of relapse. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is required for the self-renewal and maintenance of AML stem cells. Here we studied the effects of a novel small molecule inhibitor of BMI-1, PTC596, in AML cells. Treatment with PTC596 reduced MCL-1 expression and triggered several molecular events consistent with induction of mitochondrial apoptosis: loss of mitochondrial membrane potential, BAX conformational change, caspase-3 cleavage and phosphatidylserine externalization. PTC596 induced apoptosis in a p53-independent manner. PTC596 induced apoptosis along with the reduction of MCL-1 and phosphorylated AKT in patient-derived CD34<sup>+</sup>CD38<sup>low/-</sup> stem/progenitor cells. Mouse xenograft models demonstrated in vivo anti-leukemia activity of PTC596, which inhibited leukemia cell growth in vivo while sparing normal hematopoietic cells. Our results indicate that PTC596 deserves further evaluation in clinical trials for refractory or relapsed AML patients, especially for those with unfavorable complex karyotype or therapy-related AML that are frequently associated with p53 mutations.
A special reactor design for investigations of mixing time effects in a scaled-down industrialL-lysine fed-batch fermentation process (1999)

A specially designed model reactor based on a 42-L laboratory fermentor was equipped with six stirrers (Rushton turbines) and five cylindrical disks. In this model reactor, the mixing time, Theta(90), turned out to be 13 times longer compared with the 42-L standard laboratory fermentor fitted with two Rushton turbines and four wall-fixed longitudinal baffles. To prove the suitability of the model reactor for scaledown studies of mixing-time-dependent processes, parallel exponential fed-batch cultivations were carried out with the leucine-auxotrophic strain, Corynebacterium glutamicum DSM 5715, serving as a microbial test system. L&HYPHEN;Leucine, the process-limiting substrate, was fed onto the liquid surface of both reactors. Cultivations were conducted using the same inoculum material and equal oxygen supply. The model reactor showed reduced sugar consumption (-14%), reduced ammonium consumption (-19%), and reduced biomass formation (-7%), which resulted in a decrease in L-lysine formation (-12%). These findings were reflected in less specific enzyme activity, which was determined for citrate synthase (CS), phosphoenolpyruvate carboxylase (PEP-C), and aspartate kinase (AK). The reduced specific activity of CS correlated with lower CO(2) evolution (-36%) during cultivation. The model reactor represents a valuable tool to simulate the conditions of poor mixing and inhomogeneous substrate distribution in bioreactors of industrial scale. Copyright 1999 John Wiley & Sons, Inc.
Growth, ageing and scaling laws of coronary arterial trees (2015)

Despite the well-known design principles of vascular systems, it is unclear whether the vascular arterial tree obeys some scaling constraints during normal growth and ageing in a given species. Based on the micro-computed tomography measurements of coronary arterial trees in mice at different ages (one week to more than eight months), we show a constant exponent of 3/4, but age-dependent scaling coefficients in a length-volume scaling law (Lc=K(length-volume) · Vc³/⁴; Lc is the crown length, Vc is the crown volume, K(length-volume) is the age-dependent scaling coefficient) during normal growth and ageing. The constant 3/4 exponent represents the self-similar fractal-like branching pattern (i.e. basic mechanism to regulate the development of vascular trees within a species), whereas the age-dependent scaling coefficients characterize the structural growth or resorption of vascular trees during normal growth or ageing, respectively. This study enhances the understanding of age-associated changes in vascular structure and function.
Challenges and Opportunities in Many-Core Computing With increasing use of computers that employ many independent processing units, commercial and technical-scientific software, as well as general-purpose operating systems, will have to undergo fundamental changes. (2008)

In this paper, we present some of the challenges and opportunities in software development based on the current hardware trends and the impact of massive parallelism on both the software and hardware industry. We indicate some of the approaches that can enable software development to effectively exploit the many-core architectures. Some of these include encapsulating domain-specific knowledge in reusable components, such as libraries, integrating concurrency with languages, and supporting explicit declarations to help compi- lers and operating system schedulers. Tighter interaction between software and underlying hardware is required to build scalable and portable applications with predictable performance and higher power-efficiency. Overall, many-core computing provides us opportunities to enable new application scenarios that support enhanced functionality and a richer experience for the user on commodity hardware.
mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient (2017)

The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of many essential amino acids out of lysosomes, including leucine, which mTORC1 senses through the cytosolic Sestrin proteins. SLC38A9 is necessary for leucine generated via lysosomal proteolysis to exit lysosomes and activate mTORC1. Pancreatic cancer cells, which use macropinocytosed protein as a nutrient source, require SLC38A9 to form tumors. Thus, through SLC38A9, arginine serves as a lysosomal messenger that couples mTORC1 activation to the release from lysosomes of the essential amino acids needed to drive cell growth.
Speech Intelligibility Enhancement by Interaural Magnification (1990)

Hearing-impaired persons suffer from loss of speech intelligibility in noisy environments as well as from a decrease in binaural performance (e.g., interaural time and intensity discrimination). In order to improve speech intelligibility for spatially separated signal and noise sources by compensating for the reduced binaural performance, we implemented an algorithm increasing binaural dissimilarity on a digital signal processor. This algorithm is a modification of the proposal by Durlach & Pang (J. Acoust. Soc. Am. 1986; 80: 1849–1850). Speech discrimination experiments were performed under simulated spatial conditions with recordings of the speech material and the interfering noise source using a dummy head. With increasing complexity of the spatial masking condition, the binaural advantage as well as the benefits from the algorithm decreased for normal listeners. For four sensorineurally hearing-impaired listeners, only one spatial condition was tested. In addition, a battery of binaural tests (binaural masking level difference, interaural time and intensity discrimination) was performed. The results indicate that the benefits from the signal-processing technique are correlated with the remaining binaural performance.
Evidence for Ovarian Granulosa Stem Cells: Telomerase Activity and Localization of the Telomerase Ribonucleic Acid Component in Bovine Ovarian Follicles1 (1999)

We have previously postulated that granulosa cells of developing follicles arise from a population of stem cells. Stem cells and cancer cells can divide indefinitely partly because they express telomerase. Telomerase is a ribonucleoprotein enzyme that repairs the ends of telomeres that otherwise shorten progressively upon each successive cell division. In this study we carried out cell cycle analyses and examined telomerase expression to examine our hypothesis. Preantral (60-100 microm) and small (1 mm) follicles, as well as granulosa cells from medium-sized (3 mm) and large (6-8 mm) follicles, were isolated. Cell cycle analyses and expression of Ki-67, a cell cycle-related protein, were undertaken on follicles of each size (n = 3) by flow cytometry; 12% to 16% of granulosa cells in all follicles were in the S phase, and less than 2% were in the G(2)/M phase. Telomerase activity (n = 3) was highest in the small preantral follicles, declining at the 1-mm stage and even further at the 3-mm stage. In situ hybridization histochemistry was carried out on bovine ovaries, and telomerase RNA was detected in the granulosa cells of growing follicles but not primordial follicles. Two major patterns of staining were observed in the membrana granulosa of antral follicles: staining in the middle and antral layers, and staining in the middle and basal layers. No staining was detected in oocytes. Our results strongly support our hypothesis that granulosa cells arise from a population of stem cells.
High numerical aperture reflection mode coherent diffraction microscopy using off-axis apertured illumination (2012)

We extend coherent diffraction imaging (CDI) to a high numerical aperture reflection mode geometry for the first time. We derive a coordinate transform that allows us to rewrite the recorded far-field scatter pattern from a tilted object as a uniformly spaced Fourier transform. Using this approach, FFTs in standard iterative phase retrieval algorithms can be used to significantly speed up the image reconstruction times. Moreover, we avoid the isolated sample requirement by imaging a pinhole onto the specimen, in a technique termed apertured illumination CDI. By combining the new coordinate transformation with apertured illumination CDI, we demonstrate rapid high numerical aperture imaging of samples illuminated by visible laser light. Finally, we demonstrate future promise for this technique by using high harmonic beams for high numerical aperture reflection mode imaging.
Salmonella Species and Campylobacter jejuni Cecal Colonization Model in Broilers (2008)

Salmonella and Campylobacter are of concern to the poultry industry because of the continuing association of poultry-borne transmission of these diseases to humans. Live, mature bird interventions can be demonstrated only by comparing colonization in nontreated groups of control birds with treated bird groups. This study attempted to create a reproducible broiler chicken colonization model. When chicks were challenged 2 d posthatch with both Salmonella and Campylobacter, cecal colonization was achieved. By 4 wk posthatch, Salmonella counts per gram of cecal content diminished to very low or nondetectable levels. Campylobacter counts remained high throughout the test period. To achieve the goal of creating a mature bird Salmonella intestinal colonization model, oral treatment of 10 to 25 mg of vancomycin was given to 4-wk-old broilers, and 3 h later a composite of 3 Salmonella isolates were gavaged into the chickens. Birds were sampled 1 and 2 wk later. The data indicated that colonization was achieved at levels of 10(6-7) cfu g(-1) of cecal materials (at wk 5) and >10(2) to 10(4) cfu g(-1) of cecal materials (at wk 6).
Abstract A10: A Cdk4-dependent phosphorylation threshold regulates the cell cycle entry decision (2016)

Abstract Cyclin-dependent kinases (Cdk's) are major cell cycle regulators and uncontrolled cell cycle entry is a hallmark of cancer. Cyclin D, the regulatory subunit of Cdk4, is misregulated in about 75% of human malignancies, leading to hyperactive Cdk4 and uncontrolled cell cycle entry. In sharp contrast, the total loss of Cyclin D-mediated activity results in permanent cell cycle arrest. Several functions of Cdk4 during cell cycle entry have been identified; however, the underlying mechanism for cell cycle arrest upon its inactivation remains unanswered. Here we employed CRISPR/Cas9 and rAAV-mediated gene editing to visualize Restriction Point passage in highly synchronized single cells and find that cyclin D:Cdk4/6 complexes perform a critical switch-like function that results in activation of cyclin E:Cdk2 complexes. Taken together, our data indicate that while cyclin E:Cdk2 is the rate-limiting step for transition across the Restriction Point, it is dependent on cyclin D:Cdk4/6 phosphorylation of an as of yet unknown molecule. Citation Format: Manuel Kaulich, Steven Dowdy. A Cdk4-dependent phosphorylation threshold regulates the cell cycle entry decision. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr A10.
Comparison Between the Viral Transforming Gene (src) of Recovered Avian Sarcoma Virus and Its Cellular Homolog (1981)

Recovered avian sarcoma viruses are recombinants between transformation-defective mutants of Rous sarcoma virus and the chicken cellular gene homologous to the src gene of Rous sarcoma virus. We have constructed and analyzed molecular clones of viral deoxyribonucleic acid from recovered avian sarcoma virus and its transformation-competent progenitor, the Schmidt-Ruppin A strain of Rous sarcoma virus. A 2.0-megadalton EcoRI fragment containing the entire src gene from each of these clones was subcloned and characterized. These fragments were also used as probes to isolate recombinant phage clones containing the cellular counterpart of the viral src gene, termed cellular src, from a lambda library of chicken deoxyribonucleic acid. The structure of cellular src was analyzed by restriction endonuclease mapping and electron microscopy. Restriction endonuclease mapping revealed extensive similarity between the src regions of Rous sarcoma virus and recovered avian sarcoma virus, but striking differences between the viral src's and cellular src. Electron microscopic analysis of heteroduplexes between recovered virus src and cellular src revealed a 1.8-kilobase region of homology. In the cellular gene, the homologous region was interrupted by seven nonhomologous regions which we interpret to be intervening sequences. We estimate the minimum length of cellular src to be about 7.2 kilobases. These findings have implications concerning the mechanism of formation of recovered virus src and possibly other cell-derived retrovirus transforming genes.
Toward a signal-processing foundation for computational sensing and imaging: electro-optical basis and merit functions (2017)

Toward a signal-processing foundation for computational sensing and imaging: electro-optical basis and merit functions david g. stork
J. L. Britton. The word problem for groups. Proceedings of the London Mathematical Society, third series, vol. 8 (1958), pp. 493–506. - John L. Britton. The word problem. Annals of mathematics, second series, vol. 77 (1963), pp. 16–32. (1964)

J. L. Britton. The word problem for groups. Proceedings of the London Mathematical Society, third series, vol. 8 (1958), pp. 493–506. - John L. Britton. The word problem. Annals of mathematics, second series, vol. 77 (1963), pp. 16–32. - Volume 29 Issue 4
Film bulk acoustic wave filters using lead titanate on silicon substrate (2002)

A film bulk acoustic wave resonator and filter at GHz frequencies is reported. The resonator and filter employ lead titanate (PbTiO/sub 3/) as the piezoelectric thin film. The films are formed by RF magnetron sputter deposition on silicon (Si) substrates. Platinum (Pt) is used as top and bottom electrodes. The thickness of the piezoelectric film is about 1 /spl mu/m, and that of the electrodes is 0.1 /spl mu/m. The chip size of the resonator and filter is 0.69/spl times/0.55 (mm). The resonant frequency of the fabricated resonator is 1.4 GHz. The top electrode size of the resonator is 50/spl times/50 (/spl mu/m), and the quality factor Q is about 70. The insertion loss of the fabricated filter is 13.6 dB at the frequency of 1.5 GHz, and the 3 dB bandwidth is 47 MHz.
Thermal and fire degradation of recycled and polluted polypropylene-based materials (2009)

International audience
Figure S6 from A Somatostatin Receptor Subtype-3 (SST<sub>3</sub>) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors (2023)

&lt;p&gt;Representative immunohistochemical staining (400X magnification; scale bar: 20μm) for SST3 measured in responsive and unresponsive NFPAs.&lt;/p&gt;
Cell Size and the Heat‐Shock Response in Rat Brain (1994)

The expression of mRNAs encoding two members of the heat-shock protein 70 family, the constitutively-expressed heat-shock cognate (hsc70) mRNA and the strictly heat-inducible (hsp70) mRNA, was quantitated in cerebellar and hippocampal cells of rats 3 h after amphetamine-induced or heat-induced hyperthermia. Intracellular heat-shock mRNA levels in specific cell types were compared with those of total polyadenylic acid [poly(A)] mRNA or 18S rRNA in the same cell type. Levels of poly(A) mRNAs, 18S rRNAs, and hsc70 mRNAs were highest in large neurons and lowest in glia. hsp70 mRNAs were also present at highest levels in large neurons, suggesting that hsp70 mRNAs accumulated as rapidly in these cell types as they did in small neurons and glia. However, compared with levels of intracellular poly(A) mRNAs or levels of rRNAs, large neurons contained two- to 12-fold lower levels of hsp70 mRNAs than neurons of intermediate size and five- to 30-fold lower levels than glia. These results suggest that hsp70 mRNAs accumulated as rapidly in large neurons as in small neurons and glia, but that the large size of these neurons precluded intracellular hsp70 mRNA concentrations increasing as quickly. The susceptibility of large neurons to stress-induced cell death could be due, in part, to their inability to synthesize rapidly hsp70 in sufficient amounts to protect these cells from the initial molecular consequences of stress.