gebhart/patrepeval huggingface dataset:
Alteration of Cardiac Progenitor Cell Potency in GRMD Dogs (2012)

Among the animal models of Duchenne muscular dystrophy (DMD), the Golden Retriever muscular dystrophy (GRMD) dog is considered the best model in terms of size and pathological onset of the disease. As in human patients presenting with DMD or Becker muscular dystrophies (BMD), the GRMD is related to a spontaneous X-linked mutation of dystrophin and is characterized by myocardial lesions. In this respect, GRMD is a useful model to explore cardiac pathogenesis and for the development of therapeutic protocols. To investigate whether cardiac progenitor cells (CPCs) isolated from healthy and GRMD dogs may differentiate into myocardial cell types and to test the feasibility of cell therapy for cardiomyopathies in a preclinical model of DMD, CPCs were isolated from cardiac biopsies of healthy and GRMD dogs. Gene profile analysis revealed an active cardiac transcription network in both healthy and GRMD CPCs. However, GRMD CPCs showed impaired self-renewal and cardiac differentiation. Population doubling and telomerase analyses highlighted earlier senescence and proliferation impairment in progenitors isolated from GRMD cardiac biopsies. Immunofluorescence analysis revealed that only wt CPCs showed efficient although not terminal cardiac differentiation, consistent with the upregulation of cardiac-specific proteins and microRNAs. Thus, the pathological condition adversely influences the cardiomyogenic differentiation potential of cardiac progenitors. Using PiggyBac transposon technology we marked CPCs for nuclear dsRed expression, providing a stable nonviral gene marking method for in vivo tracing of CPCs. Xenotransplantation experiments in neonatal immunodeficient mice revealed a valuable contribution of CPCs to cardiomyogenesis with homing differences between wt and dystrophic progenitors. These results suggest that cardiac degeneration in dystrophinopathies may account for the progressive exhaustion of local cardiac progenitors and shed light on cardiac stemness in physiological and pathological conditions. Furthermore, we provide essential information that canine CPCs may be used to alleviate cardiac involvement in a large preclinical model of DMD.
Transport of Single-Walled Carbon Nanotubes in Porous Media: Filtration Mechanisms and Reversibility (2008)

Deposition of nanomaterials onto surfaces is a key process governing their transport, fate, and reactivity in aquatic systems. We evaluated the transport and deposition behavior of carboxyl functionalized single-walled carbon nanotubes (SWNTs) in a well-defined porous medium composed of clean quartz sand over a range of solution chemistries. Our results showthat increasing solution ionic strength or addition of calcium ions result in increased SWNT deposition (filtration). This observation is consistent with conventional colloid deposition theories, thereby suggesting that physicochemical filtration plays an important role in SWNT transport. However, the relatively insignificant change of SWNT filtration at low ionic strengths (< or = 3.0 mM KCl) and the incomplete breakthrough of SWNTs in deionized water (C/Co = 0.90) indicate that physical straining also plays a role in the capture of SWNTs within the packed sand column. It is proposed that SWNT shape and structure, particularly the very large aspect ratio and its highly bundled (aggregated) state in aqueous solutions, contribute considerably to straining in flow through porous media. We conclude that both physicochemical filtration and straining play a role at low (< 3.0 mM) ionic strength, while physicochemical filtration is the dominant mechanism of SWNT filtration at higher ionic strengths. Our results further show that deposited SWNTs are mobilized (released) from the quartz sand upon introduction of low ionic strength solution following deposition experiments with monovalent salt (KCl). In contrast, SWNTs deposited in the presence of calcium ions were not released upon introduction of low ionic strength solution to the packed column, even when humic acid was present in solution during SWNT deposition.
Characterization of masking materials for deep glass micromachining (2003)

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Fast MRI of RF heating via phase difference mapping (2002)

A method is presented for the rapid acquisition of temperature maps derived from phase difference maps. The temperature-dependent chemical shift coefficients (TDCSCs) of various concentrations of aqueous cobalt and dysprosium-based compounds were measured. The largest TDCSC calculated was for 100 mM DyEDTA, which had a TDCSC of -0.09 PPM/K; 160 mM CoCl2 had a TDCSC of -0.04 PPM/K. These temperature-dependent chemical shifts (TDCSs) result in phase changes in the MR signal with changing temperature. Agarose phantoms were constructed with each paramagnetic metal. A fast gradient-echo (FGRE) MR image was acquired to serve as the baseline image. A "test" MRI procedure was then performed on the phantom. Immediately afterwards, a second FGRE MR image was acquired, serving as the probing image. Proper image processing as a phase difference map between the probing image and the baseline image resulted in an image which quantitatively described the temperature increase of the phantom in response to a particular "test" imaging experiment. Applications of this technique in assessing the safety of pulse sequences and MR coils are discussed.
Temperature selective growth of carbon nanotubes by chemical vapor deposition (2002)

Randomly oriented and vertically aligned carbon nanotubes were synthesized by chemical vapor deposition varying the growth temperature between 550 °C and 850 °C. Transmission electron microscopy (TEM) was used to investigate the growth process and in particular the role of the Ni catalyst. It was found that a catalytic particle was always situated at the tip of the tube thus implying a tip growth mechanism. The TEM analysis revealed a strong correlation between the size and shape of the Ni particle encapsulated at the tip of the tubes and the growth temperature, suggesting that temperature is an influential process parameter in determining an optimum size and shape for the catalytic particle and hence select the diameter, and the wall thickness of the growing tubes.
Ki-67 is a Luminal B marker that identifies a high-risk subgroup in hormone receptor positive and node negative breast cancer (2007)

10521 Background: Gene expression profiling studies have revealed prognostically significant intrinsic breast cancer subtypes, designated Luminal A, Luminal B, Basal and Her2. Expression of ER and associated genes characterizes the luminal breast cancers. The Lum B subgroup is associated with poor outcome, but we lack immunohistochemical (IHC) markers to distinguish Lum A and Lum B subgroups. MKI67 is one gene known to be highly expressed in Lum B tumors, encoding the Ki-67 protein, a robust marker of cell proliferation. In this study, we perform IHC analysis of Ki-67 in a large breast cancer tissue microarray. Methods: Our patient cohort consists of 2222 consecutive cases of invasive breast cancer referred to the BC Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct a tissue microarray that was then stained for Ki-67 using a commercially available mouse monoclonal antibody. Ki-67 staining was scored quantitatively by automated image analysis and a tumor was positive if the percent positive nuclei was &gt;30%’ Results: Of the 2,222 patients, there are 1,437 Luminal tumors as defined by IHC (ER or PR positive). As Her2 positive status is an established marker of poor prognosis, we excluded these tumors from our analysis. Of the remaining tumors, 9% were Ki-67 positive when using a ki-67 cut off of 30% positive nuclei. In survival analysis of patients ER/PR positive and Her2 negative, we found that Ki-67 identifies a population with poor prognosis (10-yr BCSS 60% vs. 80%). In a multivariate Cox regression we found that Ki-67 is independently prognostic. We repeated Cox regression analysis including only node negative patients and again found that Ki-67 is an independent predictor of poor outcome. Conclusions: Ki-67 has prognostic significance on multivariate survival analysis. Hormone receptor positive and node negative status is typically associated with a favorable outcome for breast cancer. However, Ki-67 is able to identify a small, but clinically significant subgroup with a particularly poor outcome. Defining the Luminal B subtype as (ER or PR) positive and (HER2 or Ki-67) positive, results in a subgroup that contains 18% of hormone receptor positive breast cancers with 10-yr BCSS of 61%. No significant financial relationships to disclose.
Disassembly of Transcriptional Regulatory Complexes by Molecular Chaperones (2002)

Many biological processes are initiated by cooperative assembly of large multicomponent complexes; however, mechanisms for modulating or terminating the actions of these complexes are not well understood. For example, hormone-bound intracellular receptors (IRs) nucleate formation of transcriptional regulatory complexes whose actions cease promptly upon hormone withdrawal. Here, we show that the p23 molecular chaperone localizes in vivo to genomic response elements in a hormone-dependent manner, disrupting receptor-mediated transcriptional activation in vivo and in vitro; Hsp90 weakly displayed similar activities. Indeed, p23 and Hsp90 also disrupted the activities of some non-IR-containing transcriptional regulatory complexes. We suggest that molecular chaperones promote disassembly of transcriptional regulatory complexes, thus enabling regulatory machineries to detect and respond to signaling changes.
A TEST OF THE SINGLET OXYGEN MECHANISM OF CATIONIC DYE PHOTOSENSITIZATION OF MITOCHONDRIAL DAMAGE (1992)

Aromatic cationic dyes have a potential as photo-chemotherapeutic agents because they are selectively concentrated into the mitochondria of cancerous cells. The mechanism of cytophototoxicity has been proposed to be primarily due to dye sensitized photogeneration of highly toxic singlet oxygen (1O2) at the mitochondria. We tested this hypothesis by measuring the relative phototoxicity of a collection of aromatic cationic dyes towards respiring rat-liver mitochondria (RLM), upon addition of 514 nm laser light. Effectiveness of dye photosensitization towards destruction of RLM function was assayed by its effect on the RLM membrane potential. Three physical parameters of dye phototoxicity were independently measured and a relative phototoxicity calculated assuming adherence of mechanism to the 1O2 hypothesis. Quantum yields of dye sensitized 1O2 production were estimated, either from time-resolved luminescence measurements of photosensitized 1O2 formed, or by comparing rates of photobleaching of 1O2 trap; the relative partition of dye into mitochondrial lipid was determined gravimetrically; and the optical density of dye was determined in a lipid like Triton X-100 micellar environment. Under the assumption of the 1O2 hypothesis, these parameters were used to predict a relative phototoxicity which was compared with that observed. For 12 of the 14 dyes investigated, the observed and predicted phototoxicities were linearly correlated (r = 0.85) suggesting support of the 1O2 hypothesis. Carbocyanines DiOC2(3) and DiSC2(3) did not correlate and were found to be 10 and 1000 times more potent than predicted, suggesting an additional factor at play in their phototoxicity.
Stability analysis of a pressure‐solution surface (1998)

We present a linear stability analysis of a dissolution surface subjected to non‐hydrostatic stress. A sinusoidal perturbation is imposed on an initially flat solid/fluid interface, and the consequent changes in elastic strain energy and surface energy are calculated. Our results demonstrate that if the far‐field lateral stresses are either greater, or much smaller than the fluid pressure, the perturbed configuration has a lower strain energy than the initial one. For wavelengths greater than a critical wavelength this energy decrease may be large enough to offset the increased surface energy. Under these conditions, the perturbation grows unstably. If these conditions are not met, the surface becomes flat. The growth rate and wavelength of the maximally unstable mode depend on the mechanism of matter transport. We conclude that the instability discussed in this paper may account for the formation of stylolites and other pressure‐solution phenomena, such as roughening of grain contacts.
Modulation of adriamycin and N-trifluoroacetyladriamycin-14-valerate induced effects on cell cycle traverse and cytotoxicity in P388 mouse leukemia cells by caffeine and the calmodulin inhibitor trifluoperazine. (1986)

1,3,7-Trimethylxanthine "caffeine" (CAF) is reported to induce a differential effect on the cytotoxicity of the DNA intercalators actinomycin-D versus Adriamycin (ADR). In the present study the effect of caffeine and/or trifluoperazine in modulating cell cycle traverse, drug accumulation, and cytotoxicity of anthracyclines was evaluated. The survival in soft agar of P388 mouse leukemia cells treated with ADR (0.05-0.25 micrograms/ml) alone for 1 h was 1.2- to 3-fold lower when the cells were incubated for 24 h in drug-free medium versus medium supplemented with 2 mM CAF. In contrast, for P388 cells treated with ADR in the presence of 2 mM CAF for 1 h and subsequently incubated for 24 h in the absence or presence of 2 mM CAF, cell killed based on colony formation in soft agar was 2- to 20-fold lower than in ADR-treated cells never exposed to 2 mM CAF. In cells treated continuously for 24 h with ADR (0.01-0.05 micrograms/ml) or the DNA nonbinding ADR analogue N-trifluoro-acetyladriamycin-14-valerate (AD32) (0.05 and 0.1 micrograms/ml) the survival in soft agar was 3- to 20-fold higher in the presence versus the absence of 2 mM CAF. The decreased cytotoxicity in cells treated with ADR or AD32 in the presence of CAF was accompanied by a significant reduction in the accumulation of cells in G2. However, in cells treated with ADR or AD32 in the presence of 2 mM CAF plus 5 microM trifluoperazine the decreased G2 accumulation was not accompanied by a reduction in anthracycline cytotoxicity. The modulation by CAF of ADR and AD32 cytotoxicity did not correlate with decreased cellular ADR and AD32 accumulation. Results from this study indicate that CAF markedly reduces the cytotoxicity of ADR or AD32 and trifluoperazine circumvents the effects of CAF.
Mechanistic and Structural Basis of Stereospecific Cβ-Hydroxylation in Calcium-Dependent Antibiotic, a Daptomycin-Type Lipopeptide (2007)

Non-ribosomally synthesized lipopeptide antibiotics of the daptomycin type are known to contain unnatural beta-modified amino acids, which are essential for bioactivity. Here we present the biochemical and structural basis for the incorporation of 3-hydroxyasparagine at position 9 in the 11-residue acidic lipopeptide lactone calcium-dependent antibiotic (CDA). Direct hydroxylation of l-asparagine by AsnO, a non-heme Fe(2+)/alpha-ketoglutarate-dependent oxygenase encoded by the CDA biosynthesis gene cluster, was validated by Fmoc derivatization of the reaction product and LC/MS analysis. The 1.45, 1.92, and 1.66 A crystal structures of AsnO as apoprotein, Fe(2+) complex, and product complex, respectively, with (2S,3S)-3-hydroxyasparagine and succinate revealed the stereoselectivity and substrate specificity of AsnO. The comparison of native and product-complex structures of AsnO showed a lid-like region (residues F208-E223) that seals the active site upon substrate binding and shields it from sterically demanding peptide substrates. Accordingly, beta-hydroxylated asparagine is synthesized prior to its incorporation into the growing CDA peptide. The AsnO structure could serve as a template for engineering novel enzymes for the synthesis of beta-hydroxylated amino acids.
Uniformly Most Powerful Detection For Integrate And Fire Time Encoding (2014)

Publication in the conference proceedings of EUSIPCO, Lisbon, Portugal, 2014
Beat the Machine (2015)

We present techniques for gathering data that expose errors of automatic predictive models. In certain common settings, traditional methods for evaluating predictive models tend to miss rare but important errors—most importantly, cases for which the model is confident of its prediction (but wrong). In this article, we present a system that, in a game-like setting, asks humans to identify cases that will cause the predictive model-based system to fail. Such techniques are valuable in discovering problematic cases that may not reveal themselves during the normal operation of the system and may include cases that are rare but catastrophic. We describe the design of the system, including design iterations that did not quite work. In particular, the system incentivizes humans to provide examples that are difficult for the model to handle by providing a reward proportional to the magnitude of the predictive model's error. The humans are asked to “Beat the Machine” and find cases where the automatic model (“the Machine”) is wrong. Experiments show that the humans using Beat the Machine identify more errors than do traditional techniques for discovering errors in predictive models, and, indeed, they identify many more errors where the machine is (wrongly) confident it is correct. Furthermore, those cases the humans identify seem to be not simply outliers, but coherent areas missed completely by the model. Beat the Machine identifies the “unknown unknowns.” Beat the Machine has been deployed at an industrial scale by several companies. The main impact has been that firms are changing their perspective on and practice of evaluating predictive models. “ There are known knowns. These are things we know that we know. There are known unknowns. That is to say, there are things that we know we don't know. But there are also unknown unknowns. There are things we don't know we don't know .” -- Donald Rumsfeld
Restoration of Hindlimb Movements after Complete Spinal Cord Injury Using Brain-Controlled Functional Electrical Stimulation (2017)

Single neuron and local field potential signals recorded in the primary motor cortex have been repeatedly demonstrated as viable control signals for multi-degree-of-freedom actuators. Although the primary source of these signals has been fore/upper limb motor regions, recent evidence suggests that neural adaptation underlying neuroprosthetic control is generalizable across cortex, including hindlimb sensorimotor cortex. Here, adult rats underwent a longitudinal study that included a hindlimb pedal press task in response to cues for specific durations, followed by brain machine interface (BMI) tasks in healthy rats, after rats received a complete spinal transection and after the BMI signal controls epidural stimulation (BMI-FES). Over the course of the transition from learned behavior to BMI task, fewer neurons were responsive after the cue, the proportion of neurons selective for press duration increased and these neurons carried more information. After a complete, mid-thoracic spinal lesion that completely severed both ascending and descending connections to the lower limbs, there was a reduction in task-responsive neurons followed by a reacquisition of task selectivity in recorded populations. This occurred due to a change in pattern of neuronal responses not simple changes in firing rate. Finally, during BMI-FES, additional information about the intended press duration was produced. This information was not dependent on the stimulation, which was the same for short and long duration presses during the early phase of stimulation, but instead was likely due to sensory feedback to sensorimotor cortex in response to movement along the trunk during the restored pedal press. This post-cue signal could be used as an error signal in a continuous decoder providing information about the position of the limb to optimally control a neuroprosthetic device.
Age‐dependent changes in response property and morphology of a thermosensory neuron and thermotaxis behavior in Caenorhabditis elegans (2020)

Age-dependent cognitive and behavioral deterioration may arise from defects in different components of the nervous system, including those of neurons, synapses, glial cells, or a combination of them. We find that AFD, the primary thermosensory neuron of Caenorhabditis elegans, in aged animals is characterized by loss of sensory ending integrity, including reduced actin-based microvilli abundance and aggregation of thermosensory guanylyl cyclases. At the functional level, AFD neurons in aged animals are hypersensitive to high temperatures and show sustained sensory-evoked calcium dynamics, resulting in a prolonged operating range. At the behavioral level, senescent animals display cryophilic behaviors that remain plastic to acute temperature changes. Excessive cyclase activity of the AFD-specific guanylyl cyclase, GCY-8, is associated with developmental defects in AFD sensory ending and cryophilic behavior. Surprisingly, loss of the GCY-8 cyclase domain reduces these age-dependent morphological and behavioral changes, while a prolonged AFD operating range still exists in gcy-8 animals. The lack of apparent correlation between age-dependent changes in the morphology or stimuli-evoked response properties of primary sensory neurons and those in related behaviors highlights the importance of quantitative analyses of aging features when interpreting age-related changes at structural and functional levels. Our work identifies aging hallmarks in AFD receptive ending, temperature-evoked AFD responses, and experience-based thermotaxis behavior, which serve as a foundation to further elucidate the neural basis of cognitive aging.
Calmodulin regulation of the calcium-leak channel Sec61 is unique to vertebrates (2011)

In eukaryotes, protein transport into the endoplasmic reticulum (ER) is facilitated by a protein-conducting channel, the Sec61 complex. The presence of large, water-filled pores with uncontrolled ion permeability, such as those formed by Sec61 complexes in the ER membrane, would interfere with the regulated release of calcium from the ER lumen into the cytosol, an essential mechanism of intracellular signaling. We identified a calmodulin (CaM) binding motif in the cytosolic N-terminus of Sec61α from Canis familiaris that binds CaM, but not Ca(2+)-free apo-CaM, with nanomolar affinity and sequence specificity. In single channel lipid bilayer measurements, CaM potently mediated Sec61-channel closure in a Ca(2+)-dependent manner. No functional CaM binding motif was identified in the corresponding region of Sec61p from Saccharomyces cerevisiae, and no channel closure occurred in the presence of CaM and Ca(2+). Therefore, CaM binding to the cytosolic N-terminus of Sec61α is involved in limiting Ca(2+)-leakage from the ER in C. familiaris but not S. cerevisiae.