gebhart/patrepeval huggingface dataset:
Perillyl alcohol and rapamycin‐mediated inhibition of migration and invasion (2013)

The plant‐derived isoprenoid perillyl alcohol (POH) exerts anti‐cancer properties via effects on mTOR (mechanistic target of rapamycin) signaling in a similar but distinct process as does rapamycin, a well‐studied mTOR inhibitor. Previously, rapamycin was shown to inhibit both matrix metalloproteinases (MMPs)‐2 and ‐9 in a human umbilical vein endothelial cell line. MMPs are key indicators of both angiogenesis induction and tumor cell metastatic activity. We evaluated clinically relevant concentrations of POH and rapamycin for their respective abilities to limit cellular migration and invasion of a highly metastatic human prostate cancer line–DU145. In a wound healing assay, POH or rapamycin significantly prevented DU145 cells from migrating into the wound area during a 24 hr period. Further, both agents inhibited DU145 movement through an ECM layer in a cell invasion assay. Gelatin zymography revealed that POH and rapamycin reduced the activity of secreted MMP‐2 and ‐9 in a time‐dependent manner. Additionally, decreased intracellular MMP‐2 activity was observed after treatment with either agent. Pre‐treatment with the proteasome inhibitor MG‐132 rescued MMP‐2 activity indicating that POH and rapamycin provoke MMP‐2 degradation. Our results establish comparable anti‐invasive abilities of POH–which displays fewer side effects–and rapamycin that are associated with MMP‐2 and ‐9 down‐regulation. Funding provided by a Golden Key Research Grant.
Further characterization of the epidermal growth factor receptor ligand 11C-PD153035 (2007)

The uptake of PET tracer (11)C-PD153035 closely correlates with the EGFR expression levels in tumor cells. (11)C-PD153035 has the potential to yield useful information for both cancer diagnosis and therapy.
Determinant of the Sample Covariance Matrix Based Spectrum Sensing Algorithm for Cognitive Radio (2011)

The presence of the primary signal changes not only the signal energy but also the correlation structure, a new spectrum sensing algorithm based on the determinant of the sample covariance matrix is then introduced. The new algorithm utilizes the fact that the determinant of the sample covariance matrixes of received signals is different from that of noise samples with high probability to detect whether the primary signal presents or not. Multivariate statistical theories are used to derive the theoretical decision threshold. The new method can execute spectrum sensing without the information about the primary signal and the communication channel. Simulation results show that the proposed method exhibits better performance than the maximum eigenvalue detection (MED) for moderate and low correlation received signals.
Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS (2002)

The pathogenesis of cell death in amyotrophic lateral sclerosis (ALS) may involve glutamate-mediated excitotoxicity, oxidative damage, and apoptosis. We used a transgenic mouse model of ALS to determine the effect of inhibition of cyclooxygenase-2 in treating the disease. Cyclooxygenase-2, present in spinal neurons and astrocytes, catalyzes the synthesis of prostaglandin E2. Prostaglandin E2 stimulates glutamate release from astrocytes, whereas cyclooxygenase-2 also plays a key role in the production of proinflammatory cytokines, reactive oxygen species, and free radicals. Treatment with a selective cyclooxygenase-2 inhibitor, celecoxib, markedly inhibited production of prostaglandin E2 in the spinal cords of ALS mice. Celecoxib treatment significantly delayed the onset of weakness and weight loss and prolonged survival by 25%. Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase-2 inhibition may benefit ALS patients.
Picometer Resolution Structure of the Coordination Sphere in the Metal-Binding Site in a Metalloprotein by NMR (2020)

Most of our understanding of chemistry derives from atomic-level structures obtained with single-crystal X-ray diffraction. Metal centers in X-ray structures of small organometallic or coordination complexes are often extremely well-defined, with errors in the positions on the order of 10<sup>-4</sup>-10<sup>-5</sup> Å. Determining the metal coordination geometry to high accuracy is essential for understanding metal center reactivity, as even small structural changes can dramatically alter the metal activity. In contrast, the resolution of X-ray structures in proteins is limited typically to the order of 10<sup>-1</sup> Å. This resolution is often not sufficient to develop precise structure-activity relations for the metal sites in proteins, because the uncertainty in positions can cover all of the known ranges of bond lengths and bond angles for a given type of metal complex. Here we introduce a new approach that enables the determination of a high-definition structure of the active site of a metalloprotein from a powder sample, by combining magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, tailored radio frequency (RF) irradiation schemes, and computational approaches. This allows us to overcome the "blind sphere" in paramagnetic proteins, and to observe and assign <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N resonances for the ligands directly coordinating the metal center. We illustrate the method by determining the bond lengths in the structure of the Co<sup>II</sup> coordination sphere at the core of human superoxide dismutase 1 (SOD) with 0.7 pm precision. The coordination geometry of the resulting structure explains the nonreactive nature of the Co<sup>II</sup>/Zn<sup>II</sup> centers in these proteins, which allows them to play a purely structural role.
Effects of CNB-001, a synthetic curcumin derivative, on thrombin-induced phosphorylation of MAP kinases in primary cultured rat microglia (2020)

We have recently found that CNB-001, a synthetic curcumin derivative, suppresses thrombin-induced nitric oxide (NO) production in cultured microglia, demonstrating that it exerts anti-neuroinflammatory effects by regulating microglial activation. In the present study, we investigated the molecular mechanisms underlying the suppressive effects of CNB-001 on thrombin-induced inflammatory responses. Western blotting analysis demonstrated that thrombin (10 U/mL) induced rapid phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). CNB-001 significantly suppressed the thrombin-induced phosphorylation of ERK and p38 MAPK, but not JNK. In addition, the suppressive effect of CNB-001 on NO production was mimicked by blockage of the ERK and p38 MAPK signaling pathways with U0126 and SB203580. These results suggest that CNB-001 suppresses thrombin-induced microglial activation through inhibition of ERK and p38 MAPK pathways.
Hypoglycemic Activity of Polysaccharide from Fruiting Bodies of the Shaggy Ink Cap Medicinal Mushroom, Coprinus comatus (Higher Basidiomycetes), on Mice Induced by Alloxan and Its Potential Mechanism (2015)

Three polysaccharide fractions from fruiting bodies of Coprinus comatus-CC30, CC60, and CC80-are obtained by water extraction and ethanol precipitation with ethanol percentages of 30%, 60%, and 80%, respectively. The hypoglycemic activity of the three fractions was tested based on mice with alloxan-induced diabetes. Results indicate that fraction CC60 is the most effective fraction in water extract from C. comatus; it can remarkably reduce the blood glucose concentration in 120 min at a dosage of 1000 mg/kg administered orally. It also presents a long-term hypoglycemic effect during 21 days of injection at the same dosage. This polysaccharide fraction provide a novel path to improve the treatment currently used for patients with diabetes. The data on mice spleen lymphocyte proliferation and protein tyrosine phosphatase 1B (PTP1B)-inhibiting activity of fractions indicate that the hypoglycemic activity of CC60 is possibly activated through immune stimulation, not PTP1B inhibition.
Generalized Hyperalgesia in Patients With Chronic Tension-Type Headache (2006)

Increased pain sensitivity in the central nervous system may play an important role in the pathophysiology of chronic tension-type headache (CTTH). Previous studies using pain thresholds as a measure of central pain sensitivity have yielded inconsistent results and only a few studies have examined perception of muscle pain without involvement of adjacent tissues. It has been suggested that suprathreshold testing might be more sensitive than threshold measurements in evaluation of central hyperexcitability in CTTH. The aim of the study was to compare pain ratings to suprathreshold single and repetitive (2 Hz) electrical stimulation of muscle and skin in cephalic (temporal and trapezius) and extracephalic (anterior tibial) regions between patients with CTTH and healthy subjects. In addition, we aimed to examine gender differences in pain ratings to suprathreshold stimulation and degree of temporal summation of pain between patients and controls. Pain ratings to both single and repetitive suprathreshold stimulation were higher in patients than in controls in both skin and muscle in all examined cephalic and extracephalic regions (P < 0.04). Pain ratings to both single and repetitive suprathreshold electrical stimulation were significantly higher in female compared with male patients (P < 0.001) and in female compared with male controls (P < or = 0.001). The degree of temporal summation of muscular and cutaneous pain tended to be higher in patients than in controls but the differences were not statistically different. This study provides evidence for generalized increased pain sensitivity in CTTH and strongly suggests that pain processing in the central nervous system is abnormal in this disorder. Furthermore, it indicates that suprathreshold stimulation is more sensitive than recording of pain thresholds for evaluation of generalized pain perception.
Relevance of octanol–water distribution measurements to the potential ecological uptake of multi-walled carbon nanotubes (2010)

Many potential applications of carbon nanotubes (CNTs) require various physicochemical modifications prior to use, suggesting that nanotubes having varied properties may pose risks in ecosystems. A means for estimating bioaccumulation potentials of variously modified CNTs for incorporation in predictive fate models would be highly valuable. An approach commonly used for sparingly soluble organic contaminants, and previously suggested for use as well with carbonaceous nanomaterials, involves measurement of their octanol-water partitioning coefficient (KOW) values. To test the applicability of this approach, a methodology was developed to measure apparent octanol-water distribution behaviors for purified multi-walled carbon nanotubes and those acid treated. Substantial differences in apparent distribution coefficients between the two types of CNTs were observed, but these differences did not influence accumulation by either earthworms (Eisenia foetida) or oligochaetes (Lumbriculus variegatus), both of which showed minimal nanotube uptake for both types of nanotubes. The results suggest that traditional distribution behavior-based KOW approaches are likely not appropriate for predicting CNT bioaccumulation.
Binding of Calcium to Individual .gamma.-Carboxyglutamic Acid Residues of Human Protein C (1995)

Selectively labeled polypeptides comprising the gamma-carboxyglutamic acid (Gla) domain (GD) and helical stack (HS) regions of human protein C (PC), and consisting of amino acid residues 1-47, have been chemically synthesized and their Ca2+ binding properties assessed by [13C]-NMR methods. A total of nine such polypeptides have been studied, each containing one of the Gla residues fully enriched with [13C] at its two gamma-carboxylate carbon atoms. Additions of Ca2+ resulted in readily measurable [13C] chemical shifts, titrations of which were used to obtain apparent dissociation constants for each Gla residue in the presence of all other such residues. The Ca2+ titration data obtained on each of the nine polypeptides showed that Gla residues 6, 16, 25, and 26 were involved in the higher affinity Ca2+ binding sites, whereas the remaining Gla residues, viz., 7, 14, 19, 20, and 29, coordinated Ca2+ more weakly. The results are consistent with conclusions drawn from functional studies obtained with site-directed mutations of individual Gla residues and with the structural model of the GD/HS of human PC. In these cases, Gla residues 6, 16, and 26 served as coordination loci for internally located Ca2+ ions, and GD-related Ca(2+)- and PL-dependent properties of PC and activated PC were dependent on the integrity of these Gla residues.
The case for RAMClouds (2010)

Disk-oriented approaches to online storage are becoming increasingly problematic: they do not scale gracefully to meet the needs of large-scale Web applications, and improvements in disk capacity have far outstripped improvements in access latency and bandwidth. This paper argues for a new approach to datacenter storage called RAMCloud, where information is kept entirely in DRAM and large-scale systems are created by aggregating the main memories of thousands of commodity servers. We believe that RAMClouds can provide durable and available storage with 100-1000x the throughput of disk-based systems and 100-1000x lower access latency. The combination of low latency and large scale will enable a new breed of dataintensive applications.
Multiple increased osteoclast functions in individuals with neurofibromatosis type 1 (2011)

Skeletal abnormalities including scoliosis, tibial dysplasia, sphenoid wing dysplasia, and decreased bone mineral density (BMD) are associated with neurofibromatosis type 1 (NF1). We report the cellular phenotype of NF1 human-derived osteoclasts and compare the in vitro findings with the clinical phenotype. Functional characteristics (e.g., osteoclast formation, migration, adhesion, resorptive capacity) and cellular mechanistic alterations (e.g., F-actin polymerization, MAPK phosphorylation, RhoGTPase activity) from osteoclasts cultured from peripheral blood of individuals with NF1 (N = 75) were assessed. Osteoclast formation was compared to phenotypic, radiologic, and biochemical data. NF1 osteoprogenitor cells demonstrated increased osteoclast forming capacity. Human NF1-derived osteoclasts demonstrated increased migration, adhesion, and in vitro bone resorption. These activities coincided with increased actin belt formation and hyperactivity in MAPK and RhoGTPase pathways. Although osteoclast formation was increased, no direct correlation of osteoclast formation with BMD, markers of bone resorption, or the clinical skeletal phenotype was observed suggesting that osteoclast formation in vitro cannot directly predict NF1 skeletal phenotypes. While NF1 haploinsufficiency produces a generalized osteoclast gain-in-function and may contribute to increased bone resorption, reduced BMD, and focal skeletal defects associated with NF1, additional and perhaps local modifiers are likely required for the development of skeletal abnormalities in NF1.
High-energy fiber optical parametric chirped-pulse oscillator (2021)

High-power wavelength-agile fiber sources are now competitive for many widespread applications such as non-linear imaging or coherent Raman scattering spectroscopy. Soliton self-frequency shift, self-mode conversion and self-phase modulation are commonly used to obtain the necessary wavelength shift but are limited in peak-power scalability due to intensity-related damages. However, it is possible to overcome this limitation by exploiting the broad tunability offered by degenerate four-wave mixing in optical fibers along with chirped-pulse amplification (CPA), then allowing the generation of high-energy fs pulses at different wavelengths [1] - [4] . Moreover, the exploitation of this principle in a fiber optical parametric oscillator (FOPO) with normal dispersion can enable record performances in terms of pulse energy [5] . Combining both concepts to build a fiber optical parametric chirped-pulse oscillator (FOPCPO) is then attractive to enable a full control of the output wavelength and bandwidth, as recently shown in a numerical study [6] . Thereby, we experimentally demonstrate here a high-energy FOPCPO, numerically analyze its operation, and discuss its potential for further energy scaling [7] .
A novel rearrangement in the syntheses of poly(3,3′‐phthalidylidene‐4,4′‐biphenylylene)s (1990)

Abstract Studies were made on the synthesis of halide‐substituted poly(phthalidylidenearylene)s by Friedel‐Crafts polycondensations of 3‐aryl‐3‐chlorophthalides containing substituents in 4‐position of the phthalide cycle. As follows from the C 13 NMR spectra, those monomers can afford polymers containing two types of isomeric units substituted in 4‐ or 7‐position. The possible routes of formation of the isomeric units are analyzed and a scheme is suggested for the monomer rearrangement in the synthetic course. The polymers containing those two types of units were shown to be highly thermostable and to contain about 30% of a crystalline phase.
Statistical methods applied to omics data (2014)

The review highlighted small sample sizes, few randomized trials and a large panel of statistical methods used in this setting. In our illustrated neoadjuvant example, causal inference methods did not outperform the penalized methods.
Stabilizing Hybrid Perovskites Via Non-Hydrolytic Atomic Layer Deposited Overlayers (2016)

A significant challenge to the practical application of hybrid perovskites remains for photovoltaic application. Specifically, the presence of hygroscopic ionic small molecules – alkylammonium cations – has been identified as a primary source of the absorber's sensitivity towards any moisture and any temperatures greater than 150 °C. CH 3 NH 3 PbI 3 , for instance, rapidly degrades upon exposure to modest relative humidity even at room temperature via: CH 3 NH 3 PbI 3 (s) → PbI 2 (s) + CH 3 NH 3 I(aq) A related, but distinct, decomposition pathway is induced by heating above 150 °C even under an inert and dry environment, where methylamine and hydroiodic acid have measurable vapor pressure: CH 3 NH 3 PbI 3 (s) → PbI 2 (s) + CH 3 NH 2 ↑ + HI↑ Various attempts have been made to improve system stability including modification of chemistry, two dimensional (2D) hybrid perovskites, and macroscopic encapsulation. While these measures may slow degradation the effect is often modest, transient, and adds significant device complexity. Synthetically-compatible, pinhole-free functional overlayers, in contrast, would provide a simple route to surface chemical passivation as well as a physical barrier to diffusion in or out of the active layer. Atomic Layer Deposition (ALD) is a vapor-phase deposition technique with the capability to produce ultra-thin and pinhole-free films with well-defined surface chemical control and precise physical thickness, providing a good match to these challenges. However, the vast majority of oxide ALD processes invoke water (H 2 O), hydrogen peroxide (H 2 O 2 ) or ozone (O 3 ) as oxygen sources, often at temperatures greater than 150 °C. Unfortunately, these chemicals and temperatures are predicted to be in direct conflict with most hybrid perovskite halides and therefore may preclude an integrated overlayer approach. However, we report low temperature non-hydrolytic (i.e. waterless) ALD to establish stabilizing overlayers of Al 2 O 3 or TiO 2 directly on CH 3 NH 3 PbI 3−x Cl x films. We demonstrate not only that oxide ALD conditions exist that are compatible with hybrid perovskite halides, but that the resulting systems exhibit dramatically improved stability against moisture (85% RH) and enhanced resistance to considerably higher temperatures (up to 250 °C) and even liquid water. We further demonstrate the capability of nh-TiO 2 to serve a dual role – stabilizing the absorber underlayer and accepting electrons in future inverted photovoltaics. The figure shows the effect of a liquid water drop after two minutes directly on a perovskite halide thin film, without and with an ultrathin hybrid ALD passivation layer. Figure 1
Apparent sterilizing immunity in BCG-immunized mice challenged with an ultra-low dose of Mycobacterium tuberculosis (2020)

Abstract Tuberculosis (TB) is a highly heterogeneous disease that develops in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). To improve upon the standard experimental mouse model, we infected mice with an ultra-low Mtb dose (ULD), consisting of 1-3 founding bacteria, which reflects the physiologic inoculum of humans. These mice exhibited a broad range of outcomes, with bacterial burdens ranging from &amp;lt;10 to ~106 CFUs in individual lungs. Furthermore, they exhibited well-circumscribed granulomas that share features with human granulomas. To monitor outcomes in live mice, we identified a blood RNA signature that correlated with lung bacterial burdens. Remarkably, this mouse-derived signature predicted Mtb infection outcomes across species, including risk of progression to active TB in humans. Given these improvements in the mouse model, we wondered whether ULD infection would provide a better platform for assessing vaccine-induced immunity. We now report that BCG-immunized mice, compared to unimmunized controls, exhibited a lower percentage of infected mice at late timepoints after ULD Mtb challenge. Interestingly, this difference was not observed at earlier timepoints. Taken together, these results suggest that some BCG-immunized mice, upon subsequent Mtb aerosol challenge, are capable of eradicating their initial infection, a finding that has not previously been observed in the TB mouse model. We are currently developing methods to verify initial infection prior to potential clearance and are also investigating immune correlates of protection.
Preparation and Characterization of Flexible Asymmetric Supercapacitors Based on Transition-Metal-Oxide Nanowire/Single-Walled Carbon Nanotube Hybrid Thin-Film Electrodes (2010)

In the work described in this paper, we have successfully fabricated flexible asymmetric supercapacitors (ASCs) based on transition-metal-oxide nanowire/single-walled carbon nanotube (SWNT) hybrid thin-film electrodes. These hybrid nanostructured films, with advantages of mechanical flexibility, uniform layered structures, and mesoporous surface morphology, were produced by using a filtration method. Here, manganese dioxide nanowire/SWNT hybrid films worked as the positive electrode, and indium oxide nanowire/SWNT hybrid films served as the negative electrode in a designed ASC. In our design, charges can be stored not only via electrochemical double-layer capacitance from SWNT films but also through a reversible faradic process from transition-metal-oxide nanowires. In addition, to obtain stable electrochemical behavior during charging/discharging cycles in a 2 V potential window, the mass balance between two electrodes has been optimized. Our optimized hybrid nanostructured ASCs exhibited a superior device performance with specific capacitance of 184 F/g, energy density of 25.5 Wh/kg, and columbic efficiency of approximately 90%. In addition, our ASCs exhibited a power density of 50.3 kW/kg, which is 10-fold higher than obtained in early reported ASC work. The high-performance hybrid nanostructured ASCs can find applications in conformal electrics, portable electronics, and electrical vehicles.