gebhart/patrepeval huggingface dataset:
Increased intracellular drug accumulation and complete chemosensitization achieved in multidrug-resistant solid tumors by co-administering valspodar(PSC 833) with sterically stabilized liposomal doxorubicin (2000)

We have previously demonstrated that liposome encapsulation of doxorubicin (DOX) can alleviate adverse interactions with non-encapsulated DOX and the cyclosporine multidrug-resistant (MDR) modulator Valspodar. We have now investigated the behavior of different liposomal DOX formulations in MDA435LCC6/MDR-1 human breast cancer solid tumor xenograft models to identify liposome characteristics associated with enhanced therapeutic activity and the mechanism whereby increased chemosensitization is achieved. Toxicity studies incorporating conventional phosphatidylcholine (PC)/cholesterol (chol) and sterically stabilized (polyethylene glycol 2000 [PEG]-containing) formulations of DOX indicated that whereas PC/Chol DOX was approximately 3-fold more toxic in the presence of Valspodar, PEG containing distearoylglycerophosphocholine (DSPC)/Chol DOX was minimally affected. In mice bearing MDR tumors, co-administration of Valspodar and egg phosphocholine (EPC)/Chol DOX resulted in modest MDR modulation and efficacy, whereas the sterically stabilized formulation induced reductions in tumor growth equivalent to that achieved for drug-sensitive tumors treated with non-encapsulated DOX. Pharmacokinetic studies revealed a 2.5-fold increase in plasma DOX area under the curve (AUC) upon co-administration of Valspodar with EPC/Chol DOX whereas no such alterations were observed with the sterically stabilized liposomes. Compared to non-encapsulated DOX combined with Valspodar, improvements in efficacy and toxicity correlated with the extent to which liposomal DOX formulations were able to circumvent pharmacokinetic interactions. Confocal microscopy demonstrated that Valspodar increased cell-associated DOX which correlated with the level of anti-tumor efficacy.
Neither gonadotropin nor cumulus cell expansion is needed for the maturation of competent porcine oocytes in vitro† (2021)

In-vitro maturation (IVM) of oocytes from immature females is widely used in assisted reproductive technologies. Here we illustrate that cumulus cell (CC) expansion, once considered a key indicator of oocyte quality, is not needed for oocytes to mature to the metaphase II (MII) stage and to gain nuclear and cytoplasmic competence to produce offspring. Juvenile pig oocytes were matured in four different media: (1) Basal (-gonadotropins (GN) - FLI); (2) -GN + FLI (supplement of FGF2, LIF, and IGF1); (3) +GN - FLI; and (4) +GN + FLI. There was no difference in maturation to MII or progression to the blastocyst stage after fertilization of oocytes that had been matured in -GN + FLI medium and oocytes matured in +GN + FLI medium. Only slight CC expansion occurred in the two media lacking GN compared with the two where GN was present. The cumulus-oocytes-complexes (COC) matured in +GN + FLI exhibited the greatest expansion. We conclude that FLI has a dual role. It is directly responsible for oocyte competence, a process where GN are not required, and, when GN are present, it has a downstream role in enhancing CC expansion. Our study also shows that elevated phosphorylated MAPK may not be a necessary correlate of oocyte maturation and that the greater utilization of glucose by COC observed in +GN + FLI medium probably plays a more significant role to meet the biosynthetic needs of the CC to expand than to attain oocyte developmental competence. Gene expression analyses have not been informative in providing a mechanism to explain how FLI medium enhances oocyte competence without promoting CC expansion.
Detection Of Amplified Or Deleted Chromosomal Regions (2023)

The present invention relates to in situ hybridization methods for the identification of new chromosomal abnormalities associated with various diseases. In particular, it provides probes which are specific to a region of amplification in chromosome 20.
Immunoparesis in newly diagnosed AL amyloidosis is a marker for response and survival (2017)

"Immunoparesis in newly diagnosed AL amyloidosis is a marker for response and survival." Amyloid, 24(sup1), pp. 40–41
DNA Sequence Preferences of GAL4 and PPR1: How a Subset of Zn 2 Cys 6 Binuclear Cluster Proteins Recognizes DNA (1996)

Biophysical and genetic experiments have defined how the Saccharomyces cerevisiae protein GAL4 and a subset of related proteins recognize specific DNA sequences. We assessed DNA sequence preferences of GAL4 and a related protein, PPR1, in an in vitro DNA binding assay. For GAL4, the palindromic CGG triplets at the ends of the 17-bp recognition site are essential for tight binding, whereas the identities of the internal 11 bp are much less important, results consistent with the GAL4-DNA crystal structure. Small reductions in affinity due to mutations at the center-most 5 bp are consistent with the idea that an observed constriction in the minor groove in the crystalline GAL4-DNA complex is sequence dependent. The crystal structure suggests that this sequence dependence is due to phosphate contacts mediated by arginine 51, as part of a network of hydrogen bonds. Here we show that the mutant protein GAL4(1-100)R51A fails to discriminate sites with alterations in the center of the site from the wild-type site. PPR1, a relative of GAL4, also recognizes palindromic CGG triplets at the ends of its 12-bp recognition sequence. The identities of the internal 6 bp do not influence the binding of PPR1. We also show that the PPR1 site consists of a 12-bp duplex rather than 16 bp as reported previously: the two T residues immediately 5' to the CGG sequence in each half site, although highly conserved, are not important for binding by PPR1. Thus, GAL4 and PPR1 share common CGG half sites, but they prefer DNA sequences with the palindromic CGG separated by the appropriate number of base pairs, 11 for GAL4 and 6 for PPR1.
A bilayer to monolayer phase transition in liquid crystal glycolipidsElectronic supplementary information (ESI) available: synthesis of compound 3. See http://www.rsc.org/suppdata/cc/b3/b308880d/ (2003)

Investigations of the thermotropic liquid-crystalline properties of 6,6'-di-O-stearoylsucrose show, for the first time, that glycolipids can exhibit phase transitions within the smectic A phase.
Fly-Tox: A panel of transgenic flies expressing pest and pollinator cytochrome P450s (2020)

There is an on-going need to develop new insecticides that are not compromised by resistance and that have improved environmental profiles. However, the cost of developing novel compounds has increased significantly over the last two decades. This is in part due to increased regulatory requirements, including the need to screen both pest and pollinator insect species to ensure that pre-existing resistance will not hamper the efficacy of a new insecticide via cross-resistance, or adversely affect non-target insect species. To add to this problem the collection and maintenance of toxicologically relevant pest and pollinator species and strains is costly and often difficult. Here we present Fly-Tox, a panel of publicly available transgenic Drosophila melanogaster lines each containing one or more pest or pollinator P450 genes that have been previously shown to metabolise insecticides. We describe the range of ways these tools can be used, including in predictive screens to avoid pre-existing cross-resistance, to identify potential resistance-breaking inhibitors, in the initial assessment of potential insecticide toxicity to bee pollinators, and identifying harmful pesticide-pesticide interactions.
Adaptive Projected Subgradient Method and its Applications to Robust Signal Processing (2006)

The adaptive projected subgradient method offers a unified mathematical perspective for the adaptive (set-membership/set-theoretic) filtering schemes. In this paper, we introduce an overview of its recent theoretical advances and successful applications to robust signal processing problems including the stereo acoustic echo canceling, the MAI suppression in DS/CDMA receivers, and the robust adaptive beamforming with array antenna systems
Impact of Technology Scaling on Metastability Performance of CMOS Synchronizing Latches (2002)

In this paper, we use circuit simulations to characterize the effects of technology scaling on the metastability parameters of CMOS latches used as synchronizers. We perform this characterization by obtaining a synchronization error probability curve from a histogram of the latch delay. The main metastability parameters of CMOS latches are /spl tau//sub m/ and T/sub w/. /spl tau//sub m/ is the exponential time constant of the rate of decay of metastability and T/sub w/ is effective metastability window size at a normal propagation delay. Both parameters can be extracted from a histogram of the latch delay. This paper also explains a way to calibrate the simulator for accuracy. The simulations indicate that /spl tau//sub m/ scales better than the technology scale factor. T/sub w/ also scales down but its factor cannot be estimated as well as that of /spl tau//sub m/. This is because T/sub w/ is a complex function of signal and clock edge rate and logic threshold level.
Effect of Componential Proportion in Bimetallic Electrocatalysts on the Aprotic Lithium‐Oxygen Battery Performance (2018)

Abstract Rechargeable lithium‐oxygen (Li‐O 2 ) batteries are one of the most promising technologies for next‐generation energy storage, which is also a critical part of the future renewable energy portfolio; however, its commercialization is still hindered by several challenges. The high charge overpotential, in particular, not only causes problems by increasing the possibility of electrolyte decomposition but also induces a low round‐trip efficiency and coulombic efficiency. Here, by choosing the right component proportion in Pt‐Cu bimetallic electrocatalysts that optimize electrocatalytic activity of electrochemical reactions, especially of oxygen evolution reactions, a superior electrochemical behavior is demonstrated, with a low charge overpotential of 0.2 V and cycleability of 50 discharge/charge cycles before capacity fading. The optimized Pt‐Cu bimetallic electrocatalysts significantly reduce the charge overpotential and furthermore enhance the efficiency, stability, and cycleability of an aprotic Li‐O 2 battery.
A range-bounding strategy for electric scooters (2012)

One of the main problems of electric vehicles, as felt by the market, is their limited range (<; 100 km for cars and <;50 km for scooters). As, typically, the driving style determines the range in a non-predictable way, in this work the approach is capsized and the desired range is used to set the optimal driving style. The proposed strategy is tested on a real electric scooter.
WNT Co-Receptor LRP6 Is Critical for Zygotic Genome Activation and Embryonic Developmental Potential by Interacting with Oviductal Paracrine Ligand WNT2 (2023)

Mammalian preimplantation development depends on the interaction between embryonic autocrine and maternal paracrine signaling. Despite the robust independence of preimplantation embryos, oviductal factors are thought to be critical to pregnancy success. However, how oviductal factors regulate embryonic development and the underlying mechanism remain unknown. In the present study, focusing on WNT signaling, which has been reported to be essential for developmental reprogramming after fertilization, we analyzed the receptor-ligand repertoire of preimplantation embryonic WNT signaling, and identified that the WNT co-receptor LRP6 is necessary for early cleavage and has a prolonged effect on preimplantation development. LRP6 inhibition significantly impeded zygotic genome activation and disrupted relevant epigenetic reprogramming. Focusing on the potential oviductal WNT ligands, we found WNT2 as the candidate interacting with embryonic LRP6. More importantly, we found that WNT2 supplementation in culture medium significantly promoted zygotic genome activation (ZGA) and improved blastocyst formation and quality following in vitro fertilization (IVF). In addition, WNT2 supplementation significantly improved implantation rate and pregnancy outcomes following embryo transfer. Collectively, our findings not only provide novel insight into how maternal factors regulate preimplantation development through maternal-embryonic communication, but they also propose a promising strategy for improving current IVF systems.
A stereologic study of the plantar fat pad in young and aged rats (2013)

Plantar fat pad (PFP) is a tissue structure that absorbs the initial impact of walking and running and ultimately bears body weight at standing. This study was designed to quantify the histomorphological changes of the PFP in aged rats. The most medial PFP was dissected from the hind feet of young rats (4 months old, n = 6) and aged rats (24 months old, n = 6). Histological structure and cellular senescence of PFP were analyzed stereologically and histomorphometrically. Immunohistochemistry of matrix metalloproteinase 9 (MMP9) was also performed on PFP tissue sections. Compared with young rats, the thickness of epidermis, dermis and septa of the PFP were significantly reduced in the aged rats. The total volume of adipose tissue in the PFP of aged rats was only about 65% of that in the young rats. The microvascular density and the number of fat pad units (FPU), a cluster of adipocytes enclosed by elastin septa, in the PFP were unchanged in the aged rats. In the aged rats, the number of adipocytes per FPU was reduced but the number of simple adipocyte clusters, without surrounding septa, was increased. The shift of the types of adipocyte clusters in the aged PFP was accompanied by degradation of elastin fibers and increased expression of MMP9. In conclusion, the PFP, particularly the elastic septa, degenerates significantly in aged rats and this may contribute to the pathology of PFP-related diseases.
Revolutional Progress of Silicon Technologies Exhibiting Very High Speed Performance Over a 50-GHz Clock Rate (2007)

Current silicon technologies are now facing very severe standstill, i.e., the operation speed is strictly limited at a clock rate of about 3.8 GHz due to the limitation of the thinning of the gate insulator film thickness because of its large amount of leakage currents through the current thermal oxide films. This typical disadvantage of current silicon technologies has been completely overcome by introducing the newly developed radical-reaction-based semiconductor manufacturing instead of the current molecule-reaction-based semiconductor manufacturing, i.e., direct nitridation films such as Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> where the gate leakage current through the insulator films has been confirmed to be decreased by a factor of at least three orders of magnitude. The speed performance of silicon large-scale integrations is enhanced to exhibit a clock rate of more than 50 GHz by introducing the balanced complementary MOS on a silicon (551) surface substrate using 3-D-structured MOS transistors, where new key technologies must be introduced, namely: 1) direct nitridation gate insulator film Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3 </sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> for 3-D MOS transistors; 2) atomic-order flat-gate insulator film/silicon interface; 3) drastically decreased series resistance of the source and drain electrodes by a factor of two orders of magnitude; and 4) introduction of the accumulation-mode MOS transistors instead of the inversion-mode MOS transistors
The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development (1998)

Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to the vascular endothelium, EPAS1 is expressed intensively in the organ of Zuckerkandl (OZ), the principle source of catecholamine production in mammalian embryos. EPAS1-deficient embryos contained substantially reduced catecholamine levels. Mid-gestational lethality was rescued by administration of the catecholamine precursor DOPS to pregnant females. We hypothesize that EPAS1 expressed in the OZ senses hypoxia during mid-gestational development and translates this signal into an altered pattern of gene expression, leading to increases in circulating catecholamine levels and proper cardiac function.
A CMOS Dual-RC frequency reference with ±250ppm inaccuracy from −45°C to 85°C (2018)

To comply with wired communication standards such as USB, SATA and PCI/PCI-E, systems-on-chip require frequency references with better than 300ppm accuracy. LC-based references achieve 100ppm accuracy [1], but suffer from high power consumption (~20mW). Thermal diffusivity (TD) references require less power (~2mW), at the expense of less accuracy (1000ppm) [2]. RC-based references offer the lowest power consumption, but their accuracy is typically limited to ~0.1% [3]. In RC relaxation oscillators, comparator offset and delay are the major sources of inaccuracy [4,5]. References based on frequency-locked loops (FLLs) circumvent these by locking an oscillator's frequency to the time-constant of an RC filter, but their accuracy is then limited by the nonlinear temperature dependency of on-chip resistors [3,6].
Computation of parameters in NMR using integral transforms: Tapered areas (2013)

This paper describes a method to compute tapered areas of a probability density function by means of integral transforms of its noisy Laplace transform. This problem is directly relevant to Nuclear Magnetic Resonance data for fluid and rock characterization. We describe integral transforms that are directly applicable to the measured magnetisation data, to estimate the tapered areas. In petrophysics, these tapered areas are useful in estimation of fluid saturations and bound and free fluid volumes. Since integral transforms are linear, uncertainty in the tapered areas can be computed as a function of signal-to-noise (SNR) in the data. Performance of these transforms is demonstrated on simulated data and compared to results from the traditional inverse Laplace transform.
Highly sensitive lidar with a thumb-sized sensor-head built using an optical fiber preamplifier (2011)

We developed a LIDAR system with a sensor head as small as 22 cc, in spite of the inclusion of a scanning mechanism. This LIDAR system not only has a small body, but is also highly sensitive. Our LIDAR system is based on time-of-flight measurements, and it incorporates an optical fiber. The main feature of our system is the utilization of optical amplifiers for both the transmitter and the receiver, and the optical amplifiers enabled us to exceed the detection limit of thermal noise. In conventional LIDAR systems the detection limit is determined by thermal noise, because the avalanche photo-diodes (APD) and trans-impedance amplifiers (TIA) that they use detect the received signals directly. In the case of our LIDAR system, received signal is amplified by an optical fiber amplifier in front of the photo diode and the TIA. Therefore, our LIDAR system can boost the signal level before the weak incoming signal is depleted by thermal noise. There are conditions under which the noise figure for the combination of an optical fiber amplifier and a photo diode is superior to the noise figure for an avalanche photo diode. We optimized the gain of the optical fiber amplifier and TIA in our LIDAR system such that it is capable of detecting a single photon. As a result, the detection limit of our LIDAR system is determined by shot noise. This small and highly sensitive measurement technology shows great potential for use in LIDAR with an optical preamplifier.
X-ray tomography using the full complex index of refraction (2012)

We report on x-ray tomography using the full complex index of refraction recorded with a grating-based x-ray phase-contrast setup. Combining simultaneous absorption and phase-contrast information, the distribution of the full complex index of refraction is determined and depicted in a bivariate graph. A simple multivariable threshold segmentation can be applied offering higher accuracy than with a single-variable threshold segmentation as well as new possibilities for the partial volume analysis and edge detection. It is particularly beneficial for low-contrast systems. In this paper, this concept is demonstrated by experimental results.
Pharmacodynamic measures within tumors expose differential activity of PD(L)-1 antibody therapeutics (2021)

Macromolecules such as monoclonal antibodies (mAbs) are likely to experience poor tumor penetration because of their large size, and thus low drug exposure of target cells within a tumor could contribute to suboptimal responses. Given the challenge of inadequate quantitative tools to assess mAb activity within tumors, we hypothesized that measurement of accessible target levels in tumors could elucidate the pharmacologic activity of a mAb and could be used to compare the activity of different mAbs. Using positron emission tomography (PET), we measured the pharmacodynamics of immune checkpoint protein programmed-death ligand 1 (PD-L1) to evaluate pharmacologic effects of mAbs targeting PD-L1 and its receptor programmed cell death protein 1 (PD-1). For PD-L1 quantification, we first developed a small peptide-based fluorine-18-labeled PET imaging agent, [<sup>18</sup>F]DK222, which provided high-contrast images in preclinical models. We then quantified accessible PD-L1 levels in the tumor bed during treatment with anti-PD-1 and anti-PD-L1 mAbs. Applying mixed-effects models to these data, we found subtle differences in the pharmacodynamic effects of two anti-PD-1 mAbs (nivolumab and pembrolizumab). In contrast, we observed starkly divergent target engagement with anti-PD-L1 mAbs (atezolizumab, avelumab, and durvalumab) that were administered at equivalent doses, correlating with differential effects on tumor growth. Thus, we show that measuring PD-L1 pharmacodynamics informs mechanistic understanding of therapeutic mAbs targeting PD-L1 and PD-1. These findings demonstrate the value of quantifying target pharmacodynamics to elucidate the pharmacologic activity of mAbs, independent of mAb biophysical properties and inclusive of all physiological variables, which are highly heterogeneous within and across tumors and patients.
Power Flow as an Algebraic System (2014)

Steady states of alternating-current (AC) circuits have been studied in considerable detail. In 1982, Baillieul and Byrnes derived an upper bound on the number of steady states in a loss-less AC circuit [IEEE TCAS, 29(11): 724--737] and conjectured that this bound holds for AC circuits in general. We prove this is indeed the case, among other results, by studying a certain multi-homogeneous structure in an algebraisation.