gebhart/patrepeval huggingface dataset:
Molecular and functional analysis of the SLIT2 gene in breast cancer (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2799 

The SLIT2 gene encodes a secreted glycoprotein that acts as a ligand for the ROBO transmembrane receptors. Studies suggest that the SLIT2-ROBO1 interaction plays an important role in migration of cells in both the nervous and immune system. SLIT2 also seems to be involved in human cancer development. In several types of cancer loss of heterozygosity (LOH) at the SLIT2 (4p15.2) locus was shown. We have previously demonstrated that the CpG island of the SLIT2 gene is frequently hypermethylated in breast, lung, colorectal and glioma primary tumours. Recently we detected methylation of the SLIT2 promoter region in DCIS (ductal carcinoma in situ ) lesions indicating that inactivation of this gene may play a role in early stages of breast cancer. We also found hypermethylation of the SLIT3 promoter region in breast and colorectal tumours albeit to a lesser degree than SLIT2. In addition we have shown that secreted SLIT2 has the ability to induce apoptosis in colorectal tumour cell lines. Colony formation and soft agar assays have also demonstrated that exogenous expression of SLIT2 can significantly suppress growth of breast tumour cell lines. SLIT2 expressing stable clones, generated from a breast tumour cell line that does not normally express this gene, were used for gene target identification. Expression microarray analysis identified 60 genes differentially regulated by SLIT2 that are now being confirmed by quantitative real-time RT-PCR. Among these targets are genes involved in cell cycle, apoptosis, cell adhesion, signalling, protein synthesis and transcription. We have also used siRNA to successfully knock down endogenous SLIT2 in a breast tumour cell line. We will investigate the properties of these cells by analysing their cell cycle profile along with carrying out apoptosis, cell migration and growth suppression assays. Overall there is increasing evidence supporting a role for SLIT2 as a tumour suppressor gene involved in breast cancer development.
Simulated evaluation of an intraoperative surface modeling method for catheter ablation by a real phantom simulation experiment (2015)

In this work, we propose a phantom experiment method to quantitatively evaluate an intraoperative left-atrial modeling update method. In prior work, we proposed an update procedure which updates the preoperative surface model with information from real-time tracked 2D ultrasound. Prior studies did not evaluate the reconstruction using an anthropomorphic phantom. In this approach, a silicone heart phantom (based on a high resolution human atrial surface model reconstructed from CT images) was made as simulated atriums. A surface model of the left atrium of the phantom was deformed by a morphological operation - simulating the shape difference caused by organ deformation between pre-operative scanning and intra-operative guidance. During the simulated procedure, a tracked ultrasound catheter was inserted into right atrial phantom - scanning the left atrial phantom in a manner mimicking the cardiac ablation procedure. By merging the preoperative model and the intraoperative ultrasound images, an intraoperative left atrial model was reconstructed. According to results, the reconstruction error of the modeling method is smaller than the initial geometric difference caused by organ deformation. As the area of the left atrial phantom scanned by ultrasound increases, the reconstruction error of the intraoperative surface model decreases. The study validated the efficacy of the modeling method.
New Butenolides from Two Marine Streptomycetes (2000)

Chemical examination of two marine Streptomycetes has resulted in the isolation of four new butenolides, namely 4, 10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), two diastereomeric 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olides (2/3), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (4). The structures were identified by interpretation of the 2D NMR and mass spectral data.
Photoinduced electron and energy transfer processes in a bichromophoric pyrene-perylene bisimide system (2004)

The synthesis and photophysical properties of a system consisting of a bay-functionalized perylene bisimide, containing four appended pyrene and two coordinating pyridine units, and its reference system are described. A complete study of their photophysical properties was obtained using UV-vis absorption, steady state and time-resolved emission, and femtosecond transient absorption. Analysis of the data, obtained from time-resolved emission and femtosecond transient absorption spectroscopy, showed the presence of both photoinduced electron and energy transfer processes. A high yield (&gt;90%) and fast photoinduced energy transfer (k(en) approximate to 6.2 x 10(9) s(-1)) is followed by efficient electron transfer (70%, k(et) approximate to 6.6 x 10(9) s(-1)) from the pyrene units to the perylene bisimide moiety. The energy donor-acceptor distance, R = 8.6 Angstrom, is calculated from the experimental energy transfer rate using Forster theory. Temperature-dependent time-resolved emission spectroscopy showed an increase of the acceptor emission lifetime with decreasing temperature. It also indicates the presence of different conformations because two different electron transfer barriers (0.08 and 0.42 eV) were found. These barrier values were corroborated by a theoretical analysis of the energetics of the process using Marcus theory, indicating average donor-acceptor distances of 4.5 Angstrom (room temperature) to 11 Angstrom (at low 7).
The Odorant (R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46 (2016)

Sensory studies showed the volatile fraction of lemon grass and its main constituent, the odor-active citronellal, to significantly decrease the perceived bitterness of a black tea infusion as well as caffeine solutions. Seven citronellal-related derivatives were synthesized and shown to inhibit the perceived bitterness of caffeine in a structure-dependent manner. The aldehyde function at carbon 1, the ( R)-configuration of the methyl-branched carbon 3, and a hydrophobic carbon chain were found to favor the bitter inhibitory activity of citronellal; for example, even low concentrations of 25 ppm were observed to reduce bitterness perception of caffeine solution (6 mmol/L) by 32%, whereas ( R)-citronellic acid (100 pm) showed a reduction of only 21% and ( R)-citronellol (100 pm) was completely inactive. Cell-based functional experiments, conducted with the human bitter taste receptors TAS2R7, TAS2R10, TAS2R14, TAS2R43, and TAS2R46 reported to be sensitive to caffeine, revealed ( R)-citronellal to completely block caffeine-induced calcium signals in TAS2R43-expressing cells, and, to a lesser extent, in TAS2R46-expressing cells. Stimulation of TAS2R43-expressing cells with structurally different bitter agonists identified ( R)-citronellal as a general allosteric inhibitor of TAS2R43. Further structure/activity studies indicated 3-methyl-branched aliphatic aldehydes with a carbon chain of ≥4 C atoms as best TAS2R43 antagonists. Whereas odor-taste interactions have been mainly interpreted in the literature to be caused by a central neuronal integration of odors and tastes, rather than by peripheral events at the level of reception, the findings of this study open up a new dimension regarding the interaction of the two chemical senses.
Heavy Metal Neurotoxicants Induce ALS-Linked TDP-43 Pathology (2018)

Heavy metals, such as lead, mercury, and selenium, have been epidemiologically linked with a risk of ALS, but a molecular mechanism proving the connection has not been shown. A screen of putative developmental neurotoxins demonstrated that heavy metals (lead, mercury, and tin) trigger accumulation of TDP-43 into nuclear granules with concomitant loss of diffuse nuclear TDP-43. Lead (Pb) and methyl mercury (MeHg) disrupt the homeostasis of TDP-43 in neurons, resulting in increased levels of transcript and increased splicing activity of TDP-43. TDP-43 homeostasis is tightly regulated, and positively or negatively altering its splicing-suppressive activity has been shown to be deleterious to neurons. These changes are associated with the liquid-liquid phase separation of TDP-43 into nuclear bodies. We show that lead directly facilitates phase separation of TDP-43 in a dose-dependent manner in vitro, possibly explaining the means by which lead treatment results in neuronal nuclear granules. Metal toxicants also triggered the accumulation of insoluble TDP-43 in cultured cells and in the cortices of exposed mice. These results provide novel evidence of a direct mechanistic link between heavy metals, which are a commonly cited environmental risk of ALS, and molecular changes in TDP-43, the primary pathological protein accumulating in ALS.
Durability Improvement of Cement Using Amphiphilic Calcium Carbonate Nanoparticles (2022)

The durability of cementitious materials is significant concerning long-term performance. Nanomaterials are promising candidates for deep refinement of cement durability. Hydrophobic calcium carbonate is a widely applied and easily accessible nanomaterial. However, its hydrophobicity and poor dispersity in water prohibit its direct application in cementitious materials. In this study, hydrophobic calcium carbonate nanoparticles (HbCC) were modified using a novel amphiphilic comb-shaped dispersant that is capable of laurinol release. The modification was conducted to improve the dispersity of HbCC and their compatibility with hydration products. The dispersion-improved calcium carbonate particles (AmphCC) were characterized and tested for cement durability improvement performance. According to the results, the AmphCC particles showed a pronounced effect on improving permeation resistance of cement mortars, with water absorption and chloride penetration considerably lowered. Moreover, the introduction of AmphCC in cement did not show significant adverse effects on strength development. Compared with AmphCC, a single addition of the unmodified HbCC and the dispersant cannot achieve equivalent effects. The superior effect of AmphCC is due to the synergistic effect of good particle dispersion and controlled release of the hydrophobic molecules, which is achieved by dispersion of HbCC with binding of the dispersant.
Model of Glycoprotein Hormone Receptor Ligand Binding and Signaling (2004)

Studies described here were initiated to develop a model of glycoprotein hormone receptor structure and function. We found that the region that links the lutropin receptor leucine-rich repeat domain (LRD) to its transmembrane domain (TMD) has substantial roles in ligand binding and signaling, hence we term it the signaling specificity domain (SSD). Theoretical considerations indicated the short SSDs in marmoset lutropin and salmon follitropin receptors have KH domain folds. We assembled models of lutropin, follitropin, and thyrotropin receptors by aligning models of their LRD, TMD, and shortened SSD in a manner that explains how substitutions in follitropin and thyrotropin receptors distant from their apparent ligand binding sites enable them to recognize lutropins. In these models, the SSD is parallel to the concave surface of the LRD and makes extensive contacts with TMD outer loops 1 and 2. The LRD appears to contact TMD outer loop 3 and a few residues in helices 1, 5, 6, and 7. We propose that signaling results from contacts of the ligands with the SSD and LRD that alter the LRD, which then moves TMD helices 6 and 7. The positions of the LRD and SSD support the notion that the receptor can be activated by hormones that dock with these domains in either of two different orientations. This would account for the abilities of some ligands and ligand chimeras to bind multiple receptors and for some receptors to bind multiple ligands. This property of the receptor may have contributed significantly to ligand-receptor co-evolution.
Matching a field tracer test with some simple models (1989)

Simple models of fluid flow and dispersion in a porous rock matrix are compared and used to match the results of tracer tests at the Wairakei (New Zealand) geothermal field. It is found that models which allow transient diffusion from fractures into the surrounding rock matrix give a better match to test results than either a model which allows only longitudinal dispersion or a pseudo steady state double porosity model. For some tests a model which includes two fractures is required to match the field data.
Interactions of the chaperone Hsp104 with yeast Sup35 and mammalian PrP (prionyprotein structureyaggregationychaperone protein) (1997)

PSI1) is a genetic element in yeast for which a heritable change in phenotype appears to be caused by a heritable change in the conformational state of the Sup35 protein. The inheritance of (PSI1) and the physical state of Sup35 in vivo depend on the protein chaperone Hsp104 (heat shock protein 104). Although these observations provide a strong genetic argument in support of the ''protein-only'' or ''prion'' hypothesis for (PSI1), there is, as yet, no direct evidence of an interaction between the two proteins. We report that when purified Sup35 and Hsp104 are mixed, the circular dichroism (CD) spectrum differs from that predicted by the addition of the proteins' individual spectra, and the ATPase activity of Hsp104 is inhibited. Similar results are obtained with two other amyloidogenic substrates, mammalian PrP and b-amyloid 1-42 peptide, but not with several control proteins. With a group of peptides that span the PrP protein sequence, those that produced the largest changes in CD spectra also caused the strongest inhibition of ATPase activity in Hsp104. Our observations suggest that (i) previously described genetic interactions between Hsp104 and (PSI1) are caused by direct interaction between Hsp104 and Sup35; (ii) Sup35 and PrP, the determinants of the yeast and mammalian prions, respec- tively, share structural features that lead to a specific inter- action with Hsp104; and (iii) these interactions couple a change in structure to the ATPase activity of Hsp104.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the analysis of polydienes (1997)

An analytical method based on matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry has been developed to provide information on oligomer structure, average molecular weight, and molecular weight distributions of polydienes (e.g., polybutadiene and polyisoprene), an important class of industrial polymers. This MALDI method involves the use of all-trans-retinoic acid as the matrix, copper (II) nitrate as the cationization reagent, and tetrahydrofuran as the solvent. The incorporation of this copper salt generates Cu+ adducts with the polymer chains. It also improves the signal strength and extends the upper mass range when used with all-trans-retinoic acid, as compared to silver nitrate. With this formulation, it is demonstrated that polybutadienes of narrow polydispersity with masses up to 300,000 u and polyisoprenes of narrow polydispersity with masses up to 150,000 u can be analyzed. The upper molecular weight limit is set by the requirement of using higher matrix-to-polymer ratios with increasing polymer molecular weight, to the point where the instrument can no longer detect the small quantity of polymer present in the matrix host. It is also shown that this sample preparation generates previously unreported adduction behavior. The practical implications of this adduction behavior on polymer structural analysis, accuracy of molecular weight determination, and the upper molecular weight limit of oligomer resolution are discussed. It is illustrated that, in a linear time-lag focusing MALDI instrument, oligomer resolution can be obtained for polydienes with molecular weights up to 24,000, providing structural confirmation of the end-groups and the repeat unit. The average molecular weights of a number of polydienes of narrow polydispersity determined by MALDI are compared to those obtained by gel permeation chromatography, and discrepancies are noted.
Learning Insertion Primitives with Discrete-Continuous Hybrid Action Space for Robotic Assembly Tasks (2022)

This paper introduces a discrete-continuous action space to learn insertion primitives for robotic assembly tasks. Primitives are sequences of elementary actions with certain exit conditions, such as “pushing down the peg until contact”. Since the primitive is an abstraction of robot control commands and encodes human prior knowledge, it reduces the exploration difficulty and yields better learning efficiency. In this paper, we learn robot assembly skills via primitives. Specifically, we formulate insertion primitives as parameterized actions: hybrid actions consisting of discrete primitive types and continuous primitive parameters. Compared with the previous work using a set of discretized parameters for each primitive, the agent in our method can freely choose primitive parameters from a continuous space, which is more flexible and efficient. To learn these insertion primitives, we propose Twin-Smoothed Multi-pass Deep Q-Network (TS-MP-DQN), an advanced version of MP-DQN with twin Q-network to reduce the Q-value over-estimation. Extensive experiments are conducted in the simulation and real world for validation. From experiment results, our approach achieves higher success rates than three baselines: MP-DQN with parameterized actions, primitives with discrete parameters, and continuous velocity control. Furthermore, learned primitives are robust to sim-to-real transfer and can generalize to challenging assembly tasks such as tight round peg-hole and complex shaped electric connectors with promising success rates. Experiment videos are available at https://msc.berkeley.edu/research/insertion-primitives.html.
Arabidopsis Downy Mildew Resistance Gene RPP27 Encodes a Receptor-Like Protein Similar to CLAVATA2 and Tomato Cf-9 (2004)

The Arabidopsis Ler-RPP27 gene confers AtSgt1b-independent resistance to downy mildew (Peronospora parasitica) isolate Hiks1. The RPP27 locus was mapped to a four-bacterial artificial chromosome interval on chromosome 1 from genetic analysis of a cross between the enhanced susceptibility mutant Col-edm1 (Col-sgt1) and Landsberg erecta (Ler-0). A Cf-like candidate gene in this interval was PCR amplified from Ler-0 and transformed into mutant Col-rpp7.1 plants. Homozygous transgenic lines conferred resistance to Hiks1 and at least four Ler-0 avirulent/Columbia-0 (Col-0) virulent isolates of downy mildew pathogen. A full-length RPP27 cDNA was isolated, and analysis of the deduced amino acid sequences showed that the gene encodes a receptor-like protein (RLP) with a distinct domain structure, composed of a signal peptide followed by extracellular Leu-rich repeats, a membrane spanning region, and a short cytoplasmic carboxyl domain. RPP27 is the first RLP-encoding gene to be implicated in disease resistance in Arabidopsis, enabling the deployment of Arabidopsis techniques to investigate the mechanisms of RLP function. Homology searches of the Arabidopsis genome, using the RPP27, Cf-9, and Cf-2 protein sequences as a starting point, identify 59 RLPs, including the already known CLAVATA2 and TOO MANY MOUTHS genes. A combination of sequence and phylogenetic analysis of these predicted RLPs reveals conserved structural features of the family.
Expression of Cancer Stem Cell-associated DKK1 mRNA Serves as Prognostic Marker for Hepatocellular Carcinoma (2017)

Expression of CSC-associated DKK1 mRNA might be an unfavorable prognostic marker for patients with HCC.
A Rhesus Macaque Model to Optimize Adoptive NK Cell Therapy (2008)

Abstract NK cell based immunotherapy represents a promising treatment approach for patients with cancer. Although preliminary clinical trials in humans suggest NK cell infusions can mediate anti-tumor effects, animal models are needed to provide insight into methods to enhance both the function and in vivo longevity of adoptively infused NK cells. Research conducted in our laboratory has shown that ex vivo expanded human NK cells are highly activated, up-regulating NKG2D, Granzyme B, TRAIL and Fas-ligand expression making them much more cytotoxic to tumor cells compared to freshly isolated NK cells. However, important questions remain regarding whether in vitro expansion alters the capacity of these cells to replicate, and traffic to tissues in vivo following their adoptive infusion into recipients. Differences in the genotype and phenotype of mouse NK cells compared to human NK cells limit the value of murine animal models to address these questions. In contrast to mice, Rhesus macaques have orthologues to most of the human MHC class I and II genes and possess NK cells expressing KIRs that are phenotypically and functionally similar to human NK cells, thus providing an excellent model system for evaluating questions related to adoptive NK cell therapy. We developed an in vitro method to expand macaque NK cells to characterize their in vivo longevity and tissue trafficking following adoptive infusion. Macaque NK cells were enriched from peripheral blood mononuclear cells by depleting CD3+ cells using immunomagnetic beads and were then expanded in vitro with autologous plasma and a human EBV-LCL feeder cell line using culture conditions identical to those used to expand NK cells from humans. NK cell cultures expanded 50- to 100-fold over 7 to 20 days, were greater than 99% CD3 negative, and had a similar phenotype to human NK cells including a large proportion of CD16/CD56 double positive cells, and ubiquitous expression of NKG2D, KIR2D, LFA-1, granzyme B, and CXCR3. In contrast to mice but analogous to human NK cells, macaque expanded NK cells upregulated surface expression of TRAIL and were highly cytotoxic to K562 cells and other human tumor lines (Figure). CFSE labelling of expanded NK cells did not alter their phenotype or tumor cytotoxic function. Data characterizing the longevity, proliferative capacity, and tissue trafficking patterns in the blood, bone marrow and lymph node of in vitro expanded and adoptively infused CFSE labeled NK cells (up to 1 × 108 NK Cells/kg i.v.) in macaque recipients will be presented from this analysis. Figure Figure
Multiple Spoofer Detection for Mobile GNSS Receivers Using Statistical Tests (2021)

We consider Global Navigation Satellite Systems (GNSS) spoofing attacks and devise a countermeasure appropriate for mobile GNSS receivers. Our approach is to design detectors that, operating after the signal acquisition, enable the victim receiver to determine with high probability whether it is under a spoofing attack or not. Namely, the binary hypothesis is that either the GNSS receiver tracks legitimate satellite signals, H0, or spoofed signals, H1. We assume that there exists an unknown number of multiple spoofers in the environment and the attack strategy (which legitimate signals are spoofed by which spoofers) is not known to the receiver. Based on these assumptions, we propose an algorithm that identifies the number of spoofers and clusters the spoofing data by using Bayesian information criterion (BIC) rule. Depending on the estimated and clustered data we propose a detector, called as generalized likelihood ratio (GLRT)-like detector. We compare the performance of the GLRT-like detector with a genie-aided detector in which the attack strategy and the number of spoofers is known by the receiver. In addition to this, we extend the GLRT-like detector for the case where the noise variance is also unknown and present the performance results.