gebhart/patrepeval huggingface dataset:
Faculty Opinions recommendation of Atypical protein kinase C regulates dual pathways for degradation of the oncogenic coactivator SRC-3/AIB1. (2008)

SRC-3/AIB1 is a steroid receptor coactivator with potent growth-promoting activity, and its overexpression is sufficient to induce tumorigenesis. Previous studies indicate that the cellular level of SRC-3 is tightly regulated by both ubiquitin-dependent and ubiquitin-independent proteasomal degradation pathways. Atypical protein kinase C (aPKC) is frequently overexpressed in cancers. In the present study, we show that aPKC phosphorylates and specifically stabilizes SRC-3 in a selective ER-dependent manner. We further demonstrate that an acidic residue-rich region in SRC-3 is an important determinant for aPKC-mediated phosphorylation and stabilization. The mechanism of the aPKC-mediated stabilization appears due to a decreased interaction between SRC-3 and the C8 subunit of the 20S core proteasome, thus preventing SRC-3 degradation. Our results demonstrate a potent signaling mechanism for regulating SRC-3 levels in cells by coordinate enzymatic inhibition of both ubiquitin-dependent and ubiquitin-independent proteolytic pathways. PMID: 18313384 Funding information This work was supported by: NICHD NIH HHS, United States Grant ID: HD08818 NICHD NIH HHS, United States Grant ID: R01 HD008188-31S1 NICHD NIH HHS, United States Grant ID: R01 HD008188
Simultaneous Topographic and Fluorescence Imagings of Recombinant Bacterial Cells Containing a Green Fluorescent Protein Gene Detected by a Scanning Near-Field Optical/Atomic Force Microscope (1997)

A scanning near-field optical/atomic force microscope (SNOAM) system was applied for simultaneous topographic and fluorescence imaging of biological samples in air and liquid. The SNOAM uses a bent optical fiber simultaneously as a dynamic mode atomic force microscopy cantilever and as a scanning near-field optical microscopy probe. Optical resolution of this system was about 50-100 nm in fluorescence mode for fluorescent latex beads on a quartz glass plate. Green fluorescent protein (GFP) is a convenient indicator of transformation and should allow cells to be separated by fluorescence-activated cell sorting. The gene coding to GFP was cloned in recombinant Escherichia coli. The SNOAM system used 458- or 488-nm irradiation from a multiline Ar ion laser for excitation of GFP, since a native GFP has been known to give a maximum at 395 nm and a broad absorption spectrum until 500 nm. Topographic and fluorescence images of recombinant E. coli were obtained simultaneously with a high spatial resolution which was apparently better than that of a conventional confocal microscope. A nanoscopic GFP fluorescence spectrum was obtained by positioning the optical fiber probe above the bright area of the E. coli cells. Comparing topographic and fluorescence images, it can be seen that individual E. coli cells expressed different fluorescence intensities. Fluorescence obtained by SNOAM indicated that GFP oxidation possibly occurred near the cell surface. A SNOAM system also indicated the possibility of precise imaging of native cells in liquid.
Thermochemical Heat Storage – from Reaction Storage Density to System Storage Density (2016)

Long-term and compact storage of solar energy is crucial for the eventual transition to a 100% renewable energy economy. For this, thermochemical materials provide a promising solution. The compactness of a long-term storage system is determined by the thermochemical reaction, operating conditions, and system implementation with the necessary additional system components. Within the MERITS project a thermochemical storage (TCS) system is being demonstrated using evacuated, closed TCS modules containing Na2S as active material. The present modules are expected to reach a heat storage density of 0.18GJ/m3. In this paper, we discuss the different factors leading to this storage density, and argue that by further optimization of the selected reaction and architecture, the result may be improved to approximately 1GJ/m3, which would be a practical value for seasonal heat storage in buildings.
Cellularity of Thymic Epithelial Cells in the Postnatal Mouse (2018)

The molecular and cellular biology of thymic epithelial cells (TECs) often relies on the analysis of TECs isolated in enzymatically digested single-cell suspensions derived from mouse thymus. Many independent studies have reported that the estimated cellularity of total TECs isolated from one adult mouse is on the order of up to 10<sup>5</sup> However, these numbers appear extremely small given that the cellularity of total thymocytes exceeds 10<sup>8</sup> and that TECs play multiple roles in thymocyte development and repertoire formation. In the present study, we aimed to measure the numbers of β5t-expressing cortical TECs and Aire-expressing medullary TECs in postnatal mouse thymus in situ without enzymatic digestion. The numbers of these TECs were manually counted in individual thymic sections and were three-dimensionally summed throughout the entire thymic lobes. The results show that the cellularity of total TECs in one 5-wk-old female mouse exceeds 10<sup>6</sup>, containing ∼9 × 10<sup>5</sup> β5t<sup>+</sup> cortical TECs and ∼1.1 × 10<sup>6</sup> Aire<sup>+</sup> medullary TECs. These results suggest that the use of conventional enzymatic digestion methods for the isolation of TECs may have resulted in the underestimation of the cellularity, and possibly the biology, of TECs.
Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target (2020)

ABSTRACT Mammalian protein N - linked glycosylation is critical for glycoprotein folding, quality control, trafficking, recognition and function. N - linked glycans are synthesized from Glc 3 Man 9 GlcNAc 2 precursors that are trimmed and modified in the endoplasmic reticulum (ER) and Golgi apparatus by glycoside hydrolases and glycosyltransferases. Endo-α-1,2-mannosidase (MANEA) is the sole endo -acting glycoside hydrolase involved in N - glycan trimming and unusually is located within the Golgi, where it allows ER escaped glycoproteins to bypass the classical N - glycosylation trimming pathway involving ER glucosidases I and II. There is considerable interest in the use of small molecules that disrupt N-linked glycosylation as therapeutic agents for diseases such as cancer and viral infection. Here we report the structure of the catalytic domain of human MANEA and complexes with substrate-derived inhibitors, which provide insight into dynamic loop movements that occur upon substrate binding. We reveal structural features of the human enzyme that explain its substrate preference and the mechanistic basis for catalysis. The structures inspired the development of new inhibitors that disrupted host protein N - glycan processing of viral glycans and reduced infectivity of bovine viral diarrhea and dengue viruses in cellular models. These results may contribute to efforts of developing broad-spectrum antiviral agents and bring about a more detailed view of the biology of mammalian glycosylation. SIGNIFICANCE STATEMENT The glycosylation of proteins is a major protein modification that occurs extensively in eukaryotes. Glycosidases in the secretory pathway that trim N-linked glycans play a key role in protein quality control and in the specific modifications leading to mature glycoproteins. Inhibition of glucosidases in the secretory pathway is a proven therapeutic strategy, and one with great promise in the treatment of viral disease. The enzyme endo-α-1,2-mannosidase, MANEA, provides an alternative processing pathway to evade glucosidase inhibitors. We report the 3D structure of human MANEA and complexes with enzyme inhibitors that we show act as antivirals for bovine viral diarrhea and human dengue viruses. The structure of MANEA will support inhibitor optimization and the development of more potent antivirals.
Antenna Integrated With a Microstrip Filter for 5G Mm-wave Applications (2018)

In this work, a filtering mm-wave antenna array is proposed for the future 5G mobile devices. The filtering antenna design is based on the fourth-order coupled line planar filter with a metal lid added in order to increase the filter sharpness and decrease loss. In this paper, the metal lid is modified so the slot antenna is formed at the end of the filter. Finally, the proposed antenna element is combined into a linear phased array on the short edge of the typical mobile ground plane.
Mobilization as a preparative regimen for hematopoietic stem cell transplantation (2006)

Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3(b) mice were treated with AMD3100 at 2 hours before the transplantation of 4 x 10(7) marrow cells, donor cell engraftment was higher (4.6% +/- 1.1%) than in control animals (no AMD3100; 1.0% +/- 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% +/- 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.
VLSI neural network implementation of a hippocampal model (2002)

As an important portion of the brain system, the hippocampus performs cognitive functions of learning and memory. VLSI implementation of a hippocampal model has been proposed and a mixed analog-digital chip which uses analog circuits for parallel computing and digital circuit for interconnection was designed. The design with one extensive hippocampal neuron has been sent for fabrication. One of the objectives of this research effort is to incorporate adequate biological constraints as possible into the hardware design.
Software evolution in AOSD (2011)

In this paper we present a model-based approach to tackle the fragility pointcut problem that occurs in Aspect Oriented Systems. We focus on evaluating our work aiming at demonstrating that the definition of model-based pointcuts at early stages of the development can improve the software evolution in AOSD.
X-ray crystallography of large RNAs: heavy-atom derivatives by RNA engineering. (1996)

For small RNAs, isomorphous heavy-atom derivatives can be obtained by crystallizing synthetic versions that incorporate modified nucleotides such as iodo- or bromouridine. However, such a synthetic approach is not yet feasible for RNAs greater than approximately 40 nt. We have been investigating P4-P6, a 160-nt domain of the self-splicing Tetrahymena intron whose structure was solved recently (Cate JH et al., 1996, Science 273:1678-1685). To incorporate iodouridine, a two-piece RNA was constructed. The 5' segment, containing the majority of the molecule, was transcribed in vitro using a self-processing hammerhead ribozyme to cleave the nascent transcript and give a homogenous 3' end. A synthetic 5-iodouridine-containing RNA corresponding to the remainder of the sequence was then annealed to the transcribed piece of RNA. The resulting RNA appeared structurally and functionally sound as judged by nondenaturing gel electrophoresis and RNA cleavage assays. Four versions of this two-piece system with 5-iodouridine substitutions at different positions crystallized under the same conditions as the native RNA, yielding two useful heavy-atom derivatives of P4-P6. The position of the iodine atoms for the derivatives could be determined in the absence of phase information, and an interpretable electron density map was calculated using only the data from the two iodouridine derivatives. This approach is expected to be readily adaptable to other large, structured RNA molecules.
Expression and chromosomal localization of the gene for the human transcriptional repressor GCF. (1992)

GCF is a human transcriptional regulator that represses transcription of certain genes and is encoded by a 3-kilobase (kb) mRNA (Kageyama, R., and Pastan, I. (1989) Cell 59, 815-825). The expression of GCF was examined in a variety of clonal cell lines. The 3.0-kb GCF mRNA was found to be expressed at the highest level in HUT 102 cells (derived from a T-cell lymphoma). Elevated levels of the GCF mRNA were also noted in KATO III and AGS (gastric carcinomas), FEM-X (melanoma), and U266B1 (myeloma) cell lines. A human fibroblast cell line (WI38) did not express GCF mRNA, and no cross-hybridization to a mouse cell line (NIH 3T3) or monkey cell line (CV-1) could be detected. The GCF cDNA also hybridizes to RNA species of 4.5 and 1.2 kb. The 4.5-kb RNA has the same general expression pattern as the GCF mRNA. Hybridization of cellular RNA with various probes derived from the 3-kb cDNA revealed that the 4.5-kb RNA species only hybridizes to GCF cDNA probes from the extreme 5' end. By using single-stranded RNA probes, hybridization to the three RNA species was detected with the antisense probe for the 5' end (nucleotides 1-561). The single-stranded antisense probe for the region encompassing nucleotides 561-1692 hybridized to the 3.0- and 1.2-kb RNA species. The sense probes for these regions did not hybridize to these RNAs. The GCF gene was localized to a single locus, the chromosome 2 p11.1-11.2 region, by in situ hybridization. Treatment of human KB epidermoid carcinoma cells with phorbol 12-myristate 13-acetate (PMA) lead to a rapid induction of GCF RNA after 1 h and a decline to lower than control levels after 6 h. Epidermal growth factor receptor mRNAs were not increased by PMA until 2 h after treatment and were at their highest level only after GCF mRNAs were decreased. The 4.5- and 1.2-kb RNAs were also induced by PMA with the same kinetics as the GCF mRNA. These results show that the GCF gene is widely expressed in human tissues and cell lines and that the 4.5- and 1.2-kb RNAs have similar expression patterns.
A Fast Reroute Scheme for IP Multicast (2009)

We propose a fast reroute scheme for the single link failure protection of IP multicast network. A multicast network connects nodes as a spanning tree, which is vulnerable to link failures. Our scheme uses ring topologies to ensure a backup path always exists to any single link failure and only a few nodes in the neighborhood of the failed link have to react to the failure. Compare to other solutions, we have four advantages: (1) The multicast tree can be arbitrary. (2) There is only a minimal disruption and there would be no packet loss. (3) Failure protection is available to a wider set of network topologies. (4) Only a small number of multicast nodes are involved and the number of spare links used are also small.
<title>Characteristics of laminated electrochromic devices using polyorganodisulfide electrodes</title> (1993)

The use of polyorganodisulfides as optically passive counter-electrodes in a variety of electrochromic devices are discussed. Characteristic data is presented for electrochromic devices using proton, and lithium coloration ions with polyethylene oxide electrolyte and polydimercaptothiadiazole positive electrodes. Solid state devices consisting of molybdenum doped WO<SUB>3</SUB>, emorphous polyethylene oxide electrolyte (a-PEO), and a polyorganodisulfide counter-electrode colored rapidly from a pale yellow to a deep blue-green, upon application of 1.2 V d.c. The photopic transmittance changed from 61 to 9%, and the solar transmittance from 45 to 5% during the coloration process. Also, our experiments with polyimidazole are detailed. This family of compounds due to its unique electrical and ion conduction properties allow a single composite ion storage and ion conductor electrode to be made, simplifying the device construction. Devices made from this family of compounds color to deep blue-gray upon application of 1.2 - 1.5 V. Bleaching occurs at -0.4 to -0.5V. The photopic transmittance changed from 55 to 9%, and the solar transmittance from 34 to 4% during coloration. Both coloration and bleaching are quite rapid.
PERFORMANCE OF THE TXDOT T202 (MOD) BRIDGE RAIL REINFORCED WITH FIBER REINFORCED POLYMER BARS (2003)

The purpose of this project was to investigate the behavior of fiber reinforced polymer (FRP) reinforcement in a concrete bridge rail when subjected to a vehicle collision. FRP reinforcement for a Texas Department of Transportation (TXDOT) T202 (MOD) bridge rail (now TXDOT T203 bridge rail) was designed, and the rail was subjected to two full-scale crash tests. Two design conditions were incorporated into the test article. One was based on strength immediately after construction, and the other was based on reduced strength after deterioration due to long-term exposure to the environment. In the first test, which was performed on the stronger section, structural performance of the rail was good, but the vehicle rolled and safety performance was unacceptable. For the second test, which was performed on the weaker section, the height of the rail was increased to 30 in. Both structural and safety performance of the rail was good.
Using Tandem Mass Spectrometry in Targeted Mode to Identify Activators of Class IA PI3K in Cancer (2011)

Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct mutation, but it is activated more commonly in cancer by mutation of upstream acting receptor tyrosine kinases (TK). At present, there is no systematic method to determine which TK signaling cascades activate PI3K in certain cancers, despite the likely utility of such information to help guide selection of tyrosine kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we present a quantitative liquid chromatography tandem mass spectrometry approach that identifies upstream activators of PI3K both in vitro and in vivo. Using non-small cell lung carcinoma to illustrate this approach, we show a correct identification of the mechanism of PI3K activation in several models, thereby identifying the most appropriate TKI to downregulate PI3K signaling. This approach also determined the molecular mechanisms and adaptors required for PI3K activation following inhibition of the mTOR kinase TORC1. We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish a mass spectrometric approach to identify functional interactions that govern PI3K regulation in cancer cells. Using this technique to define the pathways that activate PI3K signaling in a given tumor could help inform clinical decision making by helping guide personalized therapeutic strategies for different patients.
Bilateral neurological deficits following unilateral minimally invasive TLIF: A review of four patients (2014)

The rate of new neurological deficits following an MI-TLIF procedure is low, as documented in this study where the rate was 1.2%. Nonetheless, acknowledgement and open discussion of this serious complication is important for surgeon education. Of interest, the specific etiology or pathophysiology behind these complications remains relatively unknown (e.g. direct neural injury, traction injury, hypoperfusion, positioning complication, and others) despite there being some similarities between the patients and their perioperative courses.
Computational modeling and fluorescence microscopy characterization of a two-phase magnetophoretic microsystem for continuous-flow blood detoxification (2018)

Magnetic beads can be functionalized to capture and separate target pathogens from blood for extracorporeal detoxification. The beads can be magnetically separated from a blood stream and collected into a coflowing buffer solution using a two-phase liquid-liquid continuous-flow microfluidic device in the presence of an external field. However, device design and process optimization, i.e. high bead recovery with minimum blood loss or dilution remain a substantial technological challenge. We introduce a CFD-based Eulerian-Lagrangian computational model that enables the rational design and optimization of such systems. The model takes into account dominant magnetic and hydrodynamic forces on the beads as well as coupled bead-fluid interactions. Fluid flow (Navier-Stokes equations) and mass transfer (Fick's law) between the coflowing fluids are solved numerically, while the magnetic force on the beads is predicted using analytical methods. The model is demonstrated via application to a prototype device and used to predict key performance metrics; degree of bead separation, flow patterns, and mass transfer, i.e. blood diffusion to the buffer phase. The impact of different process variables and parameters - flow rates, bead and magnet dimensions and fluid viscosities - on both bead recovery and blood loss or dilution is quantified for the first time. The performance of the prototype device is characterized using fluorescence microscopy and the experimental results are found to match theoretical predictions within an absolute error of 15%. While the model is demonstrated here for analysis of a detoxification device, it can be readily adapted to a broad range of magnetically-enabled microfluidic applications, e.g. bioseparation, sorting and sensing.
Lab-Scale Preparation of a Novel Cyclopenta[b]furan Chemokine Receptor Antagonist (2014)

The preparation of a chemokine receptor type 2 (CCR-2) antagonist bearing a cyclopenta[b]furan core is described on a 600 g scale. Compared to our previously reported synthesis of the all-carbon core CCR-2 antagonist with a similar peripheral 3-methoxypyran appendage, our work required a redesign of the original Discovery Chemistry route and took advantage of a side product seen in the diastereoselective alkylation reaction. Elaboration by reduction and oxy-cyclization eventually led to the required N-Boc acid method. After amidation using a traditional coupling reaction, a reductive amination using enantiomerically enriched 3-methoxy-4-pyranone led to the final compound. Although several steps of the syntheses involved reagents such as selenium and chromium that would not be used in a large-scale process setting, the overall route went through intermediates that could certainly be used for future scale-up campaigns. The synthesis provided a method to make lab-scale quantities of the final succinate salt to support tox/toleration studies. Relative to the Discovery Chemistry route, this lab-scale route featured novel intermediates that could open new avenues for future research in this area.