gebhart/patrepeval huggingface dataset:
An Important Role for Polymeric Ig Receptor-Mediated Transport of IgA in Protection against Streptococcus pneumoniae Nasopharyngeal Carriage (2004)

The importance of IgA for protection at mucosal surfaces remains unclear, and in fact, it has been reported that IgA-deficient mice have fully functional vaccine-induced immunity against several bacterial and viral pathogens. The role of respiratory Ab in preventing colonization by Streptococcus pneumoniae has now been examined using polymeric IgR knockout (pIgR(-/-)) mice, which lack the ability to actively secrete IgA into the mucosal lumen. Intranasal vaccination with a protein conjugate vaccine elicited serotype-specific anti-capsular polysaccharide Ab locally and systemically, and pIgR(-/-) mice produced levels of total serum Ab after vaccination that were similar to wild-type mice. However, pIgR(-/-) mice had approximately 5-fold more systemic IgA and 6-fold less nasal IgA Ab than wild-type mice due to defective transport into mucosal tissues. Wild-type, but not pIgR(-/-) mice were protected against infection with serotype 14 S. pneumoniae, which causes mucosal colonization but does not induce systemic inflammatory responses in mice. The relative importance of secretory IgA in host defense was further shown by the finding that intranasally vaccinated IgA gene-deficient mice were not protected from colonization. Although secretory IgA was found to be important for protection against nasal carriage, it does not appear to have a crucial role in immunity to systemic pneumococcus infection, because both vaccinated wild-type and pIgR(-/-) mice were fully protected from lethal systemic infection by serotype 3 pneumococci. The results demonstrate the critical role of secretory IgA in protection against pneumococcal nasal colonization and suggest that directed targeting to mucosal tissues will be needed for effective vaccination in humans.
Genesis of ER stress in Huntington’s Disease (2015)

Abstract Recent research has identified ER stress as a major mechanism implicated in cytotoxicity in many neurodegenerative diseases, among them Huntington’s disease. This genetic disorder is of late-onset, progressive and fatal, affecting cognition and movement. There is presently no cure nor any effective therapy for the disease. This review focuses on recent findings that shed light on the mechanisms of the advent and development of ER stress in Huntington’s disease and on its implications, highlighting possible therapeutic avenues that are being or could be explored.
Effect of regional ischemia on the left ventricular end-systolic pressure-volume relationship of isolated canine hearts. (1983)

We studied the effects of regional ischemia on the left ventricular isovolumic end-systolic pressure-volume relationship (ESPVR) in six excised, blood-perfused canine ventricles. We created different extents of regional ischemia by ligating various branches of the coronary arteries while keeping the coronary arterial pressure constant (80 mm Hg). The extent of regional ischemia (Rm) relative to the total mass of the left ventricular myocardium was determined by regional myocardial blood flow measured by the radioactive microsphere technique. With regional ischemia, the ESPVR shifted rightward without significant change in slope in the physiologic end-systolic pressure range. In the subphysiological end-systolic pressure range, however, its slope became lower than control. In order to quantify the degree of the rightward shift, we measured the extrapolated volume axis intercept (Vo) by fitting a straight line to the ESPVR in the physiological range under control and ischemic conditions. The shift in Vo (delta Vo) associated with ischemia was linearly correlated with Rm (delta Vo = 50.7Rm-0.6, n = 28, r = 0.944, P less than 0.001). We conclude that the major effect of acute regional ischemia on the ESPVR in the physiological pressure range is a parallel rightward shift. This forms a striking contrast to the effect of global ischemia (under which only the slope is affected without a substantial change in Vo).
Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines (2015)

Nanoparticulate delivery systems represent an area of particular promise for nanoneuromedicines. They possess significant potential for desperately needed therapies designed to combat a range of disorders associated with aging. As such, the field was selected as the focus for the 2014 meeting of the American Society for Nanomedicine. Regenerative, protective, immune modulatory, anti-microbial and anti-inflammatory products, or imaging agents are readily encapsulated in or conjugated to nanoparticles and as such facilitate the delivery of drug payloads to specific action sites across the blood-brain barrier. Diagnostic imaging serves to precisely monitor disease onset and progression while neural stem cell replacement can regenerate damaged tissue through control of stem cell fates. These, taken together, can improve disease burden and limit systemic toxicities. Such enabling technologies serve to protect the nervous system against a broad range of degenerative, traumatic, metabolic, infectious and immune disorders. From the clinical editor: Nanoneuromedicine is a branch of nanomedicine that specifically looks at the nervous system. In the clinical setting, a fundamental hurdle in nervous system disorders is due to an inherent inability of nerve cells to regenerate after damage. Nanotechnology can offer new approaches to overcome these challenges. This review describes recent developments in nanomedicine delivery systems that would affect stem cell repair and regeneration in the nervous system.
A FOXO1-dependent transcription network is a targetable vulnerability of mantle cell lymphomas (2022)

Targeting lineage-defined transcriptional dependencies has emerged as an effective therapeutic strategy in cancer treatment. Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), we identified a set of transcription factors (TFs) including FOXO1, EBF1, PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network reconstruction analysis revealed FOXO1 as a master regulator that acts upstream in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to drive MCL lineage commitment through supporting the lineage-specific transcription programs. We further show that FOXO1, but not its close paralog FOXO3, can reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 inhibitor library, induces a robust cytotoxic response in MCL cells in vitro and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition as a therapeutic strategy targeting lineage-driven transcriptional addiction in MCL.
Stereospecific intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to (−)-abietadiene catalyzed by recombinant cyclase from grand fir (Abies grandis) (1998)

The cyclization–rearrangement of deuterated geranylgeranyl diphosphate (GGPP) and (+)-copalyl diphosphate (CPP) catalyzed by recombinant (–)-abietadiene synthase from grand fir proceeds with intramolecular proton transfer from C-19 of GGPP, and from the C-17 pro-E position of CPP, to form the C-16 pro-S methyl group of (–)-abietadiene.
The human hair follicle, a bistable organ? (2012)

The hair cycle and its control remain today an object of debate. A number of factors, which can modulate this process, have been identified but its choreography remains elusive. For years, the hunt for the conductor has been on, but nobody ever caught him. Intuitively, the process being considered as cyclic, an automaton controlling this cycle should be looked for, by analogy with a clock. However, the putative hair follicle oscillator that would control hair cycle failed to be identified and characterized. In fact, we have revealed that human hair follicle has an autonomous behaviour and that the transitions from one phase to the next occur independently for each follicle, after time intervals given stochastically by a lognormal distribution characterized by a mean and a variance. From this analysis, one can conclude that instead of a cyclical behaviour with an intrinsic automaton, a bistable steady state controls human hair follicle behaviour, which under a stochastic way jumps from the dormant to the active steady state and vice versa.
Microglia-independent peripheral neuropathic pain in male and female mice (2022)

The dominant view in the field of pain is that peripheral neuropathic pain is driven by microglia in the somatosensory processing region of the spinal dorsal horn. Here, to the contrary, we discovered a form of neuropathic pain that is independent of microglia. Mice in which the nucleus pulposus (NP) of the intervertebral disc was apposed to the sciatic nerve developed a constellation of neuropathic pain behaviours: hypersensitivity to mechanical, cold, and heat stimuli. However, NP application caused no activation of spinal microglia nor was pain hypersensitivity reversed by microglial inhibition. Rather, NP-induced pain hypersensitivity was dependent on cells within the NP which recruited macrophages to the adjacent nerve. Eliminating macrophages systemically or locally prevented NP-induced pain hypersensitivity. Pain hypersensitivity was also prevented by genetically disrupting the neurotrophin brain-derived neurotrophic factor selectively in macrophages. Moreover, the behavioural phenotypes as well as the molecular mechanisms of NP-induced pain hypersensitivity were not different between males and females. Our findings reveal a previously unappreciated mechanism for by which a discrete peripheral nerve lesion may produce pain hypersensitivity, which may help to explain the limited success of microglial inhibitors on neuropathic pain in human clinical trials.
A minimally invasive technique for percutaneous lumbar facet augmentation: Technical description of a novel device (2011)

This novel technique allows for percutaneous posterior dynamic stabilization of the lumbar facet complex. The use of this procedure may allow a less invasive alternative to traditional approaches to the lumbar spine as well as an alternative to other newly developed posterior dynamic stabilization systems.
Influence of Cation Type on Structure and Dynamics in Sulfonated Polystyrene Ionomers (2011)

The structure and dynamics of Na-, Cs-, and Zn-neutralized sulfonated polystyrene (SPS) ionomers were investigated using scanning transmission electron microscopy (STEM), X-ray scattering, and dielectric relaxation spectroscopy. Aggregates ∼2 nm in diameter were revealed by STEM and X-ray scattering. Additional information on aggregate diameter, radius of closest approach, and number density were determined by fitting the scattering data with a modified hard sphere model. A single broad segmental relaxation was identified in dielectric loss spectra for the ionomers neutralized with monovalent ions Cs and Na. The relaxation time of the segmental process was found to slow down systematically with increasing degree of sulfonation but is not significantly affected by monovalent ion type. For Cs-neutralized SPS, two high temperature relaxations associated with Maxwell–Wagner–Sillars and ion association/disassociation dynamics were identified.
Comparative Proteomic Analysis of Enterohemorrhagic E. coli (EHEC) Grown In Vitro Versus In Vivo using a 2-DE Gel Approach. (2010)

The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term "non-conventional" dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.
Development of Technologies for Early Detection and Stratification of Breast Cancer (2012)

Abstract : The overall goal of this work is to develop ultra-sensitive detection techniques to identify a panel of new biomarkers and indicators with diagnostic and predictive value in breast cancer. This year, multiple ultrasensitive assays for candidate breast cancer biomarkers were developed. Initial screens with commercially purchased samples showed some promising leads with diagnostic potential. Progress has also been made in the area of single cell analysis, which would be useful for analyzing both circulating tumor cells and single cells from tissue biopsies. Circulating tumor cell isolation using microfluidics has been accomplished with multiple platforms and these methods are being refined for high throughput and implementation. Good progress has been made on identifying additional markers (mtDNA, ADAM8, Tiam1) and correlations with various aspects of breast cancer invasiveness are apparent. Finally, a cancer mouse model was developed and a single molecule assay was used to detect a cancer biomarker in the blood after an inoculum of cultured cancer cells that is more than 300 times lower than a conventional inoculation. This bodes well for prospects of being able detect biomarkers in blood for early diagnosis, for monitoring recurrence, or for determining therapeutic efficacy.
Identification and Creation of the Room-Temperature Coherently Controllable ST1 Spin Center in Diamond (2022)

Among hundreds of optically active solid-state defects, very few of them hold the promise of spin qubits coherently operating at room temperature. Besides the prominent nitrogen-vacancy (NV) center in diamond, the more recently discovered ST1 center possesses advantageous electronic and spin properties such as a spin-free ground state and a large spin readout contrast (>50%) at 300 K. However, because of its unknown nature, the ST1 center was never created on demand or computed theoretically. Here, we show that both oxygen and the lattice vacancy are constituents of the ST1 center. The involvement of oxygen is unambiguously proved from two independent experiments conducted on two different samples. The creation efficiency of ST1 at 1200 °C annealing is about 10–5 for oxygen implantation of energy 6–50 keV. The addition of vacancies followed by a thermal treatment activate further oxygen into ST1 centers, as it does for native nitrogen into NV centers. Possible ST1 configurations are discussed. The ST1 creation competes with the likely more efficient formation of OV and OVH defects. The controlled fabrication of ST1 and NV centers opens up the way to scalable room-temperature hybrid qubit systems and universal nuclear spin gates.
Effects of an axisymmetric contraction on a turbulent pipe flow (2011)

Abstract The flow in an axisymmetric contraction fitted to a fully developed pipe flow is experimentally and numerically studied. The reduction in turbulence intensity in the core region of the flow is discussed on the basis of the budgets for the various turbulent stresses as they develop downstream. The contraction generates a corresponding increase in energy in the near-wall region, where the sources for energy production are quite different and of opposite sign compared to the core region, where these effects are caused primarily by vortex stretching. The vortices in the pipe become aligned with the flow as the stretching develops through the contraction. Vortices which originally have a spanwise component in the pipe are stretched into pairs of counter-rotating vortices which become disconnected and aligned with the mean flow. The structures originating in the pipe which are inclined at an angle with respect to the wall are rotated towards the local mean streamlines. In the very near-wall region and the central part of the contraction the flow tends towards two-component turbulence, but these structures are different. The streamwise and azimuthal stresses are dominant in the near-wall region, while the lateral components dominate in the central part of the flow. The two regions are separated by a rather thin region where the flow is almost isotropic.
Liquid phase separation of 1-butene from 2-butenes on all-silica zeolite RUB-41 (2008)

The all-silica zeolite RUB-41, containing 8- and 10-membered rings, is able to separate trans-2-butene and cis-2-butene from 1-butene and represents a possible improvement in isolating pure 1-butene from a butene mixture.
Reducing Oyster-Associated Bacteria Levels using Supercritical Fluid CO2 as an Agent of Cold Pasteurization (2008)

The effect of SCF CO2 on bacterial contaminants trapped in the digestive track of oysters (cultured and wild type harvested from Gulf Coast areas) was investigated. This study was completed after establishing the bactericidal potential of SCF CO2 in vitro using 3 bacteria: E. coli, V. fisherii and S. aureus. The effect of SCF CO2 on bacteria was monitored utilizing plate spreading techniques. SCF CO2 showed a bactericidal effect in vitro at 100 bar; the pattern of inactivation did not improve after the atmospheric pressure was increased from 100–200 bars. Under non-supercritical conditions the bactericidal potential of CO2 was significantly reduced (from 100% to 86%). It was shown that SCF CO2 can readily diffuse through oysters' tissues and inactivate ~ 94%–100% of bacteria that contaminate their digestive tract. No change in the color, smell or pH of the oysters as a result of this treatment was recorded. Acknowledgements: We would like to thank Dr. Melissa Jacob, NCNPR, School of Pharmacy, The University of Mississippi for providing the E. coli. The work was supported by NIH (NIAID) (1R01A136596) and a pre-doctoral fellowship from the Medicines for Malaria Venture (MMV). References: [1] Czyz A, et al. (2002) J. Appl. Genet. 43: 377–389. [2] Collins CH, et al. (1995) In “Microbiological Methods” p.114–115. [3] Damar S, Balaban MO (2006) J. Food Sci. 71: R1–11. [4] Dillow AK, et al. (1999) Proc. Natl. Acad. Sci. 96: 10344–10348. [5] Dunlap PV (1989) J. Bacteriol. 171: 1199–1202. [6] Hemmer JD, et al. (2007) J. Biomed. Mater. Res. B Appl. Biomater. 80: 511–518. [7] Potasman I et al. (2002) Clin. Infect. Dis. 35: 921–928. [8] Spilimbergo S, Bertucco A (2003) Biotech. and Bioeng. 84: 627–638. [9] Smelt J, Rijke G (1992) In “High Pressure Biotechnology” p.361–364. [10] Werner BG, Hotchkiss JH (2006) J. Dairy Sci. 86: 1932–1940.
Abstract 747: A new class of DNA alkylating indolino-benzodiazepine agents (BIAs) linked with a DNA binding moiety for use with antibody-drug conjugates (ADCs) (2018)

Abstract We have previously disclosed antibody-drug conjugates (ADCs) that incorporate our highly potent novel DNA alkylating indolino-benzodiazepine (termed IGN) pseudo dimer. ADCs of these DNA alkylating IGNs were found preclinically to demonstrate better tolerability and an improved overall therapeutic index (TI) compared with those of DNA crosslinking IGNs (Miller, et al., AACR 2017 #53). In our ongoing effort to further explore DNA alkylating effector molecules for ADCs, we disclose here a new class of IGNs (termed BIAs) in which one IGN monomer subunit is connected to a bis-aryl moiety with affinity for the DNA binding pocket. Our initial structure activity relationship (SAR) studies around a series of BIAs identified a set of scaffolds that met our requirement for high in vitro potency. These scaffolds were subsequently modified to incorporate functionalities that allow linkage to an antibody using various linker chemistries. These linkable BIAs displayed high in vitro potency across a panel of cell lines, indicating that the incorporation of a linker was not detrimental to their overall potency. Furthermore, we found that the potency of these linkable BIAs could be modulated by careful selection of substituents on the bis-aryl moiety providing enhanced binding affinity with DNA. Upon identification of lead BIA molecules, conjugates with a folate receptor-α (FRα)-binding antibody were prepared. These ADCs displayed potent, antigen-specific in vitro activity across a panel of FRα-expressing cell lines. In vivo, these ADCs demonstrated potent efficacy in xenograft models at doses well below the maximum tolerated dose. In light of these findings, BIA ADCs represent a promising new class of DNA alkylating effector molecules for use in the development of ADCs. Citation Format: Michael L. Miller, Emily E. Reid, Katie E. Archer, Manami Shizuka, Molly A. McShea, Erin K. Maloney, Olga Ab, Leanne Lanieri, Alan J. Wilhelm, Jose F. Ponte, Nicholas C. Yoder, Ravi V. Chari. A new class of DNA alkylating indolino-benzodiazepine agents (BIAs) linked with a DNA binding moiety for use with antibody-drug conjugates (ADCs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 747.
On-chip silicon-based waveguide with light guiding in low-index core materials (2005)

A new on-chip silicon-based Bragg cladding waveguide with full CMOS compatibility is developed. This novel optical waveguide has a low refractive index core (SiO<sub>2</sub>) surrounded by a 1D photonic crystal cladding. The cladding consists of several dielectric bilayers, where each bilayer consists of a high index-contrast pair of layers of Si and Si<sub>3</sub>N<sub>4</sub>. This new waveguide guides light based on omnidirectional reflection, reflecting light at any angle or polarization back into the core. Its fabrication is fully compatible with current microelectronics processes. In principle, a core of any low-index material can be realized with our novel structure, including air. Potential applications include tight turning radii, high power transmission, nonlinear properties engineering and biomaterials sensors on silicon chip.
Verification on the extreme scalability of STT-MRAM without loss of thermal stability below 15 nm MTJ cell (2014)

Scalability of interface driven perpendicular magnetic anisotropy (i-PMA) magnetic tunnel junctions (MTJs) has been improved down to 1X node which verifies STT-MRAM for future standalone memory. With developing a novel damage-less MTJ patterning process, robust magnetic and electrical performances of i-PMA MTJ cell down to 15 nm node could be achieved.
Agile wide-angle beam steering with electrowetting microprisms (2006)

A novel basis for beam steering with electrowetting microprisms (EMPs) is reported. EMPs utilize electrowetting modulation of liquid contact angle in order to mimic the refractive behavior for various classical prism geometries. Continuous beam steering through an angle of 14 degrees (+/-7 degrees ) has been demonstrated with a liquid index of n=1.359. Experimental results are well-matched to theoretical behavior up to the point of electrowetting contact-angle saturation. Projections show that use of higher index liquids (n~1.6) will result in steering through ~30 degrees (+/-15 degrees ). Fundamental factors defining achievable deflection range, and issues for Ladar use, are reviewed. This approach is capable of good switching speed (~ms), polarization independent operation, modulation of beam field-of-view (lensing), and high steering efficiency that is independent of deflection angle.