gebhart/patrepeval huggingface dataset:
Macrophage, the potential key mediator in CAR-T related CRS (2020)

Chimeric antigen receptor (CAR) T cell therapy is a new frontier in cancer therapy. The toxicity of cytokine release syndrome (CRS) has become one of the major challenges that limits the wider use of CAR T cells to fight cancer. Exploration of CRS pathogenesis and treatment is becoming the main focus of ongoing studies. Myeloid-derived macrophages were found to play a critical role in CRS pathogenesis, and these cells mediate the major production of core cytokines, including IL-6, IL-1 and interferon (IFN)-γ. Colocalization of macrophages and CAR T cells was also identified as necessary for inducing CRS, and CD40L-CD40 signaling might be the key cell-cell interaction in the tumor microenvironment. Macrophages might also take part in endocrine and self-amplified catecholamine loops that can directly activate cytokine production and release by macrophages during CRS. In addition to tocilizumab and corticosteroids, several novel CRS therapies targeting macrophage-centered pathways have shown much potential, including GM-CSF blockade and administration of atrial natriuretic peptide (ANP) and α-methyltyrosine (metyrosine, MTR). In the present review, we summarized the role of macrophages in CRS and new developments in therapeutic strategies for CRS-associated toxicities.
Crystal structure of the HLA-Cw3 allotype-specific killer cell inhibitory receptor KIR2DL2 (1999)

Killer cell inhibitory receptors (KIR) protect class I HLAs expressing target cells from natural killer (NK) cell-mediated lysis. To understand the molecular basis of this receptor-ligand recognition, we have crystallized the extracellular ligand-binding domains of KIR2DL2, a member of the Ig superfamily receptors that recognize HLA-Cw1, 3, 7, and 8 allotypes. The structure was determined in two different crystal forms, an orthorhombic P212121 and a trigonal P3221 space group, to resolutions of 3.0 and 2.9 A, respectively. The overall fold of this structure, like KIR2DL1, exhibits K-type Ig topology with cis-proline residues in both domains that define beta-strand switching, which sets KIR apart from the C2-type hematopoietic growth hormone receptor fold. The hinge angle of KIR2DL2 is approximately 80 degrees, 14 degrees larger than that observed in KIR2DL1 despite the existence of conserved hydrophobic residues near the hinge region. There is also a 5 degrees difference in the observed hinge angles in two crystal forms of 2DL2, suggesting that the interdomain hinge angle is not fixed. The putative ligand-binding site is formed by residues from several variable loops with charge distribution apparently complementary to that of HLA-C. The packing of the receptors in the orthorhombic crystal form offers an intriguing model for receptor aggregation on the cell surface.
Preparation and Evaluation in Vitro and Vivo of Copoly (lactic/glycolic) acid Microspheres Containing Norethisterone (1993)

Poly (lactic/glycolic) acid (PLGA) microspheres containing 20% norethisterone (NET) were prepared and the preparation methodology was optimised. The microspheres showed a slow and steady release pattern up to more than 96 hours in 27.5 wt% ethanol solution. In vivo performance of the microspheres indicated that a single intramuscular injection of 80 mg of microspheres could significantly prolong the duration of estrus suppression up to 45 days in rats. In addition, the studies on the stability of microspheres showed that there was no significant change both in the NET content of microspheres and the NET release rate in vitro after storage for one year.
Computer structures (1976)

Over the PDP-11'S six year life about 20,000 specimens have been built based on 10 species (models). Although range was a design goal, it was unquantified; the actual range has exceeded expectations (500:1 in memory size and system price). The range has stressed the basic mini(mal) computer architecture along all dimensions. The main PMS structure, i.e. the UNIBUS, has been adopted as a de facto standard of interconnection for many micro and minicomputer systems. The architectural experience gained in the design and use of the PDP-11 will be described in terms of its environment (initial goals and constraints, technology, and the organization that designs, builds and distributes the machine).
Linking Microbial Community Function to Phylogeny of Sulfate-Reducing <i>Deltaproteobacteria</i> in Marine Sediments by Combining Stable Isotope Probing with Magnetic-Bead Capture Hybridization of 16S rRNA (2009)

We further developed the stable isotope probing, magnetic-bead capture method to make it applicable for linking microbial community function to phylogeny at the class and family levels. The main improvements were a substantial decrease in the protocol blank and an approximately 10-fold increase in the detection limit by using a micro-elemental analyzer coupled to isotope ratio mass spectrometry to determine (13)C labeling of isolated 16S rRNA. We demonstrated the method by studying substrate utilization by Desulfobacteraceae, a dominant group of complete oxidizing sulfate-reducing Deltaproteobacteria in marine sediments. Stable-isotope-labeled [(13)C]glucose, [(13)C]propionate, or [(13)C]acetate was fed into an anoxic intertidal sediment. We applied a nested set of three biotin-labeled oligonucleotide probes to capture Bacteria, Deltaproteobacteria, and finally Desulfobacteraceae rRNA by using hydrophobic streptavidin-coated paramagnetic beads. The target specificities of the probes were examined with pure cultures of target and nontarget species and by determining the phylogenetic composition of the captured sediment rRNA. The specificity of the final protocol was generally very good, as more than 90% of the captured 16S rRNA belonged to the target range of the probes. Our results indicated that Desulfobacteraceae were important consumers of propionate but not of glucose. However, the results for acetate utilization were less conclusive due to lower and more variable labeling levels in captured rRNA. The main advantage of the method in this study over other nucleic acid-based stable isotope probing methods is that (13)C labeling can be much lower, to the extent that delta(13)C ratios can be studied even at their natural abundances.
Diversion colitis: a trigger for ulcerative colitis in the in-stream colon? (1999)

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.
Phase I and Pharmacokinetic Study of Irinotecan Administered as a Low-Dose, Continuous Intravenous Infusion Over 14 Days in Patients With Malignant Solid Tumors (1999)

The recommended dosage is 10 mg/m(2)/d for 14 days, repeated every 3 weeks. Enhanced metabolism of irinotecan to SN-38 may explain in part the low recommended dose for this schedule.
Coupling High Throughput Microfluidics and Small-Angle X-ray Scattering to Study Protein Crystallization from Solution (2017)

In this work, we propose the combination of small-angle X-ray scattering (SAXS) and high throughput, droplet based microfluidics as a powerful tool to investigate macromolecular interactions, directly related to protein solubility. For this purpose, a robust and low cost microfluidic platform was fabricated for achieving the mixing of proteins, crystallization reagents, and buffer in nanoliter volumes and the subsequent generation of nanodroplets by means of a two phase flow. The protein samples are compartmentalized inside droplets, each one acting as an isolated microreactor. Hence their physicochemical conditions (concentration, pH, etc.) can be finely tuned without cross-contamination, allowing the screening of a huge number of saturation conditions with a small amount of biological material. The droplet flow is synchronized with synchrotron radiation SAXS measurements to probe protein interactions while minimizing radiation damage. To this end, the experimental setup was tested with rasburicase (known to be very sensitive to denaturation), proving the structural stability of the protein in the droplets and the absence of radiation damage. Subsequently weak interaction variations as a function of protein saturation was studied for the model protein lysozime. The second virial coefficients (A2) were determined from the X-ray structure factors extrapolated to the origin. A2 obtained values were found to be in good agreement with data previously reported in literature but using only a few milligrams of protein. The experimental results presented here highlight the interest and convenience of using this methodology as a promising and potential candidate for studying protein interactions for the construction of phase diagrams.
Colloidal electroconvection in a thin horizontal cell. III. Interfacial and transient patterns on electrodes (2012)

Previously we have reported a family of convective patterns formed by charge-stabilized aqueous colloidal suspensions under constant (dc) vertical electric fields [Y. Han and D. G. Grier, J. Chem. Phys. 122, 164701 (2005); and ibid. 125, 144707 (2006)]. These patterns form in the bulk when electrokinetic forces act in the opposite direction to gravity. Here, we report on cellular patterns that silica colloidal spheres form on a horizontal electrode when electrokinetic forces act in the same direction as gravity. We suggest that these cellular patterns form as a result of bulk electroconvection mediated by charge injection into the supporting aqueous electrolyte. This charge-injection mechanism also accounts for some aspects of electroconvective pattern formation in our earlier reports. Cellular patterns reorganize themselves into distinct transient patterns after the driving voltage is turned off. These transients cast new light on the complex interplay between the motions of charged colloidal spheres and the ionic relaxation of water undergoing electrolysis.
Blockade of B7-H1 (Programmed Death Ligand 1) Enhances Humoral Immunity by Positively Regulating the Generation of T Follicular Helper Cells (2011)

T follicular helper (T(FH)) cells are critical initiators in the development of T cell-dependent humoral immunity and the generation of protective immunity. We demonstrate that T(FH) cell accumulation and Ab production are negatively regulated by B7-H1 (programmed death ligand 1) in response to both helminth infection and active immunization. Following immunization of B7-H1(-/-) mice with keyhole limpet hemocyanin or helminth Ags, there is a profound increase in induction of T(FH) cells as a result of increased cell cycling and decreased apoptosis relative to wild-type mice. The increase in T(FH) cells in the absence of B7-H1 was associated with significant elevations in Ag-specific Ig response. Cotransfer experiments in vivo demonstrated that B7-H1 expression on B cells was required for negatively regulating T(FH) cell expansion and production of Ag-specific Ig. Treatment of immunized wild-type mice with anti-B7-H1 or anti-programmed death 1 mAbs, but not anti-B7-DC, led to a significant expansion of the T(FH) cell population and an enhanced Ag-specific Ig response. Our results demonstrate that the coinhibitory B7-H1/programmed death 1 pathway can limit the expansion of T(FH) cells and constrain Ag-specific Ig responses. This finding has direct implications for investigations examining the feasibility of therapeutically manipulating this pathway and reveals new insights into the regulation of the humoral immune response.
A facile synthesis of methyl 2‐substituted‐4‐benzoxazolecarboxylates (1990)

Abstract Methyl 2‐substituted‐4‐benzoxazolecarboxylates were synthesized from methyl 2‐amino‐3‐hydroxybenzoate and the corresponding acid chloride or ortho acetal with pyridinium p ‐toluenesulfonate as an acid catalyst. Decomposition due to hydration at the 2‐position was seen for some compounds during purification.
Spontaneous Chiral Induction in a Cubic Phase (2005)

The optical property and the molecular packing structure of achiral bent-rod-shaped liquid crystalline compound 1 possessing an amide group and a flexible spacer were investigated by polarized optical microscopy (POM), circular dichroism (CD) spectroscopy, and X-ray diffraction (XRD). The molecules generated highly ordered liquid crystal phases by lateral intermolecular hydrogen bonds. The cubic phase observed in this study showed a chirality in CD spectroscopy even without the aid of a dopant. Further, its chirality was enhanced by doping with chiral dopant compound 4. The origin of the spontaneous chiral induction was postulated, and the packing structure in the aggregates was proposed.
Rock Degradation by Alkali Metals: A Possible Lunar Erosion Mechanism (1965)

When rocks melt under ultrahigh-vacuum conditions, their alkali components volatilize as metals. These metal vapors act to comminute polycrystalline rocks to their component minerals. The resultant powder is porous and loosely packed and its characteristics may be compatible with the lunar surface as revealed by the Ranger photographs. If meteorite impact or lunar volcanism has produced vaporization or areas of molten lava, alkali erosion may have given dust of this character in adjacent solid areas.
[Mechanism of flagellin polymerization in Bacillus brevis]. (1983)

The optical properties of acid-dissociated and tetranitromethane-modified flagellin has been studied by circular dichroism (CD) techniques. The flagellins have the same CD spectra which do not change over the 2.9-10.0 range. The spectra character depends on pH in the presence of polyethylene glycol (PEG) and ammonium sulphate which accelerate polymerization. As the content of PEG goes up to 20% and ammonium sulphate to 1 M, the value of the molecular ellipticity at 222 nm ([O]222) of the both flagellins considerably increases at pH 4.3-10.0, however [O]222 does not achieve the value for bacterial flagella. PEG and ammonium sulphate addition at pH 2.9-3.9 gives less dramatic increase of the [O]222 value. It has been concluded that the changes in the CD spectra at pH 4.3-10.0 is a result of conformational rearrangements in flagellin before it incorporates into the flagella.
Do Chronic Diseases Have an Infectious Root? (2001)

MICROBIOLOGYA wealth of evidence suggests that pathogens may play a role--perhaps even a causal one--in chronic diseases like Alzheimer's or MS. Proving that theory, however, is another matter. Every step of the research is fraught with controversy, from isolating the pathogens to determining how they might cause the disease to sorting out how a host's genetic profile influences the course of disease. And because these illnesses are chronic, scientists have to confront frustrating questions about cause and effect that don't come up with acute illnesses like Ebola or the mumps.
Real-time periodic motion detection, analysis, and applications (2003)

We describe a new technique to detect and analyze periodic motion as seen from both a static and moving camera. By tracking objects of interest, we compute an object's self-similarity as it evolves in time. For periodic motion, the self-similarity measure is also periodic, and we apply time-frequency analysis to detect and characterize the periodic motion. A real-time system has been implemented to track and classify objects using periodicity. Examples of object classification, person counting, and non-stationary periodicity are provided.
ADARC: A New Multi-Instruction Issue Approach. (1996)

The Associative Dataflow Architecture (ADARC) combines features usually associated with either VLIW or with dataflow architectures to achieve an efficient exploitation of the instructionlevel parallelism of numerical algorithms on a modular, scalable, parallel hardware with distributed memory. While the ADARC architecture does not favorize any final implementation considering the complexity of the used functional units, this paper focuses on a realization which is similar to VLIW-based processors. ADARC extends the synchronous issuing of operations in VLIWs to an asynchronous mechanism allowing arbitrary execution times and different issuing times of the simple instructions out of one VLIW. This new sequencing method is efficiently supported by an intelligent interconnection network performing transport triggering mechanisms using associatively controlled switches as routing elements. Keywords: computer architecture, multi-instruction issue, scalable interconnection networks, dataflow...
Design and Application of a High Sensitivity Piezoresistive Pressure Sensor for Low Pressure Conditions (2015)

In this paper, a pressure sensor for low pressure detection (0.5 kPa-40 kPa) is proposed. In one structure (No. 1), the silicon membrane is partly etched to form a crossed beam on its top for stress concentration. An aluminum layer is also deposited as part of the beam. Four piezoresistors are fabricated. Two are located at the two ends of the beam. The other two are located at the membrane periphery. Four piezoresistors connect into a Wheatstone bridge. To demonstrate the stress concentrate effect of this structure, two other structures were designed and fabricated. One is a flat membrane structure (No. 2), the other is a structure with the aluminum beam, but without etched silicon (No. 3). The measurement results of these three structures show that the No.1 structure has the highest sensitivity, which is about 3.8 times that of the No. 2 structure and 2.7 times that of the No. 3 structure. They also show that the residual stress in the beam has some backside effect on the sensor performance.
<title>Frequency-Stabilized Continuous Wave (CW) Ring Dye Laser</title> (1980)

The CW ring dye laser is capable of high-power, single mode operation in the visible and near infrared spectral region. This laser's performance is enhanced by frequency stabilizing the laser to an external reference Fabry-Perot yielding a jitter-induced linewidth of about 150 kHz rms. Systems of this type may mode hop due to bubbles in the dye laser jet stream or other perturbations and lock to another fringe of the reference Fabry-Perot. Locking to another fringe means that laser frequency has changed by at least one equivalent free spectral range of the reference Fabry-Perot. We will describe the properties of a stabilized CW, ring dye laser system which has the feature of automatically reacquiring lock to the original fringe of the reference in the presence of mode hopping.
Photodegradation of α-Pinene Secondary Organic Aerosol Dominated by Moderately Oxidized Molecules (2021)

Atmospheric secondary organic aerosol (SOA) undergoes chemical and physical changes when exposed to UV radiation, affecting the atmospheric lifetime of the involved molecules. However, these photolytic processes remain poorly constrained. Here, we present a study aimed at characterizing, at a molecular level and in real time, the chemical composition of α-pinene SOA exposed to UV-A light at 50% relative humidity in an atmospheric simulation chamber. Significant SOA mass loss is observed at high loadings (∼100 μg m<sup>-3</sup>), whereas the effect is less prevalent at lower loadings (∼20 μg m<sup>-3</sup>). For the vast majority of molecules measured by the extractive electrospray time-of-flight mass spectrometer, there is a fraction that is photoactive and decays when exposed to UV-A radiation and a fraction that appears photorecalcitrant. The molecules that are most photoactive contain between 4 and 6 oxygen atoms, while the more highly oxygenated compounds and dimers do not exhibit significant decay. Overall, photolysis results in a reduction of the volatility of SOA, which cannot be explained by simple evaporative losses but requires either a change in volatility related to changes in functional groups or a change in physical parameters (i.e., viscosity).
Sri Lanka Wind Farm Analysis and Site Selection Assistance (2003)

The United States Department of Energy (DOE), through the National Renewable Energy Laboratory (NREL), has been working in partnership with the U.S. Agency for International Development (USAID) in an on-going process to quantify the Sri Lanka wind energy potential and foster wind energy development. Work to date includes completion of the NREL wind atlas for Sri Lanka. In addition, the Ceylon Electricity Board (CEB) has conducted a wind resource assessment of several areas of the country and has successfully completed and is currently operating a 3-MW pilot wind project. A review of the work completed to date indicates that additional activities are necessary to provide Sri Lanka with the tools necessary to identify the best wind energy development opportunities. In addition, there is a need to identify key policy, regulatory, business and infrastructure issues that affect wind energy development and to recommend steps to encourage and support wind power development and investment.
Gas Turbine Performance Improvement Direct Mixing Evaporative Cooling System American Atlas Cogeneration Facility Rifle, Colorado (1990)

This paper discusses the design, installation, operation and performance of a direct mixing evaporative cooling system as an alternate to conventional wetted rigid media systems used for gas turbine power augmentation. The economic return on investment, the ease of installation, and the potential problems as they apply to a typical gas turbine based cogeneration facility are discussed and analyzed. Especially of interest is the low capital cost of this system, approximately one fourth that of a conventional system.
Repair of critical bone defects with injectable platelet rich plasma/bone marrow-derived stromal cells composite: experimental study in rabbits. (2008)

These data implicated that BMSCs delivered from PRP gel can repair bony defect in immunocompetent animals, and the tissue engineered bone in BMSCs/PRP group is comparable to autogenous particulate cancellous bone group for the repair of critical-sized bone defect.
Unconventional secretory pathway activation restores hair cell mechanotransduction in an USH3A model (2019)

The pathogenic variant c.144T>G (p.N48K) in the clarin1 gene (<i>CLRN1</i>) results in progressive loss of vision and hearing in Usher syndrome IIIA (USH3A) patients. CLRN1 is predicted to be an essential protein in hair bundles, the mechanosensory structure of hair cells critical for hearing and balance. When expressed in animal models, CLRN1 localizes to the hair bundle, whereas glycosylation-deficient CLRN1<sup>N48K</sup> aggregates in the endoplasmic reticulum, with only a fraction reaching the bundle. We hypothesized that the small amount of CLRN1<sup>N48K</sup> that reaches the hair bundle does so via an unconventional secretory pathway and that activation of this pathway could be therapeutic. Using genetic and pharmacological approaches, we find that clarin1 knockout (<i>clrn1</i><sup><i>KO/KO</i></sup> ) zebrafish that express the <i>CLRN1</i><sup><i>c.144T>G</i></sup> pathogenic variant display progressive hair cell dysfunction, and that CLRN1<sup>N48K</sup> is trafficked to the hair bundle via the GRASP55 cargo-dependent unconventional secretory pathway (GCUSP). On expression of <i>GRASP55</i> mRNA, or on exposure to the drug artemisinin (which activates GCUSP), the localization of CLRN1<sup>N48K</sup> to the hair bundles was enhanced. Artemisinin treatment also effectively restored hair cell mechanotransduction and attenuated progressive hair cell dysfunction in <i>clrn1</i><sup><i>KO/KO</i></sup> larvae that express <i>CLRN1</i><sup><i>c.144T>G</i></sup> , highlighting the potential of artemisinin to prevent sensory loss in <i>CLRN1</i><sup><i>c.144T>G</i></sup> patients.