gebhart/patrepeval huggingface dataset:
The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation (1996)

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV-specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T-cell-depleted (TCD) grafts from EBV-seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV-specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T-cell populations that occurred contemporaneously with the clinical regression of disease.
Redox-Switched Oxidation of Dihydrogen Using a Non-Innocent Ligand (2007)

Organometallic complexes containing non-innocent ligands of the type Cp*Ir(tBAFPh)(1), where H2tBAFPh is 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol, were found to activate H2 in a redox-switchable manner. The 16e- complex 1 was inert with respect to H2, CO, as well as conventional basic substrates until oxidation. Oxidation of 16-electron 1 with 1 equiv of Ag+ resulted in ligand-centered oxidation affording salts of [1]+, which were characterized by crystallographically, EPR, and elemental analyses. [1]+ was reduced to 1 in the presence of H2 and the sterically hindered base, 2,6-(tBu)2C5H3N, via a pathway that is first-order in both metal and dihydrogen. Compound [1]+ forms adducts with MeCN, which inhibits catalysis. The catalytic oxidation of H2 was established by electrochemical methods to be associated with the monocation.
Mutational analysis of the murine AIDS-defective viral genome reveals a high reversion rate in vivo and a requirement for an intact Pr60gag protein for efficient induction of disease (1995)

Pr60gag appears to be the only protein encoded by the murine AIDS (MAIDS)-defective virus. To study the role of Pr60gag or some other sequences of the viral genome in the pathogenicity of the virus, we have generated mutants of the defective viral genome. These mutant defective viruses, prepared as helper-free stocks, were inoculated into susceptible C57BL/6 mice. Mutant Du5H-A virus, which had a stop codon within gag MA(p15), did not induce target cell proliferation or MAIDS. Mutants Du5H-B and -C encoded truncated Pr60gag proteins containing, respectively, MA(p15)-p12 or MA(p15)-p12 and part of CA(p30). These mutants showed a very limited capacity to induce early cell expansion and were poorly pathogenic. Only recombinant (revertant) viruses were recovered from organs of diseased mice inoculated with these two mutants. Mutant Du5H-D was generated by deleting 1.4 kbp of the 3'-end sequences, outside the gag coding region. The levels of RNA and proteins made by this mutant were low. This mutant also reverting frequently but was nevertheless able to induce MAIDS at a low efficiency without reverting. Our results indicate that the Pr60gag protein is necessary and sufficient to induce MAIDS. These data also suggest that the Pr60gag protein needs to be relatively intact to be fully pathogenic. In addition, our study shows a very high reversion rate of some mutants and emphasizes the need to check for the presence of revertant (recombinant) viruses in diseased organs when working with mutants of the MAIDS-defective virus.
An Adjustable Polygon Connecting Method for 3D Mesh Refinement (2014)

Subdivision schemes are commonly used to generate smooth surfaces from sparse discrete points. The final subdivided surface of the most existing subdivision algorithms cannot be adjusted. In this paper, a novel adjustable subdivision method is introduced to solve the problems mentioned above. First, the mapping points are generated by mapping the central point of a triangle to the tangent planes. Then, after moving the mapping points to a certain proportion, the adjustable polygons on the tangent plane are obtained by connecting the moving points anticlockwise. Finally, the adjustable triangles and quadrilaterals are formed to fill the gap between the adjustable polygons. The subdivided surface generated by our method can be flexibly adjusted according to the different moving coefficient. Experimental results demonstrate that the proposed method is effective and robust to the mesh refinement.
Live bacteria as anticancer agents and tumor-selective protein delivery vectors. (2002)

The development of novel cancer therapies that are selective for cancer cells with limited toxicity to normal tissues is a challenge for oncology researchers. Microorganisms, such as viruses with selectivity for tumor cells or tumor micro-environments, have been investigated as potential arsenals for decades. Genetically-modified, non-pathogenic bacteria have begun to emerge as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Attenuated Salmonella, Clostridium and Bifidobacterium are capable of multiplying selectively in tumors and inhibiting their growth, representing a new approach for cancer treatment. Because of their selectivity for tumor tissues, these bacteria would also be ideal vectors for delivering therapeutic proteins to tumors. VNP20009, an attenuated strain of Salmonella typhimurium, and its derivative, TAPET-CD, which expresses an Escherichia coli cytosine deaminase (CD), are particularly promising, and are currently undergoing phase I clinical trials in cancer patients.
Compassionate Use of Remdesivir in Pregnant Women With Severe Coronavirus Disease 2019 (2020)

Among 86 pregnant and postpartum women with severe COVID-19 who received compassionate-use remdesivir, recovery rates were high, with a low rate of serious AEs.
Activated non-neural specific T cells open the blood–brain barrier to circulating antibodies (1999)

Previous studies have shown that activated T cells can successfully cross endothelial barriers and will accumulate in tissue which contains their specific antigen. Myelin specific T cells (e.g. myelin basic protein specific) are recognized to play an important role in the induction of experimental autoimmune demyelinating disease of the CNS and have been shown to induce blood-brain barrier breakdown effectively. In this study we injected T cells reactive to a non-neural antigen (ovalbumin) systemically into Lewis rats and caused them to accumulate in the thoracic dorsal column by a prior injection of ovalbumin. Selected rats were given systemic demyelinating antibody, antimyelin oligodendrocyte antibody (anti-MOG antibody), to provide evidence of permeability changes to the blood-brain barrier. These animals were compared with control rats given systemic anti-P0 monoclonal antibody and to other rats given a direct micro-injection (3 microliters) of anti-MOG antibody into the thoracic dorsal column. All animals were monitored by serial neurophysiological studies and by histological examination. Direct anti-MOG antibody injection produced a focal block in conduction at the injection site and a large circumscribed area of primary demyelination with axonal preservation within the dorsal column. An even more profound conduction block and more extensive plaque-like region of demyelination were seen in animals given antigen, activated T cells and systemic antibody. However, animals given antigen and T cells without relevant antibody did not show conduction impairment or demyelination, except when very large numbers of T cells were given; such rats developed severe irreversible axonal damage. This study demonstrates the blood-brain barrier is disrupted by activated T cells of non-neural specificity and allows large plaque-like regions of demyelination to form in the presence of circulating antimyelin antibody. The relevance of this finding to multiple sclerosis is discussed.
Optimal Concentration of Epinephrine for Vasoconstriction in Neck Surgery (1996)

The addition of epinephrine to local anesthetics decreases bleeding, reduces systemic toxicity, and increases duration of action. However, epinephrine has significant side effects. Four concentrations of epinephrine were compared to determine the minimum concentration required for maximal vasoconstriction. Eighty-one subjects undergoing surgical procedures with general anesthesia were injected with 1% lidocaine containing varying concentrations of epinephrine. Blood flow measurements were then made at 1-minute intervals for 10 minutes using a laser Doppler flowmeter. There were no differences in blood flow reduction between epinephrine concentrations of 1:100,000, 1:200,000, and 1:400,000. However, epinephrine 1:800,000 provided significantly less vasoconstriction. We recommend using an epinephrine concentration of 1:200,000 or 1:400,000 to provide optimal initial hemostasis while minimizing potential side effects.
Prevention of Human Diaphragm Atrophy with Short Periods of Electrical Stimulation (1999)

We determined whether prolonged complete inactivation of the human diaphragm results in atrophy and whether this could be prevented by brief periods of electrical phrenic nerve stimulation. We studied a subject with high spinal cord injury who required removal of his left phrenic nerve pacemaker (PNP) and the reinstitution of positive-pressure ventilation for 8 mo. During this time, the right phrenic nerve was stimulated 30 min per day. Thickness of each diaphragm (tdi) was determined by ultrasonography. Maximal tidal volume (VT) was measured during stimulation of each diaphragm separately. After left PNP reimplantation, VT and tdi were measured just before the resumption of electrical stimulation and serially for 33 wk. On the previously nonfunctioning side, there were substantial changes in VT (from 220 to 600 ml) and tdi (from 0.18 to 0.34 cm). On the side that had been stimulated, neither VT nor tdi changed appreciably (VT from 770 to 900 ml; tdi from 0.25 to 0.28 cm). We conclude that prolonged inactivation of the diaphragm causes atrophy which may be prevented by brief periods of daily phrenic nerve stimulation.
An Enzyme-Linked Immunosorbent Assay for Therapeutic Drug Monitoring of Infliximab (2006)

An enzyme-linked immunosorbent assay (ELISA) measuring serum infliximab concentrations in treated patients was developed. Microtiter plates were sensitized with tumor necrosis factor alpha (TNF-alpha) and saturated with phosphate-buffered saline (PBS) containing 1% bovine serum albumin (BSA). Samples diluted 1:100 in PBS-1% BSA were added and bound infliximab was detected using peroxidase-conjugated goat anti-human immunoglobulin G specific for Fc fragment (HRP-anti hIgG). Reading was performed using an ELISA plate reader. The limit of detection, calculated by assaying 10 replicates of a drug-free serum sample or blank sample and defined as the lowest concentration distinguishable from zero at 2 standard deviations, was 0.014 microg/mL. Each quality control sample was tested on 7 occasions on 1 day and on 5 separate days. The intraday precision indices of the method were (percent coefficients of variation, CV%) 11.7%, 6.2%, and 6.9% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias measures (percent deviation) were -5.5%, -1.9%, and -7.9%, respectively. The between-days precision was 9.8%, 5.3%, and 5.3% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias were +0.3%, -0.3%, and -7.8%, respectively. Lower limit of quantitation and upper limit of quantitation were 0.04 microg/mL and 4.5 microg/mL, respectively. Trough serum concentrations of infliximab were measured in 6 adult patients with various diseases and in 5 pediatric patients with Crohn's disease. For the latter group, samples drawn 1 hour after the end of the infusion and repeated measurements also were available. Data were described using a 1-compartment population pharmacokinetic model. Terminal elimination half-life was 10.9 days. This method is rapid, accurate, and reproducible, and may be useful in therapeutic drug monitoring of infliximab.
Application of nanotechnology for enhancing oil recovery – A review (2016)

Nanotechnology has attracted a great attention in enhancing oil recovery (EOR) due to the cost-effective and environmental friendly manner. The size of nanoparticles for EOR usually is in a range of 1e100 nm, which may slightly differ from various international organisations. Nanoparticles exhibit significantly different properties compared to the same fine or bulk molecules because of much higher concentration of atoms at their surface as a result of ultra-small size. In particular, one of the most useful and fascinating properties of these particles is to creating a massive diffusion driving force due to the large surface area, especially at high temperatures. Previous studies have shown that nanoparticles can enhance oil recovery by shifting reservoir wettability towards more water-wet and reducing interfacial tension, yet this area is still open for discussion. It is worth noting that the potential of nanoparticles to reduce the oil viscosity, increase the mobility ratio, and to alter the reservoir permeability has not been investigated to date. Depending on the operational conditions of the EOR process, some nanoparticles perform more effectively than others, thus leading to different levels of enhanced recovery. In this study, we aim to provide a summary on each of the popular and available nanoparticles in the market and list their optimum operational conditions. We classified nanoparticles into the three categories of metal oxide, organic and inorganic particles in this article.
Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis (2009)

IL-6 is responsible for causing ocular inflammation, and it is, at least partially, due to IL-6-dependent Th17 differentiation. IL-6 may be a target for therapy of refractory endogenous uveitis in humans.
The "Deroofing" of Schlemm's Canal in Patients With Open-Angle Glaucoma Through Placement of a Collagen Drainage Device (1998)

The nonpenetrating technique for deroofing the canal effectively allows the drainage of aqueous to acceptable levels (in the range of 15 to 17 mm Hg) without the complications associated with penetrating trabeculectomy. Complications are rare, and the collagen drainage device appears to be effective for allowing the drainage site to remain patent after its dissolution.
Functional Correction of CNS Phenotypes in a Lysosomal Storage Disease Model Using Adeno-Associated Virus Type 4 Vectors (2005)

Lysosomal storage diseases (LSDs) represent a significant portion of inborn metabolic disorders. More than 60% of LSDs have CNS involvement. LSD therapies for systemic diseases have been developed, but efficacy does not extend to the CNS. In this study, we tested whether adeno-associated virus type 4 (AAV4) vectors could mediate global functional and pathological improvements in a murine model of mucopolysaccharidosis type VII (MPS VII) caused by beta-glucuronidase deficiency. Recombinant AAV4 vectors encoding beta-glucuronidase were injected unilaterally into the lateral ventricle of MPS VII mice with established disease. Transduced ependyma expressed high levels of recombinant enzyme, with secreted enzyme penetrating cerebral and cerebellar structures, as well as the brainstem. Immunohistochemical studies revealed close association of recombinant enzyme and brain microvasculature, indicating that beta-glucuronidase reached brain parenchyma via the perivascular spaces lining blood vessels. Aversive associative learning was tested by context fear conditioning. Compared with age-matched heterozygous controls, affected mice showed impaired conditioned fear response and context discrimination. This behavioral deficit was reversed 6 weeks after gene transfer in AAV4 beta-glucuronidase-treated MPS VII mice. Our data show that ependymal cells can serve as a source of enzyme secretion into the surrounding brain parenchyma and CSF. Secreted enzymes subsequently spread via various routes to reach structures throughout the brain and mediated pathological and functional disease correction. Together, our proof-of-principal experiments suggest a unique and efficient manner for treating the global CNS deficits in LSD patients.
Seasonal and biological variation of blood concentrations of total cholesterol, dehydroepiandrosterone sulfate, hemoglobin A(1c), IgA, prolactin, and free testosterone in healthy women. (2000)

Collecting samples at specific hours of the day or times of the year may reduce high biological variation. Alternatively, the number of individuals may be increased and a paired study design chosen to obtain adequate statistical power.
Full-Wafer Voltage Contrast Inspection for Detection of BEOL Defects (2015)

This paper details an application where E-beam inspection (EBI) can be used for 100% full wafer inspection, generally considered a mythical target for EBI. For process layers where the line-widths and defects of interest are large, very large pixel size and high scan frequency can be used, thereby making full wafer inspection feasible. The metal layers in the back-end-of-line fit this bill when scanned in voltage contrast (VC) mode. Shorts or opens at any previous layer connected to the surface nodes can cause a VC signal, therefore the electrical health of each wafer is assessed for multiple layers simultaneously across the full wafer. The advantage of this scan is that failure sites can be identified and somewhat localized well before wafer final test. This application is more appropriate for semi-mature technologies where there are few defects per wafer, and therefore a full wafer scan is needed to catch a reasonable number of defects. The challenge with this type inspection is in identification of the root cause. A number of studies to map VC defect strength to types of physical defects are described. These studies demonstrated that this technique successfully finds yield limiting defects, but not all yield limiting defects will be detected. A plan for how to use the VC inspection to find root cause is presented.
Development of V-6 3.5-liter Engine Adopting New Direct Injection System (2006)

&lt;div class="htmlview paragraph"&gt;A new V-6 3.5-liter gasoline engine (2GR-FSE) uses a newly developed stoichiometric direct injection system with two fuel injectors in each cylinder (D-4S: Direct injection 4-stroke gasoline engine system Superior version). One is a direct injection injector generating a dual-fan-shaped spray with wide dispersion, while the other is a port injector. With this system, the engine achieves a power level among the highest for production engines of this displacement and a fuel economy rating of 24mpg on the EPA cycle. Emissions are among the lowest level for this class of sedans, meeting Ultra Low Emission Vehicle standards (ULEV-II).&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The dual-fan-shaped spray was adopted to improve full-load performance. The new spray promotes a homogeneous mixture without any devices to generate intense in-cylinder air-motion at lower engine speeds. For this reason the engine has improved volumetric efficiency compared to engines having these charge motion devices, resulting in improved full-load performance throughout the engine speed range. Together with Dual VVT-i (Variable intake and exhaust Valve Timing intelligence), the engine achieves specific power near the top of all naturally aspirated production gasoline engines in the world: 66kW/L, 228kW at 6400r/min.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Fuel economy is improved compared to a conventional DISI engine with both injectors optimized to improve combustion. As for improvement of the exhaust emissions, simultaneous injection by the two injectors is effective in reduction of HC emissions during cold start.&lt;/div&gt;
Effect of a Recombinant N-Terminal Fragment of Bactericidal/Permeability-Increasing Protein (rBPI23) on Cerebrospinal Fluid Inflammation Induced by Endotoxin (1995)

Endotoxin triggers the subarachnoid inflammation of gram-negative meningitis. This study examined the ability of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) to block endotoxin-induced meningitis in rabbits. Intracisternal (ic) injection of 10-20 ng of meningococcal endotoxin induced high cerebrospinal fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pleocytosis and increased CSF lactate concentrations. ic administration of rBPI23 significantly reduced meningococcal endotoxin-induced TNF release into CSF (P < .005), lactate concentrations (P < .001), and CSF white blood cell counts (P < .01). No such effect was observed in animals receiving intravenous rBPI23. Concentrations of rBPI23 in CSF were high after ic administration but low or undetectable after systemic administration. Thus, high concentrations of rBPI23 can effectively neutralize meningococcal endotoxin in CSF, but low CSF concentrations after systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.
HA22 (R490A) Is a Recombinant Immunotoxin with Increased Antitumor Activity without an Increase in Animal Toxicity (2005)

Protein engineering can be used to increase the efficacy of recombinant immunotoxins. Because HA22 (R490A) has increased antitumor activity without increased animal toxicity, immunotoxins with this mutation are candidates for clinical development.
Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma (2005)

Acoustic injury results in destruction of hair cells and numerous nonsensory cells of the cochlea. How these injured structures undergo repair is not well understood. This study was designed to examine the cochlea for the presence of mononuclear phagocytes after tissue injury caused by noise damage. We used octave band noise (8--16 kHz) at three levels (106, 112, and 120 dB) for 2 hours and studied the mice at 1, 3, 7, and 14 days after noise exposure to determine how noise affected hearing thresholds, hair cell number, and tissue injury in the cochlea. Furthermore, we assessed the cochlea for presence of inflammation by performing immunohistochemistry for CD45, common leukocyte antigen. We counted the number of CD45(+) cells that were present in the cochlea at the above-mentioned time points after noise. CD45 is present on all bone marrow-derived white blood cells and is not otherwise expressed in the inner ear. We found that, after noise exposure, there is a large increase in CD45(+) cells. These marrow-derived cells are concentrated in the spiral ligament and spiral limbus, areas that are known to be susceptible to acoustic injury. It is possible that this inflammatory response plays a role in propagating cellular damage in these areas. Immunohistochemistry demonstrates that these cochlear cells are derived from the monocyte/macrophage lineage and serve a phagocytic function in the inner ear.