gebhart/patrepeval huggingface dataset:
THE TREATMENT OF CHRONIC MESANGIOCAPILLARY (MEMBRANOPROLIFERATIVE) GLOMERULONEPHRITIS WITH IMPAIRED RENAL FUNCTION (1972)

Mesangiocapillary (membranoproliferative) glomerulonephritis carries a poor prognosis when associated with impaired renal function, the nephrotic syndrome and hypertension. Treatment with combined cyclophosphamide, dipyridamole and anticoagulants in a group of 16 patients with impaired renal function, all of whom had the nephrotic syndrome and half of whom had malignant hypertension, produced a highly significant improvement in cumulative survival curves (at 30 months, P < 0.0001). The course in treated patients differed strikingly from that reported by other groups and from the course in our own untreated patients. Serial renal biopsies showed considerable improvement in condition during treatment and the characteristic features of increased mesangial matrix and “double contours” in the peripheral capillary loops disappeared in some patients. In addition, in five patients the proteinuria disappeared or was present in only trace amounts, and there was considerable reduction in quantitative counts of red blood cells in the urine.
Improving Accessibility of the Impedance-Based Structural Health Monitoring Method (2004)

This paper presents current research on impedance-based structural health monitoring technique. The basic principle behind this technique is to apply high-frequency structural excitations (typically higher than 30 kHz) through the surface-bonded piezoelectric transducers, and measure the impedance of structures by monitoring the current and voltage applied to the piezoelectric transducers. Changes in impedance indicate changes in the structure, which in turn can indicate that damage has occurred. Three examples, including a bolted joint, gas pipeline, and composite structure, are presented to illustrate the effectiveness of this health monitoring technique to a wide variety of practical field applications. Although many proof-of-concept experiments have been performed using the impedance methods, the impedance-measuring device (HP4194A) is still bulky and expensive. Therefore, an operational amplifier-based turnkey device that can measure and record the electric impedance of a PZT has been developed. The performance of this miniaturized and portable device has been compared to our previous results and its effectiveness has been demonstrated. This paper summarizes the experimental setup, procedures, and considerations needed to implement the device in field applications.
Continuous, flow-through immunomagnetic cell sorting in a quadrupole field (1998)

A flow-through quadrupole magnetic cell separator has been designed, built, and evaluated by using a cell model system of human peripheral T lymphocytes (CD4+, CD8+, and CD45+ cells). The immunomagnetic labeling was accomplished by using a sandwich of mouse anti-human monoclonal antibody conjugated to fluorescein isothiocyanate and rat anti-mouse polyclonal antibody conjugated to a colloidal magnetic nanoparticle. The feed and sorted fractions were analyzed by FACScan flow cytometry. The magnetically labeled cells were separated from nonlabeled ones in a flow-through cylindrical column within a quadrupole field, which exerted a radial, outward force on the magnetic cells. The flow rate of the cell samples was 0.1-0.75 ml/min, and the flow rate of sheath fluid was 1.5-33.3 times that of the sample flow rate. The maximum shear stress exerted on the cell was less than 1 dyne/cm2, which was well below the level that would threaten cell integrity and membrane disruption. The maximum magnetic field was 0.765 T at the channel wall, and the gradient was 0.174 T/mm. The highest purity of selected cells was 99.6% (CD8 cells, initial purity of 26%), and the highest recovery of selected cells was 79% (CD4 cells, initial purity of 20%). The maximum throughput of the quadrupole magnetic cell separator was 7,040 cells/s (CD45 cells, initial purity of 5%). Theoretical calculations showed that the throughput can be increased to 10(6) cells/s by a scale-up of the current prototype.
Adjuvant and Salvage Radiotherapy After Prostatectomy: AUA/ASTRO Guideline (2013)

Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy (i.e., seminal vesicle invasion, positive surgical margins, extraprostatic extension) and should offer salvage radiotherapy to patients with prostatic specific antigen or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiotherapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiotherapy as well as the potential benefits of preventing recurrence. The decision to administer radiotherapy should be made by the patient and the multi-disciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. Please visit the ASTRO and AUA websites (http://www.redjournal.org/webfiles/images/journals/rob/RAP%20Guideline.pdf and http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm) to view this guideline in its entirety, including the full literature review.
T cell-intrinsic role of IL-6 signaling in primary and memory responses (2014)

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1β to block the suppressive effect of Tregs on CD4(+) T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Rα-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4(+) T cell memory formation.DOI: http://dx.doi.org/10.7554/eLife.01949.001.
HDAC6 Inhibitor Blocks Amyloid Beta-Induced Impairment of Mitochondrial Transport in Hippocampal Neurons (2012)

Even though the disruption of axonal transport is an important pathophysiological factor in neurodegenerative diseases including Alzheimer's disease (AD), the relationship between disruption of axonal transport and pathogenesis of AD is poorly understood. Considering that α-tubulin acetylation is an important factor in axonal transport and that Aβ impairs mitochondrial axonal transport, we manipulated the level of α-tubulin acetylation in hippocampal neurons with Aβ cultured in a microfluidic system and examined its effect on mitochondrial axonal transport. We found that inhibiting histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, significantly restored the velocity and motility of the mitochondria in both anterograde and retrograde axonal transports, which would be otherwise compromised by Aβ. The inhibition of HDAC6 also recovered the length of the mitochondria that had been shortened by Aβ to a normal level. These results suggest that the inhibition of HDAC6 significantly rescues hippocampal neurons from Aβ-induced impairment of mitochondrial axonal transport as well as mitochondrial length. The results presented in this paper identify HDAC6 as an important regulator of mitochondrial transport as well as elongation and, thus, a potential target whose pharmacological inhibition contributes to improving mitochondrial dynamics in Aβ treated neurons.
Flowing through the CRISPR-CAScade: Will genome editing boost cell therapies? (2013)

Recent years have seen great advancements in genome editing technologies, allowing for efficient and specific targeting of DNA sequences into the genome. In parallel, advancements in stem cell research, and especially the ability to induce pluripotency in somatic cells, have brought stem cell-derived therapies closer to the clinic. In this commentary, I envision how groundbreaking genome editing technologies will influence stem cell biology research, paving the way to regenerative medicine with genetically engineered cells.
Effectiveness of Immunomodulating Treatment (Thymostimulin) in Chronic Obstructive Pulmonary Disease (1997)

We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg/day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multi-test or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.
Chiral Peptide Nucleic Acids (PNAs): Helix Handedness and DNA Recognition (1999)

Peptide Nucleic Acids (PNAs) are DNA mimics in which the deoxyribose phosphate backbone has been replaced by a pseudo-peptide skeleton composed of N-(2-aminoethyl)glycine units; they bind to complementary DNA strands with high affinity and selectivity. In order to study the effect of stereogenic centers within the backbone on PNA preorganization and DNA binding properties, chiral PNA decamers were synthesized which contained thymine monomers derived from L-Leu and D- or L-Lys inserted either at C-terminus and/or in the middle of an achiral PNA strand. PNAs containing three chiral thymine monomers derived from L-Leu, D- or L-Lys, L-Asp, or D-Glu were also synthesized. CD spectral analyses showed that a charged chiral monomer inserted in the middle of the strand is able to induce a strong preference in the helix handedness of a PNA-PNA duplex. The effect is increased by the presence of three chiral charged monomers. The L-Lys- and L-Asp-PNAs induced a preference for the left-handed and the D-Lys and D-Glu-PNAs for the right-handed conformation. As expected, the PNA-DNA duplexes are dominated by the DNA strand and thus are right-handed with both D- and L-PNAs. However, the D-PNAs, being inherently right-handed, lead to more stable PNA-DNA duplexes than the L-PNAs. The lysine-based PNAs form more stable complexes with the DNA at low ionic strength, due to the electrostatic interactions between the charged lysine side chain and DNA.
Investigation of the Cause of Death in a Gene-Therapy Trial (2009)

We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.)
Fluid Pipelines: Elastic circuitry meets Out-of-Order execution (2016)

Pipeline depth and cycle time are fixed early in the chip design process but their impact can only be assessed when the implementation is mostly done and changing them is impractical. Elastic Systems are latency insensitive systems, and allow changes in the pipeline depth late in the design process with little design effort. Nevertheless, they have significant throughput penalty when new stages are added in the presence of pipeline loops. We propose Fluid Pipelines, an evolution that allows pipeline transformations without a throughput penalty. Formally, we introduce “or-causality” in addition to the already existing “and-causality” in Elastic Systems. It gives more flexibility than previously possible at the cost of having the designer to specify the intended behavior of the circuit. In an Out-of-Order core benchmark, Fluid Pipelines improve the optimal energy-delay point by shifting both performance (by 17%) and energy (by 13%). We envision a scenario where tools would be able to generate different pipeline configurations from the same RTL e.g., low power, high performance.
Using ancient protein kinases to unravel a modern cancer drug’s mechanism (2015)

Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein's function by altering its energy landscape. Here, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre-steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disrupted in the clinical T315I resistance mutation. This work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve.
Aortic input impedance in normal man: relationship to pressure wave forms. (1980)

The relationship between the shape of the ascending aortic pressure wave form and aortic input impedance was studied in 18 patients who underwent elective cardiac catheterization but in whom no heart dis- ease was found.Ascending aortic flow velocity and pressure were simultaneously recorded from a multisensor catheter with an electromagnetic velocity probe and a pressure sensor mounted at the same location.Another pressure sensor at the catheter tip provided left ventricular pressure or a second aortic pressure to determine pulse-wave velocity.Fick cardiac outputs were used to scale the velocity signal to instantaneous volumetric flow.Input impedance was calculated from 10 harmonics of aortic pressure and flow.For each patient, im- pedance moduli and phases from a minimum of 15 beats during a steady state were averaged.Peripheral resistance was 1137 ± 39 dyn-sec-cm' (4 SEM) and characteristic impedance was 47 4 4 dyn-sec-cm-; pulse- wave velocity was 6.68 ± 0.32 m-sec-'.In all patients, a well-defined systolic inflection point divided the aortic pressure wave form into an early and late systolic phase.The patients were classified into three groups: group A (n = 7) patients whose late systolic pressure exceeded early systolic pressure; group B (n = 7) pa- tients whose early and late systolic pressures were nearly equal; group C (n = 4) -patients whose early systolic pressure exceeded late systolic pressure.Group A and B patients all demonstrated oscillations of the impedance moduli about the characteristic impedance.Group C patients demonstrated flatter impedance spec- tra.Thus, a larger secondary rise in pressure was associated with a more oscillatory impedance spectrum.These results suggest that the differences in pressure wave forms are due to differences in reflections in the arterial tree and not secondary to differences in cardiac function.Using pulse-wave velocity, the "effective" reflection site distance was determined from both pressure (48 cm) and impedance (44 cm) data, implying that the region of the terminal abdominal aorta acts as the major reflection site in normal adult man.THE CHARACTER of the arterial pulse as palpated by the physician at the bedside or displayed by laboratory pulse recording techniques has long been an important part of the clinical evaluation of the patient with heart disease.Arterial pressure is the result of an interaction between the heart and the arterial system, so that the magnitude and shape of the pressure pulse will be affected by changes in the peripheral circulation or alterations in cardiac func- tion.Recent improvements in intravascular pressure measurement techniques have revealed major differences in the configuration of aortic pressure waves among patients, even in the absence of car- diovascular disease.'One way to determine whether these observations are secondary to differences in car- diac function or differences in the periphery is to use methods that selectively describe the arterial system.To do so, special relationships involving both pressure and flow must be developed.The best known of these
Complement in Pancreatic Disease—Perpetrator or Savior? (2017)

The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas-complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting.
Vasectomy (1988)

The study by Dr Alderman<sup>1</sup>in this issue concerns the operation most commonly performed on adult men, elective vasectomy for family planning. The author, using the most popular technique of vasectomy (ie, cutting the vas deferens, excising a segment, and ligating the cut ends), reports 97 failures among 5331 men who were available for follow-up. In some of these failures the semen was never clear of sperm; in others sperm reappeared, sometimes several years after initial negative testing. These findings document the fact that the patient can eliminate the sperm from the urethral side of the vas deferens only to have the ducts rejoin later. This should be of deep concern to both the patient and his surgeon. Both need to know when sterility can be considered permanent. An operation with an uncertain result is not a good operation. See also p 3142. Consent to perform surgery is a
Thermoreversible Gelation of PEG−PLGA−PEG Triblock Copolymer Aqueous Solutions (1999)

Aqueous solutions of new biodegradable triblock copolymers, poly(ethylene glycol-b-(dl-lactic acid-co-glycolic acid)-b-ethylene glycol) (PEG−PLGA−PEG), have shown to have sol-to-gel (lower transition) and gel-to-sol (upper transition) transitions as temperature monotonically increases. The lower transition is important for drug delivery application because the solution flows freely at room temperature and becomes a gel at body temperature. In this paper, the mechanism of gelation was proposed, and the structure−property relationship of the sol−gel transition was investigated. The lower transition may be related to micellar growth and intra- and intermicelle phase mixing and packing, while the upper transition involves breakage of micellar structure. Critical gel concentration and critical gel temperature are controlled by polymer molecular parameters, such as block length and composition of PEG−PLGA−PEG triblock copolymers, and additives, such as salts.
Novel Mechanism of Lapatinib Resistance in HER2-Positive Breast Tumor Cells: Activation of AXL (2009)

HER2-directed therapies, such as trastuzumab and lapatinib, are important treatments for breast cancer. However, some tumors do not respond or develop resistance to these agents. We isolated and characterized multiple lapatinib-resistant, HER2-positive, estrogen receptor (ER)-positive breast cancer clones derived from lapatinib-sensitive BT474 cells by chronic exposure to lapatinib. We show overexpression of AXL as a novel mechanism of acquired resistance to HER2-targeted agents in these models. GSK1363089 (foretinib), a multikinase inhibitor of AXL, MET, and vascular endothelial growth factor receptor currently in phase II clinical trials, restores lapatinib and trastuzumab sensitivity in these resistant cells that exhibit increased AXL expression. Furthermore, small interfering RNA to AXL, estrogen deprivation, or fulvestrant, an ER antagonist, decreases AXL expression and restores sensitivity to lapatinib in these cells. Taken together, these data provide scientific evidence to assess the expression of AXL in HER2-positive, ER-positive patients who have progressed on either lapatinib or trastuzumab and to test the combination of HER2-targeted agents and GSK1363089 in the clinic.
Mediating connectors: a non-bypassable process wrapping technology (2002)

We have developed a technology for mediating all shared library calls. These mediators can be used to instrument these interfaces, monitor their behavior, integrate legacy components together, or encapsulate potentially harmful or unreliable components. They can be dynamically installed and removed during execution or installed before execution begins. Since modern commercial operating systems promote packaging third party functionality as shared libraries and are themselves composed of shared libraries the ability to mediate these interfaces provides access to the broad range of services available on that platform. We have hardened this mediation technology to prevent its bypass or removal by malicious code and applied it to increase the security and integrity of processes. An implementation of this technology is available for Windows NT.