gebhart/patrepeval huggingface dataset:
Combination Drug Therapy for Familial Combined Hyperlipidemia (1988)

Although gemfibrozil with either colestipol or lovastatin favorably altered lipoprotein levels in patients with hypertriglyceridemia and familial combined hyperlipidemia, the combination of gemfibrozil and lovastatin appeared superior overall.
Noncompetitive inhibitors of TNFR1 probe conformational activation states (2019)

Tumor necrosis factor receptor 1 (TNFR1) is a central mediator of the inflammatory pathway and is associated with several autoimmune diseases such as rheumatoid arthritis. A revision to the canonical model of TNFR1 activation suggests that activation involves conformational rearrangements of preassembled receptor dimers. Here, we identified small-molecule allosteric inhibitors of TNFR1 activation and probed receptor dimerization and function. Specifically, we used a fluorescence lifetime-based high-throughput screen and biochemical, biophysical, and cellular assays to identify small molecules that noncompetitively inhibited the receptor without reducing ligand affinity or disrupting receptor dimerization. We also found that residues in the ligand-binding loop that are critical to the dynamic coupling between the extracellular and the transmembrane domains played a key gatekeeper role in the conformational dynamics associated with signal propagation. Last, using a simple structure-activity relationship analysis, we demonstrated that these newly found molecules could be further optimized for improved potency and specificity. Together, these data solidify and deepen the new model for TNFR1 activation.
A Multiproduct Terpene Synthase from Medicago truncatula Generates Cadalane Sesquiterpenes via Two Different Mechanisms (2010)

Terpene synthases are responsible for a large diversity of terpene carbon skeletons found in nature. The multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula produces 27 products from farnesyl diphosphate (1, FDP). In this paper, we report the reaction steps involved in the formation of these products using incubation experiments with deuterium-containing substrates; we determined the absolute configuration of individual products to establish the stereochemical course of the reaction cascade and the initial conformation of the cycling substrate. Additional labeling experiments conducted with deuterium oxide showed that cadalane sesquiterpenes are mainly produced via the protonation of the neutral intermediate germacrene D (5). These findings provide an alternative route to the general accepted pathway via nerolidyl diphosphate (2, NDP) en route to sesquiterpenes with a cadalane skeleton. Mutational analysis of the enzyme demonstrated that a tyrosine residue is important for the protonation process.
Validation of rheumatoid arthritis improvement criteria that include simplified joint counts (1998)

Improvement criteria that include 28-joint counts are as valid as the original improvement criteria that included more comprehensive joint counts.
Synthesis and Characterisation of a Degradable Poly(lactic acid)−Poly(ethylene glycol) Copolymer with Biotinylated End Groups (2001)

Poly(lactic acid)-poly(ethylene glycol)-biotin (PLA-PEG-biotin) is a degradable polymer with protein resistant properties that can undergo rapid surface engineering in aqueous media to create biomimetic surfaces. Surface engineering of this polymer is dependent on biomolecular interactions between the biotin end group and the protein avidin. Given the vigorous conditions of synthesis, it is essential that the manufacture of the polymer does not alter the biotin structure or its molecular recognition. Equally, it is important that the incorporation of biotin does not adversely affect the physicochemical properties of the polymer. (1)H NMR provides evidence of biotin attachment and structural integrity. (1)H NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC) analysis shows there is no significant effect on bulk properties induced by the biotin end group. Surface plasmon resonance (SPR) and fluorescent spectroscopy studies using the 2-(4'-hydroxyazobenzene) benzoic acid (HABA)/avidin complex show that the biotin moieties binding capabilities are not impaired by the synthesis.
Inhibition of retinal pigment epithelial cell-induced tractional retinal detachment by disintegrins, a group of Arg-Gly-Asp-containing peptides from viper venom. (1996)

The disintegrins were effective in inhibiting RPE cell attachment to the ECM and vitreous contraction in vitro. They also were effective in suppressing RPE cell-induced tractional retinal detachment in the rabbit eyes. They were nontoxic. Disintegrins and their analogs might be potential anti-adhesion therapeutic agents in the treatment of proliferative vitreoretinopathy.
The Impact of Image Reconstruction Bias on PET/CT 90Y Dosimetry After Radioembolization (2015)

TO THE EDITOR: We read with great interest the paper entitled “The Impact of Image Reconstruction Bias on PET/CT 90Y Dosimetry After Radioembolization” ([1][1]). In this paper, Tapp et al. showed that commercial software that truncates the negative pixels (resulting from random-coincidence
Colorimetric quantification of erythema-a comparison of two colorimeters (Lange Micro Color and Minolta Chroma Meter CR-200) with a clinical scoring scheme and laser-Doppler flowmetry (1990)

Erythema elicited by the local irritant sodium lauryl sulphate was studied in comparison with unexposed skin. Colour coordinates of the CIE system were recorded using two commercially available colorimeters. With both colorimeters a positive movement of the alpha-axis (toward red, P less than 0.001) and a negative movement on the L-axis (toward dark, P less than 0.01) were registered. Technical and in-vivo experimentation showed the two pieces of equipment to be accurate. However, a simple conversion factor cannot be established. Both pieces of equipment correlated positively with clinical scoring of erythema and with measurement of cutaneous blood flow by laser-Doppler flowmetry. In conclusion, the two colorimeters appeared comparable. Colorimetry by the CIE system, which takes into account the non-linear colour perception of the human eye, was found useful with potential value in both experimental and clinical dermatology. The techniques appeared suitable for routine testing.
Characterizing the d -TLB behavior of SPEC CPU2000 benchmarks (2002)

Despite the numerous optimization and evaluation studies that have been conducted with TLBs over the years, there is still a deficiency in an indepth understanding of TLB characteristics from an application angle. This paper presents a detailed characterization study of the TLB behavior of the SPEC CPU2000 benchmark suite. The contributions of this work are in identifying important application characteristics for TLB studies, quantifying the SPEC2000 application behavior for these characteristics, as well as making pronouncements and suggestions for future research based on these results.Around one-fourth of the SPEC2000 applications (ammp, apsi, galgel, lucas, mcf, twolf and vpr) have significant TLB missrates. Both capacity and associativity are influencing factors on miss-rates, though they do not necessarily go hand-in-hand. Multi-level TLBs are definitely useful for these applications in cutting down access times without significant miss rate degradation. Superpaging to combine TLB entries may not be rewarding for many of these applications. Software management of TLBs in terms of determining what entries to prefetch, what entries to replace, and what entries to pin has a lot of potential to cut down miss rates considerably. Specifically, the potential benefits of prefetching TLB entries is examined, and Distance Prefetching is shown to give good prediction accuracy for these applications.
A Distributed Wearable, Wireless Sensor System for Evaluating Professional Baseball Pitchers and Batters (2009)

This paper introduces a compact, wireless, wearable system that measures signals indicative of forces, torques and other descriptive and evaluative features that the human body undergoes during bursts of extreme physical activity (such as during athletic performance). Standard approaches leverage highspeed camera systems, which need significant infrastructure and provide limited update rates and dynamic accuracy. This project uses 6 degree-of-freedom inertial measurement units worn on various segments of an athlete's body to directly make these dynamic measurements. A combination of low and high range sensors enables sensitivity for both slow and fast motion, and the addition of a compass helps in tracking joint angles. Data from the battery powered nodes is acquired using a custom wireless protocol over an RF link and analyzed offline. Several professional pitchers and batters were instrumented with the system and data was gathered over many pitches and swings. We show some biomechanically descriptive parameters extracted from this data, and highlight ongoing work and system improvements.
Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis. (2007)

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.
[Effect of physical training on the clinical course and the status of blood coagulation hemostasis in patients with ischemic heart disease]. (1988)

The effect of intensive rationed exercise on coagulation hemostasis was assessed in 92 males, including 10 normal subjects and 82 coronary patients. Twenty male coronary patients, treated with antianginal drugs, were taken as controls. There were no significant changes in coagulation hemostasis between normal subjects after an exercise course and coronary patients on antianginal treatment. Intensive rationed exercise normalized coagulation hemostasis in coronary patients, as evidenced by reduced thrombinemia owing to smaller concentrations of factors VIII and X and an increase in protein C content.
Using pulsed direct current power for reactive sputtering of Al2O3 (1999)

Application of steady direct current (DC) power to the reactive sputtering of dielectrics such as Al2O3 is seriously hampered by arcing. This arcing can be alleviated to a great extent when pulsed dc power is applied. By pulsed dc power we mean that the power is applied for a short “on” period, and then removed for a short “off” period. During the “off” period the plasma can discharge the surfaces, provided certain conditions are met. The dependence of adequate discharging, and thus arc prevention, on the duration of the “on” and “off” periods is examined. In addition, the dynamics of plasma density loss in the “off” period and its reestablishment in the initial part of the “on” period are discussed. Reactive sputtering takes place only during the “on” period, and part of this period is lost for effective sputtering due to the time required for full plasma reestablishment. This produces a dependence of the deposition rate on both the duty cycle and the frequency of pulsing, but not on the power consumed. This dependence is examined and the power efficiencies of alternating current and pulsed power dc reactive sputtering are compared and the differences between single and dual cathode systems in published results is discussed.
Ischemic stroke in elderly patients treated with a free radical scavenger–glycolytic intermediate solution: A preliminary pilot trial (2002)

The safety and tolerability of a free radical scavenger with Na+ channel blocking activity (dimethyl sulfoxide (DMSO)) combined with a glycolytic intermediate and high energy substrate (fructose 1,6-disphosphate (FDP)) were assessed in a mostly elderly patient group presenting with acute and subacute ischemic stroke. Eleven patients (average age 65) were given i.v. infusions of DMSO-FDP twice daily for an average of 12 days, while five control patients (average age 63) were given standard therapy. Safety and tolerability were evaluated by clinical adverse effects to drug therapy. Efficacy of DMSO-FDP was assessed by MRI lesion size, by magnetic resonance angiography of ischemic territory, and by a 5-point neurologic recovery scale that rated sensory-motor function and level of consciousness. Results suggest that DMSO-FDP administration is safe, well-tolerated and may be of benefit when given within 12 h after the onset of stroke symptoms. No significant changes in blood pressure, EKG, heart rate or hematology and chemistry profiles, were recorded in any patient receiving DMSO-FDP. Neurologic evaluation at 1, 3 and 6 months after treatments revealed that 7 of 11 (63%) patients given DMSO-FDP achieved 'improved' or 'markedly improved' status while 1 of 5 (20%) standard treated patients showed 'improved' status and only at the 3-month follow-up. This preliminary trial indicates that DMSO-FDP is well tolerated by this group of elderly patients and could be of benefit in reducing neurologic disability after stroke.
Indirect evidence of TTV replication in bone marrow cells, but not in hepatocytes, of a subacute hepatitis/aplastic anemia patient (2000)

The presence of a new DNA virus (TTV) has been reported in sera from patients with posttransfusion hepatitis of unknown etiology. The precise replication site of TTV, however, has not been established. In this study, the presence of TTV in liver autopsy material, and in bone marrow biopsy and autopsy samples taken from a subacute hepatitis/aplastic anemia patient was determined by PCR and Southern blot analyses. Liver cells were found to contain only TTV DNA and not mRNA. Bone marrow material, especially that taken at biopsy, contained high levels of TTV DNA. It is suggested that the TTV replication site was in the bone marrow rather than in the liver, and that TTV infection was the cause of this patient's aplastic anemia. The precise etiological association of TTV with hepatitis remains to be established.
Eyes in the sky—watching for weapons work (2001)

Commercial satellites can be used to pick up many of the telltale signs of fissile material production.
Transcranial Direct Current Stimulation during Sleep Improves Declarative Memory (2004)

In humans, weak transcranial direct current stimulation (tDCS) modulates excitability in the motor, visual, and prefrontal cortex. Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas. To experimentally induce widespread extracellular negative DC potentials, we applied anodal tDCS (0.26 mA) [correction] repeatedly (over 30 min) bilaterally at frontocortical electrode sites during a retention period rich in SWS. Retention of declarative memories (word pairs) and also nondeclarative memories (mirror tracing skills) learned previously was tested after this period and compared with retention performance after placebo stimulation as well as after retention intervals of wakefulness. Compared with placebo stimulation, anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (p < 0.005). When applied during the wake retention interval, tDCS did not affect declarative memory. Procedural memory was also not affected by tDCS. Mood was improved both after tDCS during sleep and during wake intervals. tDCS increased sleep depth toward the end of the stimulation period, whereas the average power in the faster frequency bands (,alpha, and beta) was reduced. Acutely, anodal tDCS increased slow oscillatory activity <3 Hz. We conclude that effects of tDCS involve enhanced generation of slow oscillatory EEG activity considered to facilitate processes of neuronal plasticity. Shifts in extracellular ionic concentration in frontocortical tissue (expressed as negative DC potentials during SWS) may facilitate sleep-dependent consolidation of declarative memories.
Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria (2000)

Many Gram-negative pathogens use a type III secretion apparatus to deliver effector molecules into host cells to subvert cellular processes in favour of the pathogen. Enteropathogenic Escherichia coli (EPEC) uses such a system to deliver the Tir effector molecule into host cells. In this paper, we show that the gene upstream of tir, orf19, encodes an additional type III secreted effector protein. Orf19 is delivered into host cells by a mechanism independent of endocytosis, but dependent on EspB. Orf19 is targeted to host mitochondria, where it appears to interfere with the ability to maintain membrane potential. Although the precise role of Orf19 remains to be elucidated, its interaction with mitochondria suggests a possible role in the subversion of key functions of these organelles, such as energy production or control of cell death. This is the first example of a type III secreted protein targeted to mitochondria; it is probable that homologues (present in EPEC and Shigella species) and other bacterial effectors will also target this organelle.
Current status of the molecular genetics of human prostatic adenocarcinomas (2002)

Molecular genetic mechanisms involved in the progression of prostate cancer are not well understood due to extensive tumor heterogeneity and lack of suitable models. New methods such as fluorescence in-situ hybridization (FISH), comparative genomic hybridization (CGH) and microsatellite analysis have documented losses or gains on various chromosomes. Altered chromosomal regions have been associated with the activation of oncogenes and the inactivation of tumor suppressor genes or defects in mismatch repair (MMR) genes. It is suggested that increased genomic instability is associated with decreased androgen-responsive and progressive behavior of human prostate tumors, but it remains unclear whether this genomic instability is causing the progression of cancer or is the consequence of cancer. Extended studies on hereditary prostate cancer have identified 7 prostate cancer susceptibility loci on several chromosomes, but no specific gene has been confined for a large proportion of susceptibility. In this review we summarize the ongoing molecular genetic events associated with the sporadic and hereditary prostate cancer development and progression.
Vlastos on Pauline Predication (1985)

In the period following his epoch-making attention to the Third Man Argument' Gregory Viastos was converted to the cause of what he has termed Pauline Predication.2 Sentences such as Justice is pious or Fire is hot seem, on the surface, to be attributing a characteristic to a Form a situation labelled by Vlastos ordinary predication (A S,3 p. 273). But, Viastos suggests, such cases are really to be read as assigning this property to instances of the Form. As applied to putative cases of self-predication,4 F-ness is F becomes, from the Pauline perspective, equivalent to Necessarily, for all x, if x partakes of F-ness, x is F (AS, p. 273; U VP, p. 235). In UVP (pp. 257-8) Vlastos urges that two notorious candidates for self-predication, Justice is just and Piety is pious, at Prot. 330c and d respectively, must be read in the Pauline fashion. We may or may not agree with him here,5 but Vlastos proceeds to reject his former thesis that, for Plato, all Forms are self-predicative. He will grant (pp. 259-63)
An experimental model to study the cytotoxic effects induced by beta-amyloid, histamine, LPS and serum from Alzheimer patients on cultured rat endothelial cells. (1997)

Lactate dehydrogenase (LDH) enzyme activity was measured in the supernatant of rat aortic endothelial cell cultures to evaluate the cytotoxic effects of two proinflammatory mediators such as LPS and histamine, as well as beta-amyloid protein (fragment 1-28) on endothelial cells. In the same culture we also studied the influence of different sera from patients with Alzheimer's disease (AD) or healthy elderly subjects. The results indicate that very low concentrations (1 microgram/ml) of beta-amyloid or histamine (1 microM) were able to produce cell damage after an incubation time of 4 h. Treatment with LPS induced cell damage at the highest concentration (2.5 micrograms/ml) after 24 h of incubation. When endothelial cells were treated with serum from AD and non-AD individuals, an inhibition of endothelial cell proliferation was observed only with activated AD serum. These results indicate that rat endothelial cell cultures represent an important model to study inflammatory mediators and to evaluate the therapeutic effect of antiinflammatory molecules in AD and other neurodegenerative disorders.
ANTIBODIES OF THE IgA TYPE IN INTESTINAL PLASMA CELLS OF GERMFREE MICE AFTER ORAL OR PARENTERAL IMMUNIZATION WITH FERRITIN (1969)

In adult germfree C(3)H mice immunized with horse spleen ferritin, either subcutaneously or intraperitoneally, plasma cells containing specific antibodies were found in lymph nodes and spleen and, in smaller numbers, also in the lamina propria of the intestine. In extraintestinal sites, these antiferritin-containing plasma cells were mainly of the IgM class after a single stimulation, and of the IgG(1) class after repeated stimulation. In the intestine, all the anti-ferritin-containing cells appeared to be of the IgA class. Circulating antibodies, after repeated stimulation, were for the major part IgG(1) and IgG(2). In germfree mice given ferritin in their drinking water, antiferritin-containing cells were abundant in the intestinal mucosa, much less numerous in the mesenteric lymph nodes, and extremely scarce in other lymphoid tissues. All these cells, whatever their location, appeared to belong exclusively to the IgA class. Similarly, all the circulating antibody in these animals was found to be IgA. These findings illustrate the role of the gut as a site of antibody synthesis, as well as its selective commitment to the production of antibodies of the IgA class.