gebhart/patrepeval huggingface dataset:
The variation in medial and lateral collateral ligament strain and tibiofemoral forces following changes in the flexion and extension gaps in total knee replacement (2007)

Achieving deep flexion after total knee replacement remains a challenge. In this study we compared the soft-tissue tension and tibiofemoral force in a mobile-bearing posterior cruciate ligament-sacrificing total knee replacement, using equal flexion and extension gaps, and with the gaps increased by 2 mm each. The tests were conducted during passive movement in five cadaver knees, and measurements of strain were made simultaneously in the collateral ligaments. The tibiofemoral force was measured using a customised mini-force plate in the tibial tray. Measurements of collateral ligament strain were not very sensitive to changes in the gap ratio, but tibiofemoral force measurements were. Tibiofemoral force was decreased by a mean of 40% (sd 10.7) after 90° of knee flexion when the flexion gap was increased by 2 mm. Increasing the extension gap by 2 mm affected the force only in full extension. Because increasing the range of flexion after total knee replacement beyond 110° is a widely-held goal, small increases in the flexion gap warrant further investigation.
Peptide Antibiotics and Their Role in Innate Immunity (1995)

CONTENTS INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 FIVE CHEMICALLY DIFFERENT GROUPS OF PEPTIDE ANTIBIOTICS . . . . . . . . . . .. 63 Linear, Mostly Helical, Peptides Without Cys, With or Without a Hinge . . . . . . . . . . . . . . . 63 Linear Pep tides Without Cys and with a High Proportion of Certain Residues . . . . . . . . . 67 Antibacterial Peptides with One Disulfide Bond . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Peptides with Two or More S-S Bonds Giving Mainly or Only fJ-Sheet Structures. . . . . . . 69 Antibacterial Peptides Derivedfrom Larger Polypeptides with Other Known Functions . . 72 ANTIBACTERIAL PROTEINS AND ACTIVE FRAGMENTS OF SUCH PROTEINS . . . . 73
Virus-Like Particle (VLP) Vaccine Conferred Complete Protection against a Lethal Influenza Virus Challenge (2005)

We have previously demonstrated the formation and release of influenza virus-like particles (VLPs) from the surface of Sf9 cells infected with either a quadruple baculovirus recombinant that simultaneously expresses the influenza structural proteins hemagglutinin (HA), neuraminidase (NA), matrix 1 (M1) and M2, or a combination of single recombinants that include the M1 protein. In this work, we present data on the immunogenicity and protective efficacy afforded by VLPs (formed by M1 and HA) following immunization of mice. VLP vaccine (approximately 1 microg HA) were formulated with or without IL-12 as adjuvant and administered twice, at two weeks intervals, by either intranasal instillation or intramuscular injection. All VLP-vaccinated and influenza-immunized control mice demonstrated high antibody titers to the HA protein; however, intranasal instillation of VLPs elicited antibody titers that were higher than those induced by either intramuscular inoculation of VLPs or intranasal inoculation with two sub-lethal doses of the challenge influenza virus (control group). Antibody responses were enhanced when VLP vaccine was formulated with IL12 as adjuvant. All mice were challenged with 5 LD50 of a mouse-adapted influenza A/Hong Kong/68 (H3N2) virus. Intramuscular administration of VLP vaccine formulated with or without IL-12 afforded 100% protection against a lethal influenza virus challenge. Similarly, intranasal instillation of VLP vaccine alone protected 100% of the mice, whereas VLP formulated with IL-12 protected 90% of the vaccinated mice. Not only do these results suggest a novel approach to the development of VLP vaccines for diverse influenza virus strains, but also the creation of multivalent vaccines by decoration of the surface of the VLPs with antigens from other pathogens.
An anatomic transcriptional atlas of human glioblastoma (2018)

Anatomically correct tumor genomics Glioblastoma is the most lethal form of human brain cancer. The genomic alterations and gene expression profiles characterizing this tumor type have been widely studied. Puchalski et al. created the Ivy Glioblastoma Atlas, a freely available online resource for the research community. The atlas, a collaborative effort between bioinformaticians and pathologists, maps molecular features of glioblastomas, such as transcriptional signatures, to histologically defined anatomical regions of the tumors. The relationships identified in this atlas, in conjunction with associated databases of clinical and genomic information, could provide new insights into the pathogenesis, diagnosis, and treatment of glioblastoma. Science , this issue p. 660
Phosphoisoprenoid Binding Specificity of Geranylgeranyltransferase Type II (2000)

Geranylgeranyltransferase type II (GGTase-II) modifies small monomeric GTPases of the Rab family by attaching geranylgeranyl moieties onto two cysteines of their C-terminus. We investigated to what extent GGTase-II discriminates between its native substrate geranylgeranyl pyrophosphate (GGpp) and other phosphoisoprenoids, including farnesyl pyrophosphate (Fpp). On the basis of a novel fluorescent assay, we demonstrated that GGpp binds to GGTase-II with an affinity of 8 +/- 4 nM, while Fpp is bound less strongly (K(d) = 60 +/- 8 nM). Analysis of the binding kinetics of four different phosphoisoprenoids indicated that in all cases association is rapid, with rate constants in the range of 0.15 nM(-1) s(-1). In contrast, the dissociation rates differed greatly, depending on the phosphoisoprenoid used, with weak binding substrates generally displaying an increased rate of dissociation. The affinity of GGpp and Fpp for GGTase-II was also determined in the presence of the Rab7-REP-1 complex. The affinity for GGpp was essentially unaffected by the presence of the complex; Fpp on the other hand bound less strongly to the GGTase-II under these conditions, resulting in a K(d) of 260 +/- 60 nM. In vitro prenylation experiments were used to establish that Fpp not only does bind to GGTase-II but also is transferred with an observed rate constant of 0.082 s(-1) which is very similar to that of GGpp. The implications of the low level of discrimination by GGTase-II for the in vivo specificity of the enzyme and the use of farnesyltransferase inhibitors in anti-cancer therapy are discussed.
Bile acid and sterol solubilization in 2-hydroxypropyl-beta-cyclodextrin. (1992)

The use of 2-hydroxypropyl-beta-cyclodextrin has made it possible to prepare stable aqueous solutions of cholesterol, 26-hydroxycholesterol, 7 alpha-hydroxycholesterol, and monohydroxy bile acids such as lithocholic and 3 beta-hydroxy-5-cholenoic acids. These solutions are suitable for cell culture studies and for parenteral administration to animals.
1,25-Dihydroxyvitamin D3 inhibits antigen-induced T cell activation. (1984)

The proliferative response of murine spleen and thymus cells to antigen but not to lectin was inhibited by the active metabolite of vitamin D3, 1,25-(OH)2D3. To directly examine the effect of 1,25-(OH)2D3 on T cell activation in the absence of other complicating interactions, we utilized a panel of cloned Ia-restricted T cell hybridomas that secrete IL 2 on activation by cloned Ia-bearing stimulator cells (TA3) or when stimulated by mitogen. Physiologic concentrations of 1,25-(OH)2D3 (0.01 to 0.1 nm) inhibited the antigen-induced secretion of IL 2 by several of these T cell hybridomas. This inhibition was dependent on the concentration of the free hormone and could be overcome by increasing the number of Ia-bearing stimulator cells used. Pretreatment of the T hybridoma but not the TA3 stimulator cell with 1,25-(OH)2D3 resulted in inhibition of activation. These results are consistent with the finding that specific 1,25-(OH)2D3 receptors are present on the T cell hybridomas but are lacking in TA3 cells. 1,25-(OH)2D3 failed, however, to inhibit the activation of the T cell hybridomas by lectin or by an anti-Thy-1 antibody. These findings suggest that 1,25-(OH)2D3 may be interfering with early events of antigen-induced T cell activation, perhaps by hindering T cell recognition of the relevant antigen on stimulator cell surfaces. This system should prove useful in studying the molecular mechanisms by which 1,25-(OH)2D3 acts to inhibit T cell activation and subsequent IL 2 production.
Shaping of wide bandwidth 20 femtosecond optical pulses (1992)

We investigate the propagation of 20 fs pulses through a generalized pulse shaper/compressor and synthesize shaped waveforms with 20 fs features by linear spectral filtering using a generalized pulse shaper consisting of gratings and reflective optics. The use of reflective optics in the pulse shaper avoids cubic phase dispersion associated with lenses which significantly broaden short 20 fs pulses. As an example of our pulse-shaping capabilities, we generate pulse trains with repetition rates in excess of 12 THz using phase-only filtering.
Vacuum microelectronics-1992 (1992)

Vacuum microelectronics is a new interdisciplinary field utilizing the mechanism of electron emission into a vacuum for devices requiring bulk and surface micromachining. By fabricating arrays of conductive or semiconductive structures that are either gated or ungated, a multitude of devices can be formed that utilize cold emission and ballistic transport of electrons from emitting cathodes to appropriate collector electrodes. Potential applications include flat panel vacuum fluorescent displays, ultrahigh-frequency power sources and amplifiers, high-speed logic and signal processing circuits, and sensors. The technology of vacuum microelectronics may be capable of operation within extremely harsh environments in terms of temperature and radiation, assuming the availability of compatible packaging materials. The author summarizes the state of the art for vacuum microelectronics, with special emphasis on operation, device fabrication, testing, experimental results, and potential applications.
Effects of serotonin 2A/1A receptor stimulation on social exclusion processing (2016)

Social ties are crucial for physical and mental health. However, psychiatric patients frequently encounter social rejection. Moreover, an increased reactivity to social exclusion influences the development, progression, and treatment of various psychiatric disorders. Nevertheless, the neuromodulatory substrates of rejection experiences are largely unknown. The preferential serotonin (5-HT) 2A/1A receptor agonist, psilocybin (Psi), reduces the processing of negative stimuli, but whether 5-HT2A/1A receptor stimulation modulates the processing of negative social interactions remains unclear. Therefore, this double-blind, randomized, counterbalanced, cross-over study assessed the neural response to social exclusion after the acute administration of Psi (0.215 mg/kg) or placebo (Pla) in 21 healthy volunteers by using functional magnetic resonance imaging (fMRI) and resting-state magnetic resonance spectroscopy (MRS). Participants reported a reduced feeling of social exclusion after Psi vs. Pla administration, and the neural response to social exclusion was decreased in the dorsal anterior cingulate cortex (dACC) and the middle frontal gyrus, key regions for social pain processing. The reduced neural response in the dACC was significantly correlated with Psi-induced changes in self-processing and decreased aspartate (Asp) content. In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience. These findings may be relevant to the normalization of negative social interaction processing in psychiatric disorders characterized by increased rejection sensitivity. The current results also emphasize the importance of 5-HT2A/1A receptor subtypes and the Asp system in the control of social functioning, and as prospective targets in the treatment of sociocognitive impairments in psychiatric illnesses.
Polysaccharide Degradation and Synthesis by Extremely Thermophilic Anaerobes (2008)

Extremely thermophilic fermentative anaerobes (growth T(opt) > or = 70 degrees C) have the capacity to use a variety of carbohydrates as carbon and energy sources. As such, a wide variety of glycoside hydrolases and transferases have been identified in these microorganisms. The genomes of three model extreme thermophiles-an archaeon Pyrococcus furiosus (T(opt) = 98 degrees C), and two bacteria, Thermotoga maritima (T(opt) = 80 degrees C) and Caldicellulosiruptor saccharolyticus (T(opt) = 70 degrees C)-encode numerous carbohydrate-active enzymes, many of which have been characterized biochemically in their native or recombinant forms. In addition to their voracious appetite for polysaccharide degradation, polysaccharide production has also been noted for extremely thermophilic fermentative anaerobes; T. maritima generates exopolysaccharides that aid in biofilm formation, a process that appears to be driven by intraspecies and interspecies interactions.
Stromal Cell–Derived Factor-1α Confers Protection Against Myocardial Ischemia/Reperfusion Injury (2007)

We conclude that SDF-1alpha and its receptor, CXCR4, constitute a paracrine or autocrine axis in cardiac myocytes that is activated in response to preconditioning and hypoxic stimuli, recruiting the antiapoptotic kinases ERK and AKT and promoting an antiapoptotic program that confers protection against ischemia/reperfusion damage.
Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound (2007)

MyD88 is an adaptor protein, which plays an essential role in the intracellular signaling elicited by IL-1R and several TLRs. Central to its function is the ability of its Toll/IL-1R translation initiation region (TIR) domain to heterodimerize with the receptor and to homodimerize with another MyD88 molecule to favor the recruitment of downstream signaling molecules such as the serine/threonine kinases IL-1R-associated kinase 1 (IRAK1) and IRAK4. Herein, we have synthesized and tested the activity of a synthetic peptido-mimetic compound (ST2825) modeled after the structure of a heptapeptide in the BB-loop of the MyD88-TIR domain, which interferes with MyD88 signaling. ST2825 inhibited MyD88 dimerization in coimmunoprecipitation experiments. This effect was specific for homodimerization of the TIR domains and did not affect homodimerization of the death domains. Moreover, ST2825 interfered with recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1beta-mediated activation of NF-kappaB transcriptional activity. After oral administration, ST2825 dose-dependently inhibited IL-1beta-induced production of IL-6 in treated mice. Finally, we observed that ST2825 suppressed B cell proliferation and differentiation into plasma cells in response to CpG-induced activation of TLR9, a receptor that requires MyD88 for intracellular signaling. Our results indicate that ST2825 blocks IL-1R/TLR signaling by interfering with MyD88 homodimerization and suggest that it may have therapeutic potential in treatment of chronic inflammatory diseases.
PLANT DISEASE RESISTANCE GENES (1997)

In "gene-for-gene" interactions between plants and their pathogens, incompatibility (no disease) requires a dominant or semidominant resistance (R) gene in the plant, and a corresponding avirulence (Avr) gene in the pathogen. Many plant/pathogen interactions are of this type. R genes are presumed to (a) enable plants to detect Avr-gene-specified pathogen molecules, (b) initiate signal transduction to activate defenses, and (c) have the capacity to evolve new R gene specificities rapidly. Isolation of R genes has revealed four main classes of R gene sequences whose products appear to activate a similar range of defense mechanisms. Discovery of the structure of R genes and R gene loci provides insight into R gene function and evolution, and should lead to novel strategies for disease control.
Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia (2006)

All eukaryotic cells utilize oxidative phosphorylation to maintain their high-energy phosphate stores. Mitochondrial oxygen consumption is required for ATP generation, and cell survival is threatened when cells are deprived of O(2). Consequently, all cells have the ability to sense O(2), and to activate adaptive processes that will enhance the likelihood of survival in anticipation that oxygen availability might become limiting. Mitochondria have long been considered a likely site of oxygen sensing, and we propose that the electron transport chain acts as an O(2) sensor by releasing reactive oxygen species (ROS) in response to hypoxia. The ROS released during hypoxia act as signalling agents that trigger diverse functional responses, including activation of gene expression through the stabilization of the transcription factor hypoxia-inducible factor (HIF)-alpha. The primary site of ROS production during hypoxia appears to be complex III. The paradoxical increase in ROS production during hypoxia may be explained by an effect of O(2) within the mitochondrial inner membrane on: (a) the lifetime of the ubisemiquinone radical in complex III; (b) the relative release of mitochondrial ROS towards the matrix compartment versus the intermembrane space; or (c) the ability of O(2) to access the ubisemiquinone radical in complex III. In summary, the process of oxygen sensing is of fundamental importance in biology. An ability to control the oxygen sensing mechanism in cells, potentially using small molecules that do not disrupt oxygen consumption, would open valuable therapeutic avenues that could have a profound impact on a diverse range of diseases.
Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans (2005)

Reductions in systemic and locomotor limb muscle blood flow and O2 delivery limit aerobic capacity in humans. To examine whether O2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O2 transport and O2 uptake during incremental and constant (372 +/- 11 W; 85% of peak power; mean +/- S.E.M.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg haemodynamics and during incremental cycling and knee-extensor exercise in male subjects (n = 10). During incremental cycling, cardiac output and systemic O2 delivery increased linearly to 80% of peak power (r2 = 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate and increased linearly until exhaustion (r2 = 0.993; P < 0.001) accompanying a rise in systemic O2 extraction to 84 +/- 2%. In the exercising legs, blood flow and O2 delivery levelled off at 73-88% of peak power, blunting leg per unit of work despite increasing O2 extraction. When blood flow increased linearly during one-legged knee-extensor exercise, per unit of work was unaltered on fatigue. During constant cycling, , SV, systemic O2 delivery and reached maximal values within approximately 5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O2 delivery was due to the decline or plateau in because arterial O2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans.
AUTOFLUORESCENCE IMAGING IS USEFUL TO ASSESS ACTIVITY OF ULCERATIVE COLITIS (2007)

The efficacy of autofluorescence imaging (AFI) for assessing ulcerative colitis (UC) activity was reviewed. AFI images of UC lesions could be classified into four categories: green; green with purple spots; purple with green spots; and purple. The strength of purple in AFI images of UC lesions is related to histologic severity, thus this classification is helpful to assess the activity of UC. The autofluorescence of AFI images was also quantified using color analysis software. Active lesions had significantly low autofluorescence/reflex ratio than inactive areas in UC patients. The ratio is inversely proportional to histologic severity. When the cut‐off is 0.9, the accuracy to predict histologic activity by AFI is 92%.
Personalized Pharmacotherapy for Type�2 Diabetes Mellitus (2009)

Genome-wide linkage and association studies have been applied to Type 2 diabetes in order to discover common genetic variation that contributes to disease risk. While there has been progress in understanding how genetic variation predisposes to diabetes, there is less of an understanding of how genetics can alter drug response. The hope is that in the future, pharmacogenetics can help guide the treatment of diabetes, thereby improving control while minimizing side effects in a large group of patients.
Corporate Operating Income Forecasting Ability (1973)

Recently, interest has materialized in the business, investment and governmental communities regarding the propriety, possibility and potential consequence of allowing or requiring publicly held corporations to routinely report income forecasts. The SEC, for example, has conducted rather extensive formal hearings to assess the attitudes, arguments and problems that might arise if accounting-based income projections or other forecasts such as expected capital expenditures are routinely included in annual financial statements (10-Ks) filed with the Commission. The SEC has tentatively concluded that corporations falling under its jurisdiction will be permitted, but presently not be required, to incorporate income projections [11]. Empirical study presupposes that public reports be decomposed into a number of properties and attributes. At least three important underlying income forecasting properties can be identified: feasibility, reliability and validity. Feasibility has two interrelated attributes: ability and capability. Forecasting ability specifies the forecasting error (accuracy and variability) that results from applying forecasting models or methods (mechanical and judgmental) to a set of data to create income projections. Forecasting ability can be established by ranking various models in terms of their forecasting error and variability. Elton and Gruber [2] used the ability criterion solely to decide whether security analysts produce more accurate income projections than those generated by mechanical methods. They concluded that there was no significant difference in terms of the accuracy of forecasting error between income projections of analysts and mechanical methods. Both ability and capability considerations must be considered. Capability, as used here, focuses on the annual incremental cost of deploying resources, such as additional man hours and so forth, to prepare, publish and revise annual income forecasts for investors and others. The significance of incremental capability costs seems to be one of the major concerns underlying the SEC's decision to permit, but not require, corporations to include income projections in required filings [10]. If the estimator is corporate management, then incremental capability costs that must be incurred to produce income budgets solely for internal use would be excluded from the analysis. Once accumulated the annualized incremental capability costs directly associated with income forecasts should be related to the measures of forecasting ability. The determination of feasibility is a form of cost/benefit analysis where cost references incremental forecasting capability, and benefit denotes the forecasting error and variability that results from a given forecasting model.