gebhart/patrepeval huggingface dataset:
Prevalence of Alzheimer's disease and other dementias in an elderly urban population (1991)

We studied the prevalence of different types of dementia in an elderly population in Stockholm, Sweden, in relation to age, sex, and education. The study confirmed Alzheimer's disease (AD) as the most frequent type of dementia and the positive association of dementias with age, even in the most advanced ages. In contrast to previously reported data, we found the same proportion of AD and vascular dementia in the different age strata, and no sex differences regarding the prevalence of different dementia types. Finally, less educated people had a higher prevalence of all dementias, due essentially to a higher prevalence of alcoholic dementia and unspecified type of dementia. The prevalence of AD was similar across different levels of education.
IMMUNO‐MAGNETIC BEAD MASS TRANSPORT AND CAPTURE EFFICIENCY AT LOW TARGET CELL DENSITIES IN PHOSPHATE‐BUFFERED SALINE1 (2002)

Anti‐salmonella immuno‐magnetic bead (IMB) capture efficiency (E) was determined by varying both IMB levels ([IMB]) and mixing time (T MIX ) and enumerating captured Salmonella enteritidis cells. We observed that E varied with T MIX as a Pseudo‐first order process with a rate constant (K) of 0.028 ± 0.001 min ‐1 and an infinite T MIX asymptote of 0.97 (97% capture). Thus, even at low target cell densities ([S. E.] ± 70 CFU mL ‐1 ), nearly 100% of the bacteria were captured as T MIX approached 2 h. We hypothesize that k is the product of both IMB mass transport (γ) and IMB concentration ([IMB]) terms. Thus, γ represents the total volume which each IMB samples per unit time of mixing. This idea appears reasonable as γ(3.2 ± 0.2 × 10 ‐9 mL min ‐1 IMB ‐1 ), determined from E‐based observations at various [IMB] levels (˜10 6 −10 8 IMB mL ‐1 ) and fixed T MIX (30 min), was nearly identical to γ(3.5 ± 0.1 × 10 ‐9 mL min ‐1 IMB ‐1 ) derived kinetically (T MIX = 0–120 min; [IMB] = 8 × 10 6 IMBs mL ‐1 ). Estimating a mass transport term (γ CALC ) founded on classical dynamics we obtained a value 5.3 × 10 ‐10 mL min ‐1 IMB ‐1 whereupon γ CALC and γ would have completely agreed were the IMB radius (r IMB = 1.4 μm) 0.8 μm larger. The apparent discrepancy in r IMB might be explained by a greater effective (hydrodynamic) r IMB which could result from some combination of IMB swelling and brownian motion. These results argue that IMB‐based target cell capture is modulated by IMB mass transport and collision probability.
Proteasome-Assisted Identification of a SSX-2-Derived Epitope Recognized by Tumor-Reactive CTL Infiltrating Metastatic Melanoma (2002)

The tumor Ag SSX-2 (HOM-MEL-40) was found by serological identification of Ags by recombinant expression cloning and was shown to be a cancer/testis Ag expressed in a wide variety of tumors. It may therefore represent a source of CD8(+) T cell epitopes useful for specific immunotherapy of cancer. To identify potential SSX-2-derived epitopes that can be recognized by CD8(+) T cells, we used an approach that combined: 1) the in vitro proteasomal digestion of precursor peptides overlapping the complete SSX-2 sequence; 2) the prediction of SSX-2-derived peptides with an appropriate HLA-A2 binding score; and 3) the analysis of a tumor-infiltrated lymph node cell population from an HLA-A2(+) melanoma patient with detectable anti-SSX-2 serum Abs. This strategy allowed us to identify peptide SSX-2(41-49) as an HLA-A2-restricted epitope. SSX2(41-49)-specific CD8(+) T cells were readily detectable in the tumor-infiltrated lymph node population by multimer staining, and CTL clones isolated by multimer-guided cell sorting were able to lyse HLA-A2(+) tumor cells expressing SSX-2.
Trajectory reconstruction techniques for evaluation of ATC systems (2008)

This paper is focused on trajectory reconstruction techniques for evaluating ATC systems, using real data of recorded opportunity traffic. We analyze different alternatives for this problem, from traditional interpolation approaches based on curve fitting to our proposed schemes based on modeling regular motion patterns with optimal smoothers. The extraction of trajectory features such as motion type (or mode of flight), maneuvers profile, geometric parameters, etc., allows a more accurate computation of the curve and the detailed evaluation of the data processors used in the ATC centre. Different alternatives will be compared with some performance results obtained with simulated and real data sets.
Viable pigs after simultaneous inactivation of porcine MHC class I and three xenoreactive antigen genes GGTA1, CMAH and B4GALNT2 (2019)

We showed that pigs carrying several xenoprotective transgenes and knockouts of xenoreactive antigens can be readily generated and these modifications will have significant effects on xenograft survival.
Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome (2000)

Fragile-X syndrome is the most common single-gene inherited form of mental retardation. Morphological studies suggest a possible failure of the synapse maturation process. Cerebral cortical spine morphology in fragile-X syndrome and in a knockout mouse model of it appears immature, with long, thin spines much more common than the stubby and mushroom-shaped spines more characteristic of normal development. In human fragile-X syndrome there is also a higher density of spines along dendrites, suggesting a possible failure of synapse elimination. While variously misshapen spines are characteristic of a number of mental retardation syndromes, the overabundance of spines seen in fragile-X syndrome is unusual. Taken with evidence of neurotransmitter activation of the synthesis of the fragile-X protein (FMRP) at synapses in vitro and evidence for behaviorally induced FMRP expression in vivo, and with evidence compatible with a role for FMRP in regulating the synthesis of other proteins, it is possible that FMRP serves as an 'immediate early protein' at the synapse that orchestrates aspects of synaptic development and plasticity.
BCL6 repression of EP300 in human diffuse large B cell lymphoma cells provides a basis for rational combinatorial therapy (2010)

B cell lymphoma 6 (BCL6), which encodes a transcriptional repressor, is a critical oncogene in diffuse large B cell lymphomas (DLBCLs). Although a retro-inverted BCL6 peptide inhibitor (RI-BPI) was recently shown to potently kill DLBCL cells, the underlying mechanisms remain unclear. Here, we show that RI-BPI induces a particular gene expression signature in human DLBCL cell lines that included genes associated with the actions of histone deacetylase (HDAC) and Hsp90 inhibitors. BCL6 directly repressed the expression of p300 lysine acetyltransferase (EP300) and its cofactor HLA-B-associated transcript 3 (BAT3). RI-BPI induced expression of p300 and BAT3, resulting in acetylation of p300 targets including p53 and Hsp90. Induction of p300 and BAT3 was required for the antilymphoma effects of RI-BPI, since specific blockade of either protein rescued human DLBCL cell lines from the BCL6 inhibitor. Consistent with this, combination of RI-BPI with either an HDAC inhibitor (HDI) or an Hsp90 inhibitor potently suppressed or even eradicated established human DLBCL xenografts in mice. Furthermore, HDAC and Hsp90 inhibitors independently enhanced RI-BPI killing of primary human DLBCL cells in vitro. We also show that p300-inactivating mutations occur naturally in human DLBCL patients and may confer resistance to BCL6 inhibitors. Thus, BCL6 repression of EP300 provides a basis for rational targeted combinatorial therapy for patients with DLBCL.
Spectroscopy and Microscopy of Spin-Sensitive Rectification Current Induced by Microwave Radiation (2005)

Amplitude-modulated microwave radiation was applied to the junction of a scanning tunneling microscope (STM). Rectification in the tunneling current was induced by the microwave because of the nonlinearity of the junction. It is shown that this rectification current is proportional to the d(2)I/dV(2) signal and exhibits spin-sensitivity. The magnetic domain at the apex of an iron-coated tip was manipulated by applying an external magnetic field. The moment of spin flip and the magnetic hysteresis were measured by changes in the spin-dependent current through the Cr(001) surface.
A Potential Role of the Curry Spice Curcumin in Alzheimers Disease (2005)

There is substantial in-vitro data indicating that curcumin has antioxidant, anti-inflammatory, and anti-amyloid activity. In addition, studies in animal models of Alzheimer's disease (AD) indicate a direct effect of curcumin in decreasing the amyloid pathology of AD. As the widespread use of curcumin as a food additive and relatively small short-term studies in humans suggest safety, curcumin is a promising agent in the treatment and/or prevention of AD. Nonetheless, important information regarding curcumin bioavailability, safety and tolerability, particularly in an elderly population is lacking. We are therefore performing a study of curcumin in patients with AD to gather this information in addition to data on the effect of curcumin on biomarkers of AD pathology.
Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. (1998)

Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating factor (M-CSF) have revealed an inhibition of atherosclerosis development in the apolipoprotein E (apo E)-deficient model and in a diet-induced model. Using LDL receptor-deficient mice, we now show that atheroma development depends on M-CSF concentration, as not only did homozygous osteopetrotic (op/op) mice have dramatically reduced lesions (approximately 0.3% of control lesion size) but heterozygous (op/+) mice had lesions < 1% of controls. Mice heterozygous for the op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+). The finding that an approximately 2-fold reduction in M-CSF expression reduced lesion size approximately 100-fold suggests the requirement for a threshold level of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated either by changes in plasma lipoprotein levels or alterations in the number of circulating monocytes, since both op/op and op/+ mice exhibited higher levels of atherogenic lipoprotein particles and (op/+) mice showed a near normal number of circulating monocytes. LDL receptor-null littermates of genotypes from op/op, op/+, to +/+ showed monocyte differentials of approximately 4.5, 8, and 10%, respectively. Taken together, these results suggest that the effects of M-CSF on atherogenesis may not be mediated by expression of M-CSF systemically or by modulation of the number of circulating monocytes. These studies support the conclusion that M-CSF participates critically in fatty streak formation and progression to a complex fibrous lesion.
The risk of Barrett's esophagus associated with abdominal obesity in males and females (2012)

Esophageal adenocarcinoma arises from Barrett's esophagus (BE). Both occur predominantly in males. The role of abdominal obesity in this sex distribution is uncertain. Our study aimed to determine whether there is an association between abdominal obesity and risk of BE and if present was it modified by sex. A structured interview and anthropometric measures were conducted within a population-based case-control study. We recruited 237 BE cases (70% male) and 247 population controls, frequency matched by age and sex. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis. In the overall group and males, all measures of abdominal obesity [waist circumference (WC), waist-hip ratio (WHR), sagittal abdominal diameter (SAD) and waist-height ratio (WHtR)] were strongly associated with risk of BE (Overall: WC OR 2.2 95% CI 1.4-3.5, WHR 1.8 95% CI 1.2-2.9, SAD 2.3 95% CI 1.4-3.7, WHtR 1.9 95% CI 1.2-3.0, males WC 2.5 95% CI 1.4-4.3, WHR 2.4 95% CI 1.3-4.2, SAD 2.5 95% CI 1.4-4.3, WHtR 1.9 95% CI 1.1-3.4). These associations were minimally attenuated by adjusting for ever-symptoms of gastroesophageal reflux (GER). These findings suggest in males, non-GER factors related to abdominal obesity may be important in the development of BE. In females, there was modest association between measures of abdominal obesity and risk of BE but these were all abolished after adjusting for ever-symptoms of GER. The power to detect differences between sexes in the risk of BE associated with abdominal obesity was limited by the number of females in the study.
Immunochemical analysis of some proteins in cerebrospinal fluid and serum of patients with ischemic strokes. (1994)

Immunochemical studies of gamma gamma-neuron specific enolase (NSE), parvalbumin (PV), S-100 protein (S-100) and acidic fibrillary glial protein (GFAP) were studied in the cerebrospinal fluid and blood serum in 7 patients with ischemic cerebral stroke, aged 57 to 81 years. Cerebrospinal fluid and the first blood sample were taken on the first or second day of the disease. Further blood samples were taken once a week till the end of patients hospitalization, ending by patients discharge or death. Immunochemical identification of proteins under study were performed with Western-blotting technique. It was found that all proteins studied were present in both cerebrospinal fluid and blood serum on the first two days of the disease in small quantities. The blood content of both NSE and PV increased significantly during the first week of the disease. Both proteins disappeared from the blood serum between the second and fourth disease weeks. S-100 protein and GFAP contents in the blood reached significantly high level within the time interval between second and fifth disease weeks, and remained at a relatively high level till patients' death. In all cases computed tomography study and/or brain autopsy revealed extensive ischemic foci localized within areas supplied by the middle cerebral artery. No clear-cut correlation between extensiveness of the ischemic cerebral damage and the content of the proteins studied in both cerebrospinal fluid and blood serum was found. However, our data indicate that serial studies of the above proteins in patients with ischemic stroke may be useful in monitoring the progress of the disease, and occasionally in the prognosis at least in some cases.
Technological advances in bedside monitoring: biosensors. (1987)

The need to monitor certain key biochemical parameters in hospitalized patients is driving the development of biosensors, a new class of medical device for real-time, on-line quantitative analysis. A biosensor is a microelectronic device that utilizes a biological molecule (eg, antibody, enzyme, or receptor) as the sensing or signal-transducing element. Biosensors can be configured into simple, rapid, and cost-effective laboratory devices that will allow the clinical pathologist to become even more responsive to the primary care physician. In those instances where measurements on discrete samples do not provide the required information, continuous monitoring with implantable biosensors could provide real-time data on levels of critical endogenous or exogenous substances. By hybridizing recent advances in transdermal substance collection with the analytical capabilities of biosensors, devices for continuous noninvasive monitoring at the bedside can be envisioned. The clinical pathologist can and should play a key role in the clinical evaluation and implementation of such technological advances.
Human tumor virus utilizes exosomes for intercellular communication (2010)

The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs.
Liquid chromatography with tandem mass spectrometry method for the simultaneous determination of multiple sweet mogrosides in the fruits of Siraitia grosvenorii and its marketed sweeteners (2016)

A high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous quantification of eight major sweet mogrosides in different batches of the fruits of Siraitia grosvenorii and its marketed sweeteners. The sample preparation procedure and chromatographic and mass spectrographic conditions were optimized. Chromatographic separation was achieved on a reversed-phase Poroshell 120 SB C<sub>18</sub> column in 10.0 min with gradient elution with acetonitrile and water, both of which contained 0.1% formic acid. The multiple reaction monitoring scanning mode was employed for quantification in the negative ion mode. The developed method was validated with acceptable linearity (r<sup>2</sup> = 0.9984-0.9998) over a wide concentration range, precision (relative standard deviations = 1.09-3.91%), stability (relative standard deviations = 1.21-3.01%), and recovery in the range of 91.22-106.58% (relative standard deviations ≤ 3.79%) under optimum conditions. The proposed method was demonstrated to be simple, rapid, specific, and reliable and was successfully applied for the quality control of the fruits of S. grosvenorii and its marketed sweeteners.
VIDEO ANALYSIS USING CORNER MOTION STATISTICS (2010)

This paper presents an approach to infer what is happening in a (crowded) scene using a statistical method. Rather than trying to segment and track the individuals in each frame, our basic idea is to detect salient points (corners) along with their motion vectors. Finally, we obtain statistical measures on this data which are highly correlated with the kind of information/events proposed in some PETS2009 problems. 1.
Nuclear factor kappaB dominant negative genetic constructs inhibit X-ray induction of cell adhesion molecules in the vascular endothelium. (1998)

X-ray-induced expression of inflammatory mediators has been proposed to contribute to radiation injury in normal tissues. Radiation-inducible inflammatory mediators include the cell adhesion molecule (CAM) E-selectin and the intercellular adhesion molecule (ICAM)-1. Nuclear factor (NF)kappaB is activated by X-rays and may participate in the transcriptional regulation of each of these inflammatory mediators. To determine whether NFkappaB inhibition abrogates X-ray induction of inflammatory mediators, we used two experimental approaches including NFkappaB inhibitory drugs and a dominant negative genetic construct. Human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells were treated with the NFkappaB inhibitors ALLN, PDTC, NAC, and MG132. After irradiation, E-selectin or ICAM-1 was measured by fluorescence-activated cell-sorting analysis. E-selectin and ICAM-1 expression was measured by use of immunofluorescence and fluorescence-activated cell-sorting analysis. E-selectin expression increased 7-fold, and ICAM-1 expression increased 4-fold after irradiation. All of the inhibitors attenuated E-selectin expression after irradiation. ALLN and MG132 attenuated radiation-induced ICAM expression. However, PDTC and NAC induced increased expression of ICAM-1 in HUVECs. Inhibition of X-ray induction of ICAM by these agents could not be demonstrated. In separate experiments, the NFkappaB dominant negative genetic construct was cotransfected with the promoter-reporter constructs by means of Lipofectin reagent. The ICAM promoter-reporter construct consists of the 1.2-kb segment of the human ICAM promoter upstream of the transcriptional start site linked to the luciferase reporter gene (pGL.FL-Luc). The E-selectin promoter-reporter construct consists of 525 bp upstream of the transcriptional start site of the human E-selectin promoter linked to the human growth hormone reporter gene (pE525-GH). Endothelial cells transfected with the ICAM-1 promoter-reporter construct showed a 3-fold induction after irradiation. Likewise, cells transfected with pE525-GH showed a 7-fold induction after irradiation. When cotransfected with the CAM reporter-promoter constructs, the NFkappaB dominant negative genetic construct abolished X-ray-induced transcriptional activation of the E-selectin and ICAM-1 promoters. NFkappaB inhibition is, therefore, a means of abrogating radiation-induced expression of CAMs.
Immunomodulating antibodies in the treatment of metastatic melanoma: The experience with anti-CTLA-4, anti-CD137, and anti-PD1 (2012)

Clinical activity of anti-CTLA-4 (cytotoxic T-lymphocyte antigen-4) monoclonal antibodies (mAb) has changed the approaches for the treatment of cancer in terms of patterns of response, duration of response, and adverse event profiles. In fact, antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including anti-tumor immunity. Two recent studies using ipilimumab (an anti-CTLA-4 mAb) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite the different dosage used and the combination with dacarbazine in the first line treatment. Ongoing clinical studies will establish the efficacy of ipilimumab as monotherapy or in combination with other drugs for the treatment of metastatic melanoma and a variety of other cancers. Other antibodies, such as CD137 agonists and PD-1 antagonists, are currently in various stages of pre-clinical and clinical development. Agonist antibodies directed against CD137 (4-1BB) on the surface of antigen-primed T-lymphocytes increase tumor immunity that is curative against some transplantable murine tumors. Programmed death-1 (PD1) is a surface molecule delivering inhibitory signals important to maintain T-cell functional silence against their cognate antigens. Interference with PD1 or its ligand PD-L1 (B7-H1) increases anti-tumor immunity. As a result, human mAbs anti-PD1 and anti-PD-L1 are under clinical development. This paper reviews recent studies in the treatment of advanced melanoma with these types of monoclonal antibodies. Ipilimumab can be considered a cornerstone of a new era in melanoma treatment. However, the aim is to optimize the therapy with anti-CTLA-4 antibodies to define the best schedule for next combination regimens (other immunomodulatory antibodies, BRAF/MEK inhibitors, vaccines, etc.) that represent the natural evolution of future melanoma therapy.
Enzymes of Ethylene Biosynthesis (1989)

The properties of enzymes involved in ethylene biosynthesis are reviewed and progress toward the purification of these enzymes is described. The enzyme whose activity usually limits ethylene biosynthesis is 1-aminocyclopropane-1-carboxylate (ACC) synthase. Even though its level in plants is extremely low, it has now been purified from several sources. The enzyme that converts ACC to ethylene does not survive homogenization, apparently because it is membrane-bound and because its activity requires membrane integrity. Properties of this enzyme have been elucidated in vivo and in vacuolar preparations which possess the capacity to convert ACC to ethylene.