gebhart/patrepeval huggingface dataset:
Comparative Pharmacokinetics, Tissue Distribution, and Tumor Accumulation of Phosphorothioate, Phosphorodithioate, and Methylphosphonate Oligonucleotides in Nude Mice (1997)

The goals of this study were to systematically compare the pharmacokinetics and tissue distribution of phosphorothioate (PS), methylphosphonate (MP), and phosphorodithioate (PS2) oligonucleotide analogs; 15-mers of sequence d-TAC GCC AAC AGC TCC (5'-3') complementary to the AUG region of K-ras were radiolabeled with carbon-14. Oligomers were administered as a single dose in the tail vein of nude mice harboring a K-ras-dependent human pancreatic tumor (CFPAC1). The kinetics of PS, PS2, and MP oligomer availability in the bloodstream was followed. Concentration versus time profiles for all oligomers were biphasic, indicative of a two-compartment model. A rapid distribution phase with t1/2 alpha values of 1 minute or less and an elimination phase with average t1/2 beta values of 24-35 minutes were observed. Volumes of distribution (Vd) were 3.2, 4.8, and 6.3 ml for PS2, MP, and PS, respectively, in comparison to 3.6 ml for sucrose, a fluid-phase marker. Relative tissue drug levels obtained at 1 and 24 hours after administration were kidney > liver > spleen > tumor > muscle. Total kidney and liver oligonucleotide accumulation was approximately 7%-15% of the initial dose, with tumor accumulating 2%-3%. Intact compound was recovered from all tissues, including tumor, as assessed by high-pressure reversed-phase HPLC coupled to radiometric detection. Integrity of the oligonucleotides ranged from 73% in blood to 43%-46% in kidney and liver. Kidney and liver appear to be the primary sites of metabolism. These results demonstrate widespread tissue availability of these compounds and suggest their development as potential antitumor agents.
Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with "anti-free radical" interventions and a free radical-generating system in the isolated perfused rat heart. (1986)

We have assessed, whether six agents, that either inhibit free radical formation or scavenge free radicals once they are produced, can reduce the incidence of reperfusion-induced arrhythmias, whether a free radical-generating system (FeCl3 X adenosine diphosphate) can increase the incidence of reperfusion-induced arrhythmias, and whether "anti-free radical" interventions can reduce reperfusion rhythm disturbances caused by the addition of FeCl3 X adenosine diphosphate. With the isolated, perfused rat heart (n = 15 in each group), inclusion of L-methionine (1 and 10 mM), superoxide dismutase (2.5 X 10(4) and 1 X 10(5) U/liter), catalase (5 X 10(4), 5 X 10(5), and 1 X 10(6) U/liter), mannitol (50 mM), glutathione (10 microM), or desferrioxamine (150 microM) significantly reduced the incidence of reperfusion-induced ventricular fibrillation and, in many cases, the incidence of reperfusion-induced ventricular tachycardia. The mean duration of sinus rhythm during reperfusion was also increased significantly. Perfusion of hearts with boiled superoxide dismutase (1 X 10(5) U/liter) or boiled catalase (1 X 10(6) U/liter) did not decrease arrhythmias. Conversely, under conditions where, in the control group, the incidence of reperfusion arrhythmias was lowered by increasing perfusate potassium to 6.5 mM, the addition of the free radical-generating system FeCl3 X adenosine diphosphate (0.1 microM X 1 microM) to the perfusion fluid increased dramatically the incidence of reperfusion-induced ventricular fibrillation and tachycardia. Simultaneous perfusion with FeCl3 X adenosine diphosphate and superoxide dismutase (1 X 10(5) U/liter), catalase (1 X 10(6) U/liter), mannitol (50 mM), methionine (10 mM), or desferrioxamine (150 microM) again reduced the incidence of reperfusion-induced arrhythmias and increased the duration of normal sinus rhythm during the reperfusion phase. Thus, addition of six "anti-free radical" interventions reduced the incidence of reperfusion-induced arrhythmias, addition of a free radical-generating system increased the incidence of reperfusion-induced arrhythmias, and simultaneous perfusion of the hearts with FeCl3 X adenosine diphosphate and "anti-free radical" interventions again reduced reperfusion rhythm disturbances. These results are further evidence supporting the hypothesis that oxygen-derived free radicals play an important role in the genesis of reperfusion-induced arrhythmias.
Beneficial effects of SPM-5185, a cysteine-containing NO donor in myocardial ischemia-reperfusion (1992)

Intravenous administration of SPM-5185 [N-nitratopivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester], a cysteine-containing nitric oxide (NO) donor, or SPM-5267 [pivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester], an analogue of SPM-5185 that lacks the NO moiety, was studied in a feline myocardial ischemia-reperfusion model. Administration of SPM-5185 (1 mg/kg), followed by a 2-mg.kg-1.h-1 infusion starting 10 min before reperfusion, resulted in significant protection 4.5 h postreperfusion. In the myocardial ischemia (MI)+SPM-5267 group, 38 +/- 4% of the area at risk was necrotic, whereas the necrotic area/area at risk was only 7 +/- 2% in the MI+SPM-5185 group (P less than 0.01). Moreover, SPM-5185 treatment markedly attenuated the endothelial dysfunction observed in the left anterior descending coronary artery after reperfusion by 50%. These beneficial effects occurred despite the absence of a significant change in myocardial oxygen demand, as measured by the pressure-rate index. In vitro experiments demonstrated that SMP-5185, but not SPM-5267, decreased adherence of neutrophils to the coronary vascular endothelium and decreased production of superoxide radicals. Therefore, a likely mechanism of the observed cardioprotection by SPM-5185 involves attenuation of polymorphonuclear leukocyte-induced endothelial dysfunction.
Cyclopamine-Induced Holoprosencephaly and Associated Craniofacial Malformations in the Golden Hamster: Anatomic and Molecular Events (1998)

Holoprosencephaly is a complex congenital malformation of the brain and is often associated with a spectrum of facial anomalies ranging from normocephaly or nondiagnostic changes to cleft lip/palate (premaxillary dysgenesis), cebocephaly, ethmocephaly, and cyclopia. The primary insult is thought to occur during gastrulation, when prechordal mesenchyme and overlying anterior neural plate undergo complex developmental interactions. Exposure to cyclopamine, a steroid isolated from the desert plant Veratrum californicum, causes holoprosencephaly in mammalian embryos. We have begun to study the pathogenesis of cyclopamine-induced holoprosencephaly and associated craniofacial anomalies in Syrian golden hamsters (Mesocricetus auratus). Embryos were exposed to a single maternal dose of cyclopamine during gastrulation on embryonic day (E) 7.0. By E13.0, 62% of fetuses showed craniofacial malformations, including premaxillary dysgenesis, ocular hypotelorism, and cebocephaly. Facial anomalies were associated with absence of the premaxilla and abnormalities of the midline cranial base, particularly the ethmoid and sphenoid bones. Histological sections from cyclopamine-treated embryos at earlier stages showed marked deficiency of cranial mesenchyme derived from the rostral neural crest. Expression of two transcription factors, HNF-3 beta and Hox-b5, which have been implicated in specification of rostral and caudal neural crest cells, respectively, were examined immunohistochemically. Treatment with cyclopamine caused a transient loss of HNF-3 beta immunoreactivity in prechordal mesenchyme, but had no effect on Hox-b5 expression. The findings suggest that an early event in the pathogenesis of cyclopamine-induced holoprosencephaly may be altered expression of selected proteins in the prechordal mesenchyme and floor plate with secondary impaired development of the adjacent neural plate and cranial neural crest.
P4‐233: Essential or toxic? The two faces of the Abeta42 peptide (2008)

Alzheimer's Disease (AD) is a devastating aging-associated neurodegenerative disorder leading to marked behavioral changes and a dramatic decline in learning and memory. One hallmark pathological feature is the appearance of large deposits of β-amyloid (Aβ) peptides, predominantly Aβ42, within neurons and amyloid plaques. These peptides are produced from the sequential cleavage of the amyloid precursor protein (APP) carried out by beta- and gamma-secretase. Pyramidal neurons of the cerebral cortex and hippocampus appear to be primarily targeted. Abeta peptides, including Aβ42 and Aβ40, are found in the blood of both normal and AD individuals. Leakage of these so-called “toxic” peptides into the brain tissue as a result of breakdown in the blood-brain barrier occurs due to age-associated changes in blood vessels, head trauma and stroke. In the brain, these peptides either remain soluble (monomeric or oligomeric) or insoluble (polymeric). Immunohistochemistry, biological assays. Surprisingly, our results show that Abeta42 is present in and on neurons in the brain and spinal cord in humans throughout life, and is detectable in neurons as early as the fetal stage. It is also detected in the retinal ganglion cells. This widespread presence of Abeta42 in neurons argues against it being toxic to neurons. Furthermore, our results also show that the Abeta42 peptide is able to activate the guanylate cyclase signal transduction pathway in normal brain. Taken together, these results suggest that Abeta42 may be an essential neuronal component, and its abundant presence in the synaptic field of neurons suggest that it may be an essential component of synaptic membranes. However, in the diseased state, an exogenous supply of the peptide, from blood-brain barrier breach, for example, leads to large deposits of Abeta42 within the neurons, displacing the cell's normal complement of protein synthetic machinery and altering the signal transduction pathways. These actions may be the key to their so-called “toxicity” during Alzheimer's disease progression.
Happy Moves, Sad Grooves (2016)

The design of shape-changing interfaces to show emotions relies on craft skill with few clear guidelines. Through two experiments, we explore how to design such interfaces using theories of the relation between biological motion and affect. In the first experiment, 19 participants viewed six shape-changing behaviors that varied the velocity, fluidity, direction, and orientation of the movement of an extrusion from a small box in accordance with existing theories of affective motion. Participants were able to recognize four of the six intended basic Ekman emotions (sadness, fear, happiness, surprise) with above-chance probability. The second experiment used 36 shape-changing behaviors that systematically varied speed, regularity of motion, and direction. For each behavior, 23 participants rated valence, arousal, and dominance. Speed, direction, and orientation impacted emotion ratings significantly and in the predicted directions. These results offer an initial basis for the systematic design of emotions in shape-changing interfaces.
Autoimmune lymphoproliferative syndrome (2003)

Autoimmune lymphoproliferative syndrome arises early in childhood in people who inherit mutations in genes that mediate lymphocyte apoptosis, or programmed cell death. In the immune system, antigen-induced lymphocyte apoptosis maintains immune homeostasis by limiting lymphocyte accumulation and minimizing reactions against self-antigens. In autoimmune lymphoproliferative syndrome, defective lymphocyte apoptosis manifests as chronic, nonmalignant adenopathy and splenomegaly; the expansion of an unusual population of CD4-CD8- T cells; and the development of autoimmune disease. Most cases of autoimmune lymphoproliferative syndrome involve heterozygous mutations in the lymphocyte surface protein Fas (CD95, Apo1) that impair a major apoptotic pathway. Prospective evaluations of patients and their families have revealed an ever-expanding spectrum of autoimmune lymphoproliferative syndrome and its major complications.
Reconstruction of movement-related intracortical activity from micro-electrocorticogram array signals in monkey primary motor cortex (2012)

Subdural electrode arrays provide stable, less invasive electrocorticogram (ECoG) recordings of neural signals than multichannel needle electrodes. Accurate reconstruction of intracortical local field potentials (LFPs) from ECoG signals would provide a critical step for the development of a less invasive, high-performance brain-machine interface; however, neural signals from individual ECoG channels are generally coarse and have limitations in estimating deep layer LFPs. Here, we developed a high-density, 32-channel, micro-ECoG array and applied a sparse linear regression algorithm to reconstruct the LFPs at various depths of primary motor cortex (M1) in a monkey performing a reach-and-grasp task. At 0.2 mm beneath the cortical surface, the real and estimated LFPs were significantly correlated (correlation coefficient (r); 0.66 ± 0.11), and the r at 3.2 mm was still as high as 0.55 ± 0.04. A time-frequency analysis of the reconstructed LFP showed clear transition between resting and movements by the monkey. These methods would be a powerful tool with wide-ranging applicability in neuroscience studies.
Heterologous gene expression in Campylobacter coli: The use of bacterial luciferase in a promoter probe vector (1993)

A novel promoter probe plasmid (pSP73) was constructed to allow the analysis of environmentally regulated gene expression in Campylobacter. The vector utilizes the luxAB genes from Xenorhabdus luminescens, which encode a thermostable luciferase, as reporters of gene expression. The utility of this reporter system was demonstrated by placing the expression of luxAB under the transcriptional control of the flaA gene promoter.
A spectrally sliced PON employing Fabry-Perot lasers (1998)

We investigate using Fabry-Perot lasers as the upstream transmitters in a wavelength-division-multiplexed passive optical network (WDM-PON). We demonstrate transmission of a 10-Mb/s signal through each port of a wavelength-grating router followed by 18 km of fiber using an uncooled Fabry-Perot laser. These signals could be subcarrier multiplexed together, so that each user would have a dedicated radio-frequency channel. Since Fabry-Perot lasers provide more output power than low-cost light-emitting diodes, this may enable deployment of WDM-PON's in areas where optical loss prohibits the use of other low cost optical sources. The bit-rate is limited by mode-fluctuations being converted into intensity noise when transmitted through the router.
Pretranslational Regulation of Type 2 Deiodinase (2005)

Type 2 deiodinase (D2) is a highly potent selenoenzyme that catalyzes the first step of thyroid hormone action and its expression is under close, multilevel control. D2 expression is tissue specific and can be regulated by transcriptional and posttranscriptional mechanisms. There is now compelling evidence that D2 is critically important in triiodothyronine (T3) homeostasis as well as in several biologic processes in which thyroid hormone is involved. A host of factors are known to influence dio2 mRNA including the transcription factors that regulate the dio2 gene in different cell types. In particular, cyclic adenosine monophosphate (cAMP) and two homeodomain- containing proteins are relevant for its defined and highly dynamic expression pattern. Single nucleotide polymorphisms of the dio2 gene and other pre-translational events such as alternative splicing can potentially modulate D2 expression and ultimately T(3) generation. Given the wealth of data accumulated over the past two decades, we have attempted in this review to provide a comprehensive update on the pretranslational regulation of D2.
Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer (2015)

Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer.
Nitrogenase and biological nitrogen fixation (1994)

Biological nitrogen fixation is catalyzed by the nitrogenase enzyme system which consists of two metalloproteins, the iron (Fe-) protein and the molybdenum-iron (MoFe-) protein. Together, these proteins mediate the ATP-dependent reduction of dinitrogen to ammonia. Recent crystallographic analyses of Fe-protein and MoFe-protein have revealed the polypeptide fold and the structure and organization of the unusual metal centers in nitrogenase. These structure provide a molecular framework for addressing the mechanism of the nitrogenase-catalyzed reaction. General features of the nitrogenase system, including conformational coupling of nucleotide hydrolysis, aspects of the cluster structures, and the general spatial organization of redox centers within the protein subunits, are relevant to a wide range of biochemical systems.
El acoso moral en el trabajo en los empleados del Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara (2005)

RESUMEN El objetivo de este trabajo fue estimar la prevalencia del acoso moral en un grupo de trabajadores administrativos y de servicio universitarios, asi como identificar las situaciones y comportamientos de acoso moral mas recurrentes. El tipo de estudio utilizado fue el no experimental, con un diseno transeccional y correlacional. La prevalencia encontrada para el acoso moral fue de 10.3 por ciento para ambos grupos de trabajadores. Los trabajadores administrativos registraron una prevalencia de 6.86 por ciento, mientras que en los trabajadores de servicio fue de 3.44 por ciento. Los comportamientos y situaciones de acoso mas frecuentes correspondieron a limitar la comunicacion. Mientras que las estrategias mas utilizadas fueron: criticar su trabajo, dificultarle la expresion, ignorar su presencia, calumniarle y murmurar a sus espaldas, exagerar sus fallos y errores.
An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression (2018)

These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors. These chromatin changes may be associated with those seen during colon cancer development.
Record‐linkage for pharmacovigilance in Scotland (1999)

Record-linkage is the linkage of patient-specific information that is stored separately. Recent advances in computerization have meant that record-linkage techniques in medical research are increasingly being used and refined. In particular, they have made a significant contribution to pharmacovigilance, which involves linking drug exposure to outcomes data. In this article, the contribution of record-linkage in Scotland to medical research is described. The two organizations that utilize record-linkage techniques are the Medicines Monitoring Unit (MEMO) of the University of Dundee and the Information and Statistics Division (ISD) of the NHS in Scotland. Pharmacovigilance is MEMO's main concern (using data from the Tayside region of Scotland), while ISD link health care datasets for Scotland for general health care research. The experience of the two groups is now being combined to carry out drug safety studies in the entire population of Scotland.
Long‐Term Use of Preservatives on Rat Nasal Respiratory Mucosa: Effects of Benzalkonium Chloride and Potassium Sorbate (2000)

It is our finding that even a low-concentration solution of preservative can lead to nasal lesion. Hence there is a strong need to develop both a preservative that can be safely and widely used and a nasal spray without preservatives.
Prophylactic treatment of chronic tension‐type headache using botulinum toxin type A (1999)

Chronic tension‐type headache is a common condition, the pathophysiology of which is not well understood. Over‐activity of the pericranial muscles is thought to play a role, although sustained muscle contraction is probably a consequence, rather than a cause, of headache. Botulinum toxin type A (BTX‐A) is useful in many conditions involving excessive muscle contraction and may therefore be effective in relieving the pain associated with this type of headache. To investigate the efficacy of BTX‐A in relieving pain associated with chronic tension‐type headache, a double‐btind, randomised, placebo‐controlled study was carried out, in which 37 patients received BTX‐A, injected into the temporalis or cervical muscles of the neck. Clinical outcome was measured over a 4‐month study period using headache diaries and chronic pain index scores. Patients treated with BTX‐A showed an improvement in headache severity over the 4‐month study period, with 13 out of 22 patients showing a 25, 50 or &gt;50% improvement in headache score at Month 3 compared with two out of 15 patients in the placebo group. The number of headache‐free days increased significantly in the BTX‐A‐treated patient group, and patients recorded an improvement in quality of life following BTX‐A injection. It can be concluded that intramuscular injection of BTX‐A is an effective treatment for chronic tension‐type headache.
LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease (2012)

Ldlr(-/-) mice, but not APOE2ki mice, developed sustained hepatic inflammation and liver damage upon long term HFC feeding due to increased sensitivity for oxLDL uptake. Therefore, the Ldlr(-/-) mice are a promising physiological model particularly vulnerable for investigating the onset of hepatic inflammation in non-alcoholic steatohepatitis.
Concentration Independent Modulation of Local Micromechanics in a Fibrin Gel (2011)

Methods for tuning extracellular matrix (ECM) mechanics in 3D cell culture that rely on increasing the concentration of either protein or cross-linking molecules fail to control important parameters such as pore size, ligand density, and molecular diffusivity. Alternatively, ECM stiffness can be modulated independently from protein concentration by mechanically loading the ECM. We have developed a novel device for generating stiffness gradients in naturally derived ECMs, where stiffness is tuned by inducing strain, while local mechanical properties are directly determined by laser tweezers based active microrheology (AMR). Hydrogel substrates polymerized within 35 mm diameter Petri dishes are strained non-uniformly by the precise rotation of an embedded cylindrical post, and exhibit a position-dependent stiffness with little to no modulation of local mesh geometry. Here we present the device in the context of fibrin hydrogels. First AMR is used to directly measure local micromechanics in unstrained hydrogels of increasing fibrin concentration. Changes in stiffness are then mapped within our device, where fibrin concentration is held constant. Fluorescence confocal imaging and orbital particle tracking are used to quantify structural changes in fibrin on the micro and nano levels respectively. The micromechanical strain stiffening measured by microrheology is not accompanied by ECM microstructural changes under our applied loads, as measured by confocal microscopy. However, super-resolution orbital tracking reveals nanostructural straightening, lengthening, and reduced movement of fibrin fibers. Furthermore, we show that aortic smooth muscle cells cultured within our device are morphologically sensitive to the induced mechanical gradient. Our results demonstrate a powerful cell culture tool that can be used in the study of mechanical effects on cellular physiology in naturally derived 3D ECM tissues.