gebhart/patrepeval huggingface dataset:
Immuno‐electron microscopic localization of estradiol receptor in cells of male and female reproductive and non‐reproductive organs (1994)

The localization of estradiol receptor (ER) in various tissues and their distribution in sub-cellular compartments were studied by means of immunogold-electron microscopic methods using a site-directed polyclonal antibody developed against a peptide from the DNA binding site of ER. This method was used to determine the presence and localization of ER in tissues and cells of male and female reproductive and non-reproductive organs. In the female reproductive tract, endometrial cells and the cells of the corpus luteum were found to contain ER. In non-reproductive organs of both sexes the following cell types showed significant labeling: hepatocytes, epithelial duodenal cells, striated muscle fibers, cells of the proximal convoluted tubules of the kidney, lymphocytes, neurons, and adipose cells. Alveolar epithelial cells were studied only in female specimens and were labeled by the anti-ER. Prostatic and epididymal epithelial cells were found to be labeled in the male reproductive organs. In all these cells a higher density of label was found in the nucleus, especially in the space between the clumps of compact chromatin, as was previously found in epithelial endometrial cells. These results suggest that estradiol exerts its effects through a common nuclear mechanism in cells of male and female reproductive and non-reproductive organs.
Endocrine Resistance in Breast Cancer: Molecular Pathways and Rational Development of Targeted Therapies (2012)

Endocrine resistance presents a major challenge in the management of estrogen receptor (ER)-positive breast cancer and is an area under intense investigation. Although the underlying mechanism is still poorly understood, many studies point towards the 'cross-talk' between ER and growth factor receptor signaling pathways as the key in the development of estrogen-independent growth in breast cancer. This review aims to provide the reader our current understanding of various molecular pathways that mediate endocrine resistance and that are being evaluated as therapeutic targets for ER-positive breast cancer. While most of the agents that target these pathways have only been tested in Phase I or small Phase II trials, some have shown encouraging results. A critical issue that remains is the development of research strategies and clinical trials that take into account the molecular heterogeneity of ER-positive breast cancer.
Dual-Purpose Polymer Labels for Fluorescent and Mass Cytometric Affinity Bioassays (2013)

We describe the synthesis and characterization of a family of poly(N-alkylacrylamide) polymers carrying 2-6 fluorescent dye molecules, ∼70 pendant DTPA (diethylenetriaminepentaacetic acid) groups, and an orthogonal maleimide end-group for covalent attachment to an antibody (Ab). These dual-purpose labels were designed for use in multiplexed immunoassays based on both mass cytometry and fluorescent flow cytometry. A challenge in the polymer synthesis was finding conditions for attaching a sufficient number of dye molecules to each polymer chain. Although attachment of a terminal maleimide to the polymers was not as efficient as anticipated, the end-functional polymers were still effective in labeling Abs. Secondary goat antimouse IgG was labeled with the four dual-label polymers as well as a control polymer, and while the resultant antibody-polymer conjugates showed positive performance in mass cytometric and fluorescent assays, some trials showed problems such as low signal and nonspecific adsorption. Four primary antibody conjugates were prepared and used to stain cells in 4-plex assays. The results of both primary assays are bittersweet in that the CD3-FITC and CD45-DyLight 649 conjugates performed well, while the CD13-DyLight 405 and the CD38-DyLight 549 conjugates did not.
Cannabinoids for the treatment of dementia (2009)

This review finds no evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia. More randomized double-blind placebo controlled trials are needed to determine whether cannabinoids are clinically effective in the treatment of dementia.
A piezoelectric vibration based generator for wireless electronics (2004)

Enabling technologies for wireless sensor networks have gained considerable attention in research communities over the past few years. It is highly desirable, even necessary in certain situations, for wireless sensor nodes to be self-powered. With this goal in mind, a vibration based piezoelectric generator has been developed as an enabling technology for wireless sensor networks. The focus of this paper is to discuss the modeling, design, and optimization of a piezoelectric generator based on a two-layer bending element. An analytical model of the generator has been developed and validated. In addition to providing intuitive design insight, the model has been used as the basis for design optimization. Designs of 1 cm3 in size generated using the model have demonstrated a power output of 375 μW from a vibration source of 2.5 m s-2 at 120 Hz. Furthermore, a 1 cm3 generator has been used to power a custom designed 1.9 GHz radio transmitter from the same vibration source.
The role of recreational sport activity in Achilles tendon rupture (1989)

During the last few decades, the incidence of tendon ruptures has increased in civilized countries. Our ma terial comprises 749 patients who had 832 tendon ruptures treated surgically between 1972 and 1985. There were no competitive athletes among the patients studied. There were 292 single ruptures of the Achilles tendon, 274 of the proximal biceps brachii, 113 of the extensor pollicis longus, and 70 of other tendons. Forty- eight patients had multiple ruptures and 35 patients had reruptures. Achilles tendon ruptures often occurred in recreational sports activities (59%), in contrast to other tendon ruptures (2%; P &lt; 0.001). The mean age for patients who had Achilles tendon rupture was 35.2 years and for patients with other ruptures, 50.7 years (P &lt; 0.001). There was a connection between the high incidence of blood group O and tendon ruptures (P&lt; 0.001). In cases of multiple ruptures and reruptures, the frequency of blood group O was 71%. Sixty-two point three percent of the patients with Achilles tendon rupture were professionals or white collar workers, which is markedly more than in the Hungarian popula tion (12.7%; P &lt; 0.001). Two hundred and six Achilles tendon ruptures were studied histologically, and all cases displayed pathological alterations. The results indicate that complete rupture of the Achilles tendon is usually a sequel to a sedentary life-style and participa tion in sports activities.
Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. (1992)

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are molecules which regulate the development and maintenance of specific functions in different populations of peripheral and central neurons, amongst them sensory neurons of neural crest and placode origin. Under physiological conditions NGF is synthesized by peripheral target tissues, whereas BDNF synthesis is highest in the CNS. This situation changes dramatically after lesion of peripheral nerves. As previously shown, there is a marked rapid increase in NGF mRNA in the nonneuronal cells of the damaged nerve. The prolonged elevation of NGF mRNA levels is related to the immigration of activated macrophages, interleukin-1 being the most essential mediator of this effect. Here we show that transsection of the rat sciatic nerve also leads to a very marked increase in BDNF mRNA, the final levels being even ten times higher than those of NGF mRNA. However, the time-course and spatial pattern of BDNF mRNA expression are distinctly different. There is a continuous slow increase of BDNF mRNA starting after day 3 post-lesion and reaching maximal levels 3-4 wk later. These distinct differences suggest different mechanisms of regulation of NGF and BDNF synthesis in non-neuronal cells of the nerve. This was substantiated by the demonstration of differential regulation of these mRNAs in organ culture of rat sciatic nerve and Schwann cell culture. Furthermore, using bioassays and specific antibodies we showed that cultured Schwann cells are a rich source of BDNF- and ciliary neurotrophic factor (CNTF)-like neurotrophic activity in addition to NGF. Antisera raised against a BDNF-peptide demonstrated BDNF-immunoreactivity in pure cultured Schwann cells, but not in fibroblasts derived from sciatic nerve.
Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells (2019)

Cisplatin is a commonly used chemotherapeutic drug for cancer treatment, but its nephrotoxicity may lead to the deterioration of renal function. Previous work has been focused on cisplatin-induced acute kidney disease, whereas the mechanism of chronic kidney disease after cisplatin chemotherapy is largely unknown. In the present study, we have characterized the mouse model of chronic kidney defects induced by repeated low-dose cisplatin treatment. We have also established a relevant cell culture model. In the animal model, C57 mice were given weekly injection of 8 mg/kg cisplatin for 4 wk. This led to a sustained decline of kidney function. These mice showed loss of kidney mass, interstitial fibrosis, continued activation of inflammatory cytokines, and appearance of atubular glomeruli. In the cell model, the BUMPT mouse proximal tubular cell line was treated four times with 1-2 μM cisplatin, resulting in low levels of apoptosis and the expression of fibrosis proteins and profibrotic factors. These data suggest that repeated treatment with low-dose cisplatin causes long-term renal pathologies with characteristics of chronic kidney disease.
Evolution of the Sabin type 1 poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis (1997)

Attenuated strains of the Sabin oral poliovirus vaccine replicate in the human gut and in rare cases cause vaccine-associated paralytic poliomyelitis (VAPP). Reversion of vaccine strains toward a pathogenic phenotype is probably one of the main causes of VAPP, a disease most frequently associated with type 3 and type 2 strains and more rarely with the type 1 (Sabin 1) strain. To identify the determinants and mechanisms of safety versus pathogenicity of the Sabin 1 strain, we characterized the genetic and phenotypic changes in six Sabin 1-derived viruses isolated from immunocompetent patients with VAPP. The genomes of these strains carried either few or numerous mutations from the original Sabin 1 genome. As assessed in transgenic mice carrying the human poliovirus receptor (PVR-Tg mice), all but one strain had lost the attenuated phenotype. Four strains presented only a moderate neurovirulent phenotype, probably due at least in part to reversions to the wild-type genotype, which were detected in the 5' noncoding region of the genome. The reversions found in most strains at nucleotide position 480, are known to be associated with an increase in neurovirulence. The construction and characterization of Sabin 1 mutants implicated a reversion at position 189, found in one strain, in the phenotypic change. The presence of 71 mutations in one neurovirulent strain suggests that a vaccine-derived strain can survive for a long time in humans. Surprisingly, none of the strains analyzed were as neurovirulent to PVR-Tg mice as was the wild-type parent of Sabin 1 (Mahoney) or a previously identified neurovirulent Sabin 1 mutant selected at a high temperature in cultured cells. Thus, in the human gut, the Sabin 1 strain does not necessarily evolve toward the genetic characteristics and high neuropathogenicity of its wild-type parent.
Miniature RT-PCR system for diagnosis of RNA-based viruses (2005)

This paper presents an innovative portable chip-based RT-PCR system for amplification of specific nucleic acid and detection of RNA-based viruses. The miniature RT-PCR chip is fabricated using MEMS (Micro-electro-mechanical-system) techniques, and comprises a micro temperature control module and a PDMS (polydimethylsiloxane)-based microfluidic control module. The heating and sensing elements of temperature control module are both made of platinum and are located within the reaction chambers in order to generate a rapid and uniform thermal cycling. The microfluidic control module is capable of automating testing process with minimum human intervention. In this paper, the proposed miniature RT-PCR system is used to amplify and detect two RNA-based viruses, namely dengue virus type-2 and enterovirus 71 (EV 71). The experimental data confirm the ability of the system to perform a two-step RT-PCR process. The developed miniature system provides a crucial tool for the diagnosis of RNA-based viruses.
Mapping and localization using GPS, lane markings and proprioceptive sensors (2013)

Estimating the pose in real-time is a primary function for intelligent vehicle navigation. Whilst different solutions exist, most of them rely on the use of high-end sensors. This paper proposes a solution that exploits an automotive type L1-GPS receiver, features extracted by low-cost perception sensors and vehicle proprioceptive information. A key idea is to use the lane detection function of a video camera to retrieve accurate lateral and orientation information with respect to road lane markings. To this end, lane markings are mobile-mapped by the vehicle itself during a first stage by using an accurate localizer. Then, the resulting map allows for the exploitation of camera-detected features for autonomous real-time localization. The results are then combined with GPS estimates and dead-reckoning sensors in order to provide localization information with high availability. As L1-GPS errors can be large and are time correlated, we study in the paper several GPS error models that are experimentally tested with shaping filters. The approach demonstrates that the use of low-cost sensors with adequate data-fusion algorithms should lead to computer-controlled guidance functions in complex road networks.
Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy (2014)

We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment-refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors, it is an attractive immunotherapy target. Antibody-based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody, and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin- chimeric antigen receptor are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin, was the first mesothelin-directed therapy to enter the clinic, and its use showed that mesothelin-targeted therapy was safe in patients. More importantly, our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers.
Topical 4% nicotinamide vs. 1% clindamycin in moderate inflammatory acne vulgaris (2013)

Nicotinamide and clindamycin gels are two popular topical medications for acne vulgaris. This study aimed to compare efficacy of the topical 4% nicotinamide and 1% clindamycin gels in these patients. In this randomized, double-blind clinical trial, patients with moderate inflammatory facial acne vulgaris were randomly allocated to receive either topical 4% nicotinamide (n = 40) or 1% clindamycin gels (n = 40) twice daily. In each group, they were further categorized in two subgroups with oily and non-oily types of facial skin. The Cook's acne grade was determined at baseline and at weeks 4 and 8 post treatment. Acne grade decreased from an average of 5.93 ± 0.83 at baseline to 4.03 ± 1.33 at week 4 and 2.08 ± 1.59 at week 8 in nicotinamide receivers, and from an average of 5.70 ± 0.94 at baseline to 3.85 ± 1.66 at week 4 and 2.03 ± 1.53 at week 8 in the clindamycin group (within-group P < 0.001, between-group P > 0.05). Comparing with each other, nicotinamide and clindamycin gels were significantly more efficacious in oily and non-oily skin types, respectively. No major side effect was encountered by any patient. Skin type is a significant factor in choosing between topical nicotinamide and clindamycin in patients with acne vulgaris.
Purification and sequence of a presynaptic peptide toxin from Conus geographus venom (1984)

A novel toxin, omega-conotoxin (omega-CgTX), from the venom of the fish-eating marine mollusc Conus geographus has been purified and biochemically characterized. Recently, this omega-conotoxin has been shown to inhibit the voltage-activated entry of Ca2+, thus providing a potentially powerful probe for exploring the vertebrate presynaptic terminal [Kerr, L. M., & Yoshikami, D. (1984) Nature (London) 308, 282-284]. The toxin is a basic 27 amino acid peptide amide with three disulfide bridges. An unusual feature is a remarkable preponderance of hydroxylated amino acids. The sequence of omega-CgTx GVIA is Cys-Lys-Ser- Hyp-Gly5-Ser-Ser-Cys-Ser-Hyp10-Thr-Ser-Tyr-Asn-Cys15-C ys-Arg-Ser- Cys-Asn20-Hyp-Tyr-Thr-Lys-Arg25-Cys-Tyr-NH2.
Collagen‐based wound dressings: Control of the pore structure and morphology (1986)

Collagen-based sponges have been used as both temporary and permanent coverings for dermal defects in animals and humans. Cellular ingrowth within such a sponge has been shown to depend on the porosity and the presence of fibrous structure. Collagen sponges were made by freezing and freeze-drying dispersions under acidic conditions. These studies involved the effects of dispersion pH and viscosity as well as freezing temperature on the surface and bulk morphology of collagen-based sponges. Using scanning electron and light microscopy, the results of these studies indicated that large surface pores that form connections (channels) with the interior of the sponge were formed using low-viscosity collagen dispersions. At high dispersion pH (3.2) and at a moderate freezing temperature (-30 degrees C), fibrous structure and a large number of channels were present. When a lower dispersion pH (2.0) and freezing temperature (-80 degrees C) were used, pores sizes were smaller with channels and fibrous structure, whereas a higher freezing temperature (-20 degrees C) resulted in a sheet-like structure and increased pore sizes. Differences in pore size and surface morphology were explained on the basis of ice crystal growth. In the case of abundant free water (high pH) and high freezing temperature, the pore size was greatest because of enhanced ice crystal growth.
Enhanced Killing of Cancer Cells by Poly(ADP-ribose) Polymerase Inhibitors and Topoisomerase I Inhibitors Reflects Poisoning of Both Enzymes (2011)

Poly(ADP-ribose) polymerase-1 (PARP1) plays critical roles in the regulation of DNA repair. Accordingly, small molecule inhibitors of PARP are being developed as agents that could modulate the activity of genotoxic chemotherapy, such as topoisomerase I poisons. In this study we evaluated the ability of the PARP inhibitor veliparib to enhance the cytotoxicity of the topoisomerase I poisons topotecan and camptothecin (CPT). Veliparib increased the cell cycle and cytotoxic effects of topotecan in multiple cell line models. Importantly, this sensitization occurred at veliparib concentrations far below those required to substantially inhibit poly(ADP-ribose) polymer synthesis and at least an order of magnitude lower than those involved in selective killing of homologous recombination-deficient cells. Further studies demonstrated that veliparib enhanced the effects of CPT in wild-type mouse embryonic fibroblasts (MEFs) but not Parp1(-/-) MEFs, confirming that PARP1 is the critical target for this sensitization. Importantly, parental and Parp1(-/-) MEFs had indistinguishable CPT sensitivities, ruling out models in which PARP1 catalytic activity plays a role in protecting cells from topoisomerase I poisons. To the contrary, cells were sensitized to CPT in a veliparib-independent manner upon transfection with PARP1 E988K, which lacks catalytic activity, or the isolated PARP1 DNA binding domain. These results are consistent with a model in which small molecule inhibitors convert PARP1 into a protein that potentiates the effects of topoisomerase I poisons by binding to damaged DNA and preventing its normal repair.
Single‐Dose Pharmacokinetics of Multilayer‐Release Methylphenidate and Immediate‐Release Methylphenidate in Children With Attention‐Deficit/Hyperactivity Disorder (2007)

The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release and immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder. Patients 6- to 12-years-old with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were randomized to receive multilayer-release methylphenidate (qd) or immediate-release methylphenidate (bid) at equivalent doses, with a 14-day washout between treatments. Plasma samples were collected predosing and 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours postdose. Pharmacokinetic analysis was conducted on 14 patients (1 female, 13 male; mean age: 9.6 +/- 2.5 years [range, 6-12]). The mean dose of methylphenidate received by these patients in both phases of the study was 38.6 mg/d (range, 20-80 mg/d). The relative AUC(0-t) and C(max 0-4) ratios for multilayer-release compared with immediate-release methylphenidate were 100.8% and 78.8%, respectively. Multilayer-release methylphenidate produces a biphasic concentration-time profile, with a rapid initial increase in plasma concentration that is maintained throughout the school day.
Altered target site specificity variants of the I-PpoI His-Cys box homing endonuclease (2007)

We used a yeast one-hybrid assay to isolate and characterize variants of the eukaryotic homing endonuclease I-PpoI that were able to bind a mutant, cleavage-resistant I-PpoI target or 'homing' site DNA in vivo. Native I-PpoI recognizes and cleaves a semi-palindromic 15-bp target site with high specificity in vivo and in vitro. This target site is present in the 28S or equivalent large subunit rDNA genes of all eukaryotes. I-PpoI variants able to bind mutant target site DNA had from 1 to 8 amino acid substitutions in the DNA-protein interface. Biochemical characterization of these proteins revealed a wide range of site-binding affinities and site discrimination. One-third of variants were able to cleave target site DNA, but there was no systematic relationship between site-binding affinity and site cleavage. Computational modeling of several variants provided mechanistic insight into how amino acid substitutions that contact, or are adjacent to, specific target site DNA base pairs determine I-PpoI site-binding affinity and site discrimination, and may affect cleavage efficiency.