gebhart/patrepeval huggingface dataset:
Noninvasive photoacoustic imaging of the developing vasculature during early tumor growth (2008)

In this study, we monitor the progress of vasculature in early tumor growth using photoacoustic imaging over a 20 day period after subcutaneous inoculation of breast cancer tumor cells in a mouse. With 532 nm laser pulses employed as an irradiation source, the photoacoustic images were obtained through the photoacoustic signals received by a hydrophone in orthogonal mode. The morphological characteristics of vasculature in tumor region are clearly resolved in the photoacoustic images, and the change in structure as well as the increase in density can be identified. Moreover, the average photoacoustic signal strength of vasculature in tumor region, which is highly correlated with the total hemoglobin concentration of blood, is enhanced during early tumor growth. These results indicate the feasibility of detecting early stage tumor and monitoring the progress of anti-angiogenic therapy by photoacoustic imaging.
Suppression of Rat Thromboxane Synthase Gene Transcription by Peroxisome Proliferator-activated Receptor γ in Macrophages via an Interaction with NRF2 (2000)

We have studied the transcription regulation of the rat thromboxane synthase (TXS) gene by peroxisome proliferator-activated receptor gamma (PPARgamma) in macrophages. The transcription activity of a cloned 5'-flanking region (1.6 kilobases) of the rat TXS gene (5'FL-TXS) was examined by luciferase reporter gene assay. TXS mRNA expression and the transcription activity of 5'FL-TXS were inhibited by PPARgamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)), and the thiazolidinedione troglitazone (TRO) in a dose-dependent manner. Overexpression of PPARgamma also significantly suppressed transcription, and further addition of PGJ(2) or TRO augmented the suppression. Deletion analysis showed that the element responsible for the PPARgamma effect is located in a region containing the nuclear factor E2 (NF-E2)/AP-1 site (-98/-88), which was indicated to be the major promoter of the TXS gene. By electrophoretic mobility shift assay using the NF-E2/AP-1 site and nuclear extracts from macrophages, we observed a specific protein-DNA complex formation, which was inhibited by a specific antibody against the transcription factor NRF2 (NF-E2-related factor 2). Moreover, the complex was decreased with PGJ(2), TRO, or in vitro translated PPARgamma. The transcription suppression by PPARgamma was confirmed using this truncated NRF2-binding element (-98/-88) by the reporter gene assay. Finally, a direct interaction between PPARgamma and NRF2 was confirmed by glutathione S-transferase pull-down assay. In conclusion, the NRF2-binding site (-98/-88) is the major promoter of 5'FL-TXS which can be suppressed by activated PPARgamma via a protein-protein interaction with NRF2 in macrophages.
An Efficient and General Synthesis of Primary Amines by Ruthenium‐Catalyzed Amination of Secondary Alcohols with Ammonia (2010)

Atom efficiency and selectivity are the key features of the first homogeneously catalyzed amination of secondary alcohols with ammonia to give the corresponding primary amines (see scheme). This novel amination method relies on the commercially available catalyst [Ru3(CO)12]/cataCXium PCy and does not require any additional source of hydrogen.
Preclinical evaluation and phase I clinical trial of a 99mTc-labeled synthetic polymer used in blood pool imaging. (1998)

Synthetic methoxypoly(ethylene glycol)-grafted polymers can have long circulation times in humans. Pharmaceuticals based on such polymers are expected to have clinical applications in cardiovascular imaging, gastrointestinal bleeding studies, and capillary leak imaging.
An Abbreviated Protocol for In Vitro Generation of Functional Human Embryonic Stem Cell-Derived Beta-Like Cells (2016)

The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems. The activation of FGF and Retinoic Acid along with the inhibition of BMP, SHH and TGF-beta led to the generation of 75% NKX6.1+/NGN3+ Endocrine Progenitors. The inhibition of Notch and tyrosine kinase receptor AXL, and the treatment with Exendin-4 and T3 in the final stage resulted in 35% mono-hormonal insulin positive cells, 1% insulin and glucagon positive cells and 30% insulin and NKX6.1 co-expressing cells. Functionally, ES-DBCs were responsive to high glucose in static incubation and perifusion studies, and could secrete insulin in response to successive glucose stimulations. Mitochondrial metabolic flux analyses using Seahorse demonstrated that the ES-DBCs could efficiently metabolize glucose and generate intracellular signals to trigger insulin secretion. In conclusion, targeting selected signaling pathways for 25-30 days was sufficient to generate ES-DBCs in vitro. The ability of ES-DBCs to secrete insulin in response to glucose renders them a promising model for the in vitro screening of drugs, small molecules or genes that may have potential to influence beta-cell function.
Progressive supranuclear palsy (2008)

In the article, “Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy,” Dr. Borroni and her coauthors ( Neurology ®2008;71:1796–1803) looked at specific medical tests that could help physicians accurately diagnose this illness. Progressive supranuclear palsy (PSP) is rare and has similarities to several other progressive neurologic disorders. Because of this, they looked at the results of these tests not only in people with PSP, but also in those who had the “similar” illnesses. In addition, the authors compared the results of the tests to test results of people who did not have progressive neurologic disease.

Dr. Borroni and coauthors carefully studied the tests results for 166 people. All had undergone a detailed history, physical examination, and neurologic examination. All were monitored for more than 2 years. The reason for this long period of monitoring is that the illnesses, especially when they begin, can look like something else. As the illness progresses and other symptoms develop, the diagnosis becomes more clear. By following this group for more than 2 years, Dr. Borroni minimized any errors in diagnosis.

Of the 166 people, 21 were diagnosed with PSP. One hundred twenty-five people had progressive neurologic conditions such as Parkinson disease and Alzheimer disease. There were also a few other illnesses. Twenty-seven patients acted as the “controls.” They were “normal.” This last group needs more explaining. The “controls” were a group of people who had an MRI and lumbar puncture for other reasons. For instance, they may have had a headache, and in the process of evaluating the headache, these tests were needed. Although not entirely “normal,” as this group had experienced a neurologic symptom (for example, headache), they did not have a progressive neurologic illness.

A subset of patients had a specialized MRI of the brain and brainstem. Dr. Borroni …
Isolation of novel cell-penetrating peptides from a random peptide library using in vitro virus and their modifications (2009)

A number of cell-penetrating peptides (CPPs) have been reported, but their transduction efficiencies are too low to be used as intracellular carriers for therapeutic purposes. We conducted a comprehensive search to find novel CPPs using an in vitro virus (IVV) library, which presented random peptides consisting of 15 amino acids (diversity of the library was >10(12)). We found 9 kinds of novel CPPs with an intracellular translocation efficiency higher than that of the TAT peptide (YGRKKKRRQRRR). Interestingly, one of the novel CPPs, No. 14 (KLWMRWYSPTTRRYG), showed a dramatic improvement in translocation activity relative to the TAT peptide in CHO cells (>10-fold efficiency in 50 microM). As the intracellular translocation efficiency of No. 14 was increased by substitution Arg for Lys1 (14-1), we carried out alanine scanning on the basis of 14-1 to determine important amino acids for the intracellular translocation. The Ala substitution analysis showed that both Arg and Trp residues were important for the cell-penetrating activity and that their contribution was in the order Trp3<Arg12<Arg1<Arg5, Arg13<Trp6. Moreover, it was possible to substitute two Trp with other bulky amino acids such as Ile or Tyr. In this study, we showed that novel CPPs could be acquired by screening random peptides and modifying some amino acids could increase their cell-penetrating activity.
In Vivo Antitumor Activity of Sindbis Viral Vectors (2002)

Sindbis viral vectors efficiently targeted tumors in vivo, were apparently delivered through the circulation, and were more effective in the presence of NK cells.
Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA Leu(UUR) gene (1994)

We have recently reported an A to G transition at nucleotide position 3243 in the mitochondrial DNA (mtDNA) tRNA(Leu(UUR)) gene in a large family with non-insulin-dependent diabetes mellitus (NIDDM). Characteristic was its maternal transmission and an associated sensorineural hearing loss. In a screening of a Dutch and French NIDDM population for the presence of the tRNA(Leu(UUR)) mutation we identified two new pedigrees in which NIDDM is present in combination with deafness. The mode of inheritance agrees with a maternal one. This result shows that patients with a phenotype of NIDDM and deafness can be identified within groups of NIDDM patients based on the tRNA(Leu(UUR)) mutation. The same mutation has also been linked to the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). How the same mutation can give rise to different clinical phenotypes is not clear. We obtained the complete mtDNA sequence from our initial pedigree and identified a number of additional mutations that could confer the phenotype of the tRNA(Leu(UUR)) mutation to diabetes. We examined the presence of these additional, potentially pathogenic mutations in the mtDNA from the two new pedigrees and from a previously described British pedigree. The absence of these mutations in all three pedigrees shows that the tRNA(Leu(UUR)) mutation alone associates with the phenotype of NIDDM and deafness. We conclude that maternally inherited diabetes and deafness is a distinct subtype of diabetes that is associated with a single mitochondrial tRNA(Leu(UUR)) mutation. We propose the abbreviation MIDD for this particular subtype.
Synthetic inhibitors of tissue kallikrein: effects in vivo in a model of allergic inflammation. (1994)

We have recently developed synthetic low molecular weight inhibitors of both tissue and plasma kallikreins. Several of these were evaluated in vivo in the ovalbumin-sensitised guinea pig for their ability to prevent the bronchoconstriction elicited by antigen challenge. The selective tissue kallikrein inhibitor CH-694 (but not the selective plasma kallikrein inhibitor CH-684) caused highly significant falls in airways resistance when it was administered at 10 mg/kg intraperitoneally 15 min before and 90 min after challenge. There was also a highly significant fall in the tissue kallikrein activity measured in broncho-alveolar lavage fluid. Inhibitors of tissue kallikrein may prove effective in the treatment of allergic inflammation in man.
Neurotransmission of Cognition, Part 2: Selective NRIs Are Smart Drugs: Exploiting Regionally Selective Actionson Both Dopamine and Norepinephrineto Enhance Cognition (2003)

Selective norepinephrine reuptake inhibitors such as atomoxetine increase both dopamine and norepinephrine in frontal cortex and may thereby enhance cognitive functioning in attention-deficit/hyperactivity disorder.
Platelet glycoprotein IIb/IIIa complex in cultured cells. Localization in focal adhesion sites in spreading HEL cells (1988)

A panel of mouse monoclonal antibodies (MoAbs) was raised that react with platelet glycoproteins (GP) IIb or IIIa. On immunofluorescence, the MoAbs reacted with 30% to 40% of the human erythroleukemia (HEL) cells. When the HEL cells were induced to spread on fibronectin in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA), the MoAbs reacted with the focal adhesion sites. Only some of the GPIIIa MoAbs reacted with cells other than platelets, megakaryocytes, or HEL cells, and these showed focal adhesion sites in cultured human endothelial cells, fibroblasts, and epithelial cells from normal kidney tubules. They did not react, however, with transformed fibroblasts, fibrosarcoma cells, cultured cells from hypernephromas, or cultured human amnion epithelial cells. The results suggest that the platelet-type GPIIb/IIIa complex is only expressed in cells showing an ability to define megakaryoblastic differentiation. Localization of the GPIIb/IIIa complex at the induced focal adhesion sites in HEL cells and localization of the GPIIIa-like molecules in other cells suggest their direct role in the adhesion process and in the actomyocin organization of adherent cells.
<title>Novel neural network model combining radial basis function, competitive Hebbian learning rule, and fuzzy simplified adaptive resonance theory</title> (1997)

In the first part of this paper a new on-line fully self- organizing artificial neural network model (FSONN), pursuing dynamic generation and removal of neurons and synaptic links, is proposed. The model combines properties of the self- organizing map (SOM), fuzzy c-means (FCM), growing neural gas (GNG) and fuzzy simplified adaptive resonance theory (Fuzzy SART) algorithms. In the second part of the paper experimental results are provided and discussed. Our conclusion is that the proposed connectionist model features several interesting properties, such as the following: (1) the system requires no a priori knowledge of the dimension, size and/or adjacency structure of the network; (2) with respect to other connectionist models found in the literature, the system can be employed successfully in: (a) a vector quantization; (b) density function estimation; and (c) structure detection in input data to be mapped topologically correctly onto an output lattice pursuing dimensionality reduction; and (3) the system is computationally efficient, its processing time increasing linearly with the number of neurons and synaptic links.
AfterStep 1.3.1 (1998)

Mr. Aznar tells us all about the developers' plans for a friendly window manager called AfterStep
Surface plasmon coupling effect in an InGaN∕GaN single-quantum-well light-emitting diode (2007)

The authors demonstrate the coupling effects between the quantum well (QW) and surface plasmon (SP) generated nearby on the p-type side in an InGaN∕GaN single-QW light-emitting diode (LED). The QW-SP coupling leads to the enhancement of the electroluminescence (EL) intensity in the LED sample designed for QW-SP coupling and reduced SP energy leakage, when compared to a LED sample of weak QW-SP coupling or significant SP energy loss. In the LED samples of significant QW-SP coupling, the blueshifts of the photoluminescence and EL emission spectra are observed, indicating one of the important features of such a coupling process. The device performance can be improved by using the n-type side for SP generation such that the device resistance can be reduced and the QW-SP coupling effect can be enhanced (by further decreasing the distance between the QW and metal) because of the higher carrier concentration in the n-type layer.
Intrathecal Chemokine Synthesis in Mild Cognitive Impairment and Alzheimer Disease (2006)

The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-gamma-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.
β-VLDL Hypercholesterolemia Relative to LDL Hypercholesterolemia Is Associated With Higher Levels of Oxidized Lipoproteins and a More Rapid Progression of Coronary Atherosclerosis in Rabbits (1997)

The accumulation of the oxidized apolipoprotein, apoB-100, containing lipoproteins in the arterial wall and the progression of coronary atherosclerotic lesions in rabbits with beta-VLDL and LDL hypercholesterolemia was compared. In New Zealand White (NZW) rabbits on a 0.125% cholesterol diet, LDL cholesterol levels increased from 14 +/- 1 mg/dL (mean +/- SEM; n = 9) to 170 +/- 34 mg/dL (n = 10, P = .0002). On 0.5% cholesterol, LDL cholesterol levels were similar, but beta-VLDL cholesterol levels increased from 60 +/- 4 mg/dL (n = 10) to 550 +/- 75 mg/dL (n = 8; P < .0001). In Watanabe heritable hyperlipidemic (WHHL) rabbits, LDL cholesterol levels were 2.3-fold higher (n = 13; P < .0001) than in NZW rabbits on 0.5% cholesterol, whereas their beta-VLDL cholesterol levels were 3.7-fold lower (P < .0001), resulting in similar total cholesterol levels. At 2 months, mean intimal areas of lesions in the coronary arteries of NZW rabbits on 0.125% cholesterol were 0.13 +/- 0.045 mm2 (n = 4; mean +/- SEM) and were 5.8-fold, (n = 4; P = .016) and 2.0-fold (n = 6; P = NS versus 0.125% cholesterol and P = .014 versus 0.5% cholesterol) higher in NZW rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. At 5 months, mean intimal areas were 0.47 +/- 0.088 mm2 (n = 6) in NZW rabbits on 0.125% cholesterol and were 4.5-fold (n = 4; P = .0001) and 2.0-fold (n = 7; P = .012 and P = .0019) higher in rabbits on 0.5% cholesterol and in WHHL rabbits, respectively. Levels of oxidized apoB-100 containing lipoproteins (both beta-VLDL and LDL) in the lesions correlated with mean intimal area (r = .88; n = 31; P < .0001) of those lesions and with the plasma levels of total beta-VLDL/LDL (r = .72; P < .0001). Levels of oxidized apoB-100 containing lipoproteins in the arterial wall correlate with progression of hypercholesterolemia-induced coronary atherosclerotic lesions. Plasma levels of beta-VLDL relative to similar increases in LDL result in a more pronounced accumulation of oxidized apoB-100 containing lipoproteins in the arterial wall and in the plasma and a more rapid progression of coronary atherosclerosis.
Cutting Edge: Ectopic Expression of the Chemokine TCA4/SLC Is Sufficient to Trigger Lymphoid Neogenesis (2000)

To test whether accumulation of naive lymphocytes is sufficient to trigger lymphoid development, we generated mice with islet expression of the chemokine TCA4/SLC. This chemokine is specific for naive lymphocytes and mature dendritic cells (DC) which express the CCR7 receptor. Islets initially developed accumulations of T cells with DC, with scattered B cells at the perimeter. These infiltrates consolidated into organized lymphoid tissue, with high endothelial venules and stromal reticulum. Infiltrate lymphocytes showed a naive CD44low CD25- CD69- phenotype, though half were CD62L negative. When backcrossed to RAG-1 knockout, DC were not recruited. Interestingly, islet lymphoid tissue developed in backcrosses to Ikaros knockout mice despite the absence of normal peripheral nodes. Our results indicate that TCA4/SLC can induce the development and organization of lymphoid tissue through diffential recruitment of T and B lymphocytes and secondary effects on stromal cell development.
Protein-coated and polysaccharide-coated liposomes as drug carriers. (1986)

Saccharides on the surface of cell membranes play an important role in cell-cell recognition, which is the most important process utilizable for targeting of drugs encapsulated in an artificial cell, liposome. To design a targetable drug carrier, hence, employing synthesized or natural glycolipids as the recognition site of the liposomal drug carrier is certainly one of useful approach. On the other hand, coating the outermost surface of liposomes with polysaccharide derivatives is also another way for liposomes to be utilized as a targetable drug carrier. In this review, from such a viewpoint, the importance and usefulness of saccharide moiety on the surface of liposomes will be discussed in conjunction with the targeting of drugs.
Melatonin and Comorbidities in Children with Autism Spectrum Disorder (2018)

Abstract Purpose of Review Melatonin is used to treat sleep difficulties associated with autism spectrum disorder (ASD). There are growing evidence that melatonin could have an effect on other symptoms than sleep, such as anxiety, depression, pain, and gastrointestinal dysfunctions. Interestingly, these symptoms frequently are found as comorbid conditions in individuals with ASD. We aimed to highlight the potential effect of melatonin on these symptoms. Recent Findings Animal and human studies show that melatonin reduces anxiety. Regarding the effect of melatonin on pain, animal studies are promising, but results remain heterogeneous in humans. Both animal and human studies have found that melatonin can have a positive effect on gastrointestinal dysfunction. Summary Melatonin has the potential to act on a wide variety of symptoms associated with ASD. However, other than sleep difficulties, no studies exist on melatonin as a treatment for ASD comorbid conditions. Such investigations should be on the research agenda because melatonin could improve a multitude of ASD comorbidities and, consequently, improve well-being.
Enhanced Immunogenicity of CD4+T-Cell Responses and Protective Efficacy of a DNA-Modified Vaccinia Virus Ankara Prime-Boost Vaccination Regimen for Murine Tuberculosis (2001)

DNA vaccines whose DNA encodes a variety of antigens from Mycobacterium tuberculosis have been evaluated for immunogenicity and protective efficacy. CD8(+) T-cell responses and protection achieved in other infectious disease models have been optimized by using a DNA immunization to prime the immune system and a recombinant virus encoding the same antigen(s) to boost the response. A DNA vaccine (D) and recombinant modified vaccinia virus Ankara (M) in which the DNA encodes early secreted antigenic target 6 and mycobacterial protein tuberculosis 63 synthesized, and each was found to generate specific gamma interferon (IFN-gamma)-secreting CD4(+) T cells. Enhanced CD4(+) IFN-gamma T-cell responses were produced by both D-M and M-D immunization regimens. Significantly higher levels of IFN-gamma were seen with a D-D-D-M immunization regimen. The most immunogenic regimens were assessed in a challenge study and found to produce protection equivalent to that produced by Mycobacterium bovis BCG. Thus, heterologous prime-boost regimens boost CD4(+) as well as CD8(+) T-cell responses, and the use of heterologous constructs encoding the same antigen(s) may improve the immunogenicity and protective efficacy of DNA vaccines against tuberculosis and other diseases.
A framework for accurate, efficient private record linkage (2012)

to the ones I love iii ACKNOWLEDGEMENTS A great number of people have been instrumental to the completion of this work, and I’d like to thank a few of them now.
Sex and race in bladder cancer: What we have learned and future directions (2008)

After controlling for prognostic variables, women and African Americans present with more advanced bladder cancer and have worse cancer‐specific survival than other patient populations. Clinicians must focus on social factors influencing this disparity and on increasing public awareness and education to help standardize the diagnosis and management of bladder cancer for all patients.