gebhart/patrepeval huggingface dataset:
Semiautomatic segmentation of liver metastases on volumetric CT images (2015)

Preliminary results have shown that volumes of liver metastases on contrast-enhanced CT images can be accurately estimated by a semiautomatic segmentation method.
Mannose 6-phosphate reduces haze following excimer laser photorefractive keratectomy (1995)

We assessed the effects of mannose 6-phosphate (M6P) on corneal wound healing following PRK in rabbits. Eight New Zealand white rabbits underwent identical excimer laser ablations and were treated with either M6P or a control drop for 4 weeks. Using objective measurements, there was a statistically significant reduction in haze at 4 weeks (p &lt; 0.05) in the M6P treated eyes. Histophathologically, the treated eyes had less subepithelial collagen and a normal lamellar architecture. We conclude that M6P is able to modulate corneal wound healing following PRK and reduce haze.
pGATA: a positive selection vector based on the toxicity of the transcription factor GATA-1 to bacteria. (1996)

The transcription factor GATA-1 is a zinc finger DNA-binding protein essential for the development of red blood cells. When we expressed different regions of the zinc finger domain in bacteria using an isopropyl-beta-D-thiogalactoside (IPTG) inducible system, growth of bacteria harboring the active DNA-binding domain of GATA-1 was rapidly inhibited upon IPTG induction. The growth inhibition pattern suggested it may be occurring at the level of the initiation of replication, and GATA-1 was found to bind to three of the four DNA A protein-binding sites in the origin of replication. This toxicity was used to develop a positive selection vector system in which cloned DNA fragments interfered with the production of the GATA-1 DNA-binding domain. Thus, vector molecules containing the insert of interest are selected for when bacteria are grown in the presence of IPTG. With this system, the vector does not need to be dephosphorylated, purified or completely digested with a restriction enzyme for the efficient cloning of DNA fragments even when the vector-to-insert DNA molar ratio in ligation reactions is 10 to 1. Moreover, no special strain of Escherichia coli is required, and the selection might also be applicable to other species of bacteria if the toxicity of GATA-1 relates to inhibition of the DNA A protein.
Autologous mesenchymal stem cell transplantation in stroke patients (2005)

Mesenchymal stem cell (MSC) transplantation improves recovery from ischemic stroke in animals. We examined the feasibility, efficacy, and safety of cell therapy using culture-expanded autologous MSCs in patients with ischemic stroke. We prospectively and randomly allocated 30 patients with cerebral infarcts within the middle cerebral arterial territory and with severe neurological deficits into one of two treatment groups: the MSC group (n = 5) received intravenous infusion of 1 x 10(8) autologous MSCs, whereas the control group (n = 25) did not receive MSCs. Changes in neurological deficits and improvements in function were compared between the groups for 1 year after symptom onset. Neuroimaging was performed serially in five patients from each group. Outcomes improved in MSC-treated patients compared with the control patients: the Barthel index (p = 0.011, 0.017, and 0.115 at 3, 6, and 12 months, respectively) and modified Rankin score (p = 0.076, 0.171, and 0.286 at 3, 6, and 12 months, respectively) of the MSC group improved consistently during the follow-up period. Serial evaluations showed no adverse cell-related, serological, or imaging-defined effects. In patients with severe cerebral infarcts, the intravenous infusion of autologous MSCs appears to be a feasible and safe therapy that may improve functional recovery.
Conformation Determines the Seeding Potencies of Native and Recombinant Tau Aggregates (2014)

Intracellular Tau inclusions are a pathological hallmark of several neurodegenerative diseases, collectively known as the tauopathies. They include Alzheimer disease, tangle-only dementia, Pick disease, argyrophilic grain disease, chronic traumatic encephalopathy, progressive supranuclear palsy, and corticobasal degeneration. Tau pathology appears to spread through intercellular propagation, requiring the formation of assembled "prion-like" species. Several cell and animal models have been described that recapitulate aspects of this phenomenon. However, the molecular characteristics of seed-competent Tau remain unclear. Here, we have used a cell model to understand the relationships between Tau structure/phosphorylation and seeding by aggregated Tau species from the brains of mice transgenic for human mutant P301S Tau and full-length aggregated recombinant P301S Tau. Deletion of motifs (275)VQIINK(280) and (306)VQIVYK(311) abolished the seeding activity of recombinant full-length Tau, suggesting that its aggregation was necessary for seeding. We describe conformational differences between native and synthetic Tau aggregates that may account for the higher seeding activity of native assembled Tau. When added to aggregated Tau seeds from the brains of mice transgenic for P301S Tau, soluble recombinant Tau aggregated and acquired the molecular properties of aggregated Tau from transgenic mouse brain. We show that seeding is conferred by aggregated Tau that enters cells through macropinocytosis and seeds the assembly of endogenous Tau into filaments.
Refined transactional lock elision (2016)

Transactional lock elision (TLE) is a well-known technique that exploits hardware transactional memory (HTM) to introduce concurrency into lock-based software. It achieves that by attempting to execute a critical section protected by a lock in an atomic hardware transaction, reverting to the lock if these attempts fail. One significant drawback of TLE is that it disables hardware speculation once there is a thread running under lock. In this paper we present two algorithms that rely on existing compiler support for transactional programs and allow threads to speculate concurrently on HTM along with a thread holding the lock. We demonstrate the benefit of our algorithms over TLE and other related approaches with an in-depth analysis of a number of benchmarks and a wide range of workloads, including an AVL tree-based micro-benchmark and ccTSA, a real sequence assembler application.
Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea* (2008)

In patients with T2DM inadequately controlled with prior SU monotherapy, addition of vildagliptin (50 or 100 mg daily) to glimepiride (4 mg once daily) improves glycaemic control and is well tolerated. Addition of vildagliptin 50 mg daily to SU monotherapy may be a particularly attractive therapy in elderly patients.
Chemical synthesis of a biologically active gene for human immune interferon-gamma. Prospect for site-specific mutagenesis and structure-function studies. (1984)

A 453-base pair DNA duplex consisting of a gene coding for human interferon-gamma and initiation and termination signals plus appropriate restriction enzyme sites for plasmid insertion has been totally synthesized. The synthesis involved preparation of 66 oligodeoxynucleotides by a modified, solid phase phosphite procedure and enzymatic ligation of the oligonucleotides. The gene, when inserted into a previously constructed expression vector, was expressed in Escherichia coli, demonstrating functional activity for the synthetic gene. Several strategically located restriction cleavage sites have been introduced into the sequence. This provides a convenient system for site-specific mutagenesis for structure-function studies.
Restoring Facial Shape in Face Lifting: The Role of Skeletal Support in Facial Analysis and Midface Soft-Tissue Repositioning (2006)

Aesthetic analysis in facial rejuvenation has traditionally been subordinate to technical solutions. While concerns regarding correction of facial laxity, a reduction in the depth of the nasolabial fold, and improvement of both the jowl and the jawline are worthy goals in rhytidectomy, the aesthetic concept of restoring facial shape to a more youthful appearance is equally important. Restoring facial shape in face lifting requires an understanding of how the face ages and then the formulation of a treatment plan that is individualized for the patient. Re-establishment of facial contour is significantly influenced by the re-elevation of descended facial fat through superficial musculoaponeurotic system manipulation; it can be approached through a variety of technical solutions. Underlying skeletal support affects not only the appearance of the face in youth but also how the face ages and influences the operative plan in terms of the requirements for fat repositioning. Formulating a treatment plan that is patient specific and based on the artistic goals as influenced by skeletal support is the key element for consistency in restoring facial shape in face lifting.
Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells (2001)

Urea-based beta-amyloid (Abeta) SDS-polyacrylamide gel electrophoresis and immunoblots were used to analyze the generation of Abeta peptides in conditioned medium from primary mouse neurons and a neuroglioma cell line, as well as in human cerebrospinal fluid. A comparable and highly conserved pattern of Abeta peptides, namely, 1-40/42 and carboxyl-terminal-truncated 1-37, 1-38, and 1-39, was found. Besides Abeta1-42, we also observed a consistent elevation of amino-terminal-truncated Abeta2-42 in a detergent-soluble pool in brains of subjects with Alzheimer's disease. Abeta2-42 was also specifically elevated in cerebrospinal fluid samples of Alzheimer's disease patients. To decipher the contribution of potential different gamma-secretases (presenilins (PSs)) in generating the amino-terminal- and carboxyl-terminal-truncated Abeta peptides, we overexpressed beta-amyloid precursor protein (APP)-trafficking mutants in PS1+/+ and PS1-/- neurons. As compared with APP-WT (primary neurons from control or PS1-deficient mice infected with Semliki Forest virus), PS1-/- neurons and PS1+/+ neurons overexpressing APP-Deltact (a slow-internalizing mutant) show a decrease of all secreted Abeta peptide species, as expected, because this mutant is processed mainly by alpha-secretase. This drop is even more pronounced for the APP-KK construct (APP mutant carrying an endoplasmic reticulum retention motif). Surprisingly, Abeta2-42 is significantly less affected in PS1-/- neurons and in neurons transfected with the endocytosis-deficient APP-Deltact construct. Our data confirm that PS1 is closely involved in the production of Abeta1-40/42 and the carboxyl-terminal-truncated Abeta1-37, Abeta1-38, and Abeta1-39, but the amino-terminal-truncated and carboxyl-terminal-elongated Abeta2-42 seems to be less affected by PS1 deficiency. Moreover, our results indicate that the latter Abeta peptide species could be generated by a beta(Asp/Ala)-secretase activity.
Intrastriatal Transforming Growth Factor α Delivery to a Model of Parkinson's Disease Induces Proliferation and Migration of Endogenous Adult Neural Progenitor Cells without Differentiation into Dopaminergic Neurons (2004)

We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor alpha (TGFalpha) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGFalpha infusion induced significant proliferation, hyperplastic nodules, and substantial migratory waves of nestin-positive progenitor cells from the adult subventricular zone (SVZ) of dopamine-denervated rats. Interestingly, SVZ cells in naive rats displayed proliferation but minimal migration in response to the TGFalpha infusion. The cells in the expanded SVZ accumulated cytoplasmic beta-catenin, indicating activation of classical Wnt signaling. However, no evidence of any neuronal differentiation was found of these recruited progenitor cells anywhere examined in the brain. Consequently, no evidence of dopaminergic (DA) neurogenesis was found in the striatum or substantia nigra in any experimental group, and amphetamine-induced behavioral rotations did not improve. In summary, the cells in the TGFalpha-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons.
phoP/phoQ-Deleted Salmonella typhi (Ty800) Is a Safe and Immunogenic Single Dose Typhoid Fever Vaccine in Volunteers (1996)

The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted, and the resultant strain (Ty800) was tested as a live attenuated typhoid fever vaccine in human volunteers. Groups of 2 or 3 subjects received single oral doses of 10(7), 10(8), 10(9), or 10(10) cfu. Two volunteers who received the largest dose had self-limited side effects; no bacteremias were detected. Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood samples. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S. typhi Ty21a. In the most sensitive assays, 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens. Ty800 is safe, and single oral doses are highly immunogenic in humans.
Vapor Detection Performance of Vertically Aligned, Ordered Arrays of Silicon Nanowires with a Porous Electrode (2011)

Vertically aligned, ordered arrays of silicon nanowires capped with a porous top electrode are used to detect gas phase ammonia and nitrogen dioxide in humidified air. The sensors had very fast response times and large signal-to-noise ratios. Calibration curves were created using both an initial slope method and a fixed-time point method. The initial-slope method had a power law dependence that correlates well with concentration, demonstrating a viable alternative for eventual quantitative vapor detection and enabling shorter sampling and regeneration times.
Genotyping single nucleotide polymorphisms directly from genomic DNA by invasive cleavage reaction on microspheres (2003)

Here we report proof-of-principle for a microsphere-based genotyping assay that detects single nucleotide polymorphisms (SNPs) directly from human genomic DNA samples. This assay is based on a structure-specific cleavage reaction that achieves single base discrimination with a 5'-nuclease which recognizes a tripartite substrate formed upon hybridization of target DNA with probe and upstream oligonucleotides. The assay is simple with two easy steps: a cleavage reaction, which generates fluorescent signal on microsphere surfaces, followed by flow cytometry analysis of the microspheres. Genomic DNA samples were genotyped for the SNP in the Apolipoprotein E gene at amino acid position 158. The assay successfully scored wild type, heterozygous and homozygous mutants. To our knowledge, this is the first report of a solid-support assay for detection of SNPs directly from genomic DNA without PCR amplification of the target.
Activating properties of cocaine and cocaethylene in a behavioral preparation of Drosophila melanogaster (1998)

The use of Drosophila as a model to study the behavioral consequences of stimulant drugs was analyzed in an active preparation of decapitated Drosophila. Application of cocaine and cocaethylene to discrete nerve cord cells regulating motor programs of behavior produced striking patterns of behavioral activity in a concentration-related manner. In general, intense circling behavior and significant wing buzzing activity were distinguishable behavioral markers in flies treated with mM concentrations of cocaine or cocaethylene. The significant changes in motor behavior induced by stimulant drugs in decapitated flies were not reproduced by the application of apomorphine, a direct dopamine (DA) agonist, or octopamine, a naturally occurring transmitter in arthropods. Because both cocaine and cocaethylene interfere with DA reuptake in mammals, we characterized the role of DA receptors mediating increased stereotypy and motor behavior in flies. Coadministration of SCH-23390, a specific D1 receptor antagonist, significantly attenuated the behavior-activating properties of cocaine and cocaethylene in this active experimental preparation. Therefore, the receptor protein mediating the behavioral responses to stimulant drugs in Drosophila is pharmacologically similar to the mammalian D1 subtype. In rats, cocaine- and cocaethylene-induced behavioral activity is complex, with increasing evidence that the D1 receptor interacts significantly with N-methyl-D-aspartate (NMDA) receptor pathways to produce an altered behavioral phenotype. To further characterize additional receptor subtypes targeted by the actions of cocaine and cocaethylene, we pretreated flies with MK-801 and dextromethorphan. Both of these drugs are potent, selective noncompetitive NMDA receptor antagonists. Interestingly, MK-801 and dextromethorphan profoundly reduced the behavior-activating properties of cocaine and cocaethylene in Drosophila. Therefore, as in rats, the NMDA (and D1) receptor pathways in this arthropod represent obligatory targets for the behavioral effects of stimulant drugs. Synapse 29:148–161,1998. © 1998 Wiley-Liss, Inc.
Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations (2014)

Hereditary diseases affecting the skeleton are heterogeneous in etiology and severity. Though many of these conditions are individually rare, the total number of people affected is great. These disorders often include dental-oral-craniofacial (DOC) manifestations, but the combination of the rarity and lack of in-depth reporting often limit our understanding and ability to diagnose and treat affected individuals. In this review, we focus on dental, oral, and craniofacial manifestations of rare bone diseases. Discussed are defects in 4 key physiologic processes in bone/tooth formation that serve as models for the understanding of other diseases in the skeleton and DOC complex: progenitor cell differentiation (fibrous dysplasia), extracellular matrix production (osteogenesis imperfecta), mineralization (familial tumoral calcinosis/hyperostosis hyperphosphatemia syndrome, hypophosphatemic rickets, and hypophosphatasia), and bone resorption (Gorham-Stout disease). For each condition, we highlight causative mutations (when known), etiopathology in the skeleton and DOC complex, and treatments. By understanding how these 4 foci are subverted to cause disease, we aim to improve the identification of genetic, molecular, and/or biologic causes, diagnoses, and treatment of these and other rare bone conditions that may share underlying mechanisms of disease.
Hydroxyl Radical Production by Mouse Epidermal Cell Lines in the Presence of Quinone Anti-Cancer Compounds (1999)

The effect of quinone anti-cancer compounds, 3,6-diaziridinyl-2, 5-bis(carboethoxyamino)-1,4-benzoquinone (diaziquone or AZQ) and 3, 6-dihydro-2,5-bis(aziridinyl)-1,4-benzoquinone (DZQ), on the production of hydroxyl radical ((*)OH) in a series of mouse epidermal cell lines was examined using a new, highly sensitive method that employs a fluorescamine-derivatized nitroxide probe. Cell lines that were examined included the mouse epidermal cell line, JB6 clone 41, and JB6 cells transfected with the human Cu-Zn superoxide dismutase (SOD) genes (SOD3 and SOD15) and human catalase (CAT) genes (CAT13 and CAT10). Bioreduction of the nitroxide probe by these cell lines was insignificant at the cell densities employed in these experiments, and thus did not interfere with the (*)OH measurements. In the presence of low concentrations of AZQ or DZQ (20-200 microM), (*)OH production rates were highest in the JB6 cells, intermediate in the SOD-transfected cells, and lowest in the CAT-transfected cells, illustrating that both superoxide and hydrogen peroxide are involved in the production of (*)OH in these systems. Further experiments in which the addition of exogenous SOD and CAT was employed, as well as measurements of probe incorporation into the cells, indicated that this probe can cross cell membranes and detect (*)OH generated intracellularly. In the presence of 100 microM diethylenetriaminepentaacetic acid (DTPA), the rate of (*)OH production in the presence of 100 microM AZQ is approximately 4.7 x 10(4) molecules s(-)(1) cell(-)(1); as much as 45% of this production appears to originate within the cells. This new method should be broadly applicable to the rapid screening of compounds or treatments thought to induce oxidative stress in mammalian cells.
Binding of Canine IgM and IgG to Protein A of Staphylococcus aureus: A Simple Method for the Isolation of Canine Immunoglobulins from Serum and the Lymphocyte Surface (1979)

The binding of normal canine serum IgG and IgM to staphylococcal protein A is described. Virtually all (greater than 99%) of IgG and up to 90% of IgM could be removed from canine serum, utilizing this phenomenon. The nature of the bound material was confirmed by immunodiffusion in agar, radioimmunoassay, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Attempts to elute differentially IgG and IgM from protein A-Sepharose columns, using gradients of pH or the chaotropic agent sodium thiocyanate, were unsuccessful. This phenomenon provides a basis for the isolation of canine IgM from serum. Lymphocyte surface IgM, studied by lactoperoxidase-catalyzed membrane radioiodination and solubilization in nonionic detergent, also showed the property of binding to staphylococcal protein A.
Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform (2014)

Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.