gebhart/patrepeval huggingface dataset:
A chimeric transactivator allows tetracycline-responsive gene expression in whole plants (1994)

The chimeric transcriptional activator tTA, a fusion between the Tn10 encoded Tet repressor and the activation domain of the Herpes simplex virion protein VP16, was stably expressed in transgenic tobacco plants. It stimulates transcription of the beta-glucuronidase (gus) gene from an artificial promoter consisting of 7 tet operators and a TATA-box. Tetracycline, which interferes with binding of tTA to operator DNA, reduces gus expression over several orders of magnitude. This stringency of regulation suggests that the system can be used to construct transgenic plants encoding a potentially lethal gene product. Furthermore, the specific and fast inactivation of tTA allows study of the stability of RNAs and proteins.
Current and evolving therapies for hepatitis C (1999)

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Therapeutic options for hepatitis C are limited. Standard monotherapy with interferon-alpha leads to a sustained response in only 10-20% of patients. Recent studies have shown improved sustained response rates for the combination of interferon-alpha and ribavirin. Despite these improvements, more effective therapies are needed. A variety of alternative agents are currently being evaluated in clinical trials. Recent advances in the molecular virology of hepatitis C have identified specific antiviral targets such as the viral NS3 serine protease, the RNA helicase, and the RNA-dependent RNA polymerase. In addition, gene therapeutic strategies aimed at inhibiting HCV gene expression and replication as well as immunotherapeutic concepts aimed at enhancing the cellular immune response against HCV are being explored in various experimental systems. These and other novel antiviral strategies may complement the existing therapeutic modalities in the future.
HUMAN POLYOMA VIRUS-ASSOCIATED INTERSTITIAL NEPHRITIS IN THE ALLOGRAFT KIDNEY1 (1999)

Polyoma virus tubulo-interstitial nephritis-associated graft dysfunction usually calls for judicious decrease in immunosuppression and monitoring for acute rejection. Development of methods to serially quantify the viral load in individual patients could potentially improve clinical outcome.
Real-time visual tracking of complex structures (2002)

Presents a framework for three-dimensional model-based tracking. Graphical rendering technology is combined with constrained active contour tracking to create a robust wire-frame tracking system. It operates in real time at video frame rate (25 Hz) on standard hardware. It is based on an internal CAD model of the object to be tracked which is rendered using a binary space partition tree to perform hidden line removal. A Lie group formalism is used to cast the motion computation problem into simple geometric terms so that tracking becomes a simple optimization problem solved by means of iterative reweighted least squares. A visual servoing system constructed using this framework is presented together with results showing the accuracy of the tracker. The paper then describes how this tracking system has been extended to provide a general framework for tracking in complex configurations. The adjoint representation of the group is used to transform measurements into common coordinate frames. The constraints are then imposed by means of Lagrange multipliers. Results from a number of experiments performed using this framework are presented and discussed.
Modulation of human type II secretory phospholipase A2 by sphingomyelin and annexin VI (1997)

Conjectural results have been reported on the capacity of inflammatory secreted phospholipase A2 (sPLA2) to hydrolyse mammalian membrane phospholipids. Development of an assay based on the release of non-esterified fatty acids by the enzyme acting on the organized phospholipid mixture constituting the membrane matrix has led to the identification of two prominent effectors, sphingomyelin (SPH) and annexin. Recombinant human type II sPLA2 hydrolyses red-cell membrane phospholipids with a marked preference for the inner leaflet. This preference is apparently related to the high content of SPH in the outer leaflet, which inhibits sPLA2. This inhibition by SPH is specific for sPLA2. Cholesterol counteracts the inhibition of sPLA2 by SPH, suggesting that the SPH-to-cholesterol ratio accounts in vivo for the variable susceptibility of cell membranes to sPLA2. Different effects were observed of the presence of the non-hydrolysable D-alpha-dipalmitoyl phosphatidylcholine (D-DPPC), which renders the membranes rigid but does not inhibit sPLA2. Annexin VI was shown, along with other annexins, to inhibit sPLA2 activity by sequestering the phospholipid substrate. The present study has provided the first evidence that annexin VI, in concentrations that inhibit hydrolysis of purified phospholipid substrates, stimulated the hydrolysis of membrane phospholipids by sPLA2. The activation requires the presence of membrane proteins. The effect is specific for type II sPLA2 and is not reproducible with type I PLA2. The activation by annexin VI of sPLA2 acting on red cell membranes results in the preferential release of polyunsaturated fatty acids. It suggests that type II sPLA2, in conjunction with annexin VI, might be involved in the final step of endocytosis and/or exocytosis providing the free polyunsaturated fatty acids acting synergistically to cause membrane fusion.
Water Softening Using Polyelectrolyte-Enhanced Ultrafiltration (1995)

Abstract The use of polyelectrolyte-enhanced ultrafiltration (PEUF) for water softening has been studied at several temperatures in the presence and absence of added salt. It is shown that in the absence of added salt. PEUF is highly effective in the rejection of up to 99.7% of hardness ions from an aqueous stream. At a low concentration of added salt. PEUF is effective in the removal of hardness. As salt concentration increases, however, hardness rejection decreases dramatically. The experimental results have been effectively modeled using an ion-binding model based on Oosawa's two-phase approximation theory.
Magnitude of Functional CD8+T-Cell Responses to the Gag Protein of Human Immunodeficiency Virus Type 1 Correlates Inversely with Viral Load in Plasma (2002)

The importance of CD8+ T-cell responses in the control of human immunodeficiency virus type 1 (HIV-1) infection has been demonstrated, yet few studies have been able to correlate these responses with markers of HIV-1 disease progression. This study measured cell-mediated immune responses using peripheral blood mononuclear cells (PBMC) obtained from 27 patients with chronic HIV-1 infection, the majority of whom were off antiretroviral therapy. The ELISPOT assay was used to detect gamma interferon-secreting PBMC after stimulation with overlapping HIV-1 peptides spanning the Gag, Pol, Env, and Nef proteins in addition to the baculovirus-derived p24 and gp160 proteins. All volunteers had responses to at least one HIV-1-specific peptide. All but one of the subjects (96%) responded to the Gag peptide pool, and 86% responded to the Pol and/or Nef peptide pools. The magnitude and the breadth of T-cell responses directed to either the Gag or p24 peptide pools correlated inversely with viral load in plasma (r = -0.60, P < 0.001 and r = -0.52, P < 0.005, respectively) and directly with absolute CD4+ T-cell counts (r = 0.54, P < 0.01 and r = 0.39, P < 0.05, respectively) using the Spearman rank correlation test. Responses to the Pol and integrase peptide pools also correlated with absolute CD4+ T-cell counts (r = 0.45, P < 0.05 and r = 0.49, P < 0.01, respectively). No correlation with markers of disease progression was seen with specific T-cell responses directed toward the Env or Nef peptides. These data serve as strong evidence that major histocompatibility complex class I presentation of Gag peptides is an essential feature for any HIV-1 vaccine designed to elicit optimal CD8+ T-cell responses.
Hippocampal and Entorhinal Cortex High‐Frequency Oscillations (100–500 Hz) in Human Epileptic Brain and in Kainic Acid‐Treated Rats with Chronic Seizures (1999)

The persistence of normal-appearing ripples in epileptic brain support the view that inhibitory processes are preserved. FRs appear to be field potentials reflecting hyper-synchronous bursting of excitatory neurons and provide an opportunity to study the role of this pathophysiologic phenomenon in epilepsy and seizure initiation. Furthermore, if FR activity is unique to brain areas capable of generating spontaneous seizures, its identification could be a powerful functional indicator of the epileptic region in patients evaluated for surgical treatment.
Tissue Engineering and Regenerative Medicine: Concepts for Clinical Application (2004)

Patients suffering from diseased and injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly given the aging population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The stem cell field is also advancing rapidly, opening new options for therapy. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.
Dynamic Imaging of Fibrin Network Formation Correlated with Other Measures of Polymerization. (2007)

Abstract The clotting time or gel point is commonly used in a variety of clinical assays, but little has been known about what it represents structurally because of the limitations of imaging technologies. The necessity of fixation and dehydration for electron microscopy means that only final clot structures, often distorted by preparation artifacts, can be observed, and there are severe limitations of image quality for conventional light microscopy. For similar reasons, we know almost nothing about the branching and lateral aggregation of fibrin that are essential for clot or thrombus stability. Turbidity, light scattering, or clot stiffness are useful to follow the time course of polymerization but reflect only overall clot properties. We visualized in real time fibrin network formation in the hydrated state, using deconvolution microscopy, which allows optical sectioning without the bleaching that accompanies confocal microscopy. Thus, the events during polymerization could be followed quantitatively over long periods of time. Videos will demonstrate the major observations. Individual mobile fibers were observed before the gel point. After gelation, an initial fibrin network, or scaffold, was seen, which evolved over time by addition of new fibers and elongation and branching of others. Furthermore, some fibers in the network moved chaotically for some time. A detailed, quantitative morphological analysis of network formation was carried out by superposition of images from different time points colorized to distinguish changes. We quantified network formation by the number of branch points, and longitudinal and lateral growth of fibers as a function of time. The distributions of fibers that reached a maximum of longitudinal growth and branch point formation both had maxima at the gel point but, surprisingly, some longitudinal growth continued and new branch points appeared after the gel point, requiring modification of existing models of fibrin polymerization. The cumulative percentage of fibers reaching their final length and the number of branch points attained maximum values at the time corresponding to that at which the turbidity reached approximately 60% of its maximum. Lateral growth reached a plateau at the same time as turbidity. Measurements of clot mechanical properties revealed that the clots achieved maximum stiffness and minimum plasticity well after branch point, as well as length changes and lateral growth of fibers, were completed. These results provide new information on the time sequence of events during fibrin network formation, which is important to understand both clotting and thrombosis and to allow modulation of clot properties.
Direct coronary surgery with saphenous vein bypass without either cardiopulmonary bypass or cardiac arrest. (1985)

From October, 1980 to April, 1983, 30 patients underwent direct coronary surgery without either cardiopulmonary bypass or cardiac arrest. Patients were selected according to the site of the lesion or the condition of the vessel, i.e. generally arteries with a good calibre (more than 1.5 mm), without big plaques in the anastomotic area and lesions limited to the left anterior descending, the diagonal or the right coronary arteries, independently from the clinical condition or state of left ventricular function. Eighteen had stable angina, 10 unstable angina, 2 post-myocardial infarction angina, and 4 had a severe concomitant disease. The operations performed were: 17 simple aorto-coronary bypasses, 11 double bypasses and 2 triple bypasses. When it was necessary to revascularize the diagonal or the left anterior descending artery, the operating table was rotated to the right, a gauze pack was applied posteriorly and the arteries were sutured with 6-0 or 7-0 prolene sutures. There were no deaths and no perioperative infarctions. It should be noted that to date this technique could be used only on 7% of our patients, but we consider this percentage could be increased in the future.
Epoxidation Catalysis by a Manganese Corrole and Isolation of an Oxomanganese(V) Corrole (2000)

If porphyrins can do it corroles can do it better! The relatively stable (oxo)manganese(V) corrole 2 can be characterized by spectroscopic methods following its ready formation from [Mn(tpfc)] (1, H3(tpfc)=5,10,15-tris(pentafluorophenyl)corrole). Complex 1 is a mild catalyst for the epoxidation of styrene by iodosylbenzene.
Parallel induction of IgE-mediated Ascaris antigen airway responses and increased carbachol airway reactivity in rhesus monkeys by infection with Ascaris suum. (1985)

In continuation of studies of four rhesus monkeys infected with Ascaris suum (J Lab Clin Med 101:864-872, 1983), we report the duration of IgE-mediated skin reactivity and airway responses to Ascaris antigen from 15 weeks to longer than 2.8 years. A second group of four rhesus monkeys was infected with A. suum ova after determination of the threshold of airway reactivity to carbachol. Evaluation of these animals confirmed the initial results of the first group of animals studied in relation to induction of skin and airway reactivity to Ascaris antigen. In addition, all animals developed increased airway reactivity, demonstrated by increased reactivity to lower concentrations of carbachol. We report this as a demonstration of induced IgE-mediated antigen airway responsiveness accompanied by induction of increased airway reactivity in a primate model. The increased airway reactivity does not appear related to the induction of IgE antibody.
Statistical analysis of drug combinations for synergism (1992)

Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140 USA ∗Correspondence to: R.J. Tallarida, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. (Received 5 August 1991; revised 18 November 1991; accepted 2 December 1991.)
Intracellular localization and epitope mapping of feline herpesvirus type 1 glycoproteins. (1990)

Monoclonal antibodies (MoAbs) were used to characterize feline herpesvirus type 1 (FHV-1) glycoproteins (gp). Intracellular localization and transport of these proteins as revealed by a sequential indirect immunofluorescence assay (IFA) on fixed infected cells showed slight differences between FHV-1 gp143/108 and gp113. Antibodies against gp143/108 first showed membrane fluorescence at 4 hrs post-infection (PI) followed by a pronounced perinuclear and cytoplasmic staining from 8 hrs PI onwards. Those reacting with gp113 showed the same pattern but fluorescence did not appear until 8 hrs PI. In contrast, MoAbs against gp60 first showed para- and perinuclear staining at 12 hrs PI which became intranuclear at 16 hrs PI, followed by intracytoplasmic staining at 20 hrs PI. Sequential IFA of unfixed infected cells revealed that the three glycoproteins were expressed on the cell surface membrane as well. Topographical mapping of the functional epitopes of gp113 by ELISA additivity test indicated the presence of 2 antigenic domains--a neutralizing domain consisting of 3 overlapping epitopes and a non-neutralizing domain. On the other hand, gp143/108 contained only one antigenic site consisting of 5 similar or overlapping epitopes, one of which seemed to be a conserved region recognized by all MoAbs reacting to this protein.
Photosynthetic regeneration of ATP using bacterial chromatophores (1976)

We have demonstrated the use of bacterial chromatophores for the continuous photosynthetic regeneration of ATP from ADP in an ultrafiltration reactor. Biphasic kinetics of the degradation of chromatophore activity are described. Using chromatophores in combination with the enzyme adenylate kinase, we have also demonstrated continuous regeneration of ATP from AMP.
SODA: Generating SQL for Business Users (2012)

The purpose of data warehouses is to enable business analysts to make better decisions. Over the years the technology has matured and data warehouses have become extremely successful. As a consequence, more and more data has been added to the data warehouses and their schemas have become increasingly complex. These systems still work great in order to generate pre-canned reports. However, with their current complexity, they tend to be a poor match for non tech-savvy business analysts who need answers to ad-hoc queries that were not anticipated. This paper describes the design, implementation, and experience of the SODA system (Search over DAta Warehouse). SODA bridges the gap between the business needs of analysts and the technical complexity of current data warehouses. SODA enables a Google-like search experience for data warehouses by taking keyword queries of business users and automatically generating executable SQL. The key idea is to use a graph pattern matching algorithm that uses the metadata model of the data warehouse. Our results with real data from a global player in the financial services industry show that SODA produces queries with high precision and recall, and makes it much easier for business users to interactively explore highly-complex data warehouses.
Emerging antisense oligonucleotide and viral therapies for amyotrophic lateral sclerosis (2018)

Advances in preclinical and clinical studies of ASO and viral directed approaches to neuromuscular disease, particularly ALS, indicate that these approaches have high specificity and are relatively well tolerated.
Phase I open-label, multiple ascending dose trial of MSB0010718C, an anti-PD-L1 monoclonal antibody, in advanced solid malignancies. (2014)

3064 Background: MSB0010718C is a fully human IgG1 monoclonal antibody targeting the coregulatory protein Programmed Death (PD)-Ligand 1 (PD-L1). PD-1/PD-L1 interactions induce T-cell anergy, protecting tumor cells from elimination by the immune system. MSB0010718C is expected to have antitumor activity by restoring immune system activity and through ADCC. Objectives: Assess the safety of MSB0010718C and determine its maximum tolerated dose, and analyze its pharmacokinetic (PK) profile and target receptor occupancy (RO). Methods: Twenty-seven patients (pts) with refractory malignancies have been enrolled and treated to date. Dose escalation (3+3 design) has been performed for 4 dose levels (1, 3, 10, and 20 mg/kg, q2w). After dose-level safety was determined, accrual of additional pts was allowed in order to generate additional safety, PK, and RO data. Results: Four, 11, 6, and 6 pts have been accrued to dose levels 1–4, respectively. Median pt age is 64 years (range 34–77), ECOG 0–1, with a median of 2 prior lines of therapy for metastatic disease (range 0–5). Eleven pts received prior immunotherapy (range 1–2 lines). Twenty-three pts have been followed for at least 4 weeks by Jan 7, 2014. To date, 12 pts (52.2%) have come off study: 9 (39.1%) for progression, 2 (8.7%) for adverse events (AEs), and 1 (4.3%) for death. Grade ≥3 AEs attributable to drug comprised laboratory abnormalities in 3 pts (2 pts with grade 3 AEs; 1 pt with a grade 4 AE). One DLT was observed in 1 pt at dose level 4: an immune-related AE with creatine kinase increase, myositis and myocarditis. Data from 25 pts were evaluable for PK and RO analysis. Median time to maximum concentration for all doses was approximately 1.5 to 2 h after infusion, with a linear PK. Half-life was 63.4, 80.7, 93.9, and 115.1 h for dose levels 1, 2, 3, and 4, respectively, as measured by ELISA. Target RO data were available for 13 pts, as measured by PD-L1 binding on peripheral leukocytes via flow cytometry. Mean RO prior to second infusion was 75.7, 93.8, and 93.2% for dose levels 1, 2, and 3, respectively. Conclusions: MSB0010718C can be safely administered in doses up to 20 mg/kg IV every 2 weeks. Clinical trial information: NCT01772004.
Modified approach to the construction of a blue noise mask (1994)

The blue noise mask (BNM) is a halftone screen that produces unstructured, visually pleasing halftone images. Since it is a point process, halftoning using the BNM can be implemented considerably faster than error diffusion and other algorithms. However, in the construction of the original BNM, a number of constraints were used to limit its characteristics in the spatial and frequency domains. These constraints were not efficient to compute and required adaptability to all gray levels in the construction process. The original BNM also contained some small but unwanted low-frequency components at some gray levels. In this paper, we present a revised approach to the generation of blue noise patterns and the construction of BNMs employing more efficient computations and eliminating more unwanted residual low-frequency components. Psychovisual evaluation shows that dithering with the new BNM gives excellent results and its rating is statistically indistinguishable from that of error diffusion with serpentine raster and perturbed weights.
Quantitative Comparison of Language Deficits Produced by Extraoperative Electrical Stimulation of Broca's, Wernicke's, and Basal Temporal Language Areas (1996)

Subdural electrodes were implanted over the language-dominant left lateral convexity in 45 patients undergoing evaluation for epilepsy surgery. In 29 patients, additional electrodes were placed over the left basal temporal cortex. We identified language areas by using intermittent electrical stimuli applied while patients read aloud. Aphasia was classified as expressive or receptive based on additional testing performed when electrical stimulation elicited reading arrest in the absence of direct excitatory or inhibitory motor effects. Using correlated logistic regression, we noted no statistically significant differences among Broca's, and Wernicke's areas and the basal temporal language area (BTLA) regarding the frequency with which electrical stimulation interfered with language. Speech production deficits, however, occurred significantly more frequently in Broca's than in Wernicke's area (p = 0.012). In contrast, language comprehension deficits occurred with equal frequency when Broca's and Wernicke's areas were stimulated. These results suggest that both Broca's and Wernicke's areas play important roles in language comprehension and that the primarily expressive aphasia of patients with lesions of Broca's area results mainly from the predominant participation of Broca's area in language production.