gebhart/patrepeval huggingface dataset:
Challenges in monoclonal antibody-based therapies (2009)

Therapeutic monoclonal antibodies (mAbs) are the fastest growing class of new therapeutic molecules. They hold great promises for the treatment of a variety of diseases, including chronic inflammatory diseases and cancer. However, the current manufacturing and purification processes cause limitations in the production capacity of therapeutic antibodies, leading to an increase in cost. Genetic delivery of therapeutic monoclonal antibodies by in vivo production offers a new potential solution to these problems. Firstly, therapeutic efficacy can be improved by maintaining stable therapeutic, non-toxic levels within the blood circulation over a long period of time. Repeated high-dose bolus injections could be avoided, thereby reducing the possibility of side-effects. Secondly, the high cost of manufacturing and purification of the therapeutic antibodies could be reduced, making an in vivo/ex vivo mAb gene transfer an economically viable and attractive option. In general, three approaches can be used for the stable long-term expression and secretion of therapeutic antibodies in vivo: 1) direct in vivo administration of integrating vectors carrying a mAb gene, 2) grafting of ex vivo genetically modified autologous cells, and 3) implantation of an encapsulated antibody producing heterologous or autologous cells. This paper describes the key factors and problems associated with the current antibody-based immunotherapies and reviews prospects for genetic in vivo delivery of therapeutic antibodies.
Phase II Trial of Mirtazapine for Cancer-Related Cachexia and Anorexia (2009)

We performed an open-label single-institution phase II trial of mirtazapine (15-30 mg by mouth [po] every day [qd]), a tetracyclic antidepressant that may lead to weight gain, for 8 weeks in nondepressed patients with cancer-related cachexia/anorexia (CRCA). The primary end point was the proportion of patients who gained > or =1 kg at week 4. Secondary end points were quality of life and appetite. From June 2006 to July 2007, 17 of 58 eligible patients were enrolled. On intention-to-treat analysis at week 4, 4 of 17 patients (24%) gained 1 kg or more, 1 patient maintained weight (gain of 400 g) and 2 patients lost weight (800 g and 1.2 kg); 24% and 6% improved appetite and health-related quality of life (HQOL), respectively. Mirtazapine is a promising agent for the treatment of CRCA.
A Sol-Gel-Derived Glass as a Fuel Cell Electrolyte (2000)

A fuel cell electrolyte based on an inorganic glass membrane with a high proton conductivity is described by these authors. The binary glass used (P2O5–SiO2)—prepared by reacting PO(CH3)3 with hydrolyzed Si(OC2H5)4—is demonstrated to not only be useful as a proton conductor in hydrogen fuel cells but also as a hydrogen gas sensor. Because of its good chemical stability and promising performance in H2–O2 fuel cells it is believed that P2O5–SiO2 could replace perfluorinated ionomers as the electrolyte in these cells.
Phosphorylation-Dependent Sumoylation Regulates Estrogen-Related Receptor-α and -γ Transcriptional Activity through a Synergy Control Motif (2007)

Interplay between different posttranslational modifications of transcription factors is an important mechanism to achieve an integrated regulation of gene expression. For the estrogen-related receptors (ERRs) alpha and gamma, regulation by posttranslational modifications is still poorly documented. Here we show that transcriptional repression associated with the ERR amino-terminal domains is mediated through sumoylation at a conserved phospho-sumoyl switch, psiKxEPxSP, that exists within a larger synergy control motif. Arginine substitution of the sumoylatable lysine residue or alanine substitution of a nearby phosphorylatable serine residue (serine 19 in ERRalpha) increased the transcriptional activity of both ERRalpha and -gamma. In addition, phospho-mimetic substitution of the serine residue with aspartate restored the sumoylation and transcriptional repression activity. The increased transcriptional activity of the sumoylation-deficient mutants was more pronounced in the presence of multiple adjacent ERR response elements. We also identified protein inhibitor of activated signal transducer and activator of transcription y as an interacting partner and a small ubiquitin-related modifier E3 ligase for ERRalpha. Importantly, analysis with a phospho-specific antibody revealed that sumoylation of ERRalpha in mouse liver requires phosphorylation of serine 19. Taken together, these results show that the interplay of phosphorylation and sumoylation in the amino-terminal domain provides an additional mechanism to regulate the transcriptional activity of ERRalpha and -gamma.
Evaluation of an In Vitro Assay System for Drug Susceptibility of Field Isolates of Plasmodium Falciparum from Southern Thailand (1988)

An in vitro assay system has been developed to evaluate the susceptibility of field isolates of Plasmodium falciparum to standard and new antimalarials. The assay used drugs which were serially diluted in the field and determined effective drug concentrations by quantitating schizont maturation after a variable incubation period. Based on the ID50 values, a series of isolates from Yala in southern Thailand were shown to be resistant to chloroquine (187 nM) but only moderately resistant to amodiaquine (23.7 nM), a structurally related 4-aminoquinoline. Five aminocarbinols were evaluated. The parasites were resistant to quinine (219 nM), but comparatively much more susceptible to mefloquine (9.04 nM), halofantrine (1.23 nM), and enpiroline (6.23 nM). The isolates were also relatively sensitive to WR 194,965 (9.04 nM). Two dihydrofolate reductase inhibitors (WR 99,210 and pyrimethamine) were tested. The isolates were comparatively sensitive to a dihydrotriazine, WR 99,210 (2.85 nM). The in vitro values for pyrimethamine (1,870 nM) were higher than the values for the other drugs tested, but were less than values from other regions of Thailand. As compared to a survey conducted in this region four years previously, values for chloroquine, pyrimethamine, amodiaquine, and mefloquine have remained relatively unchanged. However, there was a greater than 20-fold rise in the susceptibility values for quinine, suggesting the introduction of quinine-resistant isolates from eastern Thailand into southern Thailand during this period.
Virtual Reality Environments for Rehabilitation of the Upper Limb after Stroke (2006)

We describe an immersive and interactive experimental protocol developed in a virtual reality environment using the CAREN system. The environment allows the user to receive enhanced feedback about the quality and outcome of varied pointing movements made in a virtual elevator. Features of the virtual environment (representation of the user's body movement; collision detection) as well as details about the feedback provided to the user (knowledge of results and knowledge of performance) are outlined. The described training environment will be used in the rehabilitation of the upper limb for patients who have motor disorders due to stroke and other neurological conditions. The advantage of training upper limb pointing movements in this environment is that the task difficulty can be manipulated according to the user's level of motor impairment and the feedback can be manipulated to provide a more motivating and task-relevant training experience
Minimizing distortion for multi-path video streaming over ad hoc networks (2005)

We present a video distortion model analyzing the performance of multi-path routing for low latency video streaming, in congestion-limited ad hoc networks. In such environments, a single node transmitting multimedia data may have an impact on the overall network conditions and may need to limit its rate to achieve the highest sustainable video quality. For this purpose, optimal routing which seeks to minimize congestion and distributes traffic over multiple paths is attractive. To predict the end-to-end rate-distortion tradeoff, we develop a model which captures the impact of quantization and of packet loss on the overall video quality. Network simulations are performed to confirm the validity of the model in different streaming scenarios over different numbers of paths.
New horizons and perspectives in the treatment of osteoarthritis (2008)

Osteoarthritis (OA) is increasingly prevalent worldwide and is associated with a significant economic burden. Despite the increasing number of patients with OA, treatments to manage the condition remain symptomatic, designed to control pain, and improve function and quality of life while limiting adverse events. Both the EULAR (European League Against Rheumatism) and the OARSI (Osteoarthritis Research Society International) issued new guidelines in 2007 and 2008 recommending a combination of nonpharmacological and pharmacological modalities to manage OA effectively. Because of gastrointestinal risks (including ulcer complications) and cardiovascular risks (including hypertension and thrombotic events associated with nonsteroidal anti-inflammatory drugs [NSAIDs]), these guidelines propose acetaminophen as the first choice anti-inflammatory agents. However, NSAIDs are considered to be more effective than acetaminophen for relief of pain. Given the efficacy, safety, and tolerability issues associated with NSAIDs, development of new agents to manage the pain associated with arthritis but without the cardiovascular and gastrointestinal adverse events remains a priority. This review considers current recommendations for the treatment of OA, the most recent evidence on the cardiovascular risks associated with current NSAID treatments, and the potential of newer anti-inflammatory agents with improved benefit-risk profiles.
Connective tissue naevus. (2007)

A case of non hereditary connective tissue naevus without any association with systemic complaints, in a 20-year old male is reported.
Longitudinal Monitoring of Listeria monocytogenes Contamination Patterns in a Farmstead Dairy Processing Facility (2007)

Contamination of dairy products with Listeria monocytogenes is a concern because multiple human listeriosis outbreaks have been linked to contaminated cheese and dairy products. Dairy production on farmstead operations may be a particular concern because L. monocytogenes is also an animal pathogen that can be shed by ruminants with and without clinical symptoms; physical proximity between production animal and dairy processing facilities may thus provide a higher risk for introduction of L. monocytogenes into the dairy production process. To better understand the risks of L. monocytogenes contamination associated with farmstead dairy production, samples from a farmstead dairy processing operation and the milking barn of the directly adjacent dairy sheep operation were tested for L. monocytogenes over a 3-yr period. Prevalence of L. monocytogenes for samples collected on the farm (n = 85) and the dairy production facility (n = 674) was 9.4 and 2.7%, respectively. Molecular subtyping using automated EcoRI ribotyping of L. monocytogenes isolates revealed that distinct subtypes were associated with the dairy production facility and the farm's milking parlor. Although a total of 5 and 4 different ribotypes were identified among isolates obtained from the dairy production facility and the milking parlor, respectively, only 1 ribotype (DUP-1030A) was isolated from both. Different ribotypes were predominant among isolates from the dairy production facility (ribotype DUP-1052A, representing 15 of 18 isolates) and the farm's milking parlor (ribotype DUP-1039A, representing 4 of 8 isolates); each of these ribotypes appeared to persist over time in the respective area. Our data support that i) in farmstead dairy processing facilities, L. monocytogenes present on the farm can largely be prevented from being introduced into the processing facility; and ii) L. monocytogenes can persist on farm and in processing areas, providing a potential high-risk source for contamination. Preventing cross contamination between dairy production and processing facilities and control of persistent L. monocytogenes are thus critical to assuring the microbial safety of farmstead dairy products.
Multi-Well Engineered Heart Tissue for Drug Screening and Predictive Toxicology (2012)

Drug development is time-and cost-intensive and, overall, inefficient. Only one out of an estimated 10.000 new chemical entities (NCEs) finally enters the market. The later the failure occurs, the higher are the costs. It is for this reason that preclinical development aims at identifying the potential for failure as early as possible and with high sensitivity. On the other hand, high sensitivity generally also means low specificity, suggesting that many potentially successful NCEs are currently excluded from further development. Common reasons for exclusion are adverse drug reactions (ADR). Among the various ADRs, cardiac toxicities and arrhythmias play an important role, because they represent about 21% of all ADRs The single most important mechanism in this context is the prolongation of cardiac repolarization bearing a proarrhythmic potential. These interferences can be visualized by standard ECGs as a prolongation of the QT-interval. Such a prolongation is called "long QT-syndrome" (LQT-syndrome) and is associated with Torsade-de-Pointes (TdP) arrhythmias and sudden cardiac death. In the past, several prominent drugs had to be withdrawn from the market due to TdP in humans, e.g. astemizole, terfenadine, cisapride, sparfloxacin, grepafloxacin and recently clobutinol (Silomat). Moreover, numerous drugs are still on the market that are associated with the potential to cause LQT and TdP, including widely prescribed drugs such as the antibiotic erythromycin. Given the fatal consequences of LQT and TdP in healthy patients without any cardiac disposition, the regulatory bodies (FDA, EMEA and others) have decided some years ago to require testing for LQT to be an obligatory part of preclinical development of any NCE. Several tests have been developed and some of them are routinely used. The three major (but by far not exclusive) tests in the field are the HERG test, rabbit Purkinje fibers and telemetry in dogs. These tests have different advantages and disadvantages and are generally employed subsequently. The HERG test can be considered an obligatory test for all NCEs and it is unlikely that any company further develops a compound that showed major inhibitory activity in this test (of a single ion channel activity). However, examples exist of successful drugs on the market that are potent inhibitors of the HERG current without ever giving rise to TdP arrhythmia (e.g. verapamil, azithromycin). Thus, the predictive value of the HERG test is limited. Reasons lie, among others, in its inability to www.intechopen.com Toxicity and Drug Testing 72 give an integrated readout of effects of drugs on the electrophysiology of the intact cardiac myocyte or the intact heart as a multicellular organ consisting of a functional syncytium of cardiac myocytes and all other cardiac cell types that make up normal heart tissue (e.g. fibroblasts, endothelial cells and smooth muscle cells).
Real-time human identification using a pyroelectric infrared detector array and hidden Markov models (2006)

This paper proposes a real-time human identification system using a pyroelectric infrared (PIR) detector array and hidden Markov models (HMMs). A PIR detector array with masked Fresnel lens arrays is used to generate digital sequential data that can represent a human motion feature. HMMs are trained to statistically model the motion features of individuals through an expectation-maximization (EM) learning process. Human subjects are recognized by evaluating a set of new feature data against the trained HMMs using the maximum-likelihood (ML) criterion. We have developed a prototype system to verify the proposed method. Sensor modules with different numbers of detectors and different sampling masks were tested to maximize the identification capability of the sensor system.
Overweight and Obesity in Relation to Perceived Caloric Intake. (2008)

Purpose: According to the 2000 U.S. census, about 9.6 million adults were found to be obese (Body Mass Index (BMI) ≥ 35 kg/m2 but ≤40 kg/m2) and 6 million were found to be morbidly obese (BMI ≥ 40 kg/m2). There is also an increasing incidence of overweight and obese adolescents. Further, a study proved that parents who had a greater knowledge of nutrition had a lower incidence of overweight children. This calls to attention the importance of decreasing and preventing the incidence of obesity and overweight. An integral part of weight loss and prevention of weight gain is caloric intake. The purpose of our study is to evaluate the relationship between estimated caloric intake and obese/overweight individuals. Methodology: In this study, we will examine if there is significant difference in caloric intake estimates between physically active and inactive individuals and between health science and non-health science majors. We will also examine if there is a difference in caloric intake estimates between those who have a normal, overweight, obese, and morbidly obese body mass index. Physically active individuals and the health science majors may be more accurate and aware of their food intake due to their knowledge of a health-conscious or well-balanced diet and their concern for how they treat their bodies as compared to those who are inactive or a non-health science major. To test our hypothesis, students and employees of Seton Hall University were verbally recruited in the cafeteria during lunch hours to fill out a survey. The survey includes questions about age, gender, height, weight, comorbidities, and physical activity level. Participants are also asked to give their best estimation of calories of the displayed items. These items included a bottle of Gatorade, Snapple Ice Tea, Coke, Snicker's bar, bag of Skittles, an apple, a sandwich and a bag of chips (which are all displayed without nutritional labels). Success will ultimately be defined as perceived caloric intake within two standard deviations (95% confidence interval) of the exact amount for each item. This study was approved by the SHU IRB. Results: Surveys are currently still being collected. It is anticipated that physically active individuals and health science majors will be more accurate and precise in the estimation of calories. Conclusions: Results will show the importance of the implementation of nutrition education and the importance of exercise as a vital part of weight loss. It will also indicate the importance and stress of nutritional education among all types of health care professionals, including physician assistants. Future studies may look at the effect of increased and continued nutrition education in school-aged children and adolescents and its relation to weight.
Strapdown Inertial Navigation Technology, Second Edition (2005)

photographing -not to mention walking in the city -plus those of us engaged with defense activities can state it is more convenient to get lost if one knows where this happ ens. Perhaps this is one of the key reasons why methods and technologies for navigation have been an area of continuing efforts and interest. After the introduction of fast moving vehicles, and later when defensive or hostile weapons came into use, it was not sufficient to know where the platform was located but it was really vital to be aware of its momentary alignment, of course , in a three dimensional space. New challenges were put to the shoulders of the navigator. When time, equipment. and location allow, navigation rel ying on external references such as radio beacons on ground or up in the space orbits are often preferred. However, such cooperative systems may not be available, or their performance is inadequat e for the short time constants of platform motion. We are thus forced to use autonomous navigation modes. It is here that inertial navigation systems have.
EFFECT OF PENTOSANASE ON DOUGH AND BREAD PROPERTIES PRODUCED BY DIFFERENT TYPES OF FLOURS (2008)

ABSTRACT The effects of pentosanase at different doses (20, 60 and 100 ppm) on physical dough properties and bread quality were studied using three types of wheat flours. Flour A was a regular bread flour, flour B had a high hardness ratio and protein content, and flour C was prepared from the same blend of flour A but had a high extraction ratio. Regarding farinograph data, water absorption values of the high extraction (86%) flour C and high hardness (65%) blend flour B increased with introduction of pentosanase. Extensibility values of the flours increased moderately with pentosanase addition, while resistance and energy values decreased. The volume of breads made with flours C and B decreased upon addition of pentosanase. But loaf volume of breads prepared with regular bread flour A with 50% hardness and 76% extraction rate increased with high levels of pentosanase addition. In conclusion, flour A as a regular bread flour gave satisfactory results with pentosanase supplementations, whereas the harder‐blend (65%) and higher‐extraction‐rate (85%) flours from the same cultivars did not. PRACTICAL APPLICATIONS Pentosanase addition was more effective on soluble pentosans than on insoluble ones. Because of these effects, it enhanced the bread‐making properties of regular flour more effectively than those of the high‐extraction and harder‐blend flours of the same cultivars.
Mortality and cancer incidence in Swedish battery workers exposed to cadmium and nickel. (1998)

There was an increased overall risk for lung cancer, but no exposure-response relation between cumulative exposure to cadmium or nickel and risk of lung cancer. There was a highly significant increased risk of cancer of the nose and nasal sinuses, which may be caused by exposure to nickel or cadmium or a combination of both exposures.
Mary Mary Quite Contrary How Does Your Biodiverse Garden Grow? An Overview of Intellectual Property Protections for Plants in the United States, Europe, and Japan, 2 J. Marshall Rev. Intell. Prop. L. 307 (2003) (2003)

As we enter further into the boom of the biotechnology era, the role that plants play in our everyday lives continues to grow increasingly more important. This article seeks to provide a general outline of the protections available on a national, as well as, international level for new plant varieties produced through both genetic engineering processes utilized by the biotechnology field, as well as, the "older" methods, such as cross germination, splicing, etc. that are still successfully being utilized by the general scientific community. In the broadest sense this article is designed to help those who are unfamiliar with the protections available for new plant varieties better understand the minimal protections available in those countries that are signatories of the TRIPS-GATT treaty, as well as, the more specific systems of protection that are available in Europe, Japan, and the United States. This article is also designed to emphasize the industrially important role that securing protections for new plant varieties plays in the world of today, as well as, the world of tomorrow, on both a monetary, as well as, humanitarian level. As the advances made in the biotech arena offers new hope in erasing world hunger, sicknesses, such as AIDS, and pollutants resulting from various industrial processes, I can only hope that the world will continue to embrace, as well as, reinforce the plant protections that are currently available.