gebhart/patrepeval huggingface dataset:
Tolerability and Safety of High Daily Doses of Repetitive Transcranial Magnetic Stimulation in Healthy Young Men (2006)

Repetitive transcranial magnetic stimulation (rTMS) is an experimental technology that involves a powerful magnetic pulse applied to the scalp, which is sufficient to cause neuronal depolarization. Transcranial magnetic stimulation has been used in treatment studies for psychiatric disorders, primarily unipolar depression, and as a tool to map brain function. Although thousands of rTMS sessions have been given with few side effects, rTMS can produce serious adverse effects such as an unintended seizure. Safety guidelines for frequency, duration, and intensity of rTMS have aided in the prevention of such adverse side effects. However, the total dose (number of stimuli) able to be delivered safely to human subjects within a day or within a week has not been established. For example, previous rTMS studies as a treatment for depression consisted of delivering 800 to 3,000 magnetic pulses per day, with 8000 to 30,000 magnetic pulses over 2 to 3 weeks. This study examined whether high doses of rTMS within a day or over a week would produce significant side effects. As part of a study to examine rTMS effects in sleep deprivation, we exposed healthy men to 12,960 magnetic pulses a day for up to 3 days in 1 week. This equals 38,880 magnetic pulses over 1 week, which is likely one of the largest exposures of TMS to date. Despite this intense treatment regimen, we failed to produce significant side effects. Doses of up to 12,960 pulses per day appear safe and tolerable in healthy young men.
Topiramate is an insulin-sensitizing compound in vivo with direct effects on adipocytes in female ZDF rats (2004)

We have studied the in vivo and in vitro effects of Topiramate (TPM) in female Zucker diabetic fatty (ZDF) rats. After weight matching, drug treatment had a marked effect to lower fasting glucose levels of relatively normoglycemic animals as well as during an oral glucose tolerance test. The glucose clamp studies revealed a approximately 30% increased glucose disposal, increased hepatic glucose output (HGO) suppression from approximately 30 to 60%, and an increased free fatty acid suppression from 40 to 75%. Therefore, TPM treatment led to enhanced insulin sensitivity at the level of tissue glucose disposal (increased ISGDR), liver (increased inhibition of HGO), and adipose tissue (enhanced suppression of lipolysis). When soleus muscle strips of control or TPM-treated ZDF rats were studied ex vivo, insulin-stimulated glucose transport was not enhanced in the drug-treated animals. In contrast, when isolated adipocytes were studied ex vivo, a marked increase (+55%) in insulin-stimulated glucose transport was observed. In vitro treatment of muscle strips and rat adipocytes showed no effect on glucose transport in muscle with a 40% increase in insulin-stimulated adipocyte glucose transport. In conclusion, 1) TPM treatment leads to a decrease in plasma glucose and increased in vivo insulin sensitivity; 2) insulin sensitization was observed in adipocytes, but not muscle, when tissues were studied ex vivo or in vitro; and 3) TPM directly enhances insulin action in insulin-resistant adipose cells in vitro. Thus the in vivo effects of TPM treatment appear to be exerted through adipose tissue.
Polyfluorophores on a DNA Backbone: Sensors of Small Molecules in the Vapor Phase (2010)

With a response for any occasion: Oligodeoxyfluorosides (ODFs) conjugated to poly(ethylene glycol)–polystyrene beads were used as fluorescent sensors of multiple organic vapors (see picture). The ODFs—DNA-like oligomers in which fluorophores, spacers, and quencher groups replace DNA bases—had sufficient electronic diversity to show a wide range of responses to chemically varied volatile organic compounds. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Simulation on photoacoustic conversion efficiency of optical fiber-based ultrasound generator using different absorbing film materials (2011)

The low energy-conversion efficiency in photoacoustic generation is the most critical hurdle preventing its wide applications. In recent studies, it was found that the selection of the energy-absorbing layer material and design of the acoustic generator structure both determine the photoacoustic conversion efficiency. The selection of the absorbing material is based on its optical, thermal, and mechanical properties. In this research, we calculated and compared the conversion efficiencies of six different absorbing film materials: <i>bulk aluminum, bulk gold, graphite foil, graphite powder-resin mixture, gold nanospheres, and gold nanorods</i>. The calculations were carried out by a finite element modeling (FEM) software, COMSOL Multiphysics. A 2D-axisymmetric model in COMSOL was built up to simulate a 3-layer structure: optical fiber tip, light absorbing film, and surrounding water. Three equations governed the thermo-elastic generation of ultrasonic waves: the heat conduction, thermal expansion and acoustic wave equations. In "thick-film" generation regime, majority of the laser energy is absorbed by the film and converted to high-frequency film vibration, and the vibration excites the ultrasound wave in the adjacent water, while the water would not be heated directly by the laser. From the results of this FEM simulation, the acoustic signal generated by gold nanosphere (or nanorod) film is over two times stronger than that generated by graphite powder-resin film of the same thickness. This simulation provides a strong support to the absorbing material selection for our proposed fiber ultrasound generator.
E‐business model design, classification, and measurements (2001)

Abstract “Business model” is one of the latest buzzwords in the Internet and electronic business world. This article has the ambition to give this term a more rigorous content. The objective is threefold. The first objective is to propose a theoretical e‐business model framework for doing business in the Internet era. The second is to propose a multidimensional classification‐scheme for e‐Business Models, as opposed to the actual tendency in academic literature to use two‐dimensional classifications. The final objective is to define critical success factors, based on a field study in order to find out and compare the performance indicators used by e‐business firms that are competing with similar business models. © 2002 John Wiley &amp; Sons, Inc.
Classification of Unattended and Stolen Objects in Video-Surveillance System (2006)

This paper describes a video surveillance system aimed at the automatic identification of events of interest, especially of abandoned and stolen objects in a guarded indoor environment. In particular the implemented system combines three phases of data processing: object extraction, object recognition and tracking, and decision about actions. Extracted objects are classified as "human" or "non-human" and static or dynamic, an event of interest following from a split between a "human" and a static "non-human" object, finally static "nonhuman" is analyzed to discriminate between abandoned or stolen object.
Broad Coverage Identification of Multiple Proteolytic Cleavage Site Sequences in Complex High Molecular Weight Proteins Using Quantitative Proteomics as a Complement to Edman Sequencing (2010)

Proteolytic processing modifies the pleiotropic functions of many large, complex, and modular proteins and can generate cleavage products with new biological activity. The identification of exact proteolytic cleavage sites in the extracellular matrix laminins, fibronectin, and other extracellular matrix proteins is not only important for understanding protein turnover but is needed for the identification of new bioactive cleavage products. Several such products have recently been recognized that are suggested to play important cellular regulatory roles in processes, including angiogenesis. However, identifying multiple cleavage sites in extracellular matrix proteins and other large proteins is challenging as N-terminal Edman sequencing of multiple and often closely spaced cleavage fragments on SDS-PAGE gels is difficult, thus limiting throughput and coverage. We developed a new liquid chromatography-mass spectrometry approach we call amino-terminal oriented mass spectrometry of substrates (ATOMS) for the N-terminal identification of protein cleavage fragments in solution. ATOMS utilizes efficient and low cost dimethylation isotopic labeling of original N-terminal and proteolytically generated N termini of protein cleavage fragments followed by quantitative tandem mass spectrometry analysis. Being a peptide-centric approach, ATOMS is not dependent on the SDS-PAGE resolution limits for protein fragments of similar mass. We demonstrate that ATOMS reliably identifies multiple proteolytic sites per reaction in complex proteins. Fifty-five neutrophil elastase cleavage sites were identified in laminin-1 and fibronectin-1 with 34 more identified by matrix metalloproteinase cleavage. Hence, our degradomics approach offers a complimentary alternative to Edman sequencing with broad applicability in identifying N termini such as cleavage sites in complex high molecular weight extracellular matrix proteins after in vitro cleavage assays. ATOMS can therefore be useful in identifying new cleavage products of extracellular matrix proteins cleaved by proteases in pathology for bioactivity screening.
Nano/Microscale Motors: Biomedical Opportunities and Challenges (2012)

Artificial nano/microscale machines hold great promise for diverse future biomedical applications. This Perspective summarizes recent advances in microscale motors, as exemplified by Hoyos and Mallouk in this issue of ACS Nano, and highlights the challenges and opportunities in translating this remarkable progress toward practical biomedical applications. Various areas of medicine, including targeted drug delivery, precision nanosurgery, biopsy, cell sorting, or diagnostic assays, would benefit from recent developments of efficient fuel-free and fuel-driven nano/microscale machines. Newly introduced ultrasound-driven propulsion mechanisms greatly enhance the prospects for these biomedical applications. With continuous innovation and attention to key challenges, we expect that man-made nano/microscale motors will have profound impact upon different medical areas.
Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases? (2003)

Low-grade systemic inflammation was present in participants with moderate to severe airflow obstruction and was associated with increased risk of cardiac injury. This may in part explain the high rates of cardiovascular complications in COPD.
DM-20, a proteolipid apoprotein, is an encephalitogen of acute and relapsing autoimmune encephalomyelitis in mice. (1986)

Experimental allergic encephalomyelitis (EAE) was successfully induced in BALB/c mice with DM-20, a protein component of proteolipid apoprotein. DM-20 was separated by ion exchange column chromatography with CM-Trisacryl from proteolipid apoprotein obtained from bovine spinal cords. Its purity was ascertained by SDS-polyacrylamide gel electrophoresis, a dot immunobinding procedure, and amino acid analysis. Nine of 15 animals with a single injection of 100 micrograms of DM-20 and five of seven animals with a booster injection developed hind leg paralysis or axial rotatory movement 16 to 27 days after sensitization (mean 21.3 days). Five of the 14 animals relapsed 2 to 6 wk after the first attack. Histological examination revealed inflammatory lesion, with significant demyelination in the central nervous system. Antibody levels to DM-20 were not related to the clinical signs. Five of 11 BALB/c nude mice reconstituted with T cells developed similar clinical and pathologic signs. This DM-20-induced EAE in mice may provide a valuable model because it is similar to multiple sclerosis and because it can be induced in inbred mice in which immune mechanisms can be easily studied.
Efficacy of Inactivated H5N2 Influenza Vaccines against Lethal A/Chicken/Queretaro/19/95 Infection (1998)

The control and eventual eradication of H5N2 influenza virus from domestic poultry in Mexico is dependent on the use of avian influenza (AI) vaccine strategies. This study was performed to determine the amount of hemagglutinin (HA) antigen required to control the signs of disease from a highly pathogenic H5N2 influenza virus (A/Chicken/ Queretaro/19/95) and the amount of antigen required to prevent shedding of virus from vaccinated birds. Six commercial inactivated water in oil H5N2 vaccines available in Mexico were compared with standardized vaccines to assess their efficacy. The amount of HA required to prevent the signs of disease from A/Chicken/Queretaro/19/95 influenza virus was approximately 0.4 microgram per dose. Each of the six commercially available vaccines prevented disease signs, and half of the vaccines significantly reduced viral shedding from vaccinated birds. There is a need for standardization of AI virus vaccine, and the antigen content should be increased in some of the commercially available AI vaccines in Mexico.
Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. (1994)

Activators of peroxisome proliferator activated receptor (PPAR) regulate fatty acid metabolism and can induce adipocyte differentiation. We show here that the gamma subtype of PPAR is expressed at high levels in adipose tissue in contrast to a variety of other tissues, where little gene expression was noted. In addition, PPAR gamma is present at low levels in 3T3-L1 preadipocytes and is induced dramatically during adipocyte conversion using either normal differentiating conditions (fetal calf serum, dexamethasone, isobutyl-methylxanthine, and insulin) or the PPAR activator, WY-14,643. Thus PPAR gamma may be important for adipose cell development and function.
Computer-assisted total hip arthroplasty: the present and the future (2006)

Computer technologies have revolutionized different aspects of medical practice and recently, computer-assisted orthopedic surgery (CAOS) has opened a new frontier in less invasive and more accurate surgical practice. This enabling technology has the ability to improve the accuracy and reproducibility of surgical techniques, allow new, demanding procedures that could not otherwise be performed, provide objective means with which to measure surgical performance and outcomes and supply powerful training tools. There are different modalities of CAOS, but navigation techniques are by far the most commonly used in clinical settings. Surgeons have used CAOS for total hip arthroplasty (THA) to plan precisely the alignment of the implants and provide exact real-time measurement during surgery. The capabilities of CAOS have also been coupled with the benefits of minimally invasive techniques in THA and resurfacing arthroplasty. Currently, the application of CAOS in THA is still in its infancy. However, future appl...
HuSiDa--the human siRNA database: an open-access database for published functional siRNA sequences and technical details of efficient transfer into recipient cells (2004)

Small interfering RNAs (siRNAs) have become a standard tool in functional genomics. Once incorporated into the RNA-induced silencing complex (RISC), siRNAs mediate the specific recognition of corresponding target mRNAs and their cleavage. However, only a small fraction of randomly chosen siRNA sequences is able to induce efficient gene silencing. In common laboratory practice, successful RNA interference experiments typically require both, the labour and cost-intensive identification of an active siRNA sequence and the optimization of target cell line-specific procedures for optimal siRNA delivery. To optimize the design and performance of siRNA experiments, we have established the human siRNA database (HuSiDa). The database provides sequences of published functional siRNA molecules targeting human genes and important technical details of the corresponding gene silencing experiments, including the mode of siRNA generation, recipient cell lines, transfection reagents and procedures and direct links to published references (PubMed). The database can be accessed at http://www.human-siRNA-database.net. We used the siRNA sequence information stored in the database for scrutinizing published sequence selection parameters for efficient gene silencing.
A Replication-Competent Adenovirus-Human Immunodeficiency Virus (Ad-HIV)tatand Ad-HIVenvPriming/Tat and Envelope Protein Boosting Regimen Elicits Enhanced Protective Efficacy against Simian/Human Immunodeficiency Virus SHIV89.6PChallenge in Rhesus Macaques (2007)

We previously demonstrated that replication-competent adenovirus (Ad)-simian immunodeficiency virus (SIV) recombinant prime/protein boost regimens elicit potent immunogenicity and strong, durable protection of rhesus macaques against SIV(mac251). Additionally, native Tat vaccines have conferred strong protection against simian/human immunodeficiency virus SHIV(89.6P) challenge of cynomolgus monkeys, while native, inactivated, or vectored Tat vaccines have failed to elicit similar protective efficacy in rhesus macaques. Here we asked if priming rhesus macaques with replicating Ad-human immunodeficiency virus (HIV) tat and boosting with the Tat protein would elicit protection against SHIV(89.6P). We also evaluated a Tat/Env regimen, adding an Ad-HIV env recombinant and envelope protein boost to test whether envelope antibodies would augment acute-phase protection. Further, expecting cellular immunity to enhance chronic viremia control, we tested a multigenic group: Ad-HIV tat, -HIV env, -SIV gag, and -SIV nef recombinants and Tat, Env, and Nef proteins. All regimens were immunogenic. A hierarchy was observed in enzyme-linked immunospot responses (with the strongest response for Env, followed by Gag, followed by Nef, followed by Tat) and antibody titers (with the highest titer for Env, followed by Tat, followed by Nef, followed by Gag). Following intravenous SHIV(89.6P) challenge, all macaques became infected. Compared to controls, no protection was seen in the Tat-only group, confirming previous reports for rhesus macaques. However, the multigenic group blunted acute viremia by approximately 1 log (P = 0.017), and both the multigenic and Tat/Env groups reduced chronic viremia by 3 and 4 logs, respectively, compared to controls (multigenic, P = 0.0003; Tat/Env, P < 0.0001). The strikingly greater reduction in the Tat/Env group than in the multigenic group (P = 0.014) was correlated with Tat and Env binding antibodies. Since prechallenge anti-Env antibodies lacked SHIV(89.6P)-neutralizing activity, other functional anti-Env and anti-Tat activities are under investigation, as is a possible synergy between the Tat and Env immunogens.
Kalign – an accurate and fast multiple sequence alignment algorithm (2005)

Kalign is a fast and robust alignment method. It is especially well suited for the increasingly important task of aligning large numbers of sequences.
Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses (2001)

We previously showed that viable Mycobacterium tuberculosis (Mtb) bacilli contain distinct ligands that activate cells via the mammalian Toll-like receptor (TLR) proteins TLR2 and TLR4. We now demonstrate that expression of a dominant negative TLR2 or TLR4 proteins in RAW 264.7 macrophages partially blocked Mtb-induced NF-kappa B activation. Coexpression of both dominant negative proteins blocked virtually all Mtb-induced NF-kappa B activation. The role of the TLR4 coreceptor MD-2 was also examined. Unlike LPS, Mtb-induced macrophage activation was not augmented by overexpression of ectopic MD-2. Moreover, cells expressing an LPS-unresponsive MD-2 mutant responded normally to Mtb. We also observed that the lipid A-like antagonist E5531 specifically inhibited TLR4-dependent Mtb-induced cellular responses. E5531 could substantially block LPS- and Mtb-induced TNF-alpha production in both RAW 264.7 cells and primary human alveolar macrophages (AM phi). E5531 inhibited Mtb-induced AM phi apoptosis in vitro, an effect that was a consequence of the inhibition of TNF-alpha production by E5531. In contrast, E5531 did not inhibit Mtb-induced NO production in RAW 264.7 cells and AM phi. Mtb-stimulated peritoneal macrophages from TLR2- and TLR4-deficient animals produced similar amounts of NO compared with control animals, demonstrating that these TLR proteins are not required for Mtb-induced NO production. Lastly, we demonstrated that a dominant negative MyD88 mutant could block Mtb-induced activation of the TNF-alpha promoter, but not the inducible NO synthase promoter, in murine macrophages. Together, these data suggest that Mtb-induced TNF-alpha production is largely dependent on TLR signaling. In contrast, Mtb-induced NO production may be either TLR independent or mediated by TLR proteins in a MyD88-independent manner.
Multi-adhesin vaccines for the protection of the neonatal piglet against "E. coli" infections. (1983)

It has been shown that the initial stages of enteric infection with E. coli organisms involve attachment of the organism to the intestinal villi. Attachment is mediated by specific protein adhesins on the surface of the organism such as K88ab, K88ac, K99 and 987P (1). Purified preparations of each of these adhesins have been used for the vaccination of pregnant gilts and been shown to confer passive protection to their piglets against homologous but not heterologous challenge with E. coli (2, 3). In this study gilts have been vaccinated with multi-adhesin vaccines combining these components (K88, K99, 987P) and litters born to them were challenged together with litters of non-vaccinated gilts, with the appropriate E. coli strains. It was shown that vaccines confer substantial protection in terms of mortality, reduction in diarrhoea and excretion of the organisms.
Computer rendering of stochastic models (1982)

A recurrent problem in generating realistic pictures by computers is to represent natural irregular objects and phenomena without undue time or space overhead. We develop a new and powerful solution to this computer graphics problem by modeling objects as sample paths of stochastic processes. Of particular interest are those stochastic processes which previously have been found to be useful models of the natural phenomena to be represented. One such model applicable to the representation of terrains, known as “fractional Brownian motion,” has been developed by Mandelbrot. The value of a new approach to object modeling in computer graphics depends largely on the efficiency of the techniques used to implement the model. We introduce a new algorithm that computes a realistic, visually satisfactory approximation to fractional Brownian motion in faster time than with exact calculations. A major advantage of this technique is that it allows us to compute the surface to arbitrary levels of details without increasing the database. Thus objects with complex appearances can be displayed from a very small database. The character of the surface can be controlled by merely modifying a few parameters. A similar change allows complex motion to be created inexpensively.