gebhart/patrepeval huggingface dataset:
Pharmacological properties of besulpamide, a new diuretic, in rats and dogs. (1987)

Besulpamide, a newly synthesized compound, has demonstrated significant diuretic activity in rats and dogs, similar to that of chlorthalidone, clopamide and xipamide. Antihypertensive activity of besulpamide is similar to that of hydrochlorothiazide and was demonstrated in rat one-kidney desoxycorticosterone acetate (DOCA)-salt hypertension. In addition, besulpamide, like hydrochlorothiazide, potentiated the antihypertensive activity of captopril in spontaneously hypertensive rats (SHR). Doses of besulpamide exceeding those normally required for pharmacological activity did not evoke adverse reactions in rats and mice.
Extending cognitive architecture with episodic memory (2007)

In this paper, we explore the hypothesis that episodic memory is a critical component for cognitive architectures that support general intelligence. Episodic memory overlaps with case-based reasoning (CBR) and can be seen as a task-independent, architectural approach to CBR. We define the design space for episodic memory systems and the criteria any implementation must meet to be useful in a cognitive architecture. We present an implementation and demonstrate how episodic memory, combined with other components of a cognitive architecture, supports a wealth of cognitive capabilities that are difficult to attain without it.
Microfluidic heart on a chip for higher throughput pharmacological studies (2013)

We present the design of a higher throughput "heart on a chip" which utilizes a semi-automated fabrication technique to process sub millimeter sized thin film cantilevers of soft elastomers. Anisotropic cardiac microtissues which recapitulate the laminar architecture of the heart ventricle are engineered on these cantilevers. Deflection of these cantilevers, termed Muscular Thin Films (MTFs), during muscle contraction allows calculation of diastolic and systolic stresses generated by the engineered tissues. We also present the design of a reusable one channel fluidic microdevice completely built out of autoclavable materials which incorporates various features required for an optical cardiac contractility assay: metallic base which fits on a heating element for temperature control, transparent top for recording cantilever deformation and embedded electrodes for electrical field stimulation of the tissue. We employ the microdevice to test the positive inotropic effect of isoproterenol on cardiac contractility at dosages ranging from 1 nM to 100 μM. The higher throughput fluidic heart on a chip has applications in testing of cardiac tissues built from rare or expensive cell sources and for integration with other organ mimics. These advances will help alleviate translational barriers for commercial adoption of these technologies by improving the throughput and reproducibility of readout, standardization of the platform and scalability of manufacture.
FDG PET and immunoscintigraphy with 99mTc-labeled antibody fragments for detection of the recurrence of colorectal carcinoma. (2000)

These results indicate that FDG PET and 99mTc-labeled anti-CEA Fab' are suitable for the diagnosis of local recurrence of colorectal carcinoma but that FDG PET is clearly superior in the detection of distant metastases (liver, bone, and lung) and lymph node involvement.
Organization of the canine major histocompatibility complex: current perspectives (1999)

The dog is a valuable model for studying several human diseases as well as one of the most important models for organ transplantation. Important to understanding the pathophysiology or development of some of these diseases is an understanding of the canine major histocompatibility complex (MHC) or dog leukocyte antigen (DLA). Initial characterization of the DLA involved primarily cellular, serological, and biochemical analyses. Later a molecular analysis of the DLA region was begun. There are at least four complete class I genes: DLA-88, DLA-12, DLA-64, and DLA-79. DLA-88 is highly polymorphic, with more than 40 alleles obtained from an examination of 50 mixed breed dogs. The other class I loci are less polymorphic, with fewer than 12 alleles each. In the class II region there is one complete DRB gene called DLA-DRB1 with at least 24 alleles and one full-length DQB gene, DLA-DQB1, with 20 alleles characterized to date. DLA-DQA is less polymorphic with nine alleles and DLA-DRA appears monomorphic. Two highly polymorphic canine microsatellite markers, one located in the class I region and one located in the class II region, can be used to identify DLA-matched and -mismatched dogs within families for organ transplantation experiments. Future projects include mapping the DLA region by pulsed-field gel electrophoresis and using a recently constructed canine bacterial artificial chromosome (BAC) library to search for new genes within the DLA. The dog has been a useful model for understanding several human diseases such as gluten-sensitive enteropathy (Hall and Batt 1990), rheumatoid arthritis (Halliwell et al. 1972), narcolepsy (Tafti et al. 1996), and systemic lupus erythematosus (Lewis and Schwartz 1971, Teichner et al. 1990), as well as an important model for solid organ and hematopoietic stem cell transplantation (Storb and Deeg 1985). Much of the impetus behind efforts to characterize the canine MHC comes from its importance in transplantation. In spite of the dog's importance in studying human disease and in immunology, molecular analysis of the DLA has lagged behind that of the mouse and human as well as several agricultural animals.
Antegrade catheterization of the superficial femoral artery. (1985)

A simple method of selective catheterization of the superficial femoral artery (SFA) following antegrade puncture of the common femoral artery is described. The method entails using a Cope-type dilator introducer, which directs the guide wire from its side hole into the SFA while the tip is secured in the deep femoral artery.
Molecular Modeling and Computer Aided Drug Design. Examples of their Applications in Medicinal Chemistry (2000)

The development of new drugs with potential therapeutic applications is one of the most complex and difficult process in the pharmaceutical industry. Millions of dollars and man-hours are devoted to the discovery of new therapeutical agents. As, the activity of a drug is the result of a multitude of factors such as bioavailability, toxicity and metabolism, rational drug design has been utopias for centuries. Very recently, impressive technological advances in areas such as structural characterization of biomacromolecules, computer sciences and molecular biology have made rational drug design feasible. The aim of this review is to give an outline of studies in the field of medicinal chemistry in which molecular modeling has helped in the discovery process of new drugs. The emphasis will be on lead generation and optimization.
Release of 17-Beta-Oestradiol from a Vaginal Ring in Postmenopausal Women: Pharmacokinetic Evaluation (1994)

Oestrogen-containing vaginal rings of various designs have been utilised in hormone replacement therapy. In contrast to the traditional ‘homogeneous’ design, rings designed with a steroid-containing core and outer polymer sheath provide a diffusion-controlled release rate which enables the delivery of low doses of drug. The aim of this investigation was to evaluate in vitro oestradiol release from a ‘core’ designed vaginal ring (Estring®) and furthermore, to establish the in vivo concentration-time course of oestradiol, oestrone and total oestrone (unconjugated plus conjugated) in consecutive applications of such an oestradiol-containing vaginal ring in postmenopausal women. Results indicate that the controlled release design of Estring® produces stable, low systemic plasma concentrations of oestradiol and has an extended time period of release.
Role of Heparanase in Platelet and Tumor Cell Interactions with the Subendothelial Extracellular Matrix (1987)

Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. Since platelets have been shown to contribute to this process, we studied the interaction in vitro of platelets and malignant cells with the vascular endothelium and its underlying basement membrane-like ECM. A metastatic subline (ESb) of the methylcholanthrene-induced DBA/2 T-lymphoma invaded the vascular endothelium at a higher rate than its parental nonmetastatic (Eb) subline. ESb cells also exhibited a much higher ability to degrade the proteoglycan scaffold of the ECM by means of a specific HS degrading endoglycosidase (heparanase). The interaction of platelets with this ECM was associated with platelet activation, aggregation, and degradation of HS by means of the platelet heparanase. Degradation of ECM-HS was facilitated by proteolytic activity that produced a more accessible substrate for further cleavage by heparanase. A similar enhancement was exerted by plasminogen via the activity of the tumor cells or ECM associated PAs. Heparin and chemically modified heparins that lack anticoagulant activity inhibited degradation of the ECM-HS by heparanase. Interaction of platelets and lymphoma cells with ECM covered with vascular endothelial cells was investigated by SEM and by determination of ECM-HS degradation products. SEM studies demonstrated that platelets may adhere to minor gaps between adjacent endothelial cells and degrade the ECM-HS. Platelets were also shown to recruit lymphoma cells into these interendothelial gaps, suggesting that by binding to ECM and release of heparanase, platelets may play an active role in tumor cell invasion and metastasis. Our observation that nonanticoagulant heparins may interfere with heparanase-mediated degradation of ECM-HS suggests a potential therapeutic use for such heparins in neoplastic disorders.
Classification of oligonucleotide fingerprints: application for microbial community and gene expression analyses (2005)

The performance of each classification/clustering procedure was compared with results from known reference data. Comparisons indicated that the approach using the Bayesian classification with normal densities followed by tree clustering out-performed all others. The paper includes a discussion of how this Bayesian approach may be useful for the analysis of gene expression data.
Cetuximab monotherapy is active in patients (pts) with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN): Results of a phase II study (2004)

5502 Background: Pts with refractory SCCHN have a poor prognosis with few therapeutic options. Cetuximab (Erbitux), an IgG1 monoclonal antibody that binds selectively to EGFR, has shown activity in combination with cisplatin or carboplatin in pts with recurrent/metastatic SCCHN progressing on the same platinum-based regimen (Baselga #900, Kies #925; ASCO 2002). Methods: This multicenter phase II study was designed to investigate the efficacy of cetuximab as monotherapy in pts with platinum-refractory SCCHN. Main inclusion criteria were: stage III/IV recurrent and/or metastatic SCCHN not suitable for local therapy, with documented progression on or within 30 days after 2 to 6 cycles of a platinum-based CT. Cetuximab was given at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression, with the option to switch to the combination of cetuximab with the same platinum that the pts had previously progressed on, after failure to cetuximab monotherapy. Results: 103 pts (84 M, 19 F) were enrolled. Median age was 57 years (23–77), median baseline KPS was 80 (60–100) and median time from diagnosis to study entry was 20 months (3–283). Drug-related adverse events occurring in >10% of pts included: skin rash/acne 80% (1% grade 3), fatigue 24% (4% grade 3), fever/chills 19% (2% grade 3), nail changes 15% (all grade 1–2) and nausea 13% (1% grade 3). There was one treatment-related death due to hypersensitivity reaction in a patient not suitable to receive mechanical ventilation. Preliminary efficacy data (based on investigator assessment) were as follows: 5 CR, 12 PR, 38 SD, 47 PD, 1 not assessable, for an overall objective response rate of 16.5% (95% CI: 9.9%–25.1%). Disease control rate was 53.4% (95% CI: 43.3%–63.3%). Median TTP and median survival were 85 and 175 days, respectively. An independent review of all pre-treatment and on-study imaging assessments is ongoing and will be available at the meeting. Conclusions: Cetuximab as single agent can produce major objective responses in pts with platinum-refractory recurrent/metastatic SCCHN, with acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck
Metal FEAs on double layer structure of polycrystalline silicon (2002)

Metal field emitter arrays were fabricated on a single polysilicon layer and on a double polysilicon layer. From the observation of metal field emitters fabricated on the single polysilicon layer, it was noticed that the irregular shape of the gate hole was caused by the large grain of polysilicon. To suppress the grain growth of doped polysilicon during oxidation, an undoped polysilicon layer was used to form a gate insulator and a doped polysilicon layer was used to serve as a conducting layer. Due to the small grain size of undoped polysilicon, the shape of gate aperture was improved to be as symmetric as in single crystal silicon.
Key role for IL-21 in experimental autoimmune uveitis (2011)

IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ(c), with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21-mCherry/Il2-emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ(c)-signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.
Species Plays an Important Role in Drug‐Induced Prolongation of Action Potential Duration and Early Afterdepolarizations in Isolated Purkinje Fibers (2001)

Species and Drug‐Induced Long APD and EADs. Introduction : Although isolated Purkinje fibers (PFs) often are used to evaluate the electrophysiologic effects of new drugs in terms of prolongation of action potential duration (APD) and induction of early afterdepolarizations (EADs), species differences in this respect remain elusive. We evaluated potential species‐specific differences in drug‐induced prolongation of APD and EADs in isolated PF from various species. Methods and Results : Using a microelectrode technique, PFs ( n = 7 to 11 per species ) were isolated from hearts of rabbits, guinea pigs, dogs, swine, goats, or sheep, superperfused in Tyrode's solution with dofetilide ( 1 × 10 −8 M ) or quinidine ( 1 × 10 −5 M ) for 25 minutes, and stimulated at 1 Hz for 20 minutes and at 0.2 Hz for another 5 minutes. Dofetilide increased APD at 90% repolarization (APD 90 ) at 1 Hz by 83% (rabbit), 24% (guinea pig), 65% (dogs), 18% (swine), 61% (goat), and 30% (sheep), and prolonged APD 90 at 0.2 Hz by 187% (rabbit), 31% (guinea pig), 154% (dog), 17% (swine), 61% (goat), and 8% (sheep). Similarly, quinidine changed APD 90 by 93% (rabbit), 0% (guinea pig), 16% (dog), −3% (swine), 0% (goat), and −24% (sheep) at 1 Hz, and by 124% (rabbit), 15% (guinea pig), 53% (dog), 17% (swine), 11% (goat), and −39% (sheep) at 0.2 Hz in PF. During superfusion of dofetilide or quinidine, EADs occurred in most preparations in rabbit PFs at 0.2 Hz, but not in any of the PFs from other species at 0.2 Hz. Conclusion : Our study demonstrates that species plays an important role in the response of PF to drug‐induced prolongation of APD and EADs. Rabbit PFs constitute the most sensitive model for detecting drug‐induced, potential long APD and proarrhythmogenic effects in vitro.
The effects of material selection for backing and wear protection/quarter-wave matching of piezoelectric polymer ultrasound transducers (2002)

Selection of the proper backing material for a piezoelectric polymer ultrasonic transducer demands careful design consideration. Many ultrasonic transducers also require a front layer to protect the otherwise exposed electroding from the environment. By carefully choosing the right front layer material, one can also improve acoustic performance with the use of a quarter-wave matching layer. However, there are few practical materials which can be effectively used for quarter-wave matching polymer transducers. This paper describes the practical selection of materials for the design of the backing substrate and front wear/matching layers for piezoelectric polymer ultrasound transducers.
Histopathologic features of the vagus nerve after electrical stimulation in swine. (2005)

This paper describes the histological features of the vagus nerve after its stimulation with an electrostimulation system that is being developed for morbid obesity treatment. An electrostimulation system was implanted laparoscopically around the ventral vagal trunk of five Large White female pigs (49.63+/-1.94 kg.). Vagal nerve stimulation was performed by continuous constant voltage current pulses. Thoracic samples of both ventral and dorsal vagal trunks were obtained thoracoscopically one month after implantation. Animals were sacrificed one month after thoracoscopic vaguectomy. Tissue samples were then harvested from the vagal nerve at the implantation site, 1cm cranial to it, thoracic portion of ventral and dorsal vagal trunks, sub-diaphragmatic dorsal vagal trunk, left and right vagus nerves. Specimens were analysed with light microscope. The severity of the lesions was graded from 0 to 4 (0: no lesion, 1: mild, 2: moderate, 3: severe and 4: extremely severe), taking into account fibrosis, vascularization, necrosis, fiber degeneration and inflammation. Electrode implantation resulted in thickened epineurium and endoneural connective tissue. The greatest lesion score was evidenced at the leads implantation site in the ventral vagal trunk, followed by, in order of decreasing lesion severity, left vagus nerve, thoracic portion of ventral vagal trunk, subdiaphragmatic dorsal vagal trunk, thoracic portion of dorsal vagal trunk and right vagus nerve. The stimulation device used in this study caused connective tissue growth, greatest in the samples located closer to the implantation site. However, there was no sign of altered vascularization in any studied specimen.
Synthesis of C-Axis-Oriented Aluminum Nitride Films by Reactive RF Magnetron Sputtering for Surface Acoustic Wave (2001)

C -axis-oriented aluminum nitride (AlN) films were deposited on SiO 2 -coated Si substrates by reactive rf magnetron sputtering. The crystallization of the AlN films, identified by X-ray diffraction (XRD) , was dependent on the deposition conditions. Highly c -axis-oriented AlN films, for fabricating AlN/SiO 2 /Si-based surface acoustic wave (SAW) devices, were obtained under an rf power of 300 W, substrate temperature of 350°C, sputtering pressure of 7.5 mTorr and N 2 concentration of 75%. A dense pebblelike surface texture of the c -axis-oriented AlN films with an average grain size of about 100 nm was observed by scanning electron microscopy (SEM). The phase velocity showed a tendency to decrease with increasing k h , where k =2π/λ is the wavenumber and h is the AlN film thickness. In partucular, the phase velocity and the electromechanical coupling coefficient of the sample at k h =0.4 were calculated to be about 6080 m/s and 1.1%, respectively.
Rapid Molecular Cloning of Rearrangements of the IGHJ Locus Using Long-Distance Inverse Polymerase Chain Reaction (1997)

Clonal rearrangements of the Ig heavy chain (IGH ) locus consisting of either intrachromosomal (VDJ ) rearrangements or interchromosomal translocations are a consistent feature of all B-cell malignancies and may be used both diagnostically and to monitor response to therapy. Many of these rearrangements are targeted to the IGHJ segments, but only some can be amplified with regular polymerase chain reaction (PCR) techniques. To permit PCR amplification of potentially all IGHJ rearrangements, we have devised a method incorporating self-ligation of restriction endonuclease-digested DNA fragments with long-distance PCR (long-distance, inverse PCR [LDI-PCR]). We show here, using only 4 nested oligonucleotide primers, the successful amplification and DNA sequencing of all IGHJ rearrangements up to 5.4 kb in length from a panel of 13 cases and cell lines of various types of B-cell malignancy. In all cases, both VDJ and DJ IGH rearrangements and translocation breakpoints were amplified. Six cases exhibited t(14; 18)(q32; q21). All translocation breakpoints were cloned and sequenced. Three cases exhibited a rearrangement to the BCL2 major breakpoint region (MBR). However, 2 other cases exhibited rearrangements between the MBR and the minor cluster region (mcr). These 2 cases broke within 44 bp of each other, confirming the presence of an additional 3′ BCL2 breakpoint cluster region. The final case fell immediately 3′ of the 3′ UTR of the BCL2 gene adjacent to an Alu repeat. No other BCL2 breakpoints within this region have been reported. Four cases exhibited t(11; 14)(q13; q32). All 3 cases with translocations targeted to the IGHJ segments were successfully amplified and sequenced, including 1 case in which the BCL1 translocation could not be detected by DNA blot using the currently available probes. All three translocation breakpoints fell outside the BCL1 major translocation cluster between 20 and 40 kb telomeric and showed no clustering. Two of the three fell within or adjacent to Alu repeat regions. LDI-PCR is a simple and robust technique that allows PCR amplification of nearly all IGHJ rearrangements.
’’1/f noise’’ in music: Music from 1/f noise (1978)

The spectral density of fluctuations in the audio power of many musical selections and of English speech varies approximately as 1/f (f is the frequency) down to a frequency of 5×10−4 Hz. This result implies that the audio-power fluctuations are correlated over all times in the same manner as ’’1/f noise’’ in electronic components. The frequency fluctuations of music also have a 1/f spectral density at frequencies down to the inverse of the length of the piece of music. The frequency fluctuations of English speech have a quite different behavior, with a single characteristic time of about 0.1 s, the average length of a syllable. The observations on music suggest that 1/f noise is a good choice for stochastic composition. Compositions in which the frequency and duration of each note were determined by 1/f noise sources sounded pleasing. Those generated by white-noise sources sounded too random, while those generated by 1/f2 noise sounded too correlated.