gebhart/patrepeval huggingface dataset:
A New Method for Simultaneous Determination of Cyclic Antidepressants and their Metabolites in Urine Using Enzymatic Hydrolysis and Fast GC-MS (2008)

A method for the simultaneous determination of six commonly prescribed cyclic antidepressants and their major metabolites in urine is presented. This method can be used for quantitation of amitriptyline, nortriptyline, imipramine, desipramine, doxepin, desmethyldoxepin, and maprotiline in human urine, in addition to the qualitative determination of their hydroxylated metabolites. This method is suitable for confirmation of drug abuse in health care professionals and overdose cases where the identity of the abused cyclic antidepressant may not be known. Samples are spiked with internal standard and hydrolyzed with beta-glucuronidase from Escherichia coli. Hydrolysis is found to be essential to the extraction procedure as the tertiary cyclic antidepressants are found to be extensively conjugated in urine. The secondary cyclic antidepressants, on the contrary, are found to be minimally conjugated. Drugs are extracted from alkalinized urine into solvent and derivatized with MSTFA/ammonium iodide/ethanethiol reagent. This reagent produces more stable derivatives compared to reagents previously employed. Gas chromatographic (GC)-mass spectrometric analysis is performed in electron ionization mode by selective ion monitoring, using hydrogen as a carrier gas, a short narrow bore GC capillary column, and fast temperature program, allowing for a rapid analytical cycle. While maintaining specificity for these drugs, concentrations in human urine ranging from 50 to 20,000 ng/mL can be measured with intraday and interday precisions, expressed as variation coefficient, of less than 2.8% for all analytes.
Analysis of higher order pitch division for sub-32nm lithography (2009)

The three knobs of optical lithography, namely process factor k1, wavelength (&#955;) and numerical aperture (NA) have been constantly pushed to print smaller features. To get an equivalent k1 value below the fundamental limit of 0.25, double patterning (DP) has recently emerged as a viable solution for the 32nm lithography node. Various DP techniques exist such as litho-etch-litho-etch (LELE), litho-freeze-litho-freeze (LFLF) and self-aligned sidewall spacer. In this paper, the potential of higher order pitch division (pitch/N, N&gt;2) for sub-32nm lithography is analyzed. Compared to double patterning, higher order pitch division lithography offers higher resolution but also faces significant challenges such as added cost and tighter process control. Several process schemes are proposed and compared in terms of complexity, susceptibility to alignment error and CD uniformity control. It is shown that the overlay budget does not necessarily decrease compared to double patterning. The main challenge in higher order pitch division comes from controlling the key processing steps that directly form lines or spaces. In addition, line CD control is easier than space (gap) control in all four "positive-tone" processes studied, similar to the double patterning case. Among the proposed processes, a freezing assisted double spacer (FADS) process that is simpler than the common sidewall spacer approach shows promise for balanced process control.
Genetic transformation of Streptococcus pneumoniae by heterologous plasmid deoxyribonucleic acid (1980)

A number of heterologous plasmid deoxyribonucleic acids (DNAs) coding for erythromycin, tylosin, lincomycin, tetracycline, or chloramphenicol resistance have been introduced into Streptococcus pneumoniae via genetic transformation with frequencies that varied between 10(-5) to as high as 5 x 10(-1) per colony-forming unit. Transformation with plasmid DNA required pneumococcal competence, was competed by chromosomal DNA, and showed a saturation at about 0.5 micrograms/ml (with a recipient population of 3 x 10(7) colony-forming units of competent cells per ml). Plasmid transformation did not occur with a recipient strain, 410, defective in endonuclease I activity and in chromosomal genetic transformation. All erythromycin-resistant transformants examined contained covalently closed circular DNA with the same electrophoretic mobility on agarose gels as the donor DNAs, and when examined in detail the plasmid reisolated from the transformants had the same restriction patterns and the same specific transforming activity as the donor DNA. In the cases of two plasmids examined in detail--pAM77 and pSA5700 Lc9--most of the transforming activity was associated with DNA monomers; DNA multimers present in pSA5700 Lc9 also had biological activity. An unexpected finding was the demonstration of transformation (2 x 10(-5) per colony-forming unit) with plasmid DNAs linearized by treatment with S1 nuclease or with restriction endonucleases.
Synthesis of 2′‐Azido‐2′,3′‐didehydro‐2′,3′‐dideoxythymidine (1993)

Abstract Compound 15 – the 2′‐azido analog of the anti‐HIV compound 2′,3′‐didehydro‐2′,3′‐dideoxythymidine – was synthesized. Treatment of 5′‐ O ‐trityl‐β‐ D ‐ribofuranosylthymine ( 1 ) with DAST or MSTF gave the 2,2′‐anhydro derivative 2 . The latter and its 3′‐ O ‐benzoate 3 were used for the synthesis of the 2′‐azido‐2′‐deoxy derivatives 4 and 5 . Two routes to the synthesis of 15 from 5 were investigated. (i) Treatment of 5 with DAST gave a mixture of the 5′‐ O ‐trityl derivatives 12 and 13 as well as 1‐(2‐azido‐2,3‐dideoxy‐3‐fluoro‐β‐ D ‐xylofuranosyl)thymine ( 16 ) along with 2,3′‐anhydro derivative 14 (2%). Detritylation of the mixture yielded 15 (39%) and 16 (12%). (ii) Mesylation of 5 gave 17 which yielded 15 upon saponification and detritylation. Compound 15 showed moderate inhibitory activity against HIV‐1 and HIV‐2 in MT‐4 cells.
Pre-protachykinin-A mRNA is increased in the airway epithelium of smokers with chronic bronchitis (2001)

These findings imply that up-regulation of tachykinin production by cells present in the airway epithelium contributes to the pathophysiology of chronic bronchitis.
Introduction of DNA into sea urchin eggs by particle gun. (1995)

We have applied the particle gun method, which was developed to introduce DNA into plant cells, to sea urchin eggs and have obtained excellent expression of the introduced DNA in the embryos. The expression can be normalized by concomitantly-introducing a reference construct. The method provides a new approach to quantitative analysis of cis-regulatory elements in sea urchin embryos.
Light-emitting devices based on solid electrolytes and polyelectrolytes (1998)

The properties of light-emitting diodes (LEDs) based on organic layers containing mobile ions, so-called light-emitting electrochemical cells (LECs), are reviewed. These devices have some unique properties: their current–voltage characteristics are antisymmetric with respect to the origin and they emit light under both forward and reverse bias. The physical processes involved in the emission from LECs are discussed in terms of a thermodynamic model. Recent work on blends of luminescent and ion-conducting polymers is summarized. In addition, the properties of novel single-component LECs and polyelectrolyte-based devices are presented. The results show that LECs with performances superior to that of conventional LED devices can be fabricated, but questions concerning the transient behavior and degradation mechanisms persist. © 1998 John Wiley & Sons, Ltd.
Cells that present both specific ligand and costimulatory activity are the most efficient inducers of clonal expansion of normal CD4 T cells. (1992)

Clonal expansion of naive CD4 T cells is a necessary step in most adaptive immune responses. Two distinct signals are required for clonal expansion to occur, ligation of T-cell receptors by an antigenic peptide bound to self major histocompatibility complex-encoded class II molecules (signal 1) and a costimulatory signal derived from an antigen-presenting cell (signal 2). To study whether these two signals need to be delivered by a single cell in order to induce clonal expansion of normal CD4 T cells, we have used anti-CD3 bound to Fc receptors as a ligand for the T-cell receptor to deliver signal 1 to all CD4T cells, and we have inactivated signal 2 with a newly generated monoclonal antibody or by using Fc receptor-positive cells that lack the costimulator. Costimulation was delivered by cells whose Fc receptors were blocked with anti-Fc receptor monoclonal antibody. Our results indicate that delivery of ligand and costimulator on one cell is at least 30-fold more efficient than separate delivery. No significant clonal expansion was observed when signals 1 and 2 were delivered by different cells. We have also carried out experiments using fibroblast transfectants that can deliver either or both of these two signals. These studies show that separate delivery of these two signals is at least 80-fold less efficient than their combined delivery by one cell. These findings may explain why tissues can express autoantigens and contain active antigen-presenting cells without inducing autoimmunity.
Pull-out strength of suture anchors for rotator cuff and Bankart lesion repairs (1993)

Surgical reconstructions of anterior-inferior shoulder instabilities and rotator cuff injuries require secure fixation of soft tissue to bone. Sutures are inserted directly through transosseous tunnels in current techniques, which are surgically complex and not always adequate for fixation strength. Using fresh-frozen cadaveric human specimens, our objectives were 1) to compare immediate pull-out strength of two versions of polyacetal suture anchors (wedge and rod) with conventional suture-only attachment techniques in Bankart lesion and rotator cuff repairs, and 2) to compare pull-out strength of the two polyacetal suture anchors with a metallic suture anchor. Our results indicate no significant differences in fixation strength of Bankart lesions or rotator cuff repairs using sutures only, or using wedge or rod polyacetal suture anchors (P = 0.70). Pull-out force did not differ significantly (P = 0.37) between the two polyacetal anchors. Polyacetal anchors exhibited higher pull-out forces than metallic anchors when inserted into metaphyseal regions of the tibia and significantly higher pull-out forces (P < 0.001) when inserted into metaphyseal regions with thicker cortical walls. Our results indicate that both polyacetal suture anchors provide adequate immediate fixation for soft tissue repairs in the human shoulder.
Microwave-Enhanced Fischer Reaction: An Efficient One-Pot Synthesis of γ-Carbolines (2007)

γ-Carbolines were obtained in a simple one-pot Fischer reaction starting from N-acetyl-3-bromo-4-piperidone hydrobromide and substituted arylhydrazine hydrochlorides in acidic media under microwave irradiation or by a thermal process. The optimization procedures are reported in detail, and the results from microwave processes are compared with conventional ones.
Acute LSD effects on response inhibition neural networks (2017)

Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.
Social interface agents: Acquiring competence by learning from users and other agents (1994)

Interface agents are computer programs that employ Artificial Intelligence techniques in order to provide assistance to a user dealing with a particular computer application. The paper discusses an interface agent which has been modeled closely after the metaphor of a personal assistant. The agent learns how to assist the user by (i) observing the user’s actions and imi-tating them, (ii) receiving user feedback when it takes wrong actions, (iii) being trained by the user on the basis of hypothetical examples and (iv) learning from other agents that assist other users with the same task. The paper discusses how this learning agent was im-plemented using memory-based learning and reinforce-ment learning techniques. It presents actual results from two prototype agents built using these techniques: one for a meeting scheduling application and one for electronic mail. It argues that the machine learning approach to building interface agents is a.feasible one which has several advantages over other approaches: it provides a customized and adaptive solution which is less costly and ensures better user acceptability.
Tissue Injury from Tricyclic Antidepressants Used as Local Anesthetics (2005)

Neurotoxicity has been reported with tricyclic antidepressants (TCAs) used as local anesthetics. We examined the hypothesis that TCAs cause tissue injury, particularly myotoxicity, as occurs with many local anesthetics. Animals were given sciatic nerve injections with 0-80 mM doxepin, amitriptyline, or bupivacaine (1.5 mL for histological studies, 0.3 mL for neurobehavioral studies). Four days after injection, the TCAs caused ischemic tissue injury. Subcutaneous tissue showed expansion and hardening, with hemorrhage and adhesion to overlying skin. Muscle was diffusely pale. Histopathology showed coagulative necrosis of muscle and surrounding soft tissues, with thrombus formation in vasculature near affected areas. These findings were much reduced with bupivacaine. TCA-injected and bupivacaine-injected animals also developed characteristic local anesthetic myotoxicity. Amitriptyline proved less potent than bupivacaine as a local anesthetic: the concentrations required to provide 100 min of nerve block were 20 mM and 3 mM, respectively. Some animals receiving large concentrations of amitriptyline developed spontaneous recrudescence of nerve blockade or had irreversible nerve blockade, both of which may reflect nerve injury. Neither finding occurred in animals injected with bupivacaine. TCAs do not appear to offer any advantages over conventional local anesthetics and do appear to risk substantially increased toxicity.
Stereoselective Synthesis of a Potent Thrombin Inhibitor by a Novel P2−P3 Lactone Ring Opening (2004)

The concise synthesis of a potent thrombin inhibitor was accomplished by a mild lactone aminolysis between an orthogonally protected bis-benzylic amine and a diastereomerically pure lactone. The lactone was synthesized by the condensation of l-proline methyl ester with an enantiomerically pure hydroxy acid, which in turn was synthesized by a highly stereoselective (>500:1 er) and productive (100,000:1, S/C) enzymatic reduction of an alpha-ketoester. In addition, a second route to the enantiomerically pure lactone was accomplished by a diastereoselective ketoamide reduction.
Spinodal Decomposition and Syneresis of PVA Gel (2001)

The phase separation of a network in the unstable region has been investigated using a homogeneous transparent poly(vinyl alcohol) (PVA) gel by volume and UV transmittance measurements as well as by time-resolved light scattering measurements. It was found that the light scattering intensity I(Q) shows a single peak which increases in intensity exponentially with time without shifting the peak position in the early stage of phase separation, suggesting that a spinodal decomposition (SD) type phase separation occurs in this system. In contrast to the usual fluids, the domain growth is extremely slowed down in the late stage because the elastic force of the gel suppresses the surface tension force, which is the driving force of domain growth. This is the so-called pinning effect. As the SD approaches the end, the UV transmittance of the gel increases gradually and the scattering intensity decreases during the shrinking process of volume (syneresis), which corresponds to a relaxation process of the microscopic internal fluctuations produced in the SD process.
Regulation of B Cell Development by Variable Gene Complexity in Mice Reconstituted with Human Immunoglobulin Yeast Artificial Chromosomes (1998)

The relationship between variable (V) gene complexity and the efficiency of B cell development was studied in strains of mice deficient in mouse antibody production and engineered with yeast artificial chromosomes (YACs) containing different sized fragments of the human heavy (H) chain and kappa light (L) chain loci. Each of the two H and the two kappa chain fragments encompasses, in germline configuration, the same core variable and constant regions but contains different numbers of unique VH (5 versus 66) or Vkappa genes (3 versus 32). Although each of these YACs was able to substitute for its respective inactivated murine counterpart to induce B cell development and to support production of human immunoglobulins (Igs), major differences in the efficiency of B cell development were detected. Whereas the YACs with great V gene complexity restored efficient development throughout all the different recombination and expression stages, the YACs with limited V gene repertoire exhibited inefficient differentiation with significant blocks at critical stages of B cell development in the bone marrow and peripheral lymphoid tissues. Our analysis identified four key checkpoints regulated by VH and Vkappa gene complexity: (a) production of functional mu chains at the transition from the pre B-I to the pre B-II stage; (b) productive VkappaJkappa recombination at the small pre B-II stage; (c) formation of surface Ig molecules through pairing of mu chains with L chains; and (d) maturation of B cells. These findings demonstrate that V gene complexity is essential not only for production of a diverse repertoire of antigen-specific antibodies but also for efficient development of the B cell lineage.
A comparison of empirical study and cognitive dimensions analysis in the evaluation of UML diagrams (2002)

It is important that all those who use representations of a system during the development process can clearly understand the representations that are used. Research has shown that structure plays an important role in whether a diagrammatic representation may be readily understood. In this paper we present the results of a study where two different approaches were taken to the evaluation of two notations which form part of the UML diagram toolkit: sequence diagrams and collaboration diagrams. First, a theoretical investigation was carried out using the cognitive dimensions framework. Second, an empirical study was carried out to investigate user understanding of such diagrams. The results of the two studies did not concur, with the theoretical approach supporting the original hypothesis that structure is an important factor in diagram comprehension, but the study providing no evidence to support this. 1.
Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease (2006)

The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].).
Filters for distortion-free two-band multirate filter banks (1985)

In this paper, conditions are given for a two-band multi-rate filter bank to be alias free and to have a unity frequency response. It is shown that the class of quadrature mirror filters (QMF's) that satisfies these conditions is quite limited. A class of filters which does satisfy these conditions is given, and a simple procedure for designing filters from this class is presented with an example.
Network-on-Chip Hardware Accelerators for Biological Sequence Alignment (2009)

The most pervasive compute operation carried out in almost all bioinformatics applications is pairwise sequence homology detection (or sequence alignment). Due to exponentially growing sequence databases, computing this operation at a large-scale is becoming expensive. An effective approach to speed up this operation is to integrate a very high number of processing elements in a single chip so that the massive scales of fine-grain parallelism inherent in several bioinformatics applications can be exploited efficiently. Network-on-chip (NoC) is a very efficient method to achieve such large-scale integration. In this work, we propose to bridge the gap between data generation and processing in bioinformatics applications by designing NoC architectures for the sequence alignment operation. Specifically, we 1) propose optimized NoC architectures for different sequence alignment algorithms that were originally designed for distributed memory parallel computers and 2) provide a thorough comparative evaluation of their respective performance and energy dissipation. While accelerators using other hardware architectures such as FPGA, general purpose graphics processing unit (GPU), and the cell broadband engine (CBE) have been previously designed for sequence alignment, the NoC paradigm enables integration of a much larger number of processing elements on a single chip and also offers a higher degree of flexibility in placing them along the die to suit the underlying algorithm. The results show that our NoC-based implementations can provide above 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> -10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> -fold speedup over other hardware accelerators and above 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> -fold speedup over traditional CPU architectures. This is significant because it will drastically reduce the time required to perform the millions of alignment operations that are typical in large-scale bioinformatics projects. To the best of our knowledge, this work embodies the first attempt to accelerate a bioinformatics application using NoC.
Enantioselective Ketone Hydrogenation:  From R&D to Pilot Scale with Industrially Viable Ru/Phosphine−Oxazoline Complexes (2007)

The development of a pilot process for the enantioselective hydrogenation of 3,5-bistrifluoromethyl acetophenone (BTMA) using a Ru/phosphine−oxazoline complex in toluene in the presence of aqueous NaOH is described. Various reaction parameters and quality risk factors such as ligand structure, substrate quality, reaction conditions, thermal safety, etc. were investigated. The reaction was carried out twice on a 140-kg scale at 20 bar and 25 °C with substrate-to-catalyst ratios of 20,000 with an enantiomeric excess of >95%. After crystallization, (R)-3,5-bistrifluoromethyl phenyl ethanol (BTMP) was obtained with an ee between 97.7 and 98.6% in 70% chemical yield.