gebhart/patrepeval huggingface dataset:
Oral Clonidine Pretreatment Prior to Venous Cannulation (2006)

Clonidine is a preferential alpha-2 agonist drug that has been used for over 35 years to treat hypertension. Recently, it has also been used as a preoperative medication and as a sedative/anxiolytic drug. This randomized, double-blind, placebo-controlled crossover clinical trial characterized the effects of oral clonidine pretreatment on intravenous catheter placement in 13 patients. Parameters measured included the bispectral index (BIS), Observer's Assessment of Alertness/Sedation Scale (OAA/S), frontal temporal electromyogram (EMG), 30-Second Blink Count (Blink), Digit Symbol Substitution Test (DSST), State Anxiety Inventory (SAI), fingertip versus forearm skin temperatures, and multiple questionnaires. Oral clonidine significantly decreased SAI scores, OAA/S, EMG, and Blink, but did not cause statistically significant BIS or DSST reductions. Subjects preferred oral clonidine pretreatment prior to venipuncture compared to placebo. Questionnaires also indicated that clonidine provided minimal sedation, considerable anxiolysis, and some analgesia. Fingertip versus forearm skin temperature differentials were decreased. Reduced fingertip versus forearm temperature differentials suggest increased peripheral cutaneous blood flow prior to venous cannulation. Oral clonidine pretreatment not only helped control patient anxiety and pain but also provided cardiovascular stability.
LEUKOCYTE PROTEIN TYROSINE KINASES:Potential Targets for Drug Discovery (1997)

Intracellular signal transduction following the extracellular ligation of a wide variety of different types of surface molecules on leukocytes involves the activation of protein tyrosine kinases. The dependence of successful intracellular signaling on the functions of the nontransmembrane class of protein tyrosine kinases coupled with the cell type-specific expression patterns for several of these enzymes makes them appealing targets for therapeutic intervention. Development of drugs that can interfere with the catalytic functions of the nontransmembrane protein tyrosine kinases or that can disrupt critical interactions with regulatory molecules and/or substrates should find clinical applications in the treatment of allergic diseases, autoimmunity, transplantation rejection, and cancer.
Functional roles of NMDA receptor NR2A and NR2B subunits in the acute intoxicating effects of ethanol in mice (2005)

The present study examined the roles of NR2A and NR2B subunit-containing NMDA receptors in the mediation of the sedative/hypnotic effects of ethanol in mice. The ability of the competitive NMDA antagonist, CGP-37849 (0, 1, or 3 mg/kg), and the NR2B-selective antagonist, Ro 25-6981 (0, 3, or 10 mg/kg), to alter (3 g/kg) ethanol-induced sleep time was measured in C57BL/6J mice and NR2A knockout (KO) mice. The results show that pretreatment with either antagonist significantly potentiated the sedative/hypnotic effects of ethanol in C57BL/6J mice. These effects were not significantly altered in NR2A KO mice. Basal sleep time responses to ethanol were also normal in NR2A KO mice. These findings confirm a major role for NMDA receptors in the acute intoxicating actions of ethanol and provide tentative support for a prepotent role of the NR2B subunit in these effects.
The effect of trimeric 2',5'-oligoadenylic acid and its epoxyderivative on the human immunodeficiency virus reproduction and retroviruses reverse transcriptase activity (1999)

Досліджено дію 2',5'-триолігоаденілату (2',5'АрАрА) та його епоксипохідного (2' ,5'-Аг(ккА)) на репродукцію вірусу імунодефіциту людини (ВІЛ-І). Показано, що 2',5'-олігоаденілати пригнічують репродукцію ВІЛ-1 у випадку їхньої попередньої інкубації з клітинами лімфобластоїдної лінії МТ-4. Вивчено можливі механізми противірусної дії 2',5'-олігоаденілатів, а саме: проаналізовано інтерфероногенну дію цих препаратів. Показано, що 2',5'АрАрА та 2' ,5'-Аг(ккА) підвищують рівень інтерферону в клітинах у 2 і 4 рази відповідно порівняно з контролем. Виявлено інгібуючу дію 2' ,5' -олігоаденілатів на активність зворотної транскриптази ендо- і екзогенних ретровірусів. Припускається, що 2',5'-триолігоаденілат та його епоксипохідне можуть використовуватися у боротьбі з ВІЛ-інфекцією.
Identification of the prfC gene, which encodes peptide-chain-release factor 3 of Escherichia coli. (1994)

The termination of protein synthesis in bacteria requires two codon-specific polypeptide release factors, RF-1 and RF-2. A third factor, RF-3, which stimulates the RF-1 and RF-2 activities, was originally identified in Escherichia coli, but it has received little attention since the 1970s. To search for the gene encoding RF-3, we selected nonsense-suppressor mutations by random insertion mutagenesis on the assumption that a loss of function of RF-3 would lead to misreading of stop signals. One of these mutations, named tos-1 (for transposon-induced opal suppressor), mapped to the 99.2 min region on the E. coli chromosome and suppressed all three stop codons. Complementation studies and analyses of the DNA and protein sequences revealed that the tos gene encodes a 59,442-Da protein, with sequence homology to elongation factor EF-G, including G-domain motifs, and that the tos-1 insertion eliminated the C-terminal one-fifth of the protein. Extracts containing the overproduced Tos protein markedly increased the formation of ribosomal termination complexes and stimulated the RF-1 or RF-2 activity in the codon-dependent in vitro termination assay. The stimulation was significantly reduced by GTP, GDP, and the beta,gamma-methylene analog of GTP, but not by GMP. These results fit perfectly with those described in the original publications on RF-3, and the tos gene has therefore been designated prfC. A completely null prfC mutation made by reverse genetics affected the cell growth under the limited set of physiological and strain conditions.
Genotype ✕ Environment Interactions in the Regional Testing of Soybean Strains<sup>1</sup> (1967)

Estimates of genotype ✕ environment interactions were obtained from seven regional Uniform Soybean Tests grown in 1954‐56. All of the second order and nearly all of the first order interactions were significantly different from zero at the .05 level of probability. Estimates of the genotype ✕ year interactions were generally smaller than estimates of the genotype ✕ location interactions but in practice will have a greater effect on the error variance of a line mean, since testing over a long period of time is seldom done. Evidence was cited to suggest that locations may be effectively substituted for years in regional tests to permit a rapid turnover of breeding material and that data from 10 to 15 locations in a single year should be sufficient to eliminate low‐yielding strains.
Shape memory polymers and their composites in aerospace applications: a review (2014)

As a new class of smart materials, shape memory polymers and their composites (SMPs and SMPCs) can respond to specific external stimulus and remember the original shape. There are many types of stimulus methods to actuate the deformation of SMPs and SMPCs, of which the thermal- and electro-responsive components and structures are common. In this review, the general mechanism of SMPs and SMPCs are first introduced, the stimulus methods are then discussed to demonstrate the shape recovery effect, and finally, the applications of SMPs and SMPCs that are reinforced with fiber materials in aerospace are reviewed. SMPC hinges and booms are discussed in the part on components; the booms can be divided again into foldable SMPC truss booms, coilable SMPC truss booms and storable tubular extendible member (STEM) booms. In terms of SMPC structures, the solar array and deployable panel, reflector antenna and morphing wing are introduced in detail. Considering the factors of weight, recovery force and shock effect, SMPCs are expected to have great potential applications in aerospace.
Tumor Exome Analysis Reveals Neoantigen-Specific T-Cell Reactivity in an Ipilimumab-Responsive Melanoma (2013)

The evidence for T-cell–mediated regression of human cancers such as non–small-cell lung carcinoma, renal cell carcinoma, and—in particular—melanoma after immunotherapy is strong. Anti-CTLA4 (ipilimumab) treatment has been approved for treatment of meta-static melanoma,1 and antibody-mediated blockade of PD-1, a second inhibitory receptor on T cells, has shown highly encouraging results in early clinical trials.2,3 Although the clinical activity of these treatments is apparent, it is still unknown which T-cell reactivities are involved in immunotherapy-induced cancer regression.4 T-cell reactivity against nonmutated tumor-associated self-antigens has been analyzed in patients treated with ipilimumab or with autologous tumor-infiltrating T cells, but the magnitude of the T-cell responses observed has been relatively modest.5,6 In part on the basis of such data, recognition of patient-specific mutant epitopes (hereafter referred to as neoantigens) has been suggested to be a potentially important component.7 A potential involvement of mutated epitopes in T-cell control would also fit well with the observation that the mutation load in sun-exposed melanomas is particularly high.8-10

Intriguingly, on the basis of animal model data, it has recently been suggested that (therapy-induced) analysis of T-cell reactivity against patient-specific neoantigens may be feasible through exploitation of cancer genome data.11,12 However, human data have thus far been lacking. Here we report a case of a patient with stage IV melanoma who exhibited a clinical response to ipilimumab treatment. Cancer exome–guided analysis of T-cell reactivity in this patient revealed reactivity against two neoantigens, including a dominant T-cell response against a mutant epitope of the ATR (ataxia telangiectasia and Rad3 related) gene product that increased strongly after ipilimumab treatment. These data provide the first demonstration (to our knowledge) of cancer exome–guided analysis to dissect the effects of melanoma immunotherapy.
Contribution of Light Chain Residues to High Affinity Binding in an HIV-1 Antibody Explored by Combinatorial Scanning Mutagenesis (2010)

Detailed analysis of factors governing high affinity antibody-antigen interactions yields important insight into molecular recognition and facilitates the design of functional antibody libraries. Here we describe comprehensive mutagenesis of the light chain complementarity determining regions (CDRs) of HIV-1 antibody D5 (which binds its target, "5-Helix", with a reported K(D) of 50 pM). Combinatorial scanning mutagenesis libraries were prepared in which CDR residues on the D5 light chain were varied among WT side chain identity or alanine. Selection of these libraries against 5-Helix and then sequence analysis of the resulting population were used to quantify energetic consequences of mutation from wild-type to alanine (DeltaDeltaG(Ala-WT)) at each position. This analysis revealed several hotspot residues (DeltaDeltaG(Ala-WT) >or= 1 kcal/mol) that formed combining site features critical to the affinity of the interaction. Tolerance of D5 light chain residues to alternative mutations was explored with a second library. We found that light chain residues located at the center and at the periphery of the D5 combining site contribute to shape complementarity and electrostatic characteristics. Thus, the affinity of D5 for 5-Helix arises from extended interactions involving both the heavy and light chains of D5. These results provide significant insight for future antibody engineering efforts.
Driving Profile Modeling and Recognition Based on Soft Computing Approach (2009)

Advancements in biometrics-based authentication have led to its increasing prominence and are being incorporated into everyday tasks. Existing vehicle security systems rely only on alarms or smart card as forms of protection. A biometric driver recognition system utilizing driving behaviors is a highly novel and personalized approach and could be incorporated into existing vehicle security system to form a multimodal identification system and offer a greater degree of multilevel protection. In this paper, detailed studies have been conducted to model individual driving behavior in order to identify features that may be efficiently and effectively used to profile each driver. Feature extraction techniques based on Gaussian mixture models (GMMs) are proposed and implemented. Features extracted from the accelerator and brake pedal pressure were then used as inputs to a fuzzy neural network (FNN) system to ascertain the identity of the driver. Two fuzzy neural networks, namely, the evolving fuzzy neural network (EFuNN) and the adaptive network-based fuzzy inference system (ANFIS), are used to demonstrate the viability of the two proposed feature extraction techniques. The performances were compared against an artificial neural network (NN) implementation using the multilayer perceptron (MLP) network and a statistical method based on the GMM. Extensive testing was conducted and the results show great potential in the use of the FNN for real-time driver identification and verification. In addition, the profiling of driver behaviors has numerous other potential applications for use by law enforcement and companies dealing with buses and truck drivers.
Shape-Selective Sorbents Based on Clay Minerals: A Review (1989)

Abstract A review is presented of work carried out over the last 40 years on non-porous sorbents and on microporous shape-selective sorbents derived from palygorskite, smectite, and vermiculite. Among such materials four kinds of behavior were observed. In some systems uptake was restricted to external surfaces; in others, intercalation also occurred but only above threshold pressures. If the interlayer region was completely filled by long-chain organic cations, imbibition was possible, but in amounts which were very strongly dependent upon the cohesive energy density of the sorbate. Finally, in certain permanently expanded derivatives of layer silicates intercalation proceeded without any threshold pressure, just as in zeolites. In this latter group, micropores existed which sometimes resulted in shape-selective sorption and molecule sieving. The micropores in clay minerals were modified by varying the size and shape of the interlayer cations, their charge, and the charge density of the siliceous layers. The interplay of these factors was investigated and the micropore sorbents were shown to be highly effective in the separation of mixtures.
Specificity of Activated CryIA Proteins from <i>Bacillus thuringiensis</i> subsp. <i>kurstaki</i> HD-1 for Defoliating Forest Lepidoptera (1991)

The insecticidal activity of the CryIA(a), CryIA(b), and CryIA(c) toxins from Bacillus thuringiensis subsp. kurstaki HD-1 was determined in force-feeding experiments with larvae of Choristoneura fumiferana, C. occidentalis, C. pinus, Lymantria dispar, Orgyia leucostigma, Malacosoma disstria, and Actebia fennica. The toxins were obtained from cloned protoxin genes expressed in Escherichia coli. The protoxins were activated with gut juice from Bombyx mori larvae. Biological activity of the individual gene products as well as the native HD-1 toxin was assessed as the dose which prevented 50% of the insects from producing frass within 3 days (frass failure dose [FFD(50)]). The three toxins were about equally active against M. disstria. In the Choristoneura species, CryIA(a) and CryIA(b) were up to fivefold more toxic than CryIA(c). In the lymantriid species, CryIA(a) and CryIA(b) were up to 100-fold more toxic than CryIA(c). The toxicity of HD-1 was similar to that of the individual CryIA(a) or CryIA(b) toxins in all of these species. None of the CryIA toxins or HD-1 exhibited and toxicity towards A. fennica. Comparison of the observed FFD(50) of HD-1 with the FFD(50) expected on the basis of its crystal composition suggested a possible synergistic effect of the toxins in the two lymantriid species. Our results further illustrate the diversity of activity spectra of these highly related proteins and provide a data base for studies with forest insects to elucidate the molecular basis of toxin specificity.
Cross-relaxation dynamics of optically excited<i>N</i>-<i>V</i>centers in diamond (1989)

Upon the cw optical excitation of N-V centers in diamond, a spin alignment in the ensemble of nonexcited N-V defects in the electron spin-triplet ground state is induced. When the diamond sample is subjected to magnetic fields of suitable directions and strengths, cross relaxation (CR) and level anticrossing are found to affect the ground-state spin alignment as well as the intensity of the emission due to the photoexcited N-V centers. In this paper, a study of the dynamics involved in the cross-relaxation and autocrossing processes is reported, utilizing techniques for the optical detection of spin-coherent transients. A major finding is that when CR conditions prevail, the stimulated spin-echo and spin-locking signals decay at a rate about three times faster than in the situation in which CR does not occur. The results are accounted for by considering the magnetic dipole-dipole interactions within the ensemble of N-V centers in the triplet ground state in a memory function approach.
Can Immunity to Breast Cancer Eliminate Residual Micrometastases? (2013)

An effective immune response has the potential for breast cancer sterilization with marked reduction in the potential for disease relapse. Adaptive type I immune cells uniquely have the capability of (i) cytotoxic T-cell activation and proliferation until all antigen expressing cells are eradicated, (ii) traversing endothelial barriers to penetrate tumor deposits wherever they occur, and (iii) immunologic memory, which allows the persistence of destructive immunity over the years it may take for breast cancer micrometastases to become clinically evident. Numerous recent investigations suggest that some breast cancers stimulate the type of immunity that results in a decreased risk of relapse. Moreover, the endogenous type I tumor microenvironment or type I immunity induced by drugs or biologic agents may improve response to standard therapies, further lowering the probability of disease recurrence.
Developmental plasticity of red blood cell homeostasis (2014)

Most human physiologic set points like body temperature are tightly regulated and show little variation between healthy individuals. Red blood cell (RBC) characteristics such as hematocrit and mean cell volume are stable within individuals but can vary by 20% from one healthy person to the next. The mechanisms for the majority of this inter-individual variation are unknown and do not appear to involve common genetic variation. Here, we show that environmental conditions present during development, namely in utero iron availability, can exert long-term influence on a set point related to the RBC life cycle. In a controlled study of rhesus monkeys and a retrospective study of humans, we use a mathematical model of in vivo RBC population dynamics to show that in utero iron deficiency is associated with a lowered threshold for RBC clearance and turnover. This in utero effect is plastic, persisting at least 2 years after birth and after the cessation of iron deficiency. Our study reports a rare instance of developmental plasticity in the human hematologic system and also shows how mathematical modeling can be used to identify cellular mechanisms involved in the adaptive control of homeostatic set points.
Advanced Fluorescent Polymer Probes for the Site-Specific Labeling of Proteins in Live Cells Using the HaloTag Technology (2019)

We report the site-specific and covalent bioconjugation of fluorescent polymer chains to proteins in live cells using the HaloTag technology. Polymer chains bearing a Halo-ligand precisely located at their α-chain-end were synthesized in a controlled manner owing to the RAFT polymerization process. They were labeled in lateral position by several organic fluorophores such as AlexaFluor 647. The resulting Halo-ligand polymer probe was finally shown to selectively recognize and label HaloTag proteins present at the membrane of live cells using confocal fluorescence microscopy. Such a polymer bioconjugation approach holds great promises for various applications ranging from cell imaging to cell surface functionalization.
Peronospora-like fungi (Chromista, Peronosporales) parasitic on Brassicaceae and related hosts (2002)

The genus Peronospora is emended and its type species, P. rumicis, is redescribed and illustrated. A new genus, Hyaloperonospora Constant., with 6 new combinations (H. floerkeae, H. lepidii-perfoliati, H. lunariae, H. niessleana, H. parasitica, and H. tri
Structure-Activity Relationship Studies on ADAM Protein-Integrin Interactions (2007)

The ADAM (a disintegrin and metalloprotease) family of proteins possess multi-domain structures composed of a signal peptide, a prodomain, a metalloprotease domain, a disintegrin-like domain, a cysteine rich domain, an epidermal growth factor-like domain, a transmembrane domain and cytoplasmic tail. The disintegrin-like domain shares sequence similarity with the soluble venom disintegrins, a family of proteins which are potent inhibitors of integrin-mediated platelet aggregation and cell adhesion. Several ADAMs have been reported to interact with integrins, and the disintegrin-like domain may be crucial part in this respect. A description of structure-activity relationship of ADAM proteins interacting with integrin is outlined in this review. The review highlights recent reports on potential integrin family for ADAMs and how ADAMs selectively modulate interaction for integrin mediated cell function. Lastly, it describes progress in understanding the structural features and functional roles of the ADAMs in normal and pathological conditions and how this insight may assist the development of new therapeutic approaches.
Transient transfection and expression of firefly luciferase in Giardia lamblia. (1995)

We have developed a gene transfer system for the protozoan parasite Giardia lamblia. This organism is responsible for many cases of diarrhea worldwide and is considered to be one of the most primitive eukaryotes. Expression of a heterologous gene was detected in this parasite after electroporation with appropriate DNA constructs. We constructed a series of transfection plasmids using flanking sequences of the Giardia glutamate dehydrogenase (GDH) gene to drive expression of the firefly luciferase reporter gene. The optimal construct consisted of a GDH/luciferase fusion gene in which the first 18 codons of the GDH gene immediately preceded the luciferase gene; this fusion gene was flanked by the upstream and downstream sequences of the GDH gene. Electroporation of this construct into Giardia yielded luciferase activity that was 3000- to 50,000-fold above background. Removal of either the 5' or 3' GDH flanking sequences from this construct resulted in significantly reduced luciferase activity, and removal of both flanking sequences reduced luciferase activity to background levels. Luciferase activity was proportional to the amount of DNA electroporated and was maximal at 6 hr after electroporation.