gebhart/patrepeval huggingface dataset:
Surfactants in nonpolar oils: agents of electric charging and nanogel templates (2012)

This thesis studies the formation of mobile and surface-bound electric charges in nonpolar liquids. Unlike aqueous media with their natural abundance of charged species, liquids of low dielectric constant do not readily accommodate charges, but can do so in the presence of certain surfactant additives. Surfactant-mediated charging in nonpolar oils has long been exploited industrially, but the underlying charging mechanisms are far from understood. The present work seeks clarification by comparing the effect of ionic and nonionic surfactants on the conductivity of nonpolar solutions and the electrophoretically observable surface charge of suspended polymer particles. Both types of surfactant are found to generate mobile ions in solution as well as particle charge; and in the more surprising case of nonionic surfactants, the occurrence of particle charge and screening ions is confirmed independently by measurements of the electrostatic particle interaction energy. A systematic variation of the particle material and functionalization, the residual water content, and the surfactant concentration above and below the critical micelle concentration provides insights about the possible charging pathways.&#13;\n&#13;\nReverse surfactant micelles are explored not only as charging agents, but also as reactors and templates for the synthesis of novel nanogels with promise for drug delivery. Synthesis via copper-free Click chemistry is shown to allow for better control of the particle size than a more conventional polymerization scheme, while avoiding metal catalysts and free radicals that are considered hazardous for most biomedical applications.
The Optics of Thermotropic Liquid Crystals (1998)

Liquid crystals form the basis of many low-power consumer display applications (calculators, watches, lap-top computers, photocopiers). This text explains how these displays work from an optical viewpoint, providing an examination of aspects of the optics of liquid crystals. This book incorporates research level developments and perspectives in optics from a materials science and physics viewpoint, as well as exploiting defect structures and non-linear optics.
Antiviral activity of Herba Patrinea (a Chinese medicinal herb) against respiratory syncytial virus in vitro (2003)

Respiratory syncytial virus (RSV) has long been considered an important cause of severe lower respiratory tract infection in infants and young children throughout the world. Unfortunately, no effective treatment of RSV exists. Therefore, New agents are needed to reduce the impact of RSV. We have studied the anti-viral effect of traditional Chinese midicinal herbs for over ten years and find Herba Patrinea (a Chinese medicinal herb) has the anti-RSV effect in vitro. In this study, the Herba Patrinea was extracted with hot water, condensed and sterilized. The cytotoxicity of the aqueous extract was tested by adding the diluted extract directly to HeLa cells and its effect on anti-RSV was estimated by the CPEI assay. As a result, the median cytotoxic concentration <TEX>$(CC_{50})$</TEX> of Herba Patrinea was 32 mg/ ml by morphological observation, the median effective concentration (50% effective concentration, <TEX>$EC_{50}$</TEX>) of the Herba Patrinea against replication of the Long strain of RSV in HeLa cells were 1.25 mg/ml. The selectivity index <TEX>$(SI=CC_{50}/EC{50})$</TEX> is 25.6. Moreover, Herba Patrinea gave a dose-dependent response in inhibiting RSV. In time of addition experiment, Herba Patrinea inhibited replication of RSV in HeLa cells when it was added at 0h, 2h, and 4h after virus infection. In summary, the results of this study suggest Herba Patrinea may be a novel anti-RSV drug and it is worthy of further studying.
Effect of CD80 and CD86 blockade and anti‐interleukin‐12 treatment on mouse acute graftversus‐host disease (1996)

We investigated the efficacy of a combination of anti-CD80 and CD86 (CD80 + 86) monoclonal antibodies (mAb), anti-interleukin (IL)-12 mAb, or both, for prophylaxis in a mouse acute graft-versus-host-disease (GVHD) model. The treatment with a combination of anti-CD80 + 86 mAb efficiently reduced the lethality of GVHD, whereas mAb against either CD80 or CD86 alone had an effect. A delay in lymphocyte reconstitution and GVHD-associated histological changes in organs was observed at 30 days post-bone marrow transplantation (BMT) even in the anti-CD80 + 86 mAb-treated mice, although these manifestations were resolved by 100 days. In vitro, host alloantigen-specific T cell proliferative responses and generation of CTL were significantly reduced by anti-CD80 + 86 treatment. Furthermore, anti-CD80 + 86 mAb preferentially inhibited the production of interferon (IFN)-gamma, but not IL-4 and IL-10, when cultures were assayed at 21 days. Although the anti-IL-12 mAb treatment alone inhibited the generation of cytotoxic T lymphocytes and IFN-gamma production in vitro, administration of anti-IL-12 mAb in vivo reversed the beneficial effects of anti-CD80 + 86 treatment on host survival post-BMT. The adverse effect of anti-IL-12 treatment seems to result from impairment of natural immunity and hematopoiesis, rather than as a consequence of an incomplete blockade of T helper (Th)1 responses. Our results suggest that the prevention of GVHD-induced death results from the efficient blockade of Th1 cell activation by the anti-CD80 + 86 treatment. However, further treatment is required for a complete prevention of GVHD, which seems to be partly mediated by Th2 cells.
p300/cAMP-responsive Element-binding Protein Interactions with Ets-1 and Ets-2 in the Transcriptional Activation of the Human Stromelysin Promoter (1999)

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.
Geographic, clinical, serologic, and molecular evidence of granulocytic ehrlichiosis, a likely zoonotic disease, in Minnesota and Wisconsin dogs (1996)

Seventeen Minnesota and Wisconsin dogs with granulocytic ehrlichosis were studied. The diagnoses were made by finding ehrlichia morulae in peripheral blood neutrophils. Eight dogs were studied retrospectively, and nine dogs were studied prospectively. The medical records of all dogs were reviewed. Eighty-eight percent of the dogs were purebred and 76% were spayed females. The median age was 8 years. Sixty-five percent of the cases were diagnosed in October and November. Fever and lethargy were the most common clinical signs. The most frequent laboratory findings were lymphopenia, thrombocytopenia, elevated activities of serum alkaline phosphatase and amylase, and hypoalbuminemia. No dogs seroreacted to Ehrlichia canis or Ehrlichia chaffeensis antigens, which are cross-reactive. Seventy-five percent of the dogs tested during the acute phase of disease and 100% of the dogs tested during convalescence were seropositive for E. equi antigens. Granulocytic ehrlichial 16S rRNA gene DNAs from six dogs were amplified by PCR. Sequence analysis of a 919-bp sequence of the ehrlichial 16S rRNA gene amplified by PCR from the blood of two dogs revealed the agent to be identical to the agent of human granulocytic ehrlichiosis in Minnesota and Wisconsin and to be very similar to E. equi and Ehrlichia phagocytophila and less similar to E. canis, Ehrlichia ewingii, and E. chaffeensis. The geographic, clinical, serologic, and molecular evidence indicates that granulocytic ehrlichiosis in Minnesota and Wisconsin dogs is not caused by E. ewingii, but suggests that it is a zoonotic disease caused by an agent closely related to E. equi and that dogs likely contribute to the enzootic cycle and human infection.
Relationship of Chemical Structure and Antimicrobial Activity of Alkyl Amides and Amines (1972)

Contrary to the limited effects of alkyl amides and their corresponding N-derivatives, alkyl amines affected both gram-positive and gram-negative organisms. As with other alkyl derivatives the most sensitive gram-negative bacteria were usually more resistant than the most resistant gram-positive bacteria. Compounds with a chain-length of 11 to 15 are most active. Although some of the general properties relating the activity of fatty acids to their antimicrobial action are similar to those of amine compounds, the amines are unique in that monounsaturation does not increase compound activity. The possible modes of action of these compounds are discussed.
Automated exercise progression in simulation-based training (1994)

As simulator-based training systems become more complex, the amount of effort required to generate, monitor, and maintain training exercises multiplies greatly. This has significantly increased the burden on the instructors, potentially making the training experience less efficient as well as less effective. Research on intelligent tutoring systems (ITS) has largely addressed this issue by replacing the instructor with a computer model of the appropriate pedagogical concepts and the domain expertise. While this approach is highly desirable, the effort required to develop and maintain an ITS can be quite significant. A more modest as well as practical alternative to an ITS is the development of intelligent computer-based tools that can support the instructors in their tasks. The advantage of this approach is that various tools can be developed to address the different aspects of the instructor's duties. Moreover, without the burden of having to replace the instructor, these tools are more easily developed and fielded in existing trainers. One aspect of an instructor's task is to assess the students' performance after each training exercise and select the next exercise based on their previous performances. It would clearly be advantageous if this exercise selection process were to be automated, thus relieving the instructor of a significant burden and allowing him to concentrate on other tasks. Therefore, the focus of this paper is the development of a stand-alone system capable of determining exercise progression and remediation automatically during a training session in a simulator-based trainer, on the basis of the students's past performance. Instructional heuristics were developed to carry out the exercise progression process. A prototype was developed and applied to gunnery training on the Army M1 main battle tank.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Biology of T memory type 1 cells (2001)

Engagement of inhibitory natural killer (NK) cell receptors for MHC class I molecules (NKR) can impair NK-cell activation programs. Inhibitory NKR thus confer to NK cells the capacity to discriminate between MHC class I+ and MHC class I- target cells, and are therefore involved in the control of NK-cell tolerance to self, as well as in the elimination of MHC class I- distressed cells by NK cells. In human and mouse, a subset of alphabeta T cells also express inhibitory NKR at their surface, but the biological function of inhibitory NKR on T cells remains to be precisely elucidated. We refer to these cells as T memory type 1 (Tm1) cells, and review here the phenotypic and functional features of this subset of memory-phenotype CD8+ alphabeta T cells. In vitro studies suggest that inhibitory NKR are involved in the peripheral control of T-cell self-tolerance. In vitro and in vivo analysis have revealed a novel biological function for inhibitory NKR when expressed on T cells. Indeed, engagement of inhibitory NKR on T cells provides them with survival signals against activation-induced cell death. Thus, sensing of self-MHC class I molecules by inhibitory NKR displayed on alphabeta T cells leads to the in vivo accumulation of Tm1 cells.
Anion‐Templated Synthesis (2003)

In contrast to the well-studied templating properties of cationic and neutral species there are relatively few examples of anion-templated syntheses. This is attributed to some of the intrinsic properties of anions such as their diffuse nature, pH sensitivity, and their relative high solvation free energies. However, the increasing number of anion-templated assemblies reported over the past few years demonstrates that these limitations are not as critical as first thought. This review summarizes the most important results on the use of anions as directing agents for the syntheses of a wide range of inorganic and organic assemblies (such as macrocycles, cages, helicates, rotaxanes, and extended structures). It is hoped that this will stimulate a closer look into this emerging area of supramolecular chemistry.
Botulinum Toxin in Movement Disorders (2007)

Botulinum toxin inhibits the vesicular release of acetylcholine in the neuromuscular junction, resulting in a transient, localized paralysis when small doses are injected. The successful use of serotypes A and B in conditions with muscle overactivity such as dystonia and spasticity has been well established. Apart from approved indications, treatment with botulinum toxin injections is attempted in a variety of new areas of neurology, including tremor, tics, and myoclonus. This article provides an update on the uses of botulinum toxin in the field of movement disorders and draws special attention to theoretical and practical treatment issues of primary and secondary dystonic disorders. Long-term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for the increasing number of off-label indications. However, controlled studies for many conditions are lacking, and more clinical trials in many different areas are warranted.
Binding Mode Characterization and Early in Vivo Evaluation of Fragment-Like Thiols as Inhibitors of the Virulence Factor LasB from Pseudomonas aeruginosa (2018)

The increasing emergence of antibiotic resistance necessitates the development of anti-infectives with novel modes of action. Targeting bacterial virulence is considered a promising approach to develop novel antibiotics with reduced selection pressure. The extracellular collagenase elastase (LasB) plays a pivotal role in the infection process of Pseudomonas aeruginosa and therefore represents an attractive antivirulence target. Mercaptoacetamide-based thiols have been reported to inhibit LasB as well as collagenases from clostridia and bacillus species. The present work provides an insight into the structure-activity relationship (SAR) of these fragment-like LasB inhibitors, demonstrating an inverse activity profile compared to similar inhibitors of clostridial collagenase H (ColH). An X-ray cocrystal structure is presented, revealing distinct binding of two compounds to the active site of LasB, which unexpectedly maintains an open conformation. We further demonstrate in vivo efficacy in a Galleria mellonella infection model and high selectivity of the LasB inhibitors toward human matrix metalloproteinases (MMPs).
Evaluation of the in Vitro Sensitivity of Neisseria Catarrhalis to Antibiotics with Respect to Acute Otitis Media (1970)

The in vitro sensitivity of 108 strains of Neisseria catarrhalis to ampicillin, penicillin G, penicillin V, erythromycin and oxytetracycline was determined. The strains were isolated, inter alia, from ear exudate of children with acute otitis media. Ampicillin was more active than penicillin G, which was followed by erythromycin, penicillin V and oxytetracycline. In acute otitis media caused by N. catarrhalis, an effect could probably be expected of ampicillin and of penicillin V treatment with daily dosages of 50 mg per kg body weight. Erythromycin would be preferred to oxytetracycline in those instances in which penicillins are contraindicated.
Development of Ionic Currents Underlying Changes in Action Potential Waveforms in Rat Spinal Motoneurons (1998)

Development of ionic currents underlying changes in action potential waveforms in rat spinal motoneurons. J. Neurophysiol. 80: 3047-3061, 1998. Differentiation of the ionic mechanism underlying changes in action potential properties was investigated in spinal motoneurons of embryonic and postnatal rats using whole cell voltage- and current-clamp recordings. Relatively slow-rising, prolonged, largely Na+-dependent action potentials were recorded in embryonic motoneurons, and afterdepolarizing potentials were elicited in response to prolonged intracellular injections of depolarizing currents. Action potential amplitude, as well as its rates of rise and repolarization significantly increased, and an afterhyperpolarizing potential (AHP) became apparent immediately after birth. Concurrently, repetitive action potential firing was elicited in response to a prolonged current injection. To determine the ionic mechanism underlying these changes, the properties of voltage-gated macroscopic Na+, Ca2+, and K+ currents were examined. Fast-rising Na+ currents (INa) and slow-rising Ca2+ currents (ICa) were expressed early in embryonic development, but only INa was necessary and sufficient to trigger an action potential. INa and ICa densities significantly increased while the time to peak INa and ICa decreased after birth. The postnatal increase in INa resulted in overshooting action potential with significantly faster rate of rise than that recorded before birth. Properties of three types of outward K+ currents were examined: transient type-A current (IA), noninactivating delayed rectifier-type current (IK), and Ca2+-dependent K+ current (IK(Ca)). The twofold postnatal increase in IK and IK(Ca) densities resulted in shorter duration action potential and the generation of AHP. Relatively large IA was expressed early in neuronal development, but unlike IK and IK(Ca) its density did not increase after birth. The three types of K+ channels had opposite modulatory actions on action potential firing behavior: IK and IA increased the firing rate, whereas IK(Ca) decreased it. Our findings demonstrated that the developmental changes in action potential waveforms and the onset of repetitive firing were correlated with large increases in the densities of existing voltage-gated ion channels rather than the expression of new channel types.
“Patient‐Like” nude mouse metastatic model of advanced human pleural cancer (1994)

Pleural cancer in humans is a frequently occurring tumor. Recently, clinical trials have suggested that chemotherapy and immunotherapy administered intrapleurally may elicit responses in early-stage diseases. However, at radiological and pleural endoscopic evaluation, most of the patients are found to have a visceral pleural involvement that is generally refractory to therapy and leads to a poor prognosis. The goal of this study was to construct a nude mouse model of human parietal- and visceral-pleural cancer that could reflect the clinical picture for this disease. The model could then be useful for drug discovery for pleural cancer. A well-differentiated human lung adenocarcinoma was used as intact tissue for implantation. Ten mice underwent parietal-pleural implantation and ten mice visceral-pleural implantation via a novel thoracotomy procedure we have developed. Symptoms of tumor growth were determined from weight loss, respiratory distress, or debilitation. Actual tumor growth and spread were measured at autopsy. The mouse survival curves of each group were estimated by the Kaplan-Meier method and the difference of the median survival times was assessed by the Log-rank test. The slopes of mean-mouse weight curves were compared using a standard two-sample t-test. A 100% take rate was achieved in constructing the pleural cancer models. Tumor growth was initially assessed by symptomatology and survival: the median survival time was, respectively, 27.9 days and 31 days for visceral-pleural and parietal-pleural implanted groups (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Disulphide bonds and protein stability (1988)

Abstract The properties of disulphide bonds relevant to their roles in stabilizing protein conformation are reviewed. Natural disulphides can stabilize folded conformations substantially, in some cases to much greater extents than would be expected from just entropic effects on the unfolded state. The linkage relationship between conformational stability and disulphide stability is illustrated. Disulphides will not, however, increase protein stability if the disulphides are not maintained in the unfolded state or if instability is caused by processes, such as chemical modification or proteolysis, that are not linked to unfolding, either local or global. This is part of the reason why some recent attempts to increase protein stability by introducing new disulphides have had only modest success. Other reasons appear to be the severe energetic constraints on disulphide bond geometry and, in some cases, unfavourable effects of introducing Cys residues by mutation.