gebhart/patrepeval huggingface dataset:
In Vivo Survival and Function of Transplanted Rat Cardiomyocytes (1996)

Recent studies have demonstrated the feasibility of transplanting fetal mouse cardiomyocytes into the hearts of adult syngeneic mice. However, the function of the transplanted cardiomyocytes and their capacity to survive in fibrous connective tissue were not assessed. In the present study, we evaluated the viability and contractility of transplanted fetal and neonatal rat cardiomyocytes in the connective tissue of the adult rat hindlimb. Purified fetal or neonatal rat cardiomyocytes were cultured. These cells contained sarcomeres, formed junctions composed of desmosomes and fascia adherens, and contracted regularly and spontaneously. A fetal or neonatal cardiomyocyte suspension was injected into the subcutaneous tissue of adult rat hindlimbs. Cyclosporin A (5 mg/kg) was administered subcutaneously daily for the 3-month duration of the study, at which time the animals were killed. The transplanted cardiomyocytes formed 'tissue' in vivo that increased in size for the first 2 weeks and remained the same size at the third week. The tissue derived from the transplanted fetal cardiomyocytes contracted spontaneously at a rate of 73 +/- 12 bpm, and that from the neonatal cardiomyocytes contracted at a rate of 43 +/- 21 bpm. The electrocardiogram was similar to that seen in myocardium with an idioventricular rhythm. Histologically, the tissue appeared to be cardiac muscle with sarcomeres. Angiogenesis occurred in the cardiomyocyte graft. In summary, a cell suspension of cultured fetal and neonatal rat cardiomyocytes transplanted into the adult rat hindlimb formed contractile cardiac tissue in the subcutaneous connective tissue.
A Controlled Study of a Lecithinized Delivery System of Curcumin (Meriva®) to Alleviate the Adverse Effects of Cancer Treatment (2013)

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view.
Control of fertility by metabolic cues (1996)

In female mammals, reproduction is extremely sensitive to the availability of oxidizable metabolic fuels. When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening, reproductive attempts are suspended in favor of processes necessary for individual survival. Both reproductive physiology and sexual behaviors are influenced by food availability. Nutritional effects on reproductive physiology are mediated by changes in the activity of gonadotropin-releasing hormone (GnRH) neurons in the forebrain, whereas the suppression of sexual behaviors appears to be due, at least in part, to decreases in estrogen receptor in the ventromedial hypothalamus. Work using pharmacological inhibitors of glucose and fatty acid oxidation indicates that reproductive physiology and behavior respond to short-term (minute-to-minute or hour-to-hour) changes in metabolic fuel oxidation, rather than to any aspect of body size or composition (e.g., body fat content or fat-to-lean ratio). These metabolic cues seem to be detected in the viscera (most likely in the liver) and in the caudal hindbrain (probably in the area postrema). This metabolic information is then transmitted to the GnRH-secreting or estradiol-binding effector neurons in the forebrain. There is no evidence to date for direct detection of metabolic cues by these forebrain effector neurons. This metabolic fuels hypothesis is consistent with a large body of evidence and seems to account for the infertility that is seen in a number of situations, including famine, eating disorders, excessive exercise, cold exposure, lactation, some types of obesity, and poorly controlled diabetes mellitus.
Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease (1995)

<h3>Objective.</h3> —Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 alal- (<i>APOE</i>ε4) is a risk factor for familial AD. To determine if<i>APOE</i>ε4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with<i>APOE</i>ε4 and 19 relatives without<i>APOE</i>ε4. We also compared them with seven patients with probable AD. <h3>Design.</h3> —After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. <h3>Setting.</h3> —University medical center. <h3>Patients.</h3> —At-risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with<i>APOE</i>ε4 did not differ from those without<i>APOE</i>ε4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). <h3>Main Outcome Measures.</h3> —Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. <h3>Results.</h3> —Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with<i>APOE</i>ε4 compared with those without<i>APOE</i>ε4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with<i>APOE</i>ε4. <h3>Conclusions.</h3> —These results suggest that the inheritance of<i>APOE</i>ε4 is associated with reduced cerebral parietal metabolism and increased asymmetry in nondemented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder. (<i>JAMA</i>. 1995;273:942-947)
Interactions Between Kinases and Phosphatases in the Rapid Control of Brain Aromatase (2005)

Aromatization of testosterone into oestradiol plays a key role in the activation of male sexual behaviour in many vertebrate species. Rapid changes in brain aromatase activity have recently been identified and the resulting changes in local oestrogen bioavailability could modulate fast behavioural responses to oestrogens. In quail hypothalamic homogenates, aromatase activity is down-regulated within minutes by calcium-dependent phosphorylations in the presence of ATP, MgCl2 and CaCl2 (ATP/Mg/Ca). Three kinases (protein kinases A and C and calmodulin kinase; PKA, PKC and CAMK) are potentially implicated in this process. If kinases decrease aromatase activity in a reversible manner, then it would be expected that the enzymatic activity would increase and/or return to baseline levels in the presence of phosphatases. We showed previously that 0.1 mM vanadate (a general inhibitor of protein phosphatases) significantly decreases aromatase activity but specific protein phosphatases that could up-regulate aromatase activity have not been identified to date. The reversibility of aromatase activity inhibition by phosphorylations was investigated in the present study using alkaline and acid phosphatase (Alk and Ac PPase). Unexpectedly, Alk PPase inhibited aromatase activity in a dose-dependent manner in the presence, as well as in the absence, of ATP/Mg/Ca. By contrast, Ac PPase completely blocked the inhibitory effects of ATP/Mg/Ca on aromatase activity, even if it moderately inhibited aromatase activity in the absence of ATP/Mg/Ca. However, the addition of Ac PPase was unable to restore aromatase activity after it had been inhibited by exposure to ATP/Mg/Ca. Taken together, these data suggest that, amongst the 15 potential consensus phosphorylation sites identified on the quail aromatase sequence, some must be constitutively phosphorylated for the enzyme to be active whereas phosphorylation of the others is involved in the rapid inhibition of aromatase activity by the competitive effects of protein kinases and phosphatases. Two out of these 15 putative phosphorylation sites occur in an environment corresponding to the consensus sites for PKC, PKA (and possibly a CAMK) and, in all probability, represent the sites whose phosphorylation rapidly blocks enzyme activity.
Passive acquired mucosal immunity to group A streptococci by secretory immunoglobulin A. (1988)

We present a model in which animals are passively immunized at a mucosal site, allowing one to evaluate immunological protection at the mucosal level only. Affinity-purified, anti-M protein sIgA administered intranasally protected mice against systemic infection after intranasal challenge with group A streptococci. In contrast, anti-M protein serum Ig administered intranasally was not protective at this site, although it neutralized the antiphagocytic property of M protein and promoted phagocytosis. Protection by sIgA occurred despite the lower immunoreactivity of sIgA to purified M protein compared with serum Ig. The data suggest that sIgA can protect at the mucosa and may preclude the need for opsonic IgG in preventing streptococcal infection.
Filter replicas and permanent collections of recombinant DNA plasmids (1979)

A permanent, ordered collection of 23,000 recombinant DNA plasmids containing Drosophila melanogaster DNA has been established. Simple and practical methods for storing and manipulating this collection were developed. In addition, an improved, simple and inexpensive method for making paper filter replicas of such an ordered collection and of a high density (10,000 colonies/petri dish) unordered collection was developed. These filter replicas are suitable for nucleic acid hybridization screens of recombinant DNA colinies and each filter replica can be used for many (greater than 5) successive screens. The kinetics of this hybridization reaction were examined and allow design of experiments that detect colony complementarity to a nucleic acid that is 0.5% of the hybridization probe.
A system for probing Casimir energy corrections to the condensation energy (2020)

In this article, we present a nanoelectromechanical system (NEMS) designed to detect changes in the Casimir energy. The Casimir effect is a result of the appearance of quantum fluctuations in an electromagnetic vacuum. Previous experiments have used nano- or microscale parallel plate capacitors to detect the Casimir force by measuring the small attractive force these fluctuations exert between the two surfaces. In this new set of experiments, we aim to directly detect the shifts in the Casimir energy in a vacuum due to the presence of the metallic parallel plates, one of which is a superconductor. A change in the Casimir energy of this configuration is predicted to shift the superconducting transition temperature (<i>T</i> <sub>c</sub>) because of the interaction between it and the superconducting condensation energy. In our experiment, we take a superconducting film, carefully measure its transition temperature, bring a conducting plate close to the film, create a Casimir cavity, and then measure the transition temperature again. The expected shifts are smaller than the normal shifts one sees in cycling superconducting films to cryogenic temperatures, so using a NEMS resonator in situ is the only practical way to obtain accurate, reproducible data. Using a thin Pb film and opposing Au surface, we observe no shift in <i>T</i> <sub>c</sub> >12 µK down to a minimum spacing of ~70 nm at zero applied magnetic field.
Anamorphic optical systems using programmable spatial light modulators (1992)

Anamorphic optical systems with different horizontal and vertical magnifications are constructed by using programmable anamorphic lenses written on a magneto-optic spatial light modulator.
A New Interpretation of Serum Albumin Surface Passivation (2004)

We report our efforts to understand the passivation behavior of bovine serum albumin (BSA) and its structural changes at interfaces using X-ray photoelectron spectroscopy and contact angle measurements. The work investigated protein adsorption on two surfaces with widely different surface free energies. We investigated a hydrophilic surface represented by clean glass and a hydrophobic surface prepared by modifying a glass surface with a fluorinated self-assembled monolayer. The experiments indicate that, on the hydrophilic surface, BSA adsorbs in a two-step process and passivation of the surface is reached. Adsorption of BSA on the hydrophobic surface also continues until passivation of the surface. In contrast, however, the process occurs in a single step. Contact angle measurements show that at the completion of the adsorption process in both cases the same contact angle is reached despite the different adsorption behavior. We believe that this strongly indicates that the same outer surface composition is obtained for both surfaces despite different passivation routes. We postulate that there is a controlled loss of tertiary structure of BSA in descrete units that allows a specific structure to be formed on the surface that inhibits further protein adsorption regardless of the initial surface composition.
Promotion of articular cartilage matrix vesicle mineralization by type I collagen (2008)

Cartilage matrix changes that occur with osteoarthritis, such as increased quantities of type I collagen and reduced proteoglycan levels, may promote ACV mineralization.
Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2. (2001)

To improve the immunogenicity of melanoma self-antigens, we used a novel strategy of nonviral genetic vaccination coupled with muscle electroporation. Electroporation-enhanced immunization with plasmids encoding either human gp100 or mouse TRP-2 antigens induced only partial rejection of B16 melanoma challenge. However, immunization with a combination of these two antigens caused tumor rejection in 100% of the immunized mice. Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2. Immune cell depletion experiments identified CD8+ T lymphocytes as the primary effectors of antitumor immunity. Most importantly, polyimmunization led to the generation of a therapeutic immune response that significantly improved the mean survival time of mice bearing established lung metastases. These results validated the usefulness of electroporation-enhanced, nonviral genetic immunization for the active immunotherapy of cancer and indicated that using a combination of different tumor antigens may be a decisive strategy for a successful therapeutic vaccination.
Meeting an expanding educational role for ambulatory care services. (1988)

The mid-1980s have been marked by a growing shift in the locus of health care delivery: from the in-patient setting to ambulatory care programs. As a result of cost containment strategies--exemplified by the diagnosis related group method for hospital reimbursement--the ambulatory care network has assumed responsibility for many patients with advanced or complicated diseases. This increased responsibility is in addition to preventive services, health maintenance, and routine care of acute and chronic conditions. This shift not only requires expansion of the current system for delivery of primary care services, but will also increase the role that organized ambulatory care programs will have to play in the education of health professionals. On the basis of a ten-year experience in utilizing two county funded neighborhood health centers for primary care training of family practice residents and medical students, undergraduate and postgraduate medical education programs are discussed in terms of the changes they impose on ambulatory care program organization (e.g., staffing, space, patient assignment and consent), proposed financing, and agreements with educational institutions. The increased administrative burden of training programs is offset by benefits which include staff satisfaction, enhanced quality of care, and an increase in the pool of appropriately trained physicians.
Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection (2003)

Engineered Cys2His2 zinc finger proteins (ZFPs) can mediate regulation of endogenous gene expression in mammalian cells. Ideally, all zinc fingers in an engineered multifinger protein should be optimized concurrently because cooperative and context-dependent contacts can affect DNA recognition. However, the simultaneous selection of key contacts in even three fingers from fully randomized libraries would require the consideration of >10(24) possible combinations. To address this challenge, we have developed a novel strategy that utilizes directed domain shuffling and rapid cell-based selections. Unlike previously described methods, our strategy is amenable to scale-up and does not sacrifice combinatorial diversity. Using this approach, we have successfully isolated multifinger proteins with improved in vitro and in vivo function. Our results demonstrate that both DNA binding affinity and specificity are important for cellular function and also provide a general approach for optimizing multidomain proteins.
Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. (2001)

The lack of functional p53 in many cancer cells offers a therapeutic target for treatment. Cells lacking p53 would not be anticipated to demonstrate a G(1) checkpoint and would depend on the G(2) checkpoint to permit DNA repair prior to undergoing mitosis. We hypothesized that the G(2) checkpoint abrogator could preferentially kill p53-inactive cancer cells by removing the only checkpoint that protects these cells from premature mitosis in response to DNA damage. Because Wee1 kinase is crucial in maintaining G(2) arrest through its inhibitory phosphorylation of Cdc2, we developed a high-throughput mass screening assay and used it to screen chemical library for Wee1 inhibitors. A pyridopyrimidine class of molecule, PD0166285 was identified that inhibited Wee1 at a nanomolar concentration. At the cellular level, 0.5 microM PD0166285 dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines tested. PD0166285 abrogates irradiation-induced G(2) arrest as shown by both biochemical markers and fluorescence-activated cell sorter analysis and significantly increases mitotic cell populations. Biologically, PD0166285 acts as a radiosensitizer to sensitize cells to radiation-induced cell death with a sensitivity enhancement ratio of 1.23 as shown by standard clonogenic assay. This radiosensitizing activity is p53 dependent with a higher efficacy in p53-inactive cells. Thus, G(2) checkpoint abrogators represent a novel class of anticancer drugs that enhance cell killing of conventional cancer therapy through the induction of premature mitosis.
Photoreversible Viscosity Changes and Gelation in Mixtures of Hydrophobically Modified Polyelectrolytes and Photosensitive Surfactants (2004)

The viscosity and gelation of mixtures of hydrophobically modified poly(acrylic acid) (HM-PAA) and a cationic photosensitive surfactant can be controlled reversibly by changing between UV and visible light irradiation of the sample. At the critical aggregation concentration (cac) of the surfactant, micellar aggregates form on the polymer and solubilize the alkyl side chains grafted on the HM-PAA, leading to physical cross-linking and gelation. The hydrophobic trans (visible light) form, with a planar azobenzene group in the surfactant tail, has a lower cac than the more polar cis (UV light) form, resulting in gelation at lower surfactant concentrations under visible light. Reversible viscosity changes of up to 2 orders of magnitude are observed upon exposure to UV or visible light. Observed viscosity maxima of 5.6 × 104 cPa for the trans form and 2.2 × 103 cPa for the cis form of the surfactant suggest that the trans-form surfactant micelles are more effective at solubilizing the alkyl side chains than are the more hydrophilic cis-form micelles. Steady-state fluorescence studies of the cationic probe crystal violet reveal an enhancement in binding of the crystal violet to sites adjacent to bound surfactant molecules as the surfactant concentration is initially increased prior to the cac, followed by a decrease in binding of crystal violet at concentrations above the cac due to a decrease in the number of available binding sites as the anionic polyelectrolyte wraps around the newly formed cationic micelles. The nearest-neighbor binding is greater in the trans form as opposed to the cis. Surface tension values decrease slowly with increasing surfactant concentration below the cac due to strong binding of the surfactant to the polyelectrolyte, followed by a large drop in the surface tension at the cac that results from release of bound surfactant upon micelle formation and subsequent wrapping of the surfactant aggregates by the polyelectrolyte. Dynamic viscoelastic measurements are typical of gel systems with G‘ > G‘ ‘ above the cac and also indicate that approximately 25% of the polymer chains are elastically effective in the presence of the trans form, while only 7.5% of polymer chains participate in cross-linking in the presence of the cis form of the surfactant.
Biomedical Applications of On-Line Preconcentration-Capillary Electrophoresis Using an Analyte Concentrator: Investigation of Design Options (1995)

Abstract A method to perform on-line sample preconcentration of serum immunoglobulin E by affinity capture is described. Purified anti-IgE antibodies were covalently bound to an analyte concentrator-reaction chamber or cartridge. The immunoglobulins (IgE) were bound to and eluted from the cartridge by the optimum dissociating buffer system, and the eluent(s) were then subjected to capillary electrophoresis. The first design used was a 5 mm solid-phase cartridge fabricated by assembling a bundle of multiple microcapillaries in which a monoclonal antibody directed against IgE was covalently bound to the surface of every microcapillary. The whole assembly was connected, through sleeve connectors, to the capillary column for affinity capillary electrophoresis. The second design used consisted of an analyte concentrator-reaction chamber that was fabricated from a solid rod of glass. Several small diameter passages or through holes containing a similar surface area was tested for the same experiments and performance as described above. A major advantage of these designs, over previously described designs, is the absence of frits and beads. The previously reported designs consisted of derivatized beads confined to the concentrator cartridge by a frit at each end. After limited usage of the cartridge, the beads tends to pack at the outer frit. This lead to restricted flow through the concentrator chamber and ultimately clogging of the system. The designs reported here allows for a constant electroosmotic flow, superior reproducibility of the electropherograms, a reduced possibility of blocking the microcapillaries, and increase number of usages of the cartridge. The use of this novel analyte concentrator design for the determination of immunoglobulins in biological fluids is demonstrated by capillary electrophoresis of IgE in serum. The general utility of this technique for a variety of biomedical applications is discussed.