gebhart/patrepeval huggingface dataset:
G protein modulation of recombinant P/Q‐type calcium channels by regulators of G protein signalling proteins (2000)

1. Fast synaptic transmission is triggered by the activation of presynaptic Ca2+ channels which can be inhibited by Gbetagamma subunits via G protein-coupled receptors (GPCR). Regulators of G protein signalling (RGS) proteins are GTPase-accelerating proteins (GAPs), which are responsible for >100-fold increases in the GTPase activity of G proteins and might be involved in the regulation of presynaptic Ca2+ channels. In this study we investigated the effects of RGS2 on G protein modulation of recombinant P/Q-type channels expressed in a human embryonic kidney (HEK293) cell line using whole-cell recordings. 2. RGS2 markedly accelerates transmitter-mediated inhibition and recovery from inhibition of Ba2+ currents (IBa) through P/Q-type channels heterologously expressed with the muscarinic acetylcholine receptor M2 (mAChR M2). 3. Both RGS2 and RGS4 modulate the prepulse facilitation properties of P/Q-type Ca2+ channels. G protein reinhibition is accelerated, while release from inhibition is slowed. These kinetics depend on the availability of G protein alpha and betagamma subunits which is altered by RGS proteins. 4. RGS proteins unmask the Ca2+ channel beta subunit modulation of Ca2+ channel G protein inhibition. In the presence of RGS2, P/Q-type channels containing the beta2a and beta3 subunits reveal significantly altered kinetics of G protein modulation and increased facilitation compared to Ca2+ channels coexpressed with the beta1b or beta4 subunit.
State‐Space Feedback Control (2004)

This chapter describes several approaches to the design of feedback controllers for systems modeled in state space form, including multiple-input multiple-output (MIMO) systems. Static state feedback is a multidimensional extension of proportional control, and dynamic state feedback can be viewed as the state-space analog to PI (proportional integral) control. Pole placement design determines the poles needed to achieve the desired closed-loop properties and then computes the feedback gains required. Linear quadratic regulation (LQR) employs an optimization technique that parameterizes the trade-off between control error and control effort.
Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury (2009)

Traumatic spinal cord injury is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should, in principle, be preventable, no effective treatment options currently exist for patients with acute spinal cord injury (SCI). Excessive release of ATP by the traumatized tissue, followed by activation of high-affinity P2X7 receptors, has previously been implicated in secondary injury, but no clinically relevant strategy by which to antagonize P2X7 receptors has yet, to the best of our knowledge, been reported. Here we have tested the neuroprotective effects of a systemically administered P2X7R antagonist, Brilliant blue G (BBG), in a weight-drop model of thoracic SCI in rats. Administration of BBG 15 min after injury reduced spinal cord anatomic damage and improved motor recovery without evident toxicity. Moreover, BBG treatment directly reduced local activation of astrocytes and microglia, as well as neutrophil infiltration. These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses. Importantly, BBG is a derivative of a commonly used blue food color (FD&C blue No. 1), which crosses the blood-brain barrier. Systemic administration of BBG may thus comprise a readily feasible approach by which to treat traumatic SCI in humans.
Conus Peptides Targeted to Specific Nicotinic Acetylcholine Receptor Subtypes (1999)

The venoms of predatory cone snails represent a rich combinatorial-like library of evolutionarily selected, neuropharmacologically active peptides. A major fraction of the venom components are conotoxins--small, disulfide-rich peptides that potently and specifically target components of the neuromuscular system, particularly ligand- and voltage-gated ion channels. This review focuses on Conus peptides, which act at nicotinic acetylcholine receptors. These nicotinic antagonist peptides from Conus are broadly divided into two groups: those that act at the neuromuscular junction and those that act at subtypes of neuronal nicotinic acetylcholine receptors. The latter include peptides specific for the alpha 7, alpha 3 beta 2, and alpha 3 beta 4 nicotinic receptor subtypes. The degree of specificity exhibited by these peptides is remarkable, particularly given their relatively small size. As a group the nicotinic acetylcholine receptor-targeted Conus peptides represent an increasingly well-defined set of tools for probing the structure, function, and physiological role of nicotinic acetylcholine receptors.
Lactobacillus acidophilus LA 1 binds to cultured human intestinal cell lines and inhibits cell attachment and cell invasion by enterovirulent bacteria. (1994)

Four human Lactobacillus acidophilus strains were tested for their ability to adhere onto human enterocyte like Caco-2 cells in culture. The LA 1 strain exhibited a high calcium independent adhesive property. This adhesion onto Caco-2 cells required a proteinaceous adhesion promoting factor, which was present in the spent bacterial broth culture supernatant. LA 1 strain also strongly bound to the mucus secreted by the homogeneous cultured human goblet cell line HT29-MTX. The inhibitory effect of LA 1 organisms against Caco-2 cell adhesion and cell invasion by a large variety of diarrhoeagenic bacteria was investigated. As a result, the following dose dependent inhibitions were obtained: (a) against the cell association of enterotoxigenic, diffusely adhering and enteropathogenic Escherichia coli, and Salmonella typhimurium; (b) against the cell invasion by enteropathogenic Escherichia coli, Yersinia pseudotuberculosis, and Salmonella typhimurium. Incubations of L acidophilus LA 1 before and together with enterovirulent E coli were more effective than incubation after infection by E coli.
The Maternal Chromosome Set Is the Target of the T-DNA in thein PlantaTransformation ofArabidopsis thaliana (2000)

In planta transformation methods are now commonly used to transform Arabidopsis thaliana by Agrobacterium tumefaciens. The origin of transformants obtained by these methods has been studied by inoculating different floral stages and examining gametophytic expression of an introduced beta-glucuronidase marker gene encoding GUS. We observed that transformation can still occur after treating flowers where embryo sacs have reached the stage of the third division. No GUS expression was observed in embryo sacs or pollen of plants infiltrated with an Agrobacterium strain bearing a GUS gene under the control of a gametophyte-specific promoter. To identify the genetic target we used an insertion mutant in which a gene essential for male gametophytic development has been disrupted by a T-DNA bearing a Basta resistance gene (B(R)). In this mutant the B(R) marker is transferred to the progeny only by the female gametes. This mutant was retransformed with a hygromycin resistance marker and doubly resistant plants were selected. The study of 193 progeny of these transformants revealed 25 plants in which the two resistance markers were linked in coupling and only one plant where they were linked in repulsion. These results point to the chromosome set of the female gametophyte as the main target for the T-DNA.
Human Amniotic Mesenchymal Cells Have Some Characteristics of Cardiomyocytes (2005)

The results of the present study suggest that hAMC possess some characteristics of cardiomyocytes.
RESEARCH ARTICLE: Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia (2008)

The cellular basis of myelin deficits detected by neuroimaging in long-term survivors of periventricular leukomalacia (PVL) is poorly understood. We tested the hypothesis that oligodendrocyte lineage (OL) cell density is reduced in PVL, thereby contributing to subsequent myelin deficits. Using computer-based methods, we determined OL cell density in sections from 18 PVL and 18 age-adjusted control cases, immunostained with the OL-lineage marker Olig2. Myelination was assessed with myelin basic protein (MBP) immunostaining. We found no significant difference between PVL and control cases in Olig2 cell density in the periventricular or intragyral white matter. We did find, however, a significant increase in Olig2 cell density at the necrotic foci, compared with distant areas. Although no significant difference was found in the degree of MBP immunostaining, we observed qualitative abnormalities of MBP immunostaining in both the diffuse and necrotic components of PVL. Abnormal MBP immunostaining in PVL despite preserved Olig2 cell density may be secondary to arrested OL maturation, damage to OL processes, and/or impaired axonal-OL signaling. OL migration toward the "core" of injury may occur to replenish OL cell number. This study provides new insight into the cellular basis of the myelin deficits observed in survivors of PVL.
Neutral Endopeptidase 24.11 and Dipeptidyl Peptidase IV are Both Involved in Regulating the Metabolic Stability of Glucagon-like Peptide-1 in vivo (2005)

ConclusionDPP IV is the enzyme responsible for the initial inactivation of GLP-1, but NEP 24.11 plays a role in the subsequent elimination of both the intact peptide and the truncated metabolite. DPP IV inhibition protects intact GLP-1 from N-terminal truncation, leading to improved insulinotropic and anti-hyperglycaemic activity. However, NEP 24.11 inhibition also contributes to improving the metabolic stability of GLP-1 in vivo. Combined NEP 24.11 and DPP IV inhibition is superior to DPP IV inhibition alone in reducing clearance and improving the anti-hyperglycaemic and insulinotropic activity of GLP-1, providing the first evidence that inhibition of NEP 24.11 may also have therapeutic potential in diabetes treatment.
The Heme Monooxygenase Cytochrome P450cam Can Be Engineered to Oxidize Ethane to Ethanol (2005)

A NADH turnover rate of 741 min−1 in the oxidition of ethane to ethanol is observed with an engineered form of the heme monooxygenase cytochrome P450cam—the first example of such activity for a P450 enzyme (GC analysis shown). Ethanol is formed at 78 min−1 (10.5 % coupling). The mutant is ≈45 % high-spin in the absence of substrate, making it a useful platform for P450 structure–function studies.
Electrochemical muscles: Micromachining fingers and corkscrews (1993)

Millimeter‐scale polymer “fingers” are reported, in which the volume changes of the conjugated polymer polypyrrole that occur in response to electrochemical reduction or oxidation are used to create electrically controlled mechanical actuators. The short bilayer gold and polypyrrole fingers in the Figure can be made to curl by reducing the polypyrrole. The primitive fabrication technique used to make these fingers points the way to the microminiaturization of these artificial muscles. magnified image
Architectures for home systems (1990)

The basic concept of the home system is to cover diverse requirements by providing a home network which can be used by all products as a general-purpose data highway supporting information transfer and control. In practice there is a spectrum of requirements, and therefore one single universal link cannot be optimum for all applications. In the home, where cost is always important and data rates vary from the room thermostat, switching every few minutes, to the high definition TV with data rates of many MHz, one needs a choice of networks. >
Ability of Circular Extrachromosomal DNA Molecules to Carry Amplified MYCN Protooncogenes in Human Neuroblastomas In Vivo (1990)

Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification.
Impaired human tissue factor-mediated activity in blood clotting factor VIINagoya (Arg304–>Trp). Evidence that a region in the catalytic domain of factor VII is important for the association with tissue factor. (1994)

A 37-year-old man was found to have an inherited abnormal factor VII (FVII) (designated FVIINagoya) that has a lower FVII procoagulant activity when tested in a one-stage assay using rabbit, simian, or human tissue factor (TF), but surprisingly has a nearly normal activity using bovine TF. DNA sequence analysis of the propositus' FVII gene revealed a C to T mutation that results in a novel amino acid substitution of Arg304 to Trp. Restriction enzyme analysis of the amplified fragment obtained from each family member demonstrated that the patient is homozygous for the point mutation, and the mother and sister of the patient are heterozygous for this mutation. To elucidate the abnormality in FVIINagoya, we compared the recombinant mutant FVII with normal FVII. In the presence of human TF, kinetic analyses demonstrated that the apparent Km values of FVIINagoya for factor Xa-mediated FVII activation and for FVIIa-mediated factor X (FX) activation were 3.6- and 4.5-fold higher than those of normal FVII, respectively. The ligand binding assay to human TF also showed that FVIINagoya had a 5.2-fold larger apparent Kd than normal. In the presence of bovine TF, however, these values showed no difference between normal and mutant FVII. These findings indicate that the major abnormality in FVIINagoya is not a catalytic dysfunction but an impaired complex-formation of human TF.FVII.FX, suggesting the importance of Arg304 in the interaction with human TF.
Accelerated Variant of Idiopathic Pulmonary Fibrosis: Clinical Behavior and Gene Expression Pattern (2007)

A subgroup of IPF patients, predominantly smoking males, display an accelerated clinical course and have a gene expression pattern that is different from those with slower progression and longer survival. These findings highlight the variability in the progression of IPF, and may explain, in part, the difficulty in obtaining significant and reproducible results in studies of therapeutic interventions in patients with IPF.
Siloxane Polymers for High-Resolution, High-Accuracy Soft Lithography (2000)

We report the formulation of siloxane polymers for high-resolution, high-accuracy stamps for soft lithography. With this technique, a molecular, polymeric, or liquid ink is applied to the surface of a stamp and then transferred by conformal contact to a substrate. Stamps for this technique are usually made of a commercial siloxane elastomer with appropriate mechanical properties to achieve conformal contact but are incapable of printing accurate, submicrometer patterns. To formulate better stamp polymers, we used models of rubber-like elasticity as guidelines. Poly(dimethylsiloxane) networks were prepared from vinyl and hydrosilane end-linked polymers and vinyl and hydrosilane copolymers, with varying mass between cross-links and junction functionality. The polymer formulations were characterized by strain at break as well as compression modulus and surface hardness measurements. This resulted in the identification of bimodal polymer networks having mechanical properties that allow the replication of high-density patterns at the 100 nm scale and that withstand the mechanical constraints during use as a stamp material. We also demonstrate advantageous implementations of the formulated polymers in hybrid stamps that achieve submicrometer-dimensional accuracy over large areas.
P-element-induced interallelic gene conversion of insertions and deletions in Drosophila melanogaster. (1993)

We studied the process by which whd, a P-element insertion allele of the Drosophila melanogaster white locus, is replaced by its homolog in the presence of transposase. These events are interpreted as the result of double-strand gap repair following excision of the P transposon in whd. We used a series of alleles derived from whd through P-element mobility as templates for this repair. One group of alleles, referred to collectively as whd-F, carried fragments of the P element that had lost some of the sequences needed in cis for mobility. The other group, whd-D, had lost all of the P insert and had some of the flanking DNA from white deleted. The average replacement frequencies were 43% for whd-F alleles and 7% for the whd-D alleles. Some of the former were converted at frequencies exceeding 50%. Our data suggest that the high conversion frequencies for the whd-F templates can be attributed at least in part to an elevated efficiency of repair of unexpanded gaps that is possibly caused by the closer match between whd-F sequences and the unexpanded gap endpoints. In addition, we found that the gene substitutions were almost exclusively in the direction of whd being replaced by the whd-F or whd-D allele rather than the reverse. The template alleles were usually unaltered in the process. This asymmetry implies that the conversion process is unidirectional and that the P fragments are not good substrates for P-element transposase. Our results help elucidate a highly efficient double-strand gap repair mechanism in D. melanogaster that can also be used for gene replacement procedures involving insertions and deletions. They also help explain the rapid spread of P elements in populations.
Challenging Pregnancy Discrimination in Drug Treatment: Does the ADAMHA Reorganization Act Provide an Answer? (1993)

Cleo Washington was seven months pregnant with her second child when she was forced to leave drug treatment; the city had cut the program from its budget. This was Washington's third attempt to seek treatment during her pregnancy. Initially, she tried acupuncture, but left the program because she was afraid that the needles might be infected and was offended by the drug dealers gathering just outside the door. Next, she attended a coed program, which placed men, women, and children in the same room during therapy. Her city caseworker then referred her to a special program for mothers and pregnant women. Three weeks later, it closed. Frustrated, Washington decided not to seek out a fourth program although she knew state authorities might place her children in foster care. "'I'll just stay home,' she said, 'I don't want the aggravation of starting over.' " The story of Cleo Washington is not unique. Across the country, pregnant women face major obstacles when seeking treatment for their drug dependence. Many are denied access to programs simply because they are pregnant. Some of those who do find treatment must resort to clinics that do not sufficiently meet their needs.
Phase II evaluation of recombinant gamma-interferon in patients with advanced pancreatic carcinoma: a Southwest Oncology Group study. (1990)

Thirty evaluable patients with advanced carcinoma of the pancreas received treatment with either daily x 5 bolus or continuous infusion x 5 days recombinant gamma-interferon. No responses were noted. Major toxicities included fever, hypotension, and flu-like symptoms. gamma-Interferon does not appear to be an active single agent for patients with advanced pancreatic cancer.
RNA interfering approach for clarifying the PPARγ pathway using lentiviral vector expressing short hairpin RNA (2004)

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in adipocyte differentiation and insulin sensitivity. Although PPARgamma also appears to regulate diverse cellular processes in other cell types such as lymphocytes, the detailed mechanisms remain unclear. In this study, we established a lentivirus-mediated short hairpin RNA expression system and identified a potent short hairpin RNA which suppresses PPARgamma expression, resulting in marked inhibition of preadipocyte-to-adipocyte differentiation in 3T3-L1 cells. Our PPARgamma-knockdown method will serve to clarify the PPARgamma pathway in various cell types in vivo and in vitro, and will facilitate the development of therapeutic applications for a variety of diseases.
Medicine in virtual environments (1995)

Virtual Environments allow a human to interact with a (computer) system in such a way that a high level of presence in a computer-synthesised world is experienced. In principle, all human senses are involved with the interaction. Many applications may benefit from this type of human-machine interfa cing, however, few have emerged so far for medicine. In this paper we elaborate on some realistic potential applications of Virtual Environment technology in the field of medicine. These applications can be found in education/training, therapy, surgery, rehabilitation, diagnosis, telemedicine and biomechanics. The value to be added to these applications by VE technology lies in the fact that patient data or patient models may be moderated to the physician in a more intuitive and natural manner. Despite these potentials, the short-term feasibility of these applications can be put into question for various reasons. Firstly, the current generation of display devices have a resolution that may show to be too low to achieve a sufficiently high degree of realism for medical applications. Secondly, there are no commercially-available actuators for tactile and force feedback which the physician desperately need for the simulation of the contact with the (virtual) patient. Thirdly, the enormous computing power required for these applications (still) needs a considerable investment. With these limitations in mind, we believe that we are at the cradle of a whole new generation of VE applications in medicine.