gebhart/patrepeval huggingface dataset:
Dopamine Gene Therapy for Parkinson’s Disease in a Nonhuman Primate Without Associated Dyskinesia (2009)

In Parkinson's disease, degeneration of specific neurons in the midbrain can cause severe motor deficits, including tremors and the inability to initiate movement. The standard treatment is administration of pharmacological agents that transiently increase concentrations of brain dopamine and thereby discontinuously modulate neuronal activity in the striatum, the primary target of dopaminergic neurons. The resulting intermittent dopamine alleviates parkinsonian symptoms but is also thought to cause abnormal involuntary movements, called dyskinesias. To investigate gene therapy for Parkinson's disease, we simulated the disease in macaque monkeys by treating them with the complex I mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces selective degeneration of dopamine-producing neurons. In this model, we demonstrated that injection of a tricistronic lentiviral vector encoding the critical genes for dopamine synthesis (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine 5'-triphosphate cyclohydrolase 1) into the striatum safely restored extracellular concentrations of dopamine and corrected the motor deficits for 12 months without associated dyskinesias. Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias.
Recursive estimation procedures for missing-data problems (1983)

Titterington (1984) proposes recursive methods for dealing with incomplete data. The present paper concentrates on versions of these for multiparameter problems involving missing data. Theorems are outlined from which asymptotic properties of the recursive procedures can be established and versions of the recursions, some of which are particularly easy to use, are written down for problems in which the missing data are missing at random. After illustration with exponential family models, the case of multivariate normal data is considered in detail. Numerical comparisons of the various methods are obtained using bivariate normal data. Application of the methods as imputation procedures is discussed.
Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice (1986)

Normal adult C57BL, BALB/c, and C3H/HeJ mice were injected intraperitoneally three times daily for up to 6 days with 102,000 U (200 ng) per injection of purified, bacterially synthesized, Multipotential colony-stimulating factor (CSF) (Interleukin-3) (rMulti- CSF) and compared with control mice injected with serum/saline with or without added endotoxin (1 ng/mL). Mice injected with rMulti-CSF exhibited tenfold rises in blood eosinophil and twofold to threefold rises in neutrophil and monocyte levels. The spleens from mice injected with rMulti-CSF showed a 50% increase in weight, elevated levels of maturing granulocytes, eosinophils, nucleated erythroid cells and megakaryocytes, and up to 100-fold rises in mast cells. Progenitor cell frequencies in the spleen were elevated sixfold to 18-fold. No significant changes were observed in the marrow. Sixfold to 15-fold rises were observed in peritoneal cell populations of mice injected with rMulti-CSF with evidence of increased peritoneal macrophage phagocytic activity. Livers of C57BL mice, but not of the other strains, exhibited increased numbers of infiltrating hematopoietic cells whereas rises in mast cell numbers were observed in the mesenteric lymph node, skin, and gut in BALB/c and C3H/HeJ mice. Endotoxin was excluded as being responsible for the observed changes except possibly those involving peritoneal macrophage phagocytic activity. The results indicate that the injection of normal mice with rMulti-CSF significantly stimulates the same types of hematopoietic populations as are stimulated in vitro by Multi-CSF and indicate that this and other CSFs should be useful in stimulating hematopoietic repopulation and functional activity in vivo.
Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. (1978)

Evidence from the peritoneal dialysis literature suggests that the peritoneal permeability of a number of hydrophilic anticancer drugs may be considerably less than plasma clearance. Pharmacokinetic calculations indicate that such drugs administered ip in large volumes are expected to maintain a significantly greater concentration in the peritoneal space than in the plasma. This concentration difference offers a potentially exploitable biochemical advantage in the treatment of patients with presumed microscopic residual ovarian cancer confined to the peritoneal cavity.
Exploring the Maze of Adverse Reactions to Foods (1994)

Nowhere in medicine is a test or battery of tests more needed than in the diagnosis of adverse reactions to foods. Such tests are not at present a reality. Research produces tests that individually appear to show validity, but when challenged with the entire range of possible adverse reactions and their results, the tests fall short. Considering the range of mechanisms involved in adverse reactions to foods, this is to be expected. There is a tendency to discount positive test results when they fail to cover all of the parameters desired. The inherent weakness in any test is that all available formats explore a single or limited reaction route. The reality is the presence of multiple routes, multiple target organs, and multiple external variables not subject to programming into a single test. Considering the range of possibilities, it is amazing that any existing tests show any clinical validity at all. We as scientists should not denigrate any study that shows a significant degree of reliability, even within a limited range. This simply halts progress. An encouraging study should be used as a stepping stone to a more comprehensive format for evaluating the overall range of adverse reactions and providing us with at least some inroads in coping with this most difficult problem. To quote Sir Peter Medawer on receiving the Nobel Prize in Science: "Nothing must be said or written that diminishes the likelihood that someone else will get at the truth."
Similarity between the interleukin 1 receptors on a murine T-lymphoma cell line and on a murine fibroblast cell line. (1986)

Interleukin 1 beta (IL-1 beta), one of two different polypeptide hormones with interleukin 1 (IL-1) biological activity, produced by activated human monocytes, is a 17.5-kDa protein. IL-1 beta binds specifically to a variety of cells; the cellular distribution of binding is consistent with reported biological responsiveness. In this report we show that two unrelated, but IL-1-responsive, cell lines, LBRM-33-1A5, a T-lymphoma line, and BALB/3T3, a fibroblast line, bind 125I-labeled IL-1 beta via similar plasma membrane receptor molecules. The T-lymphoma cells possess 238 +/- 16 plasma membrane receptors per cell and bind 125I-labeled IL-1 beta with an affinity of 3.6 +/- 0.9 X 10(9) M-1. The IL-1 receptor has a molecular size of approximately equal to 79.5 kDa, as estimated by affinity cross-linking. The fibroblasts possess 4.8 +/- 0.5 X 10(3) IL-1 receptors per cell and bind 125I-labeled IL-1 beta with an affinity of 2.6 +/- 0.5 X 10(9) M-1. The molecular size of the receptor molecule on the fibroblasts is approximately equal to 78 kDa. Despite the similarity in the characteristics of the ligand-receptor system on the two different cell types, the biological responses of the two cell types to IL-1 beta occur at IL-1 beta concentrations that differ by four orders of magnitude.
In vivo Measurements of Iron, Copper and Zinc in the Skin of Prurigo nodularis Patients Treated with Thalidomide (1981)

The concentration of iron, cooper and zinc in the skin of patients with prurigo nodularis was measured by diagnostic X-ray spectrometry before and after treatment with thalidomide. Before treatment, larger skin lesions were associated with significantly higher zinc levels and higher iron levels than the smaller ones. Upon treatment the zinc and iron content in these lesions decreased towards normal range. Copper values were found to be within the normal range in lesions before and after thalidomide treatment.
320 fs soliton generation with passively mode-locked erbium fibre laser (1991)

The generation of ultrashort 320fs soliton pulses at 1560nm from an all-fibre, passively mode-locked erbium fibre is reported. Repetition rates a s high as 10GHz have been observed demonstrating the device&apos;s potential as a telecommunication soliton source.
Diffusion tensor imaging of cerebral white matter: a pictorial review of physics, fiber tract anatomy, and tumor imaging patterns. (2004)

We review the normal anatomy of the white matter (WM) tracts as they appear on directional diffusion tensor imaging (DTI) color maps, which will almost certainly be available to the general radiologist as part of a commercial DTI software package in the near future. Anatomic drawings and gross
Effects of high‐intensity intermittent training on potassium kinetics and performance in human skeletal muscle (2003)

A rise in extracellular potassium concentration in human skeletal muscle may play an important role in development of fatigue during intense exercise. The aim of the present study was to examine the effect of intense intermittent training on muscle interstitial potassium kinetics and its relationship to the density of Na(+),K(+)-ATPase subunits and K(ATP) channels, as well as exercise performance, in human skeletal muscle. Six male subjects performed intense one-legged knee-extensor training for 7 weeks. On separate days the trained leg (TL) and the control leg (CL) performed a 30 min exercise period of 30 W and an incremental test to exhaustion. At frequent intervals during the exercise periods interstitial potassium ([K(+)](I)) was determined by microdialysis, femoral arterial and venous blood samples were drawn and thigh blood flow was measured. Time to fatigue for TL was 28% longer (P < 0.05) than for CL (10.6 +/- 0.7 (mean +/-s.e.m.) versus 8.2 +/- 0.7 min). The amounts of Na(+),K(+)-ATPase alpha(1) and alpha(2) subunits were, respectively, 29.0 +/- 8.4 and 15.1 +/- 2.7% higher (P < 0.05) in TL than in CL, while the amounts of beta(1) subunits and ATP-dependent K(+) (K(ATP)) channels were the same. In CL [K(+)](I) increased more rapidly and was higher (P < 0.05) throughout the 30 W exercise bout, as well at 60 and 70 W, compared to TL, whereas [K(+)](I) was similar at the point of fatigue (9.9 +/- 0.7 and 9.1 +/- 0.5 mmol l(-1), respectively). During the 30 W exercise bouts and at 70 W during the incremental exercise femoral venous potassium concentration ([K(+)](v)) was higher (P < 0.05) in CL than in TL, but identical at exhaustion (6.2 +/- 0.2 mmol l(-1)). Release of potassium to the blood was not different in the two legs. The present data demonstrated that intense intermittent training reduce accumulation of potassium in human skeletal muscle interstitium during exercise, probably through a larger re-uptake of potassium due to greater activity of the muscle Na(+),K(+)-ATPase pumps. The lower accumulation of potassium in muscle interstitium in the trained leg was associated with delayed fatigue during intense exercise, supporting the hypothesis that interstitial potassium accumulation is involved in the development of fatigue.
The involvement of human tumor necrosis factors- alpha and - beta in the mixed lymphocyte reaction. (1988)

The influence of recombinant human TNF-alpha and -beta (rHuTNF-alpha and -beta) in a human mixed lymphocyte reaction (MLR) was investigated. The addition of 1000 U/ml of either cytokine at the initiation of culture caused up to a sixfold increase in [3H]thymidine incorporation by responder cells. Furthermore, it was found that endogenous HuTNF-alpha is produced after allogeneic cell interaction and can be detected in the MLR supernatant within 1 h of culture initiation. The results also show that, in the absence of exogenous HuTNF-alpha, antibodies to rHuTNF-alpha can cause a significant inhibition of the MLR. These observations indicate the importance of TNF-alpha in allogeneic cell interaction and raise considerations for the use of antibodies, or other antagonists, to TNF-alpha as regulators of disease states associated with cell-mediated immune reactions.
Cysteine 148 in the Lactose Permease of Escherichia coli Is a Component of a Substrate Binding Site. 2. Site-Directed Fluorescence Studies (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCysteine 148 in the Lactose Permease of Escherichia coli Is a Component of a Substrate Binding Site. 2. Site-Directed Fluorescence StudiesJianhua Wu and H. Ronald KabackCite this: Biochemistry 1994, 33, 40, 12166–12171Publication Date (Print):October 11, 1994Publication History Published online1 May 2002Published inissue 11 October 1994https://pubs.acs.org/doi/10.1021/bi00206a020https://doi.org/10.1021/bi00206a020research-articleACS PublicationsRequest reuse permissionsArticle Views111Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Preparation of Low-Surface-Energy Poly[2-(perfluorooctyl)ethyl acrylate] Microparticles and Its Application to Liquid Marble Formation (2011)

We demonstrate the successful preparation of stable liquid marbles from various liquids. This is accomplished by using low-surface-energy poly[2-(perfluorooctyl)ethyl acrylate] (PFA-C(8)) as microparticles. The PFA-C(8) microparticles were prepared by the spontaneous self-organized microparticulation of PFA-C(8). The physical properties remained intact in the polymer morphology as confirmed by wide-angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) measurements. The extremely low surface energy of PFA-C(8) provides a high solid-liquid spreading coefficient (S(S/L)) value for various combinations of liquids. As a result, liquid marbles were obtained from various liquids, unlike the case with other fluorine polymer particles such as poly(tetrafluoroethylene) (PTFE) and poly(vinilydene fluoride) (PVDF). These results suggest that the technique is widely applicable for preparing novel functional materials.
SinI modulates the activity of SinR, a developmental switch protein of Bacillus subtilis, by protein-protein interaction. (1993)

SinR, a 111-amino-acid DNA-binding protein, is a pleiotropic regulator of several late growth processes in Bacillus subtilis. It acts as a developmental switch, positively regulating genes for competence and motility and repressing aprE and stage II sporulation genes. It is encoded by the second gene in a two gene operon, but previous results have also indicated that these two genes are differently regulated. We show in this discussion that the product of sinI, the first open reading frame (ORF) of this operon, interferes with the function of SinR. In vivo experiments have demonstrated that overexpression of sinI results in phenotypes that are observed in cells with a null mutation of sinR. A chromosomal in-frame deletion of sinI gives rise to a phenotype associated with higher levels of SinR. Thus, SinI acts as an antagonist to SinR. In vitro experiments have shown that the interaction between these two proteins is a direct one. SinI prevents SinR from binding to its target sequence on aprE, and the two proteins form a complex that can be immunoprecipitated with antibodies to either SinR or SinI.
Regulation of p53 by Metal Ions and by Antioxidants: Dithiocarbamate Down-Regulates p53 DNA-Binding Activity by Increasing the Intracellular Level of Copper (1997)

Mutations in the p53 tumor suppressor gene frequently fall within the specific DNA-binding domain and prevent the molecule from transactivating normal targets. DNA-binding activity is regulated in vitro by metal ions and by redox conditions, but whether these factors also regulate p53 in vivo is unclear. To address this question, we have analyzed the effect of pyrrolidine dithiocarbamate (PDTC) on p53 DNA-binding activity in cell lines expressing wild-type p53. PDTC is commonly regarded as an antioxidant, but it can also bind and transport external copper ions into cells and thus exert either pro- or antioxidant effects in different situations. We report that PDTC, but not N-acetyl-L-cysteine, down-regulated the specific DNA-binding activity of p53. Loss of DNA binding correlated with disruption of the immunologically "wild-type" p53 conformation. Using different chelators to interfere with copper transport by PDTC, we found that bathocuproinedisulfonic acid (BCS), a non-cell-permeable chelator of Cu1+, prevented both copper import and p53 down-regulation. In contrast, 1,10-orthophenanthroline, a cell-permeable chelator of Cu2+, promoted the redox activity of copper and up-regulated p53 DNA-binding activity through a DNA damage-dependent pathway. We have previously reported that p53 protein binds copper in vitro in the form of Cu1+ (P. Hainaut, N. Rolley, M. Davies, and J. Milner, Oncogene 10:27-32, 1995). The data reported here indicate that intracellular levels and redox activity of copper are critical for p53 protein conformation and DNA-binding activity and suggest that copper ions may participate in the physiological control of p53 function.
Cardiac disease recognition in echocardiograms using spatio-temporal statistical models (2008)

In this paper we present a method of automatic disease recognition by using statistical spatio-temporal disease models in cardiac echo videos. Starting from echo videos of known viewpoints as training data, we form a statistical model of shape and motion information within a cardiac cycle for each disease. Specifically, an active shape model (ASM) is used to model shape and texture information in an echo frame. The motion information derived by tracking ASMs through a heart cycle is then represented compactly using eigen-motion features to constitute a joint spatio-temporal statistical model per disease class and observation viewpoint. Each of these models is then fit to a new cardiac echo video of an unknown disease, and the best fitting model is used to label the disease class. Results are presented that show the method can discriminate patients with hypokinesia from normal patients.
CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer (2017)

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.
In-111 labeled monoclonal anti-(fibrin-specific) antibody: Detection of pulmonary emboli (1985)

The monoclonal antifibrin-64C5, radiolabeled with In-111 via diethylene triamine pentaacetyl-residues, may be used for in vivo detection of experimental pulmonary emboli. Although this antifibrin binds specifically to human fibrin even in the presence of fibrinogen, it crossreacted effectively with canine fibrin thus permitting the use of a canine model. Experimental thrombi were formed in an isolated segment of the jugular vein by mixing thrombin, canine blood and I-125 Fibrinogen. After 1 hr, the restraining ligatures wee removed to release the I-125 -thrombi which could be found in the lungs by imaging for I-125 activity. About 1 hr later, 1.5-2 mCi In-111 bound to 4-10 mg of 64C5 were injected intravenously and imaged for the next 24 hr. At the end of 24 hr, the animals were killed and the lungs imaged ex vivo for I-125 and In-111 activities. The excised lungs were examined by gross inspection, then sliced to ascertain the location of the emboli in the lungs. Tissue samples were obtained for scintillation counting. Control animals (n=3) were treated identically except they were injected with 4 mg In-111 labeled non-fibrin specific IgGl monoclonal antibody. Discrete in vivo localization was found in 4 of 6 animals injected with In-111 64C5more » in areas of emboli. This was confirmed by gross visual inspection of the excised lungs. Control animals did not show localization in the areas of pulmonary emboli, even in the images of the excised lungs. Thus, these studies demonstrate the potential of monoclonal antibody-64C5 for the non-invasive localization and visualization of pulmonary emboli.« less
The Development of Topically Acting Carbonic Anhydrase Inhibitors as Antiglaucoma Agents (2008)

Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms present in the eyes (CA I, II, IV and XII), with sulfonamides such as acetazolamide, methazolamide, ethoxzolamide and dichlorophenamide, is still widely used for the systemic treatment of glaucoma. The mechanism of action of these drugs consists in inhibition of CA isozymes present in ciliary processes of the eye, with the consequent reduction of bicarbonate and aqueous humour secretion, and of elevated intraocular pressure (IOP) characteristic of this disease. As isoforms CA II/IV/XII are present in many other tissues/organs, generally, systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi and transient myopia. For avoiding these side effects, recently, topically effective CAIs have been developed in the last 10 years, with two drugs available clinically: dorzolamide and brinzolamide. Both these drugs are applied topically as water solutions/suspensions, alone or in combination with other agents (beta-blockers, prostaglandin derivatives, etc) and produce a consistent and prolonged reduction of IOP. Furthermore, recent reports show both the systemically as well as topically acting sulfonamide CAIs to be effective in the treatment of macular edema, macular degeneration disease, or diabetic retinopathy, for which pharmacological treatment is unavailable up to now. Much research is in act in the search of more effective topically acting CAIs, free of the inconveniences and side effects of the presently available drugs. For achieving this goal, two recently reported strategy, the tail approach and its variant, the sugar-tail approach, were extensively applied for the synthesis of large numbers of derivatives possessing desired physico-chemical properties. Many such new sulfonamides showed promising antiglaucoma activity in animal models of the disease.