gebhart/patrepeval huggingface dataset:
Efficient Estimation of Detailed Single-Neuron Models (2006)

Biophysically accurate multicompartmental models of individual neurons have significantly advanced our understanding of the input-output function of single cells. These models depend on a large number of parameters that are difficult to estimate. In practice, they are often hand-tuned to match measured physiological behaviors, thus raising questions of identifiability and interpretability. We propose a statistical approach to the automatic estimation of various biologically relevant parameters, including 1) the distribution of channel densities, 2) the spatiotemporal pattern of synaptic input, and 3) axial resistances across extended dendrites. Recent experimental advances, notably in voltage-sensitive imaging, motivate us to assume access to: i) the spatiotemporal voltage signal in the dendrite and ii) an approximate description of the channel kinetics of interest. We show here that, given i and ii, parameters 1-3 can be inferred simultaneously by nonnegative linear regression; that this optimization problem possesses a unique solution and is guaranteed to converge despite the large number of parameters and their complex nonlinear interaction; and that standard optimization algorithms efficiently reach this optimum with modest computational and data requirements. We demonstrate that the method leads to accurate estimations on a wide variety of challenging model data sets that include up to about 10(4) parameters (roughly two orders of magnitude more than previously feasible) and describe how the method gives insights into the functional interaction of groups of channels.
Coronary collateral development in swine after coronary artery occlusion. (1992)

We have quantified the development of the coronary collateral circulation in the pig. The collateral circulation was induced to grow by placing an ameroid occluder on the left circumflex coronary artery. Two to 16 weeks after ameroid placement, the coronary collateral circulation was identified after the injection of several colors of a silicone polymer into the coronary arteries and the aorta. We identified intercoronary and extracardiac collaterals and quantified their number, location, size, and wall thickness. Intercoronary collaterals grew to a level that represents a 14-fold increase in normal collateral blood flow under resting conditions compared with the values in an animal not subjected to coronary artery occlusion. Extracardiac collaterals could potentially supply approximately 30% of resting flow. The sources of the extracardiac collaterals were the bronchial and internal mammary arteries. Coronary collateral morphometry and DNA synthesis in the pig heart also were examined. Coronary collaterals had significantly less smooth muscle than did normal arterioles. This may account, in part, for the reduced response of the coronary collaterals to vasodilators. We observed intense DNA synthesis in endothelial and smooth muscle cells in the first 2 or 3 weeks of ischemia. However, DNA synthesis rapidly ceased after this time, coincident with coronary collateral reserve values (ischemic/nonischemic regional blood flow ratios during maximal vasodilation) reaching their maximum level. This suggests that failure of the vessels to continue proliferating accounts for the occurrence of the plateau in blood flow levels.
Isolation of maxadilan, a potent vasodilatory peptide from the salivary glands of the sand fly Lutzomyia longipalpis (1991)

Blood feeding by the sand fly Lutzomyia longipalpis is aided by the presence of a vasodilator in its salivary glands. This novel vasodilator has been isolated by reversed-phase high-performance liquid chromatography. Ten nanograms of the vasodilator are present in the extract of a pair of sand fly salivary glands. It has 500 times the vasodilatory activity of calcitonin gene-related peptide, previously the most potent vasodilator peptide known. This novel peptide is thus called maxadilan.
Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia (1991)

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.
Crystal Structure of a Human VH:  Requirements for Maintaining a Monomeric Fragment, (2003)

The variable domain of dromedary immunoglobulins comprises only the heavy chain and is missing the light-chain variable domain. This single domain is sufficient for antigen recognition and binding-half that required by other mammals. Human antibody-VHs have previously been camelized to be soluble stable fragments that retain antigen binding. Such engineered VHH are of interest in drug development, since they are nonimmunogenic, and in other biotechnology applications. We present the structure of a camelized human antibody fragment (cVH), which is a competitive and reversible inhibitor of the NS3 serine protease of the hepatitis C virus (HCV). In solution, this cVH undergoes a concentration-dependent monomer-dimer equilibrium. The structure confirms the minimum mutational requirements of the VL-binding face. The fragment also suggests a means by which the observed dimerization occurs, highlighting the importance of the composition of the CDR3 in maintaining a truly camelized VH.
Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy (2001)

We characterized a rabbit polyclonal antibody raised against human recombinant connective tissue growth factor (CTGF). The antibody recognised a higher molecular mass form (approx. 56kDa) of CTGF in mesangial cell lysates as well as the monomeric (36–38kDa) and lower molecular mass forms (&amp;lt; 30kDa) reported previously. Immunohistochemistry detected CTGF protein in glomeruli of kidneys of non-obese diabetic mice 14 days after the onset of diabetes, and this was prominent by 70 days. CTGF protein is also present in glomeruli of human patients with diabetic nephropathy. No CTGF was detected in either normal murine or human glomeruli. Transient transfection of a transformed human mesangial cell line with a CTGF–V5 epitope fusion protein markedly increased fibronectin and plasminogen activator inhibitor-1 synthesis in cultures maintained in normal glucose (4mM) conditions; a CTGF-antisense construct reduced the elevated synthesis of these proteins in high glucose (30mM) cultures. Culture of primary human mesangial cells for 14 days in high glucose, or in low glucose supplemented with recombinant CTGF or transforming growth factor β1, markedly increased CTGF mRNA levels and fibronectin synthesis. However, whilst co-culture with a CTGF-antisense oligonucleotide reduced the CTGF mRNA pool by greater than 90% in high glucose, it only partially reduced fibronectin mRNA levels and synthesis. A chick anti-CTGF neutralizing antibody had a similar effect on fibronectin synthesis. Thus both CTGF and CTGF-independent pathways mediate increased fibronectin synthesis in high glucose. Nevertheless CTGF expression in diabetic kidneys is likely to be a key event in the development of glomerulosclerosis by affecting both matrix synthesis and, potentially through plasminogen activator inhibitor-1, its turnover.
Phenotypic Changes in Drug Susceptibility Associated with Failure of Human Immunodeficiency Virus Type 1 (HIV‐1) Triple Combination Therapy (1999)

The emergence of drug-resistant human immunodeficiency virus type 1 is a frequent cause of failure of combination therapies comprising reverse transcriptase and protease inhibitors. Rational design of salvage therapies requires new methods to assess drug susceptibility. A novel phenotypic drug susceptibility assay was developed and used to measure the drug susceptibilities of viruses obtained from 2 patients treated with zidovudine, lamivudine, and nelfinavir. Results showed that phenotypic drug resistance may be detectable before virus load rebound, treatment failure does not always imply viral resistance to all drugs in a treatment regimen, and persons with similar antiviral treatment histories and clinical courses may have different phenotypic drug resistance profiles at the time that treatment fails.
The Nuclear Gene Rf3 Affects the Expression of the Mitochondrial Chimeric Sequence R Implicated in S-Type Male Sterility in Maize (1997)

The mitochondrial genomes of maize plants exhibiting S-type cytoplasmic male sterility (cms-S) contain a repeated DNA region designated R. This region was found to be rearranged in the mitochondria of all cms-S cytoplasmically revertant fertile plants in all nuclear backgrounds analyzed. A 1.6-kb mRNA transcribed from the R region in mitochondria of sterile plants was absent from all cytoplasmic revertants examined. The nuclear gene Rf3, which suppresses the cms-S phenotype, was found to have a specific effect on the expression of the R sequence; the abundance of the major R transcripts, including the cms-S-specific 1.6-kb mRNA, is decreased in mitochondria of restored plants. Nucleotide sequence analysis of R has revealed similarities to the R1 plasmid found in some South American maize races with RU cytoplasm, to the M1 plasmid found in one source of Zea luxurians teosinte, to the atp9 mitochondrial gene and its 3' flanking sequence, and also to a region 3' to the orf221 gene. The derived amino acid sequence of the R region predicts two open reading frames (ORFs). These ORFs contain the similarities to R1, M1, atp9 and orf221. The present report reveals the chimeric nature of the R region, describes the complex effect of Rf3 on the expression of the R sequence and implicates R in the sterile phenotype of cms-S maize.
Extension of target registration error theory to the composition of transforms (2002)

This paper is an extension of work first published by Fitzpatrick et al. in 1998, and concerns accuracy prediction in point-based image registration. Fitzpatrick et al. derived a formula to predict target registration error (TRE), i.e the error introduced in identifying a target point because of the inherent errors in locating the point used to calculate the registration transform. In this work, we extend Fitzpatrick's derivation to the case in which an optically tracked probe has its position measured relative to a coordinate reference frame (CRF), which is an optically tracked device that is rigidly affixed to the patient. In this case, the registration transformation is actually a composition of two transforms. Our derivation shows that the existing TRE theory may be applied independently to the two transforms that compose the registration, and the resulting values add in quadrature to give the overall TRE. We have confirmed this result using statistical numerical simulations. This derivation has important implications for designing optically tracked instruments for image-guided surgery. Probes and CRFs may be designed separately so that each has maximal accuracy, and the configuration of the two instruments will remain optimal when they are used in conjunction.
Herpes-Type Virus Particles in Tissue Culture of Kaposi's Sarcoma From Different Geographic Regions2 (1972)

Typical herpes-type virus particles were observed in 5 of 8 selected tissue culture lines derived from different cases of Kaposi's sarcoma from 2 equatorial African regions, Congo and Uganda. Common and different traits of cellular morphology related to viral involvement were found. In one line, morphologic aspects and preliminary immunologic characterization suggested a virus resembling cytomegalovirus. The other 4 cases presented one important trait in common: The appearance of viruses (at an early stage in lines 13, 16, 19) in undifferentiated cells that resembled fibroblastoid or macrophage elements.
The potassium paradox: Implications for soil fertility, crop production and human health (2013)

Abstract Intensive fertilizer usage of KCl has been inculcated as a prerequisite for maximizing crop yield and quality, and relies on a soil test for exchangeable K in the plow layer to ensure that soil productivity will not be limited by nutrient depletion. The interpretive value of this soil test was rigorously evaluated by: (1) field sampling to quantify biweekly changes and seasonal trends, (2) characterizing the variability induced by air drying and the dynamic nature of soil K reserves and (3) calculating the K balance in numerous cropping experiments. These evaluations leave no alternative but to question the practical utility of soil K testing because test values cannot account for the highly dynamic interchange between exchangeable and non-exchangeable K, exhibit serious temporal instability with or without air drying and do not differentiate soil K buildup from depletion. The need for routine K fertilization should also be questioned, considering the magnitude and inorganic occurrence of profile reserves, the recycling of K in crop residues and the preferential nature of K uptake. An extensive survey of more than 2100 yield response trials confirmed that KCl fertilization is unlikely to increase crop yield. Contrary to the inculcated perception of KCl as a qualitative commodity, more than 1400 field trials predominately documented a detrimental effect of this fertilizer on the quality of major food, feed and fiber crops, with serious implications for soil productivity and human health.
Differences in encapsulating lead tissue in patients who underwent transvenous lead removal (2012)

Granulation in encapsulating tissue was present in patients with younger leads. Vasculogenesis was observed more often in IE and CPI patients, which might indirectly indicate thickness of the sheath. Eosinophila may indicate allergic component of inflammation. Insulation damage frequently concerned the intracardiac part.
The DNA polymerase gene from the methanogenic archaeon Methanococcus voltae (1994)

Previous studies have identified intervening sequences that encode homing endonucleases within the genes encoding several archaeal DNA polymerases. We report the sequence of the gene encoding the DNA polymerase of Methanococcus voltae and describe evidence that it lacks analogous intervening sequences.
Evaluation of coalbed-methane reserves involves different techniques (1989)

The gas-production mechanisms in coalbeds are significantly different than in conventional reservoirs. Because of this and other reasons, coalbed methane is considered an unconventional gas resource. According to the authors, when evaluating a prospective coal-bed methane site, there is no substitute for site-specific information systematically gathered from wells as a site is developed. The first few wells are the key link in site characterization. A sizeable collection of information can be constructed with regional geologic data and logging coring, and testing of one well. This information can be used to help make sound decisions about the production potential and economic viability of the site, design hydraulic-fracture treatments, and provide the preliminary lay-out and spacing of the field. Conventional and specialized methods, including well logging, core desorption and analysis, and well testing, are available to collect this information. The STEP (short term permeability test) is discussed as are other well tests. Reservoir simulation is presented as the most reliable method of prediction.
Topological Control in Heterometallic Metal−Organic Frameworks by Anion Templating and Metalloligand Design (2006)

Several new heterometallic metal-organic frameworks (MOFs) based on tris(dipyrrinato) metalloligands and Ag+ salts are reported. MOFs were prepared systematically to examine the effects of the core metal ion, counteranion, and ligand structure on the topology of the resultant network. The effect of the metal ion (Fe3+ vs Co3+) on MOF structure was generally found to be negligible, thereby permitting the facile synthesis of trimetallic Fe/Co/Ag networks. The choice of anion (e.g., silver salt) was found to have a pronounced effect on the MOF topology. Networks prepared with salts of AgO3SCF3 and AgBF4 reliably formed three-dimensional (10,3) nets, whereas use of AgPF6 and AgSbF6 produced two-dimensional (6,3) honeycomb nets. The topology generated upon formation of the MOF was found to be robust in certain cases, as demonstrated by anion-exchange experiments. Anion exchange was confirmed by X-ray crystallography in a rare set of apparent single-crystal-to-single-crystal transformations. The data presented here strongly suggest that the coordinative ability of the anion does not play a significant role in the observed templating effect. Finally, changes in the length of the tris(dipyrrinato) metalloligand were found to override the anion templating effect, resulting exclusively in two-dimensional (6,3) nets. These studies provide a basis for the rational design of MOF topologies by choice of ligand structure and anion templating effects. Furthermore, the results demonstrate the ability of carefully designed metalloligands to generate MOFs of structure strikingly similar to that of their organic counterparts.
Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view (2001)

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.
A micromolar pool of antigenically distinct precursors is required to initiate cooperative assembly of hepatitis B virus capsids in Xenopus oocytes (1993)

Assembly of hepatitis B virus capsid-like (core) particles occurs efficiently in a variety of heterologous systems via aggregation of approximately 180 molecules of a single 21.5-kDa core protein (p21.5), resulting in an icosahedral capsid structure with T = 3 symmetry. Recent studies on the assembly of hepatitis B virus core particles in Xenopus oocytes suggested that dimers of p21.5 represent the major building block from which capsids are generated. Here we determined the concentration dependence of this assembly process. By injecting serially diluted synthetic p21.5 mRNA into Xenopus oocytes, we expressed different levels of intracellular p21.5 and monitored the production of p21.5 dimers and capsids by radiolabeling and immunoprecipitation, by radioimmunoassay, or by quantitative enzyme-linked immunosorbent assay analysis. The data revealed that (i) p21.5 dimers and capsids are antigenically distinct, (ii) capsid assembly is a highly cooperative and concentration-dependent process, and (iii) p21.5 must accumulate to a signature concentration of approximately 0.7 to 0.8 microM before capsid assembly initiates. This assembly process is strikingly similar to the assembly of RNA bacteriophage R17 as defined by in vitro studies.
Biosynthetic preparation of L-[13C]- and [15N]glutamate by Brevibacterium flavum (1987)

The biosynthesis of isotopically labeled L-glutamic acid by the microorganism Brevibacterium flavum was studied with a variety of carbon-13-enriched precursors. The purpose of this study was twofold: to develop techniques for the efficient preparation of labeled L-glutamate with a variety of useful labeling patterns which can be used for other metabolic studies, and to better understand the metabolic events leading to label scrambling in these strains. B. flavum, which is used commercially for the production of monosodium glutamate, has the capability of utilizing glucose or acetate as a sole carbon source, an important criterion from the standpoint of developing labeling strategies. Unfortunately, singly labeled glucose precursors lead to excessive isotopic dilution which reduces their usefulness. Studies with [3-13C]pyruvate indicate that this problem can in principle be overcome by using labeled three-carbon precursors; however, conditions could not be found which would lead to an acceptable yield of isotopically labeled L-glutamate. In contrast, [1-13C]- or [2-13C]acetate provides relatively inexpensive, readily available precursors for the production of selectively labeled, highly enriched L-glutamate. The preparation of L-[15N]glutamate from [15N]ammonium sulfate was carried out and is a very effective labeling strategy. Analysis of the isotopic distribution in labeled glutamate provides details about the metabolic pathways in these interesting organisms.