gebhart/patrepeval huggingface dataset:
The Assembly of the CAAT-box Binding Complex at a Photosynthesis Gene Promoter Is Regulated by Light, Cytokinin, and the Stage of the Plastids (1999)

A functionally important region in the promoter of the spinach photosynthesis gene AtpC, which encodes the subunit gamma of the chloroplast ATP synthase, is located immediately upstream of the CAAT-box. A single nucleotide exchange in this region (AAAATTCAAT --> AAGATCAAT) uncouples the expression of an AtpC promoter::uidA gene fusion from the regulation by light, cytokinin, and functional plastids and results in a high constitutive expression of the reporter gene. By screening an Arabidopsis thaliana expression library with a double-stranded wild-type oligonucleotide from this promoter region, we have isolated cDNAs from Arabidopsis libraries that code for plant homologs of the CAAT-box binding factor (CBF)-C. Binding occurs only in the presence of nuclear extracts, consistent with reports from metazoa CBFs that the subunits A and B in addition to C are required for the formation of the CBF-DNA complex. At least eight genes with homologies to CBF-C are present in the Arabidopsis genome; one of them exhibits striking similarities to the gene for the human global transcriptional repressor Drap1. In gel mobility shift assays, low binding activity of CBF to the wild-type AtpC promoter sequence was observed with nuclear extracts from tissue with low AtpC expression levels, i.e. extracts from etiolated and photobleached seedlings, whereas high binding activity was detectable with extracts from tissues with high AtpC expression levels, i.e. extracts from light-grown seedlings and etiolated seedlings treated with cytokinin. Binding to the mutant sequence, which directs constitutive high level uidA expression in vivo, is significantly stronger than to the wild-type sequence. The data are consistent with the idea that the assembly of CBF at the AtpC promoter is regulated in response to light and cytokinin and that the low level of expression in etiolated and photobleached material is caused by an inhibitory effect. The structure/function relationships of the Arabidopsis CBFs are discussed in relation to their regulatory function in AtpC gene expression.
Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Tremelimumab (CP-675,206) (2008)

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade therapies have been evaluated in clinical trials and have shown promise as possible options for treating patients with cancer. One agent under investigation is tremelimumab (CP-675,206), a monoclonal antibody that has been demonstrated to be a safe and efficacious treatment in patients with malignant melanoma. Results of a phase I clinical trial suggested that a dose of 15 mg/kg of tremelimumab would be the maximum-tolerated dose, with the most common grade 3-4 toxicities being diarrhea and rash. Pharmacokinetic studies showed that the postinfusion plasma concentration and area under the plasma disposition curve both increased in an approximately proportional manner with dose. Studies also showed that tremelimumab has a low clearance (0.132 ml/h x kg), a small volume of distribution (81.2 ml/kg), and a long terminal-phase half-life (22.1 days). A pivotal phase II clinical trial assessing single-agent tremelimumab as second-line therapy in metastatic melanoma has completed accrual, with response rate as the primary endpoint. A pivotal phase III trial has also completed accrual; that study compared the overall survival of previously untreated patients receiving single-agent tremelimumab versus dacarbazine or temozolomide.
Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models (2016)

Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs demonstrate specific cell killing in clinic, but the basis of their antitumor activity is not fully understood. In this study, we investigated the degree to which payload release predicts ADC activity in vitro and in vivo ADCs were generated to target different receptors on the anaplastic large cell lymphoma line L-82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and we found that the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression or drug:antibody ratios. Intratumoral MMAE concentrations consistently correlated with the extent of tumor growth inhibition in tumor xenograft models. In addition, we developed a robust admixed tumor model consisting of CD30(+) and CD30(-) cancer cells to study how heterogeneity of target antigen expression, a phenomenon often observed in cancer specimens, affects the treatment response. CD30-targeting ADC delivering membrane permeable MMAE or pyrrolobenzodiazepine dimers demonstrated potent bystander killing of neighboring CD30(-) cells. In contrast, a less membrane permeable payload, MMAF, failed to mediate bystander killing in vivo, suggesting local diffusion and distribution of released payloads represents a potential mechanism of ADC-mediated bystander killing. Collectively, our findings establish that the biophysical properties and amount of released payloads are chief factors determining the overall ADC potency and bystander killing. Cancer Res; 76(9); 2710-9. ©2016 AACR.
A global perspective on the magnitude of suicide mortality (2009)

Abstract The lay press and clinical literature usually address suicide in terms of individual cases, whereas the epidemiological literature refers to rates, that is, the proportion of the sum of individual cases divided by a given population basis. Actually, both approaches have their place in a discussion on a worldwide perspective of suicide mortality; accordingly, in this chapter, both will be used, in order to better understand some of the implications of suicide. With a particular view to the prevention of suicide, it is important to use disaggregated rates, at least by gender and age, in order to identify specific groups at risk for suicide. In addition, information about the methods used for suicide is essential, as it has been demonstrated that the restriction of access to methods can reduce suicide.
TREATMENT OF NEUROGENIC DETRUSOR OVERACTIVITY IN SPINAL CORD INJURED PATIENTS BY CONDITIONAL ELECTRICAL STIMULATION (2005)

This study demonstrates the feasibility of automatic, event driven electrical stimulation in the treatment of NDO. Although the setup in this experiment is not suitable in a clinical setting, the treatment modality is promising and it warrants further investigation.
A mouse brain homolog of the Drosophila Shab K+ channel with conserved delayed-rectifier properties (1991)

We have cloned and expressed a mouse brain K+ channel that is the homolog of the Drosophila Shab K+ channel. Mouse and Drosophila Shab K+ channels (mShab and fShab, respectively) represent an instance of K+ channels and structurally related species that are both functionally and structurally conserved; most kinetic, voltage-sensitive, and pharmacological properties are similar for the 2 channels. The greatest functional difference between the currents is recovery from inactivation, which is several times slower for mShab than for fShab currents. In addition to conserved structure, the mShab polypeptide has an unusually long nonconserved region at the carboxyl end of the protein. Truncation of 293 residues from the carboxyl end produced no noticeable change in voltage-sensitive, kinetic, or pharmacological properties. Thus, the measured functional properties of mShab are determined by the remaining 564 residues, most of which are conserved. The mShab and fShab channels are naturally occurring structural variants having substitutions in conserved portions that appear relatively neutral with respect to all measured properties except for, possibly, the rate of recovery from inactivation. The mShab current closely resembles a native delayed-rectifier-type potassium current, IK, in hippocampal neurons.
Topological Methods for the Analysis of High Dimensional Data Sets and 3D Object Recognition (2007)

We present a computational method for extracting simple descriptions of high dimensional data sets in the form of simplicial complexes. Our method, called Mapper, is based on the idea of partial clustering of the data guided by a set of functions defined on the data. The proposed method is not dependent on any particular clustering algorithm, i.e. any clustering algorithm may be used with Mapper. We implement this method and present a few sample applications in which simple descriptions of the data present important information about its structure.
Interferometric-spatial-phase imaging for sub-nanometer three-dimensional positioning (2004)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2004.
VEGF Trap In Combination With Radiotherapy Improves Tumor Control In U87 Glioblastoma (2008)

Purpose To determine the effect of vascular endothelial growth factor VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor growth in U87 glioblastoma xenografts in nude mice. Methods and Materials U87 cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF Trap (2.5–25 mg/kg) was administered every 3 days for 3 weeks alone or in combination with a single dose of 10 Gy or fractionated RT (3 x 5 Gy). In addition, three scheduling protocols for VEGF Trap plus fractionated RT were examined. Results Improved tumor control was seen when RT (either single dose or fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg). Scheduling did not significantly affect the efficacy of combined therapy. Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor growth over that of RT alone, there was no additional benefit to combining high-dose VEGF Trap with RT. Conclusions Vascular endothelial growth factor Trap plus radiation is clearly better than radiation alone in a U87 subcutaneous xenograft model. Although high doses of VEGF Trap alone are highly efficacious, it is unclear whether such high doses can be used clinically without incurring normal tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing radiation is of clinical relevance. Int. J. Radiation Oncol. Biol. Physics, Volume 67, Issue 5, pages 1526-1537, 2007.
The Use of Dual-Energy X-ray Absorptiometry in Animals (1996)

The use of dual-energy absorptiometry (DXA) to measure bone mineral content (BMC) and bone mineral density (BMD) is widespread in humans and has been adapted to animals because of the need to examine bone and body composition in longitudinal studies. In this review, the indications and techniques for DXA in small-sized animals (rodents, cats, and rabbits) and large-sized animals (dogs, swine, nonhuman primates, sheep, and horses) are discussed. Now that software has been developed for measuring BMD in small laboratory animals, the most frequent use of DXA in animals is in rats. An ultrahigh-resolution mode of acquisition is used for their small bones but also is necessary for other small-sized animals such as rabbits and cats. In larger-sized animals such as dogs, pigs, and sheep, software used in humans has been adapted successfully to measure BMC/BMD and body composition. The human spine and left and right hip protocols are adapted easily to animals of this size, and the software for body composition has been adapted to dogs. Measurement of bone mass around metallic implants is possible in animals and most studies have involved dogs. To ensure precision of DXA in the noninvasive measurement of BMD in animals, attention to positioning and ability of the operator to define the same region of interest using clearly defined anatomical landmarks on the scan image cannot be overemphasized. This is one of the essential requirements for successful densitometry in animals.
Poisson‐Based Weight Reduction of Animated Meshes (2010)

Abstract While animation using barycentric coordinates or other automatic weight assignment methods has become a popular method for shape deformation, the global nature of the weights limits their use for real‐time applications. We present a method that reduces the number of control points influencing a vertex to a user‐specified number such that the deformations created by the reduced weight set resemble that of the original deformation. To do so we show how to set up a Poisson minimization problem to solve for a reduced weight set and illustrate its advantages over other weight reduction methods. Not only does weight reduction lower the amount of storage space necessary to deform these models but also allows GPU acceleration of the resulting deformations. Our experiments show that we can achieve a factor of 100 increase in speed over CPU deformations using the full weight set, which makes real‐time deformations of large models possible.
Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus (1989)

The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. The single conformational determinant responsible for HBc antigenicity in the assembled core (HBc) and a linear HBe-related determinant (HBe1) were both mapped to an overlapping hydrophilic sequence around amino acid 80; a second HBe determinant (HBe2) was assigned to a location in the vicinity of amino acid 138 but found to require for its antigenicity the intramolecular participation of the extended sequence between amino acids 10 and 140. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis B virus nucleocapsid.
The problems of eukaryotic and prokaryotic DNA packaging and in vivo conformation posed by superhelix density heterogeneity (1977)

Systems for gel electrophoresis in the presence of one of the intercalative unwinding ligands, ethidium or chloroquine, have been developed which permit the resolution of highly supercoiled closed circular DNA molecules differing by unit values of the topological winding number, alpha. All native closed circular DNAs examined, including the viral and intracellular forms of SV40 and polyoma DNA, bacterial plasmid DNAs, and the double stranded closed circular DNA genome of the marine bacteriophage, PM2, are more heterogeneous with respect to the number of superhelical turns present than are the thermal distributions observed in the limit products of the action of nicking-closing (N-C) enzyme on the respective DNAs. In the cases of SV40 and polyoma, where it has been shown that the supercoiling is a combined consequence of the binding of the four nucleosomal histones, H2a, H2b, H3 and H4, and the action of N-C enzyme, the breadth of the distributions within the form I DNAs poses specific problems since the work of other laboratories indicates that the number of nucleosomes on the respective minichromosomes falls within a narrow distribution of 21. If it is assumed that all nucleosomes have identical structures, and that the DNA within a nucleosome is not free to rotate, the native DNA would be anticipated to be less heterogeneous than the thermal equilibrium mixtures present in N-C enzyme relaxed SV40 and polyoma DNAs. The absolute number of superhelical turns (at 37 degrees C in 0.2 M NaCl) in virion polyoma DNA has been determined to be 26 +/- 1, which is the same value obtained for virion SV40 DNA. This is consistent with the observations that polyoma DNA has a higher molecular weight, a lower superhelix density, but the same number of nucleosomes as SV40 DNA. In addition, the distributions within the virion and intracellular form I DNAs of both SV40 and polyoma were found to be indistinguishable.Images
Use of Exhaled Nitric Oxide Measurement to Identify a Reactive, at-Risk Phenotype among Patients with Asthma (2010)

Grouping of asthma by Fe(NO) provides an independent classification of asthma severity, and among patients with severe asthma identifies the most reactive and worrisome asthma phenotype.
Comparison of the Effects of a Pure Steroidal antiestrogen With Those of Tamoxifen in a Model of Human Breast Cancer (1995)

ICI 182,780 is a more effective estrogen antagonist than tamoxifen in the MCF-7 tumor cell/nude mouse model system.
Improving Web search using image snippets (2008)

The Web has become the largest information repository in the world; thus, effectively and efficiently searching the Web becomes a key challenge. Interactive Web search divides the search process into several rounds, and for each round the search engine interacts with the user for more knowledge of the user's information requirement. Previous research mainly uses the text information on Web pages, while little attention is paid to other modalities. This article shows that Web search performance can be significantly improved if imagery is considered in interactive Web search. Compared with text, imagery has its own advantage: the time for “reading” an image is as little as that for reading one or two words, while the information brought by an image is as much as that conveyed by a whole passage of text. In order to exploit the advantages of imagery, a novel interactive Web search framework is proposed, where image snippets are first extracted from Web pages and then provided, along with the text snippets, to the user for result presentation and relevance feedback, as well as being presented alone to the user for image suggestion. User studies show that it is more convenient for the user to identify the Web pages he or she expects and to reformulate the initial query. Further experiments demonstrate the promise of introducing multimodal techniques into the proposed interactive Web search framework.
Astrocyte-Synapse Structural Plasticity (2014)

The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmission. Astrocytic structures are frequently observed in close association with glutamatergic synapses, providing a morphological entity for bidirectional interactions with synapses. Experimental evidence indicates that astrocytes sense neuronal activity by elevating their intracellular calcium in response to neurotransmitters and may communicate with neurons. The precise role of astrocytes in regulating synaptic properties, function, and plasticity remains however a subject of intense debate and many aspects of their interactions with neurons remain to be investigated. A particularly intriguing aspect is their ability to rapidly restructure their processes and modify their coverage of the synaptic elements. The present review summarizes some of these findings with a particular focus on the mechanisms driving this form of structural plasticity and its possible impact on synaptic structure and function.
Cyclic peptide template combinatorial libraries: synthesis and identification of chymotrypsin inhibitors. (1995)

A cyclic peptide template combinatorial library in a positional scanning format, composed of three positional libraries, was synthesized using solid-phase chemistry and four orthogonal protecting groups (Fmoc, Boc, Dde, OAll). The cyclic peptide template is composed of three lysine residues and one glutamic acid residue. The chemical diversity was introduced by acylating the epsilon-amino groups of the lysine residues using 10 carboxylic acids in addition to the 20 proteinogenic amino acids. The library components have been shown to be stable towards proteolytic degradation. Compounds with chymotrypsin inhibitory activity were identified through the screening of this library.
Review article (1991)

Currently, all methods of prenatal diagnosis require an invasive approach. The next step in the continuing challenge to make prenatal diagnosis more accessible is the development of a noninvasive test. The presence of fetal cells in the maternal circulation has been debated for several decades, but traditional attempts to identify the rare fetal cell within the pool of maternal cells have met with partial success at best. Today, with the aid of highly sensitive and specific techniques such as fluorescent activated cell sorting, polymerase chain reaction, and in-situ hybridization, the task of finding the "on-in-a-million" fetal cell is moving from the realm of the imagination into that of reality.
Anticancer strategies involving the vasculature: vascular targeting and the inhibition of angiogenesis. (1992)

Progress in our understanding of tumour angiogenesis and an appreciation of the marked differences between quiescent and proliferating endothelium are revealing new strategies for anticancer therapy. This article outlines these strategies and critically assesses their chances of success.
ErbB-2 Activates Stat3α in a Src- and JAK2-dependent Manner (2002)

Stats (signal transducer and activator of transcription) are latent transcription factors that translocate from the cytoplasm to the nucleus. Constitutive activation of Stat3 alpha by upstream oncoproteins and receptor tyrosine kinases has been found in many human tumors and tumor-derived cell lines. Constitutively activated Stat3 alpha is often correlated with the activation of ErbB-2, a member of the EGFR family. To explore the involvement of ErbB-2 in the activation of Stat3 and the mechanism underlying this event, an ErbB-2 point mutant was used as a model of constitutively activated receptor. Phenylalanine mutations (Y-->F) were made in the autophosphorylation sites of the receptor, and their ability to activate Stat3 alpha was evaluated. Our results suggest that Stat3 alpha and JAK2 associates with ErbB-2 prior to phosphorylation of the receptor and that full activation of Stat3 alpha by ErbB-2 requires the participation of other non-receptor tyrosine kinases. Both Src and Jak2 kinases contribute to the activation of Stat3 alpha but Src binds to ErbB-2 only when the receptor is phosphorylated. Our results also suggest that tyrosine 1139 may be important for Src homology 2 domain association because a mutant lacking this tyrosine reduces the ability of the Src homology 2 domain to bind to ErbB-2 and significantly decreases its ability to activate Stat3 alpha.