gebhart/patrepeval huggingface dataset:
Phase I study of liposome encapsulated irinotecan (PEP02) in advanced solid tumor patients (2008)

2565 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan aiming to enhance tumor localization and improve pharmacokinetic properties of irinotecan and its active metabolite-SN38. The aims of the study are to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02 in patients with advanced refractory solid tumors. Methods: Pts with advanced refractory solid tumors, ECOG PS 0–1, and adequate hematological, hepatic and renal functions were eligible. PEP02 was given as 90mins i.v. infusion, repeated every 3 weeks. The doses would have been escalated from 60, 120, 180 to 240 mg/m2 in a single-patient cohort accelerated titration design. PK samples were collected on days 1, 2, 3, 8 and 21. Results: A total of 11 pts (M/F 1/10; median age 47, range 41–67) were enrolled onto three dose levels, with 1, 6 and 4 pts at dose level I (60 mg/m2), II (120 mg/m2) and III (180 mg/m2), respectively. DLT was observed in 3 pts, including 1 at dose level II (grade 3 catheter-related infection) and 2 at dose level III (grade 3 diarrhea and febrile neutropenia in 1 and treatment-related mortality secondary to grade 4 diarrhea and neutropenia in 1). MTD was determined as 120 mg/m2. The PK of total irinotecan after PEP02 dosing were characterized by, i.e. after 120 mg/m2, low clearance (mean = 0.0591 L/m2/hr), small volume of distribution (mean = 1.8 L/m2, similar to plasma volume), and prolonged terminal half-life (mean=29.5 hr). The plasma concentration-time profiles of encapsulated irinotecan (PEP02) in each pt matched approximately with those of total irinotecan indicating that the release of irinotecan from liposomes occurred slowly over time. Comparing with published PK parameters after 125 mg/m2 of irinotecan, the Cmax of SN-38 after 120 mg/m2 of PEP02 was lower (9.2±3.5 vs 26.3±11.9 ng/mL), the terminal t1/2 of SN-38 was longer (75.4±43.8 vs 10.4±3.1 hrs) and the AUC of SN-38 was larger (710±395 vs 229±108 ng.h/mL). The best response of 10 evaluable pts was PR in 2 (cervical and pancreatic cancer) and SD in 3. Conclusions: The MTD of PEP02 monotherapy at 3-week interval is 120 mg/m2, which will be the recommended dose for future phase II studies. Preliminary data suggest that PEP02 exhibits encouraging pharmacokinetic, safety and efficacy profiles. No significant financial relationships to disclose.
A Novel Gibberellin-Induced Gene from Rice and Its Potential Regulatory Role in Stem Growth (2000)

Os-GRF1 (Oryza sativa-GROWTH-REGULATING FACTOR1) was identified in a search for genes that are differentially expressed in the intercalary meristem of deepwater rice (Oryza sativa L.) internodes in response to gibberellin (GA). Os-GRF1 displays general features of transcription factors, contains a functional nuclear localization signal, and has three regions with similarities to sequences in the database. One of these regions is similar to a protein interaction domain of SWI2/SNF2, which is a subunit of a chromatin-remodeling complex in yeast. The two other domains are novel and found only in plant proteins of unknown function. To study its role in plant growth, Os-GRF1 was expressed in Arabidopsis. Stem elongation of transformed plants was severely inhibited, and normal growth could not be recovered by the application of GA. Our results indicate that Os-GRF1 belongs to a novel class of plant proteins and may play a regulatory role in GA-induced stem elongation.
Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation. (1984)

In this report we examine the effects of chronic anaerobic exposure and subsequent reoxygenation on protein synthesis patterns in Chinese hamster ovary cells. It is observed by two-dimensional gel electrophoresis (isoelectric focusing/NaDodSO4/PAGE) that the transition from an atmospheric environment to an anaerobic state transiently induces the major heat-shock proteins (at 68 and 89 kDa). As the period of anaerobiosis increases, this heat-shock induction disappears and a new set of proteins (at 76 and 97 kDa) is induced. By two-dimensional gel electrophoresis and partial proteolytic mapping, these new proteins, which are induced by anaerobic exposures exceeding 12 hr, are identical to 76 and 97 kDa (p76 and p97, respectively) proteins induced by extended periods of glucose deprivation (greater than 14 hr) when oxygen is present. Furthermore, the induction of these proteins under anoxia occurs in the presence of glucose, and increasing the glucose content of the starting media does not affect the induction. When anaerobic p76 and p97 induced cells are returned to atmospheric oxygen, p76 and p97 are repressed, while the heat-shock proteins are again transiently induced. This work further suggests the importance of deprivation and release environments in controlling the expression of these two stress protein systems. It is suggested that their natural expression may be determined by comparable circumstances.
Capture and Dewarping of Page Spreads with a Handheld Compact 3D Camera (2012)

This paper describes a system for capturing images of books with a handheld 3D stereo camera, which performs dewarping to produce images that are flattened. A Fuji film consumer grade 3D camera provides a highly mobile and low-cost 3D capture device. Applying standard computer vision algorithms, camera calibration is performed, the captured images are stereo rectified, and the depth information is computed by block matching. Due to technical limitations, the resulting point cloud has defects such as splotches and noise, which make it hard to recover the precise 3D locations of the points on the book pages. We address this problem by computing curve profiles of the depth map and using them to build a cylinder model of the pages. We then employ meshes to facilitate the flattening and rendering of the cylinder model in virtual space. We have implemented a prototype of the system and report on a preliminary evaluation based on measuring the straightness of resulting text lines.
Chromium(III) Octaethylporphyrinato Tetracarbonylcobaltate:  A Highly Active, Selective, and Versatile Catalyst for Epoxide Carbonylation (2005)

The development of a highly active and selective porphyrin-based epoxide carbonylation catalyst, [(OEP)Cr(THF)2][Co(CO)4] (1; OEP = octaethylporphyrinato; THF = tetrahydrofuran), is detailed. Complex 1 is a separated ion pair composed of a tetracarbonylcobaltate anion and an octahedral chromium porphyrin complex axially ligated by two THF ligands. Regarding the carbonylation of epoxides to beta-lactones, catalyst 1 exhibits excellent turnover numbers (up to 10,000) and turnover frequencies (up to 1670 h(-1)), with regioselective carbonyl insertion occurring between the oxygen and the sterically less hindered carbon of the epoxide substrate. Complex 1 is highly tolerant of nonprotic functional groups, carbonylating an array of aliphatic and cycloaliphatic epoxides, as well as epoxides with pendant ethers, esters, and amides. With careful control of reaction conditions in the carbonylation of glycidyl esters, the exclusive production of either the beta- or gamma-lactone isomer was achieved. Through analysis of reaction stereochemistry, a mechanism for the formation of gamma-lactone products was proposed. Overall, a broad array of synthetically useful lactones has been synthesized in a rapid and selective fashion by catalytic carbonylation using [(OEP)Cr(THF)2][Co(CO)4].
Microbiology of Sinusitis (2011)

Most sinus infections are viral, and only a small proportion develops a secondary bacterial infection. Rhinoviruses, influenza viruses, and parainfluenza viruses are the most common causes of sinusitis. The most common bacteria isolated from pediatric and adult patients with community-acquired acute purulent sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic bacteria (Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.) are the main isolates in chronic sinusitis. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are commonly isolated from patients with nosocomial sinusitis, the immunocompromised host, those with HIV infection, and in cystic fibrosis. Fungi and Pseudomonas aeruginosa are the most common isolates in neutropenic patients. The microbiology of sinusitis is influenced by the previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens.
Formation of Actin Stress Fibers and Focal Adhesions Enhanced by Rho-Kinase (1997)

The small guanosine triphosphatase (GTPase) Rho is implicated in the formation of stress fibers and focal adhesions in fibroblasts stimulated by extracellular signals such as lysophosphatidic acid (LPA). Rho-kinase is activated by Rho and may mediate some biological effects of Rho. Microinjection of the catalytic domain of Rho-kinase into serum-starved Swiss 3T3 cells induced the formation of stress fibers and focal adhesions, whereas microinjection of the inactive catalytic domain, the Rho-binding domain, or the pleckstrin-homology domain inhibited the LPA-induced formation of stress fibers and focal adhesions. Thus, Rho-kinase appears to mediate signals from Rho and to induce the formation of stress fibers and focal adhesions.
Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma (2012)

MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.
Anti-T cell monoclonal antibodies conjugated to ricin as potential reagents for human GVHD prophylaxis: effect on the generation of cytotoxic T cells in both peripheral blood and bone marrow. (1984)

Three murine anti-human monoclonal antibodies broadly reactive with human T cells were conjugated to intact ricin toxin. The purgative effects of these immunotoxins (IT) on alloreactive T cells after in vitro pretreatment was tested in an in vitro assay measuring the generation of cytotoxic T cells (CTL). Pretreatment was performed in the presence of lactose to block the native binding of ricin, thus rendering IT antibody specific. Blocking studies with free antibody showed that selective toxicity was determined by the antibody moiety of the antibody-toxin conjugate. Our assay system permitted the measurement of significant CTL levels in the bone marrow. Thus, we were able to determine the differential selectivity of IT for T cells as compared with stem cells in the same donor preparation. Our studies show that antibody-intact ricin conjugates have great potential as T cell purgative reagents for GVHD prophylaxis in human BMT.
Assignment of Biochemical Functions to Glycosyl Transferase Genes Which Are Essential for Biosynthesis of Exopolysaccharides in Sphingomonas Strain S88 and Rhizobium leguminosarum (1998)

Glycosyl transferases which recognize identical substrates (nucleotide-sugars and lipid-linked carbohydrates) can substitute for one another in bacterial polysaccharide biosynthesis, even if the enzymes originate in different genera of bacteria. This substitution can be used to identify the substrate specificities of uncharacterized transferase genes. The spsK gene of Sphingomonas strain S88 and the pssDE genes of Rhizobium leguminosarum were identified as encoding glucuronosyl-(B1-->4)-glucosyl transferases based on reciprocal genetic complementation of mutations in the spsK gene and the pssDE genes by segments of cloned DNA and by the SpsK-dependent incorporation of radioactive glucose (Glc) and glucuronic acid (GlcA) into lipid-linked disaccharides in EDTA-permeabilized cells. By contrast, glycosyl transferases which form alternative sugar linkages to the same substrate caused inhibition of polysaccharide synthesis or were deleterious or lethal in a foreign host. The negative effects also suggested specific substrate requirements: we propose that spsL codes for a glucosyl-(beta1-->4)-glucuronosyl transferase in Sphingomonas and that pssC codes for a glucuronosyl-(beta1-->4)-glucuronosyl transferase in R. leguminosarum. Finally, the complementation results indicate the order of attachment of sphingan main-chain sugars to the C55-isoprenylphosphate carrier as -Glc-GlcA-Glc-isoprenylpyrophosphate.
unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA (1999)

Initiation of translation of the animal picornavirus RNAs occurs via a mechanism of direct ribosome entry, which requires a segment of the 5' UTR of the RNA, known as the internal ribosome entry site (IRES). In addition, translation of the enterovirus and rhinovirus (HRV) subgroups requires cellular trans-acting factors that are absent from, or limiting in rabbit reticulocytes, but are more abundant in HeLa cell extracts. It has been shown previously that HeLa cells contain two separable activities, each of which independently stimulates HRV IRES-dependent translation when used to supplement reticulocyte lysate; one of these activities was identified as polypyrimidine tract-binding protein (PTB). Here, the purification of the second activity is achieved by use of an RNA-affinity column based on the HRV 5' UTR. It comprises two components: a 38-kD protein (p38), which is a novel member of the GH-WD repeat protein family and has no intrinsic RNA-binding activity; and a 96- to 97-kD protein doublet, which was identified as unr, an RNA-binding protein with five cold-shock domains. Coimmunoprecipitation with antibodies against either protein shows that the two proteins interact with each other, and thus p38 is named unrip (unr-interacting protein). Recombinant unr acts synergistically with recombinant PTB to stimulate translation dependent on the rhinovirus IRES. In contrast, unr did not significantly augment the PTB-dependent stimulation of poliovirus IRES activity.
Fermentative production of isobutene (2012)

Isobutene (2-methylpropene) is one of those chemicals for which bio-based production might replace the petrochemical production in the future. Currently, more than 10 million metric tons of isobutene are produced on a yearly basis. Even though bio-based production might also be achieved through chemocatalytic or thermochemical methods, this review focuses on fermentative routes from sugars. Although biological isobutene formation is known since the 1970s, extensive metabolic engineering is required to achieve economically viable yields and productivities. Two recent metabolic engineering developments may enable anaerobic production close to the theoretical stoichiometry of 1isobutene + 2CO(2) + 2H(2)O per mol of glucose. One relies on the conversion of 3-hydroxyisovalerate to isobutene as a side activity of mevalonate diphosphate decarboxylase and the other on isobutanol dehydration as a side activity of engineered oleate hydratase. The latter resembles the fermentative production of isobutanol followed by isobutanol recovery and chemocatalytic dehydration. The advantage of a completely biological route is that not isobutanol, but instead gaseous isobutene is recovered from the fermenter together with CO(2). The low aqueous solubility of isobutene might also minimize product toxicity to the microorganisms. Although developments are at their infancy, the potential of a large scale fermentative isobutene production process is assessed. The production costs estimate is 0.9 Euro kg(-1), which is reasonably competitive. About 70% of the production costs will be due to the costs of lignocellulose hydrolysate, which seems to be a preferred feedstock.
Anaerobic storage of red blood cells in a novel additive solution improves in vivo recovery (2009)

Anaerobically stored RBCs in OFAS3 have superior recovery at 6 weeks compared to the controls and equivalent recovery at 9 weeks with no change in life span. Anaerobic storage of RBCs may provide improved RBCs for transfusion at 6 weeks of storage and may enable extending storage beyond the current 42-day limit.
Hepatocyte growth factor/scatter factor effects on epithelia. Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-met receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium. (1994)

Intestinal epithelial cells rest on a fibroblast sheath. Thus, factors produced by these fibroblasts may influence epithelial function in a paracrine fashion. We examined modulation of intestinal epithelial function by one such fibroblast product, scatter factor/hepatocyte growth factor (HGF/SF). This effect was studied in vitro by using model T84 intestinal epithelial cells. When applied to confluent T84 monolayers, HGF/SF attenuates transepithelial resistance to passive ion flow in a dose-dependent manner (maximum fall at 300 ng/ml, 28% control monolayer resistance, P < 0.001, ED50 of 1.2 nM), t1/2 of 20 h. This functional effect of HGF/SF and distribution of its receptor, c-met, are polarized to the basolateral membranes of T84 intestinal epithelial cells. HGF/SF effects on resistance are not attributable to altered transcellular resistance (opening of Cl- and/or basolateral K+ channels), cytotoxicity, or enhanced cell proliferation; they therefore represent specific regulation of paracellular tight junction resistance. Analysis with biochemically purified rodent HGF/SF and Madin-Darby canine kidney cells reveals that effects on paracellular tight junctions also occur in other nontransformed epithelia. Binding of HGF/SF to its receptor in T84 intestinal epithelial cells is accompanied by tyrosine phosphorylation of the receptor. Because loosening of intercellular junctions between cells could facilitate separation, spreading, and migration of epithelial cells during physiologic processes such as wound resealing, we determined the effects of HGF/SF on intestinal epithelial wound resealing using our previously published in vitro model (Nusrat, A., C. Delp, and J. L. Madara. 1992. J. Clin. Invest. 89:1501-1511). HGF/SF markedly enhanced wound closure (> 450% increase in rate, P < 0.001) by influencing the migratory and spreading response in not only cells adjoining the wound but also cells many positions removed from the wound. We thus speculate that HGF/SF may serve as an important cytokine that influences epithelial parameters such as transepithelial resistance and wound resealing. Further pharmacological approaches to manipulate HGF/SF signaling pathways may provide novel therapeutic strategies to enhance repair of intestinal epithelial erosions/ulcerations.
Adoptively transferred effector cells derived from naïve rather than central memory CD8+T cells mediate superior antitumor immunity (2009)

Effector cells derived from central memory CD8(+) T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting that they are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacy of effector cells derived from naïve T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naïve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specific T-cell receptor. We found that naïve, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naïve T cells lost the expression of CD62L more rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminal differentiation and replicative senescence. Consistent with this KLRG-1(-) phenotype, naïve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptive transfer. These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8(+) T cells may allow superior efficacy upon adoptive transfer.
Multi-view geometry of 1D radial cameras and its application to omnidirectional camera calibration (2005)

We study the multi-view geometry of 1D radial cameras. A broad a class of both central and non-central cameras, such as fish-eye and catadioptric cameras, can be reduced to 1D radial cameras under the assumption of known center of radial distortion. For cameras in general configuration, we introduce a quadrifocal tensor that can be computed linearly from 15 or more features seen in four views. From this tensor a metric reconstruction of the 1D cameras as well as the observed features can be obtained. In a second phase this reconstruction can then be used as a calibration object to estimate a non-parametric non-central model for the cameras. We study some degenerate cases, including pure rotation. In the case of a purely rotating camera we obtain a trifocal tensor that can be estimated linearly from 7 points in three views. This allows us to obtain a metric reconstruction of the plane at infinity. Next, we use the plane at infinity as a calibration device to non-parametrically estimate the radial distortion. We demonstrate the results of our approach on real and synthetic images
Endogenous Sex Hormones, Breast Cancer Risk, and Tamoxifen Response: An Ancillary Study in the NSABP Breast Cancer Prevention Trial (P-1) (2006)

These data do not support the use of endogenous sex hormone levels to identify women who are at particularly high risk of breast cancer and who are most likely to benefit from chemoprevention with tamoxifen.
Branch migration inhibition in PCR-amplified DNA: homogeneous mutation detection (2000)

A novel method for detection of any mutation located within a PCR-amplified DNA sequence was demonstrated. The method is based on the inhibition of spontaneous DNA branch migration. Partial duplexes produced by PCR amplification of a test and a reference genomic DNA sample anneal to form four-stranded cruciform structures. Spontaneous DNA branch migration results in dissociation of these structures when the test and reference sequences are identical. Any base substitution, deletion or insertion inhibits branch migration and produces stable cruciform structures. When suitable ligands are attached to the PCR primers, the cruciform structures can be detected by standard immunochemical methods. This approach was tested using several commonly occurring mutations within the human cystic fibrosis gene. New methods for increasing the specificity of PCR amplifications are described that were used for successful mutation analysis.