gebhart/patrepeval huggingface dataset:
Heterogeneity of Natural Killer Cells (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Preparation of a Cathepsin D Sensitive Near-Infrared Fluorescence Probe for Imaging (1999)

A variety of proteases are overexpressed or activated during pathogenesis and represent important targets for therapeutic drugs. We have previously shown that optical imaging probes sensitive in the near-infrared fluorescence (NIRF) spectrum can be used for in vivo imaging of enzyme activity. In the current study, we show that these probes can be designed with specificity for specific enzymes, for example, cathepsin D which is known to be overexpressed in many tumors. A NIR cyanine fluorochrome served as the optical reporter and was attached to the amino terminal of an 11 amino acid peptide sequence with specificity for cathepsin D. The peptides were subsequently attached to a synthetic graft copolymer for efficient tumoral delivery. The close spatial proximity of the multiple fluorochromes resulted in quenching of fluorescence in the bound state. A 350-fold signal amplification was observed post cleavage during in vitro testing. Cell culture experiments using a rodent tumor cell line stably transfected with human cathepsin D confirmed enzyme specific activation within cells. This sequence but not a scrambled control sequence showed enzyme specificity in vitro. We conclude that activatable NIRF optical probes can be synthesized to potentially probe for specific enzymes in living organisms.
Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women--a clinical research center study. (1996)

Abdominal fat distribution is influenced by androgen levels in both men and women. The purpose of this study was to assess the effects on fat distribution of administering nandrolone decanoate (ND; an anabolic steroid with weak androgenic activity) or spironolactone (SP; an antiandrogen) in obese postmenopausal women. The design was a randomized, placebo-controlled, 9-month trial with simultaneous calorie restriction for weight loss. Women in all three groups lost comparable amounts of weight, but the ND-treated women gained lean mass relative to the other two groups (P < 0.0005) and lost more body fat than women in the SP group (P < 0.01). The resting metabolic rate also increased slightly in the ND group. ND treatment produced a gain in visceral fat, as determined by computed tomography scan, and a relatively greater loss of sc abdominal fat. SP-treated women lost significantly less sc fat than the other two groups. Serum cholesterol decreased in the placebo group, but increased slightly in the other two groups (significant for SP vs. placebo, P < 0.05). High density lipoprotein cholesterol decreased significantly in the ND-treated women. There were no significant changes in fasting glucose or insulin sensitivity. We conclude that administration of exogenous androgens modulates body composition in obese postmenopausal women and independently affects visceral and sc abdominal fat.
<title>DepthCube solid-state 3D volumetric display</title> (2004)

The DepthCube 3D Volumetric Display is a solid state, rear projection, volumetric display that consists of two main components: a high-speed video projector, and a multiplanar optical element composed of a air-spaced stack of liquid crystal scattering shutters. The high-speed video projector projects a sequence of slices of the 3D image into the multiplanar optical element where each slice is halted at the proper depth. Proprietary multiplanar anti-aliasing algorithms smooth the appearance of the resultant stack of image slices to produce a continuous appearing truly three-dimensional image. The resultant 3D image is of exceptional quality and provides all the 3D vision cues found in viewing real object.
Tumor regionality in the mouse intestine reflects the mechanism of loss of Apc function (2004)

Inherited colorectal cancer syndromes in humans exhibit regional specificity for tumor formation. By using mice with germline mutations in the adenomatous polyposis coli gene (Apc) and/or DNA mismatch repair genes, we have analyzed the genetic control of tumor regionality in the mouse small intestine. In C57BL/6 mice heterozygous for the Apc multiple intestinal neoplasia mutation (Apc(Min)), in which tumors are initiated by loss of heterozygosity by means of somatic recombination, tumors form preferentially in the distal region of the small intestine. By contrast, the formation of tumors initiated by allelic silencing on the AKR Apc(Min) genetic background is strongly skewed toward the ileocecal junction. A third tumor regionality is displayed by tumors that develop in MMR-deficient Apc(Min/+) mice, in which mutation of the Apc gene is responsible for tumor initiation. Thus, tumor regionality in the small intestine of Apc(Min/+) reflects the mechanism by which the wild-type allele of Apc is inactivated. We have reexamined the mechanism of Apc loss in tumors from Apc(1638N/+) mice, in which tumors of the small intestine develop in a regional pattern overlapping that of mismatch repair-deficient mice. In contrast to previous reports, we find that tumors from Apc(1638N/+) mice on a congenic C57BL/6 background maintain the wild-type allele of Apc. Our studies demonstrate a pathway-specific regionality for tumor development in mouse models for inherited intestinal cancer, an observation that is reminiscent of the regional preference for tumor development in the human colon. Perhaps, the power of mouse genetics and biology can be harnessed to identify genetic and other factors that contribute to tumor regionality.
Construction, purification, and characterization of a hybrid protein comprising the DNA binding domain of the LexA repressor and the Jun leucine zipper: a circular dichroism and mutagenesis study (1991)

An increasing number of eukaryotic transcription factors interacting specifically with DNA comprise a dimerization motif called the "leucine zipper". These leucine zipper proteins form homodimers and/or heterodimers with another protein containing a leucine zipper motif. The leucine zipper of the oncoprotein Jun is particular in that Jun may form homodimers as well as heterodimers with the oncoprotein Fos, which are however more stable than the Jun-Jun homodimers. Leucine zipper dimerization is thought to occur through a coiled-coil arrangement of parallel alpha-helices, but the rules governing the specificity of homo- and/or heterodimerization are still largely unknown. To address this question in the case of the Jun leucine zipper, we constructed a fusion protein containing the amino-terminal DNA binding domain of the LexA repressor from Escherichia coli fused to the Jun leucine zipper. This hybrid protein (LexA-JunZip) is stable in E. coli and confers much tighter repression in vivo than the DNA binding domain of LexA alone. DNA binding competition experiments with synthetic Jun and Fos leucine zipper peptides in vitro showed that the leucine zipper mediated dimerization of LexA-JunZip is essential for DNA binding of the fusion protein. The purified LexA-JunZip protein dimerizes in vitro with a dimerization constant of 2 x 10(7) M-1 at 5 degrees C. Dimerization is very sensitive to temperature, since the dimerization constant drops at 20 degrees C to 2 x 10(6) M-1 and at 30 degrees C to only 3 x 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Self-Assembling Cytotoxins (1986)

Decanal and N-amino-N'-1-octylguanidine (AOG), combined at 28 microM each, mediated erythrocyte lysis within 80 minutes under physiological conditions. By contrast, no lysis was observed after 20 hours with either decanal (56 microM) or AOG (100 microM) alone. The pronounced synergism observed for these chemicals and similar reactive pairs of chemicals is due to the self-assembly of more cytotoxic hydrazones in situ. Decanal and AOG also exhibit synergistic activity against cultured human cells (HeLa) and bacteria (Escherichia coli J96). This synergism may be useful in the design of cytotoxins that would self-assemble selectively from nontoxic precursors within tumors, while sparing normal tissue.
KRN951, a Highly Potent Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, Has Antitumor Activities and Affects Functional Vascular Properties (2006)

Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis by stimulating the proangiogenic signaling of endothelial cells via activation of VEGF receptor (VEGFR) tyrosine kinases. Therefore, VEGFRs are an attractive therapeutic target for cancer treatment. In the present study, we show that a quinoline-urea derivative, KRN951, is a novel tyrosine kinase inhibitor for VEGFRs with antitumor angiogenesis and antigrowth activities. KRN951 potently inhibited VEGF-induced VEGFR-2 phosphorylation in endothelial cells at in vitro subnanomolar IC50 values (IC50 = 0.16 nmol/L). It also inhibited ligand-induced phosphorylation of platelet-derived growth factor receptor-beta (PDGFR-beta) and c-Kit (IC50 = 1.72 and 1.63 nmol/L, respectively). KRN951 blocked VEGF-dependent, but not VEGF-independent, activation of mitogen-activated protein kinases and proliferation of endothelial cells. In addition, it inhibited VEGF-mediated migration of human umbilical vein endothelial cells. Following p.o. administration to athymic rats, KRN951 decreased the microvessel density within tumor xenografts and attenuated VEGFR-2 phosphorylation levels in tumor endothelium. It also displayed antitumor activity against a wide variety of human tumor xenografts, including lung, breast, colon, ovarian, pancreas, and prostate cancer. Furthermore, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis revealed that a significant reduction in tumor vascular hyperpermeability was closely associated with the antitumor activity of KRN951. These findings suggest that KRN951 is a highly potent, p.o. active antiangiogenesis and antitumor agent and that DCE-MRI would be useful in detecting early responses to KRN951 in a clinical setting. KRN951 is currently in phase I clinical development for the treatment of patients with advanced cancer.
The development of an anchorage-independence assay using human lung tumor cells to screen potential chemopreventive agents. (1996)

Advances in tumor biology research have led to the possibility of early detection of cancers and rational intervention of cancer development using chemopreventive agents. A significant number of potential chemopreventive agents have been identified from epidemiological surveys, independent research efforts, clinical data or based on structural homology with known chemopreventive agents. We have developed a fast, reliable in vitro model for screening potential chemopreventive agents using inhibition of anchorage-independent growth of a human lung tumor cell line, A427.A427 cells were plated in soft agarose containing a known chemopreventive agent, 13-cis-retinoic acid as the test agent and allowed to develop colonies for 28 days. A cytotoxicity test was used concurrently with anchorage independent assay for measuring the relative survival of cells to ensure that any observed inhibition of anchorage independent growth is due to the biological activity of the chemopreventive agent and not due to cellular toxicity. At the end of 28 days of growth, the stained colonies were enumerated, and the inhibition of spontaneous colony formation was measured. 13-cis-Retinoic acid inhibited the growth of A427 colonies in a concentration dependent manner. Data from 25 successive experiments indicate that a concentration of 33 microM consistently inhibited colony formation by 66.2 +/- 16.5 percent, ranging from 27 to 96.1% inhibition. This assay is a useful tool for screening potential chemopreventive agents, as it uses human cells as substrates rendering the efficacy data feasible for direct extrapolation to humans.
The Hypermedia Authoring Research Toolkit (HART) (1994)

A major obstacle hindering the advancement and commercial acceptance of hypermedia is the cost of converting paper based information into hypermedia form. The Hypermedia Authoring Research Toolkit (HART) was developed to support the human editor during this media-to-hypermedia conversion process. The tool's goal is to help improve the correctness and completeness of the hypermedia database, as well as reduce the media-to-hypermedia conversion cost.
Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer (2020)

Sacituzumab govitecan is a novel targeted treatment with promising activity in mTNBC.
The mdm-2 gene is induced in response to UV light in a p53-dependent manner. (1993)

Irradiation of mammalian cells with UV light results in a dose-dependent accumulation of the p53 tumor-suppressor gene product that is evident within 2 hr. UV treatment causes a dramatic increase in p53-specific transcriptional transactivation activity and an increase in expression of the p53-responsive gene mdm-2. UV-stimulated mdm-2 expression is not directly correlated with the level of p53 protein in a cell because mdm-2 induction is delayed at high UV doses even though p53 levels rise almost immediately. Cells lacking p53 protein do not respond to UV by increasing their expression of mdm-2. The delayed induction of mdm-2 at high UV doses suggests that, in addition to p53 protein levels, other factors contribute to the regulation of mdm-2 expression following UV treatment. The time of induction of mdm-2 in cells treated with UV light correlates with recovery of normal rates of DNA synthesis, presumably after DNA repair. These data indicate a possible role for mdm-2 in cell cycle progression.
Temperature-dependent development and reproduction of the spider mite, Schizotetranychus bambusae Reck (Acari: Tetranychidae) (2000)

Development, survivorship, and reproduction of the mite Schizotetranychus bambusae Reck reared on fresh bamboo leaf were evaluated at 5 constant temperatures (21, 24, 27, 30, and 33°C). The development time from egg to adult varied from 16.7 d at 21°C to 7.6 d at 33°C. The developmental thresholds for egg, larva, protonymph, deurtonymph, pre-oviposition and combined immature stages were estimated at 12.4, 15.3, 14.0, 15.2, 10.7 and12.5°C, respectively. High temperature (33°C) engendered a decline in larval and protonymphal development.A modified nonlinear Logan model describing the relationship between developmental rate and temperature for all immature stages was constructed. Survivorship was highest (88.3%) at 27°C; whereas at 21 and 33°C, it came to 61.7 and 55.7%, respectively. After emergence the adult had a pre-oviposition period that ranged from 1.9 d at 21°C to 1.0 d at 33°C. The highest number of eggs (23.4) was produced at 27°C, the lowestat 33°C. The longest reproductive duration (15.5 d) was recorded at 21°C, and the shortest (4.3 d) at 33°C. Mites reared at 27°C had the highest net reproductive rate (15.6), whereas at 33°C they had the highest intrinsic rate of increase (0.1686). Our results suggest that S. bambusae could develop and reproduce within a wide range of temperatures.
Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb. (1998)

We have previously shown that monocytes adhere to the vascular wall during collateral vessel growth (arteriogenesis) and capillary sprouting (angiogenesis). In this study we investigated the association of monocyte accumulation with both the production of the cytokines-basic fibroblast growth factor (bFGF) and TNF-alpha-and vessel proliferation in the rabbit after femoral artery occlusion. In particular, we studied the effects of an increase in monocyte recruitment by LPS on capillary density as well as collateral and peripheral conductance after 7 d of occlusion. Monocytes accumulated around day 3 in collateral arteries when maximal proliferation was observed, and stained strongly for bFGF and TNF-alpha. In the lower limb where angiogenesis was shown to be predominant, macrophage accumulation was also closely associated with maximal proliferation (around day 7). LPS treatment significantly increased capillary density (424+/-26.1 n/mm2 vs. 312+/-20.7 n/mm2; P < 0.05) and peripheral conductance (109+/-33.8 ml/min/100 mmHg vs. 45+/-6.8 ml/min/100 mmHg; P < 0.05) as compared with untreated animals after 7 d of occlusion. These results indicate that monocyte activation plays a major role in angiogenesis and collateral artery growth.
The Extrapancreatic Effects of Glucagon-Like Peptide-1 and Related Peptides (2009)

GLP-1 and its metabolite have important extrapancreatic effects particularly with regard to the cardiovascular system and insulinomimetic effects with respect to glucose homeostasis. These effects may be particularly important in the obese state. GLP-1, GLP-1m, and exendin-4 therefore have potential therapeutic roles because of their diffuse extrapancreatic actions.
Design and Application of Antibody Cysteine Variants (2010)

Antibodies are multidomain proteins that are extensively used as a research tool in molecular biology and as therapeutics in medicine. In many cases, antibodies are engineered to contain surface cysteines for the site-specific conjugation of payloads. These antibodies can serve as payload vehicles in targeting a diseased cell to which the conjugated molecules exercise their activity. Here, we design and analyze a set of fourteen new IgG1 cysteine variants, with at least one variant per immunoglobulin fold domain. The cross-linking propensity of these mutants correlates very well with a tool we have developed for measuring aggregation propensity in silico, called spatial aggregation propensity (SAP). Our results indicate the utility of the SAP technology in selecting antibody cysteine variants with desired properties. Moreover, the different oligomerization propensity of the variants suggests a variety of applications in molecular biology and medicine, such as payload delivery, structural analysis, electrophoresis, and chromatography.
Surface loss limit of the power scaling of a thin-disk laser (2006)

We show that the general limit of power scaling of thin-disk lasers comes not only from the overheating and amplified spontaneous emission (ASE) but also from the surface loss. Overheating or thermal fracture increases the transverse size at the scaling, whereas ASE limits the gain-size product. The gain coefficient should decrease at the scaling. However, the round-trip gain should remain larger than the background loss; hence, the thickness should increase at the scaling. The limit of the output power per single active element occurs when the medium becomes too thick and cannot work efficiently without overheating. The maximum output power scales inversely with the cube of the surface loss coefficient. In the quasi-continuous regime, the average power scales inversely to the product of the duration of pulses to the repetition rate.
Assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an RNA aptamer for precise gene editing (2017)

Writing specific DNA sequences into the human genome is challenging with non-viral gene-editing reagents, since most of the edited sequences contain various imprecise insertions or deletions. We developed a modular RNA aptamer-streptavidin strategy, termed S1mplex, to complex CRISPR-Cas9 ribonucleoproteins with a nucleic acid donor template, as well as other biotinylated molecules such as quantum dots. In human cells, tailored S1mplexes increase the ratio of precisely edited to imprecisely edited alleles up to 18-fold higher than standard gene-editing methods, and enrich cell populations containing multiplexed precise edits up to 42-fold. These advances with versatile, preassembled reagents could greatly reduce the time and cost of in vitro or ex vivo gene-editing applications in precision medicine and drug discovery and aid in the development of increased and serial dosing regimens for somatic gene editing in vivo.
Precise Gene Deletion and Replacement Using the CRISPR/Cas9 System in Human Cells (2017)

Protocol Summary Here, we describe targeted gene deletion and replacement in human cells via the CRISPR/Cas9 system using two guide RNAs. The system effectively generated targeted deletions of varied length, regardless of the transcriptional status of the target gene. It is notable that targeted gene deletions generated via CRISPR/Cas9 and two guide RNAs resulted in the formation of correct junctions at high efficiency. Moreover, in the presence of a homology repair donor, the CRISPR/Cas9 system could guide precise gene replacement. Our results illustrate that the CRISPR/Cas9 system can be used to precisely and effectively generate targeted deletions or gene replacement in human cells, which will facilitate characterization of functional domains in protein-coding genes as well as noncoding regulatory sequences in animal genomes.
Early diagnosis of acute kidney injury with urinary biomarkers in the newborn (2009)

Biomarkers are biological parameters that can be objectively measured and evaluated, which act as indicators of normal or pathological processes, or of the response to intervention. Acute Kidney Injury (AKI) biomarkers must be easy to detect and measure, must correlate with severity (offering accurate prognosis), quantitatively describing the level of injury even in the absence of clinical signs. Finally, they must be adequate to indicate treatment initiation. So, the sensitivity (early appearance), specificity (typical of organ injury) and time-course are critical factors in determining the utility of a particular biomarker in the disease process. It is unlikely that a single biomarker will satisfy all of these requirements. As AKI is multifactorial in origin, a panel of biomarkers will be required on one hand to differentiate subtypes of AKI, on the other hand to define the phase and severity of injury. The aim of this review is to present the principal urinary biomarkers used in neonatology.
Detection of tumour cells in peripheral blood and bone marrow from ewing tumour patients by rt‐pcr (1995)

The Ewing family of tumours (ET) is characterised at the cytogenetic level by unique chromosome 22 rearrangements. The breakpoints have been cloned and were shown to fuse the EWS gene on chromosome 22 to one of two closely related ETS proto-oncogenes, FLI-I or ERG, which reside on chromosomes II and 21, respectively. The rearrangement results in the expression of chimaeric transcripts, which can be identified by means of reverse transcriptase-polymerase chain reaction (RT-PCR). We applied this method for the monitoring of ET cells circulating in the peripheral blood or infiltrating the bone marrow. The presence of tumour cells could be detected with a sensitivity of I in I x 10(6) nucleated cells. When samples were kept at 4 degrees C, tumour cells could still be identified after 48 hr of storage. Positive RT-PCR signals originated from intact ET cells rather than from free RNA released by ruptured tumour cells. We analysed peripheral blood, bone marrow samples and peripheral blood stem cell collections from 16 ET patients. At diagnosis, bone marrow specimens collected from 6 patients and I peripheral blood specimen tested positive for EWS chimaeric RNA. During therapy tumour cells were detected in bone marrow aspirations obtained from 2 patients. Our results show that ET cells infiltrating the bone marrow or circulating in peripheral blood can be identified by RT-PCR. The clinical implications for the presence of ET cells in samples detected by RT-PCR at diagnosis and during therapy requires further evaluation.