gebhart/patrepeval huggingface dataset:
Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein. (1992)

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.
<title>Excimer laser processing of diamond-like films</title> (1991)

Basic regimes of the KrF-laser-assisted patterning of a-C:H and of W-alloyed a-C/Si/O:H diamond-like films (DLF) of dielectrical and metal-like varieties are studied. Laser-induced processes of the film graphitization and ablation under the multipulsed irradiation are considered. The submicron resolution of the film structurization is shown to be possible by using the ablative projection UV laser lithography.
Metal−Polymer Hybrid Colloidal Particles with an Eccentric Structure (2009)

We have synthesized metal-polymer hybrid colloidal particles characterized by an eccentric structure by precipitation polymerization in the presence of metal colloids. The key to the formation of an eccentric core-shell structure was to introduce metal colloids a few minutes after (rather than before) starting the polymerization. The hybrid particles were uniform in size, and each one of them contained only one metal nanoparticle at its surface after the experimental procedures had been optimized. This method could be extended to a number of different metal colloids stabilized by small molecules, and the yield was found to be more or less independent of the size of the metal nanoparticles. In addition, the position of the metal nanoparticle in the hybrid particle could be controlled by changing the concentration of cross-linker, and the overall size of the hybrid particles could be altered by solvent treatment. Because of the simplicity of this procedure, it should be possible to use it for the large-scale production of colloidal particles having a hybrid, complex structure.
RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc (1993)

The largest subunit of mammalian RNA polymerase II (RNAP II) contains at its carboxyl terminus an unusual domain consisting of 52 tandem repeats of the consensus sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser. This domain, designated the COOH-terminal domain (CTD), is essential for viability and is extensively phosphorylated during the transition from preinitiation complex assembly to elongation (1). Indeed, phosphorylation of the CTD may play an important regulatory role in this transition. We show here that the CTD is also modified by a novel form of protein glycosylation, O-GlcNAc. This modification has been found on numerous transcription factors and other nuclear and cytosolic proteins (2). Glycopeptides obtained by proteolytic digestion of the CTD were purified by reverse-phase high performance liquid chromatography and sequenced. Results from such experiments suggest that glycosylation occurs at multiple sites throughout the CTD, similar to the phosphorylation of this domain. The carbohydrate, however, is not detectable on the phosphorylated form of the enzyme. This observation is consistent with the idea that phosphorylation and glycosylation are mutually exclusive modifications. The CTD of RNAP II, therefore, appears to exist in three distinct conformational states: unmodified, phosphorylated, and glycosylated. The differential modification of the CTD may play an important role in the regulated expression of genes transcribed by RNA polymerase II.
Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo (2015)

Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine. Our study also revealed that the intestinal stem cell marker OLFM4 is expressed at very low levels in fetal intestine and in HIOs, but is robust in adult crypts. We validated our findings using in vivo transplantation to show that HIOs become more adult-like after transplantation. Our study emphasizes important maturation events that occur in the intestine during human development and demonstrates that HIOs can be used to model fetal-to-adult maturation.
Total Synthesis of Capsanthin Using Lewis Acid-Promoted Regio- and Stereoselective Rearrangement of Tetrasubstituted Epoxide. (2001)

The synthesis of capsanthin 1 was accomplished via the C15-cyclopentyl ketone 13 prepared by Lewis acid-promoted regio- and stereoselective rearrangement of the epoxide 12.
An Integrated Approach To Optimizing a Large Asset (2002)

Abstract A major integrated study was performed to optimize the development of a complex field and to find opportunities to increase oil production. The field is composed of eight stacked reservoirs. The field was developed with more than 160 wells and has been producing since 1960. A pilot gas injection project was installed in the early 1990's. Despite the large number of wells and long production history, only 10% of the OOIP was recovered to date. An integrated approach was used to construct a dynamic model for the field and couple it to economical calculations. The model was used to optimize the performance of the field, increase recovery factor, and accelerate production. Unique to this paper is the procedure of history matching large amounts of data and long history. A relatively large model was constructed and then was broken down to seven models. The history match was attempted for each model separately. The seven parts of the field were then combined and the history match was refined. This history matching procedure resulted in significant time savings in the study and allowed the study team to dedicate most of their time to field optimization and to understanding the reservoir behavior.
Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility studyex vivo (2012)

Magnetic resonance imaging (MRI) and ultrasonography have been used simultaneously in this ex vivo study for the image-guidance of high intensity focused ultrasound (HIFU) treatment in moving tissue. A ventilator-driven balloon produced periodic and non-rigid (i.e. breathing-like) motion patterns in phantoms. MR-compatible ultrasound (US) imaging enabled near real-time 2D motion tracking based on optical flow detection, while near-harmonic reference-free proton resonance frequency shift (PRFS) MR thermometry (MRT) was used to monitor the thermal buildup on line. Reference-free MRT was applied to gradient-echo echo-planar imaging phase maps acquired at the frame rate of 250 to 300 ms/slice with voxel size 1.25×1.25×5 mm(3). The MR-US simultaneous imaging was completely free of mutual interferences while minor RF interferences from the HIFU device were detected in the far field of the US images. The effective duty-cycle of the HIFU sonication was close to 100 % and no off-interval was required to temporally decouple it from the ultrasonography. The motion compensation of the HIFU sonication was achieved with an 8 Hz frame rate and sub-millimeter spatial accuracy, both for single-focus mode and for an iterated multi-foci line scan. Near harmonic reference-less PRFS MRT delivered motion-robust thermal maps perpendicular or parallel to the HIFU beam (0.7 °C precision, 0.5 °C absolute accuracy). Out-of-plane motion compensation was not addressed in this study.
A distributed multihop protocol for mobile stations to contact a stationary infrastructure (1991)

One of the common problems in mobile packet radio networks (PR'nets) is that mobile subscribers have to reach a stationary infrastructure. Multihop protocols enable communication to infrastructure contact points (beacons) which are out of transmission range. To meet the special requirements of a decentral and highly mobile network the new multihop strategy MARION (multiple adaptive routing in mobile networks) is introduced. Efficiency and packet delay are the main criteria for the final evaluation.
Analysis of repeated low‐dose challenge studies (2015)

Preclinical evaluation of candidate human immunodeficiency virus (HIV) vaccines entails challenge studies whereby non-human primates such as macaques are vaccinated with either an active or control vaccine and then challenged (exposed) with a simian-version of HIV. Repeated low-dose challenge (RLC) studies in which each macaque is challenged multiple times (either until infection or some maximum number of challenges is reached) are becoming more common in an effort to mimic natural exposure to HIV in humans. Statistical methods typically employed for the testing for a vaccine effect in RLC studies include a modified version of Fisher's exact test as well as large sample approaches such as the usual log-rank test. Unfortunately, these methods are not guaranteed to provide a valid test for the effect of vaccination. On the other hand, valid tests for vaccine effect such as the exact log-rank test may not be easy to implement using software available to many researchers. This paper details which statistical approaches are appropriate for the analysis of RLC studies, and how to implement these methods easily in SAS or R.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation (2013)

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.
Studies with Chimeric Mpl/JAK2 Receptors Indicate That Both JAK2 and the Membrane-proximal Domain of Mpl Are Required for Cellular Proliferation (2002)

The thrombopoietin (TPO) receptor c-Mpl, like other members of the cytokine receptor superfamily, requires the association and activation of Janus kinases (JAKs) for normal signal transduction. The membrane-proximal portion of the signaling domain, containing conserved box1 and box2 motifs, is sufficient to support the proliferation of cytokine-dependent cell lines and basal megakaryocytopoiesis in vivo. We hypothesized that activation of the JAK2 kinase alone might be sufficient for proliferative signaling. To test this premise, we constructed chimeric receptors in which the extracellular and transmembrane portions of Mpl were fused to the pseudokinase and kinase domains of murine JAK2 kinase. When expressed in the interleukin-3-dependent cell line Ba/F3, the chimeric receptors were appropriately expressed on the cell surface and were able to initiate tyrosine kinase activity upon exposure to TPO. However, chimeric receptors lacking an intact box2 domain of Mpl were unable to support proliferation at any concentration of TPO. Only chimeric receptors containing both JAK2 kinase activity and the box2 region initiated proliferative signaling. Within the box2 motif, we determined that the sequence Glu(56)-Ile(57)-Leu(58) of the Mpl cytoplasmic domain is critical for proliferation of the chimeric receptors. Furthermore, TPO-dependent induction of c-myc transcription is also dependent on this motif. These results indicate that JAK2 activation alone is not sufficient for TPO-induced proliferation and that one or more essential signaling pathways must arise from the cytoplasmic domain of Mpl that includes box2. Although the nature of the signal transduction pathway is not yet known, this second proliferative event is likely to regulate c-myc expression.
Experimental study of recombinant human vascular endostatin for breast cancer in nude mice model (2009)

Objective To explore the effect of recombinant human vascular endostatin(Endostar,YH-16) on MCF-7 human breast cancer cells in nude mice. Methods Forty nude mice were randomized into four groups and received injection with MCF-7 cells. When gross tumor volume reached 1.0 cm3 ,mice were injected subcutaneously once every two days as following for 20 days: (1) O. 9% NS(0. 2 mg/kg) in negative control group;(2) YH-16(20 mg/kg) in YH-16 group; (3) DDP (1 mg/kg) in positive control group; (4) DDP (1 mg/kg) plus YH-16(20 mg/kg) in DDP plus YH-16 group. Mice were killed by cervical spine disloca-tion. And the body weight, tumor volume, rate of tumor inhibited, VEGF, apoptosis rate of tumor cells and pul-monary metastasis rate were detected. Results The means (SD) of tumor volume in DDP plus YH-16 group,positive control group, YH- 16 group and negative control group were 0. 686 (0. 229), 1. 258 (0. 101), 1. 888 (0. 215), 3. 366 (0. 284) cm3, respectively (P <0. 05) ; the rates of tumor inhibited in the four groups were 92. 1% ,57.3 %, 36. 5 % and 0, respectively (P < 0. 05) ; pulmonary metastasis rates were 0, 10%, 20% and 90% ,respectively(P <0. 05) ;the mean (SD) of apoptosis rates of tumor ceils were 31.6% (2. 7%) ,28. 1%(2. 7%), 19. 4% (2. 9%), 15.7% (3.2%), respectively (P < 0. 05). The mean of absorbance of VEGF in the four groups were 0. 530 ± 0. 164,0. 759 ± 0. 210,1. 063 ± 0. 295,1. 268 ±0. 145 (RT-PCR) and O. 260 ±0. 082,0. 348 ±0. 085,0. 461 ±0. 099,0. 556 ± 0. 113(Western blot) ,respectively(P < 0. 05). Conclusion YH-16 can inhibit MCF-7 breast cancer cell growth and distant metastasis in nude mice with little adverse reac-tion. YH-16 has synergistic effect combined with DDP.

Key words: 
Endostatins;  Breast neoplasms;  Angiogenesis inhibitors;  Vascular endothelial growth factors
A murine fibroblast growth factor (FGF) receptor expressed in CHO cells is activated by basic FGF and Kaposi FGF. (1990)

We have cloned a murine cDNA encoding a tyrosine kinase receptor with about 90% similarity to the chicken fibroblast growth factor (FGF) receptor and the human fms-like gene (FLG) tyrosine kinase. This mouse receptor lacks 88 amino acids in the extracellular portion, leaving only two immunoglobulin-like domains compared to three in the chicken FGF receptor. The cDNA was cloned into an expression vector and transfected into receptor-negative CHO cells. We show that cells expressing the receptor can bind both basic FGF and Kaposi FGF. Although the receptor binds basic FGF with a 15- to 20-fold higher affinity, Kaposi FGF is able to induce down-regulation of the receptor to the same extent as basic FGF. The receptor is phosphorylated upon stimulation with both FGFs, DNA synthesis is stimulated, and a proliferative response is produced in cells expressing the receptor, whereas cells expressing the cDNA in the antisense orientation show none of these responses to basic FGF or Kaposi FGF. Thus this receptor can functionally interact with two growth factors of the FGF family.
Low biological activity of Helicobacter pylori lipopolysaccharide (1992)

Lipopolysaccharide from the gastroduodenal pathogen Helicobacter pylori was tested for its ability to induce mitogenicity in mouse spleen cells, pyrogenicity in rabbits, and toxic lethality in galactosamine-sensitized mice. Compared with those for enterobacterial lipopolysaccharide, mitogenicity and pyrogenicity were a thousand-fold lower and lethal toxicity was 500-fold lower. We suggest that the phosphorylation pattern and acylation in lipid A are responsible for the low biological activity.
Role of Disulfide Bonds in the Structure and Activity of Human Insulin (2003)

Insulin contains two inter-chain disulfide bonds between the A and B chains (A7-B7 and A20-B19), and one intra-chain linkage in the A chain (A6-A11). To investigate the role of each disulfide bond in the structure, function and stability of the molecule, three des mutants of human insulin, each lacking one of the three disulfide bonds, were prepared by enzymatic conversion of refolded mini-proinsulins. Structural and biological studies of the three des mutants revealed that all three disulfide bonds are essential for the receptor binding activity of insulin, whereas the different disulfide bonds make different contributions to the overall structure of insulin. Deletion of the A20-B19 disulfide bond had the most substantial influence on the structure as indicated by loss of ordered secondary structure, increased susceptibility to proteolysis, and markedly reduced compactness. Deletion of the A6-A11 disulfide bond caused the least perturbation to the structure. In addition, different refolding efficiencies between the three des mutants suggest that the disulfide bonds are formed sequentially in the order A20-B19, A7-B7 and A6-A11 in the folding pathway of proinsulin.
Half-QWERTY (1993)

is a new one-handed typing technique, designed to facilitate the transfer of two-handed typing skill to the one-handed condition.
Transfection with trk restores "slow" NGF binding, efficient NGF uptake, and multiple NGF responses to NGF-nonresponsive PC12 cell mutants (1993)

NGF binds to and activates the protein tyrosine kinase gp 140prototrk. Expression of this receptor is required for at least some responses to NGF. Three outstanding issues are addressed in the present work. First, we determined whether expression of gp 140prototrk is required for all neuronal NGF responses. Second, we examined the role of gp 140prototrk in NGF binding and internalization. Third, we addressed the utility of NGF-nonresponsive PC12nnr5 cells for study of the NGF mechanism. In contrast to wild-type PC12 cells, PC12nnr5 cells do not express endogenous gp 140prototrk. We therefore asked whether they possess other defects that compromise NGF signaling pathways. To answer these questions, we transfected PC12nnr5 cells with a cDNA encoding full-length human gp 140prototrk and isolated cell lines permanently expressing the receptor. Introduction of trk rescued all of the many and varied NGF responses assessed, including enhanced protein tyrosine phosphorylation, induction of immediate-early and neural-specific genes, neurite outgrowth and regeneration, maintenance of survival in serum-free medium, and stimulation of AChE activity. In contrast to PC12nnr5 cells, the trk-transfected lines also bind and internalize NGF with wild-type PC12 cell characteristics. These findings indicate that gp 140prototrk is required for many, if not all, responses of neuronal cells to NGF and is necessary for proper NGF binding and internalization. Additionally, as no signaling defect other than the absence of trk expression was revealed in PC12nnr5 cells, this work supports the utility of this line for genetic dissection of the NGF mechanism of action.
Dual interaction of factor H with C3d and glycosaminoglycans in host–nonhost discrimination by complement (2011)

The alternative pathway of complement is important in innate immunity, attacking not only microbes but all unprotected biological surfaces through powerful amplification. It is unresolved how host and nonhost surfaces are distinguished at the molecular level, but key components are domains 19-20 of the complement regulator factor H (FH), which interact with host (i.e., nonactivator surface glycosaminoglycans or sialic acids) and the C3d part of C3b. Our structure of the FH19-20:C3d complex at 2.3-Å resolution shows that FH19-20 has two distinct binding sites, FH19 and FH20, for C3b. We show simultaneous binding of FH19 to C3b and FH20 to nonactivator surface glycosaminoglycans, and we show that both of these interactions are necessary for full binding of FH to C3b on nonactivator surfaces (i.e., for target discrimination). We also show that C3d could replace glycosaminoglycan binding to FH20, thus providing a feedback control for preventing excess C3b deposition and complement amplification. This explains the molecular basis of atypical hemolytic uremic syndrome, where mutations on the binding interfaces between FH19-20 and C3d or between FH20 and glycosaminoglycans lead to complement attack against host surfaces.
Triggered Release from Liposomes through Magnetic Actuation of Iron Oxide Nanoparticle Containing Membranes (2011)

The ideal nanoscale drug delivery vehicle allows control over the released dose in space and time. We demonstrate that this can be achieved by stealth liposomes comprising self-assembled superparamagnetic iron oxide nanoparticles (NPs) individually stabilized with palmityl-nitroDOPA incorporated in the lipid membrane. Alternating magnetic fields were used to control timing and dose of repeatedly released cargo from such vesicles by locally heating the membrane, which changed its permeability without major effects on the environment.