gebhart/patrepeval huggingface dataset:
14-3-3 activation of DNA binding of p53 by enhancing its association into tetramers (2008)

Activation of the tumour suppressor p53 on DNA damage involves post-translational modification by phosphorylation and acetylation. Phosphorylation of certain residues is critical for p53 stabilization and plays an important role in DNA-binding activity. The 14-3-3 family of proteins activates the DNA-binding affinity of p53 upon stress by binding to a site in its intrinsically disordered C-terminal domain containing a phosphorylated serine at 378. We have screened various p53 C-terminal phosphorylated peptides for binding to two different isoforms of 14-3-3, epsilon and gamma. We found that phosphorylation at either S366 or T387 caused even tighter binding to 14-3-3. We made by semi-synthesis a tetrameric construct comprised of the tetramerization plus C-terminal domains of p53 that was phosphorylated on S366, S378 and T387. It bound 10 times tighter than did the monomeric counterpart to dimeric 14-3-3. We showed indirectly from binding curves and directly from fluorescence-detection analytical ultracentrifugation that 14-3-3 enhanced the binding of sequence-specific DNA to p53 by causing p53 dimers to form tetramers at lower concentrations. If the in vitro data extrapolate to in vivo, then it is an attractive hypothesis that p53 activity may be subject to control by accessory proteins lowering its tetramer-dimer dissociation constant from its normal value of 120-150 nM.
Advances in high-power short-pulse fiber laser systems and technology (Invited Paper) (2005)

We review recent advances in Yb fiber lasers and amplifiers for high power short pulse systems. We go on to describe associated recent developments in fiber components for use in such systems. Examples include microstructured optical fibers for pulse compression and supercontinuum generation, and advanced fiber grating technology for chirped-pulse amplifier systems.
Cancer cell proliferation is inhibited by specific modulation frequencies (2011)

These findings uncover a novel mechanism controlling the growth of cancer cells at specific modulation frequencies without affecting normal tissues, which may have broad implications in oncology.
T‐DNA insertion mutagenesis in Arabidopsis: mutational spectrum (1991)

Summary More than 8000 transformants of Arabidopsis have been generated by treating germinating seeds with cultures of Agrobacterium tumefaciens. Genetic characterization of a subset of the transformants indicates that they contain an average of 1.4 inserts each, as assayed by kanamycin resistance. Molecular analysis shows that the inserts are predominantly concatamers of T‐DNAs arranged as direct and inverted repeats. More recently these 8000 lines have been screened under a variety of growth conditions for visible alterations in phenotype. More than 1000 putative mutants were observed during the application of these screening procedures. These mutants fall into several general classes: seedling‐lethals, size variants, pigment, embryo‐defective, reduced‐fertility, dramatic (morphological), and physiological. The majority of the mutants (88%) segregate in a Mendelian manner for the mutant phenotype. An analysis of approximately 50 mutants in this group shows that &gt; 80% are tagged with a functional insert. The wide spectrum of mutants observed suggests that it may be feasible to develop a comprehensive collection of mutant lines in which each gene is tagged by a T‐DNA insertion.
Citric acid or orange juice for the 13C‐urea breath test: the impact of pH and gastric emptying (1999)

13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.
A progressive refinement approach to fast radiosity image generation (1988)

A reformulated radiosity algorithm is presented that produces initial images in time linear to the number of patches. The enormous memory costs of the radiosity algorithm are also eliminated by computing form-factors on-the-fly. The technique is based on the approach of rendering by progressive refinement. The algorithm provides a useful solution almost immediately which progresses gracefully and continuously to the complete radiosity solution. In this way the competing demands of realism and interactivity are accommodated. The technique brings the use of radiosity for interactive rendering within reach and has implications for the use and development of current and future graphics workstations.
Polarity of heteroduplex formation promoted by Escherichia coli recA protein. (1981)

When recA protein pairs circular single strands with linear duplex DNA, the circular strand displaces its homolog from only one end of the duplex molecule and rapidly creates heteroduplex joints that are thousands of base pairs long [DasGupta, C., Shibata, T., Cunningham, R. P. & Radding, C. M. (1980) Cell 22, 437-446]. To examine this apparently polar reaction, we prepared chimeric duplex fragments of DNA that had M13 nucleotide sequences at one end and G4 sequences at the other. Circular single strands homologous to M13 DNA paired with a chimeric fragment when M13 sequences were located at the 3' end of the complementary strand but did not pair when the M13 sequences were located at the 5' end. Likewise circular single-stranded G4 DNA paired with chimeric fragments only when G4 sequences were located at the 3' end of the complementary strand. To confirm these observations, we prepared fd DNA labeled only at the 5' or 3' end of the plus strand, and we examined the susceptibility of these labeled ends to digestion by exonucleases when joint molecules were formed. Eighty percent of the 5' label in joint molecules became sensitive to exonuclease VII. Displacement of that 5' end by recA protein was concerted because it did not occur in the absence of single-stranded DNA or in the presence of heterologous single strands. By contrast, only a small fraction of the 3' label became sensitive to exonuclease VII or exonuclease I. These observations show that recA protein forms heteroduplex joints in a concerted and polarized way.
New reaction conditions using trifluoroethanol for the E-I Hofmann rearrangement (1999)

The Hofmann rearrangement of N2-protected glutamine esters to N2-protected (2S)-4-[(2,2,2-trifluoroethoxy)carbonylamino]-2-aminobutyric acid esters was successfully achieved by an electrochemical method using a trifluoroethanol (TFE)–MeCN solvent system where the TFE may play an important role in controlling the basicity caused by electrochemically generated bases.
Structure validation in chemical crystallography (2009)

Automated structure validation was introduced in chemical crystallography about 12 years ago as a tool to assist practitioners with the exponential growth in crystal structure analyses. Validation has since evolved into an easy-to-use checkCIF/PLATON web-based IUCr service. The result of a crystal structure determination has to be supplied as a CIF-formatted computer-readable file. The checking software tests the data in the CIF for completeness, quality and consistency. In addition, the reported structure is checked for incomplete analysis, errors in the analysis and relevant issues to be verified. A validation report is generated in the form of a list of ALERTS on the issues to be corrected, checked or commented on. Structure validation has largely eliminated obvious problems with structure reports published in IUCr journals, such as refinement in a space group of too low symmetry. This paper reports on the current status of structure validation and possible future extensions.
Regulation of Islet β-Cell Proliferation by Prolactin in Rat Islets (1994)

This study examined the effects of prolactin on beta-cell proliferation in pancreatic islet of Langerhans. Insulin secretion and beta-cell proliferation were significantly increased from neonatal rat islets cultured for 4 days in the presence of either 500 ng/ml ovine prolactin (oPRL) or rat prolactin (rPRL). These effects could be prevented by including anti-oPRL serum in the culture media. Although insulin secretion and beta-cell proliferation were slightly higher during the first 24 h of exposure to rPRL, maximal response was observed after 4 days for insulin secretion and 6-10 days for beta-cell proliferation. The initial mitogenic response of beta-cell to rPRL occurred by the limited recruitment of nondividing beta-cells into the cell cycle and by most daughter cells proceeding directly into additional cell division cycles. Subsequently, the maximal effect of rPRL on beta-cell proliferation was maintained by a higher rate of recruitment of previously nondividing beta-cells into cell cycle with only one fourth of the daughter cells continuing to divide. These observations are difficult to reconcile with the proposal that a limited pool of beta-cells capable of undergoing cell division exists in islets. Instead, these observations suggest that individual beta-cells are transiently re-entering the cell cycle and dividing infrequently in response to rPRL. In this case, the majority of the beta-cells would not be expected to be in an irreversible Go phase. We also demonstrated that the effects of rPRL on beta-cell proliferation occur at normal serum glucose concentrations and are affected by inhibitors of polyamine metabolism. Additional studies on the effects of rPRL on beta-cells should provide important information on the regulation of beta-cell proliferation during conditions of increased insulin demand.
The secA inhibitor, azide, reversibly blocks the translocation of a subset of proteins across the chloroplast thylakoid membrane. (1994)

The presence of secA and secY gene homologues in the plastid genomes of red algae and cyanophytes has raised the possibility that the products of these genes are involved in protein translocation across the thylakoid membrane. Bacterial SecA proteins are effectively inhibited by azide, and we have tested the effects of this compound on the transport of lumenal proteins across the thylakoid membrane in pea chloroplasts. Recent studies have shown that lumenal proteins are transported by two different mechanisms, one dependent on the thylakoidal delta pH and the other requiring the presence of a stromal protein factor and ATP. In this report we show that azide inhibits the transport across the thylakoid membrane of the latter group of proteins, which includes plastocyanin and the lumenal 33-kDa protein of photosystem II; translocation of proteins by the delta pH-dependent pathway is unaffected. Following import into isolated chloroplasts in the presence of azide, a substantial proportion of plastocyanin and the 33-kDa protein is found as the stromal intermediate form; the proportion increases with lower ATP concentrations, suggesting that azide and ATP may compete for a single site. The presence of azide completely inhibits the import of the 33-kDa protein by isolated thylakoids, but import is restored if the azide is removed from the stromal extract or thylakoids, prior to the import incubation. The data thus indicate that azide reversibly inhibits the transport of a subset of proteins across the thylakoid membrane, consistent with the involvement of a SecA homolog. The results also indicate that azide is potentially a valuable tool for the future assignment of novel lumenal proteins to one of the thylakoidal protein transport mechanisms.
Comparative Study Between Gadobenate Dimeglumine and Gadobutrol in Rats with Brain Ischemia (2001)

Based on these results, three conclusions can be drawn: (1) the evaluation of SEPs in ischemic rats is a useful tool for assessing the potential neurological effects of a new contrast agent because ischemic and contrast agent effects can be clearly differentiated; (2) the experimental conditions used allow the contrast agents to penetrate into the brain, where their activity can be manifested and evaluated; and (3) the complete absence of neurological activity of gadobenate dimeglumine shows its safety profile and confirms its suitability for use in neurological diseases for which contrast-enhanced magnetic resonance imaging is indicated.
Development of chip-size silicon solar cells (2002)

SunPower is developing a novel 250-Sun concentrator module that, because of a compact nonimaging optics design, is very low profile and looks much like a conventional flat plate module. This "micro-concentrator" requires very small, "chip-size" solar cells, with approximate dimensions of 2.3/spl times/2.3 mm. The authors have adapted their all-back point-contact silicon solar cell technology to this application. This cell technology has several advantages over competing Ill-V technologies including lower cost, elimination of grid shading, and more tolerance of nonuniform and off-normal cell illumination due to all-backside carrier collection and texture, respectively. A major problem for such small silicon cells, however, is the efficiency loss due to the sawed edges of the cell. An "edge surface field" created by a through-wafer diffusion is one possible solution to the problem. Modeling and preliminary experimental results are presented.
Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis (2006)

Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.
The development of regional pigmentation patterns in black and tan (at) Mice (1976)

Abstract Mice which express the black and tan ( a t ) allele at the agouti locus have black dorsal and yellow ventral hairs. To determine the site of action of this allele, the kind of hair pigment produced by various dermal‐epidermal recombinations of dorsal and ventral black and tan ( a t / a t ), ventral nonagouti ( a t / a t ) and ventral yellow ( A y / a ) embryonic skin has been investigated. The results indicate that it is the dermis which is responsible for the development of regional pigmentation patterns in black and tan mice.
The Telomere Lengthening Mechanism in Telomerase-Negative Immortal Human Cells Does Not Involve the Telomerase RNA Subunit (1997)

According to the telomere hypothesis of senescence, the progressive shortening of telomeres that occurs upon division of normal somatic cells eventually leads to cellular senescence. The immortalisation of human cells is associated with the acquisition of a telomere maintenance mechanism which is usually dependent upon expression of the enzyme telomerase. About one third of in vitro immortalised human cell lines, however, have no detectable telomerase but contain telomeres that are abnormally long. The nature of the alternative telomere maintenance mechanism (referred to as ALT, for Alternative Lengthening of Telomeres) that must exist in these telomerase-negative cells has not been elucidated. It has previously been shown that abnormal lengthening of yeast telomeres may occur due to mutations in the yeast telomerase RNA gene. That this is not the mechanism of the abnormally long telomeres in ALT cell lines was demonstrated by the finding that seven of seven ALT lines have wild-type human telomerase RNA (hTR) sequence, including a novel polymorphism that is present in 30% of normal individuals. We found that two ALT cell lines have no detectable expression of the hTR gene. This shows that the ALT mechanism in these cell lines is not dependent on hTR. Expression of exogenous hTR via infection of these cells with a recombinant hTR-adenovirus vector did not result in telomerase activity, indicating that their lack of telomerase activity is not due to absence of hTR expression. We conclude that the ALT mechanism is not dependent on the expression of hTR, and does not involve mutations in the hTR sequence.
MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte. (1999)

It is generally considered that MHC class I-restricted antigens are recognized by CD8+ T cells, whereas MHC class II-restricted antigens are recognized by CD4+ T cells. In the present study, we report an MHC class I-restricted CD4+ T cell isolated from the tumor infiltrating lymphocytes (TILs) of a patient with metastatic melanoma. TIL 1383 I recognized HLA-A2+ melanoma cell lines but not autologous transformed B cells or fibroblasts. The antigen recognized by TIL 1383 I was tyrosinase, and the epitope was the 368-376 peptide. Antibody blocking assays confirmed that TIL 1383 I was MHC class I restricted, and the CD4 and CD8 coreceptors did not contribute significantly to antigen recognition. TIL 1383 I was weakly cytolytic and secreted cytokines in a pattern consistent with it being a Th1 cell. The avidity of TIL 1383 I for peptide pulsed targets is 10-100-fold lower than most melanoma-reactive CD8+ T cell clones. These CD4+ T cells may represent a relatively rare population of T cells that express a T-cell receptor capable of cross-reacting with an MHC class I/peptide complex with sufficient affinity to allow triggering in the absence of the CD4 coreceptor.
Satellite and Receiver Phase Bias Calibration for Undifferenced Ambiguity Resolution (2008)

Precise point positioning (PPP), considered an alternative to differential positioning, is used in a significantly increased number of applications. Its integration into many practical areas is, however, slowed down by the long convergence time required in order to obtain cmlevel accuracy. This drawback is caused by the difficulty in fixing carrier-phase ambiguities to integers. As opposed to the differential mode, where many error sources are eliminated or greatly reduced, PPP has to properly account for all of them. Some of these error sources, such as code and phase biases, are complex to model as they tend to merge with the ambiguity parameters during the estimation process, leading to unsuccessful ambiguity resolution. This paper focuses on the receiver and satellite phase bias calibration required to recover the integer nature of carrier-phase ambiguities. A proper estimation of these biases would allow correcting the measurements and using the ambiguity resolution techniques developed for differential positioning. In this way, instantaneous cmlevel accuracy could be something conceivable even with a single GPS receiver, considering that the other error sources have been reduced to a significant level. The first step taken to achieve this objective is to clearly understand PPP’s functional model representing the code and phase measurements made by the GPS receiver. Special attention is paid to hardware delays, such as code and phase biases, which play a crucial role in the estimation process using undifferenced measurements. The impact of these quantities on some estimated parameters is described in order to have a better understanding of the concepts presented throughout this paper. In the second step, a receiver phase-bias calibration technique using a GPS signal simulator is introduced. A simulator has been used to generate errorless signals which are ideal to isolate the biases inherent to the receiver. Results show that this calibration process is complex due mainly to the correlation between the receiver clock and the ambiguity parameters. As such, between-satellite single differencing still seems to be the best way to eliminate receiver phase biases. The last part of this paper concerns satellite phase-bias calibration. To properly calibrate the satellite phase biases, the impact of code biases has to be carefully taken into consideration. For this purpose, an alternate widelane phase-bias calibration method is proposed and is shown to be coherent with PPP’s functional model.
Toxicity of the Protein Kinase C Inhibitor Safingol Administered Alone and in Combination with Chemotherapeutic Agents (1995)

Safingol [(2S,3S)-2-amino-1,3-octadecanediol] potentiates the toxicity of doxorubicin (DOX) and cisplatin (CIS) against tumor cells in vitro and in vivo. The present studies were conducted in rats and dogs to evaluate safingol toxicity when administered iv as a single agent and to evaluate safingol's ability to potentiate the toxicity of established chemotherapeutic agents to normal tissues in vivo. In an escalating dose study, dogs were administered safingol iv at 5, 10, 20, 30, 40, and 75 mg/kg on Days 1 through 6. Necropsies were performed on Day 7. Red urine was observed at 10 mg/kg and higher. Icterus was observed following 40 mg/kg with additional signs of hypoactivity and anorexia occurring after 75 mg/kg. Clinical and microscopic pathology revealed marked hepatotoxicity, venous degeneration and necrosis at injection sites, and evidence of intra-vascular hemolysis. Doses of 5, 20, or 40 mg safingol/kg were utilized in single iv dose rat and dog studies. No evidence of adverse systemic toxicity was seen up to 20 mg/kg in either species [for rats: Cmax = 12,600 (males) or 17,133 (females) ng/ml, AUC = 3853 (males) or 4365 (females) ng × hr/ml; for dogs: Cmax = 2533 ng/ml, AUC = 2851 ng × hr/ml (no sex differences)]. Local effects of venous irritation or intravascular hemolysis were observed at all doses in rats and at 20 and 40 mg/kg in dogs. A dose of 40 mg/kg [for rats: Cmax = 31,233 (males) or 91,300 (females) ng/ml, AUC = 11,519 (males) or 18,620 (females) ng × hr/ml; for dogs: Cmax = 9033 ng/ml, AUC = 11,094 ng × hr/ml (combined sex)] was associated with clinical pathologic and renal histomorphologic changes considered consequent to intravascular hemolysis in both species, lethality and testicular toxicity in rats, and clinical biochemical changes indicative of hepatobiliary injury in dogs. Studies indicated that hemolysis occurred during infusion, was not caused by circulating levels of safingol, and was a function of dose concentration and vein of delivery. Safingol at 10 or 20 mg/kg was administered iv to rats 30–60 min prior to myelosuppressive iv doses of DOX, CIS, or cyclophosphamide (CYP). Hematology, plus renal function and morphology for CIS-treated animals, was assessed 4 and 14 days later. Safingol did not potentiate DOX-, CIS-, or CYP-mediated leukopenia/thrombocytopenia. A minimal enhancement of CIS-mediated decrease in GFR and increase in creatinine was observed at 20 mg safingol/kg. Dogs were administered 20 mg safingol/kg iv followed 60 min later by 0.5 or 1.25 mg DOX/kg or 0.75 or 2.0 mg CIS/kg. A complete toxicologic assessment 4 and 29 days postdose failed to show potentiation of DOX toxicity by safingol or vice versa. A renal lesion was inferred in dogs administered 20 mg/kg safingol and 2 mg/kg CIS based on minimal to slight renal tubular regeneration observed 4 weeks post-treatment. There were no effects of safingol on the pharmacokinetic profiles of DOX or CIS or vice versa.