gebhart/patrepeval huggingface dataset:
Old-age-induced obesity reversed by a methionine-deficient diet or oral administration of recombinant methioninase-producing Escherichia coli in C57BL/6 mice (2023)

Obesity increases with aging. Methionine restriction affects lipid metabolism and can prevent obesity in mice. In the present study we observed C57BL/6 mice to double their body weight from 4 to 48 weeks of age and become obese. We evaluated the efficacy of oral administration of recombinant-methioninase (rMETase)-producing <i>E. coli</i> (<i>E. coli</i> JM109-rMETase) or a methionine-deficient diet to reverse old-age-induced obesity in C57BL/6 mice. Fifteen C57BL/6 male mice aged 12-18 months with old-age-induced obesity were divided into three groups. Group 1 was given a normal diet supplemented with non-recombinant <i>E. coli</i> JM109 cells orally by gavage twice daily; Group 2 was given a normal diet supplemented with recombinant <i>E. coli</i> JM109-rMETase cells by gavage twice daily; and Group 3 was given a methionine-deficient diet without treatment. The administration of <i>E. coli</i> JM109-rMETase or a methionine-deficient diet reduced the blood methionine level and reversed old-age-induced obesity with significant weight loss by 14 days. There was a negative correlation between methionine levels and negative body weight change. Although the degree of efficacy was higher in the methionine-deficient diet group than in the <i>E. coli</i> JM109-rMETase group, the present findings suggested that oral administration of <i>E. coli</i> JM109-rMETase, as well as a methionine-deficient diet, are effective in reversing old-age-induced obesity. In conclusion, the present study provides evidence that restricting methionine by either a low-methionine diet or <i>E. coli</i> JM109-rMETase has clinical potential to treat old-age-induced obesity.
ELFbac: Using the Loader Format for Intent-Level Semantics and Fine-Grained Protection (2013)

Adversaries get software to do bad things by rewriting memory and changing control flow. Current approaches to protecting against these attacks leave many exposures; for example, OS-level filesystem protection and OS/architecture support of the userspace/kernelspace distinction fail to protect corrupted userspace code from changing userspace data. In this paper we present a new approach: using the ELF/ABI sections already produced by the standard binary toolchain to define, specify, and enforce fine-grained policy within an application’s address space. We experimentally show that enforcement of such policies would stop a large body of current attacks and discuss ways we could extend existing architecture to more efficiently provide such enforcement. Our approach is designed to work with existing ELF executables and the GNU build chain, but it can be extended into the compiler toolchains to support code annotations that take advantage of ELFbac enforcement—while maintaining full compatibility with the existing ELF ABI. 1
Surviving as a therapeutic target and biomarker for non-small-cell lung cancer (2004)

7153 Background: Survivin inhibits apoptosis and promotes mitosis. Its expression has been restricted to malignant tissues. High levels of survivin expression are associated with poor survival of cancer patients. Both nuclear and cytoplasmic staining of survivin was observed. However, the prognostic value of cellular compartmentation of survivin has been a subject of debate. Methods: Antisense oligonucleotides (ASO) against survivin were used to examine the impact of survivin inhibition upon mitosis, apoptosis and viability of H460 lung cancer cells. Immunohistochemistry was used to determine whether nuclear or cytoplasmic localization of survivin predicts survival of 48 patients with resected NSCLC. Results: The anti-Survivin ASO specifically attenuated the protein expression of survivin in H460 cells. Survivin inhibition using antisense oligonucleotides resulted in increases of apoptosis and mitotic arrests of H460 cells. H460 cells had significantly decreased viability following the treatment of the antisense oligonucleotides. Patients with nuclear staining of survivin had significantly shorter overall survival (relative risk: 3.9, p=0.02). Conclusions: Our data suggest that survivin is a potential therapeutic target and a prognostic biomarker for NSCLC. No significant financial relationships to disclose.
Rabbit model of Lyme borreliosis: erythema migrans, infection-derived immunity, and identification of Borrelia burgdorferi proteins associated with virulence and protective immunity. (1995)

Erythema migrans (EM), persistent skin infection, and visceral dissemination can be induced reproducibly in the adult male New Zealand White rabbit by intradermal injection of as few as 10(3) Borrelia burgdorferi. EM was found to persist for 7 +/- 3 d. Skin culture positivity (infection) cleared within a mean of 6.7 +/- 1.4 wk after infection and similarly visceral infection was not demonstrated after 8 wk; infection-derived immunity to intradermal challenge was evident 5 mo after initial infection. The extent of the protection against EM and dermal infection induced by untreated infection was directly related to the extent of prior in vitro passage of the B31 strain. Initial infection with as few as 4 x 10(3) B31 passage 4 induced complete protection against EM and skin infection upon subsequent challenge with 4 x 10(7) B31, passage 4. Initial infection with B31 passage 27 led to partial protection against EM along with complete protection against skin infection. Initial infection with passage 47 led to partial protection against EM, but conferred no protection against skin infection. Using serum from rabbits fully immune to reinfection, we defined a set of B. burgdorferi proteins present in virulent B31, but absent in the avirulent American Type Culture Collection B31 strain, termed "va" for virulent strain associated. The va proteins of B31 passages 1, 27, and 47 differed strikingly, thus raising the possibility that these changes may relate in a causal way to the differences in induction of protective immunity observed.
Abnormality of the contralateral ligament after injuries of the medial collateral ligament. An experimental study in rabbits. (1994)

The right medial collateral ligament of ninety-four adult, female rabbits was transected operatively. At three, six, fourteen, or forty weeks after the operation, the uninjured, contralateral (left) medial collateral ligaments of seventy-eight of the animals were tested biomechanically and compared with the left medial collateral ligaments of thirty-three normal female rabbits. The diameters of the mid-substance collagen fibrils in the medial collateral ligaments were also measured in the uninjured, contralateral hindlimbs of four animals at each interval and compared with the fibril diameters in three normal animals at each of three corresponding intervals. Subtle but significant differences between the uninjured, contralateral and the normal medial collateral ligaments with regard to biomechanical properties of collagen fibril diameters were found at all time-intervals. These results support the notion of a significant effect on the contralateral ligament after an injury to the medial collateral ligament and suggest that contralateral ligaments cannot be considered as a normal control group even in this relatively benign model of knee injury.
Phospholipid Diffusion Coefficients of Cushioned Model Membranes Determined via Z-Scan Fluorescence Correlation Spectroscopy (2013)

Model cellular membranes enable the study of biological processes in a controlled environment and reduce the traditional challenges associated with live or fixed cell studies. However, model membrane systems based on the air/water or oil/solution interface do not allow for incorporation of transmembrane proteins or for the study of protein transport mechanisms. Conversely, a phospholipid bilayer deposited via the Langmuir-Blodgett/Langmuir-Schaefer method on a hydrogel layer is potentially an effective mimic of the cross section of a biological membrane and facilitates both protein incorporation and transport studies. Prior to application, however, such membranes must be fully characterized, particularly with respect to the phospholipid bilayer phase transition temperature. Here we present a detailed characterization of the phase transition temperature of the inner and outer leaflets of a chitosan supported model membrane system. Specifically, the lateral diffusion coefficient of each individual leaflet has been determined as a function of temperature. Measurements were performed utilizing z-scan fluorescence correlation spectroscopy (FCS), a technique that yields calibration-free diffusion information. Analysis via the method of Wawrezinieck and co-workers revealed that phospholipid diffusion changes from raftlike to free diffusion as the temperature is increased-an insight into the dynamic behavior of hydrogel supported membranes not previously reported.
Oligomerization of Methyl Methacrylate and Acrylic Acids in Triethylphosphite (1968)

開始剤にα,α′-アゾビスイソブチロニトリル(AIBN)を用いてトリエチルホスファイト中でメタクリル酸メチル(MMA)の低重合反応を行なった。低重合体生成に及ぼす大きな因子は溶媒とモノマーのモル比[(C2H5O)3P]/[MMA],重合温度である。この系の停止反応は溶媒の連鎖移動によるが,条件によっては均化停止または不均化停止反応も生起する。オリゴメタクリル酸メチル(OMMA)の構造は,赤外スペクトル,分子量測定などから片末端に(C2H5O)2P(O)-基を,他末端にエチル基を保有する。OMMAは四～五量体を境として透明油液から白色粉末として得られ,生成物の融点は重合度約15以上でシンジオタクチックポリMMAの融点135℃に収束する傾向を示す。数平均分子量1万以下のOMMAのベンゼン溶液中25℃における極限粘度[η]と数平均分子量Mnは次の関係式を満足する。[η]=1.33×10-4Mn0.48さらに同じ系におけるアクリル酸(AA)およびメタクリル酸(MAA)について検討した。この結果,AA,MAAの重合反応はアニオン重合により反応が進行する。生成物の構造は赤外スペクトルにより,連鎖中にポリエステル型構造を保有し,このことからカルボキシル基の水素が移動反応を起こしていることが明らかとなった。
Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer (2019)

More than 75% of breast cancers are estrogen receptor alpha (ERα) positive (ER+), and resistance to current hormone therapies occurs in one-third of ER+ patients. Tumor resistance is still ERα-dependent, but mutations usually confer constitutive activation to the hormone receptor, rendering ERα modulator drugs such as tamoxifen and aromatase inhibitors ineffective. Fulvestrant is a potent selective estrogen receptor degrader (SERD), which degrades the ERα receptor in drug-resistant tumors and has been approved for the treatment of hormone-receptor-positive metastatic breast cancer following antiestrogen therapy. However, fulvestrant shows poor pharmacokinetic properties in human, low solubility, weak permeation, and high metabolism, limiting its administration to inconvenient intramuscular injections. This Drug Annotation describes the identification and optimization of a new series of potent orally available SERDs, which led to the discovery of 6-(2,4-dichlorophenyl)-5-[4-[(3<i>S</i>)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7<i>H</i>-benzo[7]annulene-2-carboxylic acid (<b>43d</b>), showing promising antitumor activity in breast cancer mice xenograft models and whose properties warranted clinical evaluation.
Holography with a neutron interferometer (2016)

We use a Mach-Zehnder interferometer to perform neutron holography of a spiral phase plate. The object beam passes through a spiral phase plate, acquiring the phase twist characteristic of orbital angular momentum states. The reference beam passes through a fused silica prism, acquiring a linear phase gradient. The resulting hologram is a fork dislocation image, which could be used to reconstruct neutron beams with various orbital angular momenta. This work paves the way for novel applications of neutron holography, diffraction and imaging.
Measuring liquid crystal elastic constants with free energy perturbations (2013)

A first principles method is proposed to calculate the Frank elastic constants of nematic liquid crystals. These include the constants corresponding to standard splay, twist and bend deformations, and an often-ignored surface-like contribution known as saddle-splay. The proposed approach is implemented on the widely studied Gay-Berne (3, 5, 2, 1) model [J. G. Gay and B. J. Berne, J. Chem. Phys., 1981, 74, 3316], and the effects of temperature and system size on the elastic constants are examined in the nematic phase. The results of simulations for splay, twist, and bend elastic constants are consistent with those from previous literature reports. The method is subsequently applied to the saddle-splay elastic constant k24 which is found to exist at the limits of the Ericksen inequalities governing positive definite free energy. Finally, extensions of the method are discussed that present a new paradigm for in silico measurements of elastic constants.
A highly efficient 1-GHz, 15-W power amplifier design based on a 50-V LDMOS transistor (2010)

We present a 15-W, 1-GHz harmonically tuned power amplifier (PA) with a power added efficiency (PAE) of 75%. The PA design is based on a packaged 50-V Si-LDMOS engineering sample. The PAE is maximized by an appropriate tuning of the fundamental and second harmonics, while the higher harmonics are shortened by the parasitic drain-source capacitance. The PA design is based on a simplified transistor model which is optimized for harmonically tuned PAs. The model parameters are extracted from IV- and S-parameter measurements of the packaged LDMOS device. A good agrement between the simulation and measurement results shows the accuracy of the modeling and PA design procedure.
Differential expression of genes during legume seed development (1986)

Abstract The accumulation of certain proteins specific to those tissues in the developing seeds of legumes represents a system of academic and practical significance in the study of differential gene expression. Besides the simple distinction between ‘seed-specific’ and ‘non-seed-specific’ expression of genes, further controls are present in determining the level of expression of a particular gene, and the variations in its expression with cell type, developmental stage and environmental perturbation. There are also genetic factors that lead to variations in the expression of homologous genes between lines or species. Gene expression can be assayed at the levels of synthesis of specific proteins, level of mRNA species, and transcription of specific genes, and the results of all these assays lead to a broad correlation between events at the level of the gene and protein deposition in the developing seed. This correlation is strong at earlier stages of seed development, but is weaker at later stages. Evidence is presented that control of gene expression occurs both at transcription and by post-transcriptional processes. Seed protein genes have conserved sequences in their 5' flanking regions that are specific to gene families, and these are suggested to be involved in transcriptional control of the expression of these genes. Although such sequences are unlikely to be solely responsible for transcription control, there is no strong evidence for changes in DNA methylation or in chromatin conformation being causally related to expression of seed protein genes. Control of gene expression in developing seeds is considered in terms of a genetically determined, conserved developmental programme, the aim of which is to produce a viable embryo. This programme will allow considerable plasticity in gene expression within constraints prescribed by seed viability. Although it may be possible to understand the immediate controls of seed protein gene expression, present systems are not adequate to study the genes that control the developmental programme. More fundamental investigations will be assisted by mutants that possess altered seed development patterns.
Benefits of Endoscopic Vein Harvesting (2000)

The purpose of this study was to evaluate and compare the benefits of endoscopic saphenous vein harvesting (EVH) with the traditional incision technique (TIT) for coronary artery bypass grafting (CABG) in respect to the technical procedure and clinical outcome. In a prospective nonrandomized, case-matched study the greater saphenous vein was harvested for CABG in 22 patients using the endoscopic technique and in 18 patients with the traditional method. Comparisons were made for the operating time, length of incision and vein harvested, graft quality, postoperative complications, and pain assessment. Patient demographics were well matched. EVH required smaller incisions than did the TIT (10.5 +/- 6.6 vs. 31.2 +/- 7.8 cm, respectively; p < 0.0001). Harvest time and vein quality were comparable in the two groups. Total vein operating time was shorter following the endoscopic technique (60 +/- 24 vs. 100 +/- 35 minutes, respectively; p < 0.0001). EVH had fewer complications (NS), and postoperative pain was significantly less (p = 0.0034). The major advantages of endoscopic vein harvesting are a significant reduction of postoperative pain and strikingly better cosmetic results. Wound complications seem to be less frequent.
Controlled polymer dewetting by physical confinement (2002)

We report ordering of polymer drops that takes place when a thin polystyrene film confined by polydimethylsiloxane walls dewets on a silicon substrate. When annealed above the glass transition temperature, the thin polymer film dewets, resulting in the formation of a regular structure inside and outside the confinement. It is found that the ordering becomes strongly suppressed as the film thickness increases and the pattern size decreases due to the physical confinement of the mold. As a result, the ordering can take place only when the wavelength of the capillary wave is smaller than the characteristic length of the physical confinement.
alpha 1-ADRENOCEPTOR ANTAGONISTS TERAZOSIN AND DOXAZOSIN INDUCE PROSTATE APOPTOSIS WITHOUT AFFECTING CELL PROLIFERATION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA (1999)

These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.
Human M1 macrophages express unique innate immune response genes after mycobacterial infection to defend against tuberculosis (2022)

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced Inregs expression. M1-MΦs and M2-MΦs express pro- and anti-inflammatory cytokine-chemokines, respectively, and M1-MΦs show nitric oxide and autophagy-dependent degradation of Mtb, leading to increased antigen presentation to T cells through an ATG-RAB7-cathepsin pathway. Despite Mtb infection, M1-MΦs show increased histone acetylation at the ATG5 promoter and pro-autophagy phenotypes, while increased histone deacetylases lead to decreased autophagy in M2-MΦs. Finally, Mtb-infected neonatal macaques express human Inregs in their lymph nodes and macrophages, suggesting that M1 and M2 phenotypes can mediate immunity to TB in both humans and macaques. We conclude that human MФ subsets show unique patterns of gene expression that enable differential control of TB after infection. These genes could serve as targets for diagnosis and immunotherapy of TB.
Evaluation of microfabricated deformable mirror systems (1998)

This paper presents recent result for aberration correction and beam steering experiments using polysilicon surface micromachined piston micromirror arrays. Microfabricated deformable mirrors offer a substantial cost reduction for adaptive optic systems. In addition to the reduced mirror cost, microfabricated mirrors typically require low control voltages, thus eliminating high voltage amplifiers. The greatly reduced cost per channel of adaptive optic systems employing microfabricated deformable mirrors promise high order aberration correction at low cost. Arrays of piston micromirrors with 128 active elements were tested. Mirror elements are on a 203 micrometers 12 by 12 square grid. The overall array size is 2.4 mm square. The arrays were fabricated in the commercially available DARPA supported MUMPs surface micromachining foundry process. The cost per mirror array in this prototyping process is less than 200 dollars. Experimental results are presented for a hybrid correcting element comprised of a lenslet array and piston micromirror array, and for a piston micromirror array only. Also presented is a novel digital deflection micromirror which requires no digital to analog converters, further reducing the cost of adaptive optics system.
Personality traits in bipolar disorder and influence on outcome (2017)

A significant minority of the patients scored ≥1 SD above the population mean on the global measures of Neuroticism, Aggressiveness and Disinhibition; scores this high are usually evident clinically. Yet, the personality profile does not seem to have prognostic value over a 2-year period.
Induction of EBV DNA Demethylation and of EBV-Specific Transcription in Daudi Cells Treated with TPA and n-Butyrate (1984)

The Epstein-Barr virus (EBV) abortive producer cell line Daudi may be induced to an incomplete cycle of viral production by chemicals such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-butyrate. These chemicals greatly increase expression of the early antigen but not that of viral capsid antigen. DNA from these cells was cleaved with various restriction enzymes specific for the mCG sites. Viral sequences (mostly in an episomal form) were tested for their methylation patterns and compared to the methylation pattern of the producer cell line B95-8. The BamHI C, V, and H EBV DNA fragments appeared to be nonmethylated in B95-8 whether or not induced by TPA. The same fragments were partially methylated in noninduced Daudi cells. Treatment of the latter with TPA and n-butyrate increased the amount of viral DNA per cell, and hypomethylation of some EBV DNA sites occurred in parallel. Transcription changes were noted only at the level of the BamHI H fragment; cytoplasmic RNA molecules specific for this region were detected only after induction.