gebhart/patrepeval huggingface dataset:
Inhibition of Intracellular Macromolecular Synthesis inStaphylococcus aureusby Thrombin‐Induced Platelet Microbicidal Proteins (2002)

Thrombin-induced platelet microbicidal proteins (tPMP-1 and tPMP-2) are believed to initiate their staphylocidal effects via cytoplasmic membrane perturbation. The aim of the present study was to investigate the role of subsequent inhibition of macromolecular synthesis in the staphylocidal mechanisms of tPMP-1 and tPMP-2 in an isogenic tPMP-susceptible and -resistant strain pair (ISP479C and ISP479R, respectively). In ISP479C, tPMP-1 and tPMP-2 (2 mg/mL) exerted significant bactericidal effects and significantly reduced DNAand RNAsynthesis (P <.05 vs. con-trol). In contrast, tPMP-1 and tPMP-2 exerted reduced staphylocidal effects and significantly reduced inhibition of DNA and RNA synthesis against ISP479R, as compared with ISP479C (P <.05). However, tPMP-1 and tPMP-2 (2 µg/mL) caused equivalent degrees of inhibition of protein synthesis in both ISP479C and ISP479R. Collectively, these observations are consistent with the hypothesis that inhibition of specific macromolecular synthesis pathways is integral to the overall staphylocidal mechanism(s) of tPMPs.
An Enantioselective Synthesis of FR182877 Provides a Chemical Rationalization of Its Structure and Affords Multigram Quantities of Its Direct Precursor (2003)

The evolution of a strategy culminating in an efficient, enantioselective synthesis of the potent microtubule-stabilizing agent FR182877 is described. Guided by a proposed biogenesis of this complex natural product, a solution emerged that involved the first reported example of a double transannular Diels-Alder reaction to fashion the key elements of its hexacyclic structure. This pivotal transformation creates a complex pentacycle from a 19-membered macrocyclic pentaene, forming seven new stereogenic centers in a fully diastereocontrolled fashion. The efficiency of the approach ultimately enabled the preparation of multigram quantities of the direct precursor of FR182877 for conversion to the relatively unstable natural product when required. The reactivity of the strained, bridgehead olefin of this secondary metabolite with biologically relevant nucleophiles is also described.
Understanding monomode optical fibers (1981)

Because optical fibers that propagate one mode only are now the most likely candidate for future long-distance high-capacity communication, there is great interest in their light transmission characteristics. Standard descriptions of such fibers are rather unattractive both to students and to the physically minded scientist from several viewpoints, but mostly because numerical methods are always required at some stage in the analysis even if only to solve a transcendental eigenvalue equation. We reduce these restrictions by deriving simple analytical forms for the fields, propagation constant, and other parameters necessary to describe the fundamental mode on graded refractive index profiles. From these fully analytical expressions, we have a clearer understanding of propagation without recourse to numerical methods. Thus the theory of monomode fibers is now more accessible to undergraduates at elementary levels.
Poly(ADP-ribose) synthetase. The DNA binding domain and the automodification domain. (1982)

Poly(ADP-ribose) synthetase is known to require double-stranded DNA for activity and to be susceptible to automodification with poly(ADP-ribose). This enzyme is cleaved into two fragments by limited proteolysis with papain. Their molecular weights are 74,000 and 46,000, respectively, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The fragment of Mr 46,000 binds to a nicked DNA-cellulose column with the same affinity as that of native enzyme, while the fragment of Mr 74,000 has little affinity for the DNA ligand. When the enzyme previously automodified with [adenine-U-14C]NAD (2 ADP-ribose units incorporated per molecule of enzyme) is digested with papain, the label is detected only in the fragment of Mr 74,000. These results indicate that poly(ADP-ribose) synthetase contains two domains, one acting as the site for binding of DNA and the other acting as the site(s) for accepting poly(ADP-ribose).
Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome (2002)

The postinduction level of minimal residual disease (MRD) was quantified with a competitive polymerase chain reaction (PCR) technique in 104 children with acute lymphoblastic leukemia (ALL) diagnosed between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day 15 (D15) and day 29 (D29) after the start of induction therapy (r(s) = 0.70, P <.0001). The 15 patients with T-cell disease had higher D29 MRD than those with B-lineage ALL (P =.01). Age was positively related to D29 MRD (r(s) = 0.32, P =.001). The 16 patients who had a relapse had higher D15 and D29 MRD levels than the patients who stayed in remission (median levels D15, 1% versus 0.1%, P =.03; D29, 0.4% versus 0.01%, P =.0001). No patients with a MRD level less than 0.01% on D29 have so far had a relapse, whereas the 7-year probability of event-free survival for patients with higher MRD levels was 0.52 (P =.0007). The group of patients with a D29 MRD less than 0.01% included patients with T-cell disease, white blood cell count more than 50 x 10(9)/L at diagnosis, or age 10 years or older, and could not be identified by up-front criteria. The best-fit Cox model to predict the risk of relapse included D29 MRD (P =.004) and age (P =.009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a very low risk of relapse. Further trials are needed to reveal whether such patients with D29 MRD less than 0.01% can be cured with less intensive chemotherapy, which would reduce the risk of serious late effects as well as the costs of therapy.
A virtual environment and model of the eye for surgical simulation (1994)

An anatomically detailed 3-D computer graphic model of the eye and surrounding face within a virtual environment has been implemented for use in a surgical simulator. The simulator forms part of a teleoperated micro-surgical robotic system being developed for eye surgery. The model has been designed to both visually and mechanically simulate features of the human eye by coupling computer graphic realism with finite element analysis.
Diseases Caused by Defects in the Visual Cycle: Retinoids as Potential Therapeutic Agents (2006)

Absorption of a photon by an opsin pigment causes isomerization of the chromophore from 11-cis-retinaldehyde to all-trans-retinaldehyde. Regeneration of visual chromophore following light exposure is dependent on an enzyme pathway called the retinoid or visual cycle. Our understanding of this pathway has been greatly facilitated by the identification of disease-causing mutations in the genes coding for visual cycle enzymes. Defects in nearly every step of this pathway are responsible for human-inherited retinal dystrophies. These retinal dystrophies can be divided into two etiologic groups. One involves the impaired synthesis of visual chromophore. The second involves accumulation of cytotoxic products derived from all-trans-retinaldehyde. Gene therapy has been successfully used in animal models of these diseases to rescue the function of enzymes involved in chromophore regeneration, restoring vision. Dystrophies resulting from impaired chromophore synthesis can also be treated by supplementation with a chromophore analog. Dystrophies resulting from the accumulation of toxic pigments can be treated pharmacologically by inhibiting the visual cycle, or limiting the supply of vitamin A to the eyes. Recent progress in both areas provides hope that multiple inherited retinal diseases will soon be treated by pharmaceutical intervention.
Efficacy of laser Doppler flowmetry for the diagnosis of revascularization of reimplanted immature dog teeth (2001)

LDF readings correctly predicted the pulp status (vital vs. non-vital) in 83.7% of the readings. 73.9% (17 of 23) were correct for the vital teeth and 95% (19 of 20) were correct for the non-vital teeth. Fisher's exact test (2-tail) indicated that there was no significant association between the efficacy of LDF and tooth type (P = 0.166), although P2 was the least accurate tooth tested. Wilcoxon's matched-pair signed rank test demonstrated that in the revascularized (vital) teeth, the flux value between the baseline and week 2 dropped significantly (P = 0.0001), increased significantly from week 2 to week 4 (P = 0.0001) and then decreased steadily until week 12. However, at week 12 the flux was still significantly higher than at week 2 (P = 0.010). In the teeth that failed to revascularize, the flux value dropped significantly by weeks 1 and 2 (P = 0.004 and P = 0.0001, respectively). Flux values did not increase from week 2. A Fast Fourier Transform (FFT) analysis confirmed a pulse of dominant frequency of 2 Hz in the teeth that returned to vitality and the lack thereof in those that stayed non-vital. One tooth in which the flux value evaluation indicated a non-vital tooth but the radiographic/histologic findings showed vital (false negative) possessed a pulse of dominant frequency and proved by this method to have successfully revascularized.
Image processing techniques to detect and filter objectionable images based on skin tone and shape recognition (2002)

In this paper we describe image-processing techniques to detect and categorize potentially objectionable images based solely on the image content. The techniques include a novel method of matching skin tones based on a fuzzy classification scheme and shape recognition techniques to match faces and other elements of the human anatomy. In particular the color matching technique is significantly more accurate than existing methods documented in literature. These techniques offer a means of filtering images, based solely on graphical content, for a new generation of home Internet appliances.
Can Molecular and Cellular Neuroprotection Be Translated Into Therapies for Patients? (2010)

The translational gap between cellular and molecular neuroscience and patient therapy may be bridged by first developing therapies for narrow stroke indications. A single success may stimulate further research, funding, and a capacity to generalize initial results to broader stroke populations.
Artificial intelligence in healthcare: past, present and future (2017)

Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI.
Methods for Genotyping Single Nucleotide Polymorphisms (2001)

One of the fruits of the Human Genome Project is the discovery of millions of DNA sequence variants in the human genome. The majority of these variants are single nucleotide polymorphisms (SNPs). A dense set of SNP markers opens up the possibility of studying the genetic basis of complex diseases by population approaches. In all study designs, a large number of individuals must be genotyped with a large number of markers. In this review, the current status of SNP genotyping is discussed in terms of the mechanisms of allelic discrimination, the reaction formats, and the detection modalities. A number of genotyping methods currently in use are described to illustrate the approaches being taken. Although no single genotyping method is ideally suited for all applications, a number of good genotyping methods are available to meet the needs of many study designs. The challenges for SNP genotyping in the near future include increasing the speed of assay development, reducing the cost of the assays, and performing multiple assays in parallel. Judging from the accelerated pace of new method development, it is hopeful that an ideal SNP genotyping method will be developed soon.
Synthesis and hybridization studies on two complementary nona(2'-O-methyl)ribonucleotides (1987)

2'-O-Methyl derivatives of the common ribonucleosides except for guanosine were synthesized via the 2'-O-methylation of appropriately-protected nucleosides with CH3I in the presence of Ag2O. The 2'-O-methylguanosine derivative was prepared by the monomethylation of a 2',3'-cis-diol system with diazomethane. These derivatives were converted to protected 2'-O-methylribonucleoside 3'-phosphates and used for oligonucleotide synthesis on polymer supports. Thus, oligo(2'-O-methyl-ribonucleotides) having the sequence identical to the consensus sequence of the 5'-splice junction CAGGUAAGU and its complement were synthesized in a stepwise manner using the phosphotriester method. Thermal stabilities (Tm's) of the duplex of these 2'-O-methyl ribo-oligomers and eight related duplexes containing ribo- or deoxyribo-oligomers were examined. It was found that the 2'-O-methyl oligoribonucleotides can be utilized as an alternative to an oligoribonucleotide probe in RNA hybridizations as the hybrid formed has a high, or a higher Tm, the probe is much easier to synthesize and it is less likely to be enzymatically degraded.
Quantum electronics: a treatise. Volume I. Nonlinear optics, Part A (1975)

Unified discussions are presented of major quantum electronics topics including theory and measurement of nonlinear optical susceptibilities, two-photon absorption spectroscopy, stimulated Mandelstam--Brillouin process, spontaneous and stimulated parametric processes, and the stimulated Raman process. (JFP)
机器人能救“哈勃”吗？ (2005)

哥伦比亚号航天飞机在2003年坠毁引起人们对安全的关注,因而采用机器人技术修理哈勃太空望远镜的决定似乎是一件很自然的事情.这样,这座集科学家宠爱和公众赞美于一身的天文台将可以采用更先进的传感器继续工作至少五年.而且,使用远距离操纵器所获得的全部经验就会成为未来半独立式维修作业的基础.然而,现在独立的分析已经提出了新的质疑,即机器人的维修使命是否能可靠地营救哈勃.
Interferon-γ and tumor necrosis factor-α sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis (2007)

The subtle interaction between the implanting embryo and the maternal endometrium plays a pivotal role during the process of implantation. Human endometrial stromal cells (ESCs) express Fas and the implanting trophoblast cells secrete Fas ligand (FASLG, FasL), suggesting a possible role for Fas-mediated signaling during early implantation. Here we show that ESCs are primarily resistant to Fas-mediated apoptosis independently of their state of hormonal differentiation. Pre-treatment of ESCs with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha sensitizes them to become apoptotic upon stimulation of Fas by an agonistic anti-Fas antibody. Incubation of ESCs with the early embryonic signal human chorionic gonadotropin (hCG, CGB) does not influence their reaction to Fas stimulation. The sensitizing effect of IFN-gamma and TNF-alpha was accompanied by a significant upregulation of Fas and FLICE-inhibitory protein (FLIP, CFLAR) expression in ESCs. Additionally, we observed an activation of caspase 3, caspase 8 and caspase 9 upon apoptotic Fas triggering. In summary, we demonstrate that IFN-gamma and TNF-alpha sensitize primarily apoptosis-resistant ESCs to Fas-mediated cell death. This might be due to an upregulation of Fas expression, and apoptosis seems to be mediated by active caspase 3, caspase 8 and caspase 9. The observed pro-apoptotic effect of IFN-gamma and TNF-alpha on ESCs could play an important role in the modulation of early implantation.
Deployment dynamics of tape springs (1999)

Tape springs are straight, thin–walled strips with a curved cross–section. Following recent proposals for large deployable structures exploiting the structural simplicity and robustness of such springs as deployment actuators, the paper investigates the dynamic deployment of a tape spring that is either coiled around a circular hub, or folded into a zig–zag pattern. It is shown that in both cases the spring deforms by forming an elastically deformed region with zero transverse curvature and uniform longitudinal curvature. The process of formation and growth of a fold belongs to a wide class of propagating instabilities. It is characterized by a high peak moment and a lower propagation moment. A compact characterization of the moment–rotation relationship for an elastic fold is presented. A key feature is that the bending moment on either side of a fold moving along a uniform tape spring, away from any end supports, is constant, whereas this moment increases near a support. Compact and accurate two–dimensional theories are developed to simulate the self–actuated deployment of tape springs. It is shown that conservative energy formulations are appropriate for coiled springs, where the velocity field is smooth, but not for springs with localized folds. To simulate the motion of such localized folds a non–conservative impulse–momentum formulation is proposed, and it is found that this model can accurately predict both the steady motion of the folds along the tape spring and their rebound against the end supports.
Tyrosine‐derived polycarbonates: Backbone‐modified “pseudo”‐poly(amino acids) designed for biomedical applications (1992)

Starting from L-tyrosine (Tyr) and its metabolites desaminotyrosine (Dat) and tyramine (Tym), four structurally related model dipeptides were prepared: Dat-Tym (neither N- or C-terminus present), Z-Tyr-Tym (N-terminus protected by benzyloxycarbonyl), Dat-Tyr-Hex (C-terminus protected by a hexyl ester group), and Z-Tyr-Tyr-Hex (both N- and C-termini present, protected by benzyloxycarbonyl and hexyl ester, respectively). The model dipeptides were used as monomers in the synthesis of polycarbonates. The polymerization reaction in the presence of either phosgene or triphosgene proceeded via the phenolic hydroxyl groups. Polymers with molecular weights of 105,000-400,000 da (by gel permeation chromatography, relative to polystyrene standards) were obtained. The physicomechanical properties (solubility, mechanical strength, glass transition and decomposition temperature, processibility) of the polymers were determined, and an attempt was made to correlate the polymer properties with the nature of the N- and C-terminus protecting groups. The presence of the urethane bond at the N-terminus protecting group was found to reduce solubility, ductility, and processibility, probably due to interchain hydrogen bonding. The presence of a C-terminus alkyl ester group increased solubility and processibility. Thus, the most promising candidate polymer for biomedical applications was obtained from Dat-Tyr-Hex, the monomer carrying a C-terminus protecting group only. Since very similar results had recently been obtained for a series of structurally related polyiminocarbonates, the structure property correlations seem to be generally valid.
Facile preparation of non-self-quenching fluorescent DNA strands with the degree of labeling up to the theoretic limit (2012)

A new aggregation-induced emission (AIE) compound 1,1-dimethyl-2,5-bis[4-(isothiocyanatemethyl)phenyl]-3,4-diphenylsilole (SITC) was synthesized and used to conjugate with aminoallyl-dUTP. The SITC-dUTP can be incorporated enzymatically into DNA strands with the degree of labeling (DOL) up to the theoretic limit.
Discovery and in Vivo Evaluation of (S)-N-(1-(7-Fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and Related PI3Kδ Inhibitors for Inflammation and Autoimmune Disease (2014)

The development and optimization of a series of quinolinylpurines as potent and selective PI3Kδ kinase inhibitors with excellent physicochemical properties are described. This medicinal chemistry effort led to the identification of 1 (AMG319), a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation.
A very high heat flux microchannel heat exchanger for cooling of semiconductor laser diode arrays (1996)

A low-cost, high heat flux heat exchanger for cooling of high power (of the order of 1000 W/cm/sup 2/) semiconductor laser diode arrays has been designed and tested. The device uses a simple copper microchannel design to obtain very high fluid-to-wall heat transfer coefficients. Experimental results show that its overall thermal resistivity is less than 0.03/spl deg/C/W, which is 2-3 times better than current state-of-the-art heat sinks. A different version of the heat sink has also been tested and has demonstrated the capability of dissipating 200-300 W from a conventionally (solder) bonded resistor of area of about 0.5 mm/sup 2/ while limiting its surface temperature rise 20-30/spl deg/C. When operated at low pressures [0.48 MPa (70 psi)], this design also has a performance comparable to existing state-of-the art heat sinks so that it can be readily used as a replacement in current high power applications.
Direct sequencing of enzymatically amplified human genomic DNA. (1988)

The polymerase chain reaction is a recently described technique that uses flanking oligonucleotide primers and repeated cycles of enzymatic primer extension to amplify a short segment of DNA by greater than 100,000-fold. By use of sequencing primers located internal to the amplification primers, direct genomic sequence was obtained from enzymatically amplified DNA by using the dideoxynucleotide chain-termination method. The method is relatively simple and offers significant advantages in identifying mutations in genes for which the normal sequence is known. Heterozygous and homozygous mutations in the human beta- and gamma-globin loci were unambiguously identified in 3 days with less than 1 microgram of genomic DNA.
Sexually transmitted papillomaviral infections (1987)

Abstract Multiple colposcopic biopsy specimens were collected from 160 women, with sampling of principal cervical and vulvar lesions as well as secondary areas of either minor acetowhitening or normal epitheluim. Papillomaviral deoxyribonucleic acid was detected by Southern blot hybridization in 197 (90%) of the 218 principal biopsy specimens and 93 (46%) of 198 secondary biopsy specimens. Although different papillomaviruses were found at different sites in 31 women, only six of 416 specimens contained multiple types within the same sample. Specific viral types were associated with specific disease patterns. Only one of 80 type 6 or 11 infections had a diagnosis greater than cervical intraepithelial neoplasia, grade 2. In contrast, 42 of 48 (90%) biopsy specimens of cervical intraepithelial neoplasia, grade 3, or invasive cancer contained type 16, 18, or 31. Nonetheless, 12 of 124 (10%) cases of condyloma and cervical intraepithelial neoplasia, grade 1, were associated with types 16, 18, and 31 infections. Of 58 women with multicentric disease, 46 had positive hybridizations for both cervical and vulvar lesions (32 showing the same type in both samples and 14 showing different viruses). Differing patterns of papillomavirus-induced disease arise partly from the predilection of specific viral types for certain anatomic sites and partly through variations in host response. Detection of viral deoxyribonucleic acid in 46% of the secondary biopsy specimens suggests that disease expression may represent focal breakdown of host surveillance within a field of latent papillomaviral infection.