gebhart/patrepeval huggingface dataset:
OXA-24, a Novel Class D β-Lactamase with Carbapenemase Activity in an <i>Acinetobacter baumannii</i> Clinical Strain (2000)

ABSTRACT Acinetobacter baumannii RYC 52763/97, a clinical isolate involved in a prolonged nosocomial outbreak at our hospital, was resistant to all β-lactams tested, including imipenem and meropenem, which had MICs of 128 and 256 μg/ml, respectively. This strain synthesized three β-lactamases: a plasmid-mediated TEM-1 β-lactamase (pI 5.4), an AmpC-type chromosomal cephalosporinase (pI 9.4), and a novel, presumptively chromosomally mediated OXA-related enzyme (pI 9.0) named OXA-24. After cloning and sequencing, the deduced amino acid sequence of the OXA-24 β-lactamase showed 40% homology with the OXA-10 (PSE-2) and OXA-7 β-lactamases, 39% homology with the OXA-11 and OXA-5 enzymes, and 33% homology with the LCR-1 β-lactamase. The amino acid sequence of the OXA-24 β-lactamase contained the STFK motif found in serine β-lactamases, but the typical class D triad KTG was replaced by KSG and the motif YGN was replaced by FGN. The OXA-24 β-lactamase hydrolyzed benzylpenicillin and cephaloridine but lacked activity against oxacillin, cloxacillin, and methicillin. The enzymatic activity was inhibited by chloride ions and by tazobactam (50% inhibitory concentration [IC 50 ], 0.5 μM), sulbactam (IC 50 , 40 μM), and clavulanic acid (IC 50 , 50 μM). Carbapenem MICs for an Escherichia coli transformant (pBMB-1) expressing the cloned OXA-24 enzyme had a fourfold increase. Relative V max / K m values of 13 and 6 were obtained with imipenem and meropenem, respectively, and a positive microbiological assay result with imipenem was obtained with a purified enzymatic extract of this transformant strain. Therefore, we consider this new β-lactamase to be involved in the carbapenem resistance of A. baumannii RYC 52763/97.
Physiological methods to study biofilm disinfection (1995)

This report reviews the development of a rapidin situ approach to study the physiological responses of bacteria within biofilms to disinfectants. One method utilized direct viable counts (DVC) to assess the disinfection efficacy when thin biofilms were exposed to chlorine or monochloramine. Results obtained using the DVC method were one log higher than plate count (PC) estimates of the surviving population after disinfection. Other methods incorporated the use of fluorogenic stains, a cryotomy technique to yield thin (5-μm) sections of biofilm communities and examination by fluorescence microscopy. The fluorogenic stains used in this approach included 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), which indicates cellular electron transport activity and Rhodamine 123, which responds specifically to proton motive force. The use of these stains allowed the microscopic discrimination of physiologically active bacteria as well as heterogeneities of active cells within thicker biofilms. The results of experiments using these techniques with pure culture and binary population biofilms on stainless steel coupons indicated biocidal activity of chlorine-based disinfectants occurred initially at the bulk-fluid interface of the communities and progressed toward the substratum. This approach provided a unique opportunity to describe the spatial response of bacteria within biofilms to antimicrobial agents and address mechanisms explaining their comparative resistance to disinfection in a way that has not been possible using traditional approaches. Results obtained using this alternative approach were also consistently higher than PC data following disinfection. These observations suggest that traditional methods involving biofilm removal and bacterial enumeration by colony formation overestimate biocide efficacy. Hence the alternative approach described here more accurately indicates the ability of bacteria surviving disinfection to recover and grow as well as demonstrate spatial heterogeneities in cellular physiological activities within biofilms.
全球化时代的比较教育:发展、使命和作用 (2002)

本次世界比较教育论坛选择全球化作为主题主要是关注其对很多方面产生影响的动态过程。比较教育也是其中的一个领域。但是这并不是一种被动的、单向的影响,比较教育对全球化的诸因素也起着推动和塑造的作用。 与其它研究领域相比,比较教育与全球化之间有着更紧密的联系。它一向都注重跨国分析,鼓励其研究人员具有开放的视野。同时,该领域主要的范式、方法论和重点研究课程都对跨国的变革力量有所反映。 本文首先考察了全球化的含义,然后分析了比较教育学的本质,之后分析了世界比较教育学会(WCCES)的发展历程及其职能。最后,本文指出了全球比较教育研究的一些特点,并着重指出了一些比较教育学者能够而且也应该涉足的具体研究领域。
Targeted Morphoproteomic Profiling of Ewing's Sarcoma Treated with Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors: Response/Resistance Signatures (2011)

Morphoproteomic analysis revealed that the mTOR pathway was activated in these two patients with advanced Ewing's sarcoma who showed response to combined IGF1R and mTOR inhibition, and the ERK pathway in the patient in whom resistance to this combination emerged. Our pilot results suggests that morphoproteomic assessment of signaling pathway activation in Ewing's sarcoma merits further investigation as a guide to understanding response and resistance signatures.
GENETIC ANALYSIS OF B CELL ANTIGEN RECEPTOR SIGNALING (1999)

In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B cell antigen receptor (BCR). Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development. Combinations of intracellular signaling pathways downstream of these PTKs determine the quality and quantity of BCR signaling. For example, concerted actions of the PLC-gamma 2 and PI3-K pathways are required for proper calcium responses. Similarly, the regulation of ERK and JNK responses involves both PLC-gamma 2 and GTPases pathways. Since the immune response in vivo is regulated by alteration of these signaling outcomes, achieving a precise understanding of intracellular molecular events leading to B lymphocyte proliferation, deletion, anergy, receptor editing, and survival still remains a challenge for the future.
Intraventricular Pressure Gradients in Heart Failure (2013)

The aim of the present study was to characterize intraventricular pressure gradients (IVPGs) in an animal model of chronic heart failure. New Zealand rabbits were treated with doxorubicin (heart failure group, n=5) or saline (control group, n=5) and instrumented with pressure catheters placed in the apex and outflow-tract of left ventricle (LV) and with sonomicrometer crystals placed in the apex and base of the LV free wall. In heart failure animals, ventricular filling was delayed and slower when compared with control animals. Moreover, the physiological nonuniformity observed between apical and basal segments in normal hearts was abolished in failing hearts. Simultaneously, physiological IVPGs observed during normal ventricular filling were entirely lost in heart failure animals. During ventricular emptying physiological nonuniformity between apical and basal segments observed in control animals was also abolished in heart failure animals. In failing hearts minimal length occurred later and almost at same time both in apical and in basal myocardial segments. Simultaneously, the characteristic IVPG pattern observed in healthy hearts during systole, which promotes ventricular emptying, was not observed in failing hearts. The present study showed that diastolic IVPGs, a marker of normal ventricular filling, and systolic IVPGs, a marker of normal ventricular emptying, are abolished in heart failure.
ABSTRACT 78 (2014)

Background and aims: In South Africa, little is known about children who have cardiac surgery; their socio-cultural backgrounds, pathway to care and how their families perceive the condition and cope. Aims: The aim was to discover each child’s pathway to care into surgery and the family’s coping strategies, support mechanisms, beliefs and cultural understandings around cardiac surgery. Methods: Ten children scheduled for cardiac surgery at the RCWMCH were recruited into this qualitative study. Children were too young to respond but observations and interviews with parents/guardians were conducted prior to and after their child’s surgery. Ethics approval was given by the UCT Human Research Ethics Committee. Interview data was transcribed and analysed for core themes and coded using a qualitative data analysis package. Results: Heart disease was initially described by parents as having no special cultural meaning and many said that their religious background had no influence on their beliefs around heart surgery. Yet during surgery and recovery parents reported feeling high levels of anxiety and uncertainty. At this time they found comfort in extended family/friends and spirituality became protective in maintaining hope and faith in a successful outcome. Parents further emphasised a significant degree of trust in the doctors, nurses, and healthcare system. Conclusions: The findings highlight the importance of extended family, psychological and emotional support, trust and spirituality in coping with heart disease and healing, for children, their families, and therefore health care professionals. Acknowledgements: The staff in the PICU. Children and parents in the Operation BraveHeart Study.
Short-term load forecasting (1987)

This paper discusses the state of the art in short-term load forecasting (STLF), that is, the prediction of the system load over an interval ranging from one hour to one week. The paper reviews the important role of STLF in the on-line scheduling and security functions of an energy management system (EMS). It then discusses the nature of the load and the different factors influencing its behavior. A detailed classification of the types of load modeling and forecasting techniques is presented. Whenever appropriate, the classification is accompanied by recommendations and by references to the literature which support or expand the discussion. The paper also presents a lengthy discussion of practical aspects for the development and usage of STLF models and packages. The annotated bibliography offers a representative selection of the principal publications in the STLF area.
Miniature drag sphere velocity probe (1978)

The development and testing of a miniature drag sphere velocity probe is described. Impetus for its development arose from a need to investigate the flow structure and turbulence beneath breaking surface water waves, i.e., a requirement for a fast-response small velocity probe which is useable in oscillatory flows. However, the presence of both drag (velocity) and inertial (acceleration) forces limits the measurable fluctuations to those having scales at least an order of magnitude larger than the sphere diameter, while the sphere diameter is itself limited by the requirement that the drag coefficient be independent of velocity. The resulting probe, with a sphere diameter of 0.43 cm, while not free of temperature drifts, pressure sensitivity, and cross-channel talk, yields encouraging results.
국내․외 대안학교의 교육과정 및 운영 비교분석 (2014)

본 연구는 국내.외 대안학교의 사례를 통하여 교육과정 및 교육운영을 비교분석함으로 대안학교 교육의 개선방안을 모색과 제안하는데 목적이 있다. 연국에 의해 얻어진 결과는 다음과 같다. 첫째, 대안학교 교육과정의 구성은 공통필수와 과정필수, 특성화 교과로 되어 있으며, 앞의 둘은 보통교과이나 특성화 교과는 기존의 학교에서는 볼 수 없는 다양한 내용으로 이루어져...
Development of the CRISPR nuclease Cas9 for high precision mammalian genome engineering (2014)

Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of genome function. Analogous to the search function in modern word processors, Cas9 can be guided to specific locations within complex genomes by a short RNA search string. Using this system, DNA sequences within the endogenous genome and their functional outputs are now easily edited or modulated in virtually any organism of choice. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes. To facilitate successful and specific Cas9 targeting, we first optimize the guide RNAs (sgRNA) to significantly enhance gene editing efficiency and consistency. We also systematically characterize Cas9 targeting specificity in human cells to inform the selection of target sites and avoid off-target mutagenesis. We find that SpCas9 tolerates mismatches between guide RNA and target DNA at different positions in a sequence-dependent manner, sensitive to the number, position and distribution of mismatches. We also show that Cas9-mediated cleavage is unaffected by DNA methylation and that the dosage of Cas9 and sgRNA can be titrated to minimize off-target modification. Additionally, we provide a web-based software tool to guide the selection and validation of target sequences as well as off-target analyses. We next demonstrate that Cas9 nickase mutants can be used with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity, simultaneous nicking via appropriately offset guide RNAs can reduce off-target activity by over 1,500-fold in human cells. In collaboration with researchers at the University of Tokyo, we further identified a PAM-interacting domain of the Cas9 nuclease that dictates Cas9 target recognition specificity. Finally, we present protocols that provide experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks. Taken together, this work enables a variety of genome engineering applications from basic biology to biotechnology and medicine.
Efficient parallel-pipelined GHASH for message authentication (2012)

AES/GCM is a common mode for authenticated encryption. One of its components is Galois HASH (GHASH) which achieves the authentication task. In this work, we present an efficient key independent hardware implementation for parallel-pipelined GHASH. Karatsuba Ofman Algorithm (KOA) is used for Galois Field (GF) multiplication. Unlike previous parallel hardware architectures based on KOA, we use only one reduction array for all parallel KOA multipliers. Therefore, an area optimized design is achieved. In addition, pipelined KOA is adopted to get higher clock frequency. 4-Parallel pipelined GHASH is evaluated using Xilinx Virtex5. It occupies 7.128k Slices and achieves 113.8 Gbps as an authentication throughput. Higher hardware efficiency (throughput/slice) in comparison with prior art (Key independent GHASH) is achieved.
Rat plasma lipoproteins: re-evaluation of a lipoprotein system in an animal devoid of cholesteryl ester transfer activity (1982)

Plasma lipoproteins from male rats were isolated by rate zonal centrifugation. Four lipoproteins were identified: VLDL, LDL, HDL1, and HDL2. LDL, HLD1, and some HDL2 distributed within the salt density interval of 1.006-1.085 g/ml, while HDL2 was found in the 1.063-1.21 g/ml interval. HDL3 was not identified in the rat. Rat VLDL is poor in cholesteryl esters (1.5-3.0% of total mass) and nearly lacks the smaller and denser particle subpopulation which is predominant in humans. Rat LDL, containing a relatively large amount of triglyceride (20.2% of total mass) and a small amount of cholesteryl ester (27.5%), could be isolated free of apoproteins other than apoB. HDL1 is a cholesteryl ester-rich lipoprotein that occupies a density interval overlapping both LDL and HDL2. ApoE is the major protein constituent of HDL1; apoA-I, A-IV, and C are also present. Apo-A-I-rich HDL2 is the only human-like HDL subpopulation found in rats. Lipoproteins from fasted and non-fasted rats were essentially similar. Arachidonic acid contributed 56.7% and 72.3% of total cholesteryl ester fatty acids in HDL1 and HDL2, respectively, but only 7.9% and 27.3% in VLDL and LDL, respectively. Palmitic, palmitoleic, and oleic acids were the major cholesteryl ester fatty acids in VLDL and LDL. In vitro incubation of biosynthetically labeled HDL2 cholesteryl ester with rat plasma demonstrated minimal transfer of the labeled cholesteryl ester to VLDL and LDL. These results indicate biological immiscibility of HDL cholesteryl esters with those of lower density lipoproteins. The finding of cholesteryl ester-poor VLDL and LDL and the presence of HDL as larger and less dense subpopulations is compatible with the absence of cholesteryl ester transfer activity in an animal with pronounced LCAT activity.
Prolonged survival of thymoma-bearing mice after vaccination with a soluble protein antigen entrapped in liposomes: a model study. (1992)

EG7-OVA cells are mouse thymoma EL4 cells stably transfected with the complementary DNA of chicken ovalbumin (OVA) and thus express OVA epitopes as a unique antigen. Cytotoxic T lymphocytes specific to OVA can be elicited by immunization of mice with OVA osmotically loaded into syngeneic splenocytes or entrapped in liposomes. Cytotoxic T lymphocytes thus induced can specifically cytolyse the EG7-OVA cells in vitro in an antigen-specific and major histocompatibility complex-restricted manner. In the present study, we have examined in this model system whether immunization with liposomal OVA can protect mice against tumors induced by EG7-OVA cells. Vaccination with OVA either entrapped in liposomes or osmotically loaded in the syngeneic splenocytes prolonged the survival of mice which had been challenged with EG7-OVA cells, but not those mice challenged with the parent EL4 cells. The antitumor effect was attributed to the induced OVA-specific cytotoxic T lymphocyte activity, since other forms of acquired immunity such as interaction of tumor cells with specific antibody could not be detected. Our results demonstrate that immunization with antigen incorporated in liposomes could be a useful means of inducing a protective antitumor response.
iTARGET: A phase II trial to assess the response to gefitinib in epidermal growth factor receptor (<i>EGFR</i>)-mutated non-small cell lung cancer (NSCLC) tumors (2007)

7504 Background: Somatic EGFR mutations correlate with increased response and survival in NSCLC patients (pts) treated with gefitinib. We conducted the 1st prospective US trial of 1st-line gefitinib in pts with advanced NSCLC harboring EGFR mutations. Methods: Chemotherapy-naïve pts with stage IIIB with effusion or IV NSCLC, measurable disease, and = 1 characteristic associated with mutations (female (F), adenocarcinoma (AC), never-smoking (NS), East Asian (EA)) underwent direct DNA sequencing of tumor tissue EGFR exons 18–24. Mutation-positive pts received gefitinib (250 mg/d) until progression or unacceptable toxicity. The primary outcome was response rate (RR) by RECIST criteria. Results: We sequenced 98 pts and detected EGFR mutations in 34 (35%); 3 were not assessable. Observed mutations were 18 (53%) exon 19 deletions (del), 9 (26%) L858R, 3 (9%) exon 20 insertions (ins), 2 T790M/L858R, 1 G719A, and 1 L861Q. Characteristics of the 98 screened pts were 69 F, 89 AC, 37 NS, and 5 EA; those of the 34 mutation pts were 20 (59%) F, 31 (91%) AC, 19 (56%) NS and 2 (6%) EA. The best predictor of EGFR mutation was NS. Of the 34 mutation pts, 31 (91%) received gefinitib. Reasons for non-treatment were pt preference (1 exon 19 del) and mutation associated with gefitinib-resistance (1 T790M/L858R, 1 exon 20 ins). Adverse events were mainly grade 1–2 rash and diarrhea; 1 case of grade 4 interstitial lung disease occurred after 2 weeks of therapy. The RR was 58% (95% confidence interval 39–75) and was 78% in L858R pts and 65% in del 19 pts. There were no responses among the G719A, L861Q, T790M/L858R and exon 20 ins pts treated. 12 pts have progressed, 18 remain on therapy. The median progression-free survival (PFS) is currently 11.8 mo and does not differ by mutation type, though follow-up is short (median 6.8 mo, range 1–24). 27 pts are still alive. Of the 31 pts treated, 22 (71%) had high EGFR gene copy number (amplification (3) or high polysomy (19)); RR and PFS did not vary by copy number. Conclusions: 1st-line gefitinib therapy in EGFR mutation-positive NSCLC pts is feasible in a multi-institutional study, well tolerated, and yields a substantial RR and PFS. This strategy should be compared to standard chemotherapy in a genotype-directed randomized trial. No significant financial relationships to disclose.
Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes (2016)

Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future.
Reptilian and avian follicular hierarchies: Models for the study of ovarian development (1990)

The presence of an ovarian follicular hierarchy is a characteristic feature of reptiles and birds. The hierarchy contains follicles at all stages of maturation and therefore, varying degrees of sensitivity to the ovulation-inducing effects of the gonadotropins. In the hen, ovulability is gained as the ability of the follicle to produce androgens and estrogens declines and the ability to produce progesterone increases. In the mature follicle, the granulosa cells are the site of progesterone production whereas the theca cells produce androgens and estrogens. Small follicles that have not yet been (and may never be) recruited into the yolk-filled hierarchy are the major producers of androgens and estrogens within the ovary. In reptiles the ovarian follicular hierarchy includes non-vitellogenic follicles and in some species includes follicles destined to become atretic. These two features distinguish the reptiles from the birds and provide experimental biologists with a unique model to investigate the physiological events that regulate the most common fate of ovarian follicles, atresia.
High sensitivity phase mapping with parallel Fourier domain optical coherence tomography at 512 000 A-scan/s (2010)

In this paper we present an ultra high speed and highly phase sensitive line-field FD-OCT system for quantitative phase mapping. The system works with a maximum speed of 512 000 A-scan/s (1000 fps) in real time mode. Along the parallel recorded direction excellent phase stability corresponding to a path length variation of only 510 pm was measured. We demonstrate how to exploit this phase accuracy for fast chemical analysis of glucose mixture processes. The system has particular potential for studying micro-fluidic processes.