gebhart/patrepeval huggingface dataset:
Screening of TB Actives for Activity against Nontuberculous Mycobacteria Delivers High Hit Rates (2017)

The prevalence of lung disease due to infections with nontuberculous mycobacteria (NTM) has been increasing and surpassed tuberculosis (TB) in some countries. Treatment outcomes are often unsatisfactory, highlighting an urgent need for new anti-NTM medications. Although NTM in general do not respond well to TB specific drugs, the similarities between NTM and <i>Mycobacterium tuberculosis</i> at the molecular and cell structural level suggest that compound libraries active against TB could be leveraged for NTM drug discovery. Here we tested this hypothesis. The Pathogen Box from the Medicines for Malaria Venture (MMV) is a collection of 400 diverse drug-like compounds, among which 129 are known to be active against <i>M. tuberculosis</i>. By screening this compound collection against two NTM species, <i>Mycobacterium abscessus</i> and <i>Mycobacterium avium</i>, we showed that indeed the hit rates for NTM among TB active compounds is significantly higher compared to compounds that are not active against TB. MIC/dose response confirmation identified 10 top hits. Bactericidal activity determination demonstrated attractive potency for a subset of the confirmed hits. <i>In vivo</i> pharmacokinetic profiling showed that some of the compounds present reasonable starting points for medicinal chemistry programs. Three of the top hits were oxazolidinones, suggesting the potential for repositioning this class of protein synthesis inhibitors to replace linezolid which suffers from low potency. Two hits were inhibitors of the trehalose monomycolate transporter MmpL3, suggesting that this transmembrane protein may be an attractive target for NTM. Other hits are predicted to target a range of functions, including cell division (FtsZ), DNA gyrase (GyrB), dihydrofolate reductase, RNA polymerase and ABC transporters. In conclusion, our study showed that screening TB active compounds for activity against NTM resulted in high hit rates, suggesting that this may be an attractive approach to kick start NTM drug discovery projects. In addition, the work identified a series of novel high value NTM hits with associated candidate targets which can be followed up in hit-to-lead projects for the discovery of new NTM antibiotics.
Amino acid sequence of pigeon egg-white lysozyme. (1985)

The amino acid sequence of pigeon egg-white lysozyme has been determined. The protein molecule contains a single polypeptide chain of 127 amino acid residues and exhibits only about 60% homology when compared to hen egg-white lysozyme.
<sup>32</sup>P-Pyrophosphate in the Treatment of Persistent Metastatic Bone Pain (1980)

Eight patients with persistent pain due to disseminated bone metastases from mammary carcinoma were given about 370 MBq (10 mCi) of 32P-pyrophosphate on 10 occasions. All but one of the patients experienced alleviation of pain lasting 1 to 4 months. The side effects, which derived mainly from haematopoetic tissue, prevent the routine use of this compound.
MicroRNA-204 Regulates Runx2 Protein Expression and Mesenchymal Progenitor Cell Differentiation (2009)

Differentiation of mesenchymal stem cells into a particular lineage is tightly regulated, and malfunction of this regulation could lead to pathological consequences. Patients with osteoporosis have increased adipocyte accumulation, but the mechanisms involved remain to be defined. In this study, we aimed to investigate if microRNAs regulate mesenchymal progenitor cells and bone marrow stromal cell (BMSC) differentiation through modulation of Runx2, a key transcription factor for osteogenesis. We found that miR-204 and its homolog miR-211 were expressed in mesenchymal progenitor cell lines and BMSCs and their expression was induced during adipocyte differentiation, whereas Runx2 protein expression was suppressed. Retroviral overexpression of miR-204 or transfection of miR-204 oligo decreased Runx2 protein levels and miR-204 inhibition significantly elevated Runx2 protein levels, suggesting that miR-204 acts as an endogenous attenuator of Runx2 in mesenchymal progenitor cells and BMSCs. Mutations of putative miR-204 binding sites upregulated the Runx2 3'-UTR reporter activity, suggesting that miR-204/211 bind to Runx2 3'-UTR. Perturbation of miR-204 resulted in altered differentiation fate of mesenchymal progenitor cells and BMSCs: osteoblast differentiation was inhibited and adipocyte differentiation was promoted when miR-204 was overexpressed in these cells, whereasosteogenesis was upregulated and adipocyte formation was impaired when miR-204 was inhibited. Together, our data demonstrated that miR-204/211 act as important endogenous negative regulators of Runx2, which inhibit osteogenesis and promote adipogenesis of mesenchymal progenitor cells and BMSCs.
A<scp>NTIBIOTIC</scp> U<scp>SE IN</scp> P<scp>LANT</scp> A<scp>GRICULTURE</scp> (2002)

▪ Abstract Antibiotics have been used since the 1950s to control certain bacterial diseases of high-value fruit, vegetable, and ornamental plants. Today, the antibiotics most commonly used on plants are oxytetracycline and streptomycin. In the USA, antibiotics applied to plants account for less than 0.5% of total antibiotic use. Resistance of plant pathogens to oxytetracycline is rare, but the emergence of streptomycin-resistant strains of Erwinia amylovora, Pseudomonas spp., and Xanthomonas campestris has impeded the control of several important diseases. A fraction of streptomycin-resistance genes in plant-associated bacteria are similar to those found in bacteria isolated from humans, animals, and soil, and are associated with transfer-proficient elements. However, the most common vehicles of streptomycin-resistance genes in human and plant pathogens are genetically distinct. Nonetheless, the role of antibiotic use on plants in the antibiotic-resistance crisis in human medicine is the subject of debate.
A tissue pressure model for palpatory perception of the cranial rhythmic impulse. (1991)

A tissue pressure model was developed to provide a possible physiologic basis for the manifestation of the cranial rhythmic impulse (CRI). The model assumes that the sensation described as the CRI is related to activation of slowly adapting cutaneous mechanoreceptors by tissue pressures of both the examiner and the subject, and that the sources of change in these tissue pressures are the combined respiratory and cardiovascular rhythms of both examiner and subject. The model generates rhythmic impulses with patterns similar to those reported for the CRI. Also, a significant correlation was found between frequencies calculated from the model and published values for CRI obtained by palpation. These comparisons suggest that the CRI may arise in soft tissues and represents a complex interaction of at least four different physiologic rhythms.
Tapered, both in dimension and in index, velocity coupler: theory and experiment (1993)

The authors consider a tapered velocity coupler (TVC) that meets the adiabatic invariance condition with sufficiently strong coupling between the fundamental modes of individual guides in the middle region of the coupler while permitting individual excitation at the input end and sorting of the modes at the output end. This approach helps reduce the device length considerably by permitting much higher taper angle. A TVC consisting of one tapered and another straight, graded index waveguide is modeled using the normal modes of the entire, composite TVC structure. The analytical results are in excellent agreement with experimental results for a TVC fabricated in Ti:LiNbO/sub 3/. It is shown that the representation of the local normal modes as the superposition of the modes of the uncoupled guides leads to erroneous results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
식물 윤리적 측면에서 본 원예치료 패러다임 발전방향에 대한 연구 (2011)

원예치료와 관련된 패러다임의 발전방향을 제시하는 것을 주목적으로 하여 최근 생명체로서의 식물에 대한 인간의 도덕적 책임, 보호할 의무 등을 제시하고 있는 식물윤리분야 최신 연구이론과 이를 바탕으로한 이론 틀을 이미 제시하고 있는 숲·환경교육 패러다임을 연계하여 원예치료의 새로운 패러다임 발전방향을 제시하고자 한다(중간생략). 이를 위한 근접 연구분야로 식물윤리의 연구이론과 행동원리-정의의 원리, 악행금지의 원리 들을 추출해 내어 식물을 대하는 인간의 개념적인 행위와 태도에 관한 정당한 방향을 수립하고자 한다. 또한 이를 식물의 다양한 속성인 생장, 발달, 적응 및 노화와 같은 식물생활사를 원리로 한 원예치료 프로그램으로서의 정체성을 확보하기 위해 보완해야 할 발전적 측면의 패러다임으로 접목해야 함을 주장한다. 이와 더불어 인간-식물 관련 분야로 패러다임 분석틀 개발과 유사 연구들이 활발히 이루어지고 있는 숲. 환경교육 분야에서의 숲을 바라보는 관점변화를 구체적인 원예치료 활동내용 및 주제로 연계하고자 하였다. 이때 현재 원예치료에서 인간-식물의 영향을 1차적 효용(생존), 2차적 효용(생활환경), 3차적 효용(삶의 질)로 구분하고 있는 관점에서 식물의 4차적 효용으로서 윤리적 가치로서의 윤리실존적 관점의 영향이 포함되어야 함을 강조하며 활동 주제는 감상적, 치료적에서 도덕적, 배려 및 상호공생적으로 전개되어야 함을 강조하였다. 숲, 환경교육 등에서의 최근 패러다임으로 ``윤리실존적 관점`` 등이 원예치료에 반영되어 ``식물을 통해 발견해 낼 수 있는 치료적 가치를 탐구하는일``에서 벗어나 ``식물``에 대한 생태철학과 도적적 태도를 아울러 견지할 수 있는 행위를 가르치는 일``임을 반영하고 구체적인 활동으로 적용되도록 하는 것이 가장 큰 패러다임의 전환이 필요한 부분이라 할 수 있다.
THE GLUCOSE AND LACTATE CONSUMPTION OF THE DOG'S HEART (1935)

1. When the volume of blood in a heart‐lung circuit was increased the lactate in the blood tended to rise, and vice versa . This is as predicted from the facts that lactate arises by glycolysis in the blood and is removed by the heart. Estimation of the amounts of glucose utilized by the heart and based on the fall of blood sugar in heart‐lung preparations are certain to be too high if the rates of glycolysis in the blood and in the lungs are ignored or assessed at too low values. 2. To obviate the attempt at such calculations in which the lungs introduce an uncertain factor, recourse was had to an isolated heartoxygenator circuit. By the use of this the glucose and lactic acid utilization of the dog's heart were assessed at an average of 70 mg. and 200 mg. respectively, per 100 grm. heart/hr., the blood being oxygenated by a mixture of 5 per cent. CO 2 and 95 per cent. oxygen, and each ventricle, doing reasonable amounts of work under normal conditions of arterial pressures, at a temperature of about 37° C. 3. There was considerable fluctuation in the glucose usages in different hearts, but a general tendency for lactate and glucose utilizations to be reciprocally related. The sum of lactate and glucose utilizations was in the majority of experiments insufficient if combusted to account for the known oxygen usages of heart muscle. The rate of usage of either constituent was increased if its concentration in the blood was increased and, below certain critical levels, was reduced when its concentration was reduced. 4. Addition of insulin, the blood sugar being normal or low, increased the utilization of glucose but did not clearly affect that of lactic acid, whether this was at high or low concentration in the blood. The authors express their thanks to the Government Grants Committee of the Royal Society for a grant to one of us (C. L. E.), which covered part of the cost of animals. Also to Mr J. Trendall and Mr V. C. Tindley for skilled help in constructing and maintaining the necessary apparatus.
Route diversity with hitless path switching (1994)

A route diversity ‘hitless’ protection switching scheme is proposed that is free from bit loss even for unpredictable system failures. Freely switching between the working and protection paths improves the signal quality at the system output because the system automatically selects the no-error frame.
Content Sharing Graphs for Deduplication-Enabled Storage Systems (2012)

Deduplication in storage systems has gained momentum recently for its capability in reducing data footprint. However, deduplication introduces challenges to storage management as storage objects (e.g., files) are no longer independent from each other due to content sharing between these storage objects. In this paper, we present a graph-based framework to address the challenges of storage management due to deduplication. Specifically, we model content sharing among storage objects by content sharing graphs (CSG), and apply graph-based algorithms to two real-world storage management use cases for deduplication-enabled storage systems. First, a quasi-linear algorithm was developed to partition deduplication domains with a minimal amount of deduplication loss (i.e., data replicated across partitioned domains) in commercial deduplication-enabled storage systems, whereas in general the partitioning problem is NP-complete. For a real-world trace of 3 TB data with 978 GB of removable duplicates, the proposed algorithm can partition the data into 15 balanced partitions with only 54 GB of deduplication loss, that is, a 5% deduplication loss. Second, a quick and accurate method to query the deduplicated size for a subset of objects in deduplicated storage systems was developed. For the same trace of 3 TB data, the optimized graph-based algorithm can complete the query in 2.6 s, which is less than 1% of that of the traditional algorithm based on the deduplication metadata.
Tasco-Forage: IV. Influence of a seaweed extract applied to tall fescue pastures on sensory characteristics, shelf-life, and vitamin E status in feedlot-finished steers. (2001)

Tasco-Forage is an Ascophyllum nodosum seaweed-based product that has increased antioxidant activity in both plants and animals. Endophyte (Neotyphodium coenophialum ([Morgan-Jones and Gams] Glenn, Bacon, and Hanlin)-infected and uninfected tall fescue (Festuca arundinacea Schreb.) pastures in Virginia and Mississippi during 1997 were treated or not with 3.4 kg Tasco/ha in April and July. There were two replications of each treatment at each location. Forty-eight steers (6/replication) grazed pastures at each location (n = 96) from April to October prior to transportation to Texas Tech, Lubbock, for finishing during a 160-d period in the feedlot. Blood (antemortem) and liver (postmortem) samples were collected. After slaughter and chilling, the left strip loins (IMPS #180) were collected from three randomly selected steers from within each pasture replication (n = 48). Strip loins were vacuum-packaged and stored at 2 degrees C. At postmortem d 7, 14, 21, and 28, strip loins were removed from packaging and fabricated into 2.54-cm steaks. Following each fabrication day postmortem, the strip loins were repackaged and stored at 2 degrees C until the following postmortem time. After the prescribed fabrication, steaks were overwrapped with polyvinyl chloride film, subjected to simulated retail display at 2 degrees C for up to 3 d, and subjective and objective color were evaluated daily by a trained panel. Steaks from Mississippi steers that had grazed Tasco-treated fescue retained higher (P < 0.05) CIE a* color scores throughout retail display. Steaks were more uniform and had less discoloration and less browning (P < 0.05) if they were from steers that had grazed Tasco-treated fescue, and the effect was greatest for steers from Mississippi (location x Tasco interaction; P < 0.05). The endophyte in tall fescue may decrease uniformity and increase lean discoloration and two-toning of beef steaks when removed from vacuum packaging on or beyond d 21 postmortem (endophyte x Tasco x postmortem day interaction: P < 0.05). Vitamin E in liver was increased (P < 0.06) and serum vitamin E was decreased (P < 0.09) in steers that had grazed the treated pastures. These experiments indicated that Tasco applied to tall fescue during the grazing season can improve color stability and extend beef shelf-life, particularly in cattle grazing infected tall fescue. The mode of action of Tasco is not clear, but antioxidants and specific vitamins may be involved.
The effect of estrogen, progesterone, thyroxine, and human placental lactogen on DNA synthesis of human breast ductal epithelium maintained in athymic nude mice (1984)

Specimens of human breast tissues from the periphery of excised benign tumors, obtained from 17 pre-menopausal patients, were processed into slices and transplanted subcutaneously to 122 female Balb/c athymic nude mice. Subsequently, the host mice were treated with estrogens, progesterone, thyroxine, and human placental lactogen (HPL) alone or in combination. Growth of the ductal epithelium within the human breast transplants, as a function of the hormone treatment, was assessed by 3H-thymidine autoradiographic analysis, i.e., the number of 3H-thymidine radiolabeled ductal cells per unit area of ductal epithelium (labeling index [LI]). The administration of estrogen or thyroxine alone significantly increased the LI. Progesterone or HPL treatments alone did not substantially influence LI. HPL treatment, but not progesterone or thyroxine treatments significantly enhanced the stimulatory effect of estrogen on LI. The athymic nude mouse as host to human breast tissues in these in vivo/ex vivo studies, has been instrumental in producing information that effectively increases understanding of the hormonal factors influencing DNA synthesis in human breast ductal epithelium.
Discovery of Naphthyl-Fused 5-Membered Lactams as a New Class of M<sub>1</sub> Positive Allosteric Modulators (2014)

Selective activation of the M1 muscarinic receptor via positive allosteric modulation represents an original approach to treat the cognitive decline in patients with Alzheimer’s disease. A series of naphthyl-fused 5-membered lactams were identified as a new class of M1 positive allosteric modulators and were found to possess good potency and in vivo efficacy.
LIMB Demonstration Project Extension and Coolside Demonstration. [Final report] (1992)

This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO{sub 2}) and nitrogen oxides (NO{sub x}) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison`s Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0{sub 2} removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0{sub 2} emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.
The Treatment of Pneumonia (1933)

Physician to the General Hospital, Southend-on-Sea.(From Lecture given at Southentd-on-Sea General Hospital.)PNEUMONIA is a disease which affects all ages and stations of life.While the diagnosis as a rule affords no difficulty, the prognosis and treatment of the individuial case call for the greatest skill and jtudgment.In the primary form of the disease, with which this lecture is in the main concerned, the infection is a self-limited one, and, barring complications, the patient will be " dead or better " in ten days.Besides natural variations in the virulence of the infecting organism and in the general resistance of the host, there are many factors which weigh the scale for or against recovery.In a disease, moreover, with a rate of spontaneous recovery as high as 70 to 8o per cent., whatever treatment be adopted, a clear judgment of the value of a particular mode of treatment is fraught with difficulty.It is easy and tempting to let enthusiasm hold the reins, and to draw pleasing but fallacious conclusions, especially from a single instance or small group of cases.Only when a large and carefully controlled series is studied can reliable information be obtained.
Regulation of growth-plate chondrocytes by insulin-like growth-factor I and basic fibroblast growth factor. (1993)

A study was performed in order to investigate the possible functional roles of insulin-like growth-factor I (IGFI) and basic fibroblast growth factor (bFGF) in the regulation of mitotic and metabolic activity of growth-plate chondrocytes. Chondrocytes from the distal radial growth plates of calves and the costal physeal cartilage of rats were exposed to these factors, individually and in combination, in primary monolayer culture, to assess their effects. The data showed that bFGF had both a greater potency and a greater efficacy as a mitogen for bovine growth-plate chondrocytes than did IGF-I. The maximum incorporation of 3H-thymidine by bFGF was 8.3 times that in serum-free (control) cultures; the maximum stimulation of incorporation by IGF-I was 2.5 times that in the control medium. In contrast, IGF-I stimulated a maximum incorporation of 35S-sulfate into glycosaminoglycans that was 2.6 times that in the IGF-I serum-free control cultures, while bFGF had no effect or was mildly inhibitory. When used together, these two factors acted synergistically. Incorporation of 3H-thymidine was more than two times greater than the sum of the effects of the growth factors when used alone and 20.5 times greater than that of the growth factor-free control cultures. Physeal chondrocytes from six-day-old rats were mitotically more responsive to bFGF than to IGF-I, but they were more responsive to IGF-I when they had been derived from twenty-eight-day-old rats. Interaction between bFGF and factors in the serum enhanced the mitotic activity of the rat chondrocytes, but bFGF did not interact with IGF-I under the same experimental conditions. In the presence of bFGF, there was a reduction in the stimulation by IGF-I of incorporation of 35S-sulfate and a decrease in the percentage of chondrocytes containing alkaline phosphatase. These growth factors also influenced cellular morphology in culture. In the presence of IGF-I or serum, the rat chondrocytes manifested the polygonal morphology typical of chondrocytes in culture, while bFGF promoted a more elongated spindle shape. Removal of bFGF and replacement by IGF-I restored the polygonal morphology, indicating that this transition is reversible.
Minimum Formalin Fixation Time for Consistent Estrogen Receptor Immunohistochemical Staining of Invasive Breast Carcinoma (2003)

To identify the minimum time necessary for consistent immunohistochemical estrogen receptor (ER) results in our laboratory, we evaluated results in timed fixation blocks and cases with disparate and similar needle core biopsy and partial mastectomy specimens. Tissue sections of 24 ER-positive, invasive breast carcinomas were fixed for 3, 6, 8, and 12 hours and 1, 2, and 7 days. ER values were quantified using the Q score (0-7). In timed fixation blocks, the mean Q score per block was 2.46 for blocks fixed for 3 hours, 5.75 for blocks fixed for 6 hours, and 6.70 for blocks fixed for 8 hours (P < .001). The difference between the case maximum and mean block Q scores was a plateau of almost 0 at 6 to 8 hours of formalin fixation. For needle core biopsy specimen fixation times, the means for specimens with ER-disparate and ER-similar results were 1.2 and 6.3 hours, respectively (P = .01). The minimum formalin fixation time for reliable immunohistochemical ER results is 6 to 8 hours in our laboratory, regardless of the type or size of specimen.
Detection of Circulating Mammary Carcinoma Cells in the Peripheral Blood of Breast Cancer Patients Via a Nested Reverse Transcriptase Polymerase Chain Reaction Assay for Mammaglobin mRNA (1999)

In contrast to healthy volunteers, hMAM transcripts were detected in the peripheral blood of BC patients. The percentage of positivity relates to the clinical stages of disease, CEA plasma level, and estrogen receptor status. Aberrant hMAM expression might occur occasionally in malignancies other than BC. The clinical relevance of hMAM RT-PCR-based tumor cell detection in the peripheral blood of BC patients should be further evaluated in prospective studies.
Nanophotonic Devices for Optical Networks-On-Chip (2009)

We describe an optical network-on-chip built from passive wavelength routing circuits and tunable micro transmitters based on microdisk sources. Operation of the different subcomponents will be demonstrated.