gebhart/patrepeval huggingface dataset:
Phase I trial of recombinant interleukin-2 and cyclophosphamide: augmentation of cellular immunity and T-cell mitogenic response with long-term administration of rIL-2. (1988)

Long-term subcutaneous (s.c.) administration of recombinant Interleukin-2 (rIL-2) was evaluated in 18 patients with advanced malignancy who received escalating doses of rIL-2 (1.0-9.8 X 10(6) U/m2) s.c. five times per week for a median of 38 days (range 5-228 days). Prior to the s.c. phase of the study, 24 patients received low doses (50 or 350 mg/m2) of cyclophosphamide (CPM) i.v. on day 1 followed by 10 doses (days 5-9 and 12-16) of rIL-2 (1 X 10(6) U/m2) given by 6 h i.v. infusion. There were no major antitumor effects. Toxicity was not clearly dose-related, with pain and induration at s.c. injection sites, fatigue, malaise, and palpitations most often observed. Pretreatment baseline ranges (PBR), which are 95% prediction intervals that reflect both intra- and interpatient variability, were calculated for nine hematologic and immunologic variables derived from 21 of the 24 patients. While pretreatment with CPM had no significant effect on these variables during the i.v. phase of the study as compared to a prior study using an identical rIL-2 i.v. infusion schedule, prolonged administration of s.c. rIL-2 was associated with (a) enhancement of natural killer (NK) cytotoxicity against K562 in 13 of 21 patients (p less than 0.00001), (b) increases in cytotoxicity against K562 (15 patients) and against Daudi (9 patients) in the presence of 10 U/ml of rIL-2 (p = 0.007), (c) increases in the proliferative response in vitro to OKT3 and rIL-2 in 12 patients (p less than 0.00001), (d) lymphocytosis with increase in percentage of Tac (13 patients, p less than 0.00001), T8 (11 patients, p = 0.0005), and T9 (8 patients, p = 0.021) expression, and (e) eosinophilia. While initial rises in some of these variables occurred during the i.v. phase of the study, maximum increases for all variables except T9 positivity occurred during prolonged s.c. therapy. Nine of 10 patients studied while on therapy greater than 50 days had anti-rIL-2 antibodies in an enzyme-linked immunosorbent assay; in only one case was the antibody neutralizing. This study demonstrates that significant enhancement of cytotoxicity against both NK-sensitive and -resistant targets and improvements in T-cell mitogenic response occur with long-term administration of rIL-2. Further evaluation of long-term administration of tolerable doses of rIL-2 is warranted.
Comparison of the pulmonary distribution and efficacy of antibodies given to mice by intratracheal instillation or aerosol inhalation. (1996)

The respiratory tract is the portal of entry and target organ of many aerosolized toxins and infective agents, and there is increasing need for testing the efficacy of potential therapeutic agents delivered directly into the lungs. Intratracheal instillation and aerosol inhalation are the two methods most often used to introduce drugs, toxins, or infective agents into the respiratory tract of experimental animals. In this study we compared the distribution and efficacy of antibodies given to mice by aerosol inhalation or intratracheal instillation. We determined the pulmonary distribution of these antibodies by immunohistochemistry and observed the distribution and severity of pulmonary lesions that developed after exposure to aerosolized ricin. Although antibodies administered by either method prevented death, we found that instilled antibodies tended to concentrate around terminal airways and often failed to reach peripheral lung fields. Sometimes entire lung lobes were missed by the instillation route. Acute and chronic pulmonary lesions developed in the unprotected areas of instillation-treated lungs. In contrast, aerosolized antibodies covered all pulmonary surfaces and effectively prevented ricin-induced lesions throughout the lungs. Our findings suggest that the aerosol inhalation method may be preferable for evaluating the efficacy of therapeutic agents in the respiratory tract because of the failure of instilled agents to reach and protect peripheral alveoli.
Nonionic Analogs of RNA with Dimethylene Sulfone Bridges (1996)

Analogs of RNA have been synthesized where each of the phosphodiester linking groups is replaced by dimethylene sulfone units (sulfone-linked nucleic acid analogs of RNA, or “rSNAs”). These are the first fully nonionic analogs of RNA to be prepared as oligomers. Sequences leading to the octamer 5‘-r(ASO2USO2GSO2GSO2USO2CSO2ASO2U)-3‘ have been prepared from 3‘,5‘-bishomo-β-ribonucleoside derivatives as building blocks prepared from diacetone d-glucose, and their chemistry has been explored. Coupling was performed in solution via SN2 reactions between a thiol from one fragment and a bromide from the other, oxidation of the resulting thioether to the sulfone, and deprotection of a terminal primary hydroxyl group and regioselective conversion of itin the presence of secondary hydroxyl groupsto an active group (thiol or bromide) to yield another fragment for coupling. Base-labile protecting groups were used for the nucleobases, and one-step full deprotection was achieved using 1 M NaOH. The target octamer and each isolated intermediate were characterized by NMR, UV spectroscopy, and mass spectrometry. While chemical reactions involving longer rSNAs were in several cases retarded relative to analogous reactions with monomers, some rates were enhanced. In water, the rSNA octamer displayed a thermal transition in the UV spectrum above 65 °C with a large hyperchromicity. The behaviors of rSNAs suggest roles for the polyanionic backbone in DNA and RNA beyond its role in conferring aqueous solubility. The repeating anionic charges in natural oligonucleotides evidently also control the potent molecular recognition properties of these richly functionalized molecules, direct strand−strand interactions to the part of the biopolymer distant from the backbone (the Watson−Crick edge of the nucleobases), cause the polymer to favor an extended conformation, and ensure that the physical properties of the oligonucleotide are largely independent of its sequence. This suggests structural features that must be built into nonionic oligonucleotide analogs generally.
Learning visual similarity for product design with convolutional neural networks (2015)

Popular sites like Houzz, Pinterest, and LikeThatDecor, have communities of users helping each other answer questions about products in images. In this paper we learn an embedding for visual search in interior design. Our embedding contains two different domains of product images: products cropped from internet scenes, and products in their iconic form. With such a multi-domain embedding, we demonstrate several applications of visual search including identifying products in scenes and finding stylistically similar products. To obtain the embedding, we train a convolutional neural network on pairs of images. We explore several training architectures including re-purposing object classifiers, using siamese networks, and using multitask learning. We evaluate our search quantitatively and qualitatively and demonstrate high quality results for search across multiple visual domains, enabling new applications in interior design.
Adaptive Selection of Motion Models for Panoramic Video Coding (2007)

A panoramic video is an image-based rendering (IBR) technique which provides users with a large field of view (e.g. 360 degree) on surrounding dynamic scenes. It includes not only the translational motions but also the non-translational motions, such as zooming, rotation and uneven stretching etc. This paper presents a motion compensated prediction scheme based on adaptive selection of motion models to predict the complex changes between successive frames efficiently in panoramic video coding. By performing the initial motion estimation phrase and the refined motion estimation phrase in the proposed scheme, simulated results show that the coding performance of the proposed scheme is much higher than the traditional motion compensated prediction scheme in panoramic video coding.
Prognostic value of epidermal growth factor receptor expression in cervical carcinoma. (1993)

Immunohistochemical demonstration of epidermal growth factor receptor expression may be useful in identifying those patients with a poor prognosis, particularly those with adenosquamous carcinomas which have not metastasised to the regional lymph nodes.
SPECIAL ARTICLE COMPARING METHODS OF MEASUREMENT (1997)

1. The purpose of comparing two methods of measurement of a continuous biological variable is to uncover systematic differences not to point to similarities. 2. There are two potential sources of systematic disagreement between methods of measurement: fixed and proportional bias. 3. Fixed bias means that one method gives values that are higher (or lower) than those from the other by a constant amount. Proportional bias means that one method gives values that are higher (or lower) than those from the other by an amount that is proportional to the level of the measured variable. 4. It must be assumed that measurements made by either method are attended by random error: in making measurements and from biological variation. 5. Investigators often use the Pearson product-moment correlation coefficient (r) to compare methods of measurement. This cannot detect systematic biases, only random error. 6. Investigators sometimes use least squares (Model I) regression analysis to calibrate one method of measurement against another. In this technique, the sum of the squares of the vertical deviations of y values from the line is minimized. This approach is invalid, because both y and x values are attended by random error. 7. Model II regression analysis caters for cases in which random error is attached to both dependent and independent variables. Comparing methods of measurement is just such a case. 8. Least products regression is the reviewer's preferred technique for analysing the Model II case. In this, the sum of the products of the vertical and horizontal deviations of the x,y values from the line is minimized. 9. Least products regression analysis is suitable for calibrating one method against another. It is also a sensitive technique for detecting and distinguishing fixed and proportional bias between methods. 10. An alternative approach is to examine the differences between methods in order to detect bias. This has been recommended to clinical scientists and has been adopted by many. 11. It is the reviewer's opinion that the least products regression technique is to be preferred to that of examining differences, because the former distinguishes between fixed and proportional bias, whereas the latter does not.
Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands (2010)

The microsomal antiestrogen binding site (AEBS) is a high-affinity target for the antitumor drug tamoxifen and its cognate ligands that mediate breast cancer cell differentiation and apoptosis. The AEBS, a hetero-oligomeric complex composed of 3β-hydroxysterol-Δ 8 -Δ 7 -isomerase (D8D7I) and 3β-hydroxysterol-Δ 7 -reductase (DHCR7), binds different structural classes of ligands, including ring B oxysterols. These oxysterols are inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), a microsomal epoxide hydrolase that has yet to be molecularly identified. We hypothesized that the AEBS and ChEH might be related entities. We show that the substrates of ChEH, cholestan-5α,6α-epoxy-3β-ol (α-CE) and cholestan-5β,6β-epoxy-3β-ol (β-CE), and its product, cholestane-3β,5α,6β-triol (CT), are competitive ligands of tamoxifen binding to the AEBS. Conversely, we show that each AEBS ligand is an inhibitor of ChEH activity, and that there is a positive correlation between these ligands’ affinity for the AEBS and their potency to inhibit ChEH ( r 2 = 0.95; n = 39; P &lt; 0.0001). The single expression of D8D7I or DHCR7 in COS-7 cells slightly increased ChEH activity (1.8- and 2.6-fold), whereas their coexpression fully reconstituted ChEH, suggesting that the formation of a dimer is required for ChEH activity. Similarly, the single knockdown of D8D7I or DHCR7 using siRNA partially inhibited ChEH in MCF-7 cells, whereas the knockdown of both D8D7I and DHCR7 abolished ChEH activity by 92%. Taken together, our findings strongly suggest that the AEBS carries out ChEH activity and establish that ChEH is a new target for drugs of clinical interest, polyunsaturated fatty acids and ring B oxysterols.
Power-aware scheduling of virtual machines in DVFS-enabled clusters (2009)

With the advent of Cloud computing, large-scale virtualized compute and data centers are becoming common in the computing industry. These distributed systems leverage commodity server hardware in mass quantity, similar in theory to many of the fastest Supercomputers in existence today. However these systems can consume a cities worth of power just to run idle, and require equally massive cooling systems to keep the servers within normal operating temperatures. This produces CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> emissions and significantly contributes to the growing environmental issue of Global Warming. Green computing, a new trend for high-end computing, attempts to alleviate this problem by delivering both high performance and reduced power consumption, effectively maximizing total system efficiency. This paper focuses on scheduling virtual machines in a compute cluster to reduce power consumption via the technique of Dynamic Voltage Frequency Scaling (DVFS). Specifically, we present the design and implementation of an efficient scheduling algorithm to allocate virtual machines in a DVFS-enabled cluster by dynamically scaling the supplied voltages. The algorithm is studied via simulation and implementation in a multi-core cluster. Test results and performance discussion justify the design and implementation of the scheduling algorithm.
Humanin inhibits cell death of serum-deprived PC12h cells (2002)

Humanin (HN) and S14G HN (HNG) are recently discovered polypeptides that rescue cells from death induced by multiple different types of familial Alzheimer's disease genes and by amyloid-beta. However, the cytoprotective activity of these peptides against other cell death-inducing stimuli remains unclear. In this study, we demonstrated, using three different methods (MTS assay, caspase-3 assay, and detection of DNA fragmentation), that both HN and HNG protect PC12 cells from death elicited by serum deprivation. This implies the potential of the peptides to rescue cells from a broad spectrum, if not all, of cell death-inducing factors. Further investigations on HN may lead the possible application of this peptide as therapeutic agent for the treatment of other neurodegenerative diseases.
Pulse-shaping OFDM/BFDM systems for time-varying channels: ISI/ICI analysis, optimal pulse design, and efficient implementation (2003)

This paper considers practically relevant aspects and advantages of pulse-shaping orthogonal/biorthogonal frequency division multiplexing (OFDM/BFDM) systems. We analyze the intersymbol/intercarrier interference (ISI/ICI) in such systems when they operate over time-varying channels. Two methods for an ISI/ICI-minimizing pulse design are proposed, and efficient FFT-based modulator and demodulator implementations are presented. Simulations show that for fast time-varying channels, optimized BFDM systems can outperform conventional OFDM systems with respect to ISI/ICI.
C-Jun N-terminal Kinase and Apoptosis in Breast Cancer. (1998)

Abstract : Understanding the biochemical mechanisms of apoptosis is important for revealing cancer biology and for improving cancer therapies. The c-Jun N-terminal kinase (JNK) pathway participates in cellular responses to both environmental stresses and mitogenic signals. JNK is involved in cellular signaling during apoptosis induced by various agents including gamma-radiation, UV-radiation, anti-carcinogenic isothiocyanates, and retinoid analog N-(4-hydroxyphenyl) retinamide (4-HPR) in various cancer cells. Interfering with the JNK pathway suppressed the induction of apoptosis. JNK activation by apoptotic stimuli can be caspase-dependent or independent. Different apoptotic stimuli induce JNK activation through distinct mechanisms. We found that oxidative stress is a major cause of JNK activation in apoptosis induced by several agents. The involvement of JNK in both mitogenic and apoptotic signaling implies that a subtle regulatory mechanism must exist for the signaling decision. Our studies reveal that the duration of JNK induction may determine cell fate. Curcumin is a potent inhibitor for JNK activation by various stimuli. This inhibitory effect may explain the anti-carcinogenic effect of curcumin. In conclusion, our study reveals the importance of the JNK pathway in apoptotic signaling. These results provide important information for the studies of oncogenesis and the mechanisms of radiation and drug resistance in cancer cells.
Putting Stem Cells to Work (1999)

Human embryonic stem (ES) cells hold great promise as a source of transplantable tissue that could, for example, replace tissues damaged as a result of aging, injury, or disease. In a Perspective on page
 1468
 of this issue, Solter and Gearhart discuss the therapeutic promise of human ES cells and the many ethical and legal complications associated with their use.
Design Strategies and Performance of Custom DNA Sequencing Primers (1999)

This study surveyed strategies of sequencing primer selection and evaluated primer performance in automated DNA sequencing. We asked participants to relate their preferred primer design strategies to identify primer characteristics that are considered most important in sequencing primer design. The participants preferred primers of 18-24 nucleotides (nt), 39%-58% G + C, a melting temperature (Tm) of 53 degrees-65 degrees C with a 1-2 nt 3' GC clamp, hairpin stems of less than 2-3 bp, homopolymeric runs of less than 4-5 nt, primer dimers of less than 3-4 bp and secondary priming sites of less than 3-4 bp. We provided a 300-bp test sequence and asked participants to submit sequences of 1-3 optimal sequencing primers. Submitted primers ranged from 17-24 nt and largely conformed to the preferred parameters. Submitted primers were distributed across the test sequence, although some sites were disfavored. Surprisingly, approximately 45% of the primers were selected "manually", more than by any software package. Each of 69 submitted and 95 control primers, distributed at 3-bp intervals across the test sequence, were synthesized, purified and tested using a Model 377 PRISM DNA Sequencer with dichlororhodamine dye terminator reagents (dRhodamine dye terminators). Approximately half of the control primers were also tested using rhodamine dye terminator reagents ("old" rhodamine dye terminators). The results indicated that primer physico-chemical characteristics thought to have a strong impact on sequencing performance had surprisingly little effect. Thus, primers with high or low percent G + C or Tm, strong secondary priming scores or long 3' homopolymeric stretches yielded excellent sequences with the dRhodamine dye terminator reagents, although these characteristics had a stronger effect when the old rhodamine reagents were used. The old rhodamine reagents gave sequences with a similar average read length, but the number of errors and ambiguities or "N's" was consistently higher. Moreover, the effects of the primer physico-chemical characteristics were also more evident with the old rhodamine dyes. We conclude that under optimal sequencing conditions with highly pure template and primer, many of the commonly applied primer design parameters are dispensable, particularly when using one of the new generation of sequencing reagents such as the dichlororhodamine dye terminators.
Highly Efficient and Specific Genome Editing in Silkworm Using Custom TALENs (2012)

Establishment of efficient genome editing tools is essential for fundamental research, genetic engineering, and gene therapy. Successful construction and application of transcription activator-like effector nucleases (TALENs) in several organisms herald an exciting new era for genome editing. We describe the production of two active TALENs and their successful application in the targeted mutagenesis of silkworm, Bombyx mori, whose genetic manipulation methods are parallel to those of Drosophila and other insects. We will also show that the simultaneous expression of two pairs of TALENs generates heritable large chromosomal deletion. Our results demonstrate that (i) TALENs can be used in silkworm and (ii) heritable large chromosomal deletions can be induced by two pairs of TALENs in whole organisms. The generation and the high frequency of TALENs-induced targeted mutagenesis in silkworm will promote the genetic modification of silkworm and other insect species.
ChemInform Abstract: Predicting Three‐Dimensional Structures of Oligopeptides (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A Fusion of GMCSF and IL-21 Initiates Hypersignaling Through the IL-21Rα Chain With Immune Activating and Tumoricidal Effects In Vivo (2010)

We hypothesized that fusing granulocyte-macrophage colony-stimulation factor (GMCSF) and interleukin (IL)-21 as a single bifunctional cytokine (hereafter GIFT-21) would lead to synergistic anticancer immune effects because of their respective roles in mediating inflammation. Mechanistic analysis of GIFT-21 found that it leads to IL-21Ralpha-dependent STAT3 hyperactivation while also contemporaneously behaving as a dominant-negative inhibitor of GMCSF-driven STAT5 activation. GIFT-21's aberrant interactions with its cognate receptors on macrophages resulted in production of 30-fold greater amounts of IL-6, TNF-alpha, and MCP-1 when compared to controls. Furthermore, GIFT-21 treatment of primary B and T lymphocytes leads to STAT1-dependent apoptosis of IL-21Ralpha(+) lymphocytes. B16 melanoma cells gene-enhanced to produce GIFT-21 were immune rejected by syngeneic C57Bl/6 mice comparable to the effect of IL-21 alone. However, a significant GIFT-21-driven survival advantage was seen when NOD-SCID mice were implanted with GIFT-21-secreting B16 cells, consistent with a meaningful role of macrophages in tumor rejection. Because GIFT-21 leads to apoptosis of IL-21Ralpha(+) lymphocytes, we tested its cytolytic effect on IL-21Ralpha(+) EL-4 lymphoma tumors implanted in C57Bl/6 mice and could demonstrate a significant increase in survival. These data indicate that GIFT-21 is a novel IL-21Ralpha agonist that co-opts IL-21Ralpha-dependent signaling in a manner permissive for targeted cancer immunotherapy.
Vine of Life (1996)

In this poem, short-life's gardener vies with death's pruning. Word chains embedded in the poem have been highlighted by capitalization. The underlying struc­ ture of the poem is diagrammed above: each 57-letter vine segment (with spaces and punctuation removed) folds back upon its predecessor in boustrophedonic form. Each alphabetized set of 19 lower-case letters sandwiched in the fold has been anagrammed into those letters of the poem located above and below it.