gebhart/patrepeval huggingface dataset:
PRINCIPAL COMPONENTS ANALYSIS TO SUMMARIZE MICROARRAY EXPERIMENTS: APPLICATION TO SPORULATION TIME SERIES (1999)

A series of microarray experiments produces observations of differential expression for thousands of genes across multiple conditions. It is often not clear whether a set of experiments are measuring fundamentally different gene expression states or are measuring similar states created through different mechanisms. It is useful, therefore, to define a core set of independent features for the expression states that allow them to be compared directly. Principal components analysis (PCA) is a statistical technique for determining the key variables in a multidimensional data set that explain the differences in the observations, and can be used to simplify the analysis and visualization of multidimensional data sets. We show that application of PCA to expression data (where the experimental conditions are the variables, and the gene expression measurements are the observations) allows us to summarize the ways in which gene responses vary under different conditions. Examination of the components also provides insight into the underlying factors that are measured in the experiments. We applied PCA to the publicly released yeast sporulation data set (Chu et al. 1998). In that work, 7 different measurements of gene expression were made over time. PCA on the time-points suggests that much of the observed variability in the experiment can be summarized in just 2 components--i.e. 2 variables capture most of the information. These components appear to represent (1) overall induction level and (2) change in induction level over time. We also examined the clusters proposed in the original paper, and show how they are manifested in principal component space. Our results are available on the internet at http:¿www.smi.stanford.edu/project/helix/PCArray .
DBD Plasma Jet in Atmospheric Pressure Argon (2008)

Nonthermal plasma jet was generated by dielectric barrier discharge (DBD) with a 34-kHz sinusoidal power supply in argon. The power consumption ranged from several to tens of watts. The flow rate of argon, which was detected by an anemometer, greatly affected the discharge images. The gas flow temperature of the DBD plasma was measured with a thermocouple, and it was shown that, when the flow rate of argon was relatively high, its temperature was similar to room temperature and the plasma jet indicated the glow discharge characteristics. The low-temperature plasma jet is suitable for medical sterilization and surface modification of materials with irregular shapes.
Chromogranin A expression in neoplastic cells affects tumor growth and morphogenesis in mouse models. (2002)

Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, has been recognized as a useful tissue and serum marker of neuroendocrine tumors. To investigate the effect of CgA secretion on neoplastic morphogenesis and progression, we have transfected mouse RMA lymphoma and TS/A adenocarcinoma cells with the cDNA encoding human CgA and selected several CgA-positive (secreting) and CgA-negative (nonsecreting) clones. In both models, the growth rate of CgA-positive clones implanted s.c. in nude mice was slower than that of CgA-negative clones. Histological analysis of each RMA tumor showed that CgA-expression was associated with multinodular growth patterns, whereas CgA-negative tumors appeared more compact and similar to wild-type RMA tumors. Moreover, CgA production was associated with increased tumor necrosis. The number of nodules in each RMA tumor correlated with the serum levels of CgA (n = 40, r = 0.537, P = 0.0004). The reduced growth rate of CgA-positive RMA and TS/A tumors was not related to reduced in vitro proliferation or to changes in cell adhesion and shape, suggesting that the mechanism is indirect and host-mediated. These results suggest that abnormal secretion of CgA by neuroendocrine neoplastic cells could affect neoplastic growth and morphogenesis.
Conformational Selection of Inhibitors and Substrates by Proteolytic Enzymes:  Implications for Drug Design and Polypeptide Processing (2000)

Inhibitors of proteolytic enzymes (proteases) are emerging as prospective treatments for diseases such as AIDS and viral infections, cancers, inflammatory disorders, and Alzheimer's disease. Generic approaches to the design of protease inhibitors are limited by the unpredictability of interactions between, and structural changes to, inhibitor and protease during binding. A computer analysis of superimposed crystal structures for 266 small molecule inhibitors bound to 48 proteases (16 aspartic, 17 serine, 8 cysteine, and 7 metallo) provides the first conclusive proof that inhibitors, including substrate analogues, commonly bind in an extended beta-strand conformation at the active sites of all these proteases. Representative superimposed structures are shown for (a) multiple inhibitors bound to a protease of each class, (b) single inhibitors each bound to multiple proteases, and (c) conformationally constrained inhibitors bound to proteases. Thus inhibitor/substrate conformation, rather than sequence/composition alone, influences protease recognition, and this has profound implications for inhibitor design. This conclusion is supported by NMR, CD, and binding studies for HIV-1 protease inhibitors/substrates which, when preorganized in an extended conformation, have significantly higher protease affinity. Recognition is dependent upon conformational equilibria since helical and turn peptide conformations are not processed by proteases. Conformational selection explains the resistance of folded/structured regions of proteins to proteolytic degradation, the susceptibility of denatured proteins to processing, and the higher affinity of conformationally constrained 'extended' inhibitors/substrates for proteases. Other approaches to extended inhibitor conformations should similarly lead to high-affinity binding to a protease.
Speech transmission in packet-switched store-and-forward networks (1975)

The past few years have seen a widespread and growing application of packet-switched store-and-forward networks for data communication between geographically separated computer installations. Such networks can provide connections between facilities with the many desirable properties of dedicated communication lines but at reduced costs which result from the time-sharing of the actual lines among many customers. Barring the failure of local terminal equipment, such a network provides connections among its customers which implicitly exist regardless of the load being placed on the network. However, the network characteristics seen by an individual customer will vary with overall network traffic, since the network will tend to deliver messages less frequently and with increased delay (possibly beyond the point of usefulness) as load increases. This property of packet-switched networks---guaranteed connections with variable throughput and delay---is just the reverse of that exhibited by circuit-switched networks such as the telephone system. When circuit-switched systems are heavily loaded, delay may be experienced in making a connection, but once it is established, its throughput and delay will not vary with other system activity.
Human Leptin Deficiency Caused by a Missense Mutation: Multiple Endocrine Defects, Decreased Sympathetic Tone, and Immune System Dysfunction Indicate New Targets for Leptin Action, Greater Central than Peripheral Resistance to the Effects of Leptin, and Spontaneous Correction of Leptin-Mediated Defects (1999)

We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozgous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperleptinemia [corrected]. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperleptinemia [corrected] may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span, humans who survive the negative effects of leptin deficiency during childhood can, in contrast to ob/ob mice, over decades compensate some of the effects of leptin deficiency on immunity and endocrine function through mechanisms that remain to be elucidated.
Cytocompatibility study of a natural biomaterial crosslinker—Genipin with therapeutic model cells (2011)

Genipin has been widely used as a natural crosslinker to substitute chemical crosslinkers such as glutaraldehyde to crosslink various biomaterials like gelatin, collagen, and chitosan. However, there are contradicting views on the cytotoxicity and safety of genipin in tissue engineering. Therefore in this study, we aimed to evaluate the toxicity of genipin on skeletal tissues cells-osteoblasts and chondrocytes as they are also representatives of typical anchorage-dependent cells (ADCs) and nontypical ADCs. Results suggest that genipin toxicity is dose dependent and acute but not time dependent on both osteoblasts and chondrocytes. In particular, chondrocytes exhibit substantial alterations in the gene expression when exposed to Maximum nontoxic concentration (MaxNC) of genipin but there were no significant changes in the genes tested in osteoblasts. Since osteoblasts are typical ADCs, cellular focal adhesion assessment was carried out with F-actin being more contracted and unorganized when exposed to minimum toxic concentration (MinTC) of genipin. The mechanisms involved in cell deaths in both cell types are believed to be similar and hence using osteoblast as the model, cells were stained positive for Annexin-V and Reactive oxygen species (ROS) level were elevated at MinTC of genipin. Collectively, genipin induced cell apoptosis via ROS production, and apparently, gene expressions could also be altered at MaxNC. For this reason, we recommend the dose of genipin to be controlled within 0.5 mM.
Transcriptional Termination Enhances Protein Expression in Human Cells (2009)

Transcriptional termination of mammalian RNA polymerase II (Pol II) requires a poly(A) (pA) signal and, often, a downstream terminator sequence. Termination is triggered following recognition of the pA signal by Pol II and subsequent pre-mRNA cleavage, which occurs either at the pA site or in transcripts from terminator elements. Although this process has been extensively studied, it is generally considered inconsequential to the level of gene expression. However, our results demonstrate that termination acts as a driving force for optimal gene expression. We show that this effect is general but most dramatic where weak or noncanonical pA signals are present. We establish that termination of Pol II increases the efficiency of pre-mRNA processing that is completed posttranscriptionally. As such, transcripts escape from nuclear surveillance.
Fluorescent Sensors for Zn2+Based on a Fluorescein Platform:  Synthesis, Properties and Intracellular Distribution (2001)

Two new fluorescent sensors for Zn(2+) that utilize fluorescein as a reporting group, Zinpyr-1 and Zinpyr-2, have been synthesized and characterized. Zinpyr-1 is prepared in one step via a Mannich reaction, and Zinpyr-2 is obtained in a multistep synthesis that utilizes 4',5'-fluorescein dicarboxaldehyde as a key intermediate. Both Zinpyr sensors have excitation and emission wavelengths in the visible range ( approximately 500 nm), dissociation constants (K(d1)) for Zn(2+) of <1 nM, quantum yields approaching unity (Phi = approximately 0.9), and cell permeability, making them well-suited for intracellular applications. A 3- to 5-fold fluorescent enhancement is observed under simulated physiological conditions corresponding to the binding of the Zn(2+) cation to the sensor, which inhibits a photoinduced electron transfer (PET) quenching pathway. The X-ray crystal structure of a 2:1 Zn(2+):Zinpyr-1 complex has also been solved, and is the first structurally characterized example of a complex of fluorescein substituted with metal binding ligands.
Synthesis of Semitelechelic Maleimide Poly(PEGA) for Protein Conjugation By RAFT Polymerization (2009)

Maleimide end functionalized polymers for site-selective conjugation to free cysteines of proteins were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. A furan-protected maleimide chain transfer agent (CTA) was employed in the RAFT polymerization of poly(ethylene glycol) methyl ether acrylate (PEGA). Gel permeation chromatography (GPC) with laser light scattering detection indicated that 20,000 and 39,000 Da polyPEGA had been made with polydispersity indices of 1.25 and 1.36, respectively. The maleimide group on the polymer chain end was exposed by heating the poly(PEGA)s for 4 h. The deprotection efficiency was estimated to be 80 and 60% for poly(PEGA)(20 kDa) and poly(PEGA)(39 kDa), respectively. Maleimide-poly(PEGA)s were conjugated to V131C T4 lysozyme (T4L), and the resultant polymer-protein conjugates were characterized by size exclusion chromatography and gel electrophoresis.
Haptic interaction with 2D images (2011)

Visual and haptic rendering pipelines exist concurrently and compete for computing resources while the refresh rate of haptic rendering is two orders of magnitude higher than that of visual rendering (1000 Hz vs. 30-50Hz). However, in many cases, 3D visual rendering can be replaced by merely displaying 2D images, thus releasing the resources to image-driven haptic rendering algorithms. These algorithms provide for haptic texture rendering in vicinity of a touch point, but usually require additional information augmented with the image to provide for haptic perception of geometry of the shapes displayed in images. We propose a framework for making tangible images which allows haptic perception of three features: scene geometry, texture and physical properties. Haptic geometry rendering technique uses depth information, that could be acquired by a multitude of ways for providing haptic interaction with images and videos in real-time. The presented method neither performs 3D reconstruction nor requires for using polygonal models. It is based on direct force calculation and allows for smooth haptic interaction even at object boundaries. We also propose dynamic mapping of haptic workspace in real-time to enable sensation of fine surface details. Alternately, one of the existing shading-based haptic texture rendering methods can be combined with the proposed haptic geometry rendering algorithm to provide believable interaction. Haptic perception of physical properties is achieved by automatic segmentation of an image into haptic regions and interactive assignment of physical properties to them.
Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera (2004)

Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera (P<0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression (P=0.0273 for MMP-2 and P=0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression (P=0.0075 for MMP-2 and P=0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade (P=0.0511 for MMP-2 and P=0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.
Expression of Insulin-Like Growth Factor Binding Protein-2 by MCF-7 Breast Cancer Cells Is Regulated through the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway (2007)

IGF binding protein-2 (IGFBP-2) has been implicated in the development and spread of a number of tumor types, and its abrogation in experimental models of cancer is associated with decreased tumor growth. This suggests that targeted inhibition of IGFBP-2 expression in some cancers may have therapeutic benefit. In this study, we investigated signaling pathways involved in extracellular IGFBP-2 expression in an IGF- and estrogen-responsive breast cancer cell line, MCF-7. IGFBP-2 was present at approximately 150 ng per 10(6) cells in serum-free MCF-7-conditioned medium and constituted the predominant IGFBP. Inhibition of the phosphatidylinositol 3-kinase signaling pathway using LY294002, or the downstream signaling intermediate mammalian target of rapamycin using rapamycin, markedly reduced IGFBP-2 in conditioned medium to approximately 25% of untreated levels (P < 0.001); there was no effect of inhibition of p38 MAPK, and an inhibitor of p44/42 MAPK activation, PD98059, caused only a slight reduction in extracellular IGFBP-2. IGFBP-2 levels were increased 25-30% by estradiol, whereas IGF-I (100 ng/ml) increased IGFBP-2 levels 2-fold (P < 0.001) by a type 1 IGF receptor (IGFR1)-dependent mechanism. Estradiol enhanced the effect of IGF-I on IGFBP-2 levels, and this was associated with increased phosphorylation of IGFR1. Basal, IGF-, or estradiol-stimulated IGFBP-2 was abrogated by LY294002 and rapamycin and an inhibitor of IGFR1 tyrosine kinase activity, AG1024. Modulation of intracellular hypoxia-inducible factor-1alpha had no effect on IGFBP-2 expression. These findings indicate that IGFBP-2 is regulated predominantly through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway, the target of a number of anticancer agents currently in clinical trial and use.
Aergia: Exploiting Packet Latency Slack in On-Chip Networks (2011)

Traditional Network-on-Chips (NoCs) employ simple arbitration strategies, such as round-robin or oldest-first, to decide which packets should be prioritized in the network. This is suboptimal since different packets can have very different effects on system performance due to, e.g., different level of memory-level parallelism (MLP) of applications. Certain packets may be performance-critical because they cause the processor to stall, whereas others may be delayed for a number of cycles with no effect on application-level performance as their latencies are hidden by other outstanding packets ’ latencies. In this paper, we define slack as a key measure that characterizes the relative importance of a packet. Specifically, the slack of a packet is the number of cycles the packet can be delayed in the network with no effect on execution time. This paper proposes new router prioritization policies that exploit the available slack of interfering packets in order to accelerate performance-critical packets and thus improve overall system performance. When two packets interfere with each other in a router, the packet with the lower slack value is prioritized. We describe mechanisms to estimate slack, prevent starvation, and combine slack-based prioritization with other recently proposed application-aware prioritization mechanisms. We evaluate slack-based prioritization policies on a 64-core CMP with an 8x8 mesh NoC using a suite of 35 diverse applications. For a representative set of case studies, our proposed policy increases average system throughput by 21.0 % over the commonlyused round-robin policy. Averaged over 56 randomly-generated multiprogrammed workload mixes, the proposed policy improves system throughput by 10.3%, while also reducing application-level unfairness by 30.8%.
PAPR reduction in OFDM transmission using Hadamard transform (2002)

An OFDM signal with large peak-to-average power ratio (PAPR) can cause power degradation (inband distortion) and spectral spreading (out-of-band radiation) by being clipped passing through a power amplifier. The PAPR characteristics are analyzed in two different aspects. From the foundation of the analysis, we propose Hadamard transform, which is ascribed to the relationship between the autocorrelation function and PAPR. Extensive computer simulations show that Hadamard transform is an effective technique to reduce PAPR.
HAEMATOPOIETIC STEM CELLS (CFUc) IN HUMAN CORD BLOOD (1978)

Colony forming units (CFUc) giving rise to myelocytic colonies in methylcellulose cultures were found among non-adherent mononuclear cells of human cord blood with a frequency of one in 1678. The number decreased makredly during the first 8 to 10 days of life. They were rarely detected in adult blood by this technique.
Blue light generation by frequency doubling of AlGaAs broad area amplifier emission (1992)

The diffraction limited emission of a traveling wave single pass 600-μm wide SQW GaAlAs amplifier injected by a Ti:Sapphire laser was frequency doubled in KNbO3 to generate 400 mW peak power 5 μs long pulses of 431 nm light. A maximum single pass frequency conversion efficiency of 6.3% was observed.