gebhart/patrepeval huggingface dataset:
Separation of shoot and floral identity in Arabidopsis (1999)

The overall morphology of an Arabidopsis plant depends on the behaviour of its meristems. Meristems derived from the shoot apex can develop into either shoots or flowers. The distinction between these alternative fates requires separation between the function of floral meristem identity genes and the function of an antagonistic group of genes, which includes TERMINAL FLOWER 1. We show that the activities of these genes are restricted to separate domains of the shoot apex by different mechanisms. Meristem identity genes, such as LEAFY, APETALA 1 and CAULIFLOWER, prevent TERMINAL FLOWER 1 transcription in floral meristems on the apex periphery. TERMINAL FLOWER 1, in turn, can inhibit the activity of meristem identity genes at the centre of the shoot apex in two ways; first by delaying their upregulation, and second, by preventing the meristem from responding to LEAFY or APETALA 1. We suggest that the wild-type pattern of TERMINAL FLOWER 1 and floral meristem identity gene expression depends on the relative timing of their upregulation.
Billing users and pricing for TCP (1995)

This paper presents a system for billing users for their TCP traffic. This is achieved by postponing the establishment of connections while the user is contacted, verifying in a secure way that they are prepared to pay. By presenting the user with cost and price information, the system can be used for cost recovery and to encourage efficient use of network resources. The system requires no changes to existing protocols or applications and can be used to recover costs between cooperating sites. Statistics collected from a four-day trace of traffic between the University of California, Berkeley, and the rest of the Internet demonstrate that such a billing system is practical and introduces acceptable latency. An implementation based on the BayBridge prototype router is described. Our study also indicates that pricing schemes may be used to control network congestion either by rescheduling time-insensitive traffic to a less expensive time of the day, or by smoothing packet transfers to reduce traffic peaks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reversal of DNA alkylation damage by two human dioxygenases (2002)

The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups and releases them as formaldehyde. Here, we identify two human AlkB homologs, ABH2 and ABH3, by sequence and fold similarity, functional assays, and complementation of the E. coli alkB mutant phenotype. The levels of their mRNAs do not appear to correlate with cell proliferation but tissue distributions are different. Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. AlkB, ABH2, and ABH3 can also repair 1-ethyladenine residues in DNA with the release of acetaldehyde.
Abstract 4951: Serum N-Terminal Pro-Brain Natriuretic Peptide Reflects the Grade of Congestive Heart Failure in Children (2008)

Background: The N-terminal pro-brain natriuretic peptide (NTproBNP) has a longer serum half-life than the brain natriuretic peptide (BNP), and it is reported to be advantageous in the accurate detection of congestive heart failure (CHF) in adults. However, it has not been sufficiently examined in children. Therefore, we investigated which of the 2 peptides is more beneficial and identified their cut-off levels at the CHF grades in children. Methods: Plasma BNP and serum NTproBNP levels were determined in 252 healthy children (median age, 3.5 years) and in 142 children with congenital heart disease (median age, 2.6 years). CHF severity was assessed by using the modified Ross score to classify the severity into 4 grades (I–IV). The BNP and NTproBNP levels were analyzed and compared with the CHF grade. Results: Both BNP and NTproBNP levels increased significantly with the CHF grades (Fig. 1 ). The change in the NTproBNP level was more remarkable in each CHF grade than in BNP. Furthermore, at CHF grades of II or higher, the area under the receiver operating characteristic curve was larger with NTproBNP than with BNP (Fig. 2 ). The cut-off levels of BNP and NTproBNP were 47.3 and 333.4 pg/mL, respectively, in CHF grade II and higher; 101.4 and 2415.5 pg/mL, respectively, in CHF grade III and higher; and 320.0 and 3617.0 pg/mL, respectively, in CHF grade IV. Conclusions: Our study clearly demonstrated that blood levels of BNP and NTproBNP reflected the severity of CHF in the children. Of these, NTproBNP showed better specificity and sensitivity for the evaluation of CHF severity in children. Therefore, we concluded that NTproBNP is beneficial as a biomarker for assessing CHF in children. This research has received full or partial funding support from the American Heart Association, AHA National Center. Fig. 1 Fig. 2
Anti-Hypertensive Agents Inhibit In Vivo the Formation of Advanced Glycation End Products and Improve Renal Damage in a Type 2 Diabetic Nephropathy Rat Model (2003)

Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal pentosidine content and proteinuria. The unsuspected AGE-lowering effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN.
vRel is an inactive member of the Rel family of transcriptional activating proteins (1991)

The vRel oncoprotein is member of a family of related proteins that also includes cRel, NF-kappa B, and Dorsal. We investigated the transcriptional regulatory properties of several Rel proteins in cotransfection assays with chicken embryo fibroblasts (CEF). Retroviral vectors expressing hybrid proteins that contain the DNA-binding domain of LexA fused to portions of the viral oncoprotein vRel or chicken, mouse, human, or Drosophila melanogaster (Dorsal) cRel proteins were cotransfected with a reporter plasmid that contains the DNA sequence recognized by LexA, a promoter, and the assayable gene for chloramphenicol acetyltransferase. In transient assays, a LexA-vRel protein did not activate transcription in CEF. Full-length chicken cRel, mouse cRel, and Dorsal fusion proteins all activated transcription weakly; however, deletion of N-terminal Rel sequences from each of these proto-oncogene encoded proteins resulted in strong activation by LexA fusion proteins containing only C-terminal sequences. Inhibition of the C-terminal chicken cRel gene activation domain by N-terminal sequences was seen in CEF and mouse and monkey fibroblasts. These results show that cRel proteins from different species have the same general organization: an N-terminal inhibitory domain and a C-terminal activation domain. Sequence comparison suggests that the inhibitory domain is conserved but the activation domain is species specific. In contrast, vRel lacks a strong C-terminal gene activation function, since a LexA fusion protein containing C-terminal vRel sequences alone only weakly activated transcription. In addition, the wild-type vRel protein (lacking LexA sequences) repressed transcription from reporter plasmids containing NF-kappa B target sequences; nontransforming vRel mutants did not repress transcription from these plasmids. Our results suggest that vRel transforms cells by interfering with transcriptional activation by cellular Rel proteins.
Targeted toxins as anticancer agents (1994)

Transformed cells, such as those found in breast cancer, often overexpress a variety of cell surface receptors and antigens. Antibodies or growth factors that specifically recognize these membrane-bound structures can be linked with protein toxins, resulting in cell-specific cytotoxic reagents. Many of these cytotoxic molecules have been produced and are referred to as oncotoxins, mitotoxins, or immunotoxins, depending on the components of the chimeric molecule. These bifunctional reagents are constructed as either chemical conjugates or fusion proteins between a ligand/antibody and a toxin. This report focuses on the use of cytotoxic proteins targeted to epidermal growth factor receptors, fibroblast growth factor receptors, erbB-2/HER-2, and tumor-associated carbohydrate antigens. Using immunotoxin therapy, total regression of established tumors in animal xenograft models have been demonstrated. These results suggest that immunotoxin molecules offer exciting opportunities for the treatment of human cancer.
Linear least squares localization in sensor networks (2015)

Localization in sensor networks is critical for search and rescue. Linear least squares (LLS) estimation is a sub-optimum but low-complexity localization algorithm based on measurements of location-related parameters. Commonly, there are two types of LLS localization algorithms using range measurements; one is based on introducing a dummy variable (called LLS-I), and the other is based on the subtraction of the reference measured range (called LLS-II). Moreover, their respective weighted LLS (WLLS) algorithms (called WLLS-I and WLLS-II) can be adopted to further improve the localization accuracy. In addition, hybridization of different types of measurements can fix the deficiencies of one type of measurements. In this paper, we compare the localization performances of different LLS and WLLS algorithms in both non-hybrid time-of-arrival (TOA) and hybrid TOA/received signal-strength (RSS) networks. Simulation results show that if the variances of measurements are unavailable, the LLS-II localization algorithm should be adopted in both non-hybrid and hybrid networks using their respective reference selection criterions. If the variances of measurements are available, the two-step WLLS-I algorithm should be utilized to localize the agent in both non-hybrid and hybrid networks.
Cytokinin Activation of Arabidopsis Cell Division Through a D-Type Cyclin (1999)

Cytokinins are plant hormones that regulate plant cell division. The D-type cyclin CycD3 was found to be elevated in a mutant of Arabidopsis with a high level of cytokinin and to be rapidly induced by cytokinin application in both cell cultures and whole plants. Constitutive expression of CycD3 in transgenic plants allowed induction and maintenance of cell division in the absence of exogenous cytokinin. Results suggest that cytokinin activates Arabidopsis cell division through induction of CycD3 at the G1-S cell cycle phase transition.
Bioluminescent Assay as a Potential Method of Rapid Susceptibility Testing (1985)

A method of rapid susceptibility testing by bioluminescent assay was developed. Correlation between the 50% inhibition dose of antimicrobics for bacterial adenosine triphosphate measured by bioluminescent assay and the minimum inhibitory concentration obtained by the broth dilution method was satisfactory. In the bioluminescent assay the incubation time required was only 90 min.
Interaction of the epidermal growth factor receptor and the DNA-dependent protein kinase pathway following gefitinib treatment (2006)

The epidermal growth factor receptor (EGFR) is an important target for cancer therapy. We previously showed that the EGFR inhibitor gefitinib modulated repair of DNA damage following exposure to cisplatin and etoposide involving the DNA-dependent protein kinase (DNA-PK) pathway. In this study, we specifically investigated the effect of EGFR inhibition by gefitinib on functional activity of DNA-PK in cancer cell lines and the interaction between EGFR and DNA-PK. The effects of DNA-PK inhibition by wortmannin and small interfering RNA to the catalytic subunit of DNA-PK (DNA-PK(CS)) on cell proliferation and DNA interstrand cross-link repair were investigated in the human MCF-7 breast cancer cell line and compared with the effects of gefitinib. DNA-PK activity was quantitated and expression measured by immunoblotting following gefitinib treatment. Immunoprecipitation experiments were done with and without gefitinib in MCF-7 cells, the AR42J pancreas cell line with high EGFR, and the human MDA-453 breast cancer cell line expressing low EGFR. Nuclear and cytoplasmic extracts were immunoblotted with antibody to DNA-PK(CS) to determine if gefitinib treatment altered cellular expression. Reduction of DNA-PK activity by wortmannin and expression by small interfering RNA to DNA-PK(CS) sensitized cells to cisplatin and inhibited repair of cisplatin-induced interstrand cross-links. Gefitinib treatment reduced DNA-PK activity in MCF-7 and AR42J but not MDA-453 cells. Immunoprecipitation experiments showed interaction between EGFR and DNA-PK(CS) in a dose-dependent and time-dependent manner following gefitinib treatment in MCF-7 and AR42J but not MDA-453 cells. Gefitinib treatment reduced nuclear expression and increased cytosolic expression of DNA-PK(CS) in MCF-7 and AR42J but not MDA-453 cells. Treatment with gefitinib modulates association of EGFR and DNA-PK(CS). This is correlated with decreased function of DNA-PK(CS). Inhibition of DNA-PK(CS) may be an important factor in sensitization to chemotherapy and radiation following treatment with inhibitors of the EGFR pathway.
Trehalose‐6‐phosphate synthase 1, which catalyses the first step in trehalose synthesis, is essential for Arabidopsis embryo maturation (2002)

Despite the recent discovery that trehalose synthesis is widespread in higher plants very little is known about its physiological significance. Here we report on an Arabidopsis mutant (tps1), disrupted in a gene encoding the first enzyme of trehalose biosynthesis (trehalose-6-phosphate synthase). The tps1 mutant is a recessive embryo lethal. Embryo morphogenesis is normal but development is retarded and stalls early in the phase of cell expansion and storage reserve accumulation. TPS1 is transiently up-regulated at this same developmental stage and is required for the full expression of seed maturation marker genes (2S2 and OLEOSN2). Sucrose levels also increase rapidly in seeds during the onset of cell expansion. In Saccharomyces cerevisiae trehalose-6-phosphate (T-6-P) is required to regulate sugar influx into glycolysis via the inhibition of hexokinase and a deficiency in TPS1 prevents growth on sugars (Thevelein and Hohmann, 1995). The growth of Arabidopsis tps1-1 embryos can be partially rescued in vitro by reducing the sucrose level. However, T-6-P is not an inhibitor of AtHXK1 or AtHXK2. Nor does reducing hexokinase activity rescue tps1-1 embryo growth. Our data establish for the first time that an enzyme of trehalose metabolism is essential in plants and is implicated in the regulation of sugar metabolism/embryo development via a different mechanism to that reported in S. cerevisiae.
Molecular Analysis of FRIGIDA , a Major Determinant of Natural Variation in Arabidopsis Flowering Time (2000)

Vernalization, the acceleration of flowering by a long period of cold temperature, ensures that many plants overwinter vegetatively and flower in spring. In Arabidopsis, allelic variation at the FRIGIDA (FRI) locus is a major determinant of natural variation in flowering time. Dominant alleles of FRI confer late flowering, which is reversed to earliness by vernalization. We cloned FRI and analyzed the molecular basis of the allelic variation. Most of the early-flowering ecotypes analyzed carry FRI alleles containing one of two different deletions that disrupt the open reading frame. Loss-of-function mutations at FRI have thus provided the basis for the evolution of many early-flowering ecotypes.
Deubiquitinase FAM/USP9X Interacts with the E3 Ubiquitin Ligase SMURF1 Protein and Protects It from Ligase Activity-dependent Self-degradation (2012)

Ubiquitination is an essential post-translational modification that mediates diverse cellular functions. SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1) belongs to the Nedd4 family of HECT ubiquitin ligases that directly catalyzes ubiquitin conjugation onto diverse substrates. As a result, SMURF1 regulates a great variety of cellular physiologies including bone morphogenetic protein (BMP) signaling, cell migration, and planar cell polarity. Structurally, SMURF1 consists of a C2 domain, two WW domain repeats, and a catalytic HECT domain essential for its E3 ubiquitin ligase activity. This modular architecture allows for interactions with other proteins, which are either substrates or adaptors of SMURF1. Despite the increasing number of SMURF1 substrates identified, current knowledge regarding regulatory proteins and their modes of action on controlling SMURF1 activity is still limited. In this study, we employed quantitative mass spectrometry to analyze SMURF1-associated cellular complexes, and identified the deubiquitinase FAM/USP9X as a novel interacting protein for SMURF1. Through domain mapping study, we found the second WW domain of SMURF1 and the carboxyl terminus of USP9X critical for this interaction. SMURF1 is autoubiquitinated through its intrinsic HECT E3 ligase activity, and is degraded by the proteasome. USP9X association antagonizes this activity, resulting in deubiquitination and stabilization of SMURF1. In MDA-MB-231 breast cancer cells, SMURF1 expression is elevated and is required for cellular motility. USP9X stabilizes endogenous SMURF1 in MDA-MB-231 cells. Depletion of USP9X led to down-regulation of SMURF1 and significantly impaired cellular migration. Taken together, our data reveal USP9X as an important regulatory protein of SMURF1 and suggest that the association between deubiquitinase and E3 ligase may serve as a common strategy to control the cellular protein dynamics through modulating E3 ligase stability.
Hyperscalar: A Novel Dynamically Reconfigurable Multi-core Architecture (2010)

This paper proposes a reconfigurable multi-core architecture, called hyperscalar that enables many scalar cores to be united dynamically as a larger superscalar processor to accelerate a thread. To accomplish this, we propose the virtual shared register files (VSRF) that allow the instructions of a thread executed in the united cores to logically face a uniform set of register files. We also propose the instruction analyzer (IA) with the capability of detecting and tagging the dependence information to the newly fetched instructions. According to the tags, instructions in the united cores can issue requests to obtain their remote operands via the VSRF. The reconfigurable feature of hyperscalar can cover a spectrum of workloads well, providing high single-thread performance when TLP is low and high throughput when TLP is high. Simulation results show that the a 8-core hyperscalar chip multiprocessor’s 2, 4, and 8-core-united configurations archive 94%, 90%, and 83% of the performance of the monolithic 2, 4, and 8-issue out-of-order superscalar processors with lower area costs and better support for software diversity.
Drug Delivery Systems Based on Trimethyl Lock Lactonization:  Poly(ethylene glycol) Prodrugs of Amino-Containing Compounds (2000)

A novel methodology for the synthesis of poly(ethylene glycol) (PEG) prodrugs of amino-containing compounds has been developed which is based on the trimethyl lock lactonization reaction. These PEG-modified double prodrugs are water soluble, and by selective modification of the specifier or trigger, plasma half-lives can be adjusted at will to result in a wide range of values. Facile syntheses of ester, carbonate, and carbamate functionalities were accomplished and combined with greater or lesser degrees of steric hindrance in the spacer group, or on the aromatic framework, to achieve predictable ranges of drug concentration in plasma. In vivo screening of PEG prodrugs was done using a M109 syngeneic solid mouse tumor model. One of the PEG-daunorubicin prodrugs, with a half-life of 2 h, was evaluated in an in vivo solid tumor panel and found to be more efficacious against ovarian tumors (SKOV3) than equivalent amounts of daunorubicin.
Intake of Lactobacillus plantarum Reduces Certain Gastrointestinal Symptoms During Treatment With Antibiotics (2010)

Our results indicate that intake of L. plantarum could have a preventive effect on milder gastrointestinal symptoms during treatment with antibiotics.
Bradykinin inhibits development of myocardial infarction through B2 receptor signalling by increment of regional blood flow around the ischaemic lesions in rats (2003)

1 To identify the roles of endogenous kinins in prevention of myocardial infarction (MI), we performed the permanent ligation of coronary artery in rats. 2 The size of MI 12, 24, and 48 h after coronary ligation in kininogen-deficient Brown Norway Katholiek (BN-Ka) rats was significantly larger (49.7+/-0.2%, 49.6+/-2%, and 51.1+/-1%, respectively) than that of kinin-replete Brown Norway Kitasato (BN-Ki) rats (42+/-2%, 38.5+/-4%, and 41.5+/-1%). 3 Hoe140, a bradykinin (BK) B(2) receptor antagonist injected (1.0 mg kg(-1), i.v.) half an hour before, and every 8 h after, coronary ligation, significantly increased the size of MI in Sprague-Dawley rats. Aprotinin, a kallikrein inhibitor, which was infused intravenously (10,000 Units kg(-1) h(-1)) with an osmotic mini-pump, significantly increased the size of an MI 24 h after ligation. 4 When evaluated using microspheres, the regional myocardial blood flow around the necrotic lesion in BN-Ka rats 6 h after ligation was reduced more than that in BN-Ki rats with MI by 41-46%. The same was true in Hoe140-treated BN-Ki rats. 5 FR190997, a nonpeptide B(2) agonist, which was infused (10 microg kg(-1) h(-1)) into the vena cava of BN-Ka rats for 24 h with an osmotic mini-pump, caused significant reduction in the size of MI (38+/-3%), in comparison with the size in vehicle solution-treated rats (51+/-3%). The size of MI in FR190997-treated BN-Ka rats was the same as in BN-Ki rats. 6 These results suggested that endogenous kinin has the capacity to reduce the size of MI via B(2) receptor signalling because of the increase in regional myocardial blood flow around the ischaemic lesion.