gebhart/patrepeval huggingface dataset:
Evi-1 Transforming and Repressor Activities Are Mediated by CtBP Co-repressor Proteins (2001)

Ectopic production of the EVI1 transcriptional repressor zinc finger protein is seen in 4--6% of human acute myeloid leukemias. Overexpression also transforms Rat1 fibroblasts by an unknown mechanism, which is likely to be related to its role in leukemia and which depends upon its repressor activity. We show here that mutant murine Evi-1 proteins, lacking either the N-terminal zinc finger DNA binding domain or both DNA binding zinc finger clusters, function as dominant negative mutants by reverting the transformed phenotype of Evi-1 transformed Rat1 fibroblasts. The dominant negative activity of the non-DNA binding mutants suggests sequestration of transformation-specific cofactors and that recruitment of these cellular factors might mediate Evi-1 transforming activity. C-terminal binding protein (CtBP) co-repressor family proteins bind PLDLS-like motifs. We show that the murine Evi-1 repressor domain has two such sites, PFDLT (site a, amino acids 553--559) and PLDLS (site b, amino acids 584--590), which independently can bind CtBP family co-repressor proteins, with site b binding with higher affinity than site a. Functional analysis of specific CtBP binding mutants show site b is absolutely required to mediate both transformation of Rat1 fibroblasts and transcriptional repressor activity. This is the first demonstration that the biological activity of a mammalian cellular transcriptional repressor protein is mediated by CtBPs. Furthermore, it suggests that CtBP proteins are involved in the development of some acute leukemias and that blocking their ability to specifically interact with EVI1 might provide a target for the development of pharmacological therapeutic agents.
Herbicide Tank Mixtures for Broad-Spectrum Weed Control in Florida Citrus (2013)

Weed control in Florida citrus is primarily based on herbicides. Saflufenacil, a POST-applied herbicide is recently registered for broadleaf weed control in citrus. Saflufenacil has very limited grass activity; therefore, it should be tank mixed with graminicides or broad-spectrum herbicides to increase the spectrum of weed control. Greenhouse and field experiments were conducted at two locations (Polk County and Orange County, FL) to evaluate the efficacy and potential antagonism or synergy of saflufenacil and sethoxydim applied alone or tank mixed, and various two- and three-way mixes with glyphosate or pendimethalin. The results suggested that tank mixing saflufenacil and sethoxydim had neither synergistic nor antagonistic effect on broadleaf and grass weed control, respectively. Tank mixing pendimethalin with saflufenacil and sethoxydim improved broadleaf and grass weed control and reduced weed density and biomass, compared with saflufenacil or sethoxydim applied alone or tank mixed at 45 and 60 d after treatment (DAT). Glyphosate tank mixed with saflufenacil and sethoxydim provided > 90% control of broadleaf and grass weeds at 15 DAT, reduced density ≤ 8 plants m −2 , and reduced biomass < 95 g m −2 at 60 DAT. Glyphosate applied alone was less effective than it was when tank mixed with saflufenacil and sethoxydim or pendimethalin for broadleaf and grass weed control, indicating an additive effect of tank mixture on glyphosate efficacy. It is concluded that saflufenacil can be tank mixed with sethoxydim for control of broadleaf and grass weeds without antagonism on the efficacy of either herbicide; however, tank mixing saflufenacil and sethoxydim with glyphosate or pendimethalin provided long-term, broad-spectrum weed control in Florida citrus.
Lewis Acid-Catalyzed Benzannulation via Unprecedented [4+2] Cycloaddition of <i>o</i>-Alkynyl(oxo)benzenes and Enynals with Alkynes (2003)

The reaction of o-alkynyl(oxo)benzenes 1 with alkynes 2 in the presence of a catalytic amount of AuCl(3) in (CH(2)Cl)(2) at 80 degrees C gave the [4+2] benzannulation products, naphthyl ketone derivatives 3 and 4, in high yields. When the reaction was carried out using AuBr(3) instead of AuCl(3), the reaction speed was enhanced and the chemical yield was increased. On the other hand, when the reaction was carried out in the presence of a catalytic amount of Cu(OTf)(2) and 1 equiv of a Brønsted acid, such as CF(2)HCO(2)H, in (CH(2)Cl)(2) at 100 degrees C, the decarbonylated naphthalene products 5 were obtained in high yields. Similarly, the Cu(OTf)(2)-H(2)O-promoted reaction of the enynals 7 with an alkyne 2 afforded the corresponding [4+2] benzannulation products, decarbonylated benzene derivatives 8, in good yields. Both AuX(3)- and Cu(OTf)(2)-catalyzed benzannulations proceed most probably through the formation of the benzo[c]pyrylium ate complex 10, the Diels-Alder addition of alkynes 2 to the ate complex, and the resulting bicyclic pyrylium ion intermediate 12. The mechanistic difference between the AuX(3) and Cu(OTf)(2)-HA system is discussed.
Mapping Transposon Insertions in Bacterial Genomes by Arbitrarily Primed PCR (2017)

Transposons can be used to easily generate and label the location of mutations throughout bacterial and other genomes. Transposon insertion mutants may be screened for a phenotype as individual isolates, or by selection applied to a pool of thousands of mutants. Identifying the location of a transposon insertion is critical for connecting phenotype to the genetic lesion. In this unit, we present an easy and detailed approach for mapping transposon insertion sites using arbitrarily-primed PCR (AP-PCR). Two rounds of PCR are used to (1) amplify DNA spanning the transposon insertion junction, and (2) increase the specific yield of transposon insertion junction fragments for sequence analysis. The resulting sequence is mapped to a bacterial genome to identify the site of transposon insertion. In this protocol, AP-PCR as it is routinely used to map sites of transposon insertion within Staphylococcus aureus, is used to illustrate the principle. Guidelines are provided for adapting this protocol for mapping insertions in other bacterial genomes. Mapping transposon insertions using this method is typically achieved in 2 to 3 days if starting from a culture of the transposon insertion mutant. © 2017 by John Wiley & Sons, Inc.
A Forward Genetic Strategy Reveals Destabilizing Mutations in the Ebolavirus Glycoprotein That Alter Its Protease Dependence during Cell Entry (2009)

Ebolavirus (EBOV) entry into cells requires proteolytic disassembly of the viral glycoprotein, GP. This proteolytic processing, unusually extensive for an enveloped virus entry protein, is mediated by cysteine cathepsins, a family of endosomal/lysosomal proteases. Previous work has shown that cleavage of GP by cathepsin B (CatB) is specifically required to generate a critical entry intermediate. The functions of this intermediate are not well understood. We used a forward genetic strategy to investigate this CatB-dependent step. Specifically, we generated a replication-competent recombinant vesicular stomatitis virus bearing EBOV GP as its sole entry glycoprotein and used it to select viral mutants resistant to a CatB inhibitor. We obtained mutations at six amino acid positions in GP that independently confer complete resistance. All of the mutations reside at or near the GP1-GP2 intersubunit interface in the membrane-proximal base of the prefusion GP trimer. This region forms a part of the "clamp" that holds the fusion subunit GP2 in its metastable prefusion conformation. Biochemical studies suggest that most of the mutations confer CatB independence not by altering specific cleavage sites in GP but rather by inducing conformational rearrangements in the prefusion GP trimer that dramatically enhance its susceptibility to proteolysis. The remaining mutants did not show the preceding behavior, indicating the existence of multiple mechanisms for acquiring CatB independence during entry. Altogether, our findings suggest that CatB cleavage is required to facilitate the triggering of viral membrane fusion by destabilizing the prefusion conformation of EBOV GP.
Metallic Nanohole Arrays on Fluoropolymer Substrates as Small Label-Free Real-Time Bioprobes (2008)

We describe a nanoplasmonic probing platform that exploits small-dimension (<or=20 microm (2)) ordered arrays of subwavelength holes for multiplexed, high spatial resolution, and real-time analysis on biorecognition events. Nanohole arrays are perforated on a super smooth gold surface (roughness rms < 2.7 A) attached on a fluoropolymer (FEP) substrate fabricated by a replica technique. The smooth surface of gold provides a superb environment for fabricating nanometer features and uniform immobilization of biomolecules. The refractive index matching between FEP and biological solutions contributes to approximately 20% improvement on the sensing performance. Spectral studies on a series of small-dimension nanohole arrays from 1 microm (2) to 20 microm (2) indicate that the plasmonic sensing sensitivity improves as the gold-solution contact area increases. Our results also demonstrate that nanohole arrays with a dimension as small as 1 microm (2) can be used to effectively detect biomolecular binding events and analyze the binding kinetics. The future scientific opportunities opened by this nanohole platform include highly multiplexed analysis of ligand interactions with membrane proteins on high quality supported lipid bilayers.
Cell Mechanical and Physiological Behavior in the Regime of Rapid Mechanical Compressions that Lead to Cell Volume Change (2019)

Cells respond to mechanical forces by deforming in accordance with viscoelastic solid behavior. Studies of microscale cell deformation observed by high speed video microscopy have elucidated a new cell behavior in which sufficiently rapid mechanical compression of cells can lead to transient cell volume loss and then recovery. This work has discovered that the resulting volume exchange between the cell interior and the surrounding fluid can be utilized for efficient, convective delivery of large macromolecules (2000 kDa) to the cell interior. However, many fundamental questions remain about this cell behavior, including the range of deformation time scales that result in cell volume loss and the physiological effects experienced by the cell. In this study, a relationship is established between cell viscoelastic properties and the inertial forces imposed on the cell that serves as a predictor of cell volume loss across human cell types. It is determined that cells maintain nuclear envelope integrity and demonstrate low protein loss after the volume exchange process. These results define a highly controlled cell volume exchange mechanism for intracellular delivery of large macromolecules that maintains cell viability and function for invaluable downstream research and clinical applications.
Understanding extended duration of therapy (DOT) among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan-based regimens. (2022)

579 Background: Few analyses have identified characteristics associated with extended DOT (eDOT) among a large group of patients (pts) treated with liposomal irinotecan. This study examines the characteristics associated with eDOT among pts with mPDAC treated with liposomal irinotecan in a real-world setting. Methods: This retrospective observational study utilized the Flatiron Health EHR database from over 280 cancer clinics in the US. Data were analyzed for adult pts with mPDAC treated with liposomal irinotecan-based regimens between January 2016 and October 2020. eDOT was defined as a DOT > 2 standard deviations (SD) above the mean. Demographic and clinical characteristics evaluated included age, sex, stage at diagnosis, ECOG performance score (PS), and the number of prior lines of therapy at the time of treatment initiation. Dose delays and dose reductions during treatment were assessed. Additionally, changes in lymphocyte counts during treatment were described. Chi-squared test and Fisher’s exact test were used to test for significance for categorical variables and the t-test was used for continuous variables. Results: 675 pts with mPDAC treated with a liposomal irinotecan-based regimen were included. The overall mean DOT was 14.6 weeks (SD: 22.1). There were 30 pts (4.4%) that met the definition for eDOT. Patient sex and median age at treatment initiation were similar between those with eDOT and non-eDOT: male, 46.7% vs. 51.9% (p = 0.582); age, median 70 years vs 69 years (p = 0.923), respectively. A higher proportion of pts with eDOT had ECOG PS of 0-1 compared to those with non-eDOT, 73.3% vs 57.7%, respectively (p = 0.397). At treatment initiation 80.0% of pts who had eDOT had a serum albumin level of ≥ 35g/L versus 55.2% of pts with non-eDOT (p = 0.013). On average, those with eDOT experienced a 55.1% reduction in lymphocyte count (baseline to nadir) during treatment compared to a 34.7% reduction among pts with non-eDOT (p < 0.0001). Pts who experienced eDOT were more likely to be treated in earlier lines of therapy than those with non-eDOT: 33.3% vs 14.1% received 0 prior lines and 46.7% vs 47.3% received 1 prior line, respectively (p = 0.008). 53.3% of pts with eDOT experienced a dose reduction (of at least 7mg/m 2 ) compared to 24.7% pts with non-eDOT (p = 0.0005). All pts with eDOT experienced a dose delay of > 16 days during treatment versus 45.3% of pts with non-eDOT (p < 0.0001). Conclusions: This real-world study identified pts treated earlier in their disease course with a liposomal irinotecan-based regimen and normal baseline serum albumin were more likely experience extended DOT. Treatment modifications and delays appear to have enabled longer treatment duration with liposomal irinotecan-based regimens. Further prospective studies should be considered to characterize factors that may predict extended DOT.
Processing of byproducts to improve nisin production by Lactococcus lactis (2011)

In the last years, disposal from dairy industries have received a special attention due its polluting power in the environment. For this reason, studies have obtained a positive support to develop different alternatives to recycle milk whey components. One of them is its utilization as culture media, aiming to produce biomolecules with noble applications. Nisin is an extracellular peptide, produced by Lactococcus lactis, this peptide has been applied as a natural additive once it presents broad antibacterial activity. Applications of this bacteriocin include dental care products, pharmaceutical products such as stomach ulcers and colon infection treatment and potential birth control. In batch cultures, L. lactis was performed in two different groups of assays. The first group milk whey was prepared in distilled water in four different concentrations: 100 g/l (S100); 50 g/l (S50); 30 g/l (S30); 10 g/l (S10). In the second group of assays, two supplements were added in milk whey with concentration 100 g/l (S100): (1) 5 g/l yeast extract (A1); (2) 5 g/l yeast extract and 10 ml (v/v) tomato extract. Nisin activity was assayed through agar diffusion utilizing Lactobacillus sakei. The results show that the utilization of powder milk whey with concentration of 100 g/l can be used as a culture medium with supplementation. This media is favorable to develop L. lactis cells and nisin production, reaching an activity of about 4 logAU. Biological processing of milk byproduct can be considered as one of the profitable utilization alternatives, generating high-value bioproducts and stimulates researches for its use.
Automated labelling and severity prediction of software bug reports (2019)

Our main aim is to develop an intelligent classifier that is capable of predicting the severity and label (type) of a newly submitted bug report through a bug tracking system. For this purpose, we build two datasets that are based on 350 bug reports from the open-source community (Eclipse, Mozilla, and Gnome). These datasets are characterised with various textual features. Based on this information, we train variety of discriminative models that are used for automated labelling and severity prediction of a newly submitted bug report. A boosting algorithm is also implemented for an enhanced performance. The classification performance is measured using accuracy and a set of other measures. For automated labelling, the accuracy reaches around 91% with the AdaBoost algorithm and cross validation test. On the other hand, for severity prediction, the classification accuracy reaches around 67% with the AdaBoost algorithm and cross validation test. Overall, the results are encouraging.
Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity (2017)

Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca<sup>2+</sup>-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5<sup>-/-</sup> mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.
Capillary zone electrophoresis of proteins with fused‐silica capillaries having polymers and surfactants adsorbed onto surfactant moieties previously covalently bound to the capillary column surface (1998)

Fused-silica capillary columns having cationic surfactant moieties (CSM) covalently attached to the capillary inner walls were introduced for the separation of proteins by capillary zone electrophoresis (CZE). The CSM capillary coating proved to be useful in the separation of basic and acidic proteins when modified hydroxypropylcellulose (HPC), namely epoxybutane-HPC (EBHPC), was adsorbed to the primary CSM coating, yielding a hybrid coating (i.e., coating consisting of a covalently bound ligand and an adsorbed ligand). The EBHPC layer rendered the capillary surface highly hydrophilic, thus permitting the separation of basic proteins with relatively high plate counts. Also, the CSM coating was useful for the separation of acidic proteins when the capillary wall had, in addition, a negatively charged polymer adsorbed to the surface, e.g., hyaluronic acid. In general, neutral and charged polymeric compounds could be readily adsorbed by the CSM coating, thus altering the zeta potential of the capillary and diminishing solute adsorption to the capillary surface. In other words, the sign of the zeta potential of the capillary surface could be tailored to be of the same sign as the charge of the analytes. Under these conditions, little or no solute-wall interaction could be observed due to electrostatic repulsion. Although the capillary surface was charged, the presence of adsorbed polymer suppressed or, in most cases, even eliminated the electroosmotic flow (EOF).
Addressing key challenges in 1T-DRAM: Retention time, scaling and variability &#x2014; Using a novel design with GaP source-drain (2013)

We propose a vertical gate all around 1-transistor DRAM cell with silicon channel and gallium phosphide source drain (GaP-SD) as a viable alternative to the present 1T-1C DRAM technology. The valence band offset at GaP and Si interface helps to store more holes in the transistor body and thus improves the retention time by 2 order over conventional Si-SD 1T DRAM. By examining body thickness variability, we conclude that GaP-SD memory cell can withstand the performance degradation due to device variability to meet the ITRS retention time requirements. Finally the GaP-SD memory cell is optimized for scaled dimensions upto 20nm body thickness to establish its superiority at lower technology nodes.
Use of ultrasound to early identify, diagnose and localize metastases in melanoma patients (2007)

Specialized medical centers perform high-resolution ultrasound of lymph nodes in melanoma patients to detect metastases early. Ultrasound represents a highly effective method for the discrimination of lymph node and soft-tissue metastases from other space-occupying lesions. Frequent follow-up examinations with ultrasound provide early detection of tumor recurrences and seem to lead to a prolonged overall survival. The ultrasound findings are validated by fine-needle aspiration cytology. Depicted and verified metastases should be removed as soon as possible. The authors recommend the performance of ultrasound before every sentinel lymph node dissection to avoid unnecessary operations.
Spatiotemporal expression of three gap junction gene products involved in fetomaternai communication during rat pregnancy (1991)

The expression of three different members of the gap junction multigene family, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26), was analysed in the rat implantation chamber (a structural unit containing fetal, extraembryonic and maternal components within the pregnant uterus) during mid- and late stages of gestation as well as in the delivering, post-partum and non-pregnant uterus. A differential, spatiotemporal and cell-type-specific regulation of gap junctional coexpression was observed for beta 1 and beta 2 in all epithelia examined (visceral, luminal and glandular), as well as for alpha 1 and beta 2 in decidual cells and keratinocytes of the fetal epidermis. alpha 1 antigen was detected in the mesometrial stroma, mesometrial myometrium, connective tissue, mesothelia of the amnion and visceral yolk sac and in the allantoic mesodermal layer throughout gestation. In addition, expression of alpha 1 in the placental basal zone and trophoblast giant cells coincided with the differentiation of these cells. beta 2 expression was observed prominently in the chorionic villi of the placental labyrinth. The presence of beta 1 and beta 2 in the visceral epithelium (visceral yolk sac = the primary route for embryonic nourishment prior to the formation of the chorioallantoic placenta) and beta 2 in the chorionic villi (placental barrier = the major fetomaternal exchange route) suggests that gap junctions have an important role in fetomaternal communication.
Synthesis and Configuration Analysis of Diastereomers of 5'-O-(2'-Deoxycytidyl)-3'-O-Thymidyl Phosphorothioate (1996)

A procedure is described for the synthesis of the title compound via phosphotriester intermediates. The preparation of and diastereomeric dinucleotide of d[Cp(S)T] was performed by the condensation of the protected deoxycytidine, the protected thymidine, 2,5-dichlorophenylphosphorodichloridothioate and 1-hydroxybenzotriazole in THF. Their designation of configuration at phosphorus as and follows from anaylsis of NMR spectroscopy and reverse-phase HPLC and the stereospecificity in the hydrolysis catalyzed by Nuclease S1 and snake venom phosphodiesterase. Diastereomerically pure and d[Cp(S)T] were utilized to synthesize oligonucleotides containing the XhoI recognition sequence with a phosphorothioate group at the cleavage site.