gebhart/patrepeval huggingface dataset:
Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting (2016)

The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance.
Recessed-gate structure approach toward normally off high-Voltage AlGaN/GaN HEMT for power electronics applications (2006)

A recessed-gate structure has been studied with a view to realizing normally off operation of high-voltage AlGaN/GaN high-electron mobility transistors (HEMTs) for power electronics applications. The recessed-gate structure is very attractive for realizing normally off high-voltage AlGaN/GaN HEMTs because the gate threshold voltage can be controlled by the etching depth of the recess without significant increase in on-resistance characteristics. With this structure the threshold voltage can be increased with the reduction of two-dimensional electron gas (2DEG) density only under the gate electrode without reduction of 2DEG density in the other channel regions such as the channel between drain and gate. The threshold-voltage increase was experimentally demonstrated. The threshold voltage of fabricated recessed-gate device increased to -0.14 V while the threshold voltage without the recessed-gate structure was about -4 V. The specific on-resistance of the device was maintained as low as 4 m/spl Omega//spl middot/cm/sup 2/ and the breakdown voltage was 435 V. The on-resistance and the breakdown voltage tradeoff characteristics were the same as those of normally on devices. From the viewpoint of device design, the on-resistance for the normally off device was modeled using the relationship between the AlGaN layer thickness under the gate electrode and the 2DEG density. It is found that the MIS gate structure and the recess etching without the offset region between recess edge and gate electrode will further improve the on-resistance. The simulation results show the possibility of the on-resistance below 1 m/spl Omega//spl middot/cm/sup 2/ for normally off AlGaN/GaN HEMTs operating at several hundred volts with threshold voltage up to +1 V.
Injectable, Highly Flexible, and Thermosensitive Hydrogels Capable of Delivering Superoxide Dismutase (2009)

Injectable hydrogels are attractive for cell and drug delivery. In this work, we synthesized a family of injectable, biodegradable, fast gelling and thermosensitive hydrogels based on N-isopropylacrylamide (NIPAAm), acrylic acid (AAc), dimethyl-gamma-butyrolactone acrylate (DBA), and 2-hydroxyethyl methacrylate-poly(trimethylene carbontate) (HEMAPTMC) macromer. Type I collagen was composited with the hydrogels to improve their biocompatibility. The hydrogel copolymer solutions were readily injectable at 4 degrees C. The solutions exhibited thermal transition temperatures ranging from 23.6 to 24.5 degrees C and were capable of gelation within 7 s at 37 degrees C to form highly flexible and soft hydrogels with moduli from 39 to 119 KPa and breaking strains >1000%, depending on the copolymer composition and collagen addition. After 2 weeks incubation in PBS, the hydrogels demonstrated weight losses ranging from 10-20%. The completely degraded hydrogels had thermal transition temperatures >40 degrees C and were soluble at body temperature. Superoxide dismutase (SOD) was encapsulated in the hydrogels for the purpose of capturing superoxide within the inflammatory tissue after being delivered in vivo. The hydrogels demonstrated a sustained release profile during a 21-day release period. The release kinetics was dependent on the SOD loading, collagen addition, hydrogel degradation and water content. The released SOD remained bioactive during the entire release period. To test in vitro if the loaded SOD could protect cells encapsulated within the hydrogel from attack by superoxide, human mesenchymal stem cells (MSC) were encapsulated in SOD-loaded hydrogels and cultured in medium containing superoxide generated by activated macrophages. It was found that SOD loading largely suppressed superoxide penetration into the hydrogel and cell membrane. Under normal culture conditions, SOD loading stimulated MSC growth. The SOD-loaded hydrogel exhibited significantly higher cell numbers than the non-SOD loaded hydrogel during a 7-day culture period. These results demonstrated that the developed hydrogels could be used as delivery vehicles for stem cell therapy and drug delivery.
The BTB/POZ domain targets the LAZ3/BCL6 oncoprotein to nuclear dots and mediates homomerisation in vivo. (1995)

The LAZ3/BCL6 gene was identified by its disruption in 3q27 translocations associated with diffuse large cell lymphomas. It is predicted to be a transcription factor as it contains six Krüppel-like Zinc finger motifs and a N-terminal BTB/POZ domain, a protein/protein interaction interface that is widely conserved in Metazoans. Using two antisera raised against non overlapping regions of the predicted ORF, we demonstrate that the LAZ3/BCL6 protein appears as a close ca. 79 kDa doublet in B lymphoid cell lines with either a rearranged or a non rearranged LAZ3/BCL6 locus. By immunofluorescence experiments on transiently transfected COS-1 or NIH3T3 cells, we show that the LAZ3/BCL6 protein displays a punctuated nuclear localisation. This appears to rely on LAZ3/BCL6 proper folding and/or activities as it is impaired in a hormone reversible-fashion through fusion of LAZ3/BCL6 to the ligand-binding domain of the oestrogen receptor. Moreover, deletion of its BTB/POZ domain leads to the disappearance of the nuclear dots although the protein remains nuclear. In addition, by using the yeast two-hybrid system, we show that the LAZ3/BCL6 BTB/POZ domain homomerises in vivo. Thus, the LAZ3/BCL6 BTB/POZ domain has the capability to self-interact and target the protein to discrete nuclear substructures.
Mismatch and G-Stack Modulated Probe Signals on SNP Microarrays (2009)

The applied method of "triple-averaging" represents a model-free approach to estimate the mean intensity contributions of different sequence motifs which can be applied in calibration algorithms to correct signal values for sequence effects. Rules for appropriate sequence corrections are suggested.
Small RNAs in streptococci (2012)

The group of streptococci includes species responsible for severe diseases in humans. To adapt to their environment and infect their hosts, streptococci depend on precise regulation of gene expression. The last decade has witnessed increasing findings of small RNAs (sRNAs) having regulatory functions in bacteria. More recently, genome-wide screens revealed that streptococcal genomes also encode multiple sRNAs. Some sRNAs including the class of CRISPR RNAs (crRNAs) play critical roles in streptococcal adaptation and virulence. Analysis of sRNA mechanisms uncovered three sRNAs that target in trans mRNA (FasX), sRNA (tracrRNA) and DNA (crRNA). Overall, the current understanding of sRNA-mediated regulation in streptococci remains very limited. Given the complexity of regulatory networks and the number of recently predicted sRNAs, future research should reveal new functions and mechanisms for the streptococcal sRNAs. Here, we provide a comprehensive summary of the information available on the topic.
Prognostic value of galectin-3, a novel marker of fibrosis (2010)

We agree that markers in heart failure like NT-proBNP and galectin-3 may be influenced by thyroid dysfunction In the diagnostic work-up in patients with heart failure thyroid function tests are routinely measured as advised by the European Society of Cardiology Before entering the DEAL-HF study, patients were extensively screened and tested according to this guideline. Patients with untreated thyroid disease were ineligible for participation in the trial. In addition, also patients with an active malignant disease were excluded During follow-up, 98 patients died. The majority of patients died from a cardiovascular cause, including 42 from worsening heart failure and 36 from sudden cardiac death. Twenty patients died from a non-cardiovascular cause. The median galectin-3 levels did not differ between the three groups (p = 0.54).
Characterization of the Calmodulin-binding and of the Catalytic Domains of Bordetella pertussis Adenylate Cyclase (1989)

The structural organization of the low molecular mass form (43 kDa) of Bordetella pertussis adenylate cyclase was dissected taking advantage of the known sequence of the bacterial cya gene (Glaser, P., Ladant, D., Sezer, O., Pichot, F., Ullmann, A., and Danchin, A. (1988) Mol. Microbiol. 2, 19-30) and its low content of Trp and Met residues. Cleavage of the 43-kDa protein and of its complementary tryptic fragments (T25 and T18 peptides) with N-chlorosuccinimide and cyanogen bromide followed by sodium dodecyl sulfate-polyacrylamide gel analysis of digestion products allowed the following conclusions: (i) the catalytically active 43-kDa form of B. pertussis adenylate cyclase is within the first 400 residues of the protein encoded by the cya gene. T25 occupies the N-terminal domain of the protein (residues 1-235/237). Isolated T25 fragment exhibits a low but measurable enzymatic activity which indicates that it harbors the catalytic site; (ii) T18 which is the main calmodulin-binding domain, occupies the C-terminal segment of protein (residues 236/238-399) and is devoid of catalytic properties; (iii) the two complementary peptides T25 and T18 reassociated only in the presence of calmodulin, leading to significant recovery of the original activity. These results demonstrate that both fragments of the 43-kDa form of adenylate cyclase are essential for a high level of enzymatic activity.
Dual Inhibition of PI3K and mTOR Mitigates Compensatory AKT Activation and Improves Tamoxifen Response in Breast Cancer (2013)

Combinatorial inhibition of the PI3K/AKT/mTOR signaling axis may enhance endocrine-based therapy in breast cancer.
A complete system to determine the speed limit by fusing a GIS and a camera (2011)

Determining the speed limit on road is a complex task based on the Highway Code and the detection of temporary speed limits. In our system, these two aspects are managed by a GIS (Geographical Information System) and a camera respectively. The vision-based system aims at detecting the roadsigns as well as the subsigns and the lane markings to filter those applicable. The two sources of information are finally fused by using the Belief Theory to select the correct speed limit. The performance of a navigation-based system is increased by 19%.
Residue Requirements for Helical Folding in Short α/β-Peptides:  Crystallographic Characterization of the 11-Helix in an Optimized Sequence (2005)

Design of functional foldamers requires knowledge of the conformational propensities of constituent residues. Here, we explore the effects of variations in both alpha-amino acid and beta-amino acid substitution on alpha/beta-peptide helicity. We also report the first X-ray crystal structure of a helical alpha/beta-peptide. We conclude that a certain amount of conformational preorganization in alpha/beta-peptides (via the inclusion of constrained beta-amino acids or alpha,alpha-disubstituted alpha-amino acids) is needed to promote helical folding; acyclic beta-amino acids and beta-branched alpha-amino acids are tolerated to only a limited extent.
Versatile protein tag, SUMO: Its enzymology and biological function (2002)

Small ubiquitin-related modifier (SUMO) is a member of a ubiquitin-like protein family that regulates cellular function of a variety of target proteins. SUMO and ubiquitin are synthesized as precursors that need to be processed prior to conjugation to target proteins, and their mature forms have a similar tertiary structure. The mechanism for SUMO conjugation is also analogous to that of the ubiquitin system, such as the utilization of E1, E2, and E3 cascade enzymes. However, the biological consequence of SUMO modification is quite different from that of the ubiquitin system. Whereas ubiquitination of most proteins is for the degradative pathway, SUMO modification of target proteins is involved in nuclear protein targeting, formation of subnuclear structures, regulation of transcriptional activities or DNA binding abilities of transcription factors, and control of protein stability. This review will summarize the recent progress made in the enzymology of SUMO and its biological significance.
Effects of variation in the structure of spermine on the association with DNA and the induction of DNA conformational changes (1990)

The effects of spermine and spermine analogues on the B-Z transition of poly(dG-me5dC) and on the aggregation and 'melting' temperature of calf thymus DNA were studied by spectroscopic methods. The association constants of these polyamines with double- and single-stranded calf thymus DNA were calculated from their effects on the melting temperature. The effect of these compounds on the release of ethidium bromide (EB) from an EB-DNA complex were measured by a spectrofluorimetric method. This efficiency of the polyamine-induced B-Z transition strongly depended on the length of the central carbon chains of the compounds and on the functional groups attached to the carbon chains. Both the terminal primary amino groups and the length of the central carbon chain affected the aggregation of DNA. The affinity of the analogues for DNA increased as the number of n-butyl groups increased, but decreased with either an increase or a decrease in the length of the central carbon chain. The effect of spermine and spermine analogues on the release of EB from an EB-DNA complex did not always correlate with the affinities of analogues for calf thymus DNA. In particular, tetra-amines with more than one n-butyl group bound better to DNA than did spermine, but released bound EB and induced aggregation of DNA less well than did spermine. We postulate that either a bend and/or other localized conformational changes of DNA are responsible for the spermine-induced aggregation of DNA and the release of EB from the EB-DNA complex.
Differentiation between adenomyoma and leiomyoma with transvaginal ultrasonography (1995)

The clinical utility of transvaginal ultrasonography in the differentiation of adenomyoma from leiomyoma was evaluated in 147 patients who had been scheduled for surgery due to symptomatic uterine masses. In all subjects, ultrasonographic images obtained preoperatively were correlated postoperatively with surgicopathological findings. Pathological findings showed that 110 patients proved to have fibroids, while 30 had adenomyomata. For the diagnosis of adenomyoma, transvaginal ultrasonography attained a sensitivity of 80%, a specificity of 94.3%, a positive predictive value of 85.7% and a negative predictive value of 90.9%, compared with a sensitivity of 94.3%, a specificity of 80%, a positive predictive value of 90.9% and a negative predictive value of 85.7% for leiomyoma diagnosis. Further to assess which characteristic used in ultrasonography was useful in the differential diagnosis, five characteristics were analyzed and compared by chi 2 test. These were position, number, margin and echogenicity of the uterine masses and the presence or absence of hypoechoic spaces (lacunae). Margin, echogenicity, mass number and lacunae were significantly different between both conditions. A stepwise logistic regression procedure revealed that margin, lacunae and echogenicity were good parameters for differentiating adenomyoma from leiomyoma. If we selected the features of distinct margin and absence of hypoechoic lacunae within the masses for analysis, leiomyoma could be correctly predicted in 97% of patients.
Transcriptome-Wide Mapping of 5-methylcytidine RNA Modifications in Bacteria, Archaea, and Yeast Reveals m5C within Archaeal mRNAs (2013)

The presence of 5-methylcytidine (m(5)C) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage of low-throughput methods. To obtain a high resolution, systematic, and comprehensive transcriptome-wide overview of m(5)C across the three domains of life, we used bisulfite treatment on total RNA from both gram positive (B. subtilis) and gram negative (E. coli) bacteria, an archaeon (S. solfataricus) and a eukaryote (S. cerevisiae), followed by massively parallel sequencing. We were able to recover most previously documented m(5)C sites on rRNA in the four organisms, and identified several novel sites in yeast and archaeal rRNAs. Our analyses also allowed quantification of methylated m(5)C positions in 64 tRNAs in yeast and archaea, revealing stoichiometric differences between the methylation patterns of these organisms. Molecules of tRNAs in which m(5)C was absent were also discovered. Intriguingly, we detected m(5)C sites within archaeal mRNAs, and identified a consensus motif of AUCGANGU that directs methylation in S. solfataricus. Our results, which were validated using m(5)C-specific RNA immunoprecipitation, provide the first evidence for mRNA modifications in archaea, suggesting that this mode of post-transcriptional regulation extends beyond the eukaryotic domain.
Platelet-activating Factor Acetylhydrolases (1997)

Platelet-activating factor acetylhydrolases are structurally diverse isoenzymes that catalyze the hydrolysis of the acyl group at the second position of glycerol in unusual, bioactive phospholipids (Fig. 1). Thus, as categorized by enzymatic activity, they are phospholipases A2 (Groups VII and VIII, Ref. 1), which often initiate signal transduction and are regulated by the state of the cell activation. However, the platelet-activating factor (PAF,1 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) acetylhydrolases have the opposite role; they were discovered by investigators who focused on the inactivation of PAF (2).
Inhibition of cell proliferation, migration and invasion by a glioma‐targeted fusion protein combining the p53 C terminus and MDM2‐binding domain (2016)

GHPc+mT is a multifunctional protein combining targeting, inhibition of glioma cell proliferation and induction of apoptosis, providing some potential to be developed into an effective protein drug delivery system for glioma therapy.
Doppler-Derived Ejection Intraventricular Pressure Gradients Provide a Reliable Assessment of Left Ventricular Systolic Chamber Function (2005)

Doppler-derived EIVPDs provide quantitative, reproducible, and relatively load-independent indices of global systolic chamber function that correlate closely with currently available reference methods.
Microfluidic Platform for Controlled Synthesis of Polymeric Nanoparticles (2008)

A central challenge in the development of drug-encapsulated polymeric nanoparticles is the inability to control the mixing processes required for their synthesis resulting in variable nanoparticle physicochemical properties. Nanoparticles may be developed by mixing and nanoprecipitation of polymers and drugs dissolved in organic solvents with nonsolvents. We used rapid and tunable mixing through hydrodynamic flow focusing in microfluidic channels to control nanoprecipitation of poly(lactic- co-glycolic acid)- b-poly(ethylene glycol) diblock copolymers as a model polymeric biomaterial for drug delivery. We demonstrate that by varying (1) flow rates, (2) polymer composition, and (3) polymer concentration we can optimize the size, improve polydispersity, and control drug loading and release of the resulting nanoparticles. This work suggests that microfluidics may find applications for the development and optimization of polymeric nanoparticles in the newly emerging field of nanomedicine.
Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression (2000)

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.
Differential capacitance-voltage profiling of Schottky barrier diodes for measuring implanted depth distributions in silicon (1982)

The National Bureau of Standards' was established by an act of Congress on March 3, 1901. The Bureau's overall goal is to strengthen