gebhart/patrepeval huggingface dataset:
BRCA1 and BRCA2 Mutations in Women from Shanghai China (2004)

Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germ-line mutations and polymorphisms in a cohort of women from Shanghai, China. Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer. The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively. Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent.
Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state (2014)

Summary The conserved Musashi (Msi) family of RNA binding proteins are expressed in stem/progenitor and cancer cells, but mostly absent from differentiated cells, consistent with a role in cell state regulation. We found that Msi genes are rarely mutated but frequently overexpressed in human cancers, and associated with an epithelial-luminal cell state. Using ribosome footprint profiling and RNA-seq analysis of genetic mouse models in neuronal and mammary cell types, we found that Msis regulate translation of genes implicated in epithelial cell biology and epithelial-to-mesenchymal transition (EMT) and promote an epithelial splicing pattern. Overexpression of Msi proteins inhibited translation of genes required for EMT, including Jagged1, and repressed EMT in cell culture and in mammary gland in vivo , while knockdown in epithelial cancer cells led to loss of epithelial identity. Our results show that mammalian Msi proteins contribute to an epithelial gene expression program and promote an epithelial-luminal state in both neural and breast cell types. Highlights Msi proteins bind UAG motifs in vitro and in 3’ UTRs of mRNAs Msi proteins are markers of epithelial state in brain and breast tumors, and cell lines The Notch regulator Jag1 mRNA is bound and translationally repressed by Msi Msi overexpression represses EMT in the mammary gland in vivo
Room Temperature Deformation Properties of High Purity AZ31 Magnesium Alloy (2007)

A high purity ternary alloy corresponding to the composition of AZ31 alloy was prepared using distilled magnesium (> 99.99%) and high purity aluminum and zinc. The tensile and cold rolling properties were then examined and compared with a commercial purity AZ31 alloy. The high purity alloy exhibited excellent tensile ductility and cold rolling workability. It was found that during tensile testing of the high purity alloy, the number of twinned grains increased linearly with strain, indicative of uniform deformation, while with the commercial alloy, active twinning occurred in the early stages of plastic deformation and twinning activity decreased in the latter half of the deformation regime. In association with the high degree of cold reduction and the uniform deformation characteristics of the high purity alloy, the material after annealing exhibited a recrystallized structure consisting of fine grains each about 2 μm in size.
Combination of Synthetic Long Peptides and XCL1 Fusion Proteins Results in Superior Tumor Control (2019)

Cross-presenting Xcr1<sup>+</sup>CD8α DCs are attractive APCs to target for therapeutic cancer vaccines, as they are able to take up and process antigen from dying tumor cells for their MHCI-restricted presentation to CD8 T cells. To this aim, we developed fusion proteins made of the Xcr1 ligand Xcl1 fused to an OVA synthetic long peptide (SLP) and IgG1 Fc fragment. We demonstrated the specific binding and uptake of the Xcl1 fusion proteins by Xcr1<sup>+</sup> DCs. Most importantly, their potent adjuvant effect on the H-2Kb/OVA specific T cell response was associated with a sustained tumor control even against the poorly immunogenic B16-OVA melanoma tumor. The increased tumor protection correlated with higher tumor infiltration of antigen-specific CD8+ T cells, increased IFNγ production and degranulation potential. Altogether, these results demonstrate that therapeutic cancer vaccines may be greatly improved by the combination of SLP antigen and Xcl1 fusion proteins.
Xanthine Oxidase-mediated Decomposition of S-Nitrosothiols (1998)

S-Nitrosothiols (RSNO) occur in vivo and have been proposed as nitric oxide (.NO) storage and transport biomolecules. Still, the biochemical mechanisms by which RSNO release .NO in biological systems are not well defined, and in particular, the interactions between reactive oxygen species and RSNO have not been studied. In this work, we show that xanthine oxidase (XO), in the presence of purine (hypoxanthine, xanthine) or pteridine (lumazine) substrates, induces S-nitrosocysteine (CysNO) and S-nitrosoglutathione (GSNO) decomposition under aerobic conditions. The decomposition of RSNO by XO was inhibitable by copper-zinc superoxide dismutase, in agreement with the participation of superoxide anion (O-2) in the process. However, while superoxide dismutase could totally inhibit aerobic decomposition of GSNO, it was only partially inhibitory for CysNO. Competition experiments indicated that O-2 reacted with GSNO with a rate constant of 1 x 10(4) M-1.s-1 at pH 7.4 and 25 degreesC. The decomposition of RSNO was accompanied by peroxynitrite formation as assessed by the oxidation of dihydrorhodamine and of cytochrome c2+. The proposed mechanism involves the O-2-dependent reduction of RSNO to yield .NO, which in turn reacts fast with a second O-2 molecule to yield peroxynitrite. Under anaerobic conditions, CysNO incubated with xanthine plus XO resulted in CysNO decomposition, .NO detection, and cysteine and uric acid formation. We found that CysNO is an electron acceptor substrate for XO with a Km of 0.7 mM. In agreement with this concept, the enzymatic reduction of CysNO by XO was inhibitable by oxypurinol and diphenyliodonium, inhibitors that interfere with the catalytic cycle at the molybdenum and flavin sites, respectively. In conclusion, XO decomposes RSNO by O-2-dependent and -independent pathways, and in the presence of oxygen it leads to peroxynitrite formation.
Exploring a New Security Framework for Future Healthcare Systems (2021)

The Internet of Things is driving impactful and significant changes in healthcare systems across the globe. The use of mobile and wireless technologies to support healthcare environments has enormous potential to transform healthcare. For example, healthcare data, which is considered to be very sensitive, must be securely accessed, processed and stored. How-ever, digital healthcare IT platforms are increasingly coming under attack by malware such as Ransomware. In addition, there is now a need to integrate eHealth and mHealth mechanisms into national healthcare systems. New technologies, such as blockchain, are being used to address these issues. What is needed is a new framework which can use these technologies to secure healthcare. This paper proposes a new security framework that responds to these security concerns. The framework is then used to design an implementation framework with new mechanisms including Capabilities, Secure Remote Procedure Calls and a Service Management Framework.
Probably Optimal Graph Motifs (2013)

We show an O^*(2^k)-time polynomial space algorithm for the k-sized Graph Motif problem. We also introduce a new optimization variant of the problem, called Closest Graph Motif and solve it within the same time bound. The Closest Graph Motif problem encompasses several previously studied optimization variants, like Maximum Graph Motif, Min-Substitute, and Min-Add. Moreover, we provide a piece of evidence that our result might be essentially tight: the existence of an O^*((2-epsilon)^k)-time algorithm for the Graph Motif problem implies an ((2-epsilon')^n)-time algorithm for Set Cover.
Investigating attitudes toward prenatal diagnosis and fetal therapy for spinal muscular atrophy (2022)

In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored.
Structural and Functional Analysis of Surface Domains Unique to Bacteriophage T4 Thymidylate Synthase (1999)

The bacteriophage T4 genome encodes most of its own enzymes for dNTP synthesis, which form a complex in infected Escherichia coli. The T4 thymidylate synthase (TS) and the T4 deoxycytidylate deaminase (CD) catalyze sequential reactions and are physically linked within this complex [McGaughey, K. M., Wheeler, L. J., Moore, J. T., Maley, G. F. , Maley, F., and Mathews, C. K. (1996) J. Biol. Chem. 271, 23037-23042]. From the crystal structure of T4TS [Finer-Moore, J. S., Maley, G. F., Maley, F., Montfort, W. R., and Stroud, R. M. (1994) Biochemistry 33, 15459-15468], it appears that three regions corresponding to insertions relative to E. coli TS lie on one side of the enzyme surface. We have investigated the residual activity of T4TS in response to complete deletion or substitution mutagenesis of these insertions. Two deletions generated in the small domain (residues 70-103) reduced the TS activity to 0.2% and 0.7% of the wild-type activity, with the latter able to complement growth of a thyA- E. coli strain in the absence of thymidine. By insertion of exogenous sequences variable in length and in sequence into these deletion mutants, enzyme activity increased to 44% that of the wild type. Restoration of the TS activity depended mostly on the hydrophobicity of the inserted residues. The sites of insertions also displayed distinct permissiveness for accommodating the exogenous insertions. Deletions and substitutions near the C-terminus resulted in complete inactivation of the T4TS. Proteolysis experiments revealed that the modified surface loops of the small domain were still accessible and flexible for protein-protein interactions. We have used ELISA to detect a physical association between T4TS and T4CD and compared the binding affinity of WT T4TS for two purified insertion mutants of T4CD. The results obtained showed that the native sequences of the small domain inserts are not required for T4TS/T4CD complex formation.
Morphology and Viscoelasticity of Actin Networks Formed with the Mutually Interacting Crosslinkers: Palladin and Alpha-actinin (2012)

Actin filaments and associated actin binding proteins play an essential role in governing the mechanical properties of eukaryotic cells. Even though cells have multiple actin binding proteins (ABPs) that exist simultaneously to maintain the structural and mechanical integrity of the cellular cytoskeleton, how these proteins work together to determine the properties of actin networks is not clearly understood. The ABP, palladin, is essential for the maintenance of cell morphology and the regulation of cell movement. Palladin coexists with α-actinin in stress fibers and focal adhesions and binds to both actin and α-actinin. To obtain insight into how mutually interacting actin crosslinking proteins modulate the properties of actin networks, we characterized the micro-structure and mechanics of actin networks crosslinked with palladin and α-actinin. We first showed that palladin crosslinks actin filaments into bundled networks which are viscoelastic in nature. Our studies also showed that composite networks of α-actinin/palladin/actin behave very similar to pure palladin or pure [Formula: see text]-actinin networks. However, we found evidence that palladin and α-actinin synergistically modify network viscoelasticity. To our knowledge, this is the first quantitative characterization of the physical properties of actin networks crosslinked with two mutually interacting crosslinkers.
Erratum: Time-Bin and Polarization Superdense Teleportation for Space Applications [Phys. Rev. Applied <b>14</b>, 014044 (2020)] (2020)

TABLE I. Tomography This table details the states that each single-photon detector is projecting onto for each setting of the tomography. Additionally, for the ninesetting tomography, it shows which coincidences are used to calibrate the relative efficiencies of Bob's four detectors for each tomography measurement. For example, C S2B1 corresponds to the coincidences with Bob's detector 1 on measurement setting 2 with one of Alice's detectors. B 1 State B 2 State B 3 State B 4 State 36-sett # 9-sett # B 1 Eff. Cor. B 2 Eff. Cor. B 3 Eff. Cor. B 4 Eff. Cor. |H 1 2 (|t 1 -|t 2 ) |H 1
The culture and transplantation of human limbal stem cells (2010)

The cornea is the clear front of the eye and its surface is composed of an epithelium. This is renewed by stem cells located at the limbus, which encircles the periphery of the cornea. These limbal stem cells become lost or deficient in the blinding disease of limbal stem cell deficiency. In this review article, we discuss the historical perspective in managing limbal stem cell deficiency as well as describing the more contemporary treatment options, and in particular the culture and transplantation of human limbal stem cells. This treatment was first proposed 13 years ago and many case series have been presented to date showing promising outcomes of this technique. However, challenges still remain in treating the debilitating disease of limbal stem cell deficiency. Here we discuss some of the questions, which remain to be answered in this field.
Basicity and coordination properties of a new phenanthroline-based bis-macrocyclic receptor (2006)

The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10-triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2, composed by two L1 moieties connected by an ethylenic bridge, are reported. Their basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis, fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal complexes in aqueous solutions, while L2 can give both mono- and dinuclear complexes. In the mononuclear L2 complexes the metal is sandwiched between the two cyclic moieties. The metal complexes with L1 and L2 do not display fluorescence emission, due to the presence of amine groups not involved in metal coordination. These amine groups can quench the excited fluorophore through an electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to cleave the phosphate ester bond in the presence has been investigated by using bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2 shows a remarkable hydrolytic activity, due to the simultaneous presence within this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act cooperatively in substrate binding, probably through a bridging interaction of the phosphate ester; the interaction is further reinforced by pi-stacking pairing and hydrophobic interactions between the phenanthroline unit(s) and the p-nitrophenyl groups of BNPP.
Oral inhalation of AP301 peptide activates pulmonary oedema clearance: Initial results from a phase IIa clinical trial in mechanically ventilated ICU patients (2014)

Acute pulmonary permeability oedema is a major component of Acute Lung Injury (ALI). AP301, a synthetic peptide structurally based on the lectin-like domain of human TNFα has been designed to activate pulmonary oedema clearance by activating the sodium ion channel (ENaC) in pulmonary epithelial cells. A randomized, double-blind, placebo-controlled, parallel-group proof of concept study was performed on 40 mechanically ventilated adult male and female patients with ALI. Every 12 hours for 7 days, 20 patients inhaled aerosolized AP301 (verum group) and 20 patients inhaled saline (placebo group). Reduction of pulmonary oedema (primary objective) was determined by measurement of the extra-vascular lung water (EVLW) content by PiCCO ® technique twice daily. PaO 2 /FiO 2 ratio was assessed once daily as part of the enhanced hemodynamic monitoring. Lung function and vital signs were measured regularly for diagnostic and safety assessment. Oral inhalation of AP301 by patients led to an earlier onset and more pronounced activation of pulmonary oedema clearance compared to placebo treated patients. Subgroup analysis revealed that oral inhalation of AP301 was even more effective in pulmonary oedema clearance in patients with a higher sequential organ failure assessment (SOFA) score and patients with initial PaO 2 /FiO 2 -ratio 100-200, if compared to placebo treated patients. Oral inhalation of AP301 led to an earlier onset and more pronounced increase in oxygenation index compared to placebo treatment. The alveolar clearance effect of AP301 was shown to be favourable, and thereby supports further clinical development of AP301.
Replication data of Buchmeiser group for: "Cationic tungsten imido alkylidene N-heterocyclic carbene complexes for stereospecific ring-opening metathesis polymerization of norbornene derivatives" (2021)

&lt;p&gt;All primary data files of measurements and processed data of the journal article mentioned under related publications from Buchmeiser group can be found here.&lt;/p&gt; &lt;p&gt;The data is structured according to figures and schemes in the research article and contains the following data types: mestrenova, excel, fid.&lt;/p&gt; &lt;p&gt;Further experimental for reproduction of experiemnts can be found in the supporting information.&lt;/p&gt;
Enhancing the Photon- and Gas-Sensing Properties of a Single SnO<sub>2</sub>Nanowire Based Nanodevice by Nanoparticle Surface Functionalization (2008)

Field-effect transistors based on a single SnO 2 nanowire were successfully fabricated, and their photon- and gas-sensing properties were investigated. It is found that the sensitivity of single SnO 2 nanowire based devices was remarkably improved by surface functionalization with ZnO or NiO nanoparticles. The heterojunction between the surface coating layers and SnO 2 and the corresponding coupling effect of the two sensing materials play a critical role in controlling device sensitivity.
Data from Undifferentiated Sarcomas in Children Harbor Clinically Relevant Oncogenic Fusions and Gene Copy-Number Alterations: A Report from the Children's Oncology Group (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy-number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Copy-number alterations were assessed by OncoScan FFPE Express on 32 UDS. Whole-exome and transcriptome libraries from eight tumors with sufficient archived material were sequenced on HiSeq (2 × 100 bp). Targeted RNA-sequencing using Archer chemistry was performed on two additional cases.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Five-year overall survival for patients with UDS was 83% (95% CI, 69%–97%) with risk-adapted therapy (surgery, chemotherapy, and radiotherapy). Both focal and arm-level copy-number alterations were common including gain of 1q (8/32, 25%) and loss of 1p (7/32, 22%), both of which occurred more often in clinically defined high-risk tumors. Tumors with both loss of 1p and gain of 1q carried an especially poor prognosis with a 5-year event-free survival of 20%. GISTIC analysis identified recurrent amplification of FGF1 on 5q31.3 (&lt;i&gt;q&lt;/i&gt; = 0.03) and loss of &lt;i&gt;CDKN2A&lt;/i&gt; and &lt;i&gt;CDKN2B&lt;/i&gt; on 9p21.3 (&lt;i&gt;q&lt;/i&gt; = 0.07). Known oncogenic fusions were identified in eight of 10 cases analyzed by next-generation sequencing.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Pediatric UDS generally has a good outcome with risk-adapted therapy. A high-risk subset of patients whose tumors have copy-number loss of 1p and gain of 1q was identified with only 20% survival. Oncogenic fusions are common in UDS, and next-generation sequencing should be considered for children with UDS to refine the diagnosis and identify potentially targetable drivers. &lt;i&gt;Clin Cancer Res; 24(16); 3888–97. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest (2002)

Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA shifts pharyngeal expression of AmphiTR2/4 anteriorly, while BMS009 extends it posteriorly. Collectively, our results suggest a model for anteroposterior patterning of the amphioxus nerve cord and pharynx, which is probably applicable to vertebrates as well, in which a low anterior level of AmphiRAR (caused, at least in part, by competitive inhibition by AmphiTR2/4) is necessary for patterning the forebrain and formation of gill slits, the posterior extent of both being set by a sharp increase in the level of AmphiRAR. Supplemental data available on-line