gebhart/patrepeval huggingface dataset:
Biosynthetic Polymers as Functional Materials (2016)

The synthesis of functional polymers encoded with biomolecules has been an extensive area of research for decades. As such, a diverse toolbox of polymerization techniques and bioconjugation methods has been developed. The greatest impact of this work has been in biomedicine and biotechnology, where fully synthetic and naturally derived biomolecules are used cooperatively. Despite significant improvements in biocompatible and functionally diverse polymers, our success in the field is constrained by recognized limitations in polymer architecture control, structural dynamics, and biostabilization. This Perspective discusses the current status of functional biosynthetic polymers and highlights innovative strategies reported within the past five years that have made great strides in overcoming the aforementioned barriers.
Oral fluids after major gastrointestinal operations. (1988)

men and women.The effect in the data from the Caerphilly study suggests that these lower concentrations in London mav have been found not because they are genuinelv lower but because the subjects were not fasting.
Liver-specific Inflammatory Signatures Predict Clinically Significant Liver Damage (2023)

ABSTRACT Background and Aims Inflammation drives progression of chronic liver disease. However, the triggers of inflammation remain undefined during chronic hepatitis B (CHB) because hepatic flares are spontaneous and difficult to capture. We used nucleoside analogue (NA) withdrawal to investigate early inflammatory events because liver damage after stopping therapy occurs in a predictable time frame. 11 CHB patients underwent 192 weeks of NA therapy before a protocol defined stop. Liver fine-needle aspirates (FNAs) were collected at baseline and 4-weeks post-withdrawal and analyzed using flow cytometry and single-cell RNA sequencing (scRNA-seq). Intrahepatic mononuclear cells (IHMCs) from uninfected livers were used to validate transcriptomic findings. At 4 weeks post NA-withdrawal, HBV DNA rebounded but alanine aminotransferase (ALT) levels remained normal, 7/11 patients developed ALT elevations (&gt;2xULN) at later timepoints. There were no changes in cell frequencies between baseline and viral rebound. ScRNA-seq revealed upregulation of IFN stimulated genes (ISGs) and pro-inflammatory cytokine MIF upon viral rebound. In vitro experiments confirmed the type I IFN-dependent ISG profile whereas MIF was induced primarily by IL-12. MIF exposure further amplified inflammatory cytokine production by myeloid cells. Our data show that innate immune activation is detectable in the liver before clinically-significant liver damage is detectable in the serum.
Assessment of the flow velocity of blood cells in a microfluidic device using joint spectral and time domain optical coherence tomography (2013)

Although Doppler optical coherence tomography techniques have enabled the imaging of blood flow in mid-sized vessels in biological tissues, the generation of velocity maps of capillary networks remains a challenge. To better understand the origin and information content of the Doppler signal from small vessels and limitations of such measurements, we used joint spectral and time domain optical coherence tomography to monitor the flow in a model, semitransparent microchannel device. The results obtained for Intralipid, whole blood, as well as separated red blood cells indicate that the technique is suitable to record velocity profiles in vitro, in a range of microchannel configurations.
Frequency of Acquisition of First-episode Genital Infection with Herpes Simplex Virus from Symptomatic and Asymptomatic Source Contacts (1985)

Sixty-six source contacts of index patients with first-episode genital infection caused by herpes simplex virus (HSV) were evaluated for evidence of current or past HSV infections. Forty-three source contacts (65%) reported a history consistent with previous recurrent HSV infection or were experiencing a first episode of genital herpes when initially examined. However, 60% of these 43 contacts were not aware that they had transmissible HSV infection. Twenty-nine (67%) of the 43 individuals had had recent sexual contact with an index patient when lesions were present. All of the remaining 23 source contacts, who were without a history of symptoms consistent with HSV infection, had detectable neutralizing antibody to HSV; HSV type 2 was isolated from the cervix of two of these asymptomatic source contacts. Efforts to identify individuals with undiagnosed genital herpes and to instruct these individuals concerning the risk of disease transmission in the presence of lesions are needed if the rate of transmission is to be decreased; however, methods designed to decrease the rate of transmission by asymptomatic individuals must also be evaluated.
Allosteric regulation of glycogen synthase and hexokinase by glucosamine-6-phosphate during glucosamine-induced insulin resistance in skeletal muscle and heart. (1999)

Glucosamine infusion induces insulin resistance in vivo, but the effect of glucosamine on intracellular metabolites of the hexosamine pathway, especially glucosamine-6-phosphate (GlcN6P) is unknown. Because of the structural similarity of glucose-6-phosphate (G-6-P) and GlcN6P, we hypothesized that accumulation of this metabolite might alter the activities of enzymes such as glycogen synthase and hexokinase. We infused glucosamine (30 micromol x kg(-1) x min(-1)) to induce insulin resistance in rats during a euglycemic-hyperinsulinemic clamp. Glucosamine induced whole-body insulin resistance, which was apparent after 90 min and continued progressively for 360 min. Despite inducing severe whole-body insulin resistance and decrease in glycogen synthase fractional activity in rectus abdominis muscle (69+/-3 vs. 83+/-1%, P<0.01) and heart (7+/-1 vs. 32+/-4%, P<0.001), glucosamine did not change the glycogen content in rectus and even increased it in the heart (209+/-13 vs. 117+/-9 mmol/kg dry wt, P<0.001). Glucosamine increased tissue concentrations of UDP-GlcNAc 4.4- and 4.6-fold in rectus abdominis and heart, respectively. However, GlcN6P concentrations increased 500- and 700-fold in glucosamine-infused animals in rectus abdominis (590+/-80 vs. 1.2+/-0.1 micromol/kg wet wt, P<0.001) and heart (7,703+/-993 vs. 11.2+/-2.3 micromol/kg wet wt, P<0.001). To assess the possible significance of GlcN6P accumulation, we measured the effect of GlcN6P on glycogen synthase and hexokinase activity in vitro. At the GlcN6P concentrations measured in rectus abdominis and heart in vivo, glycogen synthase was activated by 21 and 542%, while similar concentrations inhibited hexokinase activity by 5 and 46%, respectively. This study demonstrates that infusion of glucosamine during a euglycemic-hyperinsulinemic clamp results in marked accumulation of intracellular GlcN6P. The GlcN6P concentrations in the heart and rectus abdominis muscle reach levels sufficient to cause allosteric activation of glycogen synthase and inhibition of hexokinase.
Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom (1985)

A series of tetrahedral oxo acids of Group VA and VIA elements and of silicon and boron were examined as inhibitors of angiotensin-converting enzyme. Arsenate is a competitive inhibitor with a Ki of 27 +/- 1 mM, at least 10-fold more potent than phosphate. Dimethylarsinate is a competitive inhibitor with a Ki of 70 +/- 9 mM, 2-fold more potent than dimethylphosphinate. Oxo acids of boron, silicon, antimony, sulphur and selenium are not inhibitors. On the basis of these results and the strong inhibition of this zinc metallopeptidase by substrate analogues containing a tetrahedral phosphorus atom, two substrate analogues containing a tetrahedral arsenic atom were prepared. 2-Arsonoacetyl-L-proline is a competitive inhibitor with a Ki of 18 +/- 7 mM, more than 2000-fold weaker than that of its phosphorus analogue 2-phosphonoacetyl-L-proline. 4-Arsono-2-benzylbutanoic acid is a mixed inhibitor with a Ki of 0.5 +/- 0.2 mM, indistinguishable in potency from its phosphorus analogue 2-benzyl-4-phosphonobutanoic acid.
Fetal developmental change in topographical relationship between the human lateral pterygoid muscle and buccal nerve (2012)

In adults, the lateral pterygoid muscle (LPM) is usually divided into the upper and lower heads, between which the buccal nerve passes. Using sagittal or horizontal sections of 14 fetuses and seven embryos (five specimens at approximately 20-25 weeks; five at 14-16 weeks; four at 8 weeks; seven at 6-7 weeks), we examined the topographical relationship between the LPM and the buccal nerve. In large fetuses later than 15 weeks, the upper head of the LPM was clearly discriminated from the lower head. However, the upper head was much smaller than the lower head in the smaller fetuses. Thus, in the latter, the upper head was better described as an 'anterior slip' extending from the lower head or the major muscle mass to the anterior side of the buccal nerve. The postero-anterior nerve course seemed to be determined by a branch to the temporalis muscle (i.e. the anterior deep temporal nerve). At 8 weeks, the buccal nerve passed through the roof of the small, fan-like LPM. At 6-7 weeks, the LPM anlage was embedded between the temporobuccal nerve trunk and the inferior alveolar nerve. Therefore, parts of the LPM were likely to 'leak' out of slits between the origins of the mandibular nerve branches at 7-8 weeks, and seemed to grow in size during weeks 14-20 and extend anterosuperiorly along the infratemporal surface of the prominently developing greater wing of the sphenoid bone. Consequently, the topographical relationship between the LPM and the buccal nerve appeared to 'change' during fetal development due to delayed development of the upper head.
Novel Transposon Directed Base Exchange Mutagenesis (TDEM) (2008)

Here, we describe an efficient and controllable method for introducing a mutation into a gene using a transposition system with specifically designed DNA inserts. One round of Transposon Directed Base‐Exchange Mutagenesis (TDEM) can remove up to 11 base pairs from a randomly selected site within the target gene and replace them with any length of DNA of a predetermined sequence. Therefore, the number of bases to be deleted and inserted can be regulated. Because each round of TDEM generates only one mutation in the target gene, the degree of mutation introduced can be controlled. As a proof of principle, we isolated a mutant of the alpha fragment of beta‐galactosidase that lacks the alpha‐complementation activity and then selected revertants showing alpha‐complementation activity after introducing a second mutation using TDEM. The sequencing results showed that this method efficiently substituted three bases at one site within the target gene with three predetermined bases resulting in revertants containing a mutation that compensates for the first mutation. Using TDEM, we also introduced a mutation into the ccdB protein in order to identify residues critical for its activity. Thus, our results demonstrated that TDEM can be used to introduce a limited and predetermined change at each round of mutagenesis providing a useful tool for protein evolution.
MiR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway (2020)

Protection against renal fibrosis is important for the management of obstructive nephropathy. We researched the roles and possible mechanism of miR-155-5p in renal interstitial fibrosis, which may provide a potential endogenous target for renal interstitial fibrosis in obstructive nephropathy. Herein, NRK-49F cells were transfected with miR-155-5p mimic, miR-155-5p inhibitor, SIRT1 plasmid and/or SIRT1 siRNA. The unilateral ureteral obstruction (UUO) model was built with male C57 black mice and administrated with SRT1720 by tail vein injection. Levels of miR-155-5p, SIRT1 and relative proteins (TGF-β1, α-SMA, Collage I and fibronectin) in NRK-49F cells or mice kidney tissues were measured with quantitative reverse transcription polymerase chain reaction or Western blot. The target gene of miR-155-5p was analyzed through TargetScan and dual-luciferase reporter assay. Mice kidney tissue was stained with Masson trichrome. It was found that miR-155-5p overexpression promoted the expressions of fibroblast related proteins expression and inhibited the SIRT1 expression in NRK-49F cells, while miR-155-5p silencing had an opposite effect. SIRT1 can bind with miR-155-5p. MiR-155-5p inhibited the level of SIRT1. Fibroblast related proteins were up-regulated by miR-155-5p and down-regulated by SIRT1 in NRK-49F cells, while the up-regulatory effect of miR-155-5p was reversed by SIRT1. MiR-155-5p expression was up-regulated and SIRT1 expression was down-regulated in the kidney tissue of UUO mice. SRT1720 attenuated the fiber deposition, up-regulated SIRT1 level and down-regulated the levels of fibroblast related proteins in UUO model mice. To conclude, miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy <i>via</i> inhibiting SIRT1 signaling pathway.
Endoskopische Stent-Implantation bei malignen Gallengangstenosen: Vergleich Metallstent mit einem Plastikstent ohne zentrales Lumen - eine prospektiv-randomisierte, multizentrische Studie (2013)

Einleitung: Die endoskopische Stent-Implantation ist eine etablierte Therapie zur palliativen Drainage bei malignen Gallengangstenosen. Mit der Entwicklung eines neuartigen Kunststoffstents ohne zentrales Lumen (Viaduct®-Stent) sollte eine Verbesserung der Offenheitsrate im Vergleich zu bisherigen Kunststoffstents erzielt werden.
Potential physiological importance of pyrroloquinoline quinone. (2009)

Pyrroloquinoline quinone (PQQ) is a novel biofactor for which a proposition can be made for physiological importance. PQQ was first recognized as an enzyme cofactor in bacteria. It has recently been tentatively identified as a component of interstellar dust. Thus, PQQ may have been present throughout early biological conception and evolution. PQQ is also a potent plant growth factor. Consequently, for animals and humans, there has been constant exposure to PQQ. In animals, PQQ is reported to participate in a range of biological functions with apparent survival benefits (e.g., improved neonatal growth and reproductive performance). There are also benefits from PQQ supplementation related to cognitive, immune, and antioxidant functions, as well as protection from cardiac and neurological ischemic events. Although PQQ is not currently viewed as a vitamin, its involvement in cell signaling pathways, particularly those important to mitochondriogenesis in experimental animal models, may eventually provide a rationale for defining PQQ as vital to life. For humans, such evidence suggests there may be similar parallels or benefits from improving PQQ status.
Radial distributions of {open_quotes}mass shifting ions{close_quotes} in a quadrupole ion trap mass spectrometer (1994)

An early problem in the development of the commercial ion trap mass spectrometer was the phenomena of {open_quotes}mass-shifts{close_quotes}, where two ions, having the same nominal m/z, appear at different points on the mass scale. Although the problem has been circumvented by the use of ion traps elongated in the z-direction (stretched geometry), the phenomena itself remains to be understood and is an area of active interest in ion trap mass spectrometry. One possible explanation is that ions having different chemical properties, e.g., polarizability, have different radial distributions in the ion trap. If these ions experience an inhomogeneous field, say from field faults introduced by holes in the endcaps, the ions will experience different average values of q for a given RF voltage and will be ejected at different times (apparent masses).
The state of water in styrene‐grafted and sulfonated poly(vinylidene fluoride) membranes (1997)

Abstract The state of water in proton exchange membranes prepared by pre‐irradiation (electron beam, 100 kGy) grafting of styrene onto poly(vinylidene fluoride) films (PVDF‐g‐PS), followed by sulfonation (PVDF‐g‐PSSA), has been studied with thermal analysis, Raman spectroscopy and small angle X‐ray diffraction (SAXS). Raman spectra show that, in addition to free liquid water in the membranes, single water molecules are weakly bound to the polymer backbone. Thermal analysis shows that there are three types of water molecules in the membrane; non‐freezable water associated with the ionic sites, freezable free water, and freezable bound water. The amount of non‐freezable water is around 10 H 2 O/SO 3 H (mol/mol), and is independent of the degree of grafting (d.o.g.). The amount of freezable water is strongly dependent on the d.o.g. as long as the grafting has not penetrated the whole of the film, and reaches a value of around 40 H 2 O/SO 3 H (mol/mol) above a d.o.g. of 50%. The conductivity of membranes containing only the non‐freezable water is low, i. e. the ionically bound water alone does not form the domains necessary for proton and water transport. SAXS measurements show that water/sulfonic acid clusters in hydrated PVDF‐g‐PSSA membranes with a Bragg distance of 25 Å are formed; these form the ion conducting channels in the membrane.
Series of transcatheter valve-in-valve implantations into degenerated bioprostheses in aortic and mitral position (2011)

Objectives: Xenograft degeneration is a potential problem long-term after biological valve replacement. Interventional techniques may be valuable in patients not suitable for surgery. We report our experience with transcatheter valve-in-valve implantations in patients with degenerated bioprostheses in aortic and mitral position.
Upper Tract Imaging Surveillance is not Effective in Diagnosing Upper Tract Recurrence in Patients Followed for Nonmuscle Invasive Bladder Cancer (2013)

Upper tract recurrence is a lifelong risk in patients with bladder cancer, but most cases will be missed on routine upper tract imaging. The majority of upper tract urothelial carcinoma can be diagnosed using a combination of thorough history taking, physical examination, urine cytology and sonography, indicating that routine surveillance imaging may not be the most efficient way to detect upper tract recurrence.
An Analysis of the Effects of RFID Tags on Narrowband Navigation and Communication Receivers (2007)

The simulated effects of the Radio Frequency Identification (RFID) tag emissions on ILS Localizer and ILS Glide Slope functions match the analytical models developed in support of DO-294B provided that the measured peak power levels are adjusted for 1) peak-to-average power ratio, 2) effective duty cycle, and 3) spectrum analyzer measurement bandwidth. When these adjustments are made, simulated and theoretical results are in extraordinarily good agreement. The relationships hold over a large range of potential interference-to-desired signal power ratios, provided that the adjusted interference power is significantly higher than the sum of the receiver noise floor and the noise-like contributions of all other interference sources. When the duty-factor adjusted power spectral densities are applied in the evaluation process described in Section 6 of DO-294B, most narrowband guidance and communications radios performance parameters are unaffected by moderate levels of RFID interference. Specific conclusions and recommendations are provided.
Alternative splicing within the I–II loop controls surface expression of T‐type Cav3.1 calcium channels (2008)

Molecular diversity of T-type/Ca(v)3 Ca2+ channels is created by expression of three genes and alternative splicing of those genes. Prompted by the important role of the I-II linker in gating and surface expression of Ca(v)3 channels, we describe here the properties of a novel variant that partially deletes this loop. The variant is abundantly expressed in rat brain, even exceeding transcripts with the complete exon 8. Electrophysiological analysis of the Delta8b variant revealed enhanced current density compared to Ca(v)3.1a, but similar gating. Luminometry experiments revealed an increase in the expression of Delta8b channels at the plasma membrane. We conclude that alternative splicing of Ca(v)3 channels regulates surface expression and may underlie disease states in which T-channel current density is increased.
Alternative clamp loaders/unloaders (2016)

Each time a cell duplicates, the whole genome must be accurately copied and distributed. The enormous amount of DNA in eukaryotic cells requires a high level of coordination between polymerases and other DNA and chromatin-interacting proteins to ensure timely and accurate DNA replication and chromatin formation. PCNA forms a ring that encircles the DNA. It serves as a processivity factor for DNA polymerases and as a landing platform for different proteins that interact with DNA and chromatin. It thus serves as a signaling hub and influences the rate and accuracy of DNA replication, the r-formation of chromatin in the wake of the moving fork and the proper segregation of the sister chromatids. Four different, conserved, protein complexes are in charge of loading/unloading PCNA and similar molecules onto DNA. Replication factor C (RFC) is the canonical complex in charge of loading PCNA, the replication clamp, during S-phase. The Rad24, Ctf18 and Elg1 proteins form complexes similar to RFC, with particular functions in the cell's nucleus. Here we summarize our current knowledge about the roles of these important factors in yeast.
MSK-ACCESS for noninvasive somatic mutation profiling of lung cancers utilizing circulating tumor DNA. (2020)

3529 Background: Circulating cell-free DNA (cfDNA) next-generation sequencing (NGS) is a promising strategy for non-invasive molecular profiling of cancers. MSK-ACCESS (Analysis of Circulating cfDNA to Evaluate Somatic Status) is a hybridization-capture targeted NGS assay that detects somatic variants in select exons of 129 genes with matched white blood cell sequencing. We present the initial clinical experience with MSK-ACCESS among patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with stage IV NSCLC underwent prospective MSK-ACCESS testing at initial diagnosis or progression of disease on targeted therapy between June 2019 and January 2020. A subset of patients had matched tissue-based NGS testing with the MSK-IMPACT 468 gene assay. We assessed oncogenic driver detection, turnaround time, plasma-tissue concordance, and matching to therapy. National Comprehensive-Cancer Network designated driver alterations were included in evaluation of tissue-plasma concordance (EGFR, ALK, KRAS, MET, RET, BRAF, HER2, ROS1, NTRK). Turnaround time was compared by a two-sided Wilcoxon signed-rank test. Results: A total of 201 patients with NSCLC had MSK-ACCESS testing at initial diagnosis (n = 79) or following progression of disease (n = 122). The median turn-around-time from plasma collection to MSK-ACCESS report was 16 days (range: 9 – 36 days) compared to 19 days from lab receipt of tissue to report (range: 12 – 57) for MSK-IMPACT (p &lt; 0.001). Among patients with a driver detected on MSK-ACCESS, 100% (92/92) had an identical driver detected on MSK-IMPACT. Among patients with a driver detected on MSK-IMPACT, 75% (92/123) had an identical driver detected on MSK-ACCESS. This rate was similar among patients who were treatment-naive (74%; 64/86) and had disease progression (76%, 28/37) at the time of MSK-ACCESS. MSK-ACCESS identified driver alterations that directly guided first-line targeted therapy (n = 18) with response in all patients with available radiographic follow-up (n = 10), including a patient without confirmatory tissue testing. MSK-ACCESS identified resistance alterations among patients with disease progression including EGFR T790M, EGFR C797S, ROS1 G2032R, as well as a BRAF fusion. Conclusions: MSK-ACCESS successfully identified driver alterations with high concordance to tissue-based testing, directly guided patients to therapy with clinical responses, and detected known and novel resistance mechanisms. This assay warrants further clinical development to guide and facilitate precision oncology.