gebhart/patrepeval huggingface dataset:
The role of pdx1 and HNF6 in proliferation and differentiation of endocrine precursors (2004)

Ex vivo expansion of embryonic stem cells (ES cells) or pancreatic stem cells for insulin delivery to diabetic patients provides potential for the restoration of islet function in these individuals. Understanding the spatial and temporal requirements of crucial factors for endocrine progenitor specification, proliferation, and terminal differentiation remains a major challenge in the field of pancreas development. Here, we provide speculation as to the role of pdx1 and HNF6 in these different stages of pancreatic endocrine cell development. At the time when islets begin to form within the pancreas, the expression patterns of pdx1 and HNF6 diverge, suggesting distinct functions for each of the genes over the course of endocrine cell development. The current body of evidence provides support for a role of both factors in early endocrine specification as well as a requirement for pdx1 in the generation of mature pancreatic endocrine cells. The precise temporal requirement of HNF6 in the production of terminally differentiated endocrine cells remains unclear. Future studies in this area will rely on conditionally manipulatable systems in combination with lineage-tracing studies for a more accurate assessment of pdx1 and HNF6 function at different stages along the pathway of endocrine cell development.
Electrophoresis combined with novel mass spectrometry techniques: Powerful tools for the analysis of proteins and proteomes (1998)

Analytical and preparative electrophoresis separation techniques have been essential tools in protein biochemistry and the biological sciences in general. The combination of high resolution electrophoresis techniques with high performance analytical procedures has dramatically enhanced analytical protein biochemistry. In this report we describe the combination of electrophoretic separation techniques with electrospray ionization (ESI) tandem mass spectrometry (MS/MS). A series of different techniques, consisting of automated high performance liquid chromatography (HPLC)-MS/MS, capillary-HPLC-MS/MS, and solid phase extraction (SPE)-capillary zone electrophoresis (CZE)-MS/MS, are described in the context of the identification of high pmol to the low fmol amounts of proteins. Application of these powerful new tools for the analysis of proteins on a large proteome-wide scale is presented. Furthermore, the combination of orthogonal separation techniques, such as immobilized metal affinity chromatography (IMAC) with SPE-CZE-MS/MS, and IMAC followed by HPLC, and by SPE-CZE-MS/MS, are presented for the detailed investigation of post-translational modifications of specific proteins.
ACETYLATION OF 4-AMINO-44-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONES (1993)

(1993). ACETYLATION OF 4-AMINO-44-DIHYDRO-1H-1,2,4-TRIAZOL-5-ONES. Organic Preparations and Procedures International: Vol. 25, No. 1, pp. 99-105.
New Building Block for Polyhydroxylated Piperidine:  Total Synthesis of 1,6-Dideoxynojirimycin (2008)

(3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1-pentene 10, an important precursor for the synthesis of polyhydroxylated piperidines, has been achieved as a single diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate to yield a range of interesting hydroxylated piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr. To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most expeditious to date.
Comparative Metagenomic Study of Alterations to the Intestinal Microbiota and Risk of NosocomialClostridum difficile–Associated Disease (2010)

This study investigated the relationship between hospital exposures, intestinal microbiota, and subsequent risk of Clostridium difficile-associated disease (CDAD), with use of a nested case-control design. The study included 599 patients, hospitalized from September 2006 through May 2007 in Montreal, Quebec, from whom fecal samples were obtained within 72 h after admission; 25 developed CDAD, and 50 matched controls were selected for analysis. Nonsteroidal anti-inflammatory drugs and antibiotic use were associated with CDAD. Fecal specimens were evaluated by 16S ribosomal RNA microarray to characterize bacteria in the intestinal microbiota during the at-risk period. Probe intensities were higher for Firmicutes, Proteobacteria, and Actinobacteria in the patients with CDAD, compared with controls, whereas probe intensities for Bacteroidetes were lower. After epidemiologic factors were controlled for, only Bacteroidetes and Firmicutes remained significantly and independently associated with development of CDAD. Hospital exposures were associated with changes in the intestinal microbiota and risk of CDAD, and these changes were not driven exclusively by antimicrobial use.
A review of antibody-based therapeutics targeting G protein-coupled receptors: an update (2020)

The GPCR-antibody pipeline has progressed significantly with a number of technical developments enabling the successful resolution of some of the challenges previously encountered and this has contributed to the growing interest in antibody-based therapeutics addressing this target class.
Fragment-Based Optimization of Small Molecule CXCL12 Inhibitors for Antagonizing the CXCL12/CXCR4 Interaction (2013)

The chemokine CXCL12 and its G protein-coupled receptor (GPCR) CXCR4 are high-priority clinical targets because of their involvement in metastatic cancers (also implicated in autoimmune disease and cardiovascular disease). Because chemokines interact with two distinct sites to bind and activate their receptors, both the GPCRs and chemokines are potential targets for small molecule inhibition. A number of chemokines have been validated as targets for drug development, but virtually all drug discovery efforts focus on the GPCRs. However, all CXCR4 receptor antagonists with the exception of MSX-122 have failed in clinical trials due to unmanageable toxicities, emphasizing the need for alternative strategies to interfere with CXCL12/CXCR4-guided metastatic homing. Although targeting the relatively featureless surface of CXCL12 was presumed to be challenging, focusing efforts at the sulfotyrosine (sY) binding pockets proved successful for procuring initial hits. Using a hybrid structure-based in silico/NMR screening strategy, we recently identified a ligand that occludes the receptor recognition site. From this initial hit, we designed a small fragment library containing only nine tetrazole derivatives using a fragment-based and bioisostere approach to target the sY binding sites of CXCL12. Compound binding modes and affinities were studied by 2D NMR spectroscopy, X-ray crystallography, molecular docking and cell-based functional assays. Our results demonstrate that the sY binding sites are conducive to the development of high affinity inhibitors with better ligand efficiency (LE) than typical protein-protein interaction inhibitors (LE ≤ 0.24). Our novel tetrazole-based fragment 18 was identified to bind the sY21 site with a K(d) of 24 μM (LE = 0.30). Optimization of 18 yielded compound 25 which specifically inhibits CXCL12-induced migration with an improvement in potency over the initial hit 9. The fragment from this library that exhibited the highest affinity and ligand efficiency (11: K(d) = 13 μM, LE = 0.33) may serve as a starting point for development of inhibitors targeting the sY12 site.
A Pancreatic β-Cell-specific Enhancer in the HumanPDX-1 Gene Is Regulated by Hepatocyte Nuclear Factor 3β (HNF-3β), HNF-1α, and SPs Transcription Factors (2001)

The PDX-1 transcription factor plays a key role in pancreas development. Although expressed in all cells at the early stages, in the adult it is mainly restricted to the beta-cell. To characterize the regulatory elements and potential transcription factors necessary for human PDX-1 gene expression in beta-cells, we constructed a series of 5' and 3' deletion fragments of the 5'-flanking region of the gene, fused to the luciferase reporter gene. In this report, we identify by transient transfections in beta- and non-beta-cells a novel beta-cell-specific distal enhancer element located between -3.7 and -3.45 kilobases. DNase I footprinting analysis revealed two protected regions, one binding the transcription factors SP1 and SP3 and the other hepatocyte nuclear factor 3beta (HNF-3beta) and HNF-1alpha. Cotransfection experiments suggest that HNF-3beta, HNF-1alpha, and SP1 are positive regulators of the herein-described human PDX-1 enhancer element. Furthermore, mutations within each motif abolished the binding of the corresponding factor(s) and dramatically impaired the enhancer activity, therefore suggesting cooperativity between these factors.
Homozygosity and Linkage Disequilibrium (2002)

We illustrate how homozygosity of haplotypes can be used to measure the level of disequilibrium between two or more markers. An excess of either homozygosity or heterozygosity signals a departure from the gametic phase equilibrium: We describe the specific form of dependence that is associated with high (low) homozygosity and derive various linkage disequilibrium measures. They feature a clear biological interpretation, can be used to construct tests, and are standardized to allow comparison across loci and populations. They are particularly advantageous to measure linkage disequilibrium between highly polymorphic markers.
Non-Thermal Irreversible Electroporation (N-TIRE) and Adjuvant Fractionated Radiotherapeutic Multimodal Therapy for Intracranial Malignant Glioma in a Canine Patient (2011)

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.
Variations in daily intakes of myristic and α-linolenic acids in sn-2 position modify lipid profile and red blood cell membrane fluidity (2006)

The present study evaluated the effects of moderate intakes of myristic acid (MA), at 1.2% and 1.8% of total energy (TE), associated with a 0.9% TE intake of alpha-linolenic acid (ALA) on lipid and fatty acid profiles and red blood cell membrane fluidity. Twenty-nine monks without dyslipidaemia were enrolled in a 1-year nutritional study in which two experimental diets were tested for 3 months each: diet 1, MA 1.2 % and ALA 0.9%; diet 2, MA 1.8% and ALA 0.9%. A control diet (MA 1.2%, ALA 0.4%) was given 3 months before diets 1 and 2. Thus, two different levels of MA (1.2%, 1.8%) and ALA (0.4%, 0.9%) were tested. Intakes of other fatty acids were at recommended levels. Samples were obtained on completion of all three diets. For fluidity analysis, the red blood cells were labelled with 16-doxylstearate and the probe incorporated the membrane where relaxation-correlation time was calculated. Diet 1 was associated with a decrease in total cholesterol, in LDL-cholesterol, in triacylglycerols and in the ratio of total to HDL-cholesterol; ALA and EPA levels were increased in both phospholipids and cholesterol esters. Diet 2 was associated with a decrease in triacylglycerols and in the ratios of total to HDL-cholesterol and of triacylglycerols to HDL-cholesterol, and with an increase in HDL-cholesterol; EPA levels were decreased in phospholipids and cholesterol esters. Red blood cell membrane fluidity was increased in both diets (P<0.0001), but the higher increase was obtained with diet 1, mainly in the oldest subjects. Intakes of myristic acid (1.2%TE) and ALA (0.9%TE), both mainly in the sn-2 position, were associated with favourable lipid and n-3 long-chain fatty acid profiles. These beneficial effects coexisted with particularly high membrane fluidity, especially among the oldest subjects.
Characterization of complementary deoxyribonucleic acid and genomic deoxyribonucleic acid for the .beta. chain of human fibrinogen (1983)

A total of 148 cDNAs coding for the beta chain of human fibrinogen have been identified from a human liver cDNA library employing a bovine cDNA as a probe. The largest cDNA insert contained 1932 base pairs cloned into the PstI site of plasmid pBR322. This cDNA insert contained 66 base pairs coding for a portion or all of a signal sequence, 1383 base pairs coding for 461 amino acids in the mature protein, a stop codon of TAG, a noncoding region of 431 base pairs, and a poly(A) tail of 19 base pairs. Most of the cDNA inserts coding for the beta chain were found to have a noncoding region of 98 or 167 base pairs rather than 431 base pairs at the 3'-end. The bovine cDNA for the beta chain was also employed as a probe for screening a lambda phage library containing human genomic DNA. Seven positive phage were identified. One of the phage, which contained the entire gene for the beta chain of fibrinogen, was examined by electron microscopy, and portions of its DNA sequence are presented. Seven intervening sequences were identified in the gene for the beta chain of human fibrinogen. The largest intervening sequence (approximately 1.3 kilobases) was found at the 5'-end of the gene and was located between amino acid residues 8 and 9, which are present in fibrinopeptide B. A sequence analysis of the 5'-end of the gene also indicated that the B chain of human fibrinogen contained a signal sequence of either 16, 27, or 30 amino acid residues.
rDNA targeted oligonucleotide primers for the identification of pathogenic yeasts in a polymerase chain reaction (1995)

Species-specific oligonucleotide primers were designed for PCR identification of the basidiomycetous yeasts Cryptococcus neoformans, Trichosporon cutaneum and Rhodotorula mucilaginosa. The procedure uses standard PCR components including DNA from the test species and three primers: two universal external (upstream and downstream) limiting primers and a species-specific internal primer. Species identification requires the formation of a species-specific rDNA nucleotide segment that is significantly smaller (approximately 200 bp) than a non-target segment (approximately 600 bp). The procedure can be used to identify yeasts from single and mixed populations.
Akt-Dependent T198 Phosphorylation of Cyclin-Dependent Kinase Inhibitor p27kip1in Breast Cancer (2004)

The localization of the cyclin-dependent kinase inhibitor p27(kip1) is dependent on the phosphorylation of one of three key amino acid residues: S10, T157 and T198. However, it was unclear whether endogenous p27(kip1) is phosphorylated at T198 in the living cell. In the present work we describe the generation and characterization of a polyclonal antibody able to recognize recombinant, transfected as well as endogenous T198-phosphorylated p27(kip1). Using this antibody, we demonstrate that: (1) endogenous p27(kip1) is phosphorylated at T198 in 4 breast cancer cells lines (MCF7, MDA-MB231, MDA- MB436 and MDA-MB468); (2) T198 phosphorylation is increased in breast cancer cells compared with normal mammary epithelial cells (HMEC); (3) T198-phosphorylated p27(kip1) is exclusively cytoplasmic; (4) T198 phosphorylation is dependent on the activity of the PI3K-PKB/Akt pathway, being it drastically reduced by the pharmacological PI3K inhibitor LY294002 or stimulated by the constitutive activation of PKB/Akt. Finally, in primary human breast carcinomas, cytoplasmic accumulation of T198-phosphorylated p27(kip1) parallels Akt activation. We conclude that in breast cancer cells p27(kip1) is phosphorylated at T198 in a PI3K/Akt dependent manner and that this phosphorylation may contribute to p27(kip1) cytoplasmic mislocalization observed in breast cancer.
Development of a Reduction‐Responsive Amino Acid that Induces Peptide Bond Cleavage in Hypoxic Cells (2012)

Hypoxia-responsive amino acids are indispensable in the preparation of hypoxic tumor-specific peptidyl prodrugs. In this paper, the design and synthesis of a reduction-responsive amino acid that induces peptide bond cleavage after reduction of the nitro group are described. Application to hypoxia-responsive peptide bond cleavage system is also reported.
A Comparison of Methodologies for the Preparation of Human Epidermal-Dermal Composites (1997)

The purpose of this study was to compare methodologies for the preparation of human skin composites based on deepidermized acellular dermal matrix, epidermal keratinocytes, and dermal fibroblasts with the aim of preparing a clinically useful skin substitute. Dermal matrices were prepared from normal human skin and we compared methods of sterilization (glycerol treatment, ethylene oxide treatment, and gamma irradiation), methods of removing the epidermis (sodium chloride, phosphate buffered saline, and dispase), and methods of seeding the composites with fibroblasts and keratinocytes. We report protocols for reproducibly preparing composites that share many of the features of normal skin after 7 days culture at an air-liquid interface. Such composites can be based on allodermis pretreated with either glycerol or ethylene oxide (although the latter gave less consistent results than the glycerol treatment). Fibroblast penetration into the dermis could be achieved by culture of cells on the reticular or papillary surface of the dermis. However, we report for the first time that fibroblast entry from the papillary surface only occurred when keratinocytes were also present.
Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects (1999)

Gangliosides are a family of sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. Although they are the major sialoglycoconjugates in the brain, their neurobiological functions remain poorly defined. By disrupting the gene for a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase; EC 2.4.1.92) we generated mice that express only simple gangliosides (GM3/GD3) and examined their central and peripheral nervous systems. The complex ganglioside knockout mice display decreased central myelination, axonal degeneration in both the central and peripheral nervous systems, and demyelination in peripheral nerves. The pathological features of their nervous system closely resemble those reported in mice with a disrupted gene for myelin-associated glycoprotein (MAG), a myelin receptor that binds to complex brain gangliosides in vitro. Furthermore, GM2/GD2 synthase knockout mice have reduced MAG expression in the central nervous system. These results indicate that complex gangliosides function in central myelination and maintaining the integrity of axons and myelin. They also support the theory that complex gangliosides are endogenous ligands for MAG. The data extend and clarify prior observations on a similar mouse model, which reported only subtle conduction defects in their nervous system [Takamiya, K., Yamamoto, A., Furukawa, K., Yamashiro, S., Shin, M., Okada, M., Fukumoto, S., Haraguchi, M., Takeda, N., Fujimura, K., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 10662-10667].
Reducing Hydration-Linked Events in Nursing Home Residents (2003)

The authors used a quasi-experimental treatment and control group design with 49 participants from four nursing homes to test the effectiveness of an 8-week hydration intervention in reducing hydration-linked events (HLEs). A Kaplan Meier survival curve with log rank test was calculated to determine incidence and time to occurrence of a HLE. Incidence of and time to a HLE did not differ between the treatment and control groups over an 8-week period (p > .05). However, treatment group participants were found to be more frail, more cognitively impaired and more at risk for acute confusion than the control group participants. Although there were no statistically significant differences between the groups, it is clinically significant that the frailer, more at-risk participants in the treatment group had a lower incidence of HLEs.
Pancreas Differentiation of Mouse ES Cells (2007)

This unit describes the derivation of pancreatic cells from mouse embryonic stem cells (ESCs). Mouse ESCs are pluripotent immortal cells derived from the inner cell mass of pre-implantation blastocyst-stage embryos that possess the ability to differentiate into any cell type within the adult animal. In vitro, ESCs can be differentiated into a variety of cell types representing derivatives of the three embryonic germ layers, mesoderm, endoderm, and ectoderm. Successfully differentiating ES cells to pancreatic cells has the potential to provide an alternative to cadaver-derived cells for treatment of type I diabetes. This unit outlines a method for the differentiation of ESCs toward pancreatic endoderm in serum-free medium from embryoid bodies (EBs) formed in suspension or spin EBs. In addition there is a protocol for maintaining ESC.
Flexible Electronics and Displays: High-Resolution, Roll-to-Roll, Projection Lithography and Photoablation Processing Technologies for High-Throughput Production (2005)

Flexible electronics are increasingly being used in a number of applications which benefit from their low profile, light weight, and favorable dielectric properties. However, despite these advantages, the range of practical, high-volume, applications for flexible electronics will remain limited in the future unless a number of challenges related to lithographic patterning on flexible substrates are successfully addressed. The most critical of these pertain to system parameters that affect the cost and performance of flexible circuits, including the resolution, panel size, process throughput, substrate distortion, material handling, and yield. We present a new class of roll-to-roll lithography systems, developed in recent years, that were designed to address the challenges in each of these critical areas. These systems provides high-resolution projection imaging over very large exposure areas, on flexible substrate materials. Additionally, they achieve high-precision alignment by means of image scaling to compensate for substrate distortion due to processing; and they also performs high-throughput photoablation, patterning millions of pixels simultaneously, by means of projection imaging. This technology is attractive for current and emerging applications, such as flexible circuit boards and flexible chip carriers, as well as for potential future applications such as such as flexible displays and macroelectronic systems.
Remdesivir use in pregnancy during the SARS-CoV-2 pandemic (2022)

Remdesivir appears to be safe, well tolerated within our cohort with no cases of recorded adverse reaction.