gebhart/patrepeval huggingface dataset:
Epicardium and Myocardium Separate From a Common Precursor Pool by Crosstalk Between Bone Morphogenetic Protein– and Fibroblast Growth Factor–Signaling Pathways (2009)

Our data show that FGF signaling via Mek1/2 is dominant over BMP signaling via Smad and is required to separate the epicardial lineage from precardiac mesoderm. Consequently, myocardial differentiation requires BMP signaling via Smad and inhibition of FGF signaling at the level of Mek1/2. These findings are of clinical interest for the development of regeneration-based therapies for heart disease.
Differentiation of ES cells into cerebellar neurons (2007)

The neuronal circuits of the cerebellar cortex are essential for motor and sensory learning, associative memory formation, and the vestibular ocular reflex. In children and young adults, tumors of the granule cell, the medulloblastomas, represent 40% of brain tumors. We report the differentiation of E14 ES cells into mature granule neurons by sequential treatment with secreted factors (WNT1, FGF8, and RA) that initiate patterning in the cerebellar region of the neural tube, bone morphogenic proteins (BMP6/7 and GDF7) that induce early granule cell progenitor markers (MATH1, MEIS1, ZIC1), mitogens (SHH, JAG1) that control proliferation and induce additional granule cell markers (Cyclin D2, PAX2/6), and culture in glial-conditioned medium to induce markers of mature granule neurons (GABAalpha(6)r), including ZIC2, a unique marker for granule neurons. Differentiated ES cells formed classic "T-shaped" granule cell axons in vitro, and implantation of differentiated Pde1c-Egfp-BAC transgenic ES cells into the external granule cell layer of neonatal mice resulted in the extension of parallel fibers, migration across the molecular layer, incorporation into the internal granule cell layer, and extension of short dendrites, typical of young granule cells forming synaptic connections with afferent mossy fibers. These results underscore the utility of treating ES cells with local, inductive signals that regulate CNS neuronal development in vivo as a strategy for cell replacement therapy of defined neuronal populations.
Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes (2001)

This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.
Generation of Rituximab Polymer May Cause Hyper-Cross-linking–Induced Apoptosis in Non-Hodgkin's Lymphomas (2005)

Abstract Purpose: Although Rituximab has produced significant tumor regressions in lymphoma patients, only 50% respond. Clinically, it has been shown that the major mechanism of action of Rituximab is antibody-dependent cytotoxicity requiring presentation by Fc-bearing cells. To improve the clinical efficacy of Rituximab for the treatment of CD20+ lymphomas, we now describe a new formulation of Rituximab, which, on direct binding to target, can induce apoptosis. Methods: In this report, enhanced apoptosis was observed by treating CD20+ lymphoma cells with a new polymer formulation of Rituximab. The polymer was produced by formation of a peptide bond using the sugar moiety of dextran (MW 6,000) to generate a clinically relevant reagent for use in vivo. Results: Comparison of Rituximab with a previously described dimer and the newly generated polymer shows that the polymer induced apoptosis more effectively in CD20+ cells as shown by the terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay (Rituximab, 3%; dimer, 3%; polymer, 58%). Consistent with these results, the polymer produced marked regression in CD20+ lymphoma xenografts, whereas the dimer and monomer reagents showed little effect. In addition, we were able to show that the level of apoptosis induced in human lymphoma cell lines was in accordance with the extent of both surface CD20 clustering and caspase-3 activation. Conclusions: These data suggest that hyper-cross-linking–induced apoptosis can be simulated by the use of a dextran polymer of Rituximab, which, when used in vivo, can directly kill CD20+ lymphoma cells and improve the clinical efficacy of this important therapeutic for human B-cell lymphomas.
Liposomes: Clinical Applications and Potential for Image-Guided Drug Delivery (2018)

Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties.
Sickle cell disease: old discoveries, new concepts, and future promise (2007)

The discovery of the molecular basis of sickle cell disease was an important landmark in molecular medicine. The modern tools of molecular and cellular biology have refined our understanding of its pathophysiology and facilitated the development of new therapies. In this review, we discuss some of the important advances in this field and the impediments that limit the impact of these advances.
Frequency-dependent refractive index of one-dimensionally structured thick metal film (2007)

The authors have studied the frequency-dependent dielectric response of thick metal film one-dimensionally perforated by a subwavelength slit waveguide array. Our theoretical approach based on a three-dimensional homogenization of the periodic metallic structure shows that an effective refractive index chromatically varying due to TE waveguide mode formation gives rise to dense Fabry-Pérot resonance population near the cutoff, which leads to an energy level continuum in the transmission spectrum. Finite difference time domain simulation numerically demonstrates the transmission spectrum and spatial field distributions of even and odd resonance modes.
Studies on the composition and structure of plasma lipoproteins. Distribution of lipoprotein families in major density classes of normal human plasma lipoproteins. (1972)

Abstract To account for the protein heterogeneity of lipoprotein preparations isolated by ultracentrifugal or precipitation techniques, we have proposed a classification system [P. Alaupovic et al., Circulation, 30, Suppl. III (1964) 1; P. Alaupovic, Prog. Biochem. Pharmacol., 4 (1968) 91; P. Alaupovic et al., Expo. Annu. Biochim. Med., 31 (1972)] of plasma lipoproteins based on apolipoproteins as the only distinct chemical components for the differentiation of lipoprotein families. At the present time this concept recognizes the existence of three lipoprotein families, each of which is characterized by the exclusive presence of a single apolipoprotein: lipoprotein family A (LP-A) is characterized by the presence of apolipoprotein A (ApoA), lipoprotein family B (LP-B) by apolipoprotein B (ApoB) and lipoprotein family C (LP-C) by apoliprotein C (ApoC). The qualitative distribution of lipoprotein families in normal human plasma very low density lipoproteins (VLDL, d The LP-A and LP-C families were detected in all lipoprotein density classes; the LP-B family was also present in all classes except the HDL3. Results of the immunological and electrophoretic experiments supported the existence of lipoprotein families as the basic components of plasma lipoprotein system and indicated that lipoprotein families exist above a density range of approximately 1.006-1.019 g/ml as individual separable entities, while at densities less than this range lipoprotein families are present primarily as associations.
Hypothyroidism and Atherosclerosis (2003)

This autopsy finding of diffuse atherosclerosis in a 58-yrold woman was published as an appendix to William Ord’s classical description of the syndrome of myxedema. Soon thereafter, the hypothesis of a causal relationship between hypothyroidism and atherosclerosis was first raised in 1883 by E. Theodor Kocher (2), who noted that arteriosclerosis commonly occurred after thyroid extirpation. Since the time of the first associations between these two common disorders, hypothyroidism and atherosclerosis have subsequently been linked by a body of clinical case reports, epidemiological studies, and biochemical observations. The hypothesis of a relationship has subsequently been tested in case-control and cohort studies. Important associations have been identified among hypercholesterolemia, hypertension, and certain newer risk factors for atherosclerosis in individuals with overt hypothyroidism and, in some cases, subclinical hypothyroidism. There have also been clinical observations and trials describing the consequences of treating hypothyroidism in patients with ischemic heart disease and of revascularizing patients with ischemic heart disease who are hypothyroid. These studies are the subject of this commentary.
Delivering drugs by the transdermal route: review and comment (2008)

To discuss the various ways in which drugs can be persuaded to cross the skin barrier and also to discuss the adverse effects of transdermal administration. Technical advances have permitted an increasing number of drugs to be offered in the transdermal format.
ChemInform Abstract: SYNTHESIS OF HETEROCYCLIC COMPOUNDS INVOLVING REACTIONS OF INDAN‐1‐ONES (1984)

Abstract Aus den Indanonen (I) werden über die Oxime (II) die Indandione (III) hergestellt, die mit den Diaminen (IV) zu den Tetracyclen (V) cyclisiert werden.
Synthesis of different nucleoside 5′‐diphospho‐sulfoquinovoses and their use for studies on sulfolipid biosynthesis in chloroplasts (1989)

6-Sulfo-alpha-D-quinovopyranosyl phosphate was reacted with different nucleoside monophosphate morpholidates to form ADP-, CDP-, GDP- and UDP-sulfoquinovose. Analytical and preparative HPLC of these nucleotides was performed on reversed-phase columns using volatile buffer systems as eluant. The isolated compounds were characterized by NMR spectroscopy (except the CDP derivative) and used for an investigation of sulfolipid biosynthesis by chloroplasts. For this purpose intact spinach chloroplasts were biosynthetically preloaded with radioactive diacylglycerol to provide a sulfoquinovosyl acceptor. When sulfosugar nucleotides were added to such prelabelled intact organelles, the background levels of sulfolipid biosynthesis did not rise. On the other hand, after osmotic shock of prelabelled chloroplasts sulfolipid labelling was significantly increased by the addition of UDP- or GDP-sulfoquinovose. The same stimulation was observed with isolated envelope membranes, and UDP-sulfoquinovose proved to be twice as active as the GDP derivative. From these results it was concluded that the final step in sulfolipid biosynthesis is catalyzed by a UDP-sulfoquinovose: 1,2-diacylglycerol 3-O-alpha-D-sulfoquinovosyltransferase. This chloroplast enzyme cannot use exogenously supplied sulfosugar nucleotides, which as membrane-impermeable compounds are expected to be formed in vivo within chloroplasts.
Individual chaperones required for Yop secretion by Yersinia. (1994)

Pathogenic yersiniae secrete anti-host proteins called Yops, by a recently discovered Sec-independent pathway. The Yops do not have a classical signal peptide at their N terminus and they are not processed during membrane translocation. The secretion domain is nevertheless contained in their N-terminal part but these domains do not resemble each other in the different Yops. We have previously shown that YopE secretion requires SycE, a 15-kDa acidic protein acting as a specific cytosolic chaperone. Here we show that the gene downstream from yopH encodes a 16-kDa acidic protein that binds to hybrid proteins made of the N-terminal part of YopH and either the bacterial alkaline phosphatase or the cholera toxin B subunit. Loss of this protein by mutagenesis led to accumulation of YopH in the cytoplasm and to a severe and selective reduction of YopH secretion. This protein thus behaves like the counterpart of SycE and we called it SycH. We also engineered a mutation in lcrH, the gene upstream from yopB and yopD, known to encode a 19-kDa acidic protein. Although this mutation was nonpolar, the mutant no longer secreted YopB and YopD. The product of lcrH could be immunoprecipitated together with cytoplasmic YopD. lcrH therefore seems to encode a YopD-specific chaperone, which we called SycD. Determination of the dependence of YopB on SycD requires further investigation. SycE, SycH, and SycD appear to be members of a new family of cytosolic chaperones required for Yop secretion.
<title>Sounding rocket payload designed for investigations of the distribution and dynamics of the hot component of the interstellar medium using a field-widened spatial heterodyne spectrometer</title> (1995)

We are developing a field-widened spatial heterodyne spectrometer (SHS) for suborbital observations of the hot component of the diffuse interstellar medium. Our goal for these observations is to obtain the first velocity-resolved (20 km/s) line profiles of the C IV 154.8, 5.1 nm emission line from the Cygnus loop and from one direction at high galactic latitude. Long term, our interest is to develop an SHS instrument for a radial-velocity-resolved sky survey of the 10<SUP>5</SUP> K 'coronal gas' in the interstellar medium using a small satellite. This paper reviews the scientific motivation and SHS concept and then discusses in more detail the optical design of the sounding rocket payload and the data taking strategy for the observations.
Survival, Persistence, and Progressive Differentiation of Adoptively Transferred Tumor-Reactive T Cells Associated with Tumor Regression (2005)

Objective clinical responses have been observed in approximately 50% of patients who received non-myeloablative chemotherapy prior to the adoptive transfer of autologous melanoma-reactive tumor-infiltrating lymphocytes (TILs). Recent studies carried out through the use of antibodies directed against T-cell-receptor beta chain variable region (TRBV) products, as well as by direct sequencing of the expressed TRBV gene products, indicated that clinical responses in this trial were associated with the level of persistence of adoptively transferred T cells. In an attempt to further characterize T cells that persist in vivo following adoptive transfer, five dominant T-cell clonotypes were identified in TIL 2035, an adoptively transferred TIL that was associated with the complete regression of multiple metastases. The most highly persistent clonotype, which expressed the BV1 TR gene product, recognized the MAGE-6 cancer/testis antigen in the context of HLA-A23. This clonotype was detected in peripheral blood for over 16 months following adoptive transfer, expressed relatively higher levels of the co-stimulatory markers CD28 and CD27, and possessed telomeres that were long relative to other clonotypes present in TIL 2035 that showed only short-term persistence. The long-term persistent BV1 clonotype appeared to differentiate more slowly toward an end-stage effector in vivo than short-term persistent clonotypes, as manifested by the downregulation of CD28, CD27, and CD45RO and upregulation of CD57 and CD45RA expression on these T cells. These results indicated that the differentiation stage and replicative history of individual TIL clonotypes might be associated with their ability to survive and to persist in vivo, and progressive differentiation of the persistent clonotypes occurred following adoptive transfer.
Association of HTRA1 Mutations and Familial Ischemic Cerebral Small-Vessel Disease (2009)

CARASIL is associated with mutations in the HTRA1 gene. Our findings indicate a link between repressed inhibition of signaling by the TGF-beta family and ischemic cerebral small-vessel disease, alopecia, and spondylosis.
The pharmacologic treatment of Dravet syndrome (2011)

Dravet syndrome (DS) is one of the most pharmacoresistant epilepsy syndromes. Valproate is used as a first-line agent to prevent the recurrence of febrile seizures and oral/nasal/rectal benzodiazepine is used for any long-lasting seizures, but these agents are most often insufficient. Lamotrigine, carbamazepine, and high doses of intravenous phenobarbital should be avoided because they may worsen seizures. Topiramate, levetiracetam, bromide, and the ketogenic diet may provide substantial efficacy as adjunctive therapy/procedure. Stiripentol is the only compound that proved its efficacy in DS through two independent randomized placebo-controlled trials, when combined with valproate and clobazam. Their dose has to be decreased to minimize the side effects (mostly loss of appetite) resulting from pharmacokinetic interactions of stiripentol powerfully inhibiting cytochromes P450. Stiripentol acts as a γ-aminobutyric acid (GABA)ergic agent, mainly via the α3 subunit of GABA(A) receptors. Stiripentol (Diacomit) was approved as an orphan drug in 2007 in Europe for adjunctive therapy in DS. Up to now, >500 children have been safely treated, and recent experiment in Japan confirmed stiripentol benefit in DS children with comedications other than valproate and clobazam. Because early status epilepticus is likely to negatively impact cognitive outcome, we recommend the introduction of stiripentol as soon as the diagnosis of DS is clinically confirmed. Topiramate and the ketogenic diet are alternatives in pharmacoresistant cases.
Developing Next-Generation Brain Sensing Technologies—A Review (2019)

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients.
A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty. M-HEART Group. (1990)

A multicenter, double-blind, placebo-controlled trial was conducted to determine if corticosteroids influence the development of restenosis after successful percutaneous transluminal coronary angioplasty (PTCA). Either placebo or 1.0 g methylprednisolone (steroid) was infused intravenously 2-24 hours before planned PTCA in 915 patients. The PTCA patient success rate was 87% (mean) in the eight centers. There were no differences in clinical or angiographic baseline variables between the two groups. End-point analysis (angiographic restenosis, death, recurrent ischemia necessitating early restudy, and coronary artery bypass graft surgery) showed that there was no significant difference comparing placebo- with steroid-treated patients. Angiographic restudy showed the lesion restenosis rate to be 39% (120 of 307 lesions) after placebo and 40% (117 of 291) after steroid treatment (p = NS). We conclude that pulse steroid pretreatment does not influence the overall restenosis rate after successful PTCA.
Streptonigrin and lavendamycin partial structures. Probes for the minimum, potent pharmacophore of streptonigrin, lavendamycin, and synthetic quinoline-5,8-diones (1987)

The preparation and evaluation of 7-amino-5,8-dioxo-2-(2'-pyridyl)quinoline-6'-carboxylic acid (5a) and 7-amino-2-(2'-aminophenyl)-5,8-dioxoquinoline-5'-carboxylic acid (6a) constituting potential minimum, potent pharmacophores of streptonigrin (1a) and lavendamycin (2a), two structurally related naturally occurring antitumor antibiotics, are detailed. In contrast to observations associated with streptonigrin and lavendamycin in which the C-ring C-6' carboxylic acid potentiates the antitumor, antimicrobial, and cytotoxic properties of the naturally occurring, substituted 7-aminoquinoline-5,8-dione AB ring systems, the C-6'/C-5' carboxylic acid of 5a/6a diminishes the observed antimicrobial and cytotoxic properties of the 2-(2'-pyridyl)- and 2-(2'-aminophenyl)-7-aminoquinoline-5,8-diones. A direct comparison of the antimicrobial and cytotoxic properties of a complete set of streptonigrin and lavendamycin partial structures is detailed in efforts to define the role peripheral substituents play in potentiating the biological properties of the naturally occurring and synthetic agents bearing the 7-aminoquinoline-5,8-dione AB ring system and in efforts to define the minimum, potent pharmacophore of the naturally occurring antitumor antibiotics. The relationship of these observations to a chemical mechanism of cellular toxicity is discussed.
A multimedia and multisource document editor of an open architecture (1992)

Two of the recent developments in electronic documents are multimedia and hypermedia systems. Current multimedia systems are limited because they can not contain general third-party media in their documents. Hypermedia systems can only link documents together and cannot merge documents into compound documents.To overcome these limitations, we have implemented a prototype editor to create documents on the X Window system. Not only it opens a door for general third-party media tools to be integrated in documents, but it also allows users to compose compound documents with other documents. The corresponding metaphor for the manipulation of included media is fold-and-paste. The folded media are clipped by viewports and displayed by live processes that operate on the original copies. The key technique used to provide these functions is embedded virtual screens. With the simple and powerful mechanism of embedded virtual screens, our editor is a multimedia and multisource document editor of an open architecture with regard to containing general media in its compound documents. it expands the capability in composing multimedia documents and it provides a simple mechanism to create documents that share some information with each other.