gebhart/patrepeval huggingface dataset:
Impurity profile: Significance in Active Pharmaceutical Ingredient (2007)

Various regulatory authorities like ICH, USFDA, Canadian Drug and Health Agency are emphasizing on the purity requirements and the identification of impurities in Active Pharmaceutical Ingredient’s (API’s). Qualification of the impurities is the process of acquiring and evaluating data that establishes biological safety of an individual impurity; thus, revealing the need and scope of impurity profiling of drugs in pharmaceutical research. Identification of impurities is done by variety of Chromatographic and Spectroscopic techniques, either alone or in combination with other techniques. There are different methods for detecting and characterizing impurities with TLC, HPLC, HPTLC, AAS etc . Conventional Liquid Chromatography, particularly, HPLC has been exploited widely in  field of impurity profiling; the wide range of detectors, and stationary phases along with its sensitivity and cost-effective separation have attributed to its varied applications. Among the various Planar Chromatographic Methods; TLC is the most commonly used separation technique, for isolation of impurities; due to its ease of operation and low cost compared to HPLC. An advancement of thin layer chromatography HPTLC, is a well-known technique for the impurity isolation. Headspace GC is one of the most preferred techniques for identification of residual solvents. The advent of hyphenated techniques has revolutionized impurity profiling, by not only separation but structural identification of impurities as well. Among all hyphenated techniques, the most exploited techniques, for impurity profiling of drugs are LC-MS-MS, LC-NMR, LC-NMR-MS, GC-MS, and LC-MS.
A General Practice Study Investigating the Effect of Minocin 50 mg b.d. for 12 Weeks in the Treatment of Acne Vulgaris (1985)

In a multicentre general practice open study, 338 acne sufferers were treated with Minocin 50 mg b.d. (254 for 12 weeks). A highly significant improvement trend (p less than 0.0001) was found following analysis of visual analogue scales measuring (i) severity of acne, (ii) area covered by acne, (iii) number of inflamed lesions, (iv) density of acne lesions. Over all, 79% of patients thought the therapy to be effective or very effective; 70% of patients continued on the same therapy after the study period. Mean first improvement was noted by the patients after 4 1/2 weeks of treatment. One hundred and twenty-two patients had taken prior oxytetracycline therapy, of these, ninety-four (77%) stopped oxytetracycline therapy because of lack of efficacy. After treatment of these oxytetracycline failures with Minocin, a highly significant improvement trend (p less than 0.0001) of acne was again seen. In this group, 75% of patients thought the Minocin therapy to be effective or very effective; 69% continued Minocin therapy after the study period. In all, 74% of patients having received prior oxytetracycline thought that Minocin therapy was better than their previous therapy. Ninety-three patients had received either no previous therapy or topical therapy alone. Once again Minocin treatment resulted in a highly significant improvement trend (p less than 0.0001) in the severity of acne. Seventy six (82%) of these patients thought that Minocin therapy was effective or very effective. A total of 73% of patients continued with Minocin therapy following the study period. Adverse events were noted in 6% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: A multicenter active‐surveillance report (2003)

Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.
Financial impact of a novel pre-eclampsia diagnostic test versus standard practice: a decision-analytic modeling analysis from a UK healthcare payer perspective (2010)

The novel test has the potential to provide substantial cost savings for NHS. Even when the novel test's cost is added to the current cost of care, the benefits exceed the additional cost, driven by the test's ability to reduce the rates of false-positive and false-negative diagnoses compared to current standard of care. Potential study limitations include the use of a pooled average of the individual sensitivities and specificities of currently used tests since no data were available on combination testing, the reliance on clinical trial data versus actual practice, and the use of clinical expert opinion when published data were unavailable.
The Cerebellum in Sagittal Plane—Anatomic-MR Correlation: 2. The Cerebellar Hemispheres (1989)

Thin (5-mm) sagittal high-field (1.5-T) MR images of the cerebellar hemispheres display (1) the superior, middle, and inferior cerebellar peduncles; (2) the primary white-matter branches to the hemispheric lobules including the central, anterior, and posterior quadrangular, superior and inferior semilunar, gracile, biventer, tonsil, and flocculus; and (3) several finer secondary white-matter branches to individual folia within the lobules. Surface features of the hemispheres including the deeper fissures (e.g., horizontal, posterolateral, inferior posterior, and inferior anterior) and shallower sulci are best delineated on T1-weighted (short TR/short TE) and T2-weighted (long TR/long TE) sequences, which provide greatest contrast between CSF and parenchyma. Correlation of MR studies of three brain specimens and 11 normal volunteers with microtome sections of the anatomic specimens provides criteria for identifying confidently these structures on routine clinical MR. MR should be useful in identifying, localizing, and quantifying cerebellar disease in patients with clinical deficits.
Nanowire transistors with ferroelectric gate dielectrics: Enhanced performance and memory effects (2004)

Integration of ferroelectric materials into nanoscale field-effect transistors offers enormous promise for superior transistor performance and also intriguing memory effects. In this study, we have incorporated lead zirconate titanate (PZT) into In2O3 nanowire transistors to replace the commonly used SiO2 as the gate dielectric. These transistors exhibited substantially enhanced performance as a result of the high dielectric constant of PZT, as revealed by a 30-fold increase in the transconductance and a 10-fold reduction in the subthreshold swing when compared to similar SiO2-gated devices. Furthermore, memory effects were observed with our devices, as characterized by a counter-clockwise loop in current-versus-gate-bias curves that can be attributed to the switchable remnant polarization of PZT. Our method can be easily generalized to other nanomaterials systems and may prove to be a viable way to obtain nanoscale memories.
Generating manipulation trajectory using motion harmonics (2015)

This paper presents a novel manipulation trajectory generating algorithm that constructs trajectories from learned motion harmonics and user defined constraints. The algorithm uses functional eigenanalysis to learn motion harmonics from demonstrated motions and then use the motion harmonics to compute the optimal trajectory that resembles the demonstrated motions and also satisfies the constraints. The algorithm has been tested on five real human motion data sets to obtain motion harmonics and then generate motions of each task for a NAO robot. The generated trajectories were compared with the trajectories generated using linear segment with parabolic blend approach and with the Open Motion Planning Library. The approach can also work with motion planners.
Building blocks of pain: the regulation of key molecules in spinal sensory neurones during development and following peripheral axotomy (1999)

The pathways, synapses and molecules involved in pain processing in the newborn are not only required to trigger repair and recuperation but are also involved in the process of forming a mature nervous system. Sensory neurons in the dorsal root ganglion and dorsal horn express a phenomenal array of molecules which contribute to their structural and functional characteristics and many of these are developmentally regulated both pre- and postnatally. In order to understand nociceptive signalling and pain in the neonate we need a clear picture of that regulation. This review concentrates on the changing expression of selected key molecules, receptors and channels in the embryo, neonate and adult, which both characterise the sensory neuron and contribute to its response to painful stimuli in normal and pathological conditions.
Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. (1993)

Krox20 is a zinc finger gene expressed in rhombomeres 3 and 5 during hindbrain development in vertebrates. Mice homozygous for a targeted mutation that deletes the majority of the Krox20 genes, including the zinc finger DNA-binding domain, died shortly after birth. The primary phenotype of the homozygous mutant animals was the loss of rhombomeres 3 and 5. This resulted in fusions of the trigeminal ganglion with the facial and vestibular ganglia, and of the superior ganglia of the glossopharyngeal and vagus nerves. These fusions resulted in a disorganization of the nerve roots of these ganglia as they entered the brain stem. These data demonstrate that Krox20 plays an essential role during development of the hindbrain and associated cranial sensory ganglia in mice.
Insulin and Messenger Ribonucleic Acid Expression of Insulin Receptor Isoforms in Ovarian Follicles from Nonhirsute Ovulatory Women and Polycystic Ovary Syndrome Patients (2004)

Insulin action is mediated by two insulin receptor (IR) isoforms, differing in mitogenic and metabolic function. IR isoform expression might occur in human granulosa cells and could be altered in polycystic ovary syndrome (PCOS) from hyperinsulinemia. To determine the relationship between granulosa cell IR isoform expression and follicular fluid insulin concentration in individual follicles, 18 normal women and seven PCOS patients receiving gonadotropins for in vitro fertilization were studied. Glucose tolerance testing was performed before pituitary desensitization, and fasting serum insulin was measured at oocyte retrieval. Granulosa cells and fluid aspirated from the first follicle were used to determine IR isoform mRNA expression and insulin concentration, respectively. IR isoform A mRNA expression was greater than that of IR isoform B expression in normal mural granulosa and cumulus cells, without a cell type effect. Intrafollicular insulin levels increased with adiposity and serum insulin levels at oocyte-retrieval but did not predict IR mRNA expression. Total IR mRNA expression, but not intrafollicular insulin levels, was elevated in PCOS patients, whereas intrafollicular insulin levels were increased in women with impaired glucose tolerance. Granulosa cell IR heterogeneity, together with adiposity-dependent intrafollicular insulin availability, introduces a novel mechanism by which insulin may affect granulosa cell function within the follicle.
New Technologies in Using Recombinant Attenuated Salmonella Vaccine Vectors (2010)

Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as "factories" to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization.
Thrombin binding to GPIbα induces platelet aggregation and fibrin clot retraction supported by resting αIIbβ3 interaction with polymerized fibrin (2003)

We have investigated the mechanisms leading to platelet aggregation following thrombin interaction with the glycoprotein (GP) Ib-IX-V complex. We show that platelets desensitized for the two thrombin receptors, PAR-1 and PAR-4, are still able to aggregate in response to thrombin and that this aggregation can be inhibited by a monoclonal antibody (VM16d) that blocks thrombin binding to GPIbalpha, or by pretreatment of platelets with Mocarhagin, a protease that specifically cleaves GPIbalpha. The thrombin/GPIbalpha-initiated signaling cascade induces platelet shape change through activation of the Rho kinase p160ROCK, independent of calcium mobilization, transient MEK-1 phosphorylation as well as the cleavage of talin through a calcium-independent mechanism. This signaling cascade does not induce the exposure of high affinity alphaIIbbeta3 integrin receptors, nor does it lead to micro -calpain cleavage of filamin or the integrin cytoplasmic tail. In contrast, we provide evidence that binding of thrombin to GPIbalpha induces fibrin binding to resting alphaIIbbeta3 leading to fibrin-dependent platelet aggregation and clot retraction, that can be selectively inhibited by alphaIIbbeta3 antagonists such as RGDS, the dodecapeptide or lamifiban, as well as by the fibrin polymerization inhibitor GPRP-amide.
Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data (2013)

Changes in cell-surface glycan patterns are markers of the presence of many different disease and cancer types, offering a relatively untapped niche for glycan-targeting reagents and therapeutics in diagnosis and treatment. Of paramount importance for the success of any glycan-targeting reagent is the ability to specifically recognize the target among the plethora of different glycans that exist in the human body. The preeminent technique for defining specificity is glycan array screening, in which a glycan-binding protein (GBP) can be simultaneously screened against multiple glycans. Glycan array screening has provided unparalleled insight into GBP specificity, but data interpretation suffers from difficulties in identifying false-negative binding arising from altered glycan presentation, associated with the linker used to conjugate the glycan to the surface. In this work, we model the structure and dynamics of the linkers employed in the glycan arrays developed by the Consortium for Functional Glycomics. The modeling takes into account the physical presence and surface polarity of the array, and provides a structure-based rationalization of false-negative results arising from the so-called "linker effect." The results also serve as a guide for interpreting glycan array screening data in a biological context; in particular, we show that attempts to employ natural amino acids as linkers may be prone to unexpected artifacts compromising glycan recognition.
Pteridine, XII: Synthese von 2‐Amino‐4‐alkoxy‐pteridinen (1961)

Abstract Die Darstellung verschiedener, in organischen Lösungsmitteln gut löslicher 2‐Amino‐4‐alkoxy‐pteridine wird beschrieben. Durch saure oder alkalische Hydrolyse lassen sie sich leicht in 2‐Amino‐4‐oxo‐dihydropteridine überführen.
Assembly of Severe Acute Respiratory Syndrome Coronavirus RNA Packaging Signal into Virus-Like Particles Is Nucleocapsid Dependent (2005)

The severe acute respiratory syndrome coronavirus (SARS-CoV) was recently identified as the etiology of SARS. The virus particle consists of four structural proteins: spike (S), small envelope (E), membrane (M), and nucleocapsid (N). Recognition of a specific sequence, termed the packaging signal (PS), by a virus N protein is often the first step in the assembly of viral RNA, but the molecular mechanisms involved in the assembly of SARS-CoV RNA are not clear. In this study, Vero E6 cells were cotransfected with plasmids encoding the four structural proteins of SARS-CoV. This generated virus-like particles (VLPs) of SARS-CoV that can be partially purified on a discontinuous sucrose gradient from the culture medium. The VLPs bearing all four of the structural proteins have a density of about 1.132 g/cm(3). Western blot analysis of the culture medium from transfection experiments revealed that both E and M expressed alone could be released in sedimentable particles and that E and M proteins are likely to form VLPs when they are coexpressed. To examine the assembly of the viral genomic RNA, a plasmid representing the GFP-PS580 cDNA fragment encompassing the viral genomic RNA from nucleotides 19715 to 20294 inserted into the 3' noncoding region of the green fluorescent protein (GFP) gene was constructed and applied to the cotransfection experiments with the four structural proteins. The SARS-CoV VLPs thus produced were designated VLP(GFP-PS580). Expression of GFP was detected in Vero E6 cells infected with the VLP(GFP-PS580), indicating that GFP-PS580 RNA can be assembled into the VLPs. Nevertheless, when Vero E6 cells were infected with VLPs produced in the absence of the viral N protein, no green fluorescence was visualized. These results indicate that N protein has an essential role in the packaging of SARS-CoV RNA. A filter binding assay and competition analysis further demonstrated that the N-terminal and C-terminal regions of the SARS-CoV N protein each contain a binding activity specific to the viral RNA. Deletions that presumably disrupt the structure of the N-terminal domain diminished its RNA-binding activity. The GFP-PS-containing SARS-CoV VLPs are powerful tools for investigating the tissue tropism and pathogenesis of SARS-CoV.
Subsets of human natural killer cells and their regulatory effects (2013)

Human natural killer (NK) cells have distinct functions as NK(tolerant) , NK(cytotoxic) and NK(regulatory) cells and can be divided into different subsets based on the relative expression of the surface markers CD27 and CD11b. CD27⁺ NK cells, which are abundant cytokine producers, are numerically in the minority in human peripheral blood but constitute the large population of NK cells in cord blood, spleen, tonsil and decidua tissues. Recent data suggest that these NK cells may have immunoregulatory properties under certain conditions. In this review, we will focus on these new NK cell subsets and discuss how regulatory NK cells may serve as rheostats or sentinels in controlling inflammation and maintaining immune homeostasis in various organs.
LASER AND LED PHOTOBIOLOGY (2010)

Low Level Light Therapy, or LLLT, is a very important new area of photomedicine. However, there are a number of reasons why LLLT has not been accepted into the main stream of science and medicine, and I will discuss a few of them below. Let me add, however, that I know from personal experience that LLLT works on wound healing, and carpal tunnel syndrome, when done properly.I have been trying for over 40 years to teach photobiology to laser people, and more recently, to LED people as well. At a laser meeting in the 1970s, at the height of the feeling that lasers were magical, I made a slide to demonstrate the biological effect of a laser. It showed a man dropping a big laser on his foot, and yelling OUCH. I said that this is the ONLY type of biological effect that a laser can have on a person. A laser is an expensive flashlight, and it is the light produced BY the laser that has a chance of producing a biological effect, assuming that it is of the correct wavelength and output, etc.Because so many bad papers have been published on LLLT, it has not achieved the universal acceptance that that it deserves. There are two main reasons for bad papers on LLLT; one is the lack of proper scientific training by the authors, and the other is their lack of knowledge of photobiology. I will give you some examples of very bad science.
Oncofetal Fibronectin in Diabetic Retinopathy (2003)

Use of a well-established animal model of chronic diabetic complications and cultured endothelial cells showed that diabetes-induced upregulation of oncofetal fibronectin is, in part, dependent on hyperglycemia-induced transforming growth factor-beta1 and endothelin-1. Furthermore, the data suggest that oncofetal fibronectin is involved in endothelial cell proliferation.
Driving CARs on the Highway to Solid Cancer: Some Considerations on the Adoptive Therapy with CAR T Cells (2017)

Adoptive therapy with chimeric antigen receptor (CAR) redirected T cells achieved lasting remissions in hematologic malignancies, even in terminal stages of the disease. Exploring CAR T cell therapy in the treatment of solid tumors has just begun, balancing efficacy versus toxicity in early phase trials. In contrast to leukemia/lymphoma, solid tumors display a tremendously variable biology demanding different strategies to make a T cell attack successful in the long term. This article summarizes current developments, discusses the hurdles, and considers some modifications to improve the CAR T cell therapy in the treatment of solid tumors.
Detection and modeling of fast attack transients (2001)

cote interne IRCAM: Rodet01a
Heteroaromatic Thioether−Boronic Acid Cross-Coupling under Neutral Reaction Conditions (2002)

[reaction: see text] Pi-deficient heteroaromatic thioethers undergo efficient palladium-catalyzed cross-coupling with boronic acids mediated by copper(I) thiophene-2-carboxylate.
Functional Dissection of the Human Bcl2 Protein: Sequence Requirements for Inhibition of Apoptosis (1996)

Overexpression of the cytoplasmic oncoprotein Bcl2 blocks programmed cell death (apoptosis) in many cellular systems. To map the sequences in Bcl2 that are necessary for its activity, we created a library of deletion-scanning mutants of this 239-amino-acid protein and tested their abilities to block staurosporine-induced fibroblast apoptosis, using a novel transient-transfection assay. Phenotypes of informative mutants were then confirmed by assaying for inhibition of steroid-induced apoptosis in stably transfected T-lymphoid cells. In accordance with earlier results, we found that Bcl2 activity was only partially reduced after deletion of the hydrophobic tail that normally anchors it in cytoplasmic membranes. Essential sequences were found in the remainder of the protein and appeared to be organized in at least two discrete functional domains. The larger, more C-terminal region (within residues 90 to 203) encompassed, but extended beyond, two oligopeptide motifs called BH1 and BH2, which are known to mediate dimerization of Bcl2 and related proteins. The second, more N-terminal regions (within residues 6 to 31) was not required for protein dimerization in vivo, but its deletion imparted a dominant negative phenotype, yielding mutants that promoted rather than inhibited apoptotic death. Residues 30 to 91 were not absolutely required for function; by deleting most of this region along with the hydrophobic tail, we derived a 155-residue mini-Bcl2 that retains significant ability to inhibit apoptosis.