gebhart/patrepeval huggingface dataset:
Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. (1993)

Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease over 27 years in one hospital. Altogether 739 patients (422 with Crohn's disease, 284 with ulcerative colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of 12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine of whom it was severe (white blood count < 2.0 x 10(9)/l). Of these nine patients, three were pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet count < 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe. Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years after starting the drug) and occurred either suddenly or over several months. Bone marrow suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is potentially severe. Leucopenia is the commonest and most important haematological complication. Regular monitoring of the full blood count is recommended during treatment.
Controlled growth of GaN nanowires by pulsed metalorganic chemical vapor deposition (2005)

Controlled and reproducible growth of GaN nanowires is demonstrated by pulsed low-pressure metalorganic chemical vapor deposition. Using self-assembled Ni nanodots as nucleation sites on (0001) sapphire substrates we obtain nanowires of wurtzite-phase GaN with hexagonal cross sections, diameters of about 100nm, and well-controlled length. The nanowires are highly oriented and perpendicular to the growth surface. The wires have excellent structural and optical properties, as determined by x-ray diffraction, cathodoluminescence, and Raman scattering. The x-ray measurements show that the nanowires are under a complex strain state consistent with a superposition of hydrostatic and biaxial components.
CDC 45 is required in conjunction with CDC 7/ DBF 4 to trigger the initiation of DNA replication (1997)

The initiation of DNA replication in Saccharomyces cerevisiae requires the protein product of the CDC45 gene. We report that although Cdc45p is present at essentially constant levels throughout the cell cycle, it completes its initiation function in late G1, after START and prior to DNA synthesis. Shortly after mitosis, cells prepare for initiation by assembling prereplicative complexes at their replication origins. These complexes are then triggered at the onset of S phase to commence DNA replication. Cells defective for CDC45 are incapable of activating the complexes to initiate DNA replication. In addition, Cdc45p and Cdc7p/Dbf4p, a kinase implicated in the G1/S phase transition, are dependent on one another for function. These data indicate that CDC45 functions in late G1 phase in concert with CDC7/DBF4 to trigger initiation at replication origins after the assembly of the prereplicative complexes.
Spatially Distinct Functional Output Regions within the Central Nucleus of the Inferior Colliculus: Implications for an Auditory Midbrain Implant (2007)

The inferior colliculus central nucleus (ICC) has potential as a new site for an auditory prosthesis [i.e., auditory midbrain implant (AMI)] for deaf patients who cannot benefit from cochlear implants (CIs). We have previously shown that ICC stimulation achieves lower thresholds, greater dynamic ranges, and more localized, frequency-specific primary auditory cortex (A1) activation than CI stimulation. However, we also observed that stimulation location along the caudorostral (isofrequency) dimension of the ICC affects thresholds and frequency specificity in A1, suggesting possible differences in functional (output) organization within the ICC. In this study, we electrically stimulated different regions along the isofrequency laminas of the ICC and recorded the corresponding A1 activity in ketamine-anesthetized guinea pigs using multisite probes to systematically assess ICC stimulation location effects. Our results indicate that stimulation of more rostral and somewhat ventral regions within an ICC lamina achieves lower thresholds, smaller discriminable level steps, and larger evoked potentials in A1. We also observed longer first spike latencies, which correlated with reduced spiking precision, when stimulating in more caudal and dorsal ICC regions. These findings suggest that at least two spatially distinct functional output regions exist along an ICC lamina: a caudal-dorsal region and a rostral-ventral region. The AMI will be implanted along the tonotopic axis of the ICC to achieve frequency-specific activation. However, stimulation location along the ICC laminas affects response properties that have shown to be important for speech perception performance, and needs to be considered when implanting future AMI patients.
Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells (2009)

In thalassemia and other iron loading anemias, ineffective erythropoiesis and erythroid signaling molecules are thought to cause inappropriate suppression of a small peptide produced by hepatocytes named hepcidin. Previously, it was reported that the erythrokine GDF15 is expressed at very high levels in thalassemia and suppresses hepcidin expression. In this study, erythroblast expression of a second molecule named twisted gastrulation (TWSG1) was explored as a potential erythroid regulator of hepcidin. Transcriptome analyses suggest TWSG1 is produced during the earlier stages of erythropoiesis. Hepcidin suppression assays demonstrated inhibition by TWSG1 as measured by quantitative polymerase chain reaction (PCR) in dosed assays (1-1000 ng/mL TWSG1). In human cells, TWSG1 suppressed hepcidin indirectly by inhibiting the signaling effects and associated hepcidin up-regulation by bone morphogenic proteins 2 and 4 (BMP2/BMP4). In murine hepatocytes, hepcidin expression was inhibited by murine Twsg1 in the absence of additional BMP. In vivo studies of Twsg1 expression were performed in healthy and thalassemic mice. Twsg1 expression was significantly increased in the spleen, bone marrow, and liver of the thalassemic animals. These data demonstrate that twisted gastrulation protein interferes with BMP-mediated hepcidin expression and may act with GDF15 to dysregulate iron homeostasis in thalassemia syndromes.
An Equivalent Circuit Model of the Traveling Wave Electrode for Carrier-Depletion-Based Silicon Optical Modulators (2012)

We propose an equivalent circuit model for the coplanar waveguide (CPW) which serves as the traveling wave electrode to drive carrier-depletion-based silicon modulators. Conformal mapping and partial capacitance techniques are employed to calculate each element of the circuit. The validity of the model is confirmed by the comparison with both finite-element simulation and experimental result. With the model, we calculate the modulation bandwidth for different CPW dimensions and termination impedances. A 3 dB modulation bandwidth of 15 GHz is demonstrated with a traveling wave electrode of 3 mm. The calculation indicates that, by utilizing a traveling wave electrode of 2 mm, we can obtain a 3 dB modulation bandwidth of 28 GHz.
Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8+ Cytolytic T Cell Responses (2016)

Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy.
Encapsulation of oligonucleotides in stealth Me.PEG-PLA50nanoparticles by complexation with structured oligopeptides (1996)

Two oligopeptides with alternating hydrophilic-hydrophobic amino acids, H-(leu-lys-lys-leu)10-OH and H-(leu-lys-leu-lys)10-OH, were shown to have higher affinity for a 13-mer oligonucleotide than H-(pro-lys-lys-leu)10-OH used as a control. This increased affinity was correlated to the secondary structure adopted by the oligopeptides (respectively, α-helix and β-sheet for LKKL and LK) when complexed to the oligonucleotide. Tight ion-pairing association between the phosphate groups of the oligonucleotide and the lysines of the oligopeptide led to efficient encapsulation of the resulting oligonucleotide/oligopeptide non-water-soluble complex in hydrophobic Me.PEG-PLA50 nanoparticles, by coprecipitation with the co-polymer.
Measurement of Factors Affecting Crop Production (1985)

This paper is concerned with characterizing the effect that environmental and induced factors have on crop yields. In this sense, a framework is outlined which can be used to estimate the characteristics of the probability distribution function (pdf) of crop yields which may not be normal or log-normal as usually is assumed. The paper is methodological in nature, but several pieces of empirical work are being done under the sponsorship of the Utah Experiment Station, particularly modeling alfalfa yield response to changes in pest control and environmental factors which influence alfalfa yields. The methodological framework developed here is in the spirit of recent work completed by Heck, et a1. (1982,1983,1984) and Adams, et al. (1984) in the area of environmental factor impacts on crop yields, and the doseresponse modeling of Rawlings and Cure (1983).
Guidelines for management of atopic dermatitis (2009)

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease characterized by pruritus and inflammation and accompanied by cutaneous physiological dysfunction (dry and barrier-disrupted skin). Most of the patients have atopic diathesis. A standard guideline for the management (diagnosis, severity classification and therapy) of AD has been established. In our guideline, the necessity of dermatological training is emphasized in order to assure diagnostic skill and to enable evaluation of the severity of AD. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution; and (iii) chronic and chronically relapsing course. For the severity classification of AD, three elements of eruption (erythema/acute papules, exudation/crusts and chronic papules/nodules/lichenification) are evaluated in the most severely affected part of each of the five body regions (head/neck, anterior trunk, posterior trunk, upper limbs and lower limbs). The areas of eruption on the five body regions are also evaluated, and both scores are totaled (maximum 60 points). The present standard therapies for AD consist of the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation, topical application of emollients to treat the cutaneous physiological dysfunction, systemic antihistamines and anti-allergic drugs as adjunctive treatments for pruritus, avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. Tacrolimus ointment (0.1%) and its low-density ointment (0.03%) are available for adult patients and 2-15-year-old patients, respectively. The importance of the correct selection of topical corticosteroids according to the severity of the eruption is also emphasized. Furthermore, deliberate use of oral cyclosporine for severe recalcitrant adult AD is referred.
Structure-activity relationships of the diuretic activity of triaza- and tetraaza-naphthalene compounds. (1976)

The diuretic activity of 219 nitrogen containing heterocyclic compounds, classified into 13 groups based on the structural features, was studied on the saline loaded rats. One hundred and four out of the 219 compounds were active at the oral doses of 10 to 30 mg/kg. Several of pyrimidopyridazines, pyridazinopyridazines and pyridopyridazines produced as potent diuresis and natriuresis as hydrochlorothiazide at the oral dose of 0.1 mg/kg, in which 2-phenyl-5, 8-dimorpholinopyrimido [4, 5-d]-pyridazine (DS-210) and 1, 4-dimorpholino-7-phenylpyrido [3, 4-d] pyridazine (DS-511) were selected for more extensive evaluation as diuretic agents. Structure-activity relationships of the tested compounds are discussed.
IDDM patients' opinions on the use of glucagon emergency kit in severe episodes of hypoglycaemia (1997)

Abstract This study investigated the coping strategies of IDDM patients with mild and severe episodes of hypoglycaemia. One hundred and two IDDM patients, aged 4–62 years old, 59% male and 41% female, were interviewed by telephone using a structured questionnaire. Most of the patients recognised the symptoms of hypoglycaemia and accordingly treated their mild episodes with either Coca Cola or fruit juice (61%), sweets (32%), milk (26%), or a slice of bread (23%). Forty two per cent of the patients treated themselves with additional chocolate, fruit or honey. While 83% of the patients reported that they had received an explanation regarding the use of the glucagon emergency kit, only 60% actually owned it. In only 19% of the patients who had ever experienced a severe episode of hypoglycaemia had this mode of treatment actually been used. Most of the patients (67%) said they would prefer the intranasal route if available and 82% assumed that the people surrounding them would prefer to administer an intranasal spray or drops in emergency hypoglycaemic situations. We conclude that only in a small percentage of patients is subcutaneous or intramuscular glucagon used in an emergency situation, and speculate that other modes of glucagon administration such as the intranasal route would increase the use of glucagon and prevent some of the IDDM patients from waiting for the emergency paramedic teams or from being referred to hospitals.
Herpes simplex virus type 1 ICP8: helix-destabilizing properties (1993)

The major single-stranded DNA-binding protein, ICP8, of herpes simplex virus type 1 (HSV-1) is one of seven virus-encoded polypeptides required for HSV-1 DNA replication. To investigate the role of ICP8 in viral DNA replication, we have examined the interaction of ICP8 with partial DNA duplexes and found that it can displace oligonucleotides annealed to single-stranded M13 DNA. In addition, ICP8 can melt small fragments of fully duplex DNA. Unlike a DNA helicase, ICP8-promoted strand displacement is ATP and Mg2+ independent and exhibits no directionality. It requires saturating amounts of ICP8 and is both efficient and highly cooperative. These properties make ICP8 suitable for a role in DNA replication in which ICP8 destabilizes duplex DNA during origin unwinding and replication fork movement.
Induced early expression ofmrf4but notmyogrescues myogenesis in themyod/myf5double-morphant zebrafish embryo (2009)

Muscle regulatory factors activate myogenesis in all vertebrates, but their role has been studied in great detail only in the mouse embryo, where all but myogenin--Myod, Myf5 and Mrf4--are sufficient to activate (albeit not completely) skeletal myogenesis. In the zebrafish embryo, myod and myf5 are required for induction of myogenesis because their simultaneous ablation prevents muscle development. Here we show that mrf4 but not myog can fully rescue myogenesis in the myod/myf5 double morphant via a selective and robust activation of myod, in keeping with its chromatin-remodelling function in vitro. Rescue does not happen spontaneously, because the gene, unlike that in the mouse embryo, is expressed only at the onset of muscle differentiation, Moreover, because of the transient nature of morpholino inhibition, we were able to investigate how myogenesis occurs in the absence of a myotome. We report that in the complete absence of a myotome, subsequent myogenesis is abolished, whereas myogenesis does proceed, albeit abnormally, when the morpholino inhibition was not complete. Therefore our data also show that the early myotome is essential for subsequent skeletal muscle differentiation and patterning in the zebrafish.
DNA released from ischemic and rejecting organs as an indicator of graft cellular damage. (2004)

Donor cellular debris contains fragments of nuclei with genetic material. The question arises whether the amount of donor graft released DNA accumulating in the recipient lymphoid tissues after transplantation could be a measure of donor organ damage caused by ischemia and preservation as well as rejection. We found that donor heart passenger cells do not contribute to the DNA disseminated in the recipient. All donor DNA was, then, derived from the damaged graft cells. Immediately and 1 day after transplantation, it was present in blood (plasma and cells) to accumulate later in the spleen. Higher values of donor DNA in the syngeneic than allogeneic combination, most evident on day 7, were presumably due to better perfusion of graft not undergoing rejection. Immunosuppression attenuated donor DNA release and accumulation in recipient tissues, nevertheless, relatively high concentrations could still be detected. Further studies are in progress on the usefulness of measuring DNA concentration for evaluation of the graft damage.
Using Sequence Package Analysis as a New Natural Language Understanding Method for Mining Government Recordings of Terror Suspects (2006)

Three years after 9/11, the Justice Department made the astounding revelation that more than 120,000 hours of potentially valuable terrorismrelated recordings had yet to be transcribed. Clearly, the government’s efforts to obtain such recordings have continued. Yet there is no evidence that the contents of the recorded calls have been analyzed any more efficiently. Perhaps analysis by conventional means would be of limited value in any event. After all, terror suspects tend to avoid words that might alarm intelligence agents, thus “outsmarting” conventional mining programs, which heavily rely on wordspotting techniques. One solution is the application of a new natural language understanding method, known as Sequence Package Analysis, which can transcend the limitations of basic parsing methods by mapping out the generic conversational sequence patterns found in the dialog. The purpose of this paper is show how this new method can efficiently mine a large volume of government recordings of the conversations of terror suspects – with the goal of reducing the backlog of unanalyzed calls.
Use of Type I Collagen Green Fluorescent Protein Transgenes to Identify Subpopulations of Cells at Different Stages of the Osteoblast Lineage (2002)

Green fluorescent protein (GFP)-expressing transgenic mice were produced containing a 3.6-kilobase (kb; pOBCol3.6GFPtpz) and a 2.3-kb (pOBCol2.3GFPemd) rat type I collagen (Col1a1) promoter fragment. The 3.6-kb promoter directed strong expression of GFP messenger RNA (mRNA) to bone and isolated tail tendon and lower expression in nonosseous tissues. The 2.3-kb promoter expressed the GFP mRNA in the bone and tail tendon with no detectable mRNA elsewhere. The pattern of fluorescence was evaluated in differentiating calvarial cell (mouse calvarial osteoblast cell [mCOB]) and in marrow stromal cell (MSC) cultures derived from the transgenic mice. The pOBCol3.6GFPtpz-positive cells first appeared in spindle-shaped cells before nodule formation and continued to show a strong signal in cells associated with bone nodules. pOBCol2.3GFPemd fluorescence first appeared in nodules undergoing mineralization. Histological analysis showed weaker pOBCol3.6GFPtpz-positive fibroblastic cells in the periosteal layer and strongly positive osteoblastic cells lining endosteal and trabecular surfaces. In contrast, a pOBCol2.3GFPemd signal was limited to osteoblasts and osteocytes without detectable signal in periosteal fibroblasts. These findings suggest that Col1a1GFP transgenes are marking different subpopulations of cells during differentiation of skeletal osteoprogenitors. With the use of other promoters and color isomers of GFP, it should be possible to develop experimental protocols that can reflect the heterogeneity of cell differentiation in intact bone. In primary culture, this approach will afford isolation of subpopulations of these cells for molecular and cellular analysis.
Highly Protective In Vivo Function of Cytomegalovirus IE1 Epitope-Specific Memory CD8 T Cells Purified by T-Cell Receptor-Based Cell Sorting (2005)

Reconstitution of antiviral CD8 T cells is essential for controlling cytomegalovirus (CMV) infection after bone marrow transplantation. Accordingly, polyclonal CD8 T cells derived from BALB/c mice infected with murine CMV protect immunocompromised adoptive transfer recipients against CMV disease. The protective population comprises CD8 T cells with T-cell receptors (TCRs) specific for defined and for as-yet-unknown viral epitopes, as well as a majority of nonprotective cells with unrelated specificities. Defined epitopes include IE1/m123 and m164, which are immunodominant in terms of the magnitude of the CD8 T-cell response, and a panel of subordinate epitopes (m04, m18, M45, M83, and M84). While cytolytic T-lymphocyte lines (CTLLs) were shown to be protective regardless of the immunodominance of the respective epitope, the individual contributions of in vivo resident epitope-specific CD8 T cells to the antiviral control awaited investigation. The IE1 peptide 168-YPHFMPTNL-176 is generated from the immediate-early protein 1 (IE1) (pp89/76) of murine CMV and is presented by the major histocompatibility complex class I (MHC-I) molecule Ld. To quantitate its contribution to the protective potential of a CD8-T memory (CD8-TM) cell population, IE1-TCR+ and IE1-TCR- CD8-TM cells were purified by epitope-specific cell sorting with IE1 peptide-loaded MHC-immunoglobulin G1 dimers as ligands of cognate TCRs. Of relevance for clinical approaches to an adoptive cellular immunotherapy, sorted IE1 epitope-specific CD8-TM cells were found to be exceedingly protective upon adoptive transfer. Compared with CTLLs specific for the same epitope and of comparable avidity and TCR beta-chain variable region (Vbeta)-defined polyclonality, sorted CD8-TM cells proved to be superior by more than 2 orders of magnitude.