gebhart/patrepeval huggingface dataset:
Aerosolized Dornase Alfa (rhDNase) for Therapy of Cystic Fibrosis (1995)

The major causes of morbidity and mortality in cystic fibrosis (CF) are the obstruction and damaged airways that result from the accumulation of viscid and infected secretions. Dornase alfa, also called recombinant human DNase I (rhDNase), cleaves extracellular DNA, which is present in inordinately high concentrations in purulent CF airway secretions. Dornase alfa has been found to increase the pourability and reduce the viscoelasticity of CF sputum in vitro and, in an animal model, to increase its mucociliary transportability. Short-term (10-day) Phase I and II clinical trials showed dornase alfa to be safe and effective in improving pulmonary function in clinically stable CF patients with mild to moderate pulmonary disease (FVC > or = 40% of predicted value). A long-term (24-week) Phase IIB clinical trial demonstrated the importance of administering dornase alfa daily to maintain its efficacy. A large-scale, long-term, Phase III clinical trial, consisting of a 24-week double-blind period and a 24-week open-label extension, confirmed these findings and further demonstrated that dornase alfa reduces the incidence of respiratory tract infectious exacerbations requiring parenteral antibiotic therapy. Dornase alfa also decreased the rate of hospitalizations, the number of days missed from work or school, and the frequency of CF-related symptoms. Adverse events were limited to upper airway irritation (i.e., voice alteration, laryngitis, pharyngitis), rash, chest pain, and conjunctivitis. These manifestations generally were mild and transient, and they did not limit the use of dornase alfa. A small proportion (2 to 4%) of patients developed serum antibodies to dornase alfa, but no patient developed anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
Simulasi Pelayanan Teller Di Bank BRI Unit Pasar Baru, Padang (2010)

Bank BRI Unit Pasar Baru merupakan unit yang baru didirikan beberapa bulan belakangan ini. BRI unit ini melayani berbagai transaksi perbankan, diantaranya menabung, penarikan uang, peminjaman bahkan melakukan transfer baik sesama bank BRI maupun ke beberapa bank yang lain. Bank ini didirikan karena banyak nasabah yang berada di sekitar Pasar Baru yang biasanya melakukan transaksi ke BRI Unit Bandar Buat sekarang sudah dapat dilakukan di BRI Unit Pasar Baru. Ini merupakan salah satu langkah dari BRI untuk meningkatkan kualitas pelayanannya kepada masyarakat. Dalam melakukan kegiatan transaksinya bank ini mempunyai dua teller. Kedua teller ini melayani semua jenis transaksi, sehingga teller harus memahami masing-masing sistem dalam setiap jenis transaksi. Berdasarkan keterangan diatas, Hal ini merupakan masalah yang menarik untuk dibahas karena sistem yang ada pada bank ini masih melakukan penyesuaian dalam operasinya dikarenakan bank ini merupakan unit baru dari Bank BRI. Setiap hari bank ini melayani banyak nasabah untuk melakukan transaksi yang berbeda-beda. Jumlah nasabah yang melakukan transaksi tertentu tidak sama setiap harinya, kadang-kadang pada hari tertentu jumlah nasabah yang menabung tinggi, misalnya pada awal bulan dan begitu juga sebaliknya. Oleh karena itu, keadaan yang dinamis seperti ini perlu dilakukan simulasi sistem agar probabilitas atau kemungkinan dari sistem pada setiap harinya dapat ditentukan. Hasil yang diperoleh dari simulasi yang dilakukan Bank BRI Unit Pasar Baru Padang adalah jumlah teller yang dimiliki sekarang yaitu sebanyak 2 teller cukup untuk melayani nasabah Bank BRI untuk wilayah Pasar Baru dan sekitarnya. Hal ini dikarenakan jumlah nasabah yang datang perhari rata-rata 13-14 nasabah, sehingga utilitas masing-masing teller adalah 0.204 pada teller 1 dan 0.221 pada teller 2.
Down-regulation of Skp2 is correlated with p27-associated cell cycle arrest induced by phenylacetate in human prostate cancer cells. (2005)

We have demonstrated that phenylacetate (PA)induced cell cycle arrest in human prostate cancer is mediated by increase of p27. In this study, we further investigated the mechanism of PA-induced p27 expression in prostate cancer cells (LNCaP, androgen-independent LNCaP [AIDL] and PC-3). A striking decrease in Skp2 mRNA and protein expression and reciprocal increase in p27 protein level were observed in three PA-treated prostate cancer cells. Interestingly, reduction of phospho-Akt and up-regulation of p27 mRNA levels were observed only in PC-3 cells. No significant differences were found in phospho-Akt and p27 mRNA levels in LNCaP and AIDL. In vitro ubiquitination assay showed a decreased p27 ubquitination in PA-treated prostate cancer cells. Our results suggest that PA attenuated Skp2 expression, thereby inhibiting ubiquitination and promoting p27 accumulation in all three prostate cancer cell lines. Therapeutic strategies designed to reduce Skp2 may clinically play an important role in the treatment of both androgen-sensitive and hormone-refractory prostate cancer.
ChemInform Abstract: Thieno Compounds. Part 5. Basically Substituted Thieno[2,3‐d]pyrimidines. (1986)

Abstract Durch Umsetzung der entsprechenden 4‐Chlor‐ bzw. 2,4‐Dichlor‐thienopyrimidine mit Aminen nach bekannten Methoden wird eine Vielzahl von Substitutionsprodukten (I) hergestellt.
Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation (2006)

A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. Here we show that this CPG structure can be integrated with reflex circuits to reproduce the reorganization of group I reflex pathways occurring during locomotion. During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. This extensor phase prolongation may occur with or without a resetting of the locomotor cycle, which (according to the model) depends on the degree to which sensory input affects the RG and PF circuits, respectively. The same stimulation delivered during flexion produces a temporary resetting to extension without changing the timing of following locomotor cycles. The model reproduces this behaviour by suggesting that this sensory input influences the PF network without affecting the RG. The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. The results of modelling provide insights into proprioceptive control of locomotion.
Generation of Cytomegalovirus-Specific Human T-Lymphocyte Clones by Using Autologous B-Lymphoblastoid Cells with Stable Expression of pp65 or IE1 Proteins: a Tool To Study the Fine Specificity of the Antiviral Response (2000)

Cytotoxic T lymphocytes (CTLs) play a central role in the control of persistent human cytomegalovirus (HCMV) infection in healthy virus carriers. Previous analyses of the specificity of HCMV-reactive CD8(+) CTLs drawn from in vitro models in which antigen-presenting cells were autologous fibroblasts infected with laboratory HCMV strains have shown focusing of CTL responses against the major tegument protein, pp65. By contrast, the 72-kDa major immediate-early protein (IE1) was identified as a minor target for this response. Here we have studied the fine specificity and T-cell-receptor features of T-cell clones generated against autologous B lymphoblastoid cell lines stably transfected with HCMV cDNA coding for either pp65 or a natural variant of IE1. This strategy allowed efficient generation of T-cell clones against IE1 and pp65 and led to the identification of several new IE1 and pp65 epitopes, including some located in polymorphic regions of IE1. Such an approach may provide relevant information about the characteristics of the CTL response to IE1 and the effect of viral polymorphism on the immune response against HCMV.
Characterizing monoclonal antibody structure by carboxyl group footprinting (2015)

Structural characterization of proteins and their antigen complexes is essential to the development of new biologic-based medicines. Amino acid-specific covalent labeling (CL) is well suited to probe such structures, especially for cases that are difficult to examine by alternative means due to size, complexity, or instability. We present here a detailed account of carboxyl group labeling (with glycine ethyl ester (GEE) tagging) applied to a glycosylated monoclonal antibody therapeutic (mAb). The experiments were optimized to preserve the structural integrity of the mAb, and experimental conditions were varied and replicated to establish the reproducibility of the technique. Homology-based models were generated and used to compare the solvent accessibility of the labeled residues, which include aspartic acid (D), glutamic acid (E), and the C-terminus (i.e., the target probes), with the experimental data in order to understand the accuracy of the approach. Data from the mAb were compared to reactivity measures of several model peptides to explain observed variations in reactivity. Attenuation of reactivity in otherwise solvent accessible probes is documented as arising from the effects of positive charge or bond formation between adjacent amine and carboxyl groups, the latter accompanied by observed water loss. A comparison of results with previously published data by Deperalta et al using hydroxyl radical footprinting showed that 55% (32/58) of target residues were GEE labeled in this study whereas the previous study reported 21% of the targets were labeled. Although the number of target residues in GEE labeling is fewer, the two approaches provide complementary information. The results highlight advantages of this approach, such as the ease of use at the bench top, the linearity of the dose response plots at high levels of labeling, reproducibility of replicate experiments (<2% variation in modification extent), the similar reactivity of the three target probes, and significant correlation of reactivity and solvent accessible surface area.
Development of new crops for industrial raw materials (1984)

Abstract Commercial fats and oils are still used extensively in chemical manufacturing processes, but their fatty acid compositions are limited in variety. An extensive screening program for potential new oilseed crops has led to the discovery of many good sources of new lipid classes and fatty acids. Among them are long‐chain acids ( Crambe, Limnanthes, Lunaria ), medium‐chain acids ( Cuphea, Umbelliferae, Lauraceae ), hydroxy acids ( Lesquerella ), epoxy acids ( Vernonia, Stokesia ), acids with special unsaturation (conjugated; acetylenic; Δ3, Δ5, Δ6, Δ17 monoenes) and liquid wax esters (Simmondsia). Many of these plant species have received further attention in terms of germplasm collection and evaluation; breeding and agronomic studies; and processing and utilization research on oil and byproduct meal. Some have been developed sufficiently for early commercialization. Recent history has shown this last step to be the most difficult. No satisfactory mechanism has been devised as yet to simplify the process of transferring research information on a developed new crop to reach the ultimate goal of sustained, large‐scale commerical production. Close cooperation between governments and private sector institutions, with some financial support, may be required for the first few years to achieve successful commercialization.
Impact of Hormone Replacement Therapy on the Body Mass and Fat Compositions of Menopausal Women: A Cross-Sectional Study (1999)

In this study, HRT seems to be associated with a significant reduction in postmenopausal weight and fat mass gains. This may be an important mechanism by which HRT exerts its beneficial long-term effects on cardiovascular health.
Phase II trial of gemcitabine plus trastuzumab in minimally pretreated HER2 overexpressing metastatic breast cancer (2005)

704 Background: Gemcitabine is an exciting novel deoxcytidine analog demonstrating synergism, when combined with trastuzumab, in human breast cancer cell lines. Trastuzumab plus chemotherapy, has yielded superior ORR, TTP, as well as survival as compared to chemotherapy alone in HER2+ tumors. This study evaluates the clinical activity of gemcitabine administered with trastuzumab in minimally pretreated HER2 amplified MBC. Methods: Eligibility: Pts with HER2 3+ or FISH + tumors, 0–1 prior MBC regimens, bidimensional disease, doxorubicin < 360 mg/m2, and LVEF ≥ 50%. Treatment consisted of gemcitabine 1000 mg/m2 days 1, 8, 15, q28 days in conjunction with 4 mg/kg trastuzumab D1 and then 2 mg/kg for 8 consecutive weeks followed by D1, 8, 15 administration of a q28d schedule with gemcitabine, both continuing until disease progression or toxicity. Results: 40 pts were enrolled between 7–5–01 & 11–19–04 with 33 evaluable for response. Median age is 57. 28 pts were HER2 3+ and 6 FISH+. Sites of metastatic disease included 13 lung, 19 liver, 16 bone, 17 soft tissue; the majority of pts had ≥ 2 metastatic sites of disease. 21 pts had prior adjuvant therapy, 21 pts prior doxorubicin & 26 pts prior taxanes. 19 pts had no prior MBC therapy, 17 pts-1 line, 3 pts ≥ 2 lines of MBC therapy. Clinical benefit rate of 66% was noted with 3 CRs, 8 PRs and 11 with SD. 11 pts progressed and 4 are unevaluable. A median of 3.5 cycles were delivered (range 1 - 14). G 3/4 heme toxicity was notable for neutropenia in 21 pts- accompanied by fever in only 1 pt, thrombocytopenia-5, and anemia-1pt. G 3/4 non-heme toxicity consisted of fatigue-5, pulmonary-4, nausea-4, vomiting-3, and edema-2 pts. Cardiac dysfunction was noted in 1 pt. Median survival was 18.8 mo with a median PFS of 3.9 mo. Conclusion: Gemcitabine plus trastuzumab is safe and well tolerated in minimally pretreated HER2+ MBC pts, the majority of whom were anthracycline and taxane pretreated. This preliminary analysis supports the suggestion of enhanced anti-tumor activity between gemcitabine and trastuzumab, with the preliminary median survival surpassing that expected for either agent alone at this juncture of treatment. Final data to be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Lilly Oncology Genentech, Lilly Oncology Genentech, Lilly Oncology
Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog (1999)

Hair follicles form in prenatal skin and mature in the postnatal period, establishing a growth cycle in 3 phases: telogen (resting), anagen (growth), and catagen (regression). Based on the knowledge that Sonic hedgehog (Shh) expression is necessary for the embryonic development of hair follicles, and that anagen in the postnatal cycling follicle has morphologic similarities to the epithelial invagination process in embryonic skin, we hypothesized that localized, but transient, enhanced expression of the Shh gene in postnatal skin would accelerate initiation of anagen in the hair follicle cycle, with concomitant accelerated hair growth. To assess this concept, an E1(-) adenovirus vector, AdShh, was used to transfer the murine Shh cDNA to skin of postnatal day 19 C57BL/6 mice. The treated skin showed increased mRNA expression of Shh, Patched (the Shh receptor), and Gli1 (a transcription factor in the Shh pathway). In mice receiving AdShh, but not in controls, acceleration into anagen was evident, since hair follicle size and melanogenesis increased and the hair-specific keratin ghHb-1 and the melanin synthesis-related tyrosinase mRNAs accumulated. Finally, C57BL/6 mice showed marked acceleration of the onset of new hair growth in the region of AdShh administration to skin 2 weeks after treatment, but not in control vector-treated or untreated areas. After 6 months, AdShh-treated skin showed normal hair and normal skin morphology. Together, these observations are consistent with the concept that upregulation of Shh activity in postnatal skin functions as a biologic switch that induces resting hair follicles to enter anagen with consequent hair growth.
The Synthesis and Properties of Some Selenopurines and Selenopyrimidines (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis and Properties of Some Selenopurines and SelenopyrimidinesHenry G. MautnerCite this: J. Am. Chem. Soc. 1956, 78, 20, 5292–5294Publication Date (Print):October 1, 1956Publication History Published online1 May 2002Published inissue 1 October 1956https://pubs.acs.org/doi/10.1021/ja01601a037https://doi.org/10.1021/ja01601a037research-articleACS PublicationsRequest reuse permissionsArticle Views383Altmetric-Citations81LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
BMPER Is an Endothelial Cell Regulator and Controls Bone Morphogenetic Protein-4–Dependent Angiogenesis (2008)

Bone morphogenetic proteins (BMPs) are involved in embryonic and adult blood vessel formation in health and disease. BMPER (BMP endothelial cell precursor-derived regulator) is a differentially expressed protein in embryonic endothelial precursor cells. In earlier work, we found that BMPER interacts with BMPs and when overexpressed antagonizes their function in embryonic axis formation. In contrast, in a BMPER-deficient zebrafish model, BMPER behaves as a BMP agonist. Furthermore, lack of BMPER induces a vascular phenotype in zebrafish that is driven by disarray of the intersomitic vasculature. Here, we investigate the impact of BMPER on endothelial cell function and signaling and elucidate its role in BMP-4 function in gain- and loss-of-function models. As shown by Western blotting and immunocytochemistry, BMPER is an extracellular matrix protein expressed by endothelial cells in skin, heart, and lung. We show that BMPER is a downstream target of FoxO3a and consistently exerts activating effects on endothelial cell sprouting and migration in vitro and in vivo. Accordingly, when BMPER is depleted from endothelial cells, sprouting is impaired. In terms of BMPER related intracellular signaling, we show that BMPER is permissive and necessary for Smad 1/5 phosphorylation and induces Erk1/2 activation. Most interestingly, BMPER is necessary for BMP-4 to exert its activating role in endothelial function and to induce Smad 1/5 activation. Vice versa, BMP-4 is necessary for BMPER activity. Taken together, BMPER is a dose-dependent endothelial cell activator that plays a unique and pivotal role in fine-tuning BMP activity in angiogenesis.
Anti-HMGB1 Neutralization Antibody Improves Pain-Related Behavior Induced by Application of Autologous Nucleus Pulposus Onto Nerve Roots in Rats (2011)

HMGB1 appears to play an important role in the development of pain-related behavior induced by the application of nucleus pulposus onto the DRG. HMGB1 from applied nucleus pulposus and actively secreted from macrophages would act as a proinflammatory mediator together with proinflammatory cytokines. HMGB1 blocking therapy might become a new treatment method for neuropathic pain.
High Breakdown Voltage AlGaN–GaN HEMTs Achieved by Multiple Field Plates (2004)

High-voltage Al/sub 0.22/Ga/sub 0.78/N-GaN high-electron mobility transistors have been fabricated using multiple field plates over dielectric passivation layers. The device breakdown voltage was found to increase with the addition of the field plates. With two field plates, the device showed a breakdown voltage as high as 900 V. This technique is easy to apply, based on the standard planar transistor fabrication, and especially attractive for the power switching applications.
Hydrogen Gas Sensing with Networks of Ultrasmall Palladium Nanowires Formed on Filtration Membranes (2010)

Hydrogen sensors based on single Pd nanowires show promising results in speed, sensitivity, and ultralow power consumption. The utilization of single Pd nanowires, however, face challenges in nanofabrication, manipulation, and achieving ultrasmall transverse dimensions. We report on hydrogen sensors that take advantage of single palladium nanowires in high speed and sensitivity and that can be fabricated conveniently. The sensors are based on networks of ultrasmall (<10 nm) palladium nanowires deposited onto commercially available filtration membranes. We investigated the sensitivities and response times of these sensors as a function of the thickness of the nanowires and also compared them with a continuous reference film. The superior performance of the ultrasmall Pd nanowire network based sensors demonstrates the novelty of our fabrication approach, which can be directly applied to palladium alloy and other hydrogen sensing materials.
Ultrasound-mediated gastrointestinal drug delivery (2015)

There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.