gebhart/patrepeval huggingface dataset:
An introduction to pharmaceutical sciences : production, chemistry, techniques and technology (2011)

This textbook is written as a unified approach to various topics, ranging from drug discovery to manufacturing, techniques and technology, regulation and marketing. The key theme of the book is pharmaceuticals - what every student of pharmaceutical sciences should know: from the active pharmaceutical ingredients to the preparation of various dosage forms along with the relevant chemistry, this book makes pharmaceuticals relevant to undergraduate students of pharmacy and pharmaceutical sciences.This book explains how a particular drug was discovered and then converted from lab-scale to manufacturing scale, to the market. It explains the motivation for drug discovery, the reaction chemistry involved, experimental difficulties, various dosage forms and the reasoning behind them, mechanism of action, quality assurance and role of regulatory agencies. After having a course based on this book, the student will be able to understand: 1) the career prospects in the pharmaceutical industry, 2) the need for interdisciplinary teamwork in science, 3) the techniques and technology involved in making pharmaceuticals starting from bulk drugs, and 4) different dosage forms and critical factors in the development of pharmaceutical formulations in relation to the principles of chemistry.A few blockbuster drugs including atorvastatin, sildanefil, ranitidine, ciprofloxacin, amoxicillin, and the longest serving drugs such as aspirin and paracetamol are discussed in detail. Finally, the book also covers the important current pharmaceutical issues like quality control, safety, counterfeiting and abuse of drugs, and future prospects for pharmaceutical industry.Unified approach explaining drug discovery, bulk drug manufacturing, formulation of dosage forms, with pharmacological and therapeutic actionsManufacturing processes of representative active pharmaceutical ingredients and their chemistry plus formulation of dosage forms presented in this book are based on actual industrial processesCovers many aspects relevant to students of the pharmaceutical sciences or newly employed pharmaceutical researchers/employees. It contains summary information about regulatory agencies of different countries
Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity (2014)

Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells vastly outperformed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. After intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced antitumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4(+) T cell activation associated with a higher intratumoral CD4/CD8 cell ratios and CD28-dependent CD4(+) T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication, or persistence. The ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through "regional distribution centers." On the basis of these results, we are opening a phase 1 clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies.
Polycyclic aromatic hydrocarbon mutagenesis of human epidermal keratinocytes in culture. (1984)

We have developed a culture system for detecting and isolating rare hypoxanthine phosphoribosyltransferase-deficient mutants of human epidermal keratinocytes. A thioguanine-resistant variant, 3T3M1, of the Swiss mouse fibroblast line 3T3 was used as a feeder layer to support clonal growth of mutant keratinocytes. A near-diploid, epidermal squamous cell carcinoma line, SCC-13Y, was used as a prototype to determine mutagen treatment conditions, plating density, and phenotypic expression time for maximum mutant recovery. To extend this system to normal keratinocytes, we improved the culture conditions by adding insulin, adenine, and Ham's nutrient mixture F-12, which increased colony-forming efficiencies to 30% in early passage and made feasible the detection of rare mutants in normal epidermal keratinocyte populations. We have quantitated mutation in SCC-13Y and three strains of normal human epidermal keratinocytes after exposure to polycyclic aromatic hydrocarbons, which are activated to their mutagenic forms by cellular mixed-function oxidases. 7,12-Dimethylbenz[a]anthracene and benzo[a]pyrene caused almost no cytotoxicity, but induced thioguanine-resistant mutants at frequencies as much as 50-fold higher than the spontaneous frequency of approximately 10(-6). The mutants were aminopterin-sensitive and possessed no measurable hypoxanthine phosphoribosyltransferase activity; their behavior was indistinguishable from that of keratinocytes cultured from individuals with Lesch-Nyhan syndrome. This mutagenesis assay system should also be applicable to other feeder layer-dependent human epithelial cell types, such as urothelial, mammary, and tracheal epithelial cells.
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. (1993)

The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.
The Changing Role of Radiation Therapy in the Treatment of Primary Breast Cancer (1989)

The role of radiation in the management of breast cancer has seen extraordinary change in the past 15 years. The primary treatment of early breast cancer once required mastectomy. Today, a local tumor excision followed by postoperative radiation is an established alternative of equal efficacy. Postoperative chest wall and/or lymphatic irradiation was once nearly routine following mastectomy; later, as adjuvant chemotherapy came into widespread use, its usage declined markedly. Today however, evidence is mounting that the addition of postoperative radiation to adjuvant chemotherapy and surgery can improve local-regional control and survival in selected subsets of these patients. In unresectable breast cancer, radiation was once the primary modality of treatment. Today it is part of a combined modality approach attempting to reduce these patients' high rates of both distant and local-regional failure.
Treatment of painful diabetic neuropathy (2014)

Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists.
Improvements to the switched parametric and transform audio coder (2003)

We introduce improvements to previous sines+transients+noise audio modeling systems, including new sinusoidal trajectory selection and quantization procedures. In a previous work by Levine and Smith (see Proc. Int. Conf. Acoustics, Speech, and Signal Processing, Phoenix, 1999), the audio is first segmented into transient and non-transient regions. The transient region is modeled using traditional transform coding techniques, while the non-transient regions are modeled using parametric sines plus noise modeling. Because such a system contains a mix of parametric and non-parametric techniques, compressed-domain processing such as time-scale modifications are possible.
Identification of Targetable ALK Rearrangements in Pancreatic Ductal Adenocarcinoma (2017)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (<i>ALK</i>) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with <i>ALK</i>-rearranged tumors. However, <i>ALK</i> translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0.16%) that harbored an <i>ALK</i> fusion gene: an exon 6 <i>EML4</i>-exon 20 <i>ALK</i> translocation (n=3), an exon 13 <i>EML4-</i>exon 20 <i>ALK</i> translocation (n=1), and an exon 3 <i>STRN</i>-exon 20 <i>ALK</i> translocation (n=1). Among the most prevalent PDAC-related genes, activating <i>KRAS</i> mutations were absent in all 5 cases, who were <50 years of age. Among patients aged <50 years in our study cohort, <i>ALK</i> translocations constituted 1.3% of PDACs. Four of 5 patients were treated with an ALK inhibitor, and 3 of these patients demonstrated stable disease, radiographic response, and/or normalization of serum CA 19-9. Although rare, <i>ALK</i> fusions occur in PDAC, and screening for <i>ALK</i> rearrangements should be considered in young patients with PDAC.
Transitions (2004)

The astute reader of this issue of TRANSFUSION will note some significant changes to the journal masthead. I had the unpleasant task of accepting the resignation of Margot Kruskall, MD, from her position of associate editor recently. Margot has reluctantly decided to leave her position because of health reasons. Margot has worked diligently as an associate editor for many years, beginning her service in 1997. At the time of her initial appointment, she became the first woman to serve as an associate editor. She is the founding editor of our Transfusion Medicine Illustrated (TMI) feature and is largely responsible for the colorful and thought-provoking images that grace our pages. These illustrated vignettes are being collected into a TRANSFUSION annual calendar that subscribers will soon receive on a yearly basis. In view of Margot's inspired work as an associate editor and her role in initiating the TMI feature and the calendar, the editors have elected to honor her by dedicating the first calendar to Dr Margot Kruskall. We are fortunate that Nancy M. Heddle, MSc, FCSMLS(D), of McMaster University in Hamilton, Ontario, Canada, has accepted a position as associate editor. Anyone following the evolving literature in transfusion medicine and the increasing number of evidence-based clinical trials will be aware of Nancy Heddle's contributions to these fields as an investigator and author. We are delighted that she is willing to bring her expertise to the review of manuscripts for TRANSFUSION in the areas of clinical and laboratory investigation and anticipate that the journal will continue to grow in stature with her increased involvement. It is also noteworthy that Nancy is the first international associate editor that has served TRANSFUSION. We believe that this action is fitting in view of the fact that 50 percent of the manuscripts received by the journal come from countries other than the United States and the acceptance rates for US and non-US manuscripts are nearing equivalence. We are expanding the number of associate editors by the addition of Jay E. Menitove, MD, to our roster. Dr Menitove has been a significant contributor to the journal as a reviewer, author, and editorialist. I expect that he will bring strength to our editorial expertise in the areas of transfusion-transmitted disease, coagulation, and blood center operations. He has also served the AABB in multiple notable roles as a member of the Board of Directors and chair of the Standards Program Committee. He is currently Executive Director and Medical Director of the Community Blood Center of Greater Kansas City. Although transitions are never easy, we are privileged to have a strong editorial board and an involved and committed readership to support these necessary changes. As always, the associate editors welcome your suggestions about how we can improve TRANSFUSION and look forward to bringing you more pages with diversified topics in the coming year.
A universal image quality index (2002)

We propose a new universal objective image quality index, which is easy to calculate and applicable to various image processing applications. Instead of using traditional error summation methods, the proposed index is designed by modeling any image distortion as a combination of three factors: loss of correlation, luminance distortion, and contrast distortion. Although the new index is mathematically defined and no human visual system model is explicitly employed, our experiments on various image distortion types indicate that it performs significantly better than the widely used distortion metric mean squared error. Demonstrative images and an efficient MATLAB implementation of the algorithm are available online at http://anchovy.ece.utexas.edu//spl sim/zwang/research/quality_index/demo.html.
Self-Inactivating Lentiviral Vectors with Enhanced Transgene Expression as Potential Gene Transfer System in Parkinson's Disease (2000)

Glial cell line-derived neurotrophic factor (GDNF) is able to protect dopaminergic neurons against various insults and constitutes therefore a promising candidate for the treatment of Parkinson's disease. Lentiviral vectors that infect quiescent neuronal cells may allow the localized delivery of GDNF, thus avoiding potential side effects related to the activation of other brain structures. To test this hypothesis in a setting ensuring both maximal biosafety and optimal transgene expression, a self-inactivating (SIN) lentiviral vector was modified by insertion of the posttranscriptional regulatory element of the woodchuck hepatitis virus, and particles were produced with a multiply attenuated packaging system. After a single injection of 2 microl of a lacZ-expressing vector (SIN-W-LacZ) in the substantia nigra of adult rats, an average of 40.1 +/- 6.0% of the tyrosine hydroxylase (TH)-positive neurons were transduced as compared with 5.0 +/- 2.1% with the first-generation lentiviral vector. Moreover, the SIN-W vector expressing GDNF under the control of the mouse phosphoglycerate kinase 1 (PGK) promoter was able to protect nigral dopaminergic neurons after medial forebrain bundle axotomy. Expression of hGDNF in the nanogram range was detected in extracts of mesencephalon of animals injected with an SIN-W-PGK-GDNF vector, whereas it was undetectable in animals injected with a control vector. Lentiviral vectors with enhanced expression and safety features further establish the potential use of these vectors for the local delivery of bioactive molecules into defined structures of the central nervous system.
Intestinal Oxalobacter formigenes Colonization in Calcium Oxalate Stone Formers and Its Relation to Urinary Oxalate (2003)

Calcium oxalate stone formers have a low rate of colonization with O. formigenes. Among stone formers, absence of intestinal Oxalobacter correlates with higher urinary oxalate concentration and an increased risk of hyperoxaluria. Introduction of the Oxalobacter bacterium or an analog of its enzyme oxalyl-CoA decarboxylase into the intestinal tract may be a treatment for calcium oxalate stone disease.
DESIGNER SOLVENTS (1998)

RETURN TO ISSUEPREVNewsNEXTDESIGNER SOLVENTSIonic liquids may boost clean technology developmentMICHAEL FREEMANTLECite this: Chem. Eng. News 1998, 76, 13, 32–37Publication Date (Print):March 30, 1998Publication History Published online16 November 2010Published inissue 30 March 1998https://pubs.acs.org/doi/10.1021/cen-v076n013.p032https://doi.org/10.1021/cen-v076n013.p032newsACS PublicationsCopyright © 1998 AMERICAN CHEMICAL SOCIETYArticle Views212Altmetric-Citations648LEARN 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 options SUBJECTS:Solvents Get e-Alerts
Upregulation of Heat Shock Proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in Tumour Tissues Is Associated with Poor Outcomes from HBV-Related Early-Stage Hepatocellular Carcinoma (2015)

The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.
INTERACTIONS OF GONOCOCCI WITH PHAGOCYTIC CELLS (1989)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Influence of Ionic Interactions on the Crystallization of Lightly Sulfonated Syndiotactic Polystyrene Ionomers (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of Ionic Interactions on the Crystallization of Lightly Sulfonated Syndiotactic Polystyrene IonomersE. Bruce Orler and Robert B. MooreCite this: Macromolecules 1994, 27, 17, 4774–4780Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ma00095a018https://doi.org/10.1021/ma00095a018research-articleACS PublicationsRequest reuse permissionsArticle Views405Altmetric-Citations55LEARN 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
Ovarian Cancer Gene Therapy Using HPV-16 Pseudovirion Carrying the HSV-tk Gene (2012)

Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.