gebhart/patrepeval huggingface dataset:
Hsp90 as a Gatekeeper of Tumor Angiogenesis: Clinical Promise and Potential Pitfalls (2010)

Tumor vascularization is an essential modulator of early tumor growth, progression, and therapeutic outcome. Although antiangiogenic treatments appear promising, intrinsic and acquired tumor resistance contributes to treatment failure. Clinical inhibition of the molecular chaperone heat shock protein 90 (Hsp90) provides an opportunity to target multiple aspects of this signaling resiliency, which may elicit more robust and enduring tumor repression relative to effects elicited by specifically targeted agents. This review highlights several primary effectors of angiogenesis modulated by Hsp90 and describes the clinical challenges posed by the redundant circuitry of these pathways. The four main topics addressed include (1) Hsp90-mediated regulation of HIF/VEGF signaling, (2) chaperone-dependent regulation of HIF-independent VEGF-mediated angiogenesis, (3) Hsp90-dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and (4) consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90-targeted strategies.
The basic domain/leucine zipper protein hXBP-1 preferentially binds to and transactivates CRE-like sequences containing an ACGT core (1996)

The transcription factor hXBP-1 belongs to the family of basic region/leucine zipper (bZIP) proteins and interacts with the cAMP responsive element (CRE) of the major histocompatibility complex (MHC) class II A alpha, DR alpha and DP beta genes. However, the developmental expression of hXBP-1 as revealed by in situ hybridization in mouse embryos, has suggested that it interacts with the promoter of additional genes. To identify other potential target genes of this factor, we performed binding site selection experiments with recombinant hXBP-1 protein. The results indicated that hXBP-1 binds preferably to the CRE-like element GAT-GACGTG(T/G)NNN(A/T)T, wherein the core sequence ACGT is highly conserved, and that it also binds to some TPA response elements (TRE). hXBP-1 can transactivate multimers of the target sequences to which it binds in COS cells, and the level of transactivation directly correlates with the extent of binding as observed in gel retardation experiments. One target sequence that is strongly bound by hXBP-1 is the 21 bp repeat in the HTLV-1 LTR, and we demonstrate here that hXBP-1 can transactivate the HTLV-1 LTR. Further, the transactivation domain of hXBP-1 encompasses a large C-terminal region of the protein, containing domains rich in glutamine, serine and threonine, and proline and glutamine residues, as shown in transient transfection experiments using hXBP-1-GAL4 fusion proteins and a reporter gene under the control of GAL4-binding sites.
Highly Sensitive and Multiplexed Protein Imaging With Cleavable Fluorescent Tyramide Reveals Human Neuronal Heterogeneity (2021)

The ability to comprehensively profile proteins in intact tissues <i>in situ</i> is crucial for our understanding of health and disease. However, the existing methods suffer from low sensitivity and limited sample throughput. To address these issues, here we present a highly sensitive and multiplexed <i>in situ</i> protein analysis approach using cleavable fluorescent tyramide and off-the-shelf antibodies. Compared with the current methods, this approach enhances the detection sensitivity and reduces the imaging time by 1-2 orders of magnitude, and can potentially detect hundreds of proteins in intact tissues at the optical resolution. Applying this approach, we studied protein expression heterogeneity in a population of genetically identical cells, and performed protein expression correlation analysis to identify co-regulated proteins. We also profiled >6,000 neurons in a human formalin-fixed paraffin-embedded (FFPE) hippocampus tissue. By partitioning these neurons into varied cell clusters based on their multiplexed protein expression profiles, we observed different sub-regions of the hippocampus consist of neurons from distinct clusters.
Illumination of the Malaria Parasite Plasmodium falciparum Alters Intracellular pH (2002)

Live cell fluorescence microscopy has been widely used to study physiological processes in the human malarial parasite Plasmodium falciparum, including pH homeostasis, Ca(2+) signaling and protein targeting. However, the reproducibility of the data is often poor. Controversial statements exist regarding cytosolic and vacuolar baseline pH, as well as regarding the subcellular localization of some of the fluorochromes used. When trying to reproduce published baseline values, we observed an unexpected light sensitivity of P. falciparum, which manifests itself in the form of a strong cytoplasmic acidification. Even short exposure times with moderate to low light intensities caused the parasite cytosol to acidify. We show that this effect arises from the selective disruption of the parasite's acidic food vacuole, brought about by lipid peroxidation initiated by light-induced generation of hydroxyl radicals. Our data suggest that heme serves as a photosensitizer in this process. Our findings have major implications for the use of live cell microscopy in P. falciparum and add a cautionary note to previous studies where live cell fluorometry has been used to determine physiological parameters in P. falciparum.
Circulating Tumor DNA as Biomarkers for Cancer Detection (2017)

Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ctDNA detection in various types of cancers has been attracting much attention, due to the great potential of ctDNA as blood-based biomarkers for early diagnosis and treatment of cancers. ctDNAs are detected and tracked primarily based on tumor-related genetic and epigenetic alterations. In this article, we reviewed the available studies on ctDNA detection and described the representative methods. We also discussed the current understanding of ctDNAs in cancer patients and their availability as potential biomarkers for clinical purposes. Considering the progress made and challenges involved in accurate detection of specific cell-free nucleic acids, ctDNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use.
Olanzapine Treatment of Children, Adolescents, and Adults with Pervasive Developmental Disorders (1999)

This pilot study examined the efficacy and tolerability of olanzapine in the treatment of children, adolescents, and adults with pervasive developmental disorders (PDDs). Eight patients with principal diagnoses (DSM-IV) of autistic disorder (N = 5) or PDD not otherwise specified (N = 3) were given olanzapine in an open-label, prospective fashion for 12 weeks. Clinical ratings were obtained at baseline and at the end of weeks (EOWs) 4, 8, and 12. Seven of eight patients completed the 12-week trial, and six of the completers were deemed clinical responders as measured by ratings at the EOW 12 of "much improved" or "very much improved" on the global improvement item of the Clinical Global Impression Scale. Significant improvements in overall symptoms of autism, motor restlessness or hyperactivity, social relatedness, affectual reactions, sensory responses, language usage, self-injurious behavior, aggression, irritability or anger, anxiety, and depression were observed. Significant changes in repetitive behaviors were not observed for the group. The EOW 12 mean +/- SD daily dose of olanzapine was 7.8 +/- 4.7 mg/day. The drug was well tolerated with the most significant adverse effects noted to be increased appetite and weight gain in six patients and sedation in three. With respect to weight gain, the mean +/- SD weight for the group increased from 137.50 +/- 55.81 pounds (62.50 +/- 25.37 kilograms) at baseline to 155.94 +/- 55.13 pounds (70.88 +/- 25.06 kilograms) at EOW 12. No evidence of extrapyramidal side effects or liver function abnormalities was seen. These preliminary results suggest that olanzapine may be an effective and well tolerated drug in targeting core and related symptoms of PDDs in children, adolescents, and adults. Further studies, particularly those that are placebo-controlled and double-blinded, are indicated to better define the clinical use of olanzapine in these patient populations.
ChemInform Abstract: Synthesis of 4‐Substituted Prolines as Conformationally Constrained Amino Acid Analogues. (1989)

Abstract The N‐protected amino acid esters (I) are alkylated to produce the diastereomeric esters (III) and (IV).
Semliki Forest virus vectors for gene therapy (2003)

Semliki Forest virus (SFV) vectors transduce a broad range of mammalian and non-mammalian cells, generating high levels of transient expression of heterologous proteins. Generally, they induce apoptosis in mammalian host cells, leading to rapid cell death. These features have made SFV attractive for various gene therapy applications. Recombinant particles, naked RNA and plasmid DNA containing SFV replicons, demonstrate a strong immune response against recombinantly expressed proteins, which has shown protection against tumour challenges. Intratumoural injection of SFV particles has resulted in tumour regression. SFV vectors have been used for production of retrovirus-like particles. Recently, encapsulation of SFV particles into liposomes has generated highly efficient targeting to tumours. Novel SFV vectors based on point mutations in the non-structural genes, and avirulent SFV strains, have further widened the application range.
Multiprocessor system verification through behavioral modeling and simulation (2002)

The long development times and high costs of multiprocessor (MP) designs arise from their design complexity. To reduce the time and costs, it is critical that design bugs are detected early in the development cycle using design verification tools. The traditional method of hardware design verification is to simulate the actual hardware designs, usually specified in a hardware description language such as VHDL. Two major drawbacks of this methodology when applied to MP systems are the huge size of MP models and the long simulation times. In addition to the difficulty of detecting incorrect behavior in hardware cache coherent systems, MP system verification presents many other challenges as well. In this paper we present a MP verification methodology that lets the actual hardware designs coexist with behavioral models that approximate the functional behavior of the designs they represent. We describe an event-driven behavioral simulation engine that drives the entire simulation, an MP test language, a test executive that injects new transactions into the system, and a coherence monitor that helps detect quickly and efficiently coherency-related bugs in hardware designs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Selecting Patients With Atrial Fibrillation for Anticoagulation (2004)

Patients with AF who have high and low rates of stroke when given aspirin can be reliably identified, allowing selection of antithrombotic prophylaxis to be individualized.
Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery (2011)

Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation of complexation, internalization, and delivery trends that could only be learned through evaluation of a large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery. Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells. Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups and potential buffering capacity. Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice. The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications.
Therapeutic peptides and proteins : formulation, processing, and delivery systems (2006)

Pharmaceutical Biotechnology: The Arrival of Recombinant Proteins What is Biotechnology The Biotechnology Industry Regulatory Aspects of Biotechnology-Derived Drugs Immunogenicity of Proteins Structure-Based Drug Design Conclusions Structure and Analysis of Therapeutic Peptides and Proteins Amino Acids: Building Blocks of Proteins Structure of Peptides and Proteins Protein Conformation and Other Structural Features Analytical Methods Conclusions Stability of Therapeutic Peptides and Proteins Introduction Physical Instability Chemical instability Well-Characterized Products and Comparability Protocols Conclusions Preformulation and Formulation of Therapeutic Peptides and Proteins Introduction Preformulation Studies Formulation Development Pharmaceutical Excipients in Formulations Aggregation in Protein Formulations Novel Formulation Approaches Accelerated Stability Testing Statistical Design for Formulation Development Conclusions Lyophilization, Pharmaceutical Processing, and Handling of Therapeutic Peptides and Proteins Introduction Protein Destabilization Induced by Pharmaceutical Processing Lyophilization as a Pharmaceutical Process Alternative Pharmaceutical Processes Handling of Therapeutic Peptides and Proteins Conclusions Parenteral Controlled Delivery and Pharmacokinetics of Therapeutic Peptides and Proteins Introduction Pharmacokinetics of Peptide and Protein Drugs Polymers Used for Controlled Delivery of Peptides and Proteins Parenteral Controlled Release Systems Innovations in Parenteral Administration of Proteins Examples of Protein Pharmacokinetics Conclusions Oral Delivery of Peptide and Protein Drugs Introduction Barriers to Protein Absorption and Pathways of Penetration Approaches to Improve Oral Delivery Methods to Study Oral Absorption Oral Immunization Conclusions Transdermal and Topical Delivery of Therapeutic Peptides and Proteins Introduction Skin Structure Approaches to Enhance Transdermal Peptide Delivery Iontophoresis Topical Delivery of Therapeutic Peptides and Proteins Conclusions Pulmonary and Other Mucosal Delivery of Therapeutic Peptides and Proteins Introduction Pulmonary Delivery Nasal Delivery Rectal Delivery Buccal Delivery Ocular Delivery Comparative Evaluation of Mucosal Routes Conclusions Recombinant Protein Subunit Vaccines and Delivery Methods Introduction Immunology Relevant to Vaccines Routes of Administration Delivery Approaches for Administration of Vaccines Case example: Hepatitis B Future Outlook and Regulatory Status Conclusions
Endotracheal temperature and humidity in laryngectomized patients in a warm and dry environment and the effect of a heat and moisture exchanger (2010)

In a warm and dry environment, both R- and F-HME significantly cool and humidify inspired air. Therefore, consistent use of an HME under these climate conditions is also probably clinically beneficial.
Enhanced FASP (eFASP) to Increase Proteome Coverage and Sample Recovery for Quantitative Proteomic Experiments (2014)

The integrity of quantitative proteomic experiments depends on the reliability and the robustness of the protein extraction, solubilization, and digestion methods utilized. Combinations of detergents, chaotropes, and mechanical disruption can yield successful protein preparations; however, the methods subsequently required to eliminate these added contaminants, in addition to the salts, nucleic acids, and lipids already in the sample, can result in significant sample losses and incomplete contaminant removal. A recently introduced method for proteomic sample preparation, filter-aided sample preparation (FASP), cleverly circumvents many of the challenges associated with traditional protein purification methods but is associated with significant sample loss. Presented here is an enhanced FASP (eFASP) approach that incorporates alternative reagents to those of traditional FASP, improving sensitivity, recovery, and proteomic coverage for processed samples. The substitution of 0.2% deoxycholic acid for urea during eFASP digestion increases tryptic digestion efficiency for both cytosolic and membrane proteins yet obviates needed cleanup steps associated with use of the deoxycholate sodium salt. For classic FASP, prepassivating Microcon filter surfaces with 5% TWEEN-20 reduces peptide loss by 300%. An express eFASP method uses tris(2-carboxyethyl)phosphine and 4-vinylpyridine to alkylate proteins prior to deposition on the Microcon filter, increasing alkylation specificity and speeding processing.
Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy (2018)

Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. Here, we will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy.
The Bromodomain: A New Target in Emerging Epigenetic Medicine (2015)

The bromodomain (BrD) is a conserved protein modular domain found in many chromatin- and transcription-associated proteins that has the ability to recognize acetylated lysine residues. This activity allows bromodomains to play a vital role in many acetylation-mediated protein-protein interactions in the cell, ranging from substrate recruitment for histone acetyltransferases (HATs) to aiding in multiple-protein complex assembly for gene transcriptional activation or suppression in chromatin. In recent years, considerable efforts have been made to develop chemical inhibitors of these bromodomains in an effort to probe their cellular functions. Potent and selective inhibitors have been extensively developed for one group of the bromodomain family termed BET proteins that consist of tandem bromodomains followed by an extra terminal domain. Drug developers are actively designing inhibitors of other bromodomains and working to move the most successful inhibitors into the clinic.
Antigenicity of Murine Skin Tumors Induced by Ultraviolet Light2 (1974)

Journal Article Antigenicity of Murine Skin Tumors Induced by Ultraviolet Light Get access Margaret L. Kripke Margaret L. Kripke 3University of Utah College of Medicine, Department of Pathology, Salt Lake City, Utah 84132. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1333–1336, https://doi.org/10.1093/jnci/53.5.1333 Published: 01 November 1974 Article history Received: 07 May 1974 Accepted: 10 July 1974 Published: 01 November 1974
Polypeptides of Pneumonia Virus of Mice. II. Characterization of the Glycoproteins (1989)

The kinetics of synthesis and the nature of the oligosaccharides of the glycoproteins of pneumonia virus of mice (PVM) were studied. Tryptic peptide mapping showed that the two major glycosylated polypeptides G1 and G2 were different forms of the same protein. G2 was derived from G1 which in turn appeared to be derived from an unidentified precursor. The G1/G2 protein of PVM is probably a haemagglutinin since a monoclonal antibody directed against it has a high haemagglutination inhibition titre. On the basis of experiments with inhibitors and glycosidases it was deduced that G1 and G2 have both N-linked and O-linked oligosaccharides. The putative fusion protein-equivalent of PVM was shown to possess N-linked oligosaccharides. In the presence of tunicamycin a high mobility form (F1t) appeared to be derived from a precursor (F0t) with the same mobility as the fully glycosylated protein. If by analogy with other paramyxoviruses this represents a cleavage event, the difference in mobility of the precursor and product suggests that the putative F2 product is smaller than the corresponding F2 protein of other paramyxoviruses. However, no F2 candidate protein was detected and evidence for an F1,2 dimer was inconclusive. The glycoproteins of PVM resemble those of respiratory syncytial virus in terms of their pattern of glycosylation, but differ in their processing.
A genome-wide DNA methylation study in colorectal carcinoma (2011)

Our genome-wide methylation study in CRC clearly supports most of the previous findings; additionally we found a large number of novel DML in CRC tissue. If confirmed in future studies, these findings may lead to identification of genomic markers for potential clinical application.
Some Heterocyclic Thiosemicarbazones (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome Heterocyclic ThiosemicarbazonesFloyd E. Anderson, Charles J. Duca, and John V. ScudiCite this: J. Am. Chem. Soc. 1951, 73, 10, 4967–4968Publication Date (Print):October 1, 1951Publication History Published online1 May 2002Published inissue 1 October 1951https://pubs.acs.org/doi/10.1021/ja01154a501https://doi.org/10.1021/ja01154a501research-articleACS PublicationsRequest reuse permissionsArticle Views578Altmetric-Citations106LEARN 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