gebhart/patrepeval huggingface dataset:
Multiple Myeloma: New Insights and Therapeutic Approaches (2000)

This review discusses the evolution of novel diagnostic and treatment strategies for multiple myeloma based upon increased understanding of basic disease pathogenesis. Although myeloma has remained an incurable illness to date, these new developments will derive treatments to improve outcome and achieve eventual cure. In Section I, Dr. Kyle reviews the results of current therapy for multiple myeloma, including high dose therapy and stem cell transplantation which have proven to achieve improved response rates, event-free, and overall survival. Supportive therapy, such as erythropoietin to treat disease-related anemia, and methods of prophylaxis against infection, which both lessen toxicities of treatment and improve quality of life for patients, are also addressed. In Section II, Dr. Dalton with Drs. Landowski, Shain, Jove and Hazlehurst discusses mechanisms of drug resistance in myeloma, with emphasis on novel treatment approaches to prevent development of drug resistance and to overcome drug resistance. Laboratory studies delineating mechanisms whereby myeloma cells resist drug-induced apoptosis provide the framework for related treatment protocols for patients with refractory disease. In Section III, Dr. Berenson reviews the management of complications in bone, which occur in the majority of patients with myeloma and are the major cause of decreased quality of life. New insights into the mediators of bone resorption and new bone formation in the marrow milieu have already derived effective bisphosphonate therapy. These drugs not only reduce bone complications and related pain, thereby improving quality of life, but also may have intrinsic anti-tumor activity by virtue of inducing tumor cell adherence to marrow, reducing interleukin-6 secretion, inducing tumor cell apoptosis, or inhibiting angiogenesis. In the last section, Dr. Anderson explores the potential for future therapies which offer great promise to improve patient outcomes. First, drugs which alter the marrow microenvironment include thalidomide and its derivative immunomodulatory drugs, which act directly on tumor cells to induce apoptosis or G1 growth arrest, alter tumor cell adhesion to marrow stroma, inhibit angiogenesis, and trigger a cellular anti-tumor response. The proteasome inhibitors both act directly on tumor cells and also inhibit the transcription factor NFkappaB-dependent upregulation of IL-6 secretion triggered by tumor cell adhesion. Second, delineation of both growth and apoptotic pathways has derived novel treatment strategies. Third, the preclinical basis and early clinical trial results using vaccination and adoptive immunotherapy to harness autoimmune and alloimmune anti-myeloma responses are presented. This review sets the stage for an evolving new biologically based treatment paradigm in myeloma targeting both the tumor and its microenvironment to improve outcome and achieve eventual cure.
TNF‐related apoptosis‐inducing ligand suppresses PRDX4 expression (2009)

TNF-related apoptosis-inducing ligand (TRAIL) is currently considered a promising target for developing anti-cancer therapies. Accumulating evidences have now shown that oxidative stress is involved in the TRAIL-mediated cell death. The peroxiredoxins (PRDXs) are a ubiquitous family of proteins involved in protection against oxidative stress through the detoxification of cellular peroxides. Here we demonstrated that endogenous expression of PRDX4 was significantly decreased by TRAIL at the transcriptional level. In addition, overexpression of PRDX4 dramatically suppressed TRAIL-induced apoptosis. Taken together, these data for the first time suggested that TRAIL suppressed the PRDX4 gene at the transcriptional level and that downregulation of PRDX4 might facilitate cell death induced by TRAIL.
Nucleotide sequences of the genes for Escherichia coli heat-stable enterotoxin I of bovine, avian, and porcine origins (1985)

The nucleotide sequences of cloned Escherichia coli heat-stable toxin 1 (STI) genes isolated from bovine, avian, and porcine origins were determined. They were found to be almost identical to that of Tn1681. The nucleotide sequences were completely preserved in bovine and avian genes, whereas the porcine gene had different sequences at 3 positions in the external region of STI structural genes, as compared with Tn1681. The amino acid sequences of the STI genes of the 3 animal origins corresponded to STIa, which had initially been found in a bovine strain.
Direct flow cytometry of anaerobic bacteria in human feces (1994)

We describe a flow cytometry method for analysis of noncultured anaerobic bacteria present in human fecal suspensions. Nonbacterial fecal compounds, bacterial fragments, and large aggregates could be discriminated from bacteria by staining with propidium iodide (PI) and setting a discriminator on PI fluorescence and by exclusion of events with large forward scatter. Since anaerobic bacteria, which account for over 99.9% of all fecal bacteria, die during sample preparation, a fixation step was not necessary. A second aim of this study was to investigate the technical possibility of measurement of in vivo IgA coating of fecal anaerobic bacteria as well as their bacterial size. Fecal samples of 22 healthy human volunteers were analyzed. The fluorescence distribution of IgA-coated bacteria labeled with fluorescein isothiocyanate (FITC)-anti-Hu-IgA had overlap with noncoated bacteria. However, with match region subtraction, detection of low levels of specific FITC fluorescence on IgA-coated bacteria was achieved. The median bacterial two-dimensional surface area was 1.0 microns2. To validate flow cytometry data, all samples were analyzed with an image analysis system as well. With this new method, a rapid evaluation of fecal flora with high sensitivity for specific FITC fluorescence is possible without culturing.
SIRT1 Is Significantly Elevated in Mouse and Human Prostate Cancer (2007)

Evidence suggests that the histone deacetylase, SIRT1, is a mediator of life span extension by calorie restriction; however, SIRT1 may paradoxically increase the risk of cancer. To better understand the relationship among SIRT1, energy balance, and cancer, two experiments were done. First, a transgenic mouse model of prostate cancer (transgenic adenocarcinoma of mouse prostate; TRAMP) was used to determine the role of energy balance on SIRT1 expression and the effect of cancer stage on SIRT1 and hypermethylated in cancer-1 (HIC-1). Second, immunohistochemistry was done on human prostate tumors to determine if SIRT1 was differentially expressed in tumor cells versus uninvolved cells. Results show that SIRT1 is not increased in the dorsolateral prostate (DLP) of calorie-restricted mice during carcinogenesis. In contrast, when examined in the DLP as a function of pathologic score, SIRT1 was significantly elevated in mice with poorly differentiated adenocarcinomas compared with those with less-advanced disease. HIC-1, which has been shown to regulate SIRT1 levels, was markedly reduced in the same tumors, suggesting that a reduction in HIC-1 may be in part responsible for the increased expression of SIRT1 in prostatic adenocarcinomas. Furthermore, immunostaining of human prostate tumors showed that cancer cells had greater SIRT1 expression than uninvolved cells. In conclusion, DLP SIRT1 expression from calorie-restricted mice was not altered during carcinogenesis. However, SIRT1 expression was increased in mice with poorly differentiated adenocarcinomas and in human prostate cancer cells. Because SIRT1 may function as a tumor promoter, these results suggest that SIRT1 should be considered as a potential therapeutic target for prostate cancer.
The Litigation Privilege as a Shelter for Miscreant Legal Counsel (2018)

ohn Nonnenmacher owes his mother an apology.Apparently unprepared for opening arguments before a federal judge, the Brooklyn lawyer told the presiding judge, in an effort to buy himself a little more time, that his mother had just passed on to the next plane. 1Fortunately (unfortunately for Mr. Nonnenmacher?),his mother was discovered very much alive upon Mr. Nonnenmacher's co-counsel's hiring of a PI to investigate his partner's dubious claim. 2 Clearly unfazed by his mother's tears and not one to break old habits, Mr. Nonnenmacher doubled down before his sanctions hearing and fibbed to the same judge, claiming
Masking of Human Transplantation Antigens by Diverse Substances (1972)

Abstract The reaction of HL-A antibodies with the HL-A determinants on the surface of lymphocytes can be blocked by preincubation of lymphocytes with diverse substances such as normal human serum, autologous plasma, fetal calf serum, newborn serum, heat-inactivated rabbit serum and guinea pig serum, serum albumins from various species, lactalbumin, dextrans, synthetic polyglucose, and polyvinylpyrrolidone. The inhibitors can be washed off readily from lymphocytes. The inhibition procedure described here differs from the conventional inhibition tests in that the inhibitor is added first to the target cells. This “masking inhibition” procedure produces substantially greater inhibition than the standard inhibition methods in which the inhibitor is added first to antiserum before the addition of the target cells. The nonspecific nature of masking inhibition indicates that numerous substances adhere to the lymphocyte surface at HL-A sites or closely adjacent sites.
Manipulation of Baculovirus Vectors (2003)

The development of expression vectors from baculoviruses has provided molecular biologists with one of the most efficient and effective ways of synthesizing foreign gene products in a heterologous system. In contrast to the other recent excellent reviews on the subject (1,2), this contribution aims to explore the various practical aspects of the system, and in consequence, to highlight particular difficulties that may be encountered by workers new to the field. However, before describing the methodology peculiar to baculovirus expression vectors, it is of value to briefly consider the isolation, structure, and replication strategy of this unique group of viruses. Detailed and more comprehensive reviews that describe the biology of baculoviruses are available (3-5).
Aberrant splicing of human Cu/Zn superoxide dismutase (SODI) RNA transcripts (2000)

Two abnormal SOD1 mRNAs, exon 2-skipping and exon 2 and 3-skipping species, were identified from occipital brain tissue of sporadic amyotrophic lateral sclerosis (ALS) patients carrying no mutations in the SOD1 gene. Both transcripts were ubiquitously expressed in non-neuronal as well as neuronal tissues from a subject without neurological diseases. The expression pattern did not show disease specificity or lesional selectivity associated with ALS. Transient expression studies revealed weak expression of the proteins derived from the exon 2-skipping SOD1 cDNA in a cell-free translation system but not in cells. The putative abnormal SOD1 protein may accumulate and exert toxic effects on motor neurons in ALS when the proteolytic system is disturbed by aging or some causal factors.
QT-Screen: High-Throughput Cardiac Safety Pharmacology by Extracellular Electrophysiology on Primary Cardiac Myocytes (2004)

Cardiac safety pharmacology focuses mostly on the drug-induced prolongation of the QT interval in the electrocardiogram. A prolonged QT interval is an important indicator for an increased risk of severe ventricular arrhythmia. Guidelines demand safety tests addressing QT prolongation in vitro and in vivo before a drug enters clinical trials. If safety risks will be detected not until an advanced stage of preclinical drug development, a considerable sum of money has already been invested into the drug development process. To prevent this, high-throughput systems have been developed to obtain information on the potential toxicity of a substance earlier. We will discuss in this publication that the QT-Screen system, which is based on primary cardiac myocytes, is able to provide a sufficient throughput for secondary screening. With this system, extracellular field potentials can be recorded from spontaneously beating cultures of mammalian or avian ventricular cardiac myocytes simultaneously on 96 channels. The system includes software-controlled and automated eight-channel liquid handling, data acquisition, and analysis. These features allow a user-friendly and unsupervised operation. The throughput is over 100 compounds in six replicates and with full dose-response relationships per day. This equals a maximum of approximately 6,000 data points per day at an average cost for consumables of 0.20 US pennies (U.S.) per data point. The system is intended for a non-good laboratory practice-compliant screening; however, it can be adapted to be used in a good laboratory practice environment.
The action of sennosides and related compounds on human colon and rectum (1970)

The direct action of intraluminal senna and related compounds on the human colon and rectum has been investigated. Motility was recorded by balloon kymography with recording units inserted into well established transverse colostomies or into the rectum. The motility of the colon was not changed by intraluminal senna glycosides but the introduction of senna previously incubated with faeces or Esch. coli stimulated the colon to peristalt. The peristalsis was similar to that stimulated by rheinanthrone, an oxanthrone produced by chemical hydrolysis and reduction of senna. Both activated senna and rheinanthrone appeared to act in the colon by contact stimulation. No peristaltic response was stimulated in the rectum, either with activated senna or with rheinanthrone.
Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting (2011)

A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future.
Analysis of NTRK Alterations in Pan-Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics (2018)

Whereas <i>NTRK</i> fusions are exceedingly rare, other <i>NTRK</i> abnormalities affect 14% of patients with cancer. Affecting these alterations has not yet been achievable in cancer. Genomic co-alterations occur frequently with <i>NTRK</i> fusions, but it is not known if co-targeting them can attenuate primary or secondary resistance to NTRK inhibitors.
Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate (2010)

Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.
Nanobodies: Chemical Functionalization Strategies and Intracellular Applications (2017)

Nanobodies can be seen as next-generation tools for the recognition and modulation of antigens that are inaccessible to conventional antibodies. Due to their compact structure and high stability, nanobodies see frequent usage in basic research, and their chemical functionalization opens the way towards promising diagnostic and therapeutic applications. In this Review, central aspects of nanobody functionalization are presented, together with selected applications. While early conjugation strategies relied on the random modification of natural amino acids, more recent studies have focused on the site-specific attachment of functional moieties. Such techniques include chemoenzymatic approaches, expressed protein ligation, and amber suppression in combination with bioorthogonal modification strategies. Recent applications range from sophisticated imaging and mass spectrometry to the delivery of nanobodies into living cells for the visualization and manipulation of intracellular antigens.
Red-emitting silicon quantum dot phosphors in warm white LEDs with excellent color rendering (2014)

We demonstrate red-emitting silicon quantum dot (SiQD) phosphors as a low-cost and environment-friendly alternative to rare-earth element phosphors or CdSe quantum dots. After surface passivation, the SiQD-phosphors achieve high photoluminescence quantum yield = 51% with 365-nm excitation. The phosphors also have a peak photoluminescence wavelength at 630 nm and a full-width-at-half-maximum of 145 nm. The relatively broadband red emission is ideal for forming the basis of a warm white spectrum. With 365-nm or 405-nm LED pumping and the addition of green- and/or blue-emitting rare-earth element phosphors, warm white LEDs with color rendering index ~95 have been achieved.
Graft copolymerization of methyl methacrylate onto rubber‐wood fiber using H2O2 and Fe2+ as an initiator system (2003)

Abstract Methyl methacrylate (MMA) was successfully grafted onto rubber‐wood fiber in a free‐radical solution polymerization initiated by ferrous ion and hydrogen peroxide. The effects of the reaction parameters (reaction temperature, reaction period, influence of hydrogen peroxide, ferrous ammonium sulfate, and monomer concentrations) were investigated. The grafting percentage showed dependency on H 2 O 2 , Fe 2+ , and monomer concentrations, as well as reaction temperature and reaction period. The optimum reaction temperature was determined to be about 60°C and the reaction period was 60 min. The optimum concentration of H 2 O 2 was 0.03 M and optimum amounts of Fe 2+ and MMA were 0.26 mmol and 2.36 × 10 −2 mol, respectively. Poly(methyl methacrylate) (PMMA) homopolymer was removed from the graft copolymer by Soxhlet extractor using acetone. The presence of PMMA on the fiber was shown by FT‐IR spectroscopy and gravimetric analysis. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2499–2503, 2003
Video Manga (1999)

This paper presents methods for automatically creating pictorial video summaries that resemble comic books. The relative importance of video segments is computed from their length and novelty. Image and audio analysis is used to automatically detect and emphasize meaningful events. Based on this importance measure, we choose relevant keyframes. Selected keyframes are sized by importance, and then efficiently packed into a pictorial summary. We present a quantitative measure of how well a summary captures the salient events in a video, and show how it can be used to improve our summaries. The result is a compact and visually pleasing summary that captures semantically important events, and is suitable for printing or Web access. Such a summary can be further enhanced by including text captions derived from OCR or other methods. We describe how the automatically generated summaries are used to simplify access to a large collection of videos.
Breast Cancer (1992)

Adjuvant Therapy of Breast CancerThe demonstration that adjuvant systemic therapy (i.e., systemic therapy given at the time of primary local treatment in the absence of demonstrated metastases) can prolong the disease-free interval and improve overall survival has been a major advance in the management of breast cancer. Randomized clinical trials of systemic adjuvant therapy were pioneered by the Istituto Nazionale per lo Studio e la Cura dei Tumori176 and the National Surgical Adjuvant Breast and Bowel Project177 and provided the first evidence of the benefit of cytotoxic chemotherapy in women with involvement of axillary lymph nodes, particularly younger women. . . .
COMBODY: one‐domain antibody multimer with improved avidity (2010)

Antibodies (Abs) have been engineered into small antigen-binding fragments and rebuilt into multivalent high-avidity molecules for improving in vivo pharmacokinetics and efficacy in clinical use. To increase the avidity of a T-cell receptor-like single-domain Ab (sdAb) specific for HLA-A2 complex, we fused the sdAb to a coiled-coil peptide derived from human cartilage oligomeric matrix protein (COMP48) to make an sdAb multimer, termed combody. The combody improved the binding avidity of sdAb significantly, whereas the specificity for the targeted cells was retained. The strategy was also expanded to create a bispecific combody by fusing an sdAb to the N-terminal and an anti-CD3 single-chain variable fragment to the C-terminal of COMP48. The dual-specific combody was able to efficiently mediate cytotoxicity against the target cells in vitro. Taken together, the strategy to make combody could be widely adopted to increase the avidity of Ab fragment for further application.
A strong propensity toward loop formation characterizes the expressed reading frames of the D segments at the Ig H and T cell receptor loci (1991)

A compilation of murine and human Ig H and TcR beta D segment sequences was used to estimate the relative usage of the various reading frames and to look for associated sequence patterns. We confirm a strong bias in the expression of the Ig H D segments, with more than 90% (murine) and 85% (human) expressed peptides resulting from a preferred reading frame. Remarkably, 86% (mouse) and 90% (human) of those peptides contain at least one glycine residue. All but one of the atypical preferred D peptides contain serine or proline residues and are found in the immediate vicinity of glycine residues provided by specific JH segments. The presence of tyrosine residues is also a characteristic feature of expressed reading frames in both mouse (75%) and human (90%). These results suggest that the constraints of forming a flexible loop within the third complementarity-determining region, is a factor in the preference for a particular reading frame in Ig H D. For the TcR beta D segments, glycine is specified in most reading frames, and no significant preference is observed.