gebhart/patrepeval huggingface dataset:
Monoclonal antibodies against oncofetal mucin M1 antigens associated with precancerous colonic mucosae. (1986)

We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALeb patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained the mucus cells of surface gastric epithelium independently of ABO or Lewis status. They did not stain normal colonic mucosae, but did stain fetal and precancerous colonic mucosae. Using serial sections, each anti-M1 MAb stained the same goblet cells in fetal and precancerous colon. Extensive search of other normal tissues showed that M1 antigens were restricted to the epithelium embryologically derived from the foregut (gastric and bronchial epithelium) and from Müllerian ducts (mucus cells of endocervix and prostatic utriculus). Some differences in the reactivities of the various anti-M1 MAb were observed in subesophageal, subtracheal, and endocervical mucus cells, suggesting that each anti-M1 MAb characterized a different M1 epitope. A mixture of these five anti-M1 MAbs allowed the estimation of M1 mucus modification in the precancerous colonic mucosae with a sensitivity near to that obtained with polyclonal anti-M1 antibodies. Papain and mercaptoethanol treatments destroyed the M1 epitopes, at variance with the A- or Lewis-related antigens. Our results therefore suggest that the expression of M1 epitopes in precancerous colonic mucosae cannot be due exclusively to alterations in mucin glycosylation but may be related to the reexpression of antigens associated with native gastric mucin which is normally produced by the fetal colon during the sixth month of gestation.
Hydroxylamine Derivatives (1998)

Twelve ethoxycarbonyl or phenylsulfonyl derivatives as prodrugs of hydroxylamine or phenylhydroxylamine were prepared and tested for antiplatelet (in vitro, Born test) antithrombotic (in vivo thrombosis model), and antihypertensive (in vivo, SHR rats) effects. In the Born test N,N-bisphenylsulfonylhydroxylamine (10) was most active (IC50 = 11 mumol/L). The N-ethoxycarbonyl-phenylhydroxylamine (7) was the most potent antithrombotic compound. It inhibited the thrombus formation in mesenteric arterioles of rats by 39% after a single p.o. dose of 60 mg/kg. Compound 7 lacked any antihypertensive activity. It, therefore, had been possible to separate completely the antithrombotic activities from antihypertensive properties in suitable hydroxylamine derivatives.
Expression of small cytoplasmic transcripts of the rat identifier element in vivo and in cultured cells. (1987)

We examined the level of expression of small RNA transcripts hybridizing to a rodent repetitive DNA element, the identifier (ID) sequence, in a variety of cell types in vivo and in cultured mammalian cells. A 160-nucleotide (160n) cytoplasmic poly(A)+ RNA (BC1) appeared in late embryonic and early postnatal rat brain development, was enriched in the cerebral cortex, and appeared to be restricted to neural tissue and the anterior pituitary gland. A 110n RNA (BC2) was specifically enriched in brain, especially the postnatal cortex, but was detectable at low levels in peripheral tissues. A third, related 75n poly(A)- RNA (T3) was found in rat brain and at lower levels in peripheral tissues but was very abundant in the testes. The BC RNAs were found in a variety of rat cell lines, and their level of expression was dependent upon cell culture conditions. A rat ID probe detected BC-like RNAs in mouse brain but not liver and detected a 200n RNA in monkey brain but not liver at lower hybridization stringencies. These RNAs were expressed by mouse and primate cell lines. Thus, tissue-specific expression of small ID-sequence-related transcripts is conserved among mammals, but the tight regulation found in vivo is lost by cells in culture.
Visual restoration and transplant connectivity in degenerate rats implanted with retinal progenitor sheets (2010)

The aim of this study was to determine whether retinal progenitor layer transplants form synaptic connections with the host and restore vision. Donor retinal sheets, isolated from embryonic day 19 rat fetuses expressing human placental alkaline phosphatase (hPAP), were transplanted to the subretinal space of 18 S334ter-3 rats with fast retinal degeneration at the age of 0.8-1.3 months. Recipients were killed at the age of 1.6-11.8 months. Frozen sections were analysed by confocal immunohistochemistry for the donor cell label hPAP and synaptic markers. Vibratome slices were stained for hPAP, and processed for electron microscopy. Visual responses were recorded by electrophysiology from the superior colliculus (SC) in 12 rats at the age of 5.3-11.8 months. All recorded transplanted rats had restored or preserved visual responses in the SC corresponding to the transplant location in the retina, with thresholds between -2.8 and -3.4 log cd/m(2). No such responses were found in age-matched S334ter-3 rats without transplants, or in those with sham surgery. Donor cells and processes were identified in the host by light and electron microscopy. Transplant processes penetrated the inner host retina in spite of occasional glial barriers between transplant and host. Labeled neuronal processes were found in the host inner plexiform layer, and formed apparent synapses with unlabeled cells, presumably of host origin. In conclusion, synaptic connections between graft and host cells, together with visual responses from corresponding locations in the brain, support the hypothesis that functional connections develop following transplantation of retinal layers into rodent models of retinal degeneration.
Exploiting the lacZ reporter gene for quantitative analysis of disseminated tumor growth within the brain: use of the lacZ gene product as a tumor antigen, for evaluation of antigenic modulation, and to facilitate image analysis of tumor growth in situ. (1993)

We extend use of the lacZ reporter gene for tumor biology. Intracerebral growth of 9L/lacZ, a gliosarcoma cell line that stably expresses lacZ, was evaluated in syngeneic rats. The reporter gene product, Escherichia coli-derived beta-galactosidase (beta-gal), was detected histochemically on tissue sections. This permits visualization of disseminated tumor and, as shown here, facilitates image analysis. We show that the beta-gal marker protein itself can serve as a tumor antigen in appropriate contexts. Quantitative image analysis of tumor areas is used to show that immunization with beta-gal protects against tumor growth. Abnormal beta-gal- areas are easily detected, facilitating study of antigenic modulation. The tumor studied did not escape through this mechanism. All abnormal beta-gal- areas examined were shown to reflect accumulation of inflammatory or reactive cells, not tumor. Taken together, these findings show several ways in which the lacZ reporter gene can be exploited to facilitate quantitative analysis of disseminated tumor growth within the brain. They draw attention to the growing appreciation that tumor antigens need not be cell surface molecules.
[Anti-RANKL antibody for treatment of patients with bone metastasis from breast cancer]. (2012)

Breast cancer is known to be associated with a high incidence of bone metastases. Recent advances in treatment for breast cancer have improved patient prognosis, including those with bone metastasis, highlighting the importance of treating bone metastasis to reduce incidence of skeletal complications and to improve patients' QOL. Currently, bisphosphonates(BP), which are recommended by domestic and international clinical practice guidelines, are commonly used for the treatment of bone metastasis. However, the outcomes of BP therapy leave room for improvement in regard to their efficacy, safety, and convenience. Prior studies have indicated that RANK ligand(RANKL), a cytokine mainly expressed in osteoblasts and bone marrow stromal cells, plays an important role in bone resorption by osteoclasts, which are key mediators in the formation and progression of bone metastasis. Denosumab is a fully human monoclonal anti-RANKL antibody which suppresses differentiation, activation, and survival of osteoclasts by inhibiting the binding of RANKL to its receptor, RANK. In a phase III clinical trial, denosumab significantly decreased the time-to-first and time-to-first-and-subsequent skeletal related events(SRE), compared with zoledronic acid in advanced breast cancer patients with bone metastases. Further more, denosumab was more effective than zoledronic acid in preventing the progression of bone pain and maintaining patients QOL. In the future, treatment of bone metastases for breast cancer patients is expected to evolve further with the introduction of denosumab, which is conveniently administered by subcutaneous injection.
Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction (2017)

Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10<sup>11</sup> vector genomes [vg]/kg). Both treatments significantly reduced glycogen content of the heart and diaphragm. Although ERT triggered anti-GAA antibody formation, there was no detectable antibody response following AAV vector administration. The efficacy of three lower dosages of AAV2/8-LSPhGAA was evaluated in GAA-KO mice, either alone or in combination with ERT. The minimum effective dose (MED) identified was 8 × 10<sup>10</sup> vg/kg to reduce glycogen content in the heart and diaphragm of GAA-KO mice. A 3-fold higher dose was required to suppress antibody responses to ERT. Efficacy from liver gene therapy was slightly greater in male mice than in female mice. Vector dose correlated inversely with anti-GAA antibody formation, whereas higher vector doses suppressed previously formed anti-GAA antibodies as late as 25 weeks after the start of ERT and achieved biochemical correction of glycogen accumulation. In conclusion, we identified the MED for effective AAV2/8-LSPhGAA-mediated tolerogenic gene therapy in Pompe disease mice.
CD40 Activation Boosts T Cell Immunity In Vivo by Enhancing T Cell Clonal Expansion and Delaying Peripheral T Cell Deletion (1999)

In this report we show that activation of APC with an agonist anti-CD40 mAb profoundly alters the behavior of CD4 T cells in vivo. Stimulation of mice with anti-CD40 2 days before, but not 1 day after, administration of superantigen (SAg) enhanced CD4 and CD8 T cell clonal expansion by approximately threefold. Further, CD40 activation also delayed peripheral T cell deletion after activation. Dying, activated T cells were quantitated by detecting extracellular phosphatidylserine with concomitant staining for SAg-reactive T cells using a TCR Vbeta-specific mAb. Upon close examination, it was shown that CD40 activation delayed the death of the activated T cells. Additionally, it was found that enhanced survival of CD4 T cells was equally dependent on APC expression of B7-1 and B7-2. This is in contrast to CD8 T cells, which did not depend as much on B7-1 as B7-2. Thus, CD40 activation indirectly promotes T cell growth and delays the death of SAg-stimulated CD4 T cells in vivo. These data suggest that one way CD40 activation promotes a more robust immune response is by indirectly increasing the production of effector T cells and by keeping them alive for longer periods of time.
The Chirality of Phosphatidylserine and the Activation of Protein Kinase C (1998)

The properties of phosphatidyl-L-serine (L-PS) and phosphatidyl-D-serine (D-PS) were compared. The two forms of PS have similar but nonidentical L to L phase transition temperatures. Mixtures of phosphatidylserine with phosphatidylethanolamine and cholesterol (molar ratio 1:1:2) show polymorphic behavior at higher temperatures and in the presence of Ca2+. Mixtures with L-PS undergo conversion to nonlamellar phases at lower temperatures than do similar mixtures with D-PS. The aggregation of vesicles upon addition of histones is greater for L-PS than for D-PS. With fluorescence digital imaging microscopy we could show differences in the extent of formation of histone-induced domains enriched in PS or in diacylglycerol. The most enriched domains were induced with histone in membranes containing L-PS. The MARCKS peptide showed no differences in domain formation between L-PS and D-PS. The maximal activity of protein kinase C was greater in the presence of L-PS when histone, which could form more enriched domains, was the substrate. However, with a MARCKS peptide substrate, which formed domains of equal enrichment with L-PS and D-PS, the maximal activity of protein kinase C was the same with D-PS and with L-PS. These observations demonstrate that L-PS and D-PS have different physical properties. These differences likely contribute to the greater ability of L-PS to activate protein kinase C.
ATP Hydrolysis and DNA Binding by the Escherichia coli RecF Protein (1999)

The Escherichia coli RecF protein possesses a weak ATP hydrolytic activity. ATP hydrolysis leads to RecF dissociation from double-stranded (ds)DNA. The RecF protein is subject to precipitation and an accompanying inactivation in vitro when not bound to DNA. A mutant RecF protein that can bind but cannot hydrolyze ATP (RecF K36R) does not readily dissociate from dsDNA in the presence of ATP. This is in contrast to the limited dsDNA binding observed for wild-type RecF protein in the presence of ATP but is similar to dsDNA binding by wild-type RecF binding in the presence of the nonhydrolyzable ATP analog, adenosine 5'-O-(3-thio)triphosphate (ATPgammaS). In addition, wild-type RecF protein binds tightly to dsDNA in the presence of ATP at low pH where its ATPase activity is blocked. A transfer of RecF protein from labeled to unlabeled dsDNA is observed in the presence of ATP but not ATPgammaS. The transfer is slowed considerably when the RecR protein is also present. In competition experiments, RecF protein appears to bind at random locations on dsDNA and exhibits no special affinity for single strand/double strand junctions when bound to gapped DNA. Possible roles for the ATPase activity of RecF in the regulation of recombinational DNA repair are discussed.
Review—Flexible and Stretchable Electrochemical Sensing Systems: Materials, Energy Sources, and Integrations (2020)

This review details the key progress made on flexible and stretchable electrochemical sensing systems, along with their relevant challenges and opportunities for the future. Stepping forward from traditional rigid electrodes, recent advancements in non-rigid electrochemical sensors offer new and exciting opportunities for various applications, such as biomedical, fitness, or environmental monitoring. The key factors in developing such devices are the materials and integrated systems needed to retain mechanical compliance while maintaining electrochemical functions. This requires a devotion to judiciously engineer both the underlying substrates and electrode materials. However, the realization of compliant electrochemical sensing devices still faces many obstacles. The requirements and potential strategies to enable flexible and stretchable electrodes are further discussed in this review. In addition to such sensing units, which mainly consist of electrodes and functionalized transducers, integrated systems also require miniaturized viable and mechanically compliant energy sources, as well as low-power electronics for controlling the device and wirelessly communicating with users. Such advancements, alongside other attractive functionalities such as self-healing and transparent properties, are also discussed. The innovative flexible and stretchable sensing systems will extend a variety of non‐invasive, minimally invasive, wearable, and implantable applications to patients. Examples of compliant sensing systems and relevant challenges are included alongside perspectives of this emerging technology.
Regulation of cellular growth by the Drosophila target of rapamycin dTOR (2000)

The TOR protein kinases (TOR1 and TOR2 in yeast; mTOR/FRAP/RAFT1 in mammals) promote cellular proliferation in response to nutrients and growth factors, but their role in development is poorly understood. Here, we show that the Drosophila TOR homolog dTOR is required cell autonomously for normal growth and proliferation during larval development, and for increases in cellular growth caused by activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As in mammalian cells, the kinase activity of dTOR is required for growth factor-dependent phosphorylation of p70 S6 kinase (p70(S6K)) in vitro, and we demonstrate that overexpression of p70(S6K) in vivo can rescue dTOR mutant animals to viability. Loss of dTOR also results in cellular phenotypes characteristic of amino acid deprivation, including reduced nucleolar size, lipid vesicle aggregation in the larval fat body, and a cell type-specific pattern of cell cycle arrest that can be bypassed by overexpression of the S-phase regulator cyclin E. Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability.
Treatment patterns, survival rate, and Parts A and B costs by line of therapy for FDA-approved/NCCN Category 1 treatments for patients with metastatic pancreatic cancer. (2019)

e18357 Background: There is currently limited real-world evidence regarding metastatic pancreatic cancer (m-PANC) FDA-approved/NCCN Category 1 treatment patterns, resource utilization, and survival rate. We analyzed these outcomes in the Medicare fee-for-service (FFS) population by chemotherapy regimen and line of therapy (LOT). Methods: We identified patients with m-PANC using ICD-9/10 diagnosis codes in the 2013-2017 Medicare 100% Limited Data Set claims, which include all Medicare paid FFS claims, except professional services, for 45 million Medicare FFS beneficiaries. We studied mean costs and survival rate by regimen and LOT. Patients in our study had two or more claims with a pancreatic cancer (PANC) diagnosis more than 30 days apart and one or more claims with a secondary malignancy (metastasis) diagnosis on or after the first PANC diagnosis date. We defined index date as the earliest metastasis diagnosis date. We excluded patients with pre-index non-PANC malignancies and those without six months pre-index and three months (or until death, if earlier) post-index Medicare FFS enrollment. LOTs were assigned based on therapies used. LOTs ended the day before a new chemotherapy began, 28 days after the last chemotherapy (if no new chemotherapy), or upon death. Results: Gemcitabine monotherapy, gemcitabine/nab-paclitaxel, and FOLFIRINOX were most commonly used as first line (1L) therapy (91%, 80%, and 80%, respectively). Mean total Parts A and B (excluding professional) cost for 1L gemcitabine monotherapy was lower than gemcitabine/nab-paclitaxel or FOLFIRINOX ($14,601, $32,447, and $33,628, respectively), but FOLFIRINOX had a higher 90-day survival rate (86%) than gemcitabine-based regimens (76-79%). Liposomal irinotecan was most commonly used in second and third lines (2L, 3L) (54% and 28%, respectively); 97% of these patients previously received gemcitabine, consistent with approved labeling. Despite disease progression, 2L and 3L liposomal irinotecan had similar costs ($36,350 and $35,010, respectively) to 1L gemcitabine/nab-paclitaxel and FOLFIRINOX. As expected, 2L and 3L liposomal irinotecan 90-day survival rates were lower (68% and 73%, respectively). Conclusions: Mean total Parts A and B (excluding professional) costs for common 1L-3L regimens varied from less than $15,000 to greater than $30,000. 90-day survival rates for common regimens varied between 1L (86%) to 3L (68%).
Quality assurance and use of PCR in clinical trials. (1994)

Qualitative and quantitative HIV-1 DNA and RNA PCR assays are proving to be useful in the diagnosis of HIV-1 infection in infants and in assessing the in vivo antiviral activity of new therapies and regimens in clinical trials. The use of these standardized commercial assays in conjunction with an external quality assurance program has ensured that results from different laboratories are comparable. In addition, real-time proficiency monitoring has the potential to detect problems immediately before patient data are compromised.
Use of multiple PCR primer sets for optimal detection of human papillomavirus (1996)

Using multiple PCR primer sets, we tried to optimize the detection of human papillomavirus (HPV) in DNA samples isolated from 361 frozen biopsy specimens from patients with invasive cervical carcinomas. The HPVs detected were placed into three distinct groups, including group I/Inex at Telelab (Skien, Norway) and group Ineg and group II at the Norwegian Radium Hospital (Oslo, Norway). The consensus primer sets were Oli-1b-oli-2i, My09-My11, Gp5-Gp6, and Gp(5+)-Gp6+ from the HPV L1 gene and CpI-CpIIG from the E1 gene. Using these consensus primers together with the type-specific primers from E6-E7, we found that 355 patients (98%) were HPV positive. Type-specific primers for HPV types 11, 16, 18, 31, 33, and 35 detected more HPV-infected patients than the most sensitive consensus primer set, while the three consensus primer sets My, Gp/Gp+, and Cp together detected more HPV-positive patients than the type-specific primers. Testing of sensitivity of the PCR with SiHa cells serially diluted in lymphocytes (HPV-negative cells) indicated a detection limit of 6,300 HPV type 16 DNA copies with consensus primers (My, Gp+, and Cp) and 126 original HPV type 16 DNA copies with type-specific primers. Comparison of the amplification results for consensus L1 primers and type-specific E6-E7 primers indicated the presence of L1 deletions in 23 of 56 samples. The conclusion is that in PCR detection systems, multiple consensus primers and type-specific primers should be used in order to detect all patients harboring HPV.
Parabolic pulse generation by use of a dispersion-decreasing fiber with normal group-velocity dispersion (2004)

We propose a new method for generating a parabolic pulse by use of a dispersion-decreasing fiber with normal group-velocity dispersion. When a hyperbolic dispersion-decreasing structure is employed, the pulse evolves into a linearly chirped pulse with an exact parabolic intensity profile without radiating dispersive waves. The highly linear chirp in the parabolic pulse allows for efficient and high-quality pulse compression.