gebhart/patrepeval huggingface dataset:
Short-Term, High-Dose Parathyroid Hormone-Related Protein as a Skeletal Anabolic Agent for the Treatment of Postmenopausal Osteoporosis (2003)

PTH-related protein (PTHrP) is homologous with PTH. PTH, an effective anabolic agent for treating osteoporosis, has been shown to stimulate both bone resorption by osteoclasts and bone formation by osteoblasts. We examined whether PTHrP might share anabolic properties in osteoporosis. A 3-month double-blind, prospective, placebo-controlled, randomized clinical trial was performed in 16 healthy postmenopausal women with osteoporosis. All received calcium and vitamin D, and all continued their prior hormone replacement therapy. One group also received daily sc PTHrP (6.56 microg/kg x d, or approximately 400 microg/d), and the other group received placebo injections. The PTHrP group displayed a 4.7% increase in lumbar spine bone mineral density (BMD) and also demonstrated an increase in osteoblastic bone formation, as assessed using serum osteocalcin measurements. In contrast, there was no increase in bone-specific alkaline phosphatase and collagen-1 propeptide or either of two markers of osteoclastic bone resorption, N-telopeptide, or deoxypyridinoline. One subject in the placebo group withdrew from the study, but there were no significant adverse events in the PTHrP group. PTHrP administered sc in high doses for only 3 months appears to be a potent anabolic agent, producing a 4.7% increase in lumbar spine BMD. This compares very favorably to available antiresorptive drugs for osteoporosis and is similar to the increases in BMD at this early time point reported for PTH. Despite the high doses, PTHrP was well tolerated. Larger clinical trials are required to confirm these results and fully assess the anabolic potential of PTHrP in osteoporosis.
Targeting YB-1 in HER-2 Overexpressing Breast Cancer Cells Induces Apoptosis via the mTOR/STAT3 Pathway and Suppresses Tumor Growth in Mice (2008)

The Y-box binding protein-1 (YB-1) is a transcription/translation factor that is highly expressed in primary breast tumors where it is consistently associated with poor survival. It induces human epidermal growth factor receptor (her-2) along with its dimerization partner egfr by directly binding to their promoters. In addition to promoting growth by inducing receptor tyrosine kinases, YB-1 also protects cells against apoptosis through mechanisms that have not been fully revealed. Given this, we addressed whether YB-1 might be an eventual therapeutic target for breast cancer by inhibiting it with small interfering RNAs in vitro and in vivo. Inhibiting YB-1 suppressed the growth of six of seven breast cancer cell lines that had amplified her-2 or were triple negative. Importantly, targeting YB-1 induced apoptosis in BT474-m1 and Au565 breast cancer cells known to have her-2 amplifications. The potential role of signal transducers and activators of transcription 3 (STAT3) was pursued to address the underlying mechanism for YB-1-mediated survival. Inhibition of YB-1 decreased P-STAT3(S727) but not P-STAT3(Y705) or total STAT3. This was accompanied by decreased P-ERK1/2(T202/Y204), P-mTOR(S2448), and total mammalian target of rapamycin mTOR. Furthering the role of STAT3 in these cells, we show that knocking it down recapitulated the induction of apoptosis. Alternatively, constitutively active P-STAT3 rescued YB-1-induced apoptosis. Finally, targeting YB-1 with 2 different siRNAs remarkably suppressed tumor cell growth in soft agar by >90% and delayed tumorigenesis in nude mice. We conclude that HER-2 overexpressing as well as triple-negative breast cancer cells are YB-1 dependent, suggesting it may be a good therapeutic target for these exceptionally aggressive tumors.
Expression, Purification, and Evaluation of Diagnostic Potential and Immunogenicity of a Recombinant NS3 Protein from All Serotypes of Dengue Virus (2012)

Dengue is one of the major public health concerns in the world. Since all the four serotypes are actively circulating in Mexico, there is a need to develop an efficient diagnosis system to improve case management of the patients. There exist few studies evaluating the use of the NS3 protein as a protective antigen against dengue virus (DENV). In this paper we show the expression of a recombinant NS3 protein from all serotypes of dengue virus (GST-DVNS3-1-4) and report a reliable "in-house detection system" for the diagnosis of dengue infection which was field-tested in a small village (Tezonapa) in the state of Veracruz, Mexico. The fusion proteins were immunogenic, inducing antibodies to be able to recognize to antigens up to a 1 : 3200 dilution. The purified proteins were used to develop an in-house detection system (ELISA) and were further tested with a panel of 239 serum samples. The in-house results were in excellent agreement with the commercial kits with κ = 0.934 ± 0.064 (95% CI = 0.808-1.061), and κ = 0.872 ± 0.048 (95% CI = 0.779-0.965) for IgM and IgG, respectively. The agreement between the NS1 antigen detection versus the rNS3 ELISA, κ = 0.837 ± 0.066 (95% CI = 0.708-0.966), was very good. Thus, these results demonstrate that recombinant NS3 proteins have potential in early diagnosis of dengue infections.
Deep Bayesian Active Learning with Image Data (2017)

Even though active learning forms an important pillar of machine learning, deep learning tools are not prevalent within it. Deep learning poses several difficulties when used in an active learning setting. First, active learning (AL) methods generally rely on being able to learn and update models from small amounts of data. Recent advances in deep learning, on the other hand, are notorious for their dependence on large amounts of data. Second, many AL acquisition functions rely on model uncertainty, yet deep learning methods rarely represent such model uncertainty. In this paper we combine recent advances in Bayesian deep learning into the active learning framework in a practical way. We develop an active learning framework for high dimensional data, a task which has been extremely challenging so far, with very sparse existing literature. Taking advantage of specialised models such as Bayesian convolutional neural networks, we demonstrate our active learning techniques with image data, obtaining a significant improvement on existing active learning approaches. We demonstrate this on both the MNIST dataset, as well as for skin cancer diagnosis from lesion images (ISIC2016 task).
The flagellin-TLR5 axis: Therapeutic opportunities (2002)

Motile bacteria synthesize large-sized surface structures known as flagella through the ordered polymerization of protein subunits. Flagellin, a protein of 40-60 kDa, is the principal constituent of the flagellum; each flagellum consists of approximately 20,000 flagellin molecules. An alignment of the amino acid sequences from different Gram-negative species shows a high degree of similarity in the amino and carboxy terminal domains. In contrast, the central hypervariable regions of these proteins are quite divergent. Recent work reveals that--in addition to playing a role in bacterial adhesion--monomeric flagellin, a protein component of flagellated bacteria, can also act as a soluble immunostimulatory and proinflammatory factor, activating the immune/inflammatory axis via the Toll-like receptor 5-nuclear factor-kappaB axis. Monocytes and macrophages, as well as intestinal and pulmonary epithelial cells, respond to monomeric flagellin at low concentrations. Administration of flagellin at doses comparable to or lower than that of bacterial lipopolysaccharide (endotoxin) can induce prominent local and systemic immune/inflammatory responses in vivo. Recognition of the flagellin-TLR5 pathway offers novel opportunities for the experimental therapy of various forms of shock, sepsis, acute respiratory distress syndrome, bacterial inflammation and infection. (c) Prous Science 2002. All rights reserved.
Aptamer Sensors (2017)

In the last years, great progress has been accomplished in the development of aptamer sensors with different transducers. In order to improve the sensitivity of these biosensors, several methodologies have been employed. In this Special Issue, the state of art and the future trends in the field of aptamer sensors have been explored.
Binding of [3H]Ro 16‐6491, a Reversible Inhibitor of Monoamine Oxidase Type B, to Human Brain Mitochondria and Platelet Membranes (1987)

The reversible inhibitor of monoamine oxidase type B (MAO-B) [3H]Ro 16-6491 binds specifically and with high affinity to a single population of binding sites in human frontal cortex crude mitochondria and platelet membranes. In both tissues binding equilibrium was reached after 1 h incubation at 20 degrees C. Dissociation of bound radioactivity was relatively fast at 20 degrees C (t1/2 = 90-120 min) whereas at 0 degrees C [3H]Ro 16-6491 showed the characteristics of a slowly dissociating ligand. Inhibitors and substrates of MAO-B inhibited binding of [3H]Ro 16-6491, whereas MAO-A blockers were much less potent. Ro 16-6491 was also a substrate for MAO-B and a stable unidentified intermediate of the oxidation of Ro 16-6491 possessing high affinity for the enzyme may account for the marked MAO-B inhibitory effect of the drug. According to this hypothesis Ro 16-6491 would behave as a mechanism-based reversible inhibitor. In conclusion, [3H]Ro 16-6491 binds selectively to MAO-B and represents an excellent new radioligand probe for studying the regional tissue distribution of this enzyme in normal and pathological conditions.
Acute myeloid leukemia stem cells and CD33-targeted immunotherapy (2012)

Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multipotent CD33(-) stem cells as well others arising from, or predominantly involving, committed CD33(+) myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets.
A new device architecture suitable for high-resolution and high-performance image sensors (1988)

A device architecture for building high-performance and high-resolution image sensors suitable for consumer TV camera applications is introduced. The sensor elements are junction field-effect transistors that are organized in an array with their gates floating and capacitively coupled to common horizontal address line. The photogenerated signal is sampled one line at a time, processed to remove the element-to-element nonuniformities, and stored in a buffer for subsequent readout. The concept, which includes an intrinsic exposure control, is demonstrated on a test image sensor that has an 8-mm sensing area diagonal and 580 (H)*488 (V) pixels. The key performance parameters, in addition to a high packing density of sensing elements with a unique hexagonal shape, include high signal uniformity, low dark current, good light sensitivity, high blooming overload protection, and no image smear. The discussion covers the design and operation of the basic image-sensing element, the architecture of the array, and the operation of the on-chip circuits needed for addressing and processing of generated signals. The overall device performance is demonstrated by typical device characterization results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of Age on Proinsulin and Insulin Secretory Patterns in Isolated Rat Islets (1981)

Although isolated islets from older rats store ample insulin, they do not respond as efficiently as do islets from young animals to a glucose or leucine challenge. The current study was conducted to determine if this decline in insulin secretion is associated with abnormalities in islet content or conversion of proinsulin, or in the mobilization of insulin that is newly synthesized. Isolated islets from 2-, 12-, and 18-mo-old rats were assayed for total islet proinsulin and insulin content, and after stimulation with glucose the incubation medium was assayed for secreted proinsulin and insulin. In addition, islets from 2- and 12-mo-old donors were pulse-labeled with 3H-leucine, after which the temporal conversion and pattern of release of newly synthesized hormone was compared. The results show that the ratio of proinsulin to insulin declines progressively with age for both the stored and secreted hormone. Incorporation of 3H-leucine into proinsulin during glucose stimulation also decreases with age. However, the onset, time course, and endpoint of the conversion of this labeled proinsulin to insulin did not change with age. Although the fractional secretion rate of newly synthesized hormone (whether proinsulin or insulin) is similar in 2- and 12-mo-old rats, it exceeds that of the unlabeled, or stored, insulin. When the wave of labeled protein enters the secretory pool it apparently equilibrates with a portion of the insulin pool, which is more rapidly secreted than the total pool of insulin. We considered this the glucose responsive pool, and estimate that this pool is actually smaller in islets from 12- as compared with 2-mo-old rats. The reduction in size of this responsive compartment of insulin in the older rats may, in part, explain the decreased rates of stimulated insulin release that OCCUr with age.
Natural Expression of the CD19 Antigen Impacts the Long-Term Engraftment but Not Antitumor Activity of CD19-Specific Engineered T Cells (2010)

T cells gene-modified to express chimeric Ag receptors (CARs) have shown potent antitumor activity in vivo and are in clinical trials at locations worldwide. However, CAR activity has been investigated in mouse models in which Ag expression is restricted to the tumor. To explore the impact of normal tissue expression of the target Ag, we developed a mouse CD19-specific CAR to investigate antitumor efficacy against a syngeneic B cell lymphoma cell line within a background of normal CD19(+) host B cells. Mouse T cells engrafted with the amCD19CD3zeta CAR specifically lysed A20 lymphoma targets and B cells in vitro. These T cells also eradicated a 12-d established disseminated A20 lymphoma in mice preconditioned with 6 Gy total body irradiation. In the short-term (7 d after adoptive transfer), amCD19z T cells underwent Ag-dependent proliferation in vivo with a concomitant depletion in host B cell levels. However, the levels of amCD19z CAR(+) T cells decreased significantly at later time points, at which point host B cells returned, eventually reaching normal levels. In contrast, CAR(+) T cells lacking a signaling domain or specificity for mCD19 persisted over extended periods in blood and spleen. Importantly, no overt clinical signs of autotoxicity were observed in tumor-free or tumor-bearing mice treated with amCD19z T cells over an extended period of time. These observations highlight the importance of studying the activity of CAR(+) T cells in autologous models that have the normal range of tissue expression of Ag.
Fifteen-year experience with screening for phenylketonuria with an automated fluorometric method. (1982)

An automated fluorometric method, rather than the Guthrie test, has been used in North Carolina for neonatal screening for phenylketonuria (PKU). Although there is no testing law, 97% of newborn infants are screened. Twelve children with PkU, not referred for dietary management, were born before the screening program was established, were born elsewhere, or were successfully identified at birth but not referred for treatment. None was missed because of laboratory error or because of the lack of a testing law. Positive skewing was noted among initial blood phenylalanine levels of 49 infants with PKU and severe hyperphenylalaninemia. Log transformations caused the values to be normally distributed and permitted the calculation of tolerance and confidence limits. These provided estimates of the percentage of phenylketonuric infants whose initial blood levels might fall below any given cutoff value.
Pharmacokinetics of sufentanil in general surgical patients under different conditions of anaesthesia (1993)

The pharmacokinetics of sufentanil were studied in 56 surgical patients after an intravenous bolus of 2 micrograms kg-1, in association with neurolept analgesia or volatile anaesthetics (halothane, enflurane and isoflurane). Plasma concentrations of sufentanil were measured by radioimmunoassay. The kinetics of sufentanil were comparable under neurolept analgesia and under anaesthesia with halothane, enflurane or isoflurane. The overall mean elimination half-life was 182 min, Vdss 169 l and the plasma clearance 910 ml min-1. Except for the isoflurane subgroup, there was no significant correlation between half-life, the volume of distribution or clearance with age (24-77 years) or body weight (45-95 kg).
Histologic Improvement of Fibrosis in Patients with Hepatitis C Who Have Sustained Response to Interferon Therapy (2000)

Although the time between biopsies partly affected the patient's clinical course, the differences observed here suggest that in patients with chronic hepatitis C, regression of fibrosis is associated with sustained virologic response to interferon therapy.
Effects of imperfect power control and user mobility on a CDMA cellular network (1996)

Code-division multiple-access (CDMA) is one of the major candidate access techniques for third generation systems. A great deal of effort has been devoted to the study of the capacity it can support. This paper presents analytical derivations which allow the determination of the link availability in the presence of user mobility and power control imperfections in a CDMA network; moreover, it provides the guidelines which permit the implementation of a simple and flexible simulation tool which is independent of the specific CDMA implementations. As a matter of fact, the reported concepts can be applied to any asynchronous CDMA system, i.e., they hold both for the American Standard IS-95 and for the European Community Standard developed in the framework of the RACE CODIT Project.
Regularizing Neural Networks by Penalizing Confident Output Distributions (2017)

We systematically explore regularizing neural networks by penalizing low entropy output distributions. We show that penalizing low entropy output distributions, which has been shown to improve exploration in reinforcement learning, acts as a strong regularizer in supervised learning. Furthermore, we connect a maximum entropy based confidence penalty to label smoothing through the direction of the KL divergence. We exhaustively evaluate the proposed confidence penalty and label smoothing on 6 common benchmarks: image classification (MNIST and Cifar-10), language modeling (Penn Treebank), machine translation (WMT'14 English-to-German), and speech recognition (TIMIT and WSJ). We find that both label smoothing and the confidence penalty improve state-of-the-art models across benchmarks without modifying existing hyperparameters, suggesting the wide applicability of these regularizers.
Case 18-1963 (1963)

Presentation of Case First admission. A sixty-five-year-old woman entered the hospital because of pain in the abdomen and vomiting.Five days before entry she had the sudden onset of severe, diffuse, crampy abdominal pain, followed by intermittent nausea and projectile vomiting. The pain was less severe after episodes of vomiting. There was no hematemesis, melena or jaundice. No stool was passed over a four-day period; the urinary output was scant, but there was no hematuria or dysuria.One year before admission the blood pressure was elevated to 190 systolic, 110 diastolic, dropping to 170 systolic, 88 diastolic, after rest; at . . .
Reversible Cell‐Specific Drug Delivery with Aptamer‐Functionalized Liposomes (2009)

Aptamer advantages: Cell-specific delivery of the anticancer drug cisplatin through a nucleolin-aptamer-conjugated, cisplatin-encapsulating liposome delivery system is described. Calcein was incorporated into the target MCF-7 cells (see top image) but not into LNCaP cells (see bottom image). More importantly, the extent of delivery can be controlled by using a complementary DNA of the aptamer as an antidote. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.