gebhart/patrepeval huggingface dataset:
A Computer-Aided Diagnosis System of Nuclear Cataract (2010)

Cataracts are the leading cause of blindness worldwide, and nuclear cataract is the most common form of cataract. An algorithm for automatic diagnosis of nuclear cataract is investigated in this paper. Nuclear cataract is graded according to the severity of opacity using slit lamp lens images. Anatomical structure in the lens image is detected using a modified active shape model. On the basis of the anatomical landmark, local features are extracted according to clinical grading protocol. Support vector machine regression is employed for grade prediction. This is the first time that the nucleus region can be detected automatically in slit lamp images. The system is validated using clinical images and clinical ground truth on >5000 images. The success rate of structure detection is 95% and the average grading difference is 0.36 on a 5.0 scale. The automatic diagnosis system can improve the grading objectivity and potentially be used in clinics and population studies to save the workload of ophthalmologists.
Concanavalin A-induced Open Neural Tube Defects in Chick Embryos (1996)

Open neural tube defects developed in 12 of 122 alive chick embryos treated with exogenous lectin (concanavalin-A) at stages between 10 or 14 as defined by Hamburger and Hamilton. Embryos treated at stage 10, the time of anterior neuropore closure, developed exencephaly or extensive neural openings from the level of rhombencephalon to the thoracic spinal cord, while embryos treated at stages between 11 and 14, at posterior neuropore closure, developed only small myeloschisis in the thoracolumbar region. The failure of neural tube closure at a critical time is a major cause of neural tube defects.
Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA–Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy (2018)

CD19-targeted chimeric antigen receptor (CAR) engineered T/natural killer (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to "on-target off-tumor" toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK cells may permit prospective control of "on-target off-tumor" toxicity. To develop a commercial product for solid tumors, mesothelin was selected as an antigen target based on its association with poor prognosis and overexpression in multiple solid cancers. It was hypothesized that selecting, activating, and expanding cells ex vivo prior to mRNA CAR transfection would not be necessary, thus simplifying the complexity and cost of manufacturing. Now, the development of anti-human mesothelin mRNA CAR transfected peripheral blood lymphocytes (CARMA-hMeso) is reported, demonstrating the manufacture and cryopreservation of multiple cell aliquots for repeat administrations from a single human leukapheresis. A rapid, automated, closed system for cGMP-compliant transfection of mRNA CAR in up to 20 × 10<sup>9</sup> peripheral blood lymphocytes was developed. Here we show that CARMA-hMeso cells recognize and lyse tumor cells in a mesothelin-specific manner. Expression of CAR was detectable over approximately 7 days in vitro, with a progressive decline of CAR expression that appears to correlate with in vitro cell expansion. In a murine ovarian cancer model, a single intraperitoneal injection of CARMA-hMeso resulted in the dose-dependent inhibition of tumor growth and improved survival of mice. Furthermore, repeat weekly intraperitoneal administrations of the optimal CARMA-hMeso dose further prolonged disease control and survival. No significant off-target toxicities were observed. These data support further investigation of CARMA-hMeso as a potential treatment for ovarian cancer and other mesothelin-expressing cancers.
Levels of Anti-Inflammatory Cytokines and Neurological Worsening in Acute Ischemic Stroke (2003)

Anti-inflammatory cytokine IL-10 is associated with the early clinical course of patients with acute ischemic stroke, especially in patients with small vessel disease or subcortical infarctions.
Estrogen and androgen differentially modulate the growth-associated protein GAP-43 (neuromodulin) messenger ribonucleic acid in postnatal rat brain (1994)

The level of expression of the gene encoding GAP-43, a protein implicated in neurite outgrowth and motility, is sexually dimorphic in the postnatal brain and modulated by testosterone (T). To determine which metabolite of T modulates the expression of GAP-43 in the postnatal brain, the present study investigated the effect of estrogen and androgen receptor antagonists, tamoxifen (TAM) and cyproterone acetate (CA), and agonists, diethylstilbestrol (DES) and dihydrotestosterone (DHT). On postnatal day 1, male rats were injected sc daily with oil, TAM, or CA, whereas additional female pups were treated with oil, DES, or DHT. On postnatal day 6, brains were collected and 16-micron cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 messenger RNA (mRNA). A comparison of hybridization signal in the cerebral cortex, bed nucleus of the stria terminalis, and medial preoptic nucleus demonstrated that the level of GAP-43 mRNA in males was significantly higher than in females. However, when male pups were injected with CA, a female-like level of GAP-43 mRNA was measured in the cerebral cortex. The low level of GAP-43 hybridization signal in the female cortex was markedly increased when females were treated with DHT. In contrast, the level of GAP-43 mRNA in the male medial preoptic nucleus was attenuated after treatment with TAM, whereas the level in the female was augmented with DES. Interestingly, the level of GAP-43 mRNA in the bed nucleus was reduced when males were treated with either TAM or CA and augmented when females were administered either DES or DHT. The results of these studies indicate that the effects of T on GAP-43 mRNA levels in the postnatal brain are modulated by estrogen- and androgen receptor-mediated events in a region-specific manner.
Sequential Chemiluminescent Detection of Target DNAs without Stripping and Reprobing (1999)

We present a simple method for sequential chemiluminescent detections of two different DNA loci on a single Southern blot. First, an enzyme-linked DNA probe for a unique sequence is detected with a horse-radish peroxidase (HRP) substrate followed by the detection of another enzyme-linked DNA probe for a different unique sequence with an alkaline phosphatase (AP) substrate that simultaneously inhibits the chemiluminescence generated by HRP. Such sequential detection steps eliminate the need to strip and reprobe blots and can be performed with no intervening steps.
Marine biofouling: a sticky problem. (2002)

Organisms that colonise underwater surfaces, such as barnacle larvae and spores of algae, use a diverse array of biological 'glues' to provide both temporary and more permanent adhesion. The practical consequence of colonisation by these organisms is biofouling - something that has plagued mariners for years - causing increased drag and, in extreme cases, corrosion. Might there be a biological solution to this biological problem?
Phase Ib clinical trial of starch‐conjugated deferoxamine (40SD02): a novel long‐acting iron chelator (2007)

The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.
Answer to “new observations on Rijndael” (2000)

The note [1] presents an interesting view on alternative representations of the Rijndael structure. The application of mathematical techniques is refreshing. The purpose of this reply is to clarify that the observations made do not contradict the security claims we made. While we are sure that the authors are fully aware of the merits and limitations of their results, we feel that a less experienced reader might easily draw wrong conclusions. From the beginning, our design strategy was to use as simple as possible components, to define clear evaluation criteria, and to use simple components with easily provable properties where possible. This paper is organised as folows. We start in Section 2 with a few comments on the used terminology. In Section 3 we restate our evaluation criterium for ‘diffusion’ and show that the results of [1] compare to it. In Section 4 we explain the advantages of using simple components, with provable properties. In Section 5 we explain the advantages of using a simple structure. This is illustrated with an analysis of the DES that contradicts the results of [1].
Computing VaR and AVaR of Skewed-T Distribution (2007)

We consider the skewed-T distribution defined as a location-scale normal mixture. Analytical formulas for its value-at-risk and average value-at-risk are derived. High-accuracy approximations are developed and numerically tested.
P4–432: Small molecules targeting Rho GTPase signaling altered in Alzheimer's disease (2013)

Altered intracellular protein transport and synaptic remodeling are two of the most prominent cellular processes that are affected in Alzheimer's disease (AD) as well as other neurodegenerative diseases. Rho subfamily of the small GTPases within the Ras superfamily is essential for modulating theses functions. Research has increasingly established the RhoA, Rac1, and Cdc42 subclasses of small G-proteins as controlling elements of secretase trafficking, Aβ production, neurotransmitter receptor signaling, and the synaptic cytoskeletal dynamics. Understanding how they operate in the context of memory and learning is pivotal for the development of Rho-GTPase based therapeutic treatments of AD. Our recent studies demonstrated the remarkable alteration of actin cytoskeleton and its regulatory proteins in AD. These proteins include filamin (Lu et al., JAD, 2010), G-actin, and components of Rho-GTPase signaling. In order to establish a repertoire of small molecule modulators of Rho-GTPase signaling, we performed a computer-assisted in silico screening of the SPECS database using GLIDE program (Schrodinger) for chemical compounds that can disrupt the interaction of Cdc42 with intersectin (Friesland et al., PNAS, 2013). This study led to the discovery of a number of small molecules targeting Rho GTPases including Cdc42, RhoA, and Rac1. The biochemical and imaging studies not only established the first small molecule ZCL278 targeting Cdc42-intersectin interaction, it also provided the proof-of-concept results showing the effectiveness of ZCL278 to interfere with Golgi organization and neuronal cytoskeleton. Additional studies on ZCL series compounds showed favorable drug tolerance, potential CNS effects, and distinct neuronal responses to staurosporine and glutamate induced neuronal toxicity. Our other studies employ isolated primary cortical neurons from triple transgenic (3xTg) mice expressing AD-like mutations in presenlin 1 (M146V), APP (695swe),and Tau P301L. In the3xTg neurons, filamin, G-actin, and Cdc42 showed redistribution in the soma and the axonal ordendritic processes, further validating the potential significant involvement of actin cytoskeleton in AD pathogenesis. The discovery of ZCL series chemicals could form a novel compound base to potentially develop into AD modifying therapeutics.
Welfare and Profit Divergence for a Tolled Link in a Road Network (1995)

This paper analyses indirect effects that arise from network interdependence. If profitability of a new, tolled link depends on extraction of user surpluses previously enjoyed on the earlier network, addition of the new link can be welfare-negative. Thus the profit test cannot displace cost-benefit analysis.
La quadrithérapie bismuthée est supérieure au traitement séquentiel pour l’éradication de Helicobacter pylori : résultats d’une étude comparative en routine (2015)

L’objectif de l’étude est de comparer, en pratique quotidienne, le traitement séquentiel standard (inhibiteur de la pompe à protons [IPP] + amoxicilline puis clarithromycine-métronidazole) à la quadrithérapie bismuthée (oméprazole + bismuth-tétracycline-métronidazole) dans une population non sélectionnée atteinte d’infection à Helicobacter pylori. Trente-sept patients recevant le traitement séquentiel ont été comparés à 43 patients recevant la quadrithérapie bismuthée. L’objectif principal était le taux d’éradication de H. pylori. Les objectifs secondaires étaient d’analyser le niveau de résistance aux antibiotiques et les effets secondaires du traitement. En intention de traiter, les taux d’éradication obtenus avec la quadrithérapie bismuthée et le traitement séquentiel sont respectivement de 86 % et 67,6 % (p=0,048), et de 90,2 % et 71,4 % en analyse per protocole (p=0,035). Avec le traitement séquentiel, les échecs thérapeutiques sont liés dans 66,7 % des cas à une résistance à la clarithromycine et/ou au métronidazole et, avec la quadrithérapie bismuthée, dans 75 % des cas à une résistance au métronidazole. Aucun effet secondaire lié à l’utilisation du bismuth n’est survenu. Dans cette étude française réalisée en routine, la quadrithérapie bismuthée s’avère significativement supérieure au traitement séquentiel. Ces résultats en font le traitement de première intention des infections à H. pylori.
Advances in Intracellular and On‐Surface Polymerization in Living Cells: Implications for Nanobiomedicines (2023)

The cellular environment offers some unique features to carry out polymerizations under controlled conditions. Polymerization of monomers in cellular compartments and on the surface of living organisms holds much promise in the engineering of biofunctional synthetic polymers for sensing and probing cell behavior and of late has received significant interest. This effort lies at the interface of synthetic biology and polymer chemistry and can pave the way for innovative solutions to many existing challenges in healthcare, environment, energy, and the study of the “origin of life”. Herein, recent advances in controlled polymerization strategies for intracellular and surface of living cells are presented with a particular emphasis on nanobiomedicines. Furthermore, polymerization strategies, cytocompatible monomer structures, compatible cell lines and microorganisms, nature of stimulus, catalysts, along with specific polymerization conditions to produce non‐natural biofunctional polymers that can undergo polymerization‐induced self‐assembly within and onto the living cells are presented in detail. Furthermore, the review offers a window into the future of such novel emerging synthetic bionano systems in biomedical sciences.
The Use of the L-Curve in the Regularization of Discrete Ill-Posed Problems (1993)

Abstract. Regularization algorithms are often used to produce reasonable solutions to ill-posed problems. The L-curve is a plot--for all valid regularization parameters--of the size of the regularized solution versus the size of the corresponding residual. Two main results are established. First a unifying characterization of various regularization methods is given and it is shown that the measurement of &amp;quot;size &amp;quot; is dependent on the particular regularization method chosen. For example, the 2-norm is appropriate for Tikhonov regularization, but a 1-norm in the coordinate system of the singular value decomposition (SVD) is relevant to truncated SVD regularization. Second, a new method is proposed for choosing the regularization parameter based on the L-curve, and it is shown how this method can be implemented efficiently. The method is compared to generalized cross validation and this new method is shown to be more robust in the presence of correlated errors.
Optimization of Subarray Partition for Large Planar Phased Array Radar Based on Weighted K-Means Clustering Method (2015)

Subarray partition is indispensable in large phased array radar system for reducing the manufacturing cost as well as realizing the system potentiality. The optimization of subarray partition for large planar phased array radar according to weighted K-means clustering method is mainly investigated in this paper. Based on the excitation matching technique, the optimization of subarray partition in monopulse application can be reformulated as a clustering of reference gain ratios to minimize the excitation matching error. However, when the element weights are non-uniform for specific intentions such as low sidelobes, the matching error could not be minimized completely by traditional K-means clustering. Therefore, in this paper, a weighted K-means clustering method is proposed to reduce the matching error by modifying the membership rule and cluster center of K-means clustering. The proposed method can provide smaller matching error compared with conventional clustering methods, especially when the elements are weighted non-uniformly. The effectiveness of proposed method is validated by numerical simulations and compared with several classical clustering methods.
Performance evaluation of COWS under real parallel applications (2004)

Clusters of workstations (COWS) are often arranged as a switch-based network with irregular topology. Usually, the evaluation of interconnection networks for COWS has been carried out by simulation using synthetic traffic and by traces from real parallel applications. Although both types of traffics are used as a first approximation of the behavior of the system, a more accurate behavior can be obtained by using real parallel applications. In this paper, a new simulation framework has been developed in order to evaluate interconnection networks under real parallel applications by using an execution-driven simulator. Moreover, the new simulator can be used to evaluate the impact on the performance of the whole system of several design parameters in addition to the interconnection network. Evaluation results show that the execution time of real parallel applications can be reduced by using an effective routing algorithm. Moreover, in some cases, the achieved improvements are higher than the ones achieved by improving other design issues, such as the processor instruction issue rate, the cache size or the network bandwidth.
Precocious Puberty (1989)

Primary care providers should have the ability to identify normal and abnormal variations of sexual development in children. The incidence of precocious puberty is approximately one child in every 10,000 children in the United States. While etiologies vary, precise differential diagnosis is essential because it will determine the course of treatment required. New forms of therapy using long-acting luteinizing releasing factor agonists are currently being investigated. Developmentally appropriate explanations for affected children regarding the diagnosis and treatment plan are a crucial component of care. Ongoing educational and emotional support for the child and family are essential as they learn to cope with early sexual development.
A Promising Wearable Solution for the Practical and Accurate Monitoring of Low Back Loading in Manual Material Handling (2021)

(1) Background: Low back disorders are a leading cause of missed work and physical disability in manual material handling due to repetitive lumbar loading and overexertion. Ergonomic assessments are often performed to understand and mitigate the risk of musculoskeletal overexertion injuries. Wearable sensor solutions for monitoring low back loading have the potential to improve the quality, quantity, and efficiency of ergonomic assessments and to expand opportunities for the personalized, continuous monitoring of overexertion injury risk. However, existing wearable solutions using a single inertial measurement unit (IMU) are limited in how accurately they can estimate back loading when objects of varying mass are handled, and alternative solutions in the scientific literature require so many distributed sensors that they are impractical for widespread workplace implementation. We therefore explored new ways to accurately monitor low back loading using a small number of wearable sensors. (2) Methods: We synchronously collected data from laboratory instrumentation and wearable sensors to analyze 10 individuals each performing about 400 different material handling tasks. We explored dozens of candidate solutions that used IMUs on various body locations and/or pressure insoles. (3) Results: We found that the two key sensors for accurately monitoring low back loading are a trunk IMU and pressure insoles. Using signals from these two sensors together with a Gradient Boosted Decision Tree algorithm has the potential to provide a practical (relatively few sensors), accurate (up to r<sup>2</sup> = 0.89), and automated way (using wearables) to monitor time series lumbar moments across a broad range of material handling tasks. The trunk IMU could be replaced by thigh IMUs, or a pelvis IMU, without sacrificing much accuracy, but there was no practical substitute for the pressure insoles. The key to realizing accurate lumbar load estimates with this approach in the real world will be optimizing force estimates from pressure insoles. (4) Conclusions: Here, we present a promising wearable solution for the practical, automated, and accurate monitoring of low back loading during manual material handling.