gebhart/patrepeval huggingface dataset:
A Non-Genotoxic Antibody Drug Conjugate Targeting C-Kit for Hematopoietic Stem Cell Transplant Conditioning (2018)

Hematopoietic stem cell transplantation (HSCT) has the potential to cure a wide variety of diseases, but patient access to this life-saving therapy is limited due to the morbidity and mortality associated with current conditioning regimens. To address this significant unmet medical need, a conditioning regimen using a non-genotoxic antibody drug conjugate (ADC) targeting C-kit (CD117) was developed to specifically deplete hematopoietic stem cells (HSCs). CD117 is highly expressed on HSCs and ligand binding promotes hematopoiesis, self-renewal, and rapid internalization of the receptor. The restricted expression and rapid internalization of CD117 make it an attractive target for an ADC-based approach to deplete HSCs and limit systemic toxicity. This approach preserves the adaptive immune system making it ideal for autologous gene modified transplants. In addition, conditioning with an anti-CD117 ADC may decrease relapse in the allogeneic transplant setting since many hematologic malignancies overexpress CD117. To advance this technology into the clinic, we developed a short half-life, fully human, anti-CD117-antibody conjugated to a non-genotoxic small molecule toxin (CD117-ADC), that kills >95% of primary human HSCs in vitro. Humanized NSG mice treated with a single dose of CD117-ADC displayed >98% depletion of human HSCs in the bone marrow, while sparing T and B cells. Preliminary tolerability data suggest a wide therapeutic index, greater than 20-fold. An unconjugated CD117 antagonist antibody was less effective with 100-fold more antibody unable to achieve similar levels of HSC depletion. The CD117-ADC is engineered to have a half-life of less than 12 hours, to facilitate clearance prior to donor cell infusion without the need for real-time pharmacokinetic monitoring. Finally, preliminary data shows that CD117-ADC may reduce tumor burden in mice challenged with CD117 expressing leukemic cells. Hematopoietic stem cell depletion with a targeted ADC has the promise to enable donor HSC engraftment, while preventing systemic toxicity associated with irradiation and chemotherapy. We have demonstrated that a short half-life ADC targeting CD117 depletes human HSCs in vitro and in vivo and has the potential to reduce tumor burden in mice. This novel conditioning approach could reduce the morbidity associated with current conditioning protocols, increase the number of patients eligible for HSCT, and enable autologous HSCT of gene modified stem cells.
Arabic sign language recognition using the leap motion controller (2014)

Sign language is important for facilitating communication between hearing impaired and the rest of society. Two approaches have traditionally been used in the literature: image-based and sensor-based systems. Sensor-based systems require the user to wear electronic gloves while performing the signs. The glove includes a number of sensors detecting different hand and finger articulations. Image-based systems use camera(s) to acquire a sequence of images of the hand. Each of the two approaches has its own disadvantages. The sensor-based method is not natural as the user must wear a cumbersome instrument while the imagebased system requires specific background and environmental conditions to achieve high accuracy. In this paper, we propose a new approach for Arabic Sign Language Recognition (ArSLR) which involves the use of the recently introduced Leap Motion Controller (LMC). This device detects and tracks the hand and fingers to provide position and motion information. We propose to use the LMC as a backbone of the ArSLR system. In addition to data acquisition, the system includes a preprocessing stage, a feature extraction stage, and a classification stage. We compare the performance of Multilayer Perceptron (MLP) neural networks with the Nave Bayes classifier. Using the proposed system on the Arabic sign alphabets gives 98% classification accuracy with the Nave Bayes classifier and more than 99% using the MLP.
Experimental autoimmune myasthenia gravis. (1980)

Injection of animals with purified acetylcholine receptor in complete Freund's adjuvant causes development of antibodies which crossreact with receptors in muscle. The crossreacting antibodies impair neuromuscular transmission. Animals with experimental autoimmune myasthenia gravis (EAMG) are excellent models for studying the complex mechanisms by which the autoimmune response to receptor in myasthenia gravis causes muscle weakness. This review first briefly describes the discovery of EAMG. Then, to provide the necessary perspective, receptor structure and function and properties of anti-receptor antibodies are discussed, followed by a brief review of the pathological mechanisms in EAMG.
Regulated morphology approach to fuzzy shape analysis with application to blood vessel extraction in thoracic CT scans (2004)

Blood vessel segmentation in volumetric data is a necessary prerequisite in various medical imaging applications. Specifically, when considering the application of automatic lung nodule detection in thoracic CT scans, segmented blood vessels can be used in order to resolve local ambiguities based on global considerations and so improve the performance of lung nodule detection algorithms. In this paper, a novel regulated morphology approach to fuzzy shape analysis is described in the context of blood vessel extraction in thoracic CT scans. The fuzzy shape representation is obtained by using regulated morphological operations. Such a representation is necessary due to noise present in the data and due to the discrete nature of the volumetric data produced by CT scans, and particularly the interslice spacing. Regulated morphological operations are a generalization of ordinary morphological operations which relax the extreme strictness inherent to ordinary morphological operations. Based on constraints of collinearity, size, and global direction, a tracking algorithm produces a set of connected trees representing blood vessels and nodules in the volume. The produced tree structures are composed of fuzzy spheres in which the degree of object membership is proportional to the ratio between the occupied volume and the volume of the discrete sphere encompassing it. The performance of the blood vessel extraction algorithm described in the paper is evaluated based on a distance measure between a known blood vessel structure and a recovered one. As the generation of synthetic data for which the true vessel network is known may not be sufficiently realistic, our evaluation is based on different versions of real data corrupted by multiplicative Gaussian noise.
Interactions of Bacteria with Contact Lenses: The Effect of Soluble Protein and Carbohydrate on Bacterial Adhesion to Contact Lenses (1998)

We could find no evidence to indicate that bacterial adhesion to contact lenses is mediated by specific interactions between bacteria and contact lens-bound tear components. The interaction between attached bacteria and lactoferrin may be important in initiating inflammatory responses to contact lens wear.
Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles (2016)

It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.
Validation of a Capillary Electrophoresis Assay for Monitoring Iodine Nutrition in Populations for Prevention of Iodine Deficiency: An Interlaboratory Method Comparison (2017)

CE offers a simple, selective, and cost-effective separation platform for surveillance of the iodine status of a population requiring only small volumes (<10 μL) of biobanked urine specimens, which is comparable to previously validated screening methods currently used in global health initiatives for prevention of iodine deficiency disorders.
Use of a tissue biomarker panel to predict which men with a rising PSA post-definitive prostate cancer therapy will have systemic progression (2007)

5017 Background: The majority of men with prostate cancer are diagnosed with cancers with low mortality. Such men are treated with radical prostatectomy, external beam radiotherapy, or brachytherapy and followed by serum PSA evaluations. Some men with a rising PSA therapy will have local recurrence or metastasis, but many will have no other evidence of recurrent disease other than a rising PSA. The PSA doubling time has been used to determine which of these men deserve adjuvant hormonal ablation, radiation therapy, or observation. We hypothesize that additional biomarkers will predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Methods: We designed a custom array containing 526 RNA targets whose expression has been reported to be altered in association with prostate cancer progression. We included targets from Mayo Clinic prostate cancer research. Together with a second commercial array, 530 genes implicated in prostate cancer progression and 420 other cancer-related genes were evaluated. A case-control design was used to test the association of the expression results with outcome. Cases were men post-radical prostatectomy who developed systemic progression within 5 years after PSA recurrence (N=213). Controls were matched men post-radical prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years (N=213). Results: Of 426 eligible patients, paraffin blocks were available on 418 (98.1%). RNA was prepared from all 418 blocks, and both arrays were both successful on 405 (96.9%) RNAs. Upon univariate analysis, 40 genes were highly significantly over- or under-expressed in the cases versus controls (1x10 -22 < p < 1x10 -7 ). Recursive partitioning (RP) selected 4 genes (TPX2, FAM13C1, TOPO2A and TSP2) that distinguished cases from controls. Random Forest analysis selected 24 genes (including 3 of the RP 4). A multivariable ROC analysis using these 24 genes generated an AUC of 0.80 (95% CI: 0.75–0.84). Conclusions: A specific gene expression pattern was significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. No significant financial relationships to disclose.
<i>Firmato</i> (2004)

In recent years packet-filtering firewalls have seen some impressive technological advances (e.g., stateful inspection, transparency, performance, etc.) and wide-spread deployment. In contrast, firewall and security <i>management</i> technology is lacking. In this paper we present <i>Firmato</i>, a firewall management toolkit, with the following distinguishing properties and components: (1) an entity-relationship model containing, in a unified form, global knowledge of the security policy and of the network topology; (2) a model definition language, which we use as an interface to define an instance of the entity-relationship model; (3) a model compiler, translating the global knowledge of the model into firewall-specific configuration files; and (4) a graphical firewall rule illustrator. We implemented a prototype of our toolkit to work with several commercially available firewall products. This prototype was used to control an operational firewall for several months. We believe that our approach is an important step toward streamlining the process of configuring and managing firewalls, especially in complex, multi-firewall installations.
Assignment of the human antithrombin III structural gene to chromosome 1q23–25 (1985)

The human antithrombin III (ATIII) structural gene was mapped by in situ hybridization and quantitative analysis of ATIII gene dosage in DNA isolated from carriers of chromosome 1 deletions. These studies indicate that the ATIII structural gene maps to human chromosome q23-q25 and so is likely identical to AT3.
Common-case computation (1999)

This paper presents a design methodology, called common-case computation (CCC), and new design automation algorithms for optimizing power consumption or performance. The proposed techniques are applicable in conjunction with any high-level design methodology where a structural register-transfer level (RTL) description and its corresponding scheduled behavioral (cycle-accurate functional RTL) description are available. It is a well-known fact that in behavioral descriptions of hardware (also in software), a small set of computations (CCCs) often accounts for most of the computational complexity. However, in hardware implementations (structural RTL or lower level), CCCs and the remaining computations a typically treated alike. This paper shows that identifying and exploiting CCCs during the design process can lead to implementations that are much more efficient in terms of power consumption or performance. We propose a CCC-based high-level design methodology with the following steps: extraction of common-case behaviors and execution conditions from the scheduled description, simplification of the common-case behaviors in a stand-alone manner, synthesis of common-case detection and execution circuits from the common-case behaviors, and composing the original design with the common-case circuits, resulting in a CCC-optimized design. We demonstrate that CCC-optimized designs reduce power consumption by up to 91.5%, or improve performance by up to 76.6% compared to designs derived without special regard for CCCs.
Systemic administration of urocortin after intracerebral hemorrhage reduces neurological deficits and neuroinflammation in rats (2012)

Systemic post-ICH treatment with UCN reduces striatal injury and neurological deficits, likely via suppression of microglial activation and inflammatory cytokine production. The low dose of UCN necessary and the clinically amenable peripheral route make UCN a potential candidate for development into a clinical treatment regimen.
Analysis of Vitamin D-Dependent Calcium-Binding Protein Messenger Ribonucleic Acid Expression in Mice Lacking the Vitamin D Receptor<sup>1</sup> (1998)

To investigate the roles of the receptor-dependent actions of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the regulation of vitamin D-dependent calcium-binding proteins (calbindin-D), the messenger RNA (mRNA) levels of calbindin-D9k and -28k were examined in vitamin D receptor (VDR)-ablated mice and control littermates. In VDR-ablated mice, calbindin-D9k mRNA was dramatically reduced in the intestine, kidneys, lungs, and brain; however, calbindin-D28k mRNA was only moderately decreased in the kidney. After 1,25-(OH)2D3 injection, calbindin-D9k mRNA levels and renal and alveolar calbindin-D28k mRNA levels were induced in control animals, but not in the homozygous mice. When the mice were fed a diet high in lactose, calcium, and phosphorus, intestinal calbindin-D9k mRNA levels in the homozygous mice were restored to those in their control littermates. However, this diet failed to normalize extraintestinal calbindin mRNA levels. These findings demonstrate that the receptor-dependent actions of 1,25-(OH)2D3 regulate calbindin-D9k gene expression and that tissue-specific factors modulate the effects of 1,25-(OH)2D3 on calbindin-D28k gene expression. These data also demonstrate that in the absence of a functional VDR, a high local concentration of calcium, phosphorus, and/or lactose in the intestinal lumen can normalize intestinal calbindin-D9k mRNA levels.
Properties of Imide Oligomers Containing Pendent Phenylethynyl Groups (1997)

As part of a programme to develop high-performance/high-temperature structural resins for aeronautical applications, imide oligomers containing pendent phenylethynyl groups were prepared, characterized, thermally cured and the cured resins evaluated as films, mouldings, adhesives and composites matrices. Initially a diamine containing a pendent phenylethynyl group (3, 5-diamino-4′-phenylethynylbenzophenone) was prepared and characterized. This compound was used to make amide acid and subsequently imide oligomers containing pendent phenylethynyl groups. In order to control the distance between reactive sites, the concentration of pendent phenylethynyl groups was varied randomly along the oligomer backbone. The amide acid oligomers in N-methyl-2-pyrrolidinone were processed into thin films, adhesive tape, carbon fibre prepreg and also converted into imide powder. After initial screening work was performed on unoriented thin films, imidized powders and neat resin mouldings to assess glass transition temperature, mechanical properties (tensile properties and fracture toughness), melt flow behaviour and processability, one particular formulation was scaled up for more comprehensive evaluation. This imide oligomer containing pendent phenylethynyl groups was fabricated into adhesive and composite specimens under 1.4 MPa for1hat 350–371 °C. Excellent mechanical properties were obtained at room temperature and 177 °C. The properties of this material are compared with those of a material of similar composition and molecular weight containing only terminal phenylethynyl groups.
An evolutionary simulated annealing algorithm for optimizing robotic task point ordering (2003)

High productivity requires that robot manipulators perform complex tasks in minimum time. The paper presents an evolutionary simulated annealing (ESA) algorithm for optimizing an important class of complex tasks of point-to-point moves, such as mechanical assembly, electronic component insertion, and spot welding. This algorithm combines the basic principles of two major heuristic search methods: simulated annealing and genetic algorithms. Indeed, these methods are commonly used to solve the well-known traveling salesman problem (TSP), and the point ordering problem in robotics is very similar to the TSP in mathematics. The three algorithms have been implemented in a computer-aided design (CAD) software system, CATIA. Experimental results show success factors for using ESA.
Identification of a Novel 1,4,8-Triazaphenanthrene Derivative as a Neuroprotectant for Dopamine Neurons Vulnerable in Parkinson’s Disease (2017)

Parkinson's disease (PD) is a chronic degenerative disorder characterized by typical motor symptoms caused by the death of dopamine (DA) neurons in the midbrain and ensuing shortage of DA in the striatum, at the level of nerve terminals. No curative treatment is presently available for PD in clinical practice. In our search for neuroprotectants in PD, we generated new 1,4,8-triazaphenanthrenes by combining 6-endo-dig-cycloisomerization of propargylquinoxalines and Suzuki or Sonogashira cross-coupling reactions. Neuroprotection assessment of newly synthesized 1,4,8-triazaphenanthrenes in a PD cellular model resulted in the discovery of a new hit compound PPQ (5m). Neuroprotection by 5m was concentration-dependent and the result of a combined effect on intracellular calcium release channels and astroglial cells. Of interest, 5m also counteracted DA cell loss in a mouse model of PD, making this molecule a promising candidate for PD treatment.
Self-starting mode-locked ring-cavity Ti:sapphire laser (1992)

A self-mode-locked ring-cavity Ti:sapphire laser is described that is self-starting within milliseconds and completely unperturbed by the self-starting mechanism while mode locked. This technique makes use of a position-modulated mirror in an external cavity in which the cavity length and alignment are noncritical. Other benefits of the ring cavity over the linear cavity configuration are described.
In vivo imaging rhodopsin distribution in the photoreceptors with nano-second pulsed scanning laser ophthalmoscopy. (2015)

The preliminary results showed that our nano-second pulsed-light SLO is promising in imaging the functional biomarker of the rod photoreceptors. By using nanosecond pulsed laser, in which one laser pulse generates one pixel of the image, the absorption of rhodopsin intermediates can be reduced.
Compact micro-optic based components for hollow core fibers (2020)

Using micro-optic collimator technology, we present compact, low-loss optical interconnection devices for hollow core fibers (HCFs). This approach is one of the key manufacturing platforms for commercially available fiber optic components and most forms of HCFs can readily be incorporated into this platform without the need for any substantial or complicated adaptation or physical deformation of the fiber structure. Furthermore, this technique can provide for very low Fresnel reflection interconnection between solid-core fiber and HCF and in addition provides a hermetic seal for HCFs, which can be a critical issue for many HCF applications. In this paper, several exemplar HCF components are fabricated with low insertion loss (0.5-2 dB), low Fresnel reflection (-45 dB) and high modal purity (>20 dB) using various state-of-the-art HCFs.