gebhart/patrepeval huggingface dataset:
Cannabinoids: Novel Medicines for the Treatment of Huntingtons Disease (2011)

Cannabinoid pharmacology has experienced a notable increase in the last 3 decades which is allowing the development of novel cannabinoid-based medicines for the treatment of different human pathologies, for example, Cesamet® (nabilone) or Marinol® (synthetic Δ9-tetrahydrocannabinol for oral administration) that were approved in 80s for the treatment of nausea and vomiting associated with chemotherapy treatment in cancer patients and in 90s for anorexiacachexia associated with AIDS therapy. Recently, the british company GW Pharmaceuticals plc has developed an oromucosal spray called Sativex®, which is constituted by an equimolecular combination of Δ9-tetrahydrocannabinol- and cannabidiol- enriched botanical extracts. Sativex® has been approved for the treatment of specific symptoms (i.e. spasticity and pain) of multiple sclerosis patients in various countries (i.e. Canada, UK, Spain, New Zealand). However, this cannabis- based medicine has been also proposed to be useful in other neurological disorders given the analgesic, antitumoral, anti-inflammatory, and neuroprotective properties of their components demonstrated in preclinical models. Numerous clinical trials are presently being conducted to confirm this potential in patients. We are particularly interested in the case of Huntington's disease (HD), an autosomal-dominant inherited disorder caused by an excess of CAG repeats in the genomic allele resulting in a polyQ expansion in the encoded protein called huntingtin, and that affects primarily striatal and cortical neurons thus producing motor abnormalities (i.e. chorea) and dementia. Cannabinoids have been studied for alleviation of hyperkinetic symptoms, given their inhibitory effects on movement, and, in particular, as disease-modifying agents due to their anti-inflammatory, neuroprotective and neuroregenerative properties. This potential has been corroborated in different experimental models of HD and using different types of cannabinoid agonists, including the phytocannabinoids present in Sativex®, and we are close to initiate a clinical trial with this cannabis-based medicine to evaluate its capability as a disease-modifying agent in a population of HD patients. The present review will address all preclinical evidence supporting the potential of Sativex® for the treatment of disease progression in HD patients. The article presents some promising patents on the cannabinoids.
Robust high-temperature sapphire cell for metal vapors (1995)

We describe a simple vacuum cell that successfully contains high-temperature and high-density alkali-metal and alkaline-earth vapors. The transparent cell, made from sapphire parts joined by melted glass powders, operates without a buffer gas. Temperatures over 700 °C and metal-vapor densities greater than 1017 cm−3 have been achieved. Such an optical cell is useful for many atomic physics experiments where collisions with buffer gas atoms are problematic or where a spatially uniform distribution of high-density, corrosive atoms is desired.
Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody–drug conjugate in development for the treatment of HER2-positive cancer (2012)

The PK profile of single-agent T-DM1 (3.6 mg/kg q3w) is predictable, well characterized, and unaffected by circulating levels of HER2 extracellular domain or residual trastuzumab. T-DM1 exposure does not correlate with clinical responses or key adverse events.
INHIBITION OF CELL-PROLIFERATION BY AN ADENOVIRUS VECTOR EXPRESSING THE HUMAN WILD TYPE-P53 PROTEIN (1993)

We have developed human adenovirus 5 (Ad5) vectors expressing the wild type human p53 protein or a mutant p53 form under the control of the human cytomegalovirus immediate early gene promoter. Human cells infected with these vectors expressed high levels of p53, accumulating 20-40 fold more protein than found in normal human fibroblasts. The ability of the vectors to affect proliferation of cells in culture was assessed by measuring cell DNA synthesis and colony forming ability after infection with viruses. When the p53 deficient ovarian carcinoma cell line, SKOV-3, was infected with Adp53wt expressing the wild type (wt) p53 protein, a significant inhibition of cellular DNA synthesis was observed, relative to cells infected with Adp53m expressing mutant p53, or a control virus, AdLacZ, expressing bacterial beta-galactosidase. Inhibition was dependent on multiplicity of infection, with no significant effect below 5 pfu/cell, and maximal effect between 25 and 100 PFU/cell which resulted in approximately 95% inhibition of SKOV-3 cell DNA synthesis relative to mock infected cells. Infection of normal human fibroblasts with Adp53wt also inhibited DNA synthesis but to a significantly lesser degree. SKOV-3 cell survival, assayed by ability to form colonies, was reduced at least 10 fold after infection with Adp53wt compared to colony forming ability of cells after infection with either AdLacZ or Adp53m. The results of these studies indicate that p53 expressed by Ad vectors can inhibit proliferation in culture of p53 negative cells by at least 95%, and suggest that such vectors might similarly inhibit the proliferation of tumor cells in vivo.
Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. (2000)

Cancer metastasis is an inefficient process. The steps in metastasis responsible for this inefficiency and how metastatic inefficiency can vary in different locations within an organ remain poorly understood. B16F10 cells were injected to target mouse lung, and at sequential times thereafter we quantified in lung the time course of: (a) overall cell survival and metastatic development; and (b) local cell survival and growth with respect to the lung surface and specific interior structures. We found high rates of initial survival of cells trapped in the lung circulation, extravasation into lung tissue, and subsequent survival of extravasated solitary cells (74% at day 3) before metastasis formation. However, at the time of initial replication of metastatic cells a major loss of cells occurred. Although only a small proportion of injected cells started to form metastases, most of these developed into macroscopic tumors. Solitary cells found at later times were dormant. Thus, overall metastatic inefficiency was largely due to postextravasation events affecting solitary cells. Regionally within the lung, cells and metastases were randomly distributed to day 4, but by day 10 preferential tumor growth was found along the lung surface and around arterial and venous vessels. Thus, trapping and early growth of injected cells was unaffected by location within the lung, whereas subsequent metastatic growth was enhanced in specific microenvironments. This study: (a) quantifies early temporal and spatial progression of metastasis in lung; (b) documents persistence of solitary dormant cells; and (c) shows that metastatic inefficiency depends on the initiation of growth in a subset of extravasated cells, whereas continued growth of metastases occurs preferentially in specific tissue environments.
Enzymatic synthesis of gene-length single-stranded DNA (2017)

Single-stranded DNA (ssDNA) increases the likelihood of homology directed repair with reduced cellular toxic ity, yet ssDNA synthesis strategies are limited by the maximum length attainable, as well control over nucleotide composition. Here, we apply purely enzymatic synthesis to generate ssDNA greater than 15 kb using asymmetric PCR, and illustrate the incorporation of diverse modified nucleotides for therapeutic and imaging applications.
Design and Implementation of Humanoid Robot Controller Based on CAN (2005)

Aiming at Humanoid Robot structure and requirement for control performance, this paper designs and realizes joint controller based on CAN, and structures an effective credible control system by connecting controllers, force sensors and harmonious level computer together. This paper includes mainly: overall structure of the system, design and implement of hardware and software, topology of control system, and bring forward some imaginations to enhance performance of the system.
Effects of fibroblasts and basic fibroblast growth factor on facilitation of dermal wound healing by type I collagen matrices (1991)

Healing of large open dermal wounds is associated with decreased values of the tensile strength even up to 6 months post-wounding. Results of previous studies have shown that healing is facilitated in the presence of a type I collagen sponge by promoting deposition of newly synthesized large-diameter collagen fibers parallel to the fibers of the sponge. In this study healing is evaluated in dermal wounds treated with a collagen sponge seeded with fibroblasts or coated with basic fibroblast growth factor (bFGF). Experimental results indicate that the presence of a collagen sponge results in increased wound tensile strength and increased collagen fiber diameters in the upper dermis 15 days post-wounding in an excisional guinea pig dermal wound model. In comparison, dermal wounds treated with collagen sponges seeded with fibroblasts or coated with bFGF showed increased tensile strengths 15 days postimplantation and increased degree of reepithelialization. These results indicate that fibroblast seeding and bFGF coating in conjunction with a type I collagen sponge matrix facilitate early dermal and epidermal wound healing.
S/MIMO MC-CDMA Heuristic Multiuser Detectors Based on Single-Objective Optimization (2009)

This paper analyzes the complexity-performance trade-off of several heuristic near-optimum multiuser detection (MuD) approaches applied to the uplink of synchronous single/multiple-input multiple-output multicarrier code division multiple access (S/MIMO MC-CDMA) systems. Genetic algorithm (GA), short term tabu search (STTS) and reactive tabu search (RTS), simulated annealing (SA), particle swarm optimization (PSO), and 1-opt local search (1-LS) heuristic multiuser detection algorithms (Heur-MuDs) are analyzed in details, using a single-objective antenna-diversity-aided optimization approach. Monte- Carlo simulations show that, after convergence, the performances reached by all near-optimum Heur-MuDs are similar. However, the computational complexities may differ substantially, depending on the system operation conditions. Their complexities are carefully analyzed in order to obtain a general complexity-performance framework comparison and to show that unitary Hamming distance search MuD (uH-ds) approaches (1-LS, SA, RTS and STTS) reach the best convergence rates, and among them, the 1-LS-MuD provides the best trade-off between implementation complexity and bit error rate (BER) performance.
Malignant conversion of murine squamous papilloma cell lines by transfection with the fos oncogene (1988)

Murine papilloma cell lines 308 and SP-1 have been used as recipients for transfected oncogenes to investigate malignant conversion. These cell lines express an activated c-rasHa gene with a codon 61 mutation and produce squamous papillomas when transplanted as skin grafts onto nude mice. They are not tumorigenic by subcutaneous injection. Both papilloma cell lines were stably transfected with plasmid DNA containing either a rearranged murine plasmacytoma-derived c-myc (minus exon 1), adenovirus 5 E1A, FBJ v-fos or a human c-fos/FBJ v-fos chimera, using cotransfection with the neomycin resistance gene contained in pSV2neo to select for transformants. Southern and northern blotting analysis confirmed the uptake and expression of exogenous DNA in both G418-selected cell lines and in the derived tumors. Unlike the E1A- and myc-containing plasmids, both fos constructs caused malignant conversion in either cell line, as defined by the squamous cell carcinoma histology of tumors from grafted cells and the development of carcinomas after subcutaneous injection into athymic nude mice. Immunofluorescence analysis for specific keratin gene expression indicated that tumors derived by introduction of either of the fos oncogenes were devoid of staining for K1, a 67 kDa epidermal keratin that is expressed in papillomas but not in squamous carcinomas. Tumors from E1A, myc, or pSV2neo transfectants expressed K1, although in a focal distribution. The malignant phenotype induced by the fos oncogene constructs was not associated with the ability to form agar colonies in vitro or to express gamma-glutamyl transpeptidase in the tumors. Since both 308 and SP-1 were sensitive to the fos oncogene for malignant conversion and insensitive to E1A or myc, it is possible that fos may cooperate with the endogenous-activated c-rasHa gene to convert these cells to malignancy. However, since gamma-glutamyl transpeptidase activity is found in the majority of chemically induced mouse skin carcinomas that possess an activated c-rasHa gene, fos activation may not be a common pathway for spontaneous malignant conversion.
Increased expression of utrophin in a slow vs. a fast muscle involves posttranscriptional events (2001)

In addition to showing differences in the levels of contractile proteins and metabolic enzymes, fast and slow muscles also differ in their expression profile of structural and synaptic proteins. Because utrophin is a structural protein expressed at the neuromuscular junction, we hypothesize that its expression may be different between fast and slow muscles. Western blots showed that, compared with fast extensor digitorum longus (EDL) muscles, slow soleus muscles contain significantly more utrophin. Quantitative RT-PCR revealed that this difference is accompanied by a parallel increase in the expression of utrophin transcripts. Interestingly, the higher levels of utrophin and its mRNA appear to occur in extrasynaptic regions of muscle fibers as shown by immunofluorescence and in situ hybridization experiments. Furthermore, nuclear run-on assays showed that the rate of transcription of the utrophin gene was nearly identical between EDL and soleus muscles, indicating that increased mRNA stability accounts for the higher levels of utrophin in slow muscles. Direct plasmid injections of reporter gene constructs showed that cis-acting elements contained within the utrophin 3'-untranslated region (3'-UTR) confer greater stability to chimeric LacZ transcripts in soleus muscles. Finally, we observed a clear difference between EDL and soleus muscles in the abundance of RNA-binding proteins interacting with the utrophin 3'-UTR. Together, these findings highlight the contribution of posttranscriptional events in regulating the expression of utrophin in muscle.
The use of poloxamer hydrogels for the assessment of biofilm susceptibility towards biocide treatments (1998)

Poloxamer F127 is a non-toxic, di-block copolymer of polyoxyethylene and polyoxypropylene. Aqueous solutions (30% w/v) show thermoreversible gelation, being liquid at temperatures < 15 degrees C and robust gels at temperatures > 15 degrees C. Chilled poloxamer (30% in tryptone soya broth) was mixed with an inoculum of Pseudomonas aeruginosa (10(4) cfu ml-1) and placed as 100 microliters drops onto separate glass cover-slips. These were placed into sealed Petri dishes containing moistened cotton wool and incubated at 35 degrees C. Viable counts could be performed on the poloxamer gels by transfer of the coverslips to diluents at < 15 degrees C. Growth curves in the gels and in liquid batch cultures were indistinguishable from one another with stationary phase cell densities, being approximately 5 x 10(10) cfu ml-1 in each at 16 h. SDS-PAGE of cell envelope preparations showed the poloxamer-grown cells to exhibit a biofilm rather than planktonic phenotype. Susceptibility towards various concentrations of chlorhexidine, iodine and hydrogen peroxide was assessed for 10 min at 35 degrees C for suspensions of broth-grown cells and for incubated poloxamer-gels (1 and 16 h). The gels were immersed in biocide, on their glass supports, before transfer to neutralizer at 10 degrees C where dissolution was complete within 5 min. Further serial dilutions and plate counts were made. While modest decreases in susceptibility towards all biocides were associated with incorporation of the inoculum with the gel (1 h incubation), substantial changes were noted after prolonged incubation and adaptation to a biofilm phenotype (16 h incubation). The gel populations mimic the localized high cell densities observed in biofilms and will also be subject to the same nutrient and chemical gradients as found within natural biofilms. Thermoreversible gelation enables complete recovery of the test inoculum without further trauma. They therefore provide an effective model for assessing biofilm susceptibility towards biocides and would be suitable for screening programmes.
Modeling the Well-Edge Proximity Effect in Highly Scaled MOSFETs (2006)

The well-edge proximity effect caused by ion scattering during implantation in highly scaled CMOS technology is explored from a physics and process perspective. Technology computer-aided design (TCAD) simulations together with silicon wafer experiments have been conducted to investigate the impact of this effect. The ion scattering model and TCAD simulations provided a physical understanding of how the internal changes of the MOSFETs are formed. A new compact model for SPICE is proposed using physics-based understanding and has been calibrated using experimental silicon test sets
Gastrointestinal Stromal Tumors: Review on Morphology, Molecular Pathology, Prognosis, and Differential Diagnosis (2006)

GISTs usually occur in older adults (median age 55-60 years) and rarely in children in the second decade (<1%) throughout the gastrointestinal tract: 60% in stomach, 35% in small intestine, and less than 5% in rectum, esophagus, omentum, and mesentery; most GISTs in the latter 2 sites are metastatic. Five percent of GISTs occur in patients with neurofibromatosis type 1 syndrome (multiple small intestinal tumors) and in Carney triad (gastric epithelioid GISTs in young females). Familial GISTs occur in patients with inheritable germline Kit or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Histologically GISTs vary from spindle cell tumors to epithelioid and pleomorphic tumors. Most GISTs (95%) express Kit (CD117), CD34 (70%), and heavy caldesmon (80%), whereas 25% are positive for smooth muscle actin and less than 5% for desmin. Tumor size and mitotic activity are best predictive prognostic features; small intestinal tumors behave more aggressively than gastric tumors with similar parameters. Mutually exclusive gain-of-function Kit or PDGFRA mutations occur in a majority of GISTs representing in-frame deletions, point mutations, duplications and insertions. Mutations in Kit juxtamembrane domain (exon 11) are the most common in GISTs of all sites, whereas rare Kit extracellular domain (exon 9) Ala502-Tyr503 duplication is specific for intestinal GISTs. Mutations in PDGFRA have been identified in juxtamembrane (exon 12) and tyrosine kinase domains (exons 14 and 18), nearly exclusively in gastric GISTs, mostly in epithelioid variants. Some Kit and PDGFRA mutations have a prognostic value. Kit/PDGFRA tyrosine kinase inhibitor imatinib has been successfully used in the treatment of metastatic GISTs for more than 5 years. However, primary and acquired secondary resistance linked to certain types of Kit and PDGFRA mutations is limiting long-term success necessitating the use of alternative treatments.
Treating New-Onset Catabolic Type 2 Diabetes With Glargine and Lispro (2006)

N.D., a 38-year-old African-American woman, was admitted to the hospital with a plasma glucose level of 793 mg/dl and 2+ urine ketones. She had no history of diabetes and last saw her primary care provider 6 months ago for her annual examination. Her plasma glucose level was normal at that time. She had lost 30 lb in the past 8 weeks, and she reported having had polyuria and polydipsia for 2 weeks. She reported anorexia with very little oral intake for the past 2 days. Her weight was 220 lb (100 kg). Physical examination showed acanthosis nigricans and morbid obesity.

She had been given 10 units of regular insulin subcutaneously and 2 l of normal saline intravenously in the emergency department, resulting in a plasma blood glucose of 525 mg/dl. Results of a basic chemistry panel were:

1. Sodium: 134 mg/dl

2. Potassium: 3.9 mg/dl

3. Bicarbonate: 20 mg/dl

4. Chloride: 100 mg/dl

5. Creatinine: 1.0 mg/dl

Overnight, she was given “sliding scale” insulin, 10 units every 6 hours, for glucose levels consistently > 400 mg/dl. The next morning, an insulin drip was started. During the next 24 hours, 100 units of intravenous lispro in a drip resulted in a fasting plasma glucose of 120 mg/dl. Her hemoglobin A1c (A1C) was 12.2%.

The next evening, she was given 50 units of glargine with premeal supplements of lispro to a total of 50 units (15 units at breakfast, 15 units at lunch, and 20 units at dinner). Her blood glucose levels now were well controlled without initial hypoglycemia.

During the next …
Characterization of a Mouse Factor IX cDNA and Developmental Regulation of the Factor IX Gene Expression in Liver (1991)

A mouse factor IX cDNA was isolated and characterized. The cDNA was 1,837 bp in length and contained the coding region as well as short 5' and 3' untranslated sequences. Northern blot analysis of liver RNA showed two mRNA species of 3.2 kb (major) and 2.2 kb (minor) for the mouse factor IX. An antisense RNA probe prepared from the mouse cDNA was employed to determine the steady state level of factor IX mRNA in mouse liver at various developmental stages. The factor IX mRNA level was very low (2-5% of the adult level) during the gestational period until day -3 (gestational day 17) followed by a rapid increase at day -2 through birth. This phase of rapid increase was followed by a gradual increase before it reached the adult level at around 20 to 24 days. At birth, the factor IX mRNA level was found to be at about 43% of that of the adult. The mRNA levels in mouse liver agreed well with the plasma factor IX activity levels. These results indicate that reduced factor IX activity in newborns is due to the low levels of factor IX mRNA available for translation.
A family of concanavalin A-binding peptides from a hexapeptide epitope library. (1992)

The lectin concanavalin A (Con A) binds methyl alpha-D-mannopyranoside (Me alpha Man) as well as alpha-D-mannosyl groups at the nonreducing terminus of oligosaccharides. Ligand peptides that mimic the binding of Me alpha Man to Con A were identified from screening an epitope library composed of filamentous phage displaying random hexapeptides. A consensus sequence was identified among affinity-purified phage; Con A binds phage bearing this sequence and is inhibited from doing so by Me alpha Man. When tested for binding against a panel of lectins, phage bearing this sequence bind only weakly to a closely related D-mannose-binding lectin, indicating that binding to Con A is highly selective. A synthetic peptide bearing the consensus sequence blocks the precipitation of Con A by dextran with an inhibition strength equivalent to that of methyl alpha-D-glucopyranoside. These results demonstrate that the specificity of Con A is not limited to carbohydrates and that highly selective sugar-mimics for lectins of plant, animal, or bacterial origin may be identified from epitope libraries.