gebhart/patrepeval huggingface dataset:
Plant nuclear gene knockout reveals a role in plastid division for the homolog of the bacterial cell division protein FtsZ, an ancestral tubulin (1998)

Little is known about the division of eukaryotic cell organelles and up to now neither in animals nor in plants has a gene product been shown to mediate this process. A cDNA encoding a homolog of the bacterial cell division protein FtsZ, an ancestral tubulin, was isolated from the eukaryote Physcomitrella patens and used to disrupt efficiently the genomic locus in this terrestrial seedless plant. Seven out of 51 transgenics obtained were knockout plants generated by homologous recombination; they were specifically impeded in plastid division with no detectable effect on mitochondrial division or plant morphology. Implications on the theory of endosymbiosis and on the use of reverse genetics in plants are discussed.
Modification of Radiation Myelopathy by the Transplantation of Neural Stem Cells in the Rat (2001)

In a novel approach, neural stem cells were transplanted to ameliorate radiation-induced myelopathy in the spinal cords of rats. A 12-mm section of the cervical spinal cord (T2-C2) of 5-week-old female Sprague-Dawley rats was locally irradiated with a single dose of 22 Gy of (60)Co gamma rays. This dose is known to produce myelopathy in all animals within 6 months of irradiation. After irradiation, the animals were subdivided into three groups, and at 90 days after irradiation, neural stem cells or saline (for controls) were injected into the spinal cord, intramedullary, at two sites positioned 6 mm apart on either side of the center of the irradiated length of spinal cord. The injection volume was 2 microl. Group I received a suspension of MHP36 cells, Group II MHP15 cells, and Group III (controls) two injections of 2 microl saline. All rats received 10 mg/kg cyclosporin (10 mg/ml) daily i.p. to produce immunosuppression. All animals that received saline (Group III) developed paralysis within 167 days of irradiation. The paralysis-free survival rates of rats that received transplanted MHP36 and MHP15 cells (Groups I and II) were 36.4% and 32% at 183 days, respectively. It was concluded that transplantation of neural stem cells 90 days after irradiation significantly (P = 0.03) ameliorated the expression of radiation-induced myelopathy in the spinal cords of rats.
Regulation of ATP-ubiquitin-dependent proteolysis in muscle wasting (1994)

Protein breakdown plays a major role in muscle growth and atrophy. However, the regulation of muscle proteolysis by nutritional, hormonal and mechanical factors remains poorly understood. In this review, the methods available to study skeletal muscle protein breakdown, and our current understanding of the role of 3 major proteolytic systems that are well characterized in this tissue (ie the lysosomal, Ca(2+)-dependent and ATP-ubiquitin-dependent proteolytic pathways) are critically analyzed. ATP-ubiquitin-dependent proteolysis is discussed in particular since recent data strongly suggest that this pathway may be responsible for the loss of myofibrillar proteins in many muscle-wasting conditions in rodents. In striking contrast to either the lysosomal or the Ca(2+)-dependent processes, ATP-ubiquitin-dependent protein breakdown is systematically influenced by nutritional manipulation (fasting and dietary protein deficiency), muscle activity and disuse (denervation atrophy and simulated weightlessness), as well as pathological conditions (sepsis, cancer, trauma and acidosis). The hormonal control of this pathway, its possible substrates, rate-limiting step, and functional associations with other proteolytic systems are discussed.
Phase annealing in SHELX-90: direct methods for larger structures (1990)

A number of extensions to the multisolution approach to the crystallographic phase problem are discussed in which the negative quartet relations play an important role. A phase annealing method, related to the simulated annealing approach in other optimization problems, is proposed and it is shown that it can result in an improvement of up to an order of magnitude in the chances of solving large structures at atomic resolution. The ideas presented here are incorporated in the program system SHELX-90; the philosophical and mathematical background to the direct-methods part (SHELXS) of this system is described.
Local and systemic tolerance of flutrimazole skin creams following single and repeated topical application in healthy volunteers. (1992)

A double-blind, randomized phase I study was performed in 21 healthy volunteers to evaluate the dermal tolerance of skin creams containing 1% and 2% 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) or only the excipient, versus a commercial skin cream containing 1% clotrimazole. The study was carried out using the patch-test procedure performed in three stages: 1. single application in the back skin; 2. induction period (usage test) using three skin areas on the volar side of the forearm of each subject, where skin cream samples were applied once a day for a period of three weeks; and 3. after a wash-out period of two weeks, challenge applications in the back and forearm skin. The systemic tolerance of the formulations was also tested. There was no evidence of allergic sensitization after the application of flutrimazole creams, or their excipients, with signs of mild and doubtful skin reactions being observed in few subjects with all formulations. Furthermore, no systemic side effects after topical administration were detected throughout the study.
Influence of Sleep on Genioglossus Muscle Activation by Negative Pressure in Normal Men (1993)

An important mechanism controlling genioglossus (GG) muscle activity is the reflex response to negative airway pressure. We hypothesize that this reflex response may be lost during sleep and believe that this loss may be important in the pathogenesis of airway collapse during sleep. Thus, we determined the effect of non-rapid eye movement (NREM) sleep on the GG electromyogram (EMG) response to brief (0.2 to 0.6 s) episodes of negative pressure generation (NPG) in the upper airway of six normal subjects. Up to 100 NPGs (mean 58 +/- 12) were recorded both awake and during stable NREM sleep. During wakefulness, the change in GG moving time average EMG from basal to peak levels (during NPG) was 17.1 +/- 2.5 au (a 154 +/- 22% increase above basal levels). This response was markedly reduced during NREM sleep (2.7 +/- 1.2 au; p < 0.01). The latency of the GG EMG response was 53.8 +/- 11.5 ms during wakefulness (n = 6), but much longer during sleep (132.7 +/- 24.5 ms; n = 3; p < 0.03). We conclude that in normal subjects (1) the GG muscle responds to negative airway pressure by reflex activation during wakefulness, and (2) this reflex activation is reduced or lost during NREM sleep. We speculate that loss of this mechanism during sleep may contribute to pharyngeal collapse in obstructive apnea patients.
Lessons Learned: Dose Selection of Small Molecule–Targeted Oncology Drugs (2016)

Evaluation of dose plays a critical role in a successful oncology development program. Typically for oncology agents, the first-in-man phase I dose-escalation trials are conducted to determine a maximum tolerated dose (MTD). This MTD is taken forward into subsequent trials to establish the safety and efficacy of the drug product. Although this approach was appropriate historically for cytotoxics, the application of MTD as the recommend phase II dose has been problematic for the newer small molecule-targeted oncology agents. Promising alternative approaches using dose and exposure exploration, including lessons learned from recent targeted oncology agent development and approvals, are summarized and discussed. Clin Cancer Res; 22(11); 2630-8. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS".
Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing (2012)

Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. IMPORTANCE Antibiotic-associated diarrhea (AAD) due to Clostridium difficile is a widespread phenomenon in hospitals today. Despite the use of antibiotics, up to 30% of patients are unable to clear the infection and suffer recurrent bouts of diarrheal disease. As a result, clinicians have resorted to fecal microbiome transplantation (FT). Donor stool for this type of therapy is typically obtained from a spouse or close relative and thoroughly tested for various pathogenic microorganisms prior to infusion. Anecdotal reports suggest a very high success rate of FT in patients who fail antibiotic treatment (>90%). We used deep-sequencing technology to explore the human microbial diversity in patients with Clostridium difficile infection (CDI) disease after FT. Genus- and species-level analysis revealed a cocktail of microorganisms in the Bacteroidetes and Firmicutes phyla that may ultimately be used as a probiotic to treat CDI.
Shikimic Acid: Metabolism and Metabolites (1993)

Commentary and Overview Chemistry of Intermediates in the Common Pathway Enzymes and Enzymology of the Common Pathway Beyond Chorismate - Primary Essential Metabolites Beyond Chorismate - Secondary Metabolism.
Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets (2008)

Resolvin E1 (RvE1) is an omega-3 eicosapentaenoic acid (EPA)-derived lipid mediator generated during resolution of inflammation and in human vasculature via leukocyte-endothelial cell interactions. RvE1 possesses anti-inflammatory and proresolving actions. Here, we report that RvE1 in human whole blood rapidly regulates leukocyte expression of adhesion molecules. RvE1 in the 10- to 100-nM range stimulated L-selectin shedding, while reducing CD18 expression in both neutrophils and monocytes. When added to whole blood, RvE1 did not stimulate reactive oxygen species by either neutrophils or monocytes, nor did it directly stimulate cytokine/chemokine production in heparinized blood. Intravital microscopy (IVM) demonstrated that RvE1 rapidly reduced leukocyte rolling (approximately 40%) in venules of mice. In human platelet-rich plasma (PRP), RvE1 selectively blocked both ADP-stimulated and thromboxane receptor agonist U46619-stimulated platelet aggregation in a concentration-dependent manner. In contrast, Delta 6,14-trans-RvE1 isomer was inactive. RvE1 did not block collagen-stimulated aggregation, and regulation of ADP-induced platelet aggregation was not further enhanced with aspirin treatment. These results indicate RvE1 is a potent modulator of leukocytes as well as selective platelet responses in blood and PRP, respectively. Moreover, the results demonstrate novel agonist-specific antiplatelet actions of RvE1 that are potent and may underlie some of the beneficial actions of EPA in humans.
Association between the interleukin‐1 family gene cluster and psoriatic arthritis (2006)

The IL1 locus appears to be a high-priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk.
Vaccines consisting of periodate-cleaved oligosaccharides from the capsule of Haemophilus influenzae type b coupled to a protein carrier: structural and temporal requirements for priming in the human infant. (1986)

Reducing oligosaccharides from the Haemophilus influenzae type b capsular polymer (PRP) coupled by reductive amination to diphtheria toxoids (DTd) had been shown to elicit potentially protective serum anti-PRP antibodies (Ab) in infants too young for an adequate response to PRP vaccine. Here we report that cleavage of PRP with periodate gives antigenic oligosaccharides that couple with high efficiency. DTd-coupled saccharides of mean length eight or 20 repeat units (Dpo8 and Dpo20, respectively) were tested for immunogenicity in young adults (single injection) and in infants 9 to 15 mo old who received a sequence of primary (1 degree) and secondary (2 degrees) injections. Both vaccines consistently induced high anti-PRP Ab responses in adults. In infants, Dpo8 elicited only modest anti-PRP responses, whereas Dpo20 gave consistently high titers; post-2 degrees responses were higher when the interval between 1 degree and 2 degrees injections was 6 to 14 wk than with an interval of 2 to 4 wk. Thus with this type of immunogen, priming responses in infancy has more stringent structural requirements than does triggering responses in adults, and the priming appears to maximize more slowly than the Ab level.
Multiple Layer‐by‐Layer Lipid‐Polymer Hybrid Nanoparticles for Improved FOLFIRINOX Chemotherapy in Pancreatic Tumor Models (2014)

The FOLFIRINOX regimen, a combination of three chemotherapy agents (5‐fluorouracil, irinotecan, oxaliplatin) and folinic acid (a vitamin B derivatives reducing the side effect of 5‐fluorouracil), has proved to be effective in the treatment of pancreatic cancer, and is more efficacious than the long‐term reference standard, gemcitabine. However, the FOLFIRINOX is associated with high‐grade toxicity, which markedly limits its clinical application. Encapsulation of drugs in nanocarriers that selectively target cancer cells promises to be an effective method for co‐delivery of drug combinations and to mitigate the side effects of conventional chemotherapy. Here we reported the development of multiple layer‐by‐layer lipid‐polymer hybrid nanoparticles with targeting capability that show excellent biocompatibility and synergistically combine the favorable properties of liposomes and polymer nanoparticles. Relative to nanoparticles consisting of polymer alone, these novel nanocarriers have a long half‐life in vivo and a higher stability in serum. The nanocarriers were loaded with the three active antitumor constituents of FOLFIRINOX regimen. Little drugs were released from the nanoparticles in phosphate buffered saline (PBS) solution, but the cargoes were quickly released after the nanoparticles were taken up by tumor cells. These innovative drug‐loaded nanoparticles achieved higher antitumor efficacy and showed minimal side effects compared with the FOLFIRINOX regimen alone. Our study suggested that the multiple layer‐by‐layer hybrid nanoparticles have great potential for improving the chemotherapeutic efficacy for the patients with pancreatic cancer. This platform also provides new opportunities for tailored design of nanoparticles that may offer therapeutics benefits for a range of other tumors.
Biosafety Assessment of Site-directed Transgene Integration in Human Umbilical Cord–lining Cells (2010)

Biosafety and efficacy considerations that impede clinical application of gene therapy could be addressed by nonviral ex vivo cell therapy, utilizing transgenic cells that have been comprehensively pre-evaluated for genotoxic potential and transgene expression. We evaluated the genotoxic potential of phiC31 bacteriophage integrase-mediated transgene integration in cord-lining epithelial cells (CLECs) readily cultured from the outer membrane of human umbilical cords, by sequencing and mapping integration sites, spectral karyotyping, high-resolution genome copy number, transcriptome, and transgene copy number analyses and in vivo tumorigenicity. Of 44 independent integration events, <5% were exonic and 85% of modified cells had integrated <or=2 transgene(s). Expression of 95.6% of genes was unaltered in modified cells. Only three small regions showed genome copy number changes that did not correlate with altered gene expression or integration sites. Spectral karyotyping revealed rare nonrecurrent occurrence of three different translocations. Integrase-modified cells were not tumorigenic in immunocompromised mice for at least 4 months. Stable integration of a human factor VIII (FVIII) construct conferred durable FVIII secretion in vitro. Xenoimplantation of FVIII-secreting CLECs in immunocompetent hemophilic mice achieved significant phenotypic correction. Pre-evaluated clonal populations of phiC31 integrase-modified CLECs could be useful as bioimplants for monogenic diseases such as hemophilia.
The Classification of Low Back Pain (1989)

The majority of patients with low back pain offer no objective clinical findings on which to make a diagnosis on the basis of physical examination. Therefore a diagnostic categorization of complaint based on duration and location is proposed. The justification for this organization is the assumption that the majority of back pain is secondary to deterioration within the disc. Thus the appropriate treatment program is focused at methods designed to find the pain source, and look to the health of the disc. It is on this basis that various treatment approaches for the nine classifications are proposed.
A cellular screening assay to test the ability of PKR to induce cell death in mammalian cells (2005)

Long double-stranded RNA (>30 bp), usually expressed in cells infected with RNA viruses, triggers antiviral responses that induce apoptosis of the infected cells. PKR can be selectively activated in glioblastoma cells by in situ generation of dsRNA following introduction of antisense RNA complementary to an RNA expressed specifically in these cells. Harnessing PKR for the selective killing of cancer cells is potentially a powerful strategy for treating cancer, but we were unable to induce apoptosis by this approach in a T cell lymphoma. We therefore established a cellular screening assay to test the ability of PKR to induce death in cell lines, especially those originating from human cancers. This "PKR killing screen" is based on the infection of cells with an adenoviral vector encoding GyrB-PKR, followed by coumermycin treatment. Cancers represented by cell lines in which PKR activation leads to cell death are good candidates for the dsRNA killing approach, using antisense to RNA molecules specifically expressed in these cells. The PKR killing screen may also serve as a tool for exploring PKR signaling and other related pathways, by identifying new cases in which PKR signaling is inhibited or impaired.
TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node cells (2006)

TRPM4 is functionally expressed in SAN cells and may be a key player in the generation and/or perturbation of heart rhythm.
Low-Power High-Speed Hybrid Temperature Heterogeneous Technology Digital Data Link (2013)

High-speed digital data links from 4-K superconductor electronics to room temperature are challenging due to the fact that energy/bit for single flux quantum logic is many (six) orders of magnitude lower than that of standard room-temperature logic. Our approach of building an energy-efficient high-speed data link involves a joint electrical-thermal design of a temperature-distributed architecture using different electronic technologies. This differential digital data link design involves superconductor, multiple cryogenic semiconductor and additional room-temperature semiconductor circuitry. The current design involves three cryogenic semiconductor ICs for integration with a multistage cryocooled digital system. The first cryogenic semiconductor IC is designed to operate at 4 K with a power consumption of 0.3 mW and interface directly with the superconductor differential single flux quantum/dc drivers. For testing it, a superconductor carrier chip containing an analog-to-digital converter has been designed for the HYPRES dual- <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$J_{c}$</tex></formula> (4.5 and 20 <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\hbox{kA/cm}^{2}$</tex></formula> ) fabrication process.
Evaluation of Tissue-Engineered Skin (Human Skin Substitute) and Secondary Intention Healing in the Treatment of Full Thickness Wounds after Mohs Micrographic or Excisional Surgery (2002)

BACKGROUND Human Skin Substitute (Apligraf, Organogenesis, Inc., Canton, MA) is a bi-layered tissue-engineered living biological dressing developed from neonatal foreskin. It consists of a bovine collagen matrix containing human fibroblasts with an overlying sheet of stratified human epithelium containing living human keratinocytes. Human Skin Substitute (HSS) appears to be immunologically inert, and has shown usefulness in the treatment of chronic and acute wounds. OBJECTIVE Primary objectives were to evaluate the safety and efficacy of HSS in the treatment of full-thickness wounds in a prospective case series. Secondary objectives were to determine the rate of complete wound reepithelialization, incidence of complete wound healing, pain at wound site, overall cosmetic outcome, and patient satisfaction. METHODS Fourteen patients were enrolled in the study, of which 12 were evaluable. HSS was applied in a blinded fashion to 6 of the patients immediately following Mohs or excisional surgery for skin cancer. The remaining 6 patients were allowed to heal by secondary intention. Both groups were evaluated at weekly appointments until complete reepithelialization occurred. During each evaluation, wound quality was assessed through the Vancouver Burn Scar Assessment Scale by the investigator and an independent blinded dermatologist. The investigator, blinded observer, and patient further evaluated the cosmetic outcome of the wound through the use of a Visual Analog Scale over a 6-month period. RESULTS HSS patients and secondary intention patients were equivalent in comorbid factors such as pain, erythema, edema, exudate, infection, or hematoma between the groups. The incidence of complete wound healing at 6 months was 100% for both groups. Both groups also appeared to heal at similar rates, as defined by the complete reepithelialization of the wound. HSS patients ultimately resulted in more pliable and less vascular wounds as defined by the Vancouver Burn Scar Assessment Scale. Patient satisfaction with cosmetic outcome in both groups was positive at 6 months. CONCLUSIONS HSS appears to be a safe, well-tolerated biological dressing with equivalent comorbid factors to secondary intention healing. HSS, however, seems to produce a more pliable and less vascular scar than those developed through healing by secondary intention. HSS also appears to produce more satisfactory cosmetic results when compared to secondary intention healing.
Designing Control Logic for Counterflow Pipeline Processor Using Petri Nets (1995)

Abstract. This paper approaches the problem of synthesising an asynchronous control circuit for a stage of the Sproull Counterflow pipeline processor (CFPP) as an exercise in exploiting formal techniques available for Petri nets. We first synthesise a Petri net model of the CFPP stage control from its original “five-state-five-event” description due to Charles Molnar. Secondly, we implement that model in asynchronous circuits, using twophase and four-phase components. The latter stage involves synthesising circuits with arbitration elements from behavioural descriptions with internal conflicts. This exercise appears to be quite instructive in the sense that it helps to estimate the scope and power of formal methods and today’s automatic tools in assisting the process of asynchronous design.