gebhart/patrepeval huggingface dataset:
Minimal essential origin of plasmid pSC101 replication: requirement of a region downstream of iterons (1993)

The minimal replication origin (ori) of the plasmid pSC101 was defined as an about 220-bp region under the condition that the Rep (or RepA) protein, a plasmid-encoded initiator protein, was supplied in trans. The DnaA box is located at one end of ori, as in other plasmids, like mini-F and P1. The other border is a strong binding site (IR-1) of Rep which is palindromic sequence and lies in an about 50-bp region beyond the repeated sequences (iterons) in ori. This IR-1 is located just upstream of another strong Rep binding site (IR-2), the operator site of the structure gene of Rep (rep), but its function has not been determined. The present study shows that the IR-1 sequence capable of binding to Rep is essential for plasmid replication with a nearly normal copy number. Furthermore, a region between the third iteron and IR-1 is also required in a sequence-specific fashion, since some one-base substitution in this region inactivate the origin function. It is likely that the region also is a recognition site of an unknown protein. Three copy number mutations of rep can suppress any one-base substitution mutation. On the other hand, the sequence of a spacer region between the second and the third iterons, which is similar to that of the downstream region of the third iteron, can be changed without loss of the origin function. The requirement of the region downstream of iterons in pSC101 seems to be unique among iteron-driven plasmid replicons.
THE PHLOGISTIC ROLE OF C3 LEUKOTACTIC FRAGMENTS IN MYOCARDIAL INFARCTS OF RATS (1971)

An improved method is described for extraction from rat myocardium of an enzyme that cleaves the third component of complement (C3) into leukotactic fragments. Direct cleavage of C3 has been shown by the use of a radiolabeled preparation of human C3. The enzyme elutes slightly beyond (retarded to) an albumin marker in gel filtration. After surgical ligation of a coronary artery, leukotactic activity can be extracted from infarcted rat myocardium. Described in terms of its time of appearance in infarcted tissue, the leukotactic activity has been identified as cleavage products of rat C3. The C3 fragments are of low molecular weight and heterogenous in size. Rats, if treated with the C3 inactivator (isolated from cobra venom) so as to ablate serum C3, fail to develop leukotactic activity in the infarcted myocardium. In turn, few if any of the usual intense accumulations of neutrophils in response to infected myocardium are seen during the first 48 hr after coronary artery ligation. These studies suggest a nonimmunologic role for C3 in the mediation of the acute inflammatory response in nonspecific tissue injury.
Bacterial biofilm on contact lenses and lens storage cases in wearers with microbial keratitis (1998)

Bacterial biofilm formation on contact lenses (CLs), and CL storage cases may be a risk factor for CL-associated corneal infection and may explain the persistence of organisms in CL storage cases. This study evaluated biofilm formation on, and microbial contamination of, CLs and CL storage cases from patients with microbial keratitis. Contact lenses and CL storage cases from 20 wearers with microbial keratitis were sampled microbiologically and visualized using scanning electron microscopy (SEM). Culture results from the cornea were also noted. Bacterial biofilm was present more frequently (P < 0.05) on CL storage case surfaces (17/20) compared with CL surfaces (11/20) and biofilm density was significantly greater on case surfaces (P < 0.05). There was no association between poor compliance and microbial contamination of the CL storage case, nor between poor compliance and biofilm formation or density on the CL or CL storage case. Biofilm formation occurred equally frequently with hydrogen peroxide and chlorine release care systems. Microbial keratitis in CL wearers is frequently associated with bacterial biofilm in the CL storage case. Despite the use of current CL disinfection systems, the CL storage case is a favourable environment for proliferation of certain organisms. Biofilm on CLs may prolong the retention time of organisms at the ocular surface and increase their potential pathogenicity.
Long‐term uninterrupted enzyme replacement therapy prevents liver disease in murine model of severe homocystinuria (2020)

Classical homocystinuria (HCU) is an inborn error of metabolism caused by loss of cystathionine β-synthase (CBS) activity with the concomitant buildup of homocysteine. In knockout (KO) mice, a mouse model of HCU, complete lack of CBS is neonatally lethal. Administration of OT-58, an enzyme therapy for HCU, during the first 5 weeks of life rescued KO mice survival by preventing liver disease. Here, we studied the impact of a long-term uninterrupted OT-58 treatment or its absence beyond the neonatal period on liver pathology and metabolism. Plasma and liver metabolites of KO mice on OT-58 treatment were substantially improved or normalized compared with those receiving vehicle. Increased plasma activities of alanine aminotransferase and aspartate aminotransferase of vehicle-injected KO mice suggested the progression of liver damage with age and lack of treatment. At 3 months of age, liver histology showed no signs of hepatopathy in both vehicle- and OT-58-treated KO mice. However, moderate to severe liver disease, characterized by steatosis, hepatocellular necroses, disorganized endoplasmic reticulum, and swollen mitochondria, developed in 6-month-old vehicle-injected KO mice. KO mice on OT-58 treatment remained asymptomatic and were indistinguishable from age-matched healthy controls. Long-term uninterrupted OT-58 treatment was essential to prevent severe liver disease in the KO mouse model of HCU.
Phase-shifting speckle interferometry (1985)

Speckle patterns have high frequency phase data, which make it difficult to find the absolute phase of a single speckle pattern; however, the phase of the difference between two correlated speckle patterns can be determined. This is done by applying phase-shifting techniques to speckle interferometry, which will quantitatively determine the phase of double-exposure speckle measurements. The technique uses computer control to take data and calculate phase without an intermediate recording step. The randomness of the speckle causes noisy data points which are removed by data processing routines. One application of this technique is finding the phase of deformations, where up to ten waves of wavefront deformation can easily be measured. Results of deformations caused by tilt of a metal plate and a disbond in a honeycomb structure brazed to an aluminum plate are shown.
Radiation Injury After a Nuclear Detonation: Medical Consequences and the Need for Scarce Resources Allocation (2011)

A 10-kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network.
Geometric theory of the grating (1974)

Geometric theory of the grating is developed, with special emphasis on the relation between the properties of holographic gratings and those of mechanically ruled gratings. The theory is applicable to practically all types of holographic and mechanically ruled gratings, including aspheric gratings. General expressions are given for the effective grating constant, the grating equation, the focal curves, and the light-path function. Possible applications of the theory to the design of aberration-corrected gratings are also described.
Purification and characterization of poly(ADP-ribose) glycohydrolase. Different modes of action on large and small poly(ADP-ribose). (1986)

Poly(ADP-ribose) glycohydrolase was purified approximately 74,000-fold to apparent homogeneity from calf thymus with a yield of 3.2%. The enzyme was a monomeric protein of Mr = 59,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The action of glycohydrolase on poly(ADP-ribose) was exoglycosidic in the direction of adenosine terminus----ribose terminus; radioactive ADP-ribose monomers were immediately produced from evenly labeled poly(ADP-ribose), but not from the polymer labeled selectively at the ribose terminus. The enzymatic degradation of large poly(ADP-ribose) (greater than 20 ADP-ribose residues) proceeded in a biphasic as well as bimodal manner. In the early and rapid phase, the enzyme degraded part of large polymers successively, leaving the remainder completely intact, and accumulated ADP-ribose monomers and small polymers of the size less than half of original polymers, indicating that the enzyme action was processive up to a certain extent. In the late and 20-fold slower phase, by contrast, the enzyme degraded the accumulated small polymers gradually and evenly, i.e. in a nonprocessive manner. The Km for large polymers was approximately 100-fold lower than that for small polymers. Similar rates and processivities were observed with large and small polymers bound to various proteins. These results suggested that the glycohydrolase may regulate differentially the levels of large and small poly(ADP-ribose) in the cell.
Characterization of a novel aquaretic agent, OPC‐31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist (1992)

1. OPC-31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v., inhibited the antidiuretic action of exogenously administered AVP in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a partial V2 receptor agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC-31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5. The results indicate that OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.
Lovastatin in the treatment of hypercholesterolemia in nephrotic syndrome due to diabetic nephropathy stage IV-V. (1992)

The efficacy and safety of lovastatin, a drug for lowering hypercholesterolemia, have been evaluated in ten adult patients with insulin-dependent diabetes mellitus (IDDM) and nephrotic syndrome due to diabetic nephropathy stage IV or V of Mogensen. For the first 8 weeks the patients received only a sugar-free isocaloric diet of which fats supplied approximately 30% of the total caloric intake and with not more than 300 mg cholesterol daily. After this run-in period patients were treated with 20 mg lovastatin once daily for 12 weeks while receiving the same isocaloric diet as previously. Body weights and glycosylated hemoglobin concentrations (HbAlc) did not change significantly during this period. The baseline plasma cholesterol concentrations (mean +/- SD) decreased only by 2% (from 310 +/- 54 to 303 +/- 46 mg/dl) during the 8 weeks with low cholesterol diet and by 25% (from 303 +/- 46 to 228 +/- 38 mg/dl) during the 12-week period on lovastatin therapy (p less than 0.005). The mean concentrations of low-density lipoprotein (LDL-)-cholesterol decreased by 3% (from 218 +/- 53 to 211 +/- 52 mg/dl) during the diet period and by 35% (from 211 +/- 52 to 137 +/- 38 mg/dl) during the period with lovastatin therapy (p less than 0.001). Concentrations of high-density lipoprotein (HDL) cholesterol increased slightly (11%) during the therapy with lovastatin (NS). Baseline plasma triglycerides fell by 22% (from 188 +/- 97 to 146 +/- 59 mg/dl) during the period with fat-restriction (p less than 0.05) and by 13% (from 146 +/- 59 to 127 +/- 54 mg/dl) during the period of lovastatin therapy (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Allergy and Clinical Immunology Services in Europe* (2006)

Allergology and Clinical Immunology (ACI) is an area of clinical medicine with a precise identity, relevant recent scientific achievements and well‐defined educational and professional needs. In spite of the high individual and socio‐economic impact of allergic diseases in Europe, the organization of ACI services is imperfect and varies among countries according to their health policies and priorities. In the firm belief of the role of ACI specialists in addressing clinical issues related to the involvement of the immune system in health and diseases—such as vaccination, immunodeficiencies, susceptibility and response to microbial agents, autoimmune and allergic diseases, immune aspects of transplantation and malignancies, in vivo and in vitro immunological tests, vaccinations, immuno‐modifiers—the European Academy of Allergology and Clinical Immunology appointed an ad hoc Task Force to produce standards for ACI Services in Europe. The resulting position paper should be used as a consulting reference for National Health Services as a necessary pre‐requisite for the free circulation to patients and health care professionals.
In vivo burn depth determination by high-speed fiber-based polarization sensitive optical coherence tomography (2001)

We report the first application of high-speed fiber-based polarization sensitive optical coherence tomography (PS-OCT) to image burned tissue in vivo. Thermal injury denatures collagen in skin and PS-OCT can measure the reduction in collagen birefringence using depth resolved changes in the polarization state of light propagated in, and reflected from, the tissue. Stokes vectors were calculated for each point in a scan and birefringence relative to incident polarization determined using four incident polarization states. Using a high-speed fiber-based PS-OCT system on rat skin burned for varying periods of time, a correlation between birefringence and actual burn depth determined by histological analysis was established. In conclusion, PS-OCT has potential use for noninvasive assessment of burn depth.
Identification of three late expression factor genes within the 33.8- to 43.4-map-unit region of Autographa californica nuclear polyhedrosis virus (1994)

A transient transactivation assay system was used in combination with an overlapping Autographa californica nuclear polyhedrosis virus clone library to identify genes involved in late and very late baculovirus gene expression. We have identified three genes within the 33.8- to 43.4-map-unit region of the A. californica nuclear polyhedrosis virus genome which contribute to expression from promoters of the vp39 major capsid protein and polyhedrin genes. One of these three genes corresponds to the previously identified DNA polymerase gene, while the other two genes encode previously unidentified polypeptides of 59,418 and 8,706 Da. None of these genes were required for expression from the early etl promoter.
MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells (2008)

The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing.
RESLVE: Leveraging User Interest to Improve Entity Disambiguation on Short Text (2013)

We address the Named Entity Disambiguation (NED) problem for short, user-generated texts on the social Web. In such settings, the lack of linguistic features and sparse lexical context result in a high degree of ambiguity and sharp performance drops of nearly 50% in the accuracy of conventional NED systems. We handle these challenges by developing a model of user-interest with respect to a personal knowledge context; and Wikipedia, a particularly well-established and reliable knowledge base, is used to instantiate the procedure. We conduct systematic evaluations using individuals' posts from Twitter, YouTube, and Flickr and demonstrate that our novel technique is able to achieve substantial performance gains beyond state-of-the-art NED methods.
An Amphipathic α-Helix Including Glutamates 509 and 516 Is Crucial for Membrane Translocation of Adenylate Cyclase Toxin and Modulates Formation and Cation Selectivity of Its Membrane Channels (1999)

The Bordetella pertussis adenylate cyclase toxin-hemolysin (ACT or CyaA) is a multifunctional protein. It forms small cation-selective channels in target cell and lipid bilayer membranes and it delivers into cell cytosol the amino-terminal adenylate cyclase (AC) domain, which catalyzes uncontrolled conversion of ATP to cAMP and causes cell intoxication. Here, we demonstrate that membrane translocation of the AC domain into cells is selectively dissociated from ACT membrane insertion and channel formation when a helix-breaking proline residue is substituted for glutamate 509 (Glu-509) within a predicted transmembrane amphipathic alpha-helix. Neutral substitutions of Glu-509 had little effect on toxin activities. In contrast, charge reversal by lysine substitutions of the Glu-509 or of the adjacent Glu-516 residue reduced the capacity of the toxin to translocate the AC domain across membrane and enhanced significantly its specific hemolytic activity and channel forming capacity in lipid bilayer membranes. Combination of the E509K and E516K mutations in a single molecule further exacerbated hemolytic and channel forming activity and ablated translocation of the AC domain into cells. The lysine substitutions strongly decreased the cation selectivity of the channels, indicating that Glu-509 and Glu-516 are located within or close to the membrane channel. These results suggest that the structure including glutamate residues 509 and 516 is critical for AC membrane translocation and channel forming activity of ACT.
Human α7 Integrin Gene (ITGΑ7) Delivered By Adeno-Associated Virus Reverses The Phenotype Of The Double Knock Out (DKO) Mouse Devoid Of Dystrophin And Utrophin (P5.099) (2014)

OBJECTIVE: Use human α7 integrin gene (ITGΑ7) delivered by adeno-associated virus (AAV) as an alternative strategy to treat Duchenne muscular dystrophy (DMD) BACKGROUND: Dystrophin links extracellular matrix (ECM) proteins to the actin cytoskeleton. Limitations for DMD gene replacement therapy include the large size of the gene and immunogenic potential when mini-genes are expressed in deleted regions of patient’s DMD gene (Mendell et al N Engl J Med 2010). α7 integrin is a laminin receptor in skeletal and cardiac muscle also linking the ECM to the actin skeleton. It is modestly upregulated in DMD and has been proposed to be an important modifier of dystrophy. rAAVrh.74.MCK.ITGΑ7 to the lower limb of mdx mice resulted in α7 overexpression at the sarcolemma and protected against loss of force following eccentric contraction-induced injury while specific force following tetanic contraction was unchanged (Heller et al. Mol Ther 2013). DESIGN/METHODS:The present study further challenged rAAVrh.74.MCK.ITGA7 to improve the more severe DMD model: the mdx/utrn-/- dko. Vector was systemically delivered through the intraperitoneal injection compared to prior regional delivery studies in mdx. Outcome measures included functional studies of the diaphragm and EDL. RESULTS:In the dko mouse, systemic delivery resulted in α7 expression in multiple muscle groups including the diaphragm, and upper and lower limb muscles. Most importantly ITGA7 significantly protected against loss of force following eccentric contraction-induced injury in the EDL and also improved muscle specific force post gene transfer. Preliminary studies further showed a reduction in kyphosis, improvement in body weight and an increase in myofiber diameter. CONCLUSIONS:AAVrh.74.ITGA7 gene transfer improves eccentric contraction induced injury in the dko mouse. The data also indicates early treatment leads to increase in specific force, improvement in overall body weight and reduction in kyphosis. Taken together, AAVrh.74.ITGΑ7 gene transfer demonstrates promise as a viable treatment for DMD. Study Supported by:
Anwendung nicht‐isothermer Kinetik auf chemilumineszente Systeme. Thermolyse von 1,2‐Dioxetanen (1976)

Abstract Die Thermolyse der 1,2‐Dioxetane 1 – 4 wird bei linear steigender Temperatur anhand der Chemilumineszenz verfolgt. Die erhaltenen Kurven für die Emissionsintensität I als Funktion der Temperatur T werden mit aus der Differential‐Thermo‐Analyse bekannten Abhängigkeiten verglichen und nach ähnlichen Verfahren ausgewertet. Durch diese Arbeitsweise wurde festgestellt, daß unter den angewandten Bedingungen die Quantenausbeute der Chemilumineszenz ø⋆ bei 1 – 4 keine Funktion der Temperatur ist.