gebhart/patrepeval huggingface dataset:
A small nucleolar RNA requirement for site-specific ribose methylation of rRNA in  Xenopus (1996)

Vertebrate cells contain a large number of small nucleolar RNA (snoRNA) species, the vast majority of which bind fibrillarin. Most of the fibrillarin-associated snoRNAs can form 10- to 21-nt duplexes with rRNA and are thought to guide 2'-O-methylation of selected nucleotides in rRNA. These include mammalian UHG (U22 host gene)-encoded U25-U31 snoRNAs. We have characterized two novel human snoRNA species, U62 and U63, which similarly exhibit 15- (with one interruption) and 12-nt complementarities and are therefore predicted to direct 2'-O-methylation of A590 in 18S and A4531 in 28S rRNA, respectively. To establish the function of antisense snoRNAs in vertebrates, we exploited the Xenopus oocyte system. Cloning of the Xenopus U25-U31 snoRNA genes indicated that they are encoded within multiple homologs of mammalian UHG. Depletion of U25 from the Xenopus oocyte abolished 2'-O-methylation of G1448 in 18S rRNA; methylation could be restored by injecting either the Xenopus or human U25 transcript into U25-depleted oocytes. Comparison of Xenopus and human U25 sequences revealed that only boxes C, D, and D', as well as the 18S rRNA complement, were invariant, suggesting that they may be the only elements required for U25 snoRNA stability and function.
Comparison of simple potential functions for simulating liquid water (1983)

Classical Monte Carlo simulations have been carried out for liquid water in the NPT ensemble at 25 °C and 1 atm using six of the simpler intermolecular potential functions for the water dimer: Bernal–Fowler (BF), SPC, ST2, TIPS2, TIP3P, and TIP4P. Comparisons are made with experimental thermodynamic and structural data including the recent neutron diffraction results of Thiessen and Narten. The computed densities and potential energies are in reasonable accord with experiment except for the original BF model, which yields an 18% overestimate of the density and poor structural results. The TIPS2 and TIP4P potentials yield oxygen–oxygen partial structure functions in good agreement with the neutron diffraction results. The accord with the experimental OH and HH partial structure functions is poorer; however, the computed results for these functions are similar for all the potential functions. Consequently, the discrepancy may be due to the correction terms needed in processing the neutron data or to an effect uniformly neglected in the computations. Comparisons are also made for self-diffusion coefficients obtained from molecular dynamics simulations. Overall, the SPC, ST2, TIPS2, and TIP4P models give reasonable structural and thermodynamic descriptions of liquid water and they should be useful in simulations of aqueous solutions. The simplicity of the SPC, TIPS2, and TIP4P functions is also attractive from a computational standpoint.
Thermotaxis of Human Sperm Cells in Extraordinarily Shallow Temperature Gradients Over a Wide Range (2012)

On the basis of the finding that capacitated (ready to fertilize) rabbit and human spermatozoa swim towards warmer temperatures by directing their movement along a temperature gradient, sperm thermotaxis has been proposed to be one of the processes guiding these spermatozoa to the fertilization site. Although the molecular mechanism underlying sperm thermotaxis is gradually being revealed, basic questions related to this process are still open. Here, employing human spermatozoa, we addressed the questions of how wide the temperature range of thermotaxis is, whether this range includes an optimal temperature or whether spermatozoa generally prefer swimming towards warmer temperatures, whether or not they can sense and respond to descending temperature gradients, and what the minimal temperature gradient is to which they can thermotactically respond. We found that human spermatozoa can respond thermotactically within a wide temperature range (at least 29-41°C), that within this range they preferentially accumulate in warmer temperatures rather than at a single specific, preferred temperature, that they can respond to both ascending and descending temperature gradients, and that they can sense and thermotactically respond to temperature gradients as low as <0.014°C/mm. This temperature gradient is astonishingly low because it means that as a spermatozoon swims through its entire body length (46 µm) it can sense and respond to a temperature difference of <0.0006°C. The significance of this surprisingly high temperature sensitivity is discussed.
Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10 (2015)

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and -rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB.
Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim (2009)

Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.
How I treat patients with diffuse large B-cell lymphoma (2007)

The disease we now call diffuse large B-cell lymphoma has gone by many names in the past. These have included reticulum cell sarcoma,[1][1] diffuse histiocytic lymphoma,[2][2] and, more recently, diffuse mixed lymphoma, diffuse large cell lymphoma, or immunoblastic lymphoma—terms from the Working
Tc-99m HMPAO SPECT in the Differential Diagnosis of the Dementias With Histopathologic Confirmation (2006)

Comparison is made with several other SPECT and PET series with histopathologic correlation. Brain blood flow SPECT is useful in the diagnosis and differential diagnosis of the dementias.
Capecitabine in hormone-resistant metastatic prostatic carcinoma – a phase II trial (2004)

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.
Molecular Association in Alkali Halide Vapors (1961)

Molecular association equilibria in alkali halide vapors were studied by measuring the temperature dependence of the molecular weights of gaseous NaCl, NaBr, NaI, KCl, KI, RbCl, and CsCl. The molecular weights were determined by measurement of the absolute pressure exerted by a known weight of completely vaporized salt contained in an isothermal fused silica bulb of known volume. The pressure sensing element was a fused silica manometer containing molten gold. The apparatus was used in the temperature range of 1175° to 1430°K and pressures of from 10 to 40 mm were measured with a precision of ±0.05 mm. The temperature dependence of the equilibrium constants for the reaction (MX)2⇌2MX yielded dissociation energies (evaluated at 1300°K) ranging from 48.0 kcal mole−1 for NaCl to 34.7 for CsCl. The entropies of dissociation were found to fall within a small range, varying from 28.3 eu for NaCl to 25.0 for KI, and a statistical calculation of the entropy changes based on an ionic model was found to agree well with the experimental values. It is shown that these systems may be adequately described with an electrostatic model, although closer attention should be paid to the nature of polarization interactions.
What's Wrong with My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice (2000)

array of choices available for assaying this behavioral construct, and seeing that there are somewhat murky borders between the constructs ‘anxiety’, ‘fear’ and ‘depression’, he or she will explore the question further with an array of tests, after careful consideration of the idiosyncratic parameters required to elicit interpretable data from each test. Such attention to detail matters in real life, even when highly experienced behavioral-testing laboratories are involved. For example, three groups recently independently produced null mutant mice for the corticotropinreleasing hormone 2 receptor. Each group was obviously interested in testing the effects of this gene deletion on anxiety. The results were published as three back-to-back-to-back papers in Nature Genetics 1‐3 . All three groups tested both male and female mice on a version of the elevated plus-maze anxiety test and reported their reluctance to enter open arms of the maze, the accepted index of anxiety. One group found no difference between knockout and wild type of either sex; one group found greater anxiety in knockouts of both sexes; and the third found greater anxiety in male knockouts only. All three also used an open field test, where reluctance to enter the center of the apparatus was the index of anxiety. Again, three different results were reported: one group found a tendency for greater anxiety in null mutants of both sexes; one found significantly greater anxiety in null mutants; and the third found that null mutant males (but not females) spent significantly more time in the center of the field, but interpreted the result to indicate greater anxiety! The different results could derive from many sources, including: differences in animal husbandry and handling before testing; relatively subtle differences in the test apparatus and test protocols; the specific genetic constructs inserted into embryonic stem cells; the stem-cell source strain (three different substrains of 129 inbred mice were used that are known to vary genetically 4
Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation (1992)

We investigated the influence of two structurally unrelated inhibitors of matrix-degrading metalloproteinases, Ro 31-4724 and Ro 31-7467, on the primary proliferation of smooth-muscle cells from rabbit aortic explants. Both agents inhibited proliferation in a concentration-dependent manner, but did not affect cell viability. Smooth-muscle cells grown out from explants secreted 95 kDa and 72 kDa gelatinase enzymes that were also inhibited in a concentration-dependent manner by Ro 31-4724 and Ro 31-7467. Interstitial collagenase and stromelysin were not detected. We conclude that metalloproteinases are likely to be involved in the initiation of smooth-muscle proliferation.
Growth factors improve muscle healing in vivo (2000)

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries.
Applications of video-content analysis and retrieval (2002)

Managing multimedia data requires more than collecting the data into storage archives and delivering it via networks to homes or offices. We survey technologies and applications for video-content analysis and retrieval. We also give specific examples.
Inhibition of a reductive function of the plasma membrane by bacitracin and antibodies against protein disulfide-isomerase. (1993)

Evidence had been provided that a disulfide-linked [125I]iodotyramine/poly(D-lysine) conjugate was reductively cleaved when bound nonspecifically to the surface of Chinese hamster ovary (CHO) cells and that this cleavage was abolished by membrane-impermeant sulfhydryl blockers. The same blockers were subsequently found to inhibit the cytotoxicity of diphtheria toxin, a disulfide-linked heterodimer that binds to a specific surface receptor and must undergo chain separation to exert its cytotoxicity. This suggested that the disulfides of both macromolecules might be cleaved by a thiol-disulfide interchange reaction, possibly mediated by protein disulfide-isomerase (PDI, EC 5.3.4.1). We tested whether inhibitors of PDI--in particular, bacitracin and anti-PDI antibodies--might mimic the two effects of sulfhydryl blockers. Both bacitracin and anti-PDI antibodies were effective in inhibiting both reductive processes. This strongly suggests that the disulfide cleavage in the two membrane-bound macromolecules is mediated by PDI and that this enzyme, besides its known retention in the endoplasmic reticulum, must also be exposed at the plasma membrane. This paper points to other potentially important disulfide reductions that might be catalyzed by surface-associated PDI. It thereby broadens the known functions of an enzyme already known for its multifunctional properties.
The effects of neuromuscular electrical stimulation training on abdominal strength, endurance, and selected anthropometric measures. (2005)

We studied the effects of self-administered neuromuscular electrical stimulation (NMES) on changes in strength, endurance, selected anthropometric measures, and subject's perceived shape and satisfaction of the abdominal wall. Twenty-four adults (experimental group) stimulated their abdominals 5 days per week (20-40 minutes per session) for 8 weeks and refrained from engaging in any additional exercise during the study. A control group (N=16) refrained from exercising the abdominals or engaging in any other exercise training during the study. Subjects were tested at the beginning, mid-point, and end of the study. Isometric strength of the abdominal muscles was tested using a isokinetic dynamometer, endurance was measured using the ACSM curl-up test, abdominal circumference was measured using a steel tape measure, and body shape and satisfaction were assessed via questionnaire. The stimulation group had a 58% increase in abdominal strength, whereas the control group did not change. The stimulation group also had a 100% increase in abdominal endurance versus a 28% increase in the control group. Waist circumference decreased by of 3.5 cm in the stimulation group compared to no significant change in the control group. All 24 subjects in the stimulation group felt that their midsections were more "toned" and "firmed" and 13/24 (54%) felt that their posture had improved as a result of the stimulation. None of the control group subjects reported changes in these parameters. There were no significant differences in body weight, BMI, or skinfold thickness over the course of the study in either group. NMES, as used in the current study, resulted in significant improvements in the muscular strength and endurance of the abdominal region, as well as subject's perceived shape and satisfaction of the mid-section. Key PointsElectrical muscle stimulation (EMS) was effective in increasing muscle strength and enduranceAll subjects perceived their abdominal muscles to be firmer and more toned as a result of EMSAbdominal and waist girth was also significantly reduced, despite no changes in body weight or subcutaneous fat.
T-Cell Tumor Elimination as a Result of T-Cell Receptor-Mediated Activation (1987)

It has recently been shown that activation of murine T-cell hybridomas with antigen inhibits their growth in vitro. The "suicide" of these neoplastic T cells upon stimulation with antigen suggested the possibility that activation via the antigen-specific receptor could also inhibit the growth of neoplastic T cells in vivo. To test this, mice were subcutaneously inoculated with antigen-specific T-cell hybridomas and then treated intraperitoneally with antigen. Administration of the appropriate antigen immediately after inoculation with the T-cell hybridoma abrogated tumor formation; antigen administered after tumors had become established decreased the tumor burden and, in a substantial fraction of animals, led to long-term survival. The efficacy of antigen therapy was due to both a direct inhibitory effect on tumor growth and the induction of host immunity. These studies demonstrate the utility of cellular activation as a means of inhibiting neoplastic T-cell growth in vivo and provide a rationale for studying the use of less selective reagents that can mimic the activating properties of antigen, such as monoclonal antibodies, in the treatment of T-cell neoplasms of unknown antigen specificity.
Dissolvable Antibiotic Beads in Treatment of Periprosthetic Joint Infection and Revision Arthroplasty - The Use of Synthetic Pure Calcium Sulfate (Stimulan®) Impregnated with Vancomycin & Tobramycin (2013)

This study reviews the clinical results using commercially pure, synthetic antibiotic-loaded Calcium Sulfate dissolvable beads (Stimulan, Biocomposites, Ltd., Keele, UK) in 250 cases of aseptic and septic revision total hip and total knee arthroplasty. A set protocol of Vancomycin and Tobramycin antibiotic was used in all cases. The rate of wound drainage in this series was 3.2%. Wound drainage was generally seen in cases using higher bead volumes. The incidence of heterotopic bone formation was 1.2%. There were nine failures in this study, six of which were due to infection. We feel that commercially pure, synthetic antibiotic-loaded dissolvable beads are an acceptable delivery tool for local antibiotic delivery in aseptic and septic revision joint arthroplasty of the hip and knee. Further studies are needed to examine the potential of improving outcomes of periprosthetic joint infection with this particular local antibiotic delivery system.Key words: Stimulan, Calcium Sulfate, Antibiotic Beads, Periprosthetic Infection, Revision Arthroplasty. Level of Evidence: AAOS Therapeutic Study Level IV.
New, Improved Procedure for the Synthesis of Structurally Diverse N-Spiro C2-Symmetric Chiral Quaternary Ammonium Bromides (2003)

Selective, direct ortho magnesiation of (S)-2,2'-bis(isopropoxycarbonyl)-1,1'-binaphthyl (6) has been achieved under mild conditions, using magnesium bis(2,2,6,6-tetramethylpiperamide) [Mg(TMP)(2)]. In combination with the subsequent reaction with the appropriate electrophiles, bromine and iodine, this method constitutes a key step in establishing a new and concise synthetic route to a wide variety of N-spiro C(2)-symmetric chiral quaternary ammonium bromides of type 1.