Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.

PURPOSE We conducted the first phase 0 clinical trial in oncology of a therapeutic agent under the Exploratory Investigational New Drug Guidance of the US Food and Drug Administration. It was a first-in-human study of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in patients with advanced malignancies. PATIENTS AND METHODS ABT-888 was administered as a single oral dose of 10, 25, or 50 mg to determine the dose range and time course over which ABT-888 inhibits PARP activity in tumor samples and peripheral blood mononuclear cells, and to evaluate ABT-888 pharmacokinetics. Blood samples and tumor biopsies were obtained pre- and postdrug administration for evaluation of PARP activity and pharmacokinetics. A novel statistical approach was developed and utilized to study pharmacodynamic modulation as the primary end point for trials of limited sample size. RESULTS Thirteen patients with advanced malignancies received the study drug; nine patients underwent paired tumor biopsies. ABT-888 demonstrated good oral bioavailability and was well tolerated. Statistically significant inhibition of poly (ADP-ribose) levels was observed in tumor biopsies and peripheral blood mononuclear cells at the 25-mg and 50-mg dose levels. CONCLUSION Within 5 months of study activation, we obtained pivotal biochemical and pharmacokinetic data that have guided the design of subsequent phase I trials of ABT-888 in combination with DNA-damaging agents. In addition to accelerating the development of ABT-888, the rapid conclusion of this trial demonstrates the feasibility of conducting proof-of-principle phase 0 trials as part of an alternative paradigm for early drug development in oncology.
Sti1 Is a Novel Activator of the Ssa Proteins*

The molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins in eukaryotes. Of specific importance in this context is a ternary multichaperone complex in which Hsp70 and Hsp90 are connected by Hop. In Saccharomyces cerevisiae two components of the complex, yeast Hsp90 (yHsp90) and Sti1, the yeast homologue of Hop, had already been identified, but it remained to be shown which of the 14 different yeast Hsp70s are part of the Sti1 complex and what were the functional consequences resulting from this interaction. With a two-hybrid approach and co-immunoprecipitations, we show here that Sti1 specifically interacts with the Ssa group of the cytosolic yeast Hsp70 proteins. Using purified components, we reconstituted the dimeric Ssa1-Sti1 complex and the ternary Ssa1-Sti1-yHsp90 complex in vitro. The dissociation constant between Sti1 and Ssa1 was determined to be 2 orders of magnitude weaker than the affinity of Sti1 for yHsp90. Surprisingly, binding of Sti1 activates the ATPase of Ssa1 by a factor of about 200, which is in contrast to the behavior of Hop in the mammalian Hsp70 system. Analysis of the underlying activation mechanism revealed that ATP hydrolysis is rate-limiting in the Ssa1 ATPase cycle and that this step is accelerated by Sti1. Thus, Sti1 is a potent novel effector for the Hsp70 ATPase.
Oxygen regulation in Salmonella typhimurium

Regulation by oxygen of the peptidase T (pepT) locus of Salmonella typhimurium was studied by measuring beta-galactosidase levels in strains containing a pepT::Mu d1(Apr lac) operon fusion. beta-Galactosidase was induced in anaerobic cultures and late-exponential and stationary-phase aerated cultures. Peptidase T activity also was induced under these growth conditions. pepT+ but not pepT strains will utilize as amino acid sources the tripeptides Leu-Leu-Leu and Leu-Gly-Gly only when grown anaerobically. Mutations at two loci, oxrA and oxrB (oxygen regulation) prevent induction of the pepT locus. The oxrA locus is homologous to the fnr locus of Escherichia coli. We have isolated 12 independent Mu d1 insertions (oxd::Mu d1, oxygen dependent) that show induction of beta-galactosidase in anaerobic cultures and stationary-phase aerated cultures. These insertions fall into nine classes based on map location. All of the oxd::Mu d1 insertions are regulated by oxrA and oxrB and therefore define a global regulon that responds to oxygen limitation.
Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial

Background. Although there is good evidence that cognitive therapy (CBT) lessens relapse and recurrence in unipolar depression, the duration of this effect is not known. Method. One hundred and fifty-eight subjects, from a randomized controlled trial of CBT plus medication and clinical management versus medication and clinical management alone, were followed 6 years after randomization (4½ years after completion of CBT) and the longitudinal course assessed. Results. Effects in prevention of relapse and recurrence were found to persist, with weakening, and were not fully lost until 3½ years after the end of CBT. Residual symptoms were also lessened. Conclusions. The effect of CBT in reduction of relapse and recurrence persists for several years. The potential value of subsequent additional CBT some time after cessation should be explored.
Temperature dependence of the direct action of ionizing radiation on beef heart lactate dehydrogenase: enzyme activity, substrate and coenzyme affinities.

Samples of lactate dehydrogenase (LDH), desalted by dialysis, were dried as hard films 0.1 to 0.25 ${\rm mg}/{\rm cm}^{2}$ in average thickness and were irradiated in a vacuum with minimum ionization electrons. After irradiation at controlled temperatures from 65°K to 395°K, samples were returned to ambient temperature, exposed to air, and dissolved in phosphate buffer. For study of effect upon solubility, samples were divided into spontaneous eluate and mechanical resuspendate fractions, each assayed for enzyme activity and for protein content. Both for total recoverable activity and for enzyme specific activity, the temperature dependence of radiation sensitivity is consistent with two principal modes of inactivation, one temperature-independent and the other characterized by an activation energy around 1200 cal/mole. The H4 isozyme and an isozyme mixture gave indistinguishable results. Some temperature dependence was also evident for effect upon protein solubility. The effect of radiation on affinity o.
Selection of splice sites in pre-mRNAs with short internal exons

Model pre-mRNAs containing two introns and three exons, derived from the human beta-globin gene, were used to study the effects of internal exon length on splice site selection. Splicing was assayed in vitro in HeLa nuclear extracts and in vivo during transient expression in transfected HeLa cells. For substrates with internal exons 87, 104, and 171 nucleotides in length, in vitro splicing proceeded via a regular splicing pathway, in which all three exons were included in the spliced product. Primary transcripts with internal exons containing 23, 29, and 33 nucleotides were spliced by an alternative pathway, in which the first exon was joined directly to the third one. The internal exon was missing from the spliced product and together with two flanking introns was included in a large lariat structure. The same patterns of splicing were retained when transcripts containing 171-, 33-, and 29-nucleotide-long internal exons were spliced in vivo. A transcript containing a 51-nucleotide-long exon was spliced in vitro via both pathways but in vivo generated only a correctly spliced product. Skipping of short internal exons was reversed both in vitro and in vivo when purines in the upstream polypyrimidine tract were replaced by pyrimidines. The changes in the polypyrimidine tract achieved by these substitutions led in vitro to complete (transcripts containing 28 pyrimidines in a row) or partial (transcripts containing 15 pyrimidines in a row) restoration of a regular splicing pathway. Splicing in vivo of these transcripts led exclusively to the spliced product containing all three exons. These results suggest that a balance between the length of the uninterrupted polypyrimidine tract and the length of the exon is an important determinant of the relative strength of the splice sites, ensuring correct splicing patterns of multiintron pre-mRNAs.
Bismuth Germanate: A High-Z Gamma-Ray and Charged Particle Detector

The room-temperature scintillation characteristics of single crystals of Bi4Ge3O2 under gamma-ray and alpha-particle excitation have been determined. The wavelength of maximum intensity in the scintillation spectrum is 480 nm. A decay constant of 0.30 microseconds was measured. Scintillation efficiency (pulse height) varied linearly with gamma-ray energy, E, and the resolution varied as E-1/2. 8% pulse height relative to NaI(Tl) with 15% resolution was measured for a 2.2 cm × 1.7 cm crystal under excitation by Cs137 0.662 Mev gamma-rays.
Accurate charge dependent nucleon nucleon potential at fourth order of chiral perturbation theory

We present the first nucleon-nucleon potential at next-to-next-to-next-to-leading order (fourth order) of chiral perturbation theory. Charge dependence is included up to next-to-leading order of the isospin-violation scheme. The accuracy for the reproduction of the nucleon-nucleon $(NN)$ data below $290\text{\ensuremath{-}}\text{MeV}$ lab energy is comparable to the one of phenomenological high-precision potentials. Since $NN$ potentials of order three and less are known to be deficient in quantitative terms, the present work shows that the fourth order is necessary and sufficient for a $NN$ potential reliable up to $290\phantom{\rule{0.3em}{0ex}}\text{MeV}$. The new potential provides a promising starting point for exact few-body calculations and microscopic nuclear structure theory (including chiral many-body forces derived on the same footing).
Human natural killer cell inhibitory receptors bind to HLA class I molecules

To obtain direct evidence that human natural killer cell (NK) inhibitory receptors physically interact with polymorphic determinants of major histocompatibility complex class I molecules, a receptor termed NK‐associated transcript‐2 has been produced as a soluble fusion protein with the human IgG1 Fc portion. This soluble receptor binds specifically to HLA‐C alleles with serine 77 and asparagine 80 in cell adhesion assays.
Temperature dependence of divalent cation induced fusion of phosphatidylserine liposomes: evaluation of the kinetic rate constants.

The effect of temperature and divalent cation binding (Ca2+, Sr2+, Ba2+) on the kinetic rate constants of aggregation and fusion of large phosphatidylserine liposomes is measured for the first time. Fusion is monitored by the Tb3+/dipicolinate assay. Fusion rate constants increase with temperature (15-35 degrees C) in a roughly linear fashion. These rate constants are not otherwise sensitive to whether the temperature is above or below the phase transition temperature of the Ba2+ or Sr2+ complex of phosphatidylserine, as measured by differential scanning calorimetry. Hence, the isothermal transition of the acyl chains from liquid-crystalline to gel phase induced by the cations is not the driving force of the initial fusion event. The aggregation rate constants increase with temperature, and it is the temperature dependence of the energetics of close approach of the liposomes which underlies this increase. On the other hand, the aggregation becomes more reversible at higher temperatures, which has also been observed with monovalent cation induced liposome aggregation where there is no fusion. Calculations on several cases show that the potential energy minimum holding the liposome dimer aggregates together is approximately 5-6 kT deep. This result implies that the aggregation step is highly reversible; i.e., if fusion were not occurring, no stable aggregates would form.
Cellulose nanowhiskers: preparation, characterization and cytotoxicity evaluation.

OBJECTIVE To characterize the structure and to evaluate the cytotoxicity of cellulose nanowhiskers (CNW) prepared from cotton linters. METHODS A series of CNW dispersions was prepared by hydrolyzing cotton linters with sulfuric acid. The structure of CNW was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The cytotoxicity of CNW dispersions to L929 cells was preliminarily investigated by cell culture and MTT assay. RESULTS SEM and TEM observation showed that the original cotton litters have been successfully acid-hydrolyzed into cellulose nanowhiskers having needle- or short rod-like structure with an average length of 250 nm and diameter of 10 nm. XRD patterns suggested that degree of crystalline in the CNW was much higher than that in the cotton linters as a result that the acid-hydrolysis process has removed the amorphous domains in the cotton linters. The results from MTT assay and cell morphology observation indicated that CNW with concentration from 0.01% to 0.2% had low toxicity to L929 cells, while cytotoxicity showed an increase tendency with an increase in the concentration of CNW. CONCLUSIONS Cellulose nanowhiskers dispersion could be prepared from cotton linters by acid-hydrolysis process. CNW showed potential applications as nanobiomaterials due to its low cytotoxicity.
A pilot study of rhuIL‐11 treatment of refractory ITP

The objective of this research was to determine whether rhuIL‐11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL‐11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy‐induced thrombocytopenia. A pilot study was initiated, intending to enroll 12 patients with ITP. These patients were to receive rhuIL‐11 (Neumega) at a dose of 50 μg/kg subcutaneously daily for 21 consecutive days and be observed afterward for 21 additional days. CBC with platelets were obtained twice weekly with visits and physical examinations weekly. The study was terminated after 7 patients were enrolled because of toxicity and lack of efficacy. All 7 patients had had ITP for >9 years and had failed splenectomy, intravenous gammaglobulin, corticosteroids, and a variety of other treatments. The patients at entry all had platelet counts <20,000/μl; 5 of 7 had counts <10,000/μl. The maximal median increase for any day of the study was 6,000/μl. No patient achieved a count of 30,000/μl, and only 3 patients achieved (once each) a platelet count >20,000/μl. Substantial toxicity was seen. The nadir hemoglobin decrease was a mean of 2 g/dl. rhuIL‐11 was not effective at increasing the platelet count in any of these patients with refractory ITP. Toxicity was substantial. The lack of platelet response to rhuIL‐11 in this study does not exclude the possibility of better effects at other doses and/or in less refractory patients. Am. J. Hematol. 66:172–177, 2001. © 2001 Wiley‐Liss, Inc.
The development of sex differences in cardiovascular disease mortality: a historical perspective.

OBJECTIVES Little is known about why males have higher cardiovascular disease (CVD) mortality rates than do females. An important factor that has hampered efforts in this regard is the lack of clarity about whether male excess mortality from CVD has existed throughout history. To answer this question, an investigation was conducted of trends in CVD mortality differences between the sexes from the time when data first became available until the present, including the full range of age groups. METHODS Mortality statistics for CVD in England and Wales from 1861 through 1992 and in the United States from 1900 through 1991 were used. RESULTS Three stages in the relationship between male and female CVD mortality were found: (1) An early stage of equal male and female mortality, (2) a stage of the appearance of sex differences in mortality, and (3) a stage with consistently present male excess mortality. CONCLUSION Male excess mortality from CVD has not always been present in the historical record. Further research is needed to elucidate the causes of this excess mortality.
Hamming Distance based Clustering Algorithm

Cluster analysis has been extensively used in machine learning and data mining to discover distribution patterns in the data. Clustering algorithms are generally based on a distance metric in order to partition the data into small groups such that data instances in the same group are more similar than the instances belonging to different groups. In this paper the authors have extended the concept of hamming distance for categorical data.As a data processing step they have transformed the data into binary representation. The authors have used proposed algorithm to group data points into clusters. The experiments are carried out on the data sets from UCI machine learning repository to analyze the performance study. They conclude by stating that this proposed algorithm shows promising result and can be extended to handle numeric as well as mixed data.
Image Super-resolution Reconstruction Algorithm Based on Convolutional Neural Network

Aiming at the problem that the existing SRCNN algorithm has too long training time, poor reconstruction performance and slow running speed, a new image super-resolution reconstruction algorithm based on convolutional neural network is proposed. The algorithm uses low-resolution images as the network input, the higher-order representation of the image is learned using the convolution operation, the high-resolution image is up-sampling by the deconvolution operation, and the residual structure is added to the network, so that the entire network can converge better. Experimental results on Set5, Set14, and BSD200 test sets show that compared with Bicubic, SRCNN and other methods, the method proposed in this paper is more efficient on super-resolution reconstruction of images and the convergence speed of the network is faster.
Exploring Factors Affecting Students' Satisfaction of M-Learning in High School

M-learning has flourished in the field of education, and it has become an important element of educational technology. To explore the developing trends in mobile learning, this study used t-tests and ANOVA to explicate the effects of different grades, genders and parents' educational levels on the degree of students' satisfaction with m-learning. Then stepwise multiple regression analysis was used to predict the factors influencing m-learning satisfaction (SA). The results showed that gender differences did not have a significant impact on satisfaction, but the differences in grades and parents' education levels did. In addition, it was found that perceived usefulness and behavioral intention can be used as positive predictors of satisfaction with mobile learning. Finally, this paper puts forward some suggestions to improve users' satisfaction with m-learning.
The Overcorrected Clubfoot in the Adult

Managing the overcorrected clubfoot in the adult patient can be a formidable task, even for the most experienced surgeon. The goal of previous surgical interventions has been to achieve a braceable, shoeable foot. The overcorrected foot is usually plantigrade and meets these criteria. If fact, many of these patients tolerate their foot position well, never coming to the point of requiring further surgery. We have noticed, however, that there are some patients who have pain despite the plantigrade position of their foot. While the literature is replete with methods for treatment of the persistent or recurrent clubfoot, suggestions for how to tackle an overcorrected deformity are rare. The modern evolution of treatment for the idiopathic clubfoot began with Kite, who in 1939 published his work advocating for conservative cast management with multiple manipulations. Kite’s method met with limited mainstream acceptance due to long periods of cast treatment and the desire of surgeons to achieve a more rapid result. The following decades saw the introduction of multiple operative techniques in an effort to surgically “unwind” the foot through capsular releases and tendon lengthening, tenotomies, and/or transfers. More recently, the Ponseti technique has gained in popularity. The success of this technique along with the potential complications of surgery have resulted in its increased use. Even though the pendulum has swung back toward the use of conservative measures for the treatment of the idiopathic clubfoot deformity, surgery is still utilized in many cases. The complications of the overcorrected clubfoot we describe in the following are not related to the Ponseti method of treatment, and anecdotally, patients with these complications arose from the array of surgical procedures that were performed prior to the current approach to treatment. It has previously been shown that overcorrection accounts for 70% of inferior results after surgical management of clubfoot. The paucity of literature regarding the management of the overcorrected clubfoot in the adult patient has prompted an attempt to elucidate the most common deformities we have encountered and present suggestions for their management (Figure 1).
Activation states as assessed by verbal report and four psychophysiological variables.

The present research was part of a program aimed at examination of the validity of controlled verbal reports of various activation states. A difference score design was used in which four psychophysiological measures and verbal ratings of various activation states were obtained in a baseline and an activation period from 41 female subjects. Verbal reports were then correlated with individual physiological measures and composites or indices of physiological measures. Specifically, two kinds of physiological index were employed, one in which the subject's physiological change score was represented by the single system showing the greatest change, and a second index weighted equally by all four physiological measures. The physiological index using the single system showing the greatest activation yielded slightly greater correlations with verbal report than the other index. Skin conductance and heart rate, the best combination of the four physiological systems measured, correlated as high as . 62 with verbal report. The results were interpreted as demonstrating the usefulness and validity of controlled self report and the relative superiority of skin conductance and heart rate among other physiological systems in correlations with verbal report.
Les estimations des paramètres tridimensionnels de la structure d'un matériau

© Société française de statistique, 1969, tous droits réservés. L’accès aux archives de la revue « Revue de statistique appliquée » (http://www. sfds.asso.fr/publicat/rsa.htm) implique l’accord avec les conditions générales d’utilisation (http://www.numdam.org/conditions). Toute utilisation commerciale ou impression systématique est constitutive d’une infraction pénale. Toute copie ou impression de ce fichier doit contenir la présente mention de copyright.