Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of mixing during acid addition on fractionally precipitated protein

Isoelectric fractionation of the two major proteins of soy is characterized. Fractions are acid precipitated and cen‐trifugally collected at pH 6.0 (glycinin) and pH 4.8 (β‐conglycinin). Two extremes in the speed of acid addition (rapid, with no mixing, and slow, via acid dialysis, with complete mixing) are compared to determine their effects on the properties of the precipitate. Total protein yield, fraction composition, and aggregate microstructure do not depend significantly on the method of acid addition. Particle size distribution and hindered settling behavior do differ and are explained using a model of aggregate strength. The rapid acid addition produces larger primary particles, because of higher supersaturation, and yields larger aggregates, because of higher interparticle potential and stronger aggregates. Further aggregation in low‐shear hindered settling is faster for the slowly precipitated aggregate because few of these bonding sites could survive the high‐shear precipitator, whereas more can contribute to aggregation during hindered settling.
Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

Objective In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL®/SILGARD®) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Methods 18,174 women were enrolled into 3 clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for ≥1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing, and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Results Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrolment. Conclusions These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
Beta blockers normalize QT hysteresis in long QT syndrome.

OBJECTIVES This study was performed to evaluate the impact of beta blockers on QT adaptation to heart rate during the exercise and recovery phases of exercise testing in long QT syndrome. BACKGROUND Long QT syndrome is characterized by familial syncope and sudden death in the context of sudden heart rate changes. QT hysteresis has been proposed as a phenotypic marker of long QT syndrome, suggesting altered QT adaptation to changes in heart rate. METHODS Fourteen patients with long QT syndrome (aged 26 +/- 16 years, 6 male) and 10 healthy volunteers (aged 37 +/- 11 years, 9 male) underwent graded exercise testing with continuous lead II electrocardiographic monitoring. Long QT patients underwent repeat assessment after 1 month of beta blockade. QT intervals at matching heart rates were compared during exercise and recovery to determine the effect of beta blockade on QT hysteresis, defined as the recovery QT peak interval subtracted from the exercise QT peak interval. RESULTS In the 14 long QT syndrome patients, beta blockers slowed the resting heart rate without affecting the corrected QT interval (502 +/- 52 ms baseline vs 481 +/- 40 ms beta blocker, P =.17). The increase in heart rate with exercise was similar in the 3 groups (P =.73). Exaggerated hysteresis of the QT interval was seen in the patients with long QT syndrome at baseline compared with controls (46 +/-19 ms vs 19 +/- 11 ms 1 minute into recovery, P =.006). Beta blockers had minimal effect on the QT interval but markedly reduced hysteresis with minimal separation of the exercise and recovery QT/RR curves (25 +/- 35 ms 1 minute into recovery, P =.027). The combined curve separation at all 6 time points analyzed was 165 +/- 95 ms in patients with long QT syndrome at baseline, 40 +/- 131 ms after beta blockade, and 29 +/- 30 ms in control subjects (P =.002). Comparison of the beta blocker effect on hysteresis in the 2 genotypes suggested a greater reduction in hysteresis in the 3 patients with long QT syndrome 1 compared with the 11 patients with long QT syndrome 2. CONCLUSIONS Beta blockers reduce QT hysteresis in patients with long QT syndrome to values seen in normal patients. This improved QT adaptation to changes in heart rate may explain the clinical benefit of beta blockers in long QT syndrome.
Direct integrated strain sensors for robust temperature behaviour

We have investigated the fundamental behavior of strain sensitive transistors with respect to different transistor parameters. Therefore, the transistors have been simulated by using a modified BSIM3.3 model. The simulations showed an increase of drain current between 3.5 % and 5.8 % at 60 MPa stress, an acceptable shift of threshold voltage, and almost no increase of leakage current. For basic characterization, pressure sensitive silicon membranes have been fabricated as strain inducing elements. Measurements with elongated membranes confirmed the simulation results regarding the transistor parameters and the robust temperature behaviour.
IL-35 Inhibits Angiogenesis through VEGF/Ang2/Tie2 Pathway in Rheumatoid Arthritis

Background/Aims: The pro-angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins (Angs) play a prominent role in synovial angiogenesis, an early and critical event in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-35 is an anti-inflammatory cytokine that attenuates collagen-induced arthritis, however, the mechanisms involved are not fully understood. Methods: The effects of IL-35 on endothelial cell migration, adhesion, and tube formation were examined using human umbilical vein endothelial cells (HUVEC) in vitro. The effects of IL-35 on vessel formation in vivo were examined using a murine Matrigel plugs model. MMP2/MMP9 and IL-6/IL-8 secretion were assessed by zymography and ELISA, respectively. The crosstalk between IL-35, VEGF, and Ang2 in HUVECs and RA synovial tissue explants was investigated. Results: IL-35 inhibited basal and VEGF-induced HUVEC migration and adhesion in vitro as well as tube formation in vitro and in vivo. VEGF increased Ang2 secretion by HUVECs and RA synovial tissue explants, and exogenous Ang2 promoted HUVEC migration, adhesion, and tube formation with similar potency to VEGF. Blocking the Ang/Tie2 pathway with a Tie2 kinase antibody inhibited the proangiogenic effects of exogenous Ang2 and VEGF in HUVECs. IL-35 inhibited basal and VEGF-induced Ang2 secretion by HUVECs and RA synovial tissue explants; it also antagonized the proangiogenic effects of exogenous Ang2 in HUVECs. Moreover, IL-35 reduced basal and VEGF/Ang2-induced MMP2/MMP9 and IL-6/IL-8 secretion. Conclusion: These results suggested that IL-35 restrains RA angiogenesis and inflammation by downregulating basal and VEGF-induced Ang2 secretion as well as disrupting Ang2/Tie2 signal transduction. Our findings extend current understanding of mechanisms regulating RA angiogenesis and may support development of novel angiogenesis-targeting therapeutics for RA treatment.
The influence of age and experience on salt preference of the rat.

The degree to which adult taste preferences can be influenced by early taste exposure is a matter of some debate. The present studies characterize the developmental course of saline preference during maturation in the rat and examine whether adult saline preference is influenced by postweaning exposure to saline solutions. Saline intake from weaning to adulthood was examined in Wistar rats allowed continuous access to demineralized water and either . 0, . 9, 1.8, or 2.7% sodium chloride (NaCl) w/v solutions. When rats were immature they expressed greater preference for saline solutions than they did as adults. It is hypothesized that the overconsumption of saline by young animals is related to lower sensitivity of the taste system to NaCl in the early postweaning period. Animals that had had continuous access to saline from weaning were compared to those that had not received saline exposure early in life, in order to determine whether extensive experience with salt solutions leads to alterations in adult salt preference. These studies failed to reveal any evidence that rearing condition affects adult salt preference; thus adult salt preference may be maturationally determined and relatively independent of postweaning environmental influences.
Retrospective comparison of mechanical percutaneous thrombectomy of hemodialysis arteriovenous grafts with the Arrow-Trerotola device and the lyse and wait technique.

OBJECTIVE The purpose of our study was to determine whether pharmacologic thrombolysis with urokinase in the lyse and wait (L&W) technique compared with mechanical declotting using the Arrow-Trerotola percutaneous thrombectomy device is more efficient, safer, or less expensive in treating thrombosed hemodialysis grafts. MATERIALS AND METHODS The files of 157 patients who underwent arteriovenous graft declotting from 2000 to 2007 at one tertiary care center were reviewed. The study group included 83 women and 74 men with a mean age of 68 +/- 12 years (range, 27-95 years). A total of 563 procedures were performed: 427 with the L&W technique and 136 with mechanical percutaneous thrombectomy using the percutaneous thrombectomy device. The two types of procedures were compared for success rate, complications, average patency time, and cost. RESULTS There were no statistically significant differences between the pharmacologic and mechanical procedures in immediate success rate (99% and 98%, respectively) or average patency time (5.44 months and 5.40 months, respectively). The L&W technique was considerably less expensive. CONCLUSION Given its lower cost and equal efficacy and safety, L&W appears to be preferable to mechanical thrombolysis with a percutaneous thrombectomy device for initial arteriovenous hemodialysis graft declotting.
Distinctiveness in the face of gene flow: hybridization between specialist and generalist gartersnakes

Patterns of divergence and polymorphism across hybrid zones can provide important clues as to their origin and maintenance. Unimodal hybrid zones or hybrid swarms are composed predominantly of recombinant individuals whose genomes are patchworks of alleles derived from each parental lineage. In contrast, bimodal hybrid zones contain few identifiable hybrids; most individuals fall within distinct genetic clusters. Distinguishing between hybrid swarms and bimodal hybrid zones can be important for taxonomic and conservation decisions regarding the status and value of hybrid populations. In addition, the causes of bimodality are important in understanding the generation and maintenance of biological diversity. For example, are distinct clusters mostly reproductively isolated and co‐adapted gene complexes, or can distinctiveness be maintained by a few ‘genomic islands’ despite rampant gene flow across much of the genome? Here we focus on three patterns of distinctiveness in the face of gene flow between gartersnake taxa in the Great Lakes region of North America. Bimodality, the persistence of distinct clusters of genotypes, requires strong barriers to gene flow and supports recognition of distinct specialist (Thamnophis butleri) and generalist (Thamnophis radix) taxa. Concordance of DNA‐based clusters with morphometrics supports the hypothesis that trophic morphology is a key component of divergence. Finally, disparity in the level of differentiation across molecular markers (amplified fragment length polymorphisms) indicates that distinctiveness is maintained by strong selection on a few traits despite high gene flow currently or in the recent past.
Single Nucleotide Polymorphism Analysis of the Nucleotide Excision Repair Genes XPC, XPA, and XPG in the Indian Population

ABSTRACT We have analyzed single nucleotide polymorphisms (SNPs) in the XPC, XPA, and XPG genes of the nucleotide excision repair (NER) pathway in the Indian population. In the XPC gene we observed nine polymorphisms in the coding region, four polymorphisms in the intronic region, and two polymorphisms in the 5′untranslated region (UTR). In the XPA gene we observed one frequent SNP (allele frequency 0.48) within the 5′UTR at the 1665 position in a large proportion of the sample. In addition, we observed three novel heterozygous polymorphisms (a C to A transversion at position 1523 and a G to A transition at positions 1418 and 1458, with an allele frequency of 0.004) within the promoter region. In silico PCR analysis demonstrated that all three novel polymorphisms lie within a putative CpG island and that the variation at position 1418 falls within the potential GATA1/2/3 transcription factor(s) binding site and also within the negative control element. We performed a gel retardation assay with HeLa cell nuclear extract with an oligonucleotide encompassing this region. One of the alleles found at position 1458 of the XPA gene showed a significant change in protein-DNA interaction. In the XPG gene we found five polymorphisms in the coding region and one each in the 5′UTR of exon 1 and in intron 13.
Site-directed alkylation of multiple opioid receptors. II. Pharmacological selectivity.

A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has been inactivated, the method can be used to characterize the pharmacological selectivity of opioid agonists. All of the smaller opioid products of the enkephalin gene were found to be delta-selective in the mouse vas deferens, but BAM-12P, BAM- 22P , and Peptide E were not. In the same tissue, beta c-endorphin was not mu-selective, but in the guinea pig ileum preparation it evidently combined with mu and kappa receptors. The presence of functional epsilon receptors, however, could not be ruled out. The approach described here is applicable to any pharmacologically active receptors of which there are multiple types, and for which site-directed alkylating agents and type-selective protector ligands are available.
Development of visual acuity

A hand-held electrically operated instrument has been devised to assess visual acuity by means of the phenomenon of opto-kinetic fixation nystagmus. An accurate determination of visual acuity has been obtained from an early age, and a graph of the normal visual acuity development produced. It has been confirmed that adult acuity is reached by 3 years of age.
Regulatory DNA‐binding proteins in yeast: An overview

The aim of this paper is to provide an overview of the transcription regulators described in yeast. Forty-three factors are listed in alphabetical order. The structural and functional characteristics of the proteins are given first. This includes the consensus DNA-binding sequence, the effect on transcription and, if relevant, particular structures, other names for the protein and names of homologous proteins in mammalian and yeast cells
Assessing estrogen and progesterone receptor status in fine needle aspirates from breast carcinomas. Results on six years of material and correlation with biochemical assay.

OBJECTIVE To evaluate the usefulness of immunocytochemical staining on breast fine needle aspiration (FNA) cytology as a routine procedure for determination of estrogen (ER) and progesterone (PR) receptor status. STUDY DESIGN FNA cytology material from 864 patients was immunostained for ER and PR using Abbott ER/PR-ICA kits. Percentage of stained nuclei, staining intensity and staining pattern was evaluated. In 259 cases comparison with biochemical assay was possible. RESULTS Of the cases, 75.6% were ER positive and 65% PR positive, and 61.6% were both ER and PR positive. Approximately 4% of the smears were inconclusive because of scant cellularity. Concordance between the immunostaining and biochemical method was 84% for ER and 71% for PR. Kappa values were 0.61 and 0.4, respectively. Major discrepancies were found in 7.7% of the specimens. CONCLUSION Inconclusive smears due to scant cellularity is a minor problem. Technical difficulties are few, and false negative and positive staining is rarely seen. The results are comparable to those from the biochemical method, and immunostaining of ER/PR on breast cancer FNA cytology smears is useful as a routine procedure for receptor determination.
GSK‐3β Inhibition Promotes Engraftment of Ex Vivo‐Expanded Hematopoietic Stem Cells and Modulates Gene Expression

Glycogen synthase kinase‐3β (GSK‐3β) has been identified as an important regulator of stem cell function acting through activation of the wingless (Wnt) pathway. Here, we report that treatment with an inhibitor of GSK‐3β, 6‐bromoindirubin 3′‐oxime (BIO) delayed cell cycle progression by increasing cell cycle time. BIO treatment resulted in the accumulation of late dividing cells enriched with primitive progenitor cells retaining the ability for sustained proliferation. In vivo analysis using a Non‐obese diabetic/severe combined immunodeficient (NOD/SCID) transplantation model has demonstrated that pretreatment with BIO promotes engraftment of ex vivo‐expanded hematopoietic stem cells. BIO enhanced the engraftment of myeloid, lymphoid and primitive stem cell compartments. Limiting dilution analysis of SCID repopulating cells (SRC) revealed that BIO treatment increased human chimerism without increasing SRC frequency. Clonogenic analysis of human cells derived from the bone marrow of transplant recipient mice demonstrated that a higher level of human chimerism and cellularity was related to increased regeneration per SRC unit. Gene expression analysis showed that treatment with BIO did not modulate the expression of canonical Wnt target genes upregulated during cytokine‐induced cell proliferation. BIO increased the expression of several genes regulating Notch and Tie2 signaling downregulated during ex vivo expansion, suggesting a role in improving stem cell engraftment. In addition, treatment with BIO upregulated CDK inhibitor p57 and downregulated cyclin D1, providing a possible mechanism for the delay seen in cell cycle progression. We conclude that transient, pharmacologic inhibition of GSK‐3β provides a novel approach to improve engraftment of expanded HSC after stem cell transplantation. STEM CELLS 2011;29:108–118
In Vivo Characterization of Cortical Bone Using Guided Waves Measured by Axial Transmission

Cortical bone loss is not fully assessed by the current X-ray methods, and there is an unmet need in identifying women at risk of osteoporotic fracture, who should receive a treatment. The last decade has seen the emergence of the ultrasound (US) axial transmission (AT) techniques to assess a cortical bone. Recent AT techniques exploit the multimode waveguide response of the long bones such as the radius. A recent ex vivo study by our group evidenced that a multimode AT approach can yield simultaneous estimates of cortical thickness (Ct.Th) and stiffness. The aim of this paper is to move one step forward to evaluate the feasibility of measuring multimode guided waves (GW) in vivo and to infer from it cortical thickness. Measurements were taken on the forearm of 14 healthy subjects with the goal to test the accuracy of the estimated thickness using the bidirectional AT method implemented on a dedicated 1-MHz linear US array. This setup allows determining in vivo the dispersion curves of GW transmitted in the cortical layer of the radius. An inverse procedure based on the comparison between the measured and modeled dispersion curves predicted by a 2-D transverse isotropic free plate waveguide model allowed an estimation of cortical thickness, despite the presence of soft tissue. The Ct.Th values were validated by comparison with the site-matched estimates derived from X-ray high-resolution peripheral quantitative computed tomography. Results showed a significant correlation between both measurements (r2 = 0.7, p <; 0.05, and RMSE = 0.21 mm). This pilot study demonstrates the potential of bidirectional AT for the in vivo assessment of cortical thickness, a bone strength-related factor.
Intrathecal Versus Intravenous Morphine in Minimally Invasive Posterior Lumbar Fusion: A Blinded Randomized Comparative Prospective Study.

STUDY DESIGN A blinded, randomized, comparative prospective study. OBJECTIVE The aim of this study was to compare the use of intrathecal morphine to endovenous morphine on postoperative pain after posterior lumbar surgery. SUMMARY OF BACKGROUND DATA Intrathecal morphine can provide significant safe analgesia for at least 12 hours and up to 24 hours in patients undergoing major surgery. Its dosages have been decreasing in the last 30 years, but currently, the optimal dose remains unknown. As of today, there are no studies comparing the efficacy and the side effects of this technique with intravenous morphine administration after minimally invasive lumbar fusion surgery. METHODS We randomized and compared two groups of 25 patients, who were given either 100 μg intrathecal (ITM group) or 5 ± 2 mg intravenous morphine delivered intravenously for 24 hours at 2 mL/h (IVM group) after minimally invasive posterior lumbar fusion. VAS score at 0, 6, 12, 24 hours, mobilization out of bed at 6 hours, hospitalization duration and complications as lower limbs paresthesia, urinary retention at 6 and 12 hours, nausea, vomit, itch, and constipation were evaluated. RESULTS Data showed a lower VAS score, a reduction of constipation, lower limbs paresthesia, or urinary retention at 12 hours in ITM rather than in the IVM group. None suffered of vomit, itch, or nausea in both groups. Urinary retention was observed more frequently in ITM group at 6 hours. Patients of ITM group were mobilized out bed earlier than those from IVM group. CONCLUSION A low dosage of intrathecal morphine is safe and effective after minimally invasive lumbar fusion surgery. The reduction of pain in the study group permitted a shorter hospitalization and earlier mobilization out of bed, augmenting patients' comfort. LEVEL OF EVIDENCE 2.