Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute modification of biomechanical properties of the bone‐ligament insertion to rat limb unweighting

We investigated the acute adaptation of the rat femur‐medial collateral ligament‐tibia (FMT) complex to 7 days of limb unweighting by means of a hind‐limb suspension protocol. Male, young adult, Harlan Sprague‐Dawley rats were randomly assigned to either control or suspended groups. Rats deprived of hind limb‐to‐ground contact forces had a 42% decrease in soleus muscle mass compared with the control group. Medial collateral ligament (MCL) length and cross‐sectional area were measured, and each FMT complex was tension tested to failure. All failed at their tibia‐MCL insertion. The ultimate load in the FMT and the peak Kirchhoff stress in the MCL (occurring immediately before insertion site failure) were significantly reduced in the suspended group. The suspended MCLs were 9.7% larger in area and 5.7% shorter in length than the controls under the same preload (0.25 N). We found no significant differences between the control and suspended MCLs in Green strain, stretch, or deformation immediately before insertion site failure, nor did we find a significant difference in the MCL tangent modulus. This study indicates that even acute periods of limb unweighting can structurally compromise bone‐ligament insertions. Further, this study implies that the adaptations responsible for this structural compromise must involve acute changes in the intrinsic zone (or zones) of the bone‐ligament insertion. — Vanderby, R. , Jr.; Vailas, A. C. ; Graf, B. K. ; Thielke, R. J.; Ulm, M. J.; Kohles, S. S. ; Kunz, D. N. Acute modification of biomechanical properties of the bone‐ligament insertion to rat limb unweighting. FASEB J. 4: 2499‐2505; 1990.
The effect of neonatal bacille Calmette-Guérin vaccination on purified protein derivative skin test results in Canadian aboriginal children.

BACKGROUND The effect that neonatal bacille Calmette-Guérin (BCG) vaccination has on tuberculin skin test (TST) results is not well evaluated in preschool children. METHODS This was a retrospective cohort study of TST results in aboriginal children in Saskatchewan reserve communities. Records from the centralized provincial tuberculosis program were searched for aboriginal children aged 0 to 4 years during the time period 1991 to 1999. Only the first TST result reported as part of infant and preschool screening programs was considered. Children with active tuberculosis and those evaluated as part of a contact-tracing program were excluded. The BCG-vaccinated and unvaccinated groups were compared using wheal size cut points of 5 mm, 10 mm, and 15 mm. RESULTS Data from 1,086 children with neonatal BCG vaccination and 1,867 unvaccinated children were analyzed. The rate of TST reactions was higher in vaccinated children at all ages, using a cut point of 5 mm. The rate of TST reactions was no different in vaccinated children >or= 1 year old when using a cut point of 15 mm. When using a cut point of 10 mm, the rate of TST reactions was higher at age 1 year but not different at age 4 years in the vaccinated children. CONCLUSION The rate of TST reactions in preschool aboriginal children living on a reserve who have received neonatal BCG vaccination is affected by the cut point and age. The BCG vaccination status and age should therefore be considered when interpreting TST reactivity in the clinical assessment of aboriginal children participating in a tuberculosis control program.
Extreme C Terminus of G Protein α-Subunits Contains a Site That Discriminates between Gi-coupled Metabotropic Glutamate Receptors*

Metabotropic glutamate receptors (mGlu receptors), the Ca2+-sensing receptor, γ-aminobutyric acid type B receptors, and one group of pheromone receptors constitute a unique family (also called family 3) of heptahelical receptors. This original family shares no sequence similarity with any other G protein-coupled receptors. The identification and comparison of the molecular determinants of receptor/G protein coupling within the different receptor families may help identify general rules involved in this protein/protein interaction. In order to detect possible contact sites important for coupling selectivity between family 3 receptors and the G protein α-subunits, we examined the coupling of the cyclase-inhibiting mGlu2 and mGlu4 receptors to chimeric αq-subunits bearing the 5 extreme C-terminal amino acid residues of either Gαi, Gαo, or Gαz. Whereas mGlu4 receptor activated all three chimeric G proteins, mGlu2 receptor activated Gαqi and Gαqo but not Gαqz. The mutation of isoleucine −4 of Gαqz into cysteine was sufficient to recover coupling of the mutant G protein to mGlu2 receptor. Moreover, the mutation of cysteine −4 of Gαqointo isoleucine was sufficient to suppress the coupling to mGlu2 receptor. Mutations at positions −5 and −1 had an effect on coupling efficiency, but not selectivity. Our results emphasize the importance of the residue −4 of the α-subunits in their specific interaction to heptahelical receptors by extending this finding on the third family of G protein-coupled receptors.
Health-Related Quality of Life after Pancreatic Islet Transplantation: A Longitudinal Study

Background. Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. Methods. Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student’s t tests. Results. Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. Conclusion. PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.
Phasic mechanoreceptor stimuli can induce phasic activation of upper airway muscles in humans

1 Upper airway dilator muscles are phasically activated throughout breathing by respiratory pattern generator neurons. Studies have shown that non‐physiological upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative pressure) also activate these muscles. Such reflexes may become activated during conditions that alter airway resistance in order to stabilise airway patency. 2 To determine the contribution of ongoing mechanoreceptive reflexes to phasic activity of airway dilators, we assessed genioglossal electromyogram (GG EMG: rectified with moving time average of 100 ms) during slow (physiological) oscillations in negative pressure generated spontaneously and passively (negative pressure ventilator). 3 Nineteen healthy adults were studied while awake, during passive mechanical ventilation across normal physiological ranges of breathing rates (13–19 breaths min−1) and volumes (0.5–1.0 l) and during spontaneous breathing across the physiological range of end‐tidal carbon dioxide (PET,CO2; 32–45 mmHg). 4 Within‐breath phasic changes in airway mechanoreceptor stimuli (negative pressure or flow) were highly correlated with within‐breath phasic genioglossal activation, probably representing a robust mechanoreceptive reflex. These reflex relationships were largely unchanged by alterations in central drive to respiratory pump muscles or the rate of mechanical ventilation within the ranges studied. A multivariate model revealed that tonic GG EMG, PET,CO2 and breath duration provided no significant independent information in the prediction of inspiratory peak GG EMG beyond that provided by epiglottic pressure, which alone explained 93 % of the variation in peak GG EMG across all conditions. The overall relationship was: Peak GG EMG = 79.7 − (11.3 x Peak epiglottic pressure), where GG EMG is measured as percentage of baseline, and epiglottic pressure is in cmH2O. 5 These data provide strong evidence that upper airway dilator muscles can be activated throughout inspiration via ongoing mechanoreceptor reflexes. Such a feedback mechanism is likely to be active on a within‐breath basis to protect upper airway patency in awake humans. This mechanism could mediate the increased genioglossal activity observed in patients with obstructive sleep apnoea (i.e. reflex compensation for an anatomically smaller airway).
Comparison of a competitive combined reverse transcription-PCR assay with a branched-DNA assay for hepatitis C virus RNA quantitation

We have developed a sensitive and reproducible one-step competitive reverse transcriptase (RT) PCR assay, which allows hepatitis C virus (HCV) RNA quantitation in plasma over a broad range of values. The RNA samples and a constant amount of an internal standard were reverse transcribed and coamplified with the same primers in the same tube. A standard curve was obtained from an additional series of tubes containing both the internal standard and known amounts of a wild-type HCV RNA transcript, thus eliminating the need for titrating samples with the competitor. Eighty-eight anti-HCV-positive samples were tested by RT-PCR and a branched-DNA (bDNA) assay which has a detection limit of 3.5 x 10(5) copies per ml. Fifty-five samples were quantifiable by both methods (correlation coefficient, 0.72), the ranges of values found by the RT-PCR and bDNA assays being, respectively, 0.127 x 10(6) to 18.4 x 10(6) and 0.44 x10(6) to 38 x 10(6) copies per ml. Six samples that had indeterminate values by the bDNA assay had RT-PCR values between 0.37 x 10(5) and 9.6 x 10(5) copies per ml. Twenty-two samples that had values below the cutoff value by the bDNA assay had RT-PCR values between 2.5 x 10(3) and 10.4 x 10(5) (18 less than and 4 more than the limit of 3.5 x 10(5) copies per ml). The remaining five samples were negative by both assays. The level of RT-PCR interassay reproducibility was high (correlation coefficient between duplicate values, 0.94). Our method, with a detection limit of 2,500 copies per ml, was markedly more sensitive than the bDNA assay. This method is convenient for following up patients with low viremia, a common situation with alpha interferon treatment.
Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35‐year period (1970–2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970–2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age‐standardized incidence and mortality, relative, cancer‐specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970–1978 and 1997–2004), 5‐year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage‐stratified, improved 5‐year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1‐year survival was mainly observed in stages III and IV. Five‐year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1‐year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.
Approaching the capacity of two-pair bidirectional Gaussian relay networks

The authors present an improved achievable rate region for two-pair bidirectional Gaussian relay networks based on successive compute-and-forward method. In these networks, one relay helps in the communication between two pairs of users. In their proposed scheme, the authors use nested lattice codes for encoding the messages at the users, and Gaussian random codes for the encoding at the relay. They use the successive compute-and-forward strategy to decode two integer linear combinations of the lattice codewords in the uplink, and successive interference cancellation for decoding the Gaussian codewords in the downlink. The downlink channel can be considered as a broadcast channel with two receiver groups, but within each group, a pair of users is considered as an additive white Gaussian noise channel (instead of a broadcast channel) because each node knows its own transmitted message. It is shown that for all channel gains of downlink channels and all channel gains of symmetric uplink channel pairs, the strategy achieves rates to within constant gaps of 1/2 and 3/4 bit/s/Hz per user of the cut-set upper bound for restricted and non-restricted models, respectively. These gaps are tighter than those previously obtained for this network, which have not exploited the successive compute-and-forward method.
Is There a Role for Therapeutic Drug Monitoring of Vitamin D Level as a Surrogate Marker for Fracture Risk?

Clinical studies have suggested a possible association of low serum vitamin D levels in patients with bone fractures. This, coupled with a high prevalence of fractures and increases in associated disability and mortality, begs the question, is there evidence to support a role for therapeutic drug monitoring of vitamin D levels to prevent bone fractures? We use a previously published nine‐step decision‐making algorithm to answer this question. Optimal dosages of vitamin D have not been determined, although daily intake guidelines are suggested. Current vitamin D assays yield varying results, making it challenging for clinicians to interpret results from clinical trials and apply them directly to patients and their specific serum level data. Fracture risk is not easily assessable clinically, with no clear relationship between vitamin D concentrations and bone mineral density. The existing primary literature shows no clear relationship between vitamin D concentrations and fracture risk; target concentrations are not well established. Although the pharmacokinetic parameters of vitamin D are unpredictable and vitamin D supplementation is frequently lifelong, results of a vitamin D assay are unlikely to make a significant difference in the clinical decision‐making process (i. e., provide more information than clinical judgment alone). Most published studies on vitamin D levels and fracture risk did not control for other potential reasons to monitor levels, multifactorial risks for fractures, and other confounders. Given limited data to support a direct relation between vitamin D levels and clinical outcome of fracture, inconsistent between‐assay results, and no consensus on optimal levels, there is insufficient evidence to recommend routine therapeutic drug monitoring of vitamin D for fracture prevention; however, other reasons for monitoring might exist that are beyond the scope of this review. Recent availability of vitamin D assay standards may lead to future improvements in comparability of research data, establishment of a target range, and interpretability of patient results.
The Accumulation of (Dis)advantage

A sizable literature examines whether and why marriage affects men’s and women’s wages. This study advances current research in two ways. First, whereas most prior studies treat the effect of marriage as time-invariant, I examine how the wage effect of marriage unfolds over the life course. Second, whereas prior work often focuses on the population-average effect of marriage or is limited to some particular gender or racial group, I examine the intersection of gender and race in the effect of marriage. Analyzing data from the National Longitudinal Survey of Youth 1979, I find that the marriage wage premium grows steadily and at a similar pace among white and black men. The marriage wage premium declines toward negative among white women, yet it grows steadily among black women. Furthermore, measured work experience explains a substantial amount of the wage premium among black men, yet it has little explanatory power among white men, pointing to the importance of unobserved factors in white men’s marriage premium. Changes in work experience negatively affect married white women’s wages, yet they positively affect married black women’s wages, pointing to the important differences between black and white families.
Planning and Spatial Working Memory: a Positron Emission Tomography Study in Humans

Previous work with both neurosurgical and neurodegenerative patient groups has suggested that high level planning is mediated by neural circuitry which includes both the prefrontal cortex and the striatum. In this study, the functional anatomy of cognitive planning was investigated further, using positron emission tomography (PET). Regional cerebral blood flow (rCBF) was measured in 12 normal volunteers while performing easy and difficult versions of (i) a modified Tower of London planning task; (ii) a mnemonic variant of this task that required short‐term retention and reproduction of problem solutions; and (iii) a control condition that involved identical visual stimuli and motor responses. Significant increases in rCBF were observed in the left hemisphere, in both the mid‐dorsolateral frontal cortex and in the head of the caudate nucleus, when the difficult planning task was compared with the control condition. Moreover, subtraction of a simple planning condition from the more difficult one revealed focal increases in rCBF in the caudate nucleus and the thalamus only. During both mnemonic variants of the planning task, changes were also observed in the mid‐dorsolateral frontal cortex and in more ventral frontopolar regions, bilaterally. When compared directly, the planning and memory conditions differed in terms of these ventral activation foci, but not in the pattern of activation observed in the mid‐dorsolateral frontal cortex. These findings further implicate frontostriatal circuitry in high‐level planning and provide evidence for functionally distinct contributions from ventral and dorsolateral frontal regions to spatial working memory.
Analysis of double‐substrate limited growth

Mathematical models which relate the growth rate of a microorganism to a single limiting substrate concentration have long been established. In recent years, it has become apparent that, under certain conditions, the growth rate of an organism may be simultaneously limited by two or more substrates. Mathematical models of double‐substrate limitation fall into two categories: interactive and no interactive models. A discussion of both types of models is presented in both conceptual and mathematical terms. An analogous case of an enzyme which requires two different substrates to produce a single product is presented. This enzyme analog indicates that both types of double‐substrate limitation models appear to be feasible under certain conditions. Based upon stoichiometry and specific growth rate‐substrate concentration contour plots, a method for determining the operational conditions which will lead to double‐substrate limitation is presented.
Impact of a 21‐gene RT‐PCR assay on treatment decisions in early‐stage breast cancer

The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction (RT‐PCR) assay underwent validation in 668 lymph node‐negative, estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program (NSABP) B‐14. The predictive accuracy for treatment efficacy also underwent validation in 651 patients randomized on NSABP B‐20 and 645 patients on NSABP B‐14.
Genotypic analysis of infant macaques infected transplacentally and orally

Abstract: The SIV‐infected macaque provides an excellent model to study factors involved in maternal‐fetal transmission of HIV. In our prenatal transmission studies, female macaques were inoculated intravenously during midgestation with either SIV/DeltaB670 or a combination of SIV/DeltaB670 and the macrophage‐tropic molecular clone SIV/17E‐Fr. The females harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants. One of two variants was transplacentally transmitted to the infants, SIV/17E‐Fr or B670‐Cl 12, a genotype contained within the SIV/DeltaB670 inoculum. Both of these variants have been identified in the central nervous system of macaques that have developed encephalitis and they replicate in vitro on primary rhesus macrophages. These results suggest a critical role for macrophages in fetal infection in utero. In our perinatal transmission studies we have evaluated the viral genotypes found in two newborn macaques infected orally with SIV/DeltaB670 and in one infant infected via amniotic inoculation in late gestation. More than one viral genotype was identified in each infant, moreover, each infant harbored different genotypes. These results suggest different mechanisms are responsible for viral infection via these routes.
Expression of p27kip1 in Basal Cell Carcinomas and Trichoepitheliomas

Immunohistochemical analysis was used to evaluate p27kip1 expression in normal hair follicles and in a series of 39 basal cell carcinomas (BCC) (13 of superficial type, 7 infiltrating, 7 morphea-like, 12 nodular) and 20 trichoepitheliomas (TE) (9 of classic type, 9 immature, 2 desmoplastic). The labeling index (LI) was derived semiautomatically by means of a computer-assisted cellular image analyzer, and statistical analysis was carried out using the Student t test. A positive reaction for p27kip1 was detected in the hair germ papillae, in supramatrical cells, and in the inner pilar sheath, whereas matrical cells and the outer pilar sheath were negative. All BCC and TE cases showed a positive immunoreaction for p27kip1, but the staining pattern was different in the two groups of lesions, being patchy with focal peripheral accentuation in TE and more diffusely dispersed in BCC. The quantitative study showed lower p27kip1 expression in BCC (LI = 27.51 ± 12.55) than in TE (LI = 45.27 ± 20.27) (P < 0.0001). Statistically significant differences were also observed between TE subgroups and nodular or infiltrating BCC subtypes. The occurrence of a wide overlap of LI values hampers the practical application of a p27kip1 LI in the differential diagnosis between BCC and TE in difficult cases, however.