Miracle-dz/UniFAR-FTUs huggingface dataset:
PREPmate automated processor: Comparison of automated and manual methods of liquid‐based gynecologic sample preparation

The development of procedures for fully automated processing of liquid‐based gynecologic samples has been the focus of considerable interest to the cytology laboratory. Liquid‐based collection and processing technology has been shown to improve sample adequacy, resulting in an overall improvement in quality of sample preparations. PREPmate™, an accessory to the PrepStain™ slide processor, automates the initial enrichment process of mixing and dispensing the specimen over a density gradient. This report describes a study evaluating cellularity and diagnostic reproducibility in SurePath™ samples processed using the PREPmate™ accessory compared to samples processed using a manual technique. Samples processed using the PREPmate™ accessory contained 8.3% more squamous cells. Exact diagnostic reproducibility between preparation types was 83.3%; when considering negative vs. abnormal (ASCUS+), in adequate samples, reproducibility was 100%. Diagn. Cytopathol. 2002;27:312–315. © 2002 Wiley‐Liss, Inc.
Postnatal Development of Arterial Pressure: Influence of the Intrauterine Environment

A substantial number of epidemiological studies have shown that small size at birth is associated with an increased risk of developing hypertension and metabolic dysfunction later in life; however these associations have not been found in all studies. In animals, several models have been used to investigate the effects of perturbations to the fetal environment on later arterial pressure, with differing effects on size at birth and arterial pressure. Ovine models include maternal dietary manipulations, antenatal glucocorticoid exposure, and restriction of placental size and function. In our laboratory, we have induced late gestational placental insufficiency and growth restriction in sheep by umbilico-placental embolisation; during the early postnatal period the growth restricted lambs remained small and were hypotensive relative to controls. More recent long-term studies indicate that these growth restricted animals were able to catch up in body weight within the first postnatal year; however, their arterial pressure remained lower than that of controls throughout the first 2 postnatal years (? MAP, –4.2 ± 1.4 mmHg). This relative hypotension may be due to altered vascular or cardiac development resulting from increased vascular resistance or nutrient restriction during fetal life. As late gestational placental insufficiency led to a persistent reduction in arterial pressure from birth to adulthood, our findings do not support the hypothesis that restricted fetal growth per se leads to hypertension after birth. It is likely that the effects of a prenatal compromise on postnatal arterial pressure will vary depending on the nature of the associated developmental perturbations and their gestational timing.
Translocation of Glycogen Synthase Kinase-3β (GSK-3β), a Trigger of Permeability Transition, Is Kinase Activity-dependent and Mediated by Interaction with Voltage-dependent Anion Channel 2 (VDAC2)*

Background: Glycogen synthase kinse-3β (GSK-3β) promotes mitochondrial permeability transition (MPT), a mechanism of cell necrosis. Results: Efficient GSK-3β translocation to mitochondria requires its kinase activity, N-terminal domain, and interaction with VDAC2 protein. Conclusion: MPT can be suppressed by inhibiting mitochondrial transport of GSK-3β. Significance: A strategy for cell protection without modifying the physiological function of GSK-3β is proposed. Glycogen synthase kinase-3β (GSK-3β) is a major positive regulator of the mitochondrial permeability transition pore (mPTP), a principle trigger of cell death, under the condition of oxidative stress. However, the mechanism by which cytosolic GSK-3β translocates to mitochondria, promoting mPTP opening, remains unclear. Here we addressed this issue by analyses of the effect of site-directed mutations in GSK-3β on mitochondrial translocation and protein/protein interactions upon oxidative stress. H9c2 cardiomyoblasts were transfected with GFP-tagged GSK-3β (WT), a mutant GSK-3β insensitive to inhibitory phosphorylation (S9A), or kinase-deficient GSK-3β (K85R). Time lapse observation revealed that WT and S9A translocated from the cytosol to the mitochondria more promptly than did K85R after exposure to oxidative stress. H2O2 increased the density of nine spots on two-dimensional gel electrophoresis of anti-GSK-3β-immunoprecipitates by more than 3-fold. MALDI-TOF/MS analysis revealed that one of the spots contained voltage-dependent anion channel 2 (VDAC2). Knockdown of VDAC2, but not VDAC1 or VDAC3, by siRNA attenuated both the mitochondrial translocation of GSK-3β and mPTP opening under stress conditions. The mitochondrial translocation of GSK-3β was attenuated also when Lys-15, but not Arg-4 or Arg-6, in the N-terminal domain of GSK-3β was replaced with alanine. The oxidative stress-induced mitochondrial translocation of GSK-3β was associated with an increase in cell death, which was suppressed by lithium chloride (LiCl), a GSK-3β inhibitor. These results demonstrate that GSK-3β translocates from the cytosol to mitochondria in a kinase activity- and VDAC2-dependent manner in which an N-terminal domain of GSK-3β may function as a mitochondrial targeting sequence.
Domestic Debt and Economic Growth in Pakistan: An Empirical Analysis

Pakistan is surrounded in serious socio-economic problems. Due to low tax base and twin deficits, Pakistan has to rely on both external and internal capital flows. The foreign capital flows are not easily accessible but domestic capital flows are approachable at all times. The study investigates the impacts of domestic debt on economic growth in Pakistan applying the OLS technique for the period of 1972 to 2009. The study indicates that the stock of domestic debt affects the economic growth positively in Pakistan. This clearly means that the resources generated through domestic borrowing have been used partially to finance those expenditures of government which contribute the economic growth. The study also observes that there is an inverse relationship between domestic debt servicing and economic growth. This result is due to the fact that huge burden of non-development expenditures impedes the economic growth. The findings of study reveal that the negative impact of domestic debt servicing on economic growth is stronger than positive impact of domestic debt on economic growth. The study also suggests some polices to settle the outstanding domestic debt.
Population Pharmacokinetics of Lopinavir/Ritonavir (Kaletra) in HIV-Infected Patients

Background: A relationship between plasma concentrations and viral suppression in patients receiving lopinavir (LPV)/ritonavir (RTV) has been observed. Therefore, it is important to increase our knowledge about factors that determine interpatient variability in LPV pharmacokinetics (PK). Methods: The study, designed to develop and validate population PK models for LPV and RTV, involved 263 ambulatory patients treated with 400/100 mg of LPV/RTV twice daily. A database of 1110 concentrations of LPV and RTV (647 from a single time-point and 463 from 73 full PK profiles) was available. Concentrations were determined at steady state using high-performance liquid chromatography with ultraviolet detection. PK analysis was performed with NONMEM software. Age, gender, height, total body weight, body mass index, RTV trough concentration (RTC), hepatitis C virus coinfection, total bilirubin, hospital of origin, formulation and concomitant administration of efavirenz (EFV), saquinavir (SQV), atazanavir (ATV), and tenofovir were analyzed as possible covariates influencing LPV/RTV kinetic behavior. Results: Population models were developed with 954 drug plasma concentrations from 201 patients, and the validation was conducted in the remaining 62 patients (156 concentrations). A 1-compartment model with first-order absorption (including lag-time) and elimination best described the PK. Proportional error models for interindividual and residual variability were used. The final models for the drugs oral clearance (CL/F) were as follows: The predictive performance of the final population PK models was tested using standardized mean prediction errors, showing values of 0.03 ± 0.74 and 0.05 ± 0.91 for LPV and RTV, and normalized prediction distribution error, confirming the suitability of both models. Conclusions: These validated models could be implemented in clinical PK software and applied to dose individualization using a Bayesian approach for both drugs.
Sports related hamstring strains – two cases with different etiologies and injury sites

Hamstring strains are common injuries in sports. Knowledge about their etiology and localization is, however, limited. The two cases described here both had acute hamstring strains, but the etiologies were entirely different. The sprinter was injured when running at maximal speed, whereas the hamstring strain in the dancer occurred during slow stretching. Also the anatomical localizations of the injuries clearly differed. Magnetic resonance imaging (MRI) revealed pathological changes in the distal semitendinosus muscle in the sprinter and the proximal tendon of the semimembranosus muscle in the dancer. Subjectively, both athletes severely underestimated the recovery time. These case observations suggest a possible link between etiology and localization of hamstring strains.
Circulatory effects of apnoea in elite breath‐hold divers

Aim: Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath‐hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black‐out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake.
HSPICE macromodel of PCRAM for binary and multilevel storage

A general macromodel of the phase change random access memory (PCRAM) elements for use in HSPICE-based computer simulator is proposed in this paper by introducing physical models of PCRAM elements. It can simulate the dc and transient behavior of PCRAM element. In this paper, the model was integrated with the standard R/W circuit and successfully simulated the R-I curve and dependence between amplitude and width of programming pulses. A comparison between experimental and simulation results were also given. Furthermore, by including the partial crystallization states, the macromodel was developed for simulating the multilevel storage.
Boundary recursion for descriptor variable systems

A linear discrete-time descriptor variable system defined on the time interval [0,N] has the form E(k+1)x(k+1) = A(k)x(k) + B(k)u(k) for k = 0,1,2,. ,N-1. For each k, x(k) is an n-dimensional vector of descriptor variables, u(k) is an m-dimensional vector of input variables, and the matrices A(k), E(k+1), B(k) are of compatible dimensions. If the system satisfies the property of solvability [1], it will have an n-dimensional family of solutions. It is shown in this paper that if the system also satisfies the property of conditionability, the solutions will each satisfy an equation of the form Z0x(0) + ZNx(N) = v(N) where the matrix Z = [Z0,ZN] is of rank n and v(N) depends on the input sequence. This equation is called a boundary mapping equation. In the case of solvable and conditionable systems the boundary mapping equation is a complete summary of the system, in the sense that there is a one-to-one correspondence between solutions to this equation and solutions to the original descriptor variable system. It therefore provides a compact representation of the system's influence on the boundary points. It is an (n-dimensional) equation which "jumps over" the intermediate values and directly links x(0) and x(N). In fact, the boundary mapping generalizes the state-transition matrix associated with state variable systems.
Effective Proliferation of Human Regulatory T Cells Requires a Strong Costimulatory CD28 Signal That Cannot Be Substituted by IL-21

The strength of immune repression by regulatory T (Treg) cells is thought to depend on the efficiency of Treg cell activation. The stimuli and their individual strength required to activate resting human Treg cells, however, have so far not been elucidated in detail. We reveal here that induction of proliferation of human CD4+C25+ Treg cells requires an extraordinary strong CD28 costimulatory signal in addition to TCR/CD3 engagement. CD28 costimulation, noteworthy, cannot be substituted by IL-2 to induce proliferation of Treg cells, which is in contrast to CD4+CD25− T cells. IL-2, in contrast, prevents spontaneous apoptosis of Treg cells, but does not initiate their amplification. IL-2 and CD28 costimulation clearly exhibit disparate effects on Treg cells which are in contrast to those on CD4+CD25− T cells. Moreover, the prerequisites for Treg cell proliferation differ strikingly from those for effector T cells, implying a balanced orchestration in initiating and limiting a T cell immune response. In addition, data are of relevance for the design of therapeutic strategies involving IL-2 administration and CD28 costimulation.
Quality of Life for Members of Swedish Prostate Cancer Patient Associations

Prostate Cancer Patient Associations (PCPAs) have become common. The aim of this study was to evaluate the quality of life of patients belonging to PCPAs. Members of 10 PCPAs in Sweden with prostate cancer completed 2 quality of life questionnaires (Quality-of-Life Questionnaire [QLQ-C30] and Prostate Cancer Symptom Scale). Of 2,028 members, 1,301 (64%) responded to the survey. Sixty percent of the members felt "healthy," and 38% were "free from the cancer. " Ninety-five percent scored >80 on the physical function scale compared with 44% on the overall quality of life/health scale. The most severe symptom was sleeping disturbances (mean = 29). Seventeen percent scored "Quite a bit/Much" tiredness. More than 50% did not report any bladder or bowel problems. Fifty percent had "Much" sexual problems, and almost 80% did not have sufficient erection. Those reported as being "disease free" scored higher on the functioning scales than those with "metastatic disease. " Those with an experience of a "metastatic disease" had more symptoms than those with less advanced disease. This is the first descriptive study of quality of life in members of Swedish PCPAs with prostate cancer. These findings show that it is possible to gain valid data to further study the situation of patients living with prostate cancer by collecting data from PCPAs.
Management of Bone Disease in Kidney Transplant Recipients

There are several types of bone disease that are commonly seen in kidney transplant recipients. These include pre-existing uremic osteodystrophy, osteopenia, osteoporosis, bone fracture, osteonecrosis and bone pain syndrome (Brandenburg et al., 2004; Cohen et al., 2004; Julian et al., 1991; Zisman and Sprague, 2006). Kidney transplant recipients are now living longer than ever, and thus, proper prevention and management of bone disease has become an increasingly important part of their long-term care. Complications from posttransplant bone disease not only cause significant morbidity, but also increase the cost of care, hospitalization, and mortality (Abbott et al., 2001; Duriex et al., 2002; Jeffrey et al., 2003; Vatour et al., 2004; Zhang et al., 2008). Bone disease after kidney transplant is a multifactorial process that includes continuing bone loss superimposed on pre-existing renal osteodystrophy (Brandenburg et al., 2004; Cohen et al., 2004; Zisman & Sprague, 2006; Zhang et al., 2008). There can be several different bone histologies and no single clinical biomarker can distinguish between the various bone disorders (Cruz et al., 2004; Cueto-Manzano et al., 2003; Monier-Faugere et al., 2000; Rolla et al., 2006). Bone biopsy, the gold standard for diagnosis and most accurate tool to guide clinical management is not commonly undertaken due to its invasive nature and difficulty with proper interpretation. The clinical disease spectrum includes four distinct phases: 1) pre-transplant osteodystrophy, 2) post-transplant bone loss exacerbated by a number of factors including immunosuppressive medications, 3) late stabilization with a functioning allograft, and 4) a return to uremic osteodystrophy when the renal allograft fails. This chapter will review the complex pathophysiology of the various types of bone diseases after kidney transplantation and explore the current evidence for their prevention and treatment.
Anatomical features of the cervical spinal canal in Chiari I deformity with presyrinx: A case-control study

Purpose The relationship between syringomyelia and presyrinx, characterized by edema in the spinal cord, has not been firmly established. Patients with syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid flow dynamics, but taper ratios in presyrinx have never been reported. We tested the hypothesis that presyrinx patients have abnormal spinal canal tapering. Materials and methods At six medical institutions, investigators searched the PACS system for patients with Chiari I and spinal cord edema unassociated with tumor, trauma, or other evident cause. In each case taper ratios were calculated for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari I patients with no syringomyelia and patients with normal MR scans, the same measurements were made. Differences between groups were tested for statistical significance with t tests. Results The study enrolled 21 presyrinx patients and equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were positive and steeper in presyrinx patients than in the normal controls (p = 0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and controls without significant differences between the groups. The difference in degree of tonsillar herniation was statistically significant between presyrinx patients and Chiari I controls (p = 0.01). Conclusions Presyrinx patients have greater than normal positive tapering in the lower cervical spine and greater degree of tonsillar herniation than the controls.
Predicting outcome and directing therapy for papillary thyroid carcinoma.

HYPOTHESIS The prognosis of papillary thyroid carcinoma has been stratified into low- and high-risk groups. Patients in the high-risk group can be substratified on the basis of increasing age, with implications for prognosis and treatment. DESIGN Retrospective study. SETTING Tertiary care center. PATIENTS A total of 727 patients with papillary thyroid cancer treated at Lahey Clinic, Burlington, Mass, from 1940 to 1998. INTERVENTIONS Stratification into low- and high-risk groups based on age, metastases, extent, and size. High-risk patients were substratified into "younger" and "older" high-risk groups by age younger than 60 years or 60 years and older, respectively. Effects of surgery, lymph node dissection, and radiation therapy were examined. Main Outcome Measure Survival. RESULTS Of the 727 patients, 585 (80.5%) were classified as low risk and 142 (19.5%) as high risk. The 20-year survival was 97.8% in low-risk patients and 61.3% in high-risk patients (P<.001); it was 72.3% in the younger high-risk group and 45.1% in the older high-risk group (P<.001). Older high-risk patients had a survival advantage with bilateral thyroidectomy: 54.7% 20-year survival for those undergoing bilateral thyroidectomy and 25.0% for unilateral thyroidectomy (P =.004). In the older high-risk group, patients with lymph node dissection (n = 22) had a 20-year survival of 72.4% vs 30.2% in patients who did not undergo lymph node dissection (n = 38) (P =.03). Twenty-year survival in low-risk, younger high-risk, and older high-risk patients receiving radioactive iodine vs no radiation was 100% vs 97.6% (P =.24), 64.2% vs 73.2% (P =.53), and 44.7% vs 44.4% (P =.53). CONCLUSIONS Papillary thyroid carcinoma in low-risk patients had a favorable prognosis regardless of treatment. Older high-risk patients had a survival benefit with total thyroidectomy and lymph node dissection. Radioactive iodine did not affect 20-year survival in any of the risk groups.
Student-Generated Critical Incidents prior to Studying Abroad

The purpose of this paper is to describe the process of having pre-departure study abroad students generate, as a preparotory measure, critical incidents based on experiences from their own lives. These critical incidents present instances of confusion or misunderstanding stemming from cultural or linguistic differences. The paper begins with an abbreviated overview of the history of critical incident usage, tracking a few relevant points in its fifty plus years of existence. This is followed by the procedure of gathering critical incidents from university students and applying them in activities designed to foster intercultural sensitivity. The paper concludes with a list of the basic categories that emerged from the class collection of critical incidents as well as an example of each and a brief commentary.
Quantitation of a 55K cellular protein: similar amount and instability in normal and malignant mouse cells

Quantitative expression of a specific 55,000 (55K)-molecular-weight cellular protein was studied in two groups of mouse embryo fibroblast (clonal) cells originating from two parent clones, one of which possessed high tumorigenicity and the other of which possessed very low tumorigenicity. From the clone with low tumorigenicity, tumor lines and clones were obtained by selecting rare spontaneously transformed highly tumorigenic (mutant) cells. Cells were labeled during exponential growth for 3 h at 37 degrees C, with [35S]methionine, and the cellular 55K protein was immunoprecipitated with a monoclonal antibody and quantitated. There were low and approximately equal amounts of 55K protein in cells (clones) with both low and high tumorigenicity from both groups of cells, and there was no correlation at all between quantitative expression of 55K protein and of cellular tumorigenicity. There was approximately 10- to 20-fold more 55K protein in all simian virus 40-transformed T antigen-positive derivative clones, as shown previously. The T antigen-negative revertant tumor lines and clones obtained by an immunological in vivo selection method had low amounts of 55K protein, similar to the parent cell before simian virus 40 transformation. In all of the T antigen-negative cells, including the highly tumorigenic cells, degradation (turnover? ) of the 55K protein was rapid, and a half-life of 15 to 60 min was estimated from pulse-chase experiments. In all of the T antigen-positive cells the 55K protein was stable (half-life greater than 10 h). In primary cells established from the tumors induced by highly tumorigenic cells there was a very low or no detectable amount of the 55K protein. This is in contrast to the primary cells obtained from early murine embryos in which we have reported high amounts of (stable) 55K proteins.