Miracle-dz/UniFAR-FTUs huggingface dataset:
Features and distribution of CD8 T cells with human leukocyte antigen class I–specific receptor expression in chronic hepatitis C

CD8+ T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune‐mediated tissue injury. Because chronic stimulation may promote the expression by CD8+ T cells of distinct human leukocyte antigen class I–specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8+ T cells with such receptors in chronic hepatitis C patients. NKR CD8+ T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)–infected patients but were not major subsets. However, the frequency of NKG2A+ CD8+ in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV‐infected patients. No such correlation was found with KIR+ T cells in liver in HCV‐infected patients and with the both NKR CD8+ T cells in hepatitis B virus (HBV) infected patients. Circulating CD8+ T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A+CD8+ T cells were committed T cells that appeared less differentiated than KIR+CD8+ T cells. In HCV‐infected patients, their content in perforin was low and similar to that observed in NKG2A−CD8+ T cells; this scenario was not observed in healthy subjects and HBV‐infected patients. Both NKG2A and KIRs could inhibit the response of HCV‐specific CD8+ T cells ex vivo. Conclusion: These results support the concept that an accumulation in the liver parenchyma of NKR+CD8+ T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver‐infiltrating CD8+ T cells in chronic hepatitis C and reveal that distinct subsets of antigen‐experienced CD8+ T cells are differentially sensitive to the pervasive influence of HCV (HEPATOLOGY 2007.)
History, haldanes and health inequities: exploring phenotypic changes in body size by generation and income level in the US-born White and Black non-Hispanic populations 1959-1962 to 2005-2008.

BACKGROUND Most public health literature on trends in population health and health inequities pertains to observed or targeted changes in rates or proportions per year or decade. We explore, in novel analyses, whether additional insight can be gained by using the 'haldane', a metric developed by evolutionary biologists to measure change in traits in standard deviations per generation, thereby enabling meaningful comparisons across species and time periods. METHODS We analysed the phenotypic embodied traits of body height, weight and body mass index of US-born White and Black non-Hispanic adults ages 20 to 44 as measured in six large nationally representative population samples spanning from the 1959-1962 National Health Examination Survey I to the 2005-2008 National Health and Nutrition Examination Survey. Setting the former as baseline, we computed the haldane for each outcome for each racial/ethnic group for each survey, overall and stratified by family income quintile. RESULTS For height, high rates of phenotypic change (haldane ≥ 0.3) occurred chiefly between 1960 and 1980, especially for the Black population in the higher income quintiles. By contrast, for weight, high rates of phenotypic change became evident for both the White and Black populations in the late 1980s and increased thereafter; for body mass index, the shift to high rates of change started in both groups in the late 1990s, especially in the middle income quintiles. CONCLUSIONS Our results support use of the haldane as a supplemental metric to place changes in population health and health inequities in a larger biological and historical context.
Analysis of block coherence based on deterministic matrices

In block compressed sensing, the retrieval of block sparse signals i.e., sparse signal having nonzero entries in the form of blocks or clusters from an under determined system of linear equations is of main interest. The successful recovery of such signals depends on the sensing matrix. Therefore, it is desired to generate a sensing matrix with optimum block coherence for guaranteed recovery. The two coherence metrics i.e., block coherence and sub-coherence are important to analyze when considering the optimally designed sensing matrix. The implication of the outcome presented lies in the fact that exploitation of block sparsity with certain conditions results in successful recovery for a higher sparsity level than treating the signal as conventionally sparse. Moreover, deterministic matrix constructions based on optimum coherence allows for an increased number of blocks as compared to random matrix constructions consequently offering better reconstruction.
The Impact of Higher Education on National Economic and Social Development: Comparative Analysis

The effect of the higher education under the conditions of knowledge-based economy and under influence of the 4th Industrial Revolution that started at the current stage of economies' development, is being experienced by each country. The purpose of this paper is to identify the economic and social aspects of obtaining higher education, the influence of higher education on the economy, the impact of higher education in the context of current changes on the necessity of the lifelong learning. Particular actuality is associated with necessity of the lifelong learning in the process of working at current economy. The study covers the relationship between the level of education and the development of social and economic potential of a country, the impact of higher education on it. As a result the basic requirements which the sector of higher education should face at modern stage, especially in the context of transformation of countries under influence of the 4th Industrial Revolution.
Accurate Modeling and Design of Graded-Index Fiber Probes for Optical Coherence Tomography Using the Beam Propagation Method

Fiber-optic probes for sensing and biomedical imaging applications such as optical coherence tomography (OCT) frequently employ sections of graded-index (GRIN) fiber to re-focus the diverging light from the delivery fiber. Such GRIN fiber microlenses often possess aberrations that cause significant distortions of the focused output beam. Current design methods based on ABCD matrix transformations of Gaussian beams cannot model such effects and are therefore inadequate for the analysis and design of high-performance probes that require diffraction-limited output beams. We demonstrate use of the beam propagation method (BPM) to analyze beam distortion in GRIN-lensed fibers resulting from index profiles that exhibit a deviation from the ideal parabolic shape or artifacts such as ripples or a central dip. Furthermore, we demonstrate the power of this method for exploring novel probe designs that incorporate GRIN phase masks to generate wavefront-shaped output beams with extended depth-of-focus (DOF). We present results using our method that are in good agreement with experimental data. The BPM enables accurate simulation of fiber probes using non-ideal or custom-engineered GRIN fibers with arbitrary refractive index profiles, which is important in the design of high-performance fiber-based micro-imaging systems for biomedical applications.
Molecular Mechanisms of Insulin Resistance: Serine Phosphorylation of Insulin Receptor Substrate-1 and Increased Expression of p85α

Initial attempts to unravel the molecular mechanism of insulin resistance have strongly suggested that a defect responsible for insulin resistance in the majority of patients lies at the postreceptor level of insulin signaling. Subsequent studies in insulin-resistant animal models and humans have consistently demonstrated a reduced strength of insulin signaling via the insulin receptor substrate (IRS)-1/phosphatidylinositol (PI) 3-kinase pathway, resulting in diminished glucose uptake and utilization in insulin target tissues. However, the nature of the triggering event(s) remains largely enigmatic. Two separate, but likely, complementary mechanisms have recently emerged as a potential explanation. First, it became apparent that serine phosphorylation of IRS proteins can reduce their ability to attract PI 3-kinase, thereby minimizing its activation. A number of serine kinases that phosphorylate serine residues of IRS-1 and weaken insulin signal transduction have been identified. Additionally, mitochondrial dysfunction has been suggested to trigger activation of several serine kinases, leading to a serine phosphorylation of IRS-1. Second, a distinct mechanism involving increased expression of p85α has also been found to play an important role in the pathogenesis of insulin resistance. Conceivably, a combination of both increased expression of p85α and increased serine phosphorylation of IRS-1 is needed to induce clinically apparent insulin resistance.
PERSPECTIVES IN PEDIATRIC PATHOLOGY Molecular Mechanisms of Human Embryogenesis: Developmental Pathogenesis of Renal Tract Malformations

The focus of this review is the normal and abnormal development of the kidney and lower urinary tract; for convenience, we will refer to the whole system as the renal tract. The content represents a convergence among the clinical disciplines of histopathology, nephrology, and urology as well the basic sciences of developmental biology and molecular genetics. The story has considerable clinical relevance since diverse renal tract malformations are increasingly detected on fetal ultrasound screening and constitute major causes of chronic renal failure necessitating dialysis and kidney transplantation in children. Evidence is emerging that at least some of these disorders have a defined genetic basis; in others, an abnormal embryonic, or even maternal, environment may contribute to the pathogenesis. This field of study is frequently updated, with new discoveries being made almost every week. Hence this review can not be exhaustive or definitive, but instead highlights some specific areas of interest.
EG0N: Portable in-situ energy measurement for low-power sensor devices

For assessing the energy consumption of an embedded system, typically measurements on a shunting resistor are conducted in a laboratory environment. While such measurements can be easily performed with high precision for stationary setups, obtaining data on the energy-consumption of mobile devices, such as body-worn electronics (wearables) is a significantly more challenging task, since the power consumption depends on the behavior of the user. For example, consider an activity sensor which transmits the detected activity type (e.g., walking, running, resting) wirelessly to a smartphone whenever the activity changes. Clearly, more current is drawn for the transmission whenever the activity needs to be updated. Connecting the device with long wires to a stationary measurement platform distorts the results and restricts the motion of the user. Therefore, the measurement platform needs to be mobile itself to measure in-situ. This imposes multiple challenges on such a system, e.g., the limited power budget for obtaining samples of the current consumption and the need for miniaturized electronics. In this paper, we propose EG0N, a mobile current measurement platform for wearables. While addressing the mentioned challenges, it supports useful advanced features, such as collaborative, context-aware measurements on the device-under-test (DUT).
A brief review on the efficacy of different possible and nonpharmacological techniques in eliminating discomfort of local anesthesia injection during dental procedures

Dental anxiety and fear of needle injection is one of the most common problems encountered by dental practitioners, especially in the pediatric patient. In consequences, it might affect the patient's quality of life. Several methods are suggested to lower the discomfort of local anesthesia injection during dental procedures. Desensitization of injection site is one of the recommended strategies. Among chemical anesthetic topical agents that are effective but might have allergic side effects, using some nonpharmacological and safe techniques might be useful. This study aimed to overview the efficacy of using cooling techniques, mostly by ice or popsicles, warming or pH buffering of drug, and using modern devices to diminish the discomfort of local anesthesia injection during dental procedures.
Structure and Biological Activity of the Short-chain Lipopolysaccharide from Bartonella henselae ATCC 49882T*

The facultative intracellular pathogen Bartonella henselae is responsible for a broad range of clinical manifestations, including the formation of vascular tumors as a result of increased proliferation and survival of colonized endothelial cells. This remarkable interaction with endotoxin-sensitive endothelial cells and the apparent lack of septic shock are considered to be due to a reduced endotoxic activity of the B. henselae lipopolysaccharide. Here, we show that B. henselae ATCC 49882T produces a deep-rough-type lipopolysaccharide devoid of O-chain and report on its complete structure and Toll-like receptor-dependent biological activity. The major short-chain lipopolysaccharide was studied by chemical analyses, electrospray ionization, and matrix-assisted laser desorption/ionization mass spectrometry, as well as by NMR spectroscopy after alkaline deacylation. The carbohydrate portion of the lipopolysaccharide consists of a branched trisaccharide containing a glucose residue attached to position 5 of an α-(2→4)-linked 3-deoxy-d-manno-oct-2-ulosonic acid disaccharide. Lipid A is a pentaacylated β-(1′→6)-linked 2,3-diamino-2,3-dideoxy-glucose disaccharide 1,4′-bisphosphate with two amide-linked residues each of 3-hydroxydodecanoic and 3-hydroxyhexadecanoic acids and one residue of either 25-hydroxyhexacosanoic or 27-hydroxyoctacosanoic acid that is O-linked to the acyl group at position 2′. The lipopolysaccharide studied activated Toll-like receptor 4 signaling only to a low extent (1,000–10,000-fold lower compared with that of Salmonella enterica sv. Friedenau) and did not activate Toll-like receptor 2. Some unusual structural features of the B. henselae lipopolysaccharide, including the presence of a long-chain fatty acid, which are shared by the lipopolysaccharides of other bacteria causing chronic intracellular infections (e.g. Legionella and Chlamydia), may provide the molecular basis for low endotoxic potency.
Axillary Staging by Ultrasound‐guided Fine‐Needle Aspiration Cytology in Breast Cancer Patients. Still Up to Date?

To investigate whether clinicopathological features of breast cancer patients could predict the likelihood of lymph node metastases and the likelihood of false‐negative results of ultrasound‐guided fine‐needle aspiration cytology of suspicious lymph nodes (US+FNAC). Between 2004 and 2009, US+FNAC was performed in 1,150 axillae (18 bilateral breast carcinomas). Based on final histologic diagnosis, the true‐ and false‐negative group of US+FNAC were defined. Subsequently, 11 clinicopathological factors were compared between these two groups. These factors were also compared between patients with and patients without lymph node metastases. Of 1,150 axillae, 429 had lymph node metastases at final histology. US+FNAC indicated metastases in 107 axillae. 1,043 axillae were negative by US+FNAC. Final histology showed metastases in 323 of these 1,043 axillae, resulting in a false‐negative group of US+FNAC of 31%. Both age <60 years and a cT2/cT3 breast carcinoma were significantly associated with lymph node metastases and with false‐negative results of US+FNAC. Lymph node metastases were found in 59.6% of patients <60 years with a cT2/cT3 breast carcinoma. In these patients, 52.3% of the negative US+FNAC results were falsely negative. In patients <60 years with a cT2/cT3 breast carcinoma, we recommend to omit US+FNAC preoperatively and perform a SNB directly, because lymph node metastases were found in 59.6% of these patients and 52.3% of negative US+FNAC results were falsely negative.
Satellite methods underestimate indirect climate forcing by aerosols

Satellite-based estimates of the aerosol indirect effect (AIE) are consistently smaller than the estimates from global aerosol models, and, partly as a result of these differences, the assessment of this climate forcing includes large uncertainties. Satellite estimates typically use the present-day (PD) relationship between observed cloud drop number concentrations (Nc) and aerosol optical depths (AODs) to determine the preindustrial (PI) values of Nc. These values are then used to determine the PD and PI cloud albedos and, thus, the effect of anthropogenic aerosols on top of the atmosphere radiative fluxes. Here, we use a model with realistic aerosol and cloud processes to show that empirical relationships for ln(Nc) versus ln(AOD) derived from PD results do not represent the atmospheric perturbation caused by the addition of anthropogenic aerosols to the preindustrial atmosphere. As a result, the model estimates based on satellite methods of the AIE are between a factor of 3 to more than a factor of 6 smaller than model estimates based on actual PD and PI values for Nc. Using ln(Nc) versus ln(AI) (Aerosol Index, or the optical depth times angstrom exponent) to estimate preindustrial values for Nc provides estimates for Nc and forcing that are closer to the values predicted by the model. Nevertheless, the AIE using ln(Nc) versus ln(AI) may be substantially incorrect on a regional basis and may underestimate or overestimate the global average forcing by 25 to 35%.
Identification of human cytochrome P-450 isoforms involved in metabolism of R(+)- and S(-)-gallopamil: utility of in vitro disappearance rate.

Isoforms of cytochrome P-450 (CYP) involved in the metabolism of gallopamil enantiomers were identified by measuring the disappearance rate of parent drug from an incubation mixture with human liver microsomes and recombinant human CYPs. Mean (+/- S.D.) intrinsic clearances (CL(int)) of R(+)- and S(-)-gallopamil in human liver microsomes were 0.320 +/- 0.165 and 0.205 +/- 0.107 ml/min/mg protein, respectively. These values were highly correlated with the 6beta-hydroxylation activity of testosterone, a marker substrate of CYP3A4 (r = 0.977 and 0.900 for R(+)- and S(-)-gallopamil, respectively, p <. 001). Ketoconazole and troleandomycin, selective inhibitors of CYP3A4, and polyclonal antibodies raised against CYP3A4/5 markedly reduced the CL(int) of gallopamil enantiomers in human liver microsomes. Among the 10 recombinant human CYP isoforms, CYP3A4 exhibited the highest CL(int) of gallopamil enantiomers, and CYP2C8 and CYP2D6 also exhibited appreciable activity. When the contribution of CYP3A4 to the total metabolic clearance of gallopamil enantiomers in human liver microsomes was estimated by relative activity factor, the mean (+/- S.D.) contributions were 92 +/- 18 and 68 +/- 19% for R(+)- and S(-)-gallopamil, respectively. These values were comparable to the rates of immunoinhibition by antibodies raised against CYP3A4/5 observed in human liver microsomes. The present study suggests that CYP3A4 is a major isoform involved in the overall metabolic clearance of gallopamil enantiomers in the human liver, and that the present approach based on disappearance rate may be applicable to identify major isoforms of CYP involved in the metabolism of a drug in human liver microsomes.
Organization of the embryonic and early postnatal murine hippocampus. I. Immunocytochemical characterization of neuronal populations in the subplate and marginal zone

Immunocytochemical techniques were used to characterize the neuronal populations in the hippocampal subplate and marginal zone from embryonic day 13 (E13) to postnatal day 5 (P5). Sections were processed for the visualization of microtubule‐associated protein 2 (MAP2) and other antigens such as neurotransmitters, neuropeptides, calcium‐binding proteins and a synaptic antigen (Mab SMI81). At E13–E14, only the ventricular zone and the primitive plexiform layer were recognized. Some cells in the later stratum displayed MAP2‐, γ‐aminobutyric acid (GABA)‐and calretinin immunoreactivities. From E15 onwards, the hippocampal and dentate plates became visible. Neurons in the plexiform layers were immunoreactive at E15–E16, whereas the hippocampal and dentate plates showed immunostaining two or three days later. Between E15 and E19 the following populations were distinguished in the plexiform layers: the subventricular zone displayed small neurons that reacted with MAP2 and GABA antibodies; the subplate (prospective stratum oriens) was poorly populated by MAP2‐ and GABA‐positive cells; the inner marginal zone (future stratum radiatum) was heavily populated by multipolar GABAergic cells; the outer marginal zone (stratum lacunosum‐moleculare) displayed horizontal neurons that showed glutamate‐ and calretinin immunoreactivities, their morphology being reminiscent of neocortical Cajal‐Retzius cells. Thus, each plexiform layer was populated by a characteristic neuronal population whose distribution did not overlap. Similar segregated neuronal populations were also found in the developing dentate gyrus. At perintal stages, small numbers of neurons in the plexiform layers began to express calbindin D‐28K and neuropeptides. During early postnatal stages, neurons in the subplate and inner marginal zones were transformed into resident cells of the stratum oriens and radiatum, respectively. In contrast, calretinin‐positive neurons in the stratum lacunosum‐moleculare disappeared at postnatal stages. At E15–E19, SMI81‐immunoreactive fibers were observed in the developing white matter, subplate and outer marginal zone, which suggests that these layers are sites of early synaptogenesis. At PO‐P5, SMI81 immunoreactivity became homogeneously distributed within the hippocampal layers.