Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the promoter region of human placental 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene.

The placenta-type isozyme of human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (HP2K) is expressed in several tissues such as placenta, brain, testis, liver, kidney, skeletal muscle, and primary blood mononuclear cells. To better understand the regulation of HP2K gene expression, we isolated and characterized its genomic DNA, which includes the promoter region. The results of oligo-capping analysis indicate that the transcription start point (tsp) is an adenine residue 329 bp upstream of the translational start codon. DNA sequence analysis of this gene shows that the promoter region that contains the TATA box sequence and the 5'-UTR is different from the other known PFK-2/F2, 6BPase genes. In addition, its 5'-flanking and 5'-UTR both have G + C-rich sequences containing Sp1 binding sites. To identify the promoter/enhancer region of HP2K gene, we performed transfection analyses of human choriocarcinoma BeWo cells with HP2K promoter-luciferase constructs. These experiments identified a promoter region 164 bp upstream from the tsp and an enhancer region between -1265 and -1329 on the 5'-flanking sequences. We also showed that Sp1 sites were not essential for HP2K transcription. Following transfection, stimulation experiments with serum, progesterone and phorbol 12-myristate 13-acetate showed that only the construct with the enhancer containing putative early growth response-1 binding motif was responsive to serum. We propose that the transcription of HP2K is strictly controlled by tissue-specific factors even though its genomic DNA contains several transcriptional elements.
Integrin-mediated Activation of Focal Adhesion Kinase Is Independent of Focal Adhesion Formation or Integrin Activation

Integrin αIIbβ3functions as the fibrinogen receptor on platelets and mediates platelet aggregation and clot retraction. Among the events that occur during either “inside-out” or “outside-in” signaling through αIIbβ3 is the phosphorylation of focal adhesion kinase (pp125FAK) and the association of pp125FAK with cytoskeletal components. To examine the role of pp125FAK in these integrin-mediated events, pp125FAK phosphorylation and association with the cytoskeleton was determined in cells expressing two mutant forms of αIIbβ3: αIIbβ3(D723A/E726A), a constitutively active integrin in which the putative binding site for pp125FAK is altered, and αIIbβ3(F727A/K729E/F730A), in which the putative binding site for α-actinin is altered. Both mutants were expressed on the cell surface and were able to bind ligand, either spontaneously or upon activation. Whereas cells expressing αIIbβ3(D723A/E726A) were able to form focal adhesions and stress fibers upon adherence to fibrinogen, cells expressing αIIbβ3(F727A/K729E/F730A) adhere to fibrinogen, but had reduced focal adhesions and stress fibers. pp125FAK is recruited to focal adhesions in adherent cells expressing αIIbβ3(D723A/E726A) and is phosphorylated in adherent cells or in cells in suspension in the presence of fibrinogen. In adherent cells expressing αIIbβ3(F727A/K729E/F730A), pp125FAK was phosphorylated despite reduced formation of focal adhesions and stress fibers. We conclude that activation of pp125FAK can be dissociated from two important events in integrin signaling, the assembly of focal adhesions in adherent cells and integrin activation following ligand occupation.
The Impact of "Gideon": The Performance of Public & Private Criminal Defense Lawyers

Has the assurance of a lawyer for criminal defendants really mattered? Is not the sophisticated response that legal aid lawyers have neither the experience nor the time and resources and commitment to give meaningful help to their clients? Professor Levine reports a study comparing the performance of private criminal lawyers and Legal Aid Society lawyers in Brooklyn, New York, notes various earlier findings, and proposes certain actions to make the right to counsel more truly effective. But the performance of the legal aid lawyers turns out to be far from inept, token representation. They are surprisingly conscientious and effective advocates. However, their clients lack confidence in them, so prefer to plea bargain, rather than go to trial. This client perception is a key difference between private and legal aid attorneys.
Spectral efficiency evaluation for non-orthogonal multiple access in Rayleigh fading

This paper presents original analysis on the downlink spectral efficiency of non-orthogonal multiple access (NOMA) in Rayleigh fading environment. According to our accurate evaluation technique, a closed-form expression of NOMA spectral efficiency is proposed. With the closed form, the exact average of NOMA spectral efficiency can be achieved at different system parameters. Moreover, this closed form can be used to evaluate other orthogonal multiple access (OMA) techniques such as orthogonal frequency division multiple access (OFDMA).
Current Status of Proximal Gastric Vagotomy, One Hundred Years after Pavlov: is it Finally History?

Abstract One hundred years ago, the role of the vagal nerve in gastric acid production was established. After the second World War, this paradigm served as the basis of treatment of peptic ulcer disease by pharmacological or surgical means. A remarkable parallelism between the developments of both approaches was observed in the 1970s. On the one hand, medication with less side effects became available. On the other hand, vagotomies were becoming more physiologic in nature and produced less postoperative symptoms. The elusive nature of peptic ulcer disease and the inability to cure this by medication were acknowledged. Very few investigators, however, had reported on a possible infectious origin of peptic ulcer disease and those reports were old. After 1984, the role of Helicobacter pylori in the disease was discovered. With this shift in paradigm, the treatment of peptic ulcer disease changed radically, despite attempts in the surgical community to develop simplified operations. This illustrates that neither the most powerful acid reducing drugs on their own, nor the most physiological and least invasive surgical techniques stand the test of time if the underlying paradigm changes. It also illustrates that old ideas should not be overlooked.
High-Gain Disturbance Observer-Based Backstepping Control With Output Tracking Error Constraint for Electro-Hydraulic Systems

We propose a high-gain disturbance observer (HGDOB)-based backstepping control with position tracking error constraint for electro-hydraulic systems to improve the position tracking performance in the presence of disturbances. The HGDOB is designed to estimate the disturbances that include the friction, the load force, and the parameter uncertainties. Auxiliary state variables are proposed to avoid amplification of the measurement noise in the HGDOB. To compensate for the disturbances while guaranteeing tolerance of the position tracking error, the backstepping controller is proposed by using the barrier Lyapunov function. As a result, the proposed method satisfies the output constraint and improves the position tracking performance in the presence of disturbances. Its performance is validated via simulations and experiments.
Modulation of proteoglycan metabolism by human fibroblasts maintained in an endogenous three-dimensional matrix.

This report describes synthesis and degradation of proteoglycans by human gingival fibroblasts growing in an endogenous three-dimensional matrix. Cells grown in the matrix cultures demonstrated a high rate of proteoglycan synthesis, varying between 2 and 4 times that of cells maintained in monolayer cultures. In addition, the relative amount deposited into the cell layer was increased in the matrix cultures, constituting 70% to 90% of the synthesized material during the first 24 h. Comparable levels for the monolayer cultures were 30% to 60%. The majority of the 35S-sulfate-labeled material in both matrix (80%) and monolayer (62%) cultures was susceptible to chondroitin ABC-lyase digestion. The major product was a low Mr (120,000) proteoglycan which could be immunoprecipitated by an antibody against PGII (decorin). In addition, the cells synthesized two chondroitin ABC-lyase-sensitive proteoglycans, one with Mr greater than 400,000, one with an apparent Mr of 250,000, as well as two heparan sulfate proteoglycans with Mr greater than 250,000. The low Mr dermatan sulfate, decorin, was also the major component deposited in the three-dimensional matrix, constituting about 60% of the total sulfate incorporation. In contrast, fibroblasts in monolayer cultures deposited only a small amount (13%) of decorin (PGII) in the cell layer, and the major proteoglycan in this compartment was heparin sulfate. The rate of release of the newly deposited proteoglycans was the same in the two culture conditions, although material released from the three-dimensional matrix cultures contained small Mr components indicating a higher degree of degradation. These studies show differences in proteoglycan metabolism by gingival fibroblasts grown in an endogenous matrix and in monolayer cultures. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of varying the threshold of alarm systems and workload on human performance

The purpose of this research was to investigate the effects of varying the threshold of alarm systems and workload on human response to alarm signals and performance on a complex task. A receiver operating characteristic (ROC) curve was selected to reflect the sensitivity of the alarm system. The threshold of the alarm system was manipulated by changing the value of beta along the ROC curve. A total of 84 students participated in experiment 1 and 48 students participated in experiment 2. Participants performed a compensatory-tracking, a resource management and a monitoring task. As expected, results showed that participants responded significantly faster to true alarm signals when they were using the system with the highest threshold under low-workload conditions. Results also indicated that changing the threshold of the alarm system had a significant effect on overall performance and this effect was greater under high-workload conditions. However, contrary to expectations, the highest level of performance was achieved by setting the threshold at a low level. Results from both experiments revealed that the advantage of faster alarm reaction time as a result of increasing the system's threshold was lost because of its increased probability of missed events.
An inductor-less transmission line based 60 GHz PA in 65-nm CMOS with analog power control

A 60 GHz PA is designed with transmission line-based replacement for magnetic circuit elements like inductors and transformers. This technique has the advantage that the traditional constraints of bandwidth, self-resonance frequency (SRF) and quality factor are easily overcome. The components are better modelled in EM simulations and are area-efficient. The PA is designed in 65-nm CMOS and occupies an area of 0.288mm2 (including pads) and produces a maximum power of 13.4 dBm at a peak PAE of 24%. At 60 GHz, an output power of 12.2 dBm with an efficiency of 17.8% is obtained. The design also demonstrates analog power control by varying the bias of the main PA in a cascade of multiple gain stages.
Protein nutrition in late pregnancy, maternal protein reserves and lactation performance in dairy cows

Empirical evidence suggests that prolonged underfeeding of protein to late-pregnant dry cows can have modest negative carry-over effects on milk volume and/or protein yield during early lactation, and may also cause increased incidence of metabolic diseases associated with fatty liver. However, assessment of requirements is hampered by lack of information on relationships between dietary intake of crude protein (N × 6·25) and metabolizable protein supply during late pregnancy, and by incomplete understanding of the quantitative metabolism of amino acids in maternal and conceptus tissues. Inability of the postparturient cow to consume sufficient protein to meet mammary and extra-mammary amino acid requirements, including a significant demand for hepatic gluconeogenesis, necessitates a substantial, albeit transient, mobilization of tissue protein during the first 2 weeks of lactation. Ultimately, much of this mobilized protein appears to be derived from peripheral tissues, especially skeletal muscle and, to a lesser extent, skin, through suppression of tissue protein synthesis, and possibly increased proteolysis. In the shorter term, soon after calving, it is likely that amino acids required for hepatic glucose synthesis are diverted from high rates of synthesis of splanchnic tissue and export proteins, including serum albumin. The prevailing endocrine milieu of the periparturient cow, including major reductions in plasma levels of insulin and insulin-like growth factor-I, together with insulin resistance in peripheral tissues, must permissively facilitate, if not actively promote, net mobilization of amino acids from these tissues.
Association of MTHFR C677T and A1298C gene polymorphisms with hypertension.

OBJECTIVES To check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region. SUBJECTS AND METHODS Participants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphisms RESULTS Total cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2-3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3-5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3-3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively). CONCLUSION This work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.
Phosphorylation of the Gq/11-coupled M3-Muscarinic Receptor Is Involved in Receptor Activation of the ERK-1/2 Mitogen-activated Protein Kinase Pathway*

We investigated the role played by agonist-mediated phosphorylation of the Gq/11-coupled M3-muscarinic receptor in the mechanism of activation of the mitogen-activated protein kinase pathway, ERK-1/2, in transfected Chinese hamster ovary cells. A mutant of the M3-muscarinic receptor, where residues Lys370–Ser425 of the third intracellular loop had been deleted, showed a reduced ability to activate the ERK-1/2 pathway. This reduction was evident despite the fact that the receptor was able to couple efficiently to the phospholipase C second messenger pathway. Importantly, the ERK-1/2 responses to both the wild-type M3-muscarinic receptor and ΔLys370–Ser425 receptor mutant were dependent on the activity of protein kinase C. Our results, therefore, indicate the existence of two mechanistic components to the ERK-1/2 response, which appear to act in concert. First, the activation of protein kinase C through the diacylglycerol arm of the phospholipase C signaling pathway and a second component, absent in the ΔLys370–Ser425 receptor mutant, that is independent of the phospholipase C signaling pathway. The reduced ability of the ΔLys370–Ser425 receptor mutant to activate the ERK-1/2 pathway correlated with an ∼80% decrease in the ability of the receptor to undergo agonist-mediated phosphorylation. Furthermore, we have previously shown that M3-muscarinic receptor phosphorylation can be inhibited by a dominant negative mutant of casein kinase 1α and by expression of a peptide corresponding to the third intracellular loop of the M3-muscarinic receptor. Expression of these inhibitors of receptor phosphorylation reduced the wild-type M3-muscarinic receptor ERK-1/2 response. We conclude that phosphorylation of the M3-muscarinic receptor on sites in the third intracellular loop by casein kinase 1α contributes to the mechanism of receptor activation of ERK-1/2 by working in concert with the diacylglycerol/PKC arm of the phospholipase C signaling pathway.
Nurses' perspectives of encouraging clients' care-of-self in a short-term rehabilitation unit within a long-term care facility.

This article presents a study conducted on a short-term rehabilitation unit in a long-term care facility. The purpose of the study was to explore, through qualitative methods, nurses' perspectives of encouraging clients to care for themselves. Although the literature suggested that encouraging self-care does not occur, the findings of this study showed that nurses have a broader view than what is currently known in nursing as "self-care. " Potential impediments to nursing practice were overcome by the development of nurse-client relationships through which the nurses encouraged clients in what is described throughout this study as "care-of-self. " Rehabilitation nurses play an important role in helping clients to integrate and reclaim the care of their emerging new selves. Care-of-self may be critical to clients not only in reaching their outcome goals for discharge but also in maintaining outcomes beyond discharge.
The Profitability of Low Volatility

Low-risk stocks exhibit higher returns than predicted by established asset pricing models, but this anomaly seems to be explained by the new Fama-French five-factor model, which includes a profitability factor. We argue that this conclusion is premature given the lack of empirical evidence for a positive relation between risk and return. We find that exposure to market beta in the cross-section is not rewarded with a positive premium, regardless of whether we control for the new factors in the five-factor model. We also observe stronger mispricing for volatility than for beta, which suggests that the low-volatility anomaly is the dominant phenomenon. We conclude that the low-risk anomaly is not explained by the five-factor model.
Molecular mechanisms of antigen retrieval: antigen retrieval reverses steric interference caused by formalin-induced cross-links

Abstract The overwhelming majority of antibodies useful for formalin fixed, paraffin embedded (FFPE) tissues require antigen retrieval to reverse the effect of formalin fixation and re-establish immunoreactivity. How this reversal happens is poorly understood. We developed a new experimental model for studying the mechanism of formalin fixation and antigen retrieval. Epitope mapping studies on nine antibodies useful for FFPE tissues revealed that each consisted of a contiguous stretch of amino acids in the native protein (linear epitope). Small peptides representing the epitopes of antibodies to human epidermal growth factor receptor type (HER2), estrogen, and progesterone receptors were attached covalently to glass microscope slides in a peptide array. Most peptides retained immunoreactivity after formalin fixation. Immunoreactivity was completely abrogated for all peptides, however, if an irrelevant large protein was present during formalin-induced cross-linking. We hypothesize that cross-linking the irrelevant protein to the peptide epitopes sterically blocked antibodies from binding. Antigen retrieval dissociates irrelevant proteins and restores immunoreactivity. Because the epitopes for clinical antibodies require only primary protein structure, the fact that antigen retrieval probably denatures the secondary and tertiary structure of the protein is irrelevant. The same mechanism may occur in tissue samples subjected to formalin fixation and antigen retrieval.
Heme oxygenase‐1 and heme oxygenase‐2 have distinct roles in the proliferation and survival of olfactory receptor neurons mediated by cGMP and bilirubin, respectively

Heme oxygenase (HO) is implicated in protection against oxidative stress, proliferation and apoptosis in many cell types, including neurons. We utilized olfactory receptor neurons (ORNs) as a model to define the roles of HO‐1 and HO‐2 in neuronal development and survival, and to determine the mediators of these effects. The olfactory system is a useful model as ORNs display neurogenesis post‐natally and do not contain nitric oxide synthase (NOS) activity, which could confound results. HO isoforms were expressed in ORNs during embryogenesis and post‐natally. Mice null for either HO‐1 or HO‐2 displayed decreased proliferation of neuronal precursors. However, apoptosis was increased only in HO‐2 null mice. Cyclic GMP immunostaining was reduced in ORNs in both genotypes, providing direct evidence that HO mediates cGMP production in vivo. Bilirubin immunostaining was reduced only in HO‐2 null mice. These roles for HO‐1 and HO‐2 were confirmed using detergent ablation of the epithelium to observe increased neurogenesis of ORNs after target disruption in HO null mice. Primary cultures of ORNs revealed that proliferative and survival effects of HO were mediated through cGMP and bilirubin, respectively. These results support a role for HO, the CO‐cGMP signaling system and bilirubin in neurodevelopment and in response to injury.
Nitrendipine blocks the nociceptive effects of chronically administered ethanol.

BACKGROUND Calcium channel blockers prevent the development of tolerance to ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium channels may also mediate the development of tolerance to the antinociceptive effects of ethanol. METHODS A radiant-heat tail-flick assay was used to assess the effects of nitrendipine, a dihydropyridine L-type calcium channel blocker, on ethanol-induced changes in nociception in rats. Chronic effects of ethanol were tested in four groups of rats, which received 10 days of exposure to a liquid diet. The groups received twice-daily injections of saline or nitrendipine (1, 5, or 10 mg/kg). Tail-flick latencies were measured on days 0 (baseline), 2, 4, 6, 8, and 10 and at 12 hr after removal of the liquid diet. RESULTS Chronic exposure to ethanol produced maximal levels of antinociception by day 4 of exposure. The observed level of antinociception gradually decreased to baseline levels by day 8. Marked decreases in tail-flick latencies below baseline (hyperalgesia) were observed during ethanol withdrawal. Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet. CONCLUSIONS L-type calcium channel blockers block hyperalgesia during ethanol withdrawal and may mediate, at least in part, the antinociceptive effects of chronic ethanol.