Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycosylation and palmitoylation of Wnt‐3a are coupled to produce an active form of Wnt‐3a

Wnt‐3a is a representative ligand that activates the β‐catenin‐dependent pathway in Wnt signaling and is modified with glycans and palmitate. In this study, we analyzed the relationship between glycosylation and lipidation of Wnt‐3a. Secretion of a Wnt‐3a mutant that lacks glycosylation (Wnt‐3a NQ) was impaired. Wnt‐3a C77A, which lacks palmitoylation at Cys77, was secreted with similar efficiency to wild‐type Wnt‐3a (Wnt‐3a WT), but did not induce the internalization of low‐density lipoprotein receptor‐related protein 6 (LRP6). Furthermore, removal of palmitate from Wnt‐3a suppressed the ability to bind to its receptors Frizzled8 and LRP6. Wnt‐3a C77A was glycosylated to an extent similar to Wnt‐3a WT, while Wnt‐3a NQ was not modified with palmitate. Expression of porcupine, which is a putative acyltransferase, enhanced palmitoylation of Wnt‐3a WT greatly, but that of Wnt‐3a NQ slightly. While Wnt‐3a WT was present in both the endoplasmic reticulum (ER) and Golgi, Wnt‐3a NQ was located to the ER only. Furthermore, Wnt‐3a was not palmitoylated but was glycosylated in the cells treated with Brefeldin A, which inhibits transport of vesicles from the ER to the Golgi. These results indicate that glycosylation of Wnt‐3a precedes palmitoylation and that both modifications are necessary for secretion of an active Wnt‐3a.
Nonsurgical management of macular hemorrhage secondary to retinal artery macroaneurysms.

OBJECTIVE To report visual acuity outcomes of nonsurgical management of macular hemorrhage secondary to retinal artery macroaneurysms. METHODS Forty-one patients at multiple centers with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone were reviewed. Time to clearance of macular hemorrhage, visual acuity at final follow-up, and presence or absence of macular pigmentary changes after absorption of the hemorrhage were recorded for each patient. RESULTS On initial examination, visual acuity was 20/200 or worse in all except 4 patients (3 with 20/70, 1 with 20/80). At an average follow-up of 15. 7 months, a final visual acuity of 20/40 or better was achieved in 15 eyes (37%), between 20/50 and 20/100 in 12 (29%), and 20/200 or worse in 14 (34%). Macular pigmentary abnormalities were noted after clearance of the hemorrhage in 23 (56%) of 41 cases, and these eyes generally had worse visual acuity outcomes. CONCLUSIONS In eyes with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone, good visual acuity outcomes can often be achieved. Poorer visual acuity outcomes are associated with macular pigmentary changes after resorption of blood. Arch Ophthalmol. 2000;118:780-785
Acute lymphoblastic leukaemia after bone marrow transplantation for aplastic anaemia

An 11 · 5‐year‐old girl developed acute lymphoblastic leukaemia 7 months after bone marrow transplantation for severe aplastic anaemia. Before transplantation there were neither morphologic nor cytogenetic abnormalities to suggest preleukaemia. The conditioning regimen consisted only of cyclophosphamide. At the time of development of acute lymphoblastic leukaemia, chromosome analysis showed the blasts to be of host origin with clonal abnormalities including monosomy 7. Such a preleukaemic syndrome presenting as severe aplastic anaemia is a very rare event (the case reported here is the only one of 436 patients in Seattle) and cannot be reliably excluded before transplantation.
The Monetary Model of CIP Deviations

A large amount of currencies has over time exhibited persistent deviations from covered interest rate parity, resulting in non-zero cross-currency basis swap spreads. The relationship between these deviations and standard macroeconomic variables, however, remains unknown. In this paper, we document a long-run relationship between cross-currency basis swap spreads and macroeconomic variables (relative money supply and relative real output). After presenting a simple model where we relax the no-arbitrage CIP assumption in a monetary model framework, we empirically show that, in the long run, tighter cross-currency basis swap spreads are associated with higher relative real output for non-European currencies, while a rise in relative money supply does not widen the cross-currency basis swap spreads associated with European currencies. Our main results are robust to different estimation techniques and the inclusion of control variables. We also perform an error-correction analysis which suggests that the mechanism governing the adjustment to equilibrium is not the same for European and non-European currencies. More generally, we show that, when there is a move away from equilibrium, it is mostly the cross-currency basis swap spreads that adjust to ensure a return to equilibrium, across all maturities and samples.
Clinical characteristics and resource utilization of patients with bipolar disorder who have frequent psychiatric interventions

Abstract Objective: To compare the demographics, clinical characteristics and resource utilization of patients with bipolar disorder who required frequent psychiatric interventions (FPIs) with those needing fewer interventions in the Duke Healthcare System database between 1999 and 2005. Methods: This retrospective analysis was conducted using electronic medical records of bipolar patients with FPIs, defined as having ≥4 clinically significant events (CSEs) in any 12-month period while in the Duke University Healthcare System. CSEs were composed of emergency room visits, inpatient hospitalizations, or a change in psychotropic medication due to psychiatric symptoms (score ≥4 on the Clinical Global Impressions–Severity scale). Data were compared between patients with and without FPIs. Results: Of 632 patients with bipolar disorder 52.5% were identified as having FPIs. These patients were younger and more often female and African American than those with fewer interventions (p < 0.01 for all). Patients with FPIs were generally prescribed more psychotropic and non-psychotropic medications, utilized more healthcare resources and experienced more psychiatric co-morbidities than those who did not require FPIs (p < 0.01 for all). Limitations: These results are from a single healthcare system and may not be generalizable to all patients with bipolar disorder. This analysis was retrospective and relied on availability of adequate information recording and coding of diagnoses by physicians. Conclusions: Patients with bipolar disorder who required FPIs were significantly different from those with fewer clinically defined interventions with respect to their demographic and clinical characteristics and prescribed medications.
The effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities.

INTRODUCTION Numerous studies indicate hyperglycemia and oxidative stress as factors responsible for endothelium dysfunction and the following development of angiopathy. Increased production of free radicals by vascular endothelium causes disturbance in production and/or decreases bioaccessibility of nitric oxide (NO). It has been suggested that L-arginine supplementation is a reasonable method to increase endothelium NO production and lower free radicals formation. There is a growing number of evidence showing that dietary supplementation of arginine reverses endothelial dysfunction associated with major cardiovascular risk factors and ameliorates many common cardiovascular disorders. OBJECTIVE The aim of the study was to evaluate the potential influence of two-months oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status (TAS). MATERIALS AND METHODS 38 patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II and coexisting type 2 diabetes and 12 healthy volunteers as control group were studied. All patients were treated with oral L-arginine (3 x 2 g/day) for two months. Fasting glucose, HbAlc, nitric oxide and total antioxidant status (TAS) were measured before and after the study. RESULTS Fasting glucose and HbAlc did not change significantly after L-arginine treatment. Statistically significant increase in NO concentration and TAS level was found. CONCLUSIONS Oral two-month supplementation with L-arginine (3 x 2 g/day) had no effect on fasting glucose and HbA1 level in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II. The supplementation of L-arginine led to substantial increase in NO concentration and TAS level in these patients, suggesting its indirect antioxidative effect.
Impact of Multiphase 68Ga-DOTATOC-PET/CT on Therapy Management in Patients with Neuroendocrine Tumors

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.
Inhibition of the GTPase dynamin or actin depolymerisation initiates outward plasma membrane tubulation/vesiculation (cytoneme formation) in neutrophils

In a previous study, we demonstrated that human neutrophils can develop membrane tubulovesicular extensions (TVEs) that are 160–250 nm in width and several micrometres long. These extensions, or cytonemes, are capable of establishing long‐range contacts with other cells or bacteria. Cytonemes consist of membrane tubules and vesicles of a uniform diameter aligned in a row. The mechanism of membrane tubulation/vesiculation to form cytonemes remains unknown. Upon endocytosis, the GTPase dynamin and an intact actin cytoskeleton are required for endocytic vesicles scission from the plasma membrane.
Development of cloned pig embryos by nuclear transfer following different activation treatments

This study compared the effects of activation treatments on the development and ploidy of nuclear transferred (NT) pig embryos. After in vitro maturation of oocytes collected from the slaughterhouse, oocytes were enucleated and reconstructed by transfer of donor cells and fusion with three DC pulses (1.4 kV/cm, 20 μsec). Oocytes were pulsed thrice electrically with 1.4 kV/cm for 20 μsec and NT eggs were divided into three treatment groups: Group 1 (no further treatment), Group 2 (10 μg/mL cycloheximide [CHX], 3 hr), and Group 3 (1.9 mM 6‐dimethylaminopurine [DMAP], 3 hr). All the eggs were cultured in sets of 30 in 60 μL drops of NCSU‐23 supplemented with 4 mg/mL fatty acid free BSA, and compared for the rates of development and ploidy. The rates of cleavage, development, and total cell number of parthenotes in Group 3 were significantly (P < 0.05) higher than those in Groups 1 and 2. Cleavage rates of NT embryos in Group 1 were significantly (P < 0.05) lower than those in Groups 2 and 3 (73% vs. 81% and 82%, respectively). Development into blastocyst stage and total cell number of NT embryos in Group 3 were significantly (P < 0.05) higher than those in Groups 1 and 2. Although the embryos in Group 3 had higher development, ∼58% of NT embryos evaluated were abnormal ploidy (6% haploidy, 9% polyploidy, and 42% mixoploid). The results suggested that although DMAP enhanced development and higher cell number, due attention should be paid to abnormal ploidy in pig NT embryos. Mol. Reprod. Dev. 70: 308–313, 2005. © 2005 Wiley‐Liss, Inc.
Efficacy and safety of ABI793, a novel human anti-human CD154 monoclonal antibody, in cynomolgus monkey renal allotransplantation1

Background. Anti-CD154 monoclonal antibodies (mAbs) cause long-term graft survival in preclinical allotransplantation experiments. This is the first report on the efficacy and safety of ABI793, a novel human anti-human CD154 mAb, in Cynomolgus renal transplant recipients. Methods. ABI793 (human immunoglobulin-G1:&kgr;) was derived from a hybridoma generated after immunization of human immunoglobulin transgenic mice (HuMAb-Mouse, Medarex Inc., Annandale, NJ). Cynomolgus monkey recipients of major histocompatibility complex-mismatched, life-supporting renal allografts were treated repeatedly with intravenous ABI793 for a 3-month period posttransplantation. Graft function was monitored by serum creatinine, and rejection was confirmed histologically. Results. ABI793 binds to human, Cynomolgus and Rhesus monkey CD154; it inhibits dose dependently in vitro CD154:CD40 binding and human mixed lymphocyte reaction. ABI793 is comparable to the mouse anti-human CD154 mAbs 5c8 and 24–31 with respect to affinity, inhibitory capacity, and species specificity; however, ABI793 binds to a different CD154 epitope. With 20 mg/kg of ABI793, five of nine recipients showed substantially prolonged graft survival after cessation of treatment, whereas four of nine recipients were killed because of high serum creatinine while still receiving treatment. ABI793 treatment was associated with episodes of severe acute tubular necrosis (which was unrelated to rejection and responded to fluid and diuretic treatment) and a decrease in platelet numbers. Chronic and acute thromboembolic vascular lesions with hemorrhages were observed in the lung and brain of two allograft recipients. None of these side effects were observed in animals that underwent autotransplantation, thus excluding direct toxicity of ABI793. Conclusions. ABI793 treatment effectively prevents graft rejection in Cynomolgus monkeys. Evidence for rare thromboembolic events, as also previously observed with different anti-human CD154 mAbs, suggests that thromboembolic complications may be a class effect of anti-CD154 mAbs, unrelated to their epitope specificity.
More appropriate discounting: the rate of social time preference and the value of the social discount rate

Abstract Recently, a number of authors, including Burgess and Zerbe, have recommended the use of a real social discount rate (SDR) in the range of 6–8% in benefit-cost analysis (BCA) of public projects. They derive this rate based on the social opportunity cost of capital (SOC) method. In contrast, this article argues that the correct method is to discount future impacts based on the rate of social time preference (STP). Flows in or out of private investment should be multiplied by the shadow price of capital (SPC). Using this method and employing recent United States data, we obtain an estimate of the rate of STP of 3.5% and an SPC of 2.2. We also re-estimate the SDR using the SOC method and conclude that, even if analysts continue to use this method, they should use a considerably lower rate of about 5%.
Activation of TRPV4 Channels (hVRL-2/mTRP12) by Phorbol Derivatives*

We have studied activation by phorbol derivatives of TRPV4 channels, the human VRL-2, and murine TRP12 channels, which are highly homologous to the human VR-OAC, and the human and murine OTRPC4 channel. 4α-Phorbol 12,13-didecanoate (4α-PDD) induced an increase in intracellular Ca2+ concentration, [Ca2+] i , in 1321N1 cells stably transfected with human VRL-2 (hVRL-2.1321N1) or HEK-293 cells transiently transfected with murine TRP12, but not in nontransfected or mock-transfected cells. Concomitantly with the increase in [Ca2+] i , 4α-PDD activated an outwardly rectifying cation channel with an Eisenman IV permeation sequence for monovalent cations that is Ca2+-permeable withP Ca/P Na = 5.8. Phorbol 12-myristate 13-acetate also induced an increase in [Ca2+] i but was ∼50 times less effective than 4α-PDD. EC50 for Ca2+ increase and current activation was nearly identical (pEC50 ∼ 6.7). Similar effects were observed in freshly isolated mouse aorta endothelial cells which express TRP12 endogenously. By using 4α-PDD as a tool to stimulate TRP12, we showed that activation of this channel is modulated by [Ca2+] i ; an increase in [Ca2+] i inhibits the channel with an IC50 of 406 nm. Ruthenium Red at a concentration of 1 μm completely blocks inward currents at −80 mV but has a smaller effect on outward currents likely indicating a voltage dependent channel block. We concluded that the phorbol derivatives activate TRPV4 (VR-OAC, VRL-2, OTRPC4, TRP12) independently from protein kinase C, in a manner consistent with direct agonist gating of the channel.
Olfactory Cues Potentiate Learning of Distant Visuospatial Information

The influence of proximal olfactory cues on place learning and memory was tested in two different spatial tasks. Rats were trained to find a hole leading to their home cage or a single food source in an array of petri dishes. The two apparatuses differed both by the type of reinforcement (return to the home cage or food reward) and the local characteristics of the goal (masked holes or salient dishes). In both cases, the goal was in a fixed location relative to distant visual landmarks and could be marked by a local olfactory cue. Thus, the position of the goal was defined by two sets of redundant cues, each of which was sufficient to allow the discrimination of the goal location. These experiments were conducted with two strains of hooded rats (Long-Evans and PVG), which show different speeds of acquisition in place learning tasks. They revealed that the presence of an olfactory cue marking the goal facilitated learning of its location and that the facilitation persisted after the removal of the cue. Thus, the proximal olfactory cue appeared to potentiate learning and memory of the goal location relative to distant environmental cues. This facilitating effect was only detected when the expression of spatial memory was not already optimal, i.e., during the early phase of acquisition. It was not limited to a particular strain.
Improving delivery of antineoplastic agents with anti‐vascular endothelial growth factor therapy

It is believed that impairments in delivery of antineoplastic agents to solid tumors result from abnormalities of the tumor microenvironment. Vascular endothelial growth factor (VEGF), the prototypical angiogenic molecule, is one of the main factors responsible for the development and maintenance of the aberrant tumor vascular network, which is characterized by chaotic, leaky blood vessels with high interstitial fluid pressure and inefficient blood flow. The authors proposed that anti‐VEGF therapy would reduce the elevated interstitial fluid pressure in tumors, thereby improving blood flow and potentially improving delivery of cytotoxic agents to tumor cells. For the current report, the authors reviewed characteristics of the abnormal tumor vasculature created under the influence of VEGF, the resulting tumor microenvironment, how the tumor microenvironment may impede delivery of antineoplastic agents, and how the combination of anti‐VEGF and cytotoxic therapy may maximize the efficacy of antineoplastic treatment regimens. Cancer 2005. © 2005 American Cancer Society.
3D effect of electrical capacitance and resistance tomography sensors

In electrical resistance tomography (ERT) sensors, small pin electrodes are commonly used. It is well known that the pin electrodes cause severe field distortions or 3D effect, and the sensing region of such an ERT sensor is not constrained to the pin electrode plane, but spreads to a large volume. This is also true for electrical capacitance tomography (ECT) sensors, even though it is less severe because of larger size electrodes in ECT sensors. However, when the length of electrodes in an ECT sensor is reduced to almost the same dimension as those in ERT sensor, the 3D effect may be equally obvious. To investigate the 3D effect of ERT and ECT sensors, simulation was carried out with different lengths of electrodes and the results are compared with the corresponding 2D simulation. It is concluded that sensors with longer electrodes usually have less 3D effect without guard electrodes. To investigate the effectiveness of grounded guards, 3D simulation was carried out for ECT sensors with grounded guards and the results are compared with the previous results in term of the 3D effect. It is found that the 3D effects of ECT and ERT sensors without guards are similar to each other, and the grounded guards can reduce the 3D effect of ECT sensors to a great extent.
An Ecological Systems Examination of Elder Abuse: A Week in the Life of Adult Protective Services

Using Bronfenbrenner’s ecological systems model, this study examined allegations of elder abuse made to Kentucky Adult Protective Services (APS) and the investigation that followed, in order to understand how APS addressed the needs of abused elders. Elder abuse allegations made to APS during the study week were collected using 3 study tools. Allegations and resulting investigations were analyzed. During the study week, APS received 1,002 calls alleging elder abuse. Of these, 483 were categorized as reports needing protective services, with 177 reports screened in for investigation and 167 actually investigated. Results describe characteristics of abuse calls, investigations, victims, perpetrators, and total investigation times. Substantiation ratio, recidivism, and whether investigation increased or decreased the risk of abuse were also assessed. An examination of APS casework through the lens of nested systems frames the study findings and discussion. Such an examination has the potential to improve the quality of services provided to older adults.